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35950889

Emerging strategies for antibody-mediated rejection.

Antibody-mediated rejection (AMR) is the leading cause of kidney graft loss. Very few treatment options are available to the clinician to counter this disease process. In this review we describe the available therapeutics and the novel approaches that are being currently developed.

35950887

Antibody-mediated rejection: prevention, monitoring and treatment dilemmas.

Antibody-mediated rejection (AMR) has emerged as the leading cause of late graft loss in kidney transplant recipients. Donor-specific antibodies are an independent risk factor for AMR and graft loss. However, not all donor-specific antibodies are pathogenic. AMR treatment is heterogeneous due to the lack of robust trials to support clinical decisions. This review provides an overview ments on practical but relevant dilemmas physicians experience in managing kidney transplant recipients with AMR.

35950890

From bench to bedside: reversing established antibody responses and desensitization.

Basic transplant immunology has primarily focused on the definition of mechanisms, but an often-stated aspirational goal is to translate basic mechanistic research into future therapy. Pretransplant donor-specific antibodies (DSA) mediate hyperacute as well as early antibody-mediated rejection (AMR), whereas DSA developing late posttransplantation may additionally mediate chronic rejection. Although contemporary immunosuppression effectively prevents early cellular rejection after transplant in nonsensitized patients, it is less effective at controlling preexisting HLA antibody responses or reversing DSA once established, thus underscoring a need for better therapies.

35950891

The SII reflects inflammation in acne vulgaris, but fails to determine categorical severity.

Systemic Immune Inflammation Index (SII; calculated by multiplying neutrophil-lymphocyte ratio and platelet count) has been investigated as a marker of inflammation.

35950893

Using systems thinking to assess the functioning of an "Age-Friendly City" governance network in Australia.

Age-Friendly Cities (AFC) is a framework for promoting healthy ageing through local actions. We use systems thinking to assess potential es of actions to support older people's mobility, undertaken within an mitment in Greater Sydney. Interviews with 20 informants involved in providing space, infrastructure, or services that affect how older people get around were analysed using causal loop diagrams (CLDs). Four approaches to support older people's mobility were identified and situated to the Multiple Governance Framework: land use, open and public space, supplementary transport, munity transport. Analysis revealed potential for unwanted consequences associated with each, which can be generalised into three generic potential es for other jurisdictions to consider. A mendation from this research is for policy actors to examine feedback interactions between actions so that they can foresee a wider range of es and take defensive action against those unwanted. By situating CLDs within the Multiple Governance Framework, this research not only identifies what to look for, in terms of potential es, but also where to look, in terms of the level of decision-making. This research offers a new way to assess the functioning of AFC governance networks by their collective es and challenges the standards for the evaluation of AFC.

35950896

Ultrasensitive Reagent for Ratiometric Detection and Detoxification of

Toxicity induced by inorganic arsenic as AsO

35950895

Fibroblast growth factor receptor 3 overexpression mediates ALK inhibitor resistance in ALK-rearranged non-small cell lung cancer.

The rearrangement of anaplastic lymphoma kinase (ALK) occurs in 3%-5% of patients with non-small cell lung cancer (NSCLC) and confers sensitivity to ALK-tyrosine kinase inhibitors (TKIs). For the treatment of patients with ALK-rearranged NSCLC, various additional ALK-TKIs have been developed. Ceritinib is a second-generation ALK-TKI and has shown great efficacy in the treatment of patients with both newly diagnosed and crizotinib (a first-generation ALK-TKI)-refractory ALK-rearranged NSCLC. However, tumors can also develop ceritinib resistance. This may result from secondary ALK mutations, but other mechanisms responsible for this have not been fully elucidated. In this study, we explored the mechanisms of ceritinib resistance by establishing ceritinib-resistant, echinoderm microtubule-associated protein-like 4 (EML4)-ALK-positive H3122 cells and ceritinib-resistant patient-derived cells. We identified a mechanism of ceritinib resistance induced by bypass signals that is mediated by the overexpression and activation of fibroblast growth factor receptor 3 (FGFR3). FGFR3 knockdown by small hairpin RNA or treatment with FGFR inhibitors was found to resensitize the resistant cells to ceritinib in vitro and in vivo. FGFR ligands from either human serum or fetal bovine serum were able to activate FGFR3 and induce ceritinib resistance. A detailed analysis of ceritinib-resistant patient-derived specimens confirmed that tyrosine-protein kinase Met (cMET) amplification induces ceritinib resistance. Amplified cMET counteractivated EGFR and/or Her3 and induced ceritinib resistance. These results reveal multiple ceritinib resistance mechanisms and suggest that ceritinib resistance might be e by identifying precise resistance mechanisms.

35950898

Crystallographically Textured Electrodes for Rechargeable Batteries: Symmetry, Fabrication, and Characterization.

The vast of majority of battery electrode materials of contemporary interest are of a crystalline nature. Crystals are, by definition, anisotropic from an atomic-structure perspective. The inherent structural anisotropy may give rise to favored mesoscale orientations and anisotropic properties whether the material is in a rest state or subjected to an external stimulus. The overall perspective of this review is that intentional manipulation of crystallographic anisotropy of electrochemically active materials constitute an untapped parameter space in energy storage systems and thus provide new opportunities for materials innovations and design. To that end, we contend that crystallographically textured electrodes, as opposed to their textureless poly crystalline or single-crystalline analogs, are promising candidates for next-generation storage of electrical energy in rechargeable batteries relevant mercial practice. This perspective is underpinned first by the fundamental─to a first approximation─uniaxial, rotation-invariant symmetry of electrochemical cells. On this basis, we show that a crystallographically textured electrode with the preferred orientation aligned out-of-plane toward the counter electrode represents an optimal strategy for utilization of the crystals' anisotropic properties. Detailed analyses of anisotropy of different types lead to a simple, but potentially useful general principle that "

35950900

Size-Controllable DNA Origami-Stacked Gold Nanoparticles for Deep Tumor-Penetrating Therapy.

With the rapid development of nanotechnology, researchers have designed a variety of intelligent nanodelivery systems to enhance tumor targeting of anticancer drugs. However, increased tumor accumulation does not indicate deeper penetration in the tumor tissue, without which the tumor cells in the core area cannot be sufficiently killed. Herein, we develop a size-controllable nanoparticle system for deep-penetrating cancer therapy, which will be programmably disassembled with the decrease of the pH from the normal tissue to the tumor microenvironment and to the intracellular area. The integrated nanoparticle posed of a gold nanoparticle (GNP, ∼30 nm) and a tetrahedral DNA nanostructure (TDN, ∼25 nm) loaded with doxorubicin (DOX). Initially, the nanoparticles maintain a larger size (∼100 nm) to accumulate in the tumor through the enhanced permeability and retention effect. At a pH of about 6.5 at the tumor microenvironment, with the linkage of DNA sequences converting into a triplex structure, the TDNs detach from the GNP and penetrate deeply into the tumor interstitium and then are internalized into the cells. Finally, in acidic lysosomes with pH 5.0, the TDNs release DOX by forming an i-motif structure. This nanosmart delivery system thus shows effective deep penetration into the tumor core with good antitumor efficacy and satisfactory patibility and provides new insights into the development of intelligent nanosystems for anti-cancer treatment.

35950899

Plain language summary of the design of the TALAPRO-2 study comparing talazoparib and enzalutamide versus enzalutamide and placebo in men with metastatic castration-resistant prostate cancer.

This summary describes the design of an ongoing research study (also known as a clinical trial) called TALAPRO-2. The TALAPRO-2 trial is testing bination of two medicines called talazoparib and enzalutamide as a first treatment in adult men with metastatic castration-resistant prostate cancer. The study began in December 2017 and has enrolled 1037 adult men with metastatic castration-resistant prostate cancer from 26 countries.

35950902

Gastrointestinal symptoms and endoscopy findings after pediatric solid organ transplantation: A case series.

Gastrointestinal symptoms mon among solid organ transplant (SOT) recipients. Information about colonoscopy findings after pediatric SOT is limited. This retrospective study reports endoscopy findings in a nationwide pediatric transplant recipient cohort.

35950905

Rational Designing of Bimetallic/Trimetallic Hydrogen Evolution Reaction Catalysts Using Supervised Machine Learning.

Cost-efficient electrocatalysts to replace precious platinum group metals- (PGMs-) based catalysts for the hydrogen evolution reaction (HER) carry significant potential for sustainable energy solutions. Machine learning (ML) methods have provided new avenues for intelligent screening and predicting efficient heterogeneous catalysts in recent years. We coalesce density functional theory (DFT) and supervised ML methods to discover earth-abundant active heterogeneous NiCoCu-based HER catalysts. An intuitive generalized microstructure model was designed to study the adsorbate's surface coverage and generate input features for the ML process. The study utilizes optimized eXtreme Gradient Boost Regression (XGBR) models to screen NiCoCu alloy-based catalysts for HER. We show that the most active HER catalysts can be screened from an extensive set of catalysts with this approach. Therefore, our approach can provide an efficient way to discover novel heterogeneous catalysts for various electrochemical reactions.

35950906

Fragmentation Dynamics of a Carbon Dioxide Dication Produced by Ion Impact.

The response of carbon dioxide to radiolysis is crucial for understanding the atmospheric chemistry of planets. Here, we present bined experimental and theoretical investigation of the three-body fragmentation dynamics of

35950907

Copper-Catalyzed Cross-Coupling of Alkyl and Phosphorus Radicals for C(sp

A Cu

35950908

One-step Endovascular Aortic Aneurysm Repair With CO2 contrast and Robotic Partial Nephrectomy for Renal Cell Carcinoma: Case Report.

Although rare, as the population ages, abdominal aortic aneurysm synchronous to abdominal malignancies, as renal cell carcinoma, is expected to e more prevalent. There are only two case reports of minimally invasive surgeries to treat these synchronous diseases, with endovascular aortic repair and laparoscopic nephrectomy, but they were performed in two stages, with iodinated contrast and without robotic assistance.

35950909

A systematic, complexity-reduction approach to dissect the kombucha tea microbiome.

One defining goal of microbiome research is to uncover mechanistic causation that dictates the emergence of structural and functional traits of microbiomes. However, the extraordinary degree of plexity has hampered the realization of the goal. Here, we developed a plexity-reducing strategy to mechanistically elucidate positional and metabolic characteristics of microbiome by using the kombucha tea microbiome as an example. The strategy centered around a two-species core that was abstracted from but recapitulated the native counterpart. The core was convergent in position, coordinated on temporal metabolic patterns, and capable for pellicle formation. Controlled fermentations uncovered the drivers of these characteristics, which were also demonstrated translatable to provide insights into the properties munities with plexity and altered conditions. This work unravels the pattern and process underlying the kombucha tea microbiome, providing a potential conceptual framework for mechanistic investigation of microbiome behaviors.

35950911

TMEM132A ensures mouse caudal neural tube closure and regulates integrin-based mesodermal migration.

Coordinated migration of the mesoderm is essential for accurate organization of the body plan during embryogenesis. However, little is known about how mesoderm migration influences posterior neural tube closure in mammals. Here, we show that spinal neural tube closure and lateral migration of the caudal paraxial mesoderm depend on transmembrane protein 132A (TMEM132A), a single-pass type I transmembrane protein, the function of which is not fully understood. Our study in Tmem132a-null mice and cell models demonstrates that TMEM132A regulates several integrins and downstream integrin pathway activation as well as cell migration behaviors. Our data also implicates mesoderm migration in elevation of the caudal neural folds and successful closure of the caudal neural tube. These results suggest a requirement for paraxial mesodermal cell migration during spinal neural tube closure, disruption of which may lead to spina bifida.

35950912

CD248 Regulates Wnt Signaling in Pericytes to Promote Angiogenesis and Tumor Growth in Lung Cancer.

The tumor microenvironment plays a central role in cancer initiation and progression. CD248 is expressed in tumor-associated stromal cells, particularly fibroblasts and pericytes. Exploring the function of CD248 has the potential to provide biological insights into tumor-supportive stroma and potential therapeutic targets. Here, we investigated the role of stromal CD248 in lung cancer. In orthotopic lung cancer transplantation models, tumor volume, density of vessels and pericytes, and functionality of tumor vessels were all lower in mice lacking Cd248 pared with Cd248 wild-type or haploinsufficient mice. Two angiogenic factors, OPN and SERPINE1, were decreased in Cd248LacZ/LacZ pericytes, and supplementation with both factors rescued their proliferation and endothelial cell tube formation-promoting ability. Mechanistically, Wnt/β-catenin signaling induced Opn and Serpine1 expression and was suppressed in Cd248LacZ/LacZ pericytes. CD248 interacted with Wnt pathway repressors IGFBP4 and LGALS3BP, leading to increased Wnt/β-catenin signaling. Correspondingly, administration of a β-catenin inhibitor in Cd248+/LacZ mice mimicked the effect of Cd248 loss and blocked the growth of transplanted lung tumor cells that were resistant to this inhibitor in vitro. In addition, CD248+ pericytes coexpressed OPN and SERPINE1 and correlated with increased tumor size in human lung cancer. Additionally, high expression of CD248, OPN, and SERPINE1 was associated with poor survival in lung cancer patients. In summary, CD248 derepresses Wnt signaling and upregulates OPN and SERPINE1 in pericytes, resulting in enhanced angiogenesis and lung cancer growth. This novel axis of CD248-Wnt signaling-angiogenic factors in pericytes provides a potential target for lung cancer therapy.

35950913

PFN4 is required for manchette development and acrosome biogenesis during mouse spermiogenesis.

Profilin 4 (Pfn4) is expressed during spermiogenesis and localizes to the plex. Here, we generated PFN4-deficient mice, with sperm displaying severe impairment in manchette formation. Interestingly, HOOK1 staining suggests that the perinuclear ring is established; however, ARL3 staining is disrupted, suggesting that lack of PFN4 does not interfere with the formation of the perinuclear ring and initial localization of HOOK1, but impedes microtubular organization of the manchette. Furthermore, amorphous head shape and flagellar defects were detected, resulting in reduced sperm motility. Disrupted cis- and trans-Golgi networks and aberrant production of proacrosomal vesicles caused impaired acrosome biogenesis. Proteomic analysis showed that the proteins ARF3, SPECC1L and FKBP1, which are involved in Golgi membrane trafficking and PI3K/AKT pathway, are more abundant in Pfn4-/- testes. Levels of PI3K, AKT and mTOR were elevated, whereas AMPK level was reduced, consistent with inhibition of autophagy. This seems to result in blockage of autophagic flux, which could explain the failure in acrosome formation. In vitro fertilization demonstrated that PFN4-deficient sperm is capable of fertilizing zona-free oocytes, suggesting a potential treatment for PFN4-related human infertility.

35950914

Clot-targeted magnetic hyperthermia permeabilizes blood clots to make them more susceptible to thrombolysis.

Thrombolysis is a frontline treatment for stroke, which involves the application of tissue plasminogen activator (tPA) to trigger endogenous clot-degradation pathways. However, it is only effective within 4.5 h of symptom onset because of clot contraction preventing tPA permeation into the clot. Magnetic hyperthermia (MH) mediated by tumor-targeted magnetic nanoparticles is used to treat cancer by using local heat generation to trigger apoptosis of cancer cells.

35950915

Non-cell-autonomous regulation of petal initiation in Arabidopsis thaliana.

In many flowering plants, petals initiate in alternate positions from first whorl sepals, suggesting possible signaling between sepal boundaries and petal initiation sites. PETAL LOSS (PTL) and RABBIT EARS (RBE) regulate petal initiation in Arabidopsis thaliana and their transcripts are expressed in sepal boundary and petal initiation sites, respectively, suggesting that PTL acts in a non-cell-autonomous manner. Here, we determined that cells expressing PTL and RBE fusion proteins did not overlap but were adjacent, confirming the non-cell-autonomous function of PTL. Genetic ablation of intersepal cells by expressing the diphtheria toxin-A chain gene driven by the PTL promoter resulted in flowers lacking petals, suggesting these cells are required for petal initiation. Transcriptome bined with a PTL induction system revealed 42 genes that were upregulated under PTL activation, including UNUSUAL FLORAL ORGANS (UFO), which likely plays an important role in petal initiation. These findings suggest a molecular mechanism in which PTL indirectly regulates petal initiation and UFO mediates positional signaling between the sepal boundary and petal initiation sites.

35950918

Teaming up to make kombucha.

Reducing the microbial diversity in a type of fermented tea reveals the core metabolic interactions responsible for the drink's signature taste and characteristics.

35950917

Targeting Plk1 Sensitizes Pancreatic Cancer to Immune Checkpoint Therapy.

Polo-like kinase 1 (Plk1) plays an important role in cell-cycle regulation. Recent work has suggested that Plk1 could be a biomarker of gemcitabine response in pancreatic ductal adenocarcinoma (PDAC). Although targeting Plk1 to treat PDAC has been attempted in clinical trials, the results were not promising, and the mechanisms of resistance to Plk1 inhibition is poorly understood. In addition, the role of Plk1 in PDAC progression requires further elucidation. Here, we showed that Plk1 was associated with poor es in patients with PDAC. In an inducible transgenic mouse line with specific expression of Plk1 in the pancreas, Plk1 overexpression significantly inhibited caerulein-induced acute pancreatitis and delayed development of acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Bioinformatics analyses identified the regulatory networks in which Plk1 is involved in PDAC disease progression, including multiple inflammation-related pathways. Unexpectedly, inhibition or depletion of Plk1 resulted in upregulation of PD-L1 via activation of the NF-κB pathway. Mechanistically, Plk1-mediated phosphorylation of RB at S758 inhibited the translocation of NF-κB to nucleus, inactivating the pathway. Inhibition of Plk1 sensitized PDAC to immune checkpoint blockade therapy through activation of an antitumor immune response. Together, Plk1 suppresses PDAC progression and inhibits NF-κB activity, and targeting Plk1 can potentiate the efficacy of immunotherapy in PDAC.

35950921

Parallel processing, hierarchical transformations, and sensorimotor associations along the 'where' pathway.

Visually guided behaviors require the brain to transform ambiguous retinal images into object-level spatial representations and implement sensorimotor transformations. These processes are supported by the dorsal 'where' pathway. However, the specific functional contributions of areas along this pathway remain elusive due in part to methodological differences across studies. We previously showed that macaque caudal intraparietal (CIP) area neurons possess robust 3D visual representations, carry choice- and saccade-related activity, and exhibit experience-dependent sensorimotor associations (Chang et al., 2020b). Here, we used mon experimental design to reveal parallel processing, hierarchical transformations, and the formation of sensorimotor associations along the 'where' pathway by extending the investigation to V3A, a major feedforward input to CIP. Higher-level 3D representations and choice-related activity were more prevalent in CIP than V3A. Both areas contained saccade-related activity that predicted the direction/timing of eye movements. Intriguingly, the time course of saccade-related activity in CIP aligned with the temporally integrated V3A output. Sensorimotor associations between 3D orientation and saccade direction preferences were stronger in CIP than V3A, and moderated by choice signals in both areas. Together, the results explicate parallel representations, hierarchical transformations, and functional associations of visual and saccade-related signals at a key juncture in the 'where' pathway.

35950920

A Distinct Chromatin State Drives Therapeutic Resistance in Invasive Lobular Breast Cancer.

Most invasive lobular breast cancers (ILC) are of the luminal A subtype and are strongly hormone receptor-positive. Yet, ILC is relatively resistant to tamoxifen and associated with inferior long-term pared with invasive ductal cancers (IDC). In this study, we sought to gain mechanistic insights into these clinical findings that are not explained by the genetic landscape of ILC and to identify strategies to improve patient es. prehensive analysis of the epigenome of ILC in preclinical models and clinical samples showed pared with IDC, ILC harbored a distinct chromatin state linked to gained recruitment of FOXA1, a lineage-defining pioneer transcription factor. This resulted in an ILC-unique FOXA1-estrogen receptor (ER) axis that promoted the transcription of genes associated with tumor progression and poor es. The ILC-unique FOXA1-ER axis led to retained ER chromatin binding after tamoxifen treatment, which facilitated tamoxifen resistance while remaining strongly dependent on ER signaling. Mechanistically, gained FOXA1 binding was associated with the autoinduction of FOXA1 in ILC through an ILC-unique FOXA1 binding site. Targeted silencing of this regulatory site resulted in the disruption of the feed-forward loop and growth inhibition in ILC. In summary, ILC is characterized by a unique chromatin state and FOXA1-ER axis that is associated with tumor progression, offering a novel mechanism of tamoxifen resistance. These results underscore the importance of conducting clinical trials dedicated to patients with ILC in order to optimize treatments in this breast cancer subtype.

35950924

Microglia-dependent remodeling of neuronal circuits.

Microglia are tissue-resident macrophages responsible for the surveillance, neuronal support, and immune defense of the brain parenchyma. Recently, the role played by microglia in the formation and function of neuronal circuits has garnered substantial attention. During development, microglia have been shown to engulf neuronal precursors and participate in pruning mechanisms while, in the mature brain, they influence synaptic signaling, provide trophic support and shape synaptic plasticity. Recently, studies have unveiled different microglial characteristics associated with specific brain regions. This emerging view suggests that the maturation and function of distinct neuronal circuits may be potentially associated with the molecular identity microglia adopts across the brain. Here, we review and summarize the known role of these cells in the thalamus, hippocampus, cortex, and cerebellum. We focus on in vivo studies to highlight the characteristics of microglia that may be important in the remodeling of these neuronal circuits and in relation to neurodevelopmental and neuropsychiatric disorders.

35950926

The dynamic proteome in Arabidopsis thaliana early embryogenesis.

The morphology of the flowering plant is established during early embryogenesis. In recent years, many studies have focused on transcriptional profiling in plant embryogenesis, but the dynamic landscape of the Arabidopsis thaliana proteome remains elusive. In this study, Arabidopsis embryos at 2/4-cell, 8-cell, 16-cell, 32-cell, globular and heart stages were collected for nanoproteomic analysis. In total, 5386 proteins were identified. Of these, 1051 proteins were universally identified in all developmental stages and a range of 27 to 2154 proteins was found to be stage specific. These proteins could be grouped into eight clusters according to their expression levels. Gene Ontology enrichment analysis showed that genes involved in ribosome biogenesis and auxin-activated signalling were enriched during early embryogenesis, indicating that active translation and auxin signalling are important events in Arabidopsis embryo development. Combining RNA-sequencing data with the proteomics analysis, the correlation between mRNA and protein was evaluated. An overall positive correlation was found between mRNA and protein. This work provides prehensive landscape of the Arabidopsis proteome in early embryogenesis. Some important proteins/transcription factors identified through network analysis may serve as potential targets for future investigation.

35950923

A First-in-Class Inhibitor of ER Coregulator PELP1 Targets ER+ Breast Cancer.

Most patients with estrogen receptor alpha-positive (ER+) breast cancers initially respond to treatment but eventually develop therapy resistance with disease progression. Overexpression of oncogenic ER coregulators, including proline, glutamic acid, and leucine-rich protein 1 (PELP1), are implicated in breast cancer progression. The lack of small molecules that inhibits PELP1 represents a major knowledge gap. Here, using a yeast-two-hybrid screen, we identified novel peptide inhibitors of PELP1 (PIP). Biochemical assays demonstrated that one of these peptides, PIP1, directly interacted with PELP1 to block PELP1 oncogenic functions. Computational modeling of PIP1 revealed key residues contributing to its activity and facilitated the development of a small-molecule inhibitor of PELP1, SMIP34, and further analyses confirmed that SMIP34 directly bound to PELP1. In breast cancer cells, SMIP34 reduced cell growth in a dose-dependent manner. SMIP34 inhibited proliferation of not only wild-type (WT) but also mutant (MT) ER+ and therapy-resistant breast cancer cells, in part by inducing PELP1 degradation via the proteasome pathway. RNA sequencing analyses showed that SMIP34 treatment altered the expression of genes associated with estrogen response, cell cycle, and apoptosis pathways. In cell line-derived and patient-derived xenografts of both WT and MT ER+ breast cancer models, SMIP34 reduced proliferation and significantly suppressed tumor progression. Collectively, these results demonstrate SMIP34 as a first-in-class inhibitor of oncogenic PELP1 signaling in advanced breast cancer.

35950927

Harmonization of the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension Blood Pressure/Hypertension Guidelines: Comparisons, Reflections, and Recommendations.

The 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension clinical practice guidelines for management of high blood pressure/hypertension are influential documents. Both guidelines prehensive, were developed using rigorous processes, and underwent extensive peer review. The most notable difference between the 2 guidelines is the blood pressure cut points mended for the diagnosis of hypertension. There are also differences in the timing and intensity of treatment, with the American College of Cardiology/American Heart Association guideline mending a somewhat more intensive approach. Overall, there is substantial concordance in the mendations provided by the 2 mittees, with greater congruity between them than their predecessors. Additional harmonization of future guidelines would help to underscore monality of their core mendations and could serve to catalyze changes in practice that would lead to improved prevention, awareness, treatment, and control of hypertension, worldwide.

35950930

How Did Veterans' Reliance on Veterans Health Administration Outpatient Care Change After Expansion of the Veterans Community Care Program?

The Veterans Community Care Program (VCCP) aims to address access constraints in the Veterans Health Administration (VA) by reimbursing care from munity providers. Little existing research explores how veterans' choice of VA versus VCCP providers has evolved as a significant VCCP expansion in 2014 as part of the Veterans Access, Choice, and Accountability Act.

35950925

Can magnetic resonance imaging enhance the assessment of potential new treatments for cognitive impairment in mood disorders? A systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force.

Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions.

35950933

Predicting molecular properties of α-synuclein using force fields for intrinsically disordered proteins.

Independent force field validation is an essential practice to keep track of developments and for performing meaningful Molecular Dynamics simulations. In this work, atomistic force fields for intrinsically disordered proteins (IDP) are tested by simulating the archetypical IDP α-synuclein in solution for 2.5 μs. binations of protein and water force fields were tested: ff19SB/OPC, ff19SB/TIP4P-D, ff03CMAP/TIP4P-D, and a99SB-disp/TIP4P-disp, with four independent repeat simulations for bination. pare our simulations to the results of a 73 μs simulation using the bination, provided by D. E. Shaw Research. From the trajectories, we predict a range of experimental observations of α-synuclein pare them to literature data. This includes protein radius of gyration and hydration, intramolecular distances, NMR chemical shifts, and

35950934

An integrated ultrasound imaging and abdominal compression device for respiratory motion management in radiation therapy.

Radiotherapy to tumors in the abdomen is challenging because of the significant organ movement and tissue deformation caused by respiration.

35950928

The NO/cGMP/PKG pathway in platelets: The therapeutic potential of PDE5 inhibitors in platelet disorders.

Platelets are the "guardians" of the blood circulatory system. At sites of vessel injury, they ensure hemostasis and promote immunity and vessel repair. However, their uncontrolled activation is one of the main drivers of thrombosis. To keep circulating platelets in a quiescent state, the endothelium releases platelet antagonists including nitric oxide (NO) that acts by stimulating the intracellular receptor guanylyl cyclase (GC). The latter produces the second messenger cyclic guanosine-3',5'-monophosphate (cGMP) that inhibits platelet activation by stimulating protein kinase G, which phosphorylates hundreds of intracellular targets. Intracellular cGMP pools are tightly regulated by a fine balance between GC and phosphodiesterases (PDEs) that are responsible for the hydrolysis of cyclic nucleotides. Phosphodiesterase type 5 (PDE5) is a cGMP-specific PDE, broadly expressed in most tissues in humans and rodents. In clinical practice, PDE5 inhibitors (PDE5i) are used as first-line therapy for erectile dysfunction, pulmonary artery hypertension, and lower urinary tract symptoms. However, several studies have shown that PDE5i may ameliorate the e of various other conditions, like heart failure and stroke. Interestingly, NO donors and cGMP analogs increase the capacity of anti-platelet drugs targeting the purinergic receptor type Y, subtype 12 (P2Y12) receptor to block platelet aggregation, and preclinical studies have shown that PDE5i inhibits platelet functions. This review summarizes the molecular mechanisms underlying the effect of PDE5i on platelet activation and aggregation focusing on the therapeutic potential of PDE5i in platelet disorders, and the es of bined therapy with PDE5i and NO donors to inhibit platelet activation.

35950935

Maternal-foetal transfer of severe acute respiratory syndrome coronavirus 2 antibodies among women with and those without HIV infection.

In pregnant women, antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein cross the placenta and can be detected in cord-blood at the time of delivery. We measured SARS-CoV-2 full-length antispike IgG in blood samples collected from women living with HIV (WLWHIV) and without HIV when presenting for labour, and from paired cord-blood samples. Antispike IgG was measured in maternal blood at delivery on the Luminex platform. Cord-blood samples from newborns of women in with detectable antispike IgG were analysed. The IgG geometric mean concentrations (GMCs) and the percentage of cord-blood samples with detectable antispike IgG pared between WLWHIV and without HIV. A total of 184 maternal and cord-blood pairs were analysed, including 47 WLWHIV and 137 without HIV. There was no difference in antispike GMCs between WLWHIV and without HIV [157 binding antibody units (BAU)/ml vs. 187 BAU/ml; P  = 0.17)]. Cord-blood samples from newborns of WLWHIV had lower pared with those without HIV (143 vs. 205 BAU/ml; P  = 0.033). Cord-to-maternal blood antibody ratio was 1.0 and similar between the two HIV groups. In WLWHIV, those who were 30 years old or less had lower cord-to-maternal blood antibody ratio (0.75 vs. 1.10; P  = 0.037) and their newborns had lower cord-blood GMCs (94 vs. 194 BAU/ml; P pared with the older women. Independently of maternal HIV infection status, there was efficient transplacental transfer of antispike antibodies. The GMCs in cord-blood from newborns of WLWHIV were lower than those in HIV-unexposed newborns.

35950937

The germ cell-specific TAP-like protein NXF-2 forms a novel granular structure and is required for tra-2 3'UTR-dependent mRNA export in Caenorhabditis elegans.

TAP is a general mRNA export receptor and is highly conserved among eukaryotes. The nematode Caenorhabditis elegans has another TAP-like protein, NXF-2, but little is known about its function. In this study, we show that NXF-2 is specifically expressed in germ cells and forms a novel granular structure that is different from that of P granules and that NXF-2 granules are anchored to the nuclear periphery in the mitotic region of the hermaphrodite gonad. In contrast, NXF-2 granules are released within the whole cytoplasm in the meiotic region, where the feminization gene tra-2 starts to function. Both inhibition of XPO-1 (an ortholog of the export receptor CRM1) and mutation of the nuclear export signal of NXF-2 caused the release of NXF-2 granules from the nuclear periphery, indicating that anchoring of NXF-2 granules depends on XPO-1 function. Moreover, inhibition of NXF-2 resulted in a substantial nuclear accumulation of the reporter mRNA carrying the tra-2 3'UTR. These results suggest that, together with XPO-1, NXF-2 exports and anchors tra-2 mRNA to the nuclear periphery to avoid precocious translation until the germ cells reach the meiotic region, thereby contributing to the regulation of tra-2 mRNA expression.

35950938

Trends in diabetes incidence and associated risk factors among people with HIV in the current treatment era.

To examine type 2 diabetes mellitus incidence and associated risk factors among people with HIV (PWH).

35950931

Evidence Based Update on Psychosocial Treatments for Eating Disorders in Children and Adolescents.

Eating disorders (EDs) are life-threatening psychiatric illnesses that occur in adolescents. Unfortunately, limited randomized controlled trials exist to address EDs in this vulnerable population. The current review updates a prior

35950941

Controlled attenuation parameter accurately detects liver steatosis in people with HIV.

Hepatic steatosis is a leading cause of cirrhosis and hepatocellular carcinoma and is highly prevalent in persons with HIV (PWH). However, most studies of hepatic steatosis diagnosis in PWH have focused on those at high risk. We determined the accuracy of vibration-controlled transient elastography (VCTE) with controlled attenuation parameter (CAP) in detecting mild or greater hepatic steatosis pared with the noninvasive gold standard magnetic resonance spectroscopy (MRS) in PWH.

35950939

Ecology and the evolution of sex chromosomes.

Sex chromosomes mon features of animal genomes, often carrying a sex determination gene responsible for initiating the development of sexually dimorphic traits. The specific chromosome that serves as the sex chromosome differs across taxa as a result of fusions between sex chromosomes and autosomes, along with sex chromosome turnover-autosomes ing sex chromosomes and sex chromosomes 'reverting' back to autosomes. In addition, the types of genes on sex chromosomes frequently differ from the autosomes, and genes on sex chromosomes often evolve faster than autosomal genes. Sex-specific selection pressures, such as sexual antagonism and sexual selection, are hypothesized to be responsible for sex chromosome turnovers, the unique gene content of sex chromosomes and the accelerated evolutionary rates of genes on sex chromosomes. Sex-specific selection has pronounced effects on sex chromosomes because their sex-biased inheritance can tilt the balance of selection in favour of one sex. Despite the general consensus that sex-specific selection affects sex chromosome evolution, most population genetic models are agnostic as to the specific sources of these sex-specific selection pressures, and many of the details about the effects of sex-specific selection remain unresolved. Here, I review the evidence that ecological factors, including variable selection across heterogeneous environments and conflicts between sexual and natural selection, can be important determinants of sex-specific selection pressures that shape sex chromosome evolution. I also explain how studying the ecology of sex chromosome evolution can help us understand important and unresolved aspects of both sex chromosome evolution and sex-specific selection.

35950940

Mechanisms linking gender-based violence to worse HIV treatment and care outcomes among women in the United States.

To test whether substance use mediates the associations between gender-based violence (GBV) and suboptimal adherence to antiretroviral therapy (ART), and GBV and poor engagement in care, among women living with HIV (WLHIV) in the United States (US).

35950943

Persistence of SARS-CoV-2 neutralizing antibodies longer than 13 months in naturally infected, captive white-tailed deer (

After identifying a captive herd of white-tailed deer in central Texas with >94% seroprevalence with SARS-CoV-2 neutralizing antibodies in September 2021, we worked retrospectively through archived serum samples of 21 deer and detected seroconversion of all animals between December 2020 and January 2021. We then collected prospective samples to conclude that the duration of persistence of neutralizing antibodies is at least 13 months for 19 (90.5%) of the animals, with two animals converting to seronegative after six and eight months. Antibody titres generally waned over this time frame, but three deer had a temporary 4- to 8-fold increases in plaque reduction neutralization test titres over a month after seroconversion; anamnestic response cannot be ruled out.

35950942

Enhancing lymphangiogenesis and lymphatic drainage to vascularized lymph nodes with nanofibrillar collagen scaffolds.

This study investigated the effect of nanofibrillar collagen scaffold (BioBridge) implantation from the affected limb to the unaffected contralateral femoral vein or lymph node in a rat model.

35950944

Penalized decomposition using residuals (PeDecURe) for feature extraction in the presence of nuisance variables.

Neuroimaging data are an increasingly important part of etiological studies of neurological and psychiatric disorders. However, mitigating the influence of nuisance variables, including confounders, remains a challenge in image analysis. In studies of Alzheimer's disease, for example, an imbalance in disease rates by age and sex may make it difficult to distinguish between structural patterns in the brain (as measured by neuroimaging scans) attributable to disease progression and those characteristic of typical human aging or sex differences. Concerningly, when not properly accounted for, nuisance variables pose threats to the generalizability and interpretability of findings from these studies. Motivated by this critical issue, in this work, we examine the impact of nuisance variables on feature extraction methods and propose Penalized position Using Residuals (PeDecURe), a new method for obtaining nuisance variable-adjusted features. PeDecURe estimates primary directions of variation which maximize covariance between partially residualized imaging features and a variable of interest (e.g., Alzheimer's diagnosis) while simultaneously mitigating the influence of nuisance variation through a penalty on the covariance between partially residualized imaging features and those variables. Using features derived using PeDecURe's first direction of variation, we train a highly accurate and generalizable predictive model, as evidenced by its robustness in testing samples with different underlying nuisance variable distributions. pare PeDecURe monly used position methods ponent analysis (PCA) and partial least squares) as well as a confounder-adjusted variation of PCA. We find that features derived from PeDecURe offer greater accuracy and generalizability and lower correlations with nuisance pared with the other methods. While PeDecURe is primarily motivated by challenges that arise in the analysis of neuroimaging data, it is broadly applicable to data sets with highly correlated features, where novel methods to handle nuisance variables are warranted.

35950945

Trans women have worse cardiovascular biomarker profiles than cisgender men independent of hormone use and HIV serostatus.

Feminizing hormonal therapy (FHT) and HIV potentially alter cardiovascular disease (CVD) risk in transgender women (TW).

35950946

Mandibular fractures in aged patients - Challenges in diagnosis.

Delayed treatment of a mandibular fracture can lead plications. Therefore, early diagnosis is important. The aim of this study was to clarify the specific features of mandibular fractures in aged patients and the effect of age on possible missed diagnoses.

35950950

Characterizing Lewy Pathology in 231 Essential Tremor Brains From the Essential Tremor Centralized Brain Repository.

The Essential Tremor Centralized Brain Repository is the largest repository of prospectively collected essential tremor (ET) brains (n = 231). Hence, we are uniquely poised to address several questions: What proportion of ET cases has Lewy pathology (LP)? What is the nature of that pathology and how does it relate to orbidities? Each brain had plete neuropathological assessment, including α-synuclein immunostaining. We created a 10-category classification scheme to fully encapsulate the patterns of LP observed. Four metrics of cerebellar pathology were also quantified. Mean age at death = 89.0 ± 6.4 years. Fifty-eight (25.1%) had LP and 46 (19.9%) had early to late stages of Parkinson disease (PD). LP was very heterogeneous. Of 58 cases with LP, 14 (24.1%) clinically developed possible PD or PD after a latency of 5 or more years. There was a similar degree of cerebellar pathology in ET cases both with and without LP. In summary, 1 in 4 ET cases had LP-a proportion that seems higher than expected based on studies among control populations. Heterogeneous LP likely reflects clinical associations between ET and PD, and ET with Alzheimer disease-type neuropathology. These data further our understanding of ET and its relatedness to other degenerative diseases.

35950949

A randomized study of intensified antiretroviral treatment monitoring versus standard-of-care for prevention of drug resistance and antiretroviral treatment switch.

Standard-of-care antiretroviral treatment (ART) monitoring in low and e countries consists of annual determination of HIV-RNA viral load with confirmatory viral load testing in case of viral rebound. We evaluated an intensified monitoring strategy of three-monthly viral load testing with additional drug exposure and drug resistance testing in case of viral rebound.

35950952

Steroid therapy has an acceptable role as the initial treatment in autoimmune pancreatitis patients with pancreatic cyst formation: Based on a Japanese nationwide study.

We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF).

35950953

Detection of the Serum Cytokines Predicts COVID-19 Pathogenesis in Egyptian Patients.

Cytokine storms can be triggered by various infectious or noninfectious diseases and cause severe damages to multiple organs. Cytokine storm plays an important role in the pathogenesis of severe cases of coronavirus disease 2019 (COVID-19). The pathogenesis of COVID-19 involves a potent inflammatory response involving plex group of mediators, including interleukin (IL)-6 and IL-10. In this study, the serum levels of IL-6 and IL-10 cytokines were evaluated in 79 COVID-19 infected patients from the National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt. And 20 healthy individuals served as a control group. The patients were divided into moderate, severe, and critically ill. In this study, IL-6 and IL-10 levels were significantly elevated in COVID-19 pared with healthy controls. IL-6 levels were significantly higher in pared with controls (

35950948

Cardiac Mechanics in Altered Hormonal States as a Surrogate for Understanding the Effects of Transgender Hormone Therapy.

Transgender individuals are increasingly seeking the care of physicians to physically transition to their self-identified gender identity. Gender-affirming hormone therapy (GAHT) has significant endocrine effects which may have cardiovascular consequences, and cardiovascular disease in transgender individuals is a growing area of study. The effects of GAHT on cardiac mechanics have yet to be characterized, but there is existing literature regarding changes to cardiac mechanics in similar altered hormonal states. We reviewed this literature, with a focus on echocardiographic findings. We found variable results between studies of different methodologies. These include findings that supraphysiological levels of testosterone may impair cardiac mechanics, whereas estrogen-containing hormonal replacement therapy may improve diastolic echocardiographic parameters. In summary, there are alterations to echocardiographic parameters in altered endocrine states related to exogenous testosterone and estrogen, in a manner that is likely dose-dependent. Encouragingly, the studies we reviewed did not suggest that hormonal changes within physiologic ranges would detrimentally affect echocardiographic parameters of systolic and diastolic function. Future research into the cardiovascular effects of long-term GAHT is warranted to safely guide the longitudinal treatment of transgender individuals.

35950955

Quality of life and lifetime achievement in adult survivors of pediatric heart transplant.

Survival in pediatric heart transplantation has improved since the first successful transplant over 35 years ago leading to increasing numbers of patients entering adulthood. We sought to examine quality of life and various lifetime achievements in our institutional population of long-term adult survivors of pediatric heart transplant.

35950956

Effects of probiotic supplementation on performance of resistance and aerobic exercises: a systematic review.

Strenuous exercise may lead to negative acute physiological effects that can impair athletic performance. Some recent studies suggest that probiotic supplementation can curtail these effects by reducing the permeability of the intestinal barrier, yet results are inconsistent.

35950954

Behavior Problems, Self-Esteem, and Prosocial Behavior in Siblings of Children With Chronic Physical Health Conditions: An Updated Meta-Analysis.

Chronic physical health conditions (CPHC) of children affect the whole family. The aim of the present meta-analysis was pare levels of internalizing, externalizing, and total problems as well as self-esteem/positive self-concept and prosocial behavior of the healthy siblings with children from families not affected by CPHC and test norms, respectively.

35950958

Transformer Neural Networks for Protein Family and Interaction Prediction Tasks.

The munity is rapidly generating protein sequence information, but only a fraction of these proteins can be experimentally characterized. While promising deep learning approaches for protein prediction tasks have emerged, they putational limitations or are designed to solve a specific task. We present a Transformer neural network that pre-trains task-agnostic sequence representations. This model is fine-tuned to solve two different protein prediction tasks: protein family classification and protein interaction prediction. Our method parable to existing state-of-the-art approaches for protein family classification while being much more general than other architectures. Further, our method outperforms other approaches for protein interaction prediction for two out of three different scenarios that we generated. These results offer a promising framework for fine-tuning the pre-trained sequence representations for other protein prediction tasks.

35950959

Alteration of Vesicle-Associated Membrane Protein-Binding Protein B in α-Synuclein Aggregates in Lewy Body Disease.

α-Synuclein (α-Syn) binds to vesicle-associated membrane protein-binding protein B (VAPB) in the endoplasmic reticulum membrane. Recent studies have shown that α-Syn-immunoreactive Lewy pathology is characterized by membrane crowding, including vesicular structures. To elucidate the role of VAPB and vesicular structures in Parkinson's disease (PD) and in dementia with Lewy bodies (DLB), the relationships among VAPB, vesicular structures, and Lewy pathology were investigated by immunohistochemistry and immunoelectron microscopy in 8 PD and 4 DLB autopsy cases. The proportions of VAPB-negative neurons in the substantia nigra in PD and in the temporal cortex in DLB were significantly higher than those in 5 controls. In PD, the incidence of α-Syn inclusions in VAPB-negative neurons was significantly higher (77.4%) than in VAPB-positive neurons (1.6%) in the substantia nigra. In DLB, the incidence of α-Syn inclusions in VAPB-negative neurons was also significantly higher (65.3%) than in VAPB-positive neurons (2.8%) in the temporal cortex. Immunoelectron microscopy revealed that α-Syn and VAPB were localized to filamentous structures of Lewy bodies (LBs). However, only a few vesicular structures labeled with anti-α-Syn were observed within LBs. These findings suggest that reduction of VAPB is involved in the disease processes of PD and DLB, although vesicular structures may not directly contribute to the formation of LBs.

35950962

Rapid Synthesis of Multifunctional Apatite via the Laser-Induced Hydrothermal Process.

Synthetic biomaterials are used to e the limited quantity of human-derived biomaterials and to impart additional biofunctionality. Although numerous synthetic processes have been developed using various phases and methods, monly used processes have some issues, such as a long process time and difficulties with extensive size control and high-concentration metal ion substitution to achieve additional functionality. Herein, we introduce a rapid synthesis method using a laser-induced hydrothermal process. Based on the thermal interaction between the laser pulses and titanium, which was used as a thermal reservoir, hydroxyapatite particles ranging from nanometer to micrometer scale could be synthesized in seconds. Further, this method enabled selective metal ion substitution into the apatite matrix with a controllable concentration. We calculated the maximum temperature achieved by laser irradiation at the surface of the thermal reservoir based on the validation of three simplification assumptions. Subsequent linear regression analysis showed that laser-induced hydrothermal synthesis follows an Arrhenius chemical reaction. Hydroxyapatite and Mg

35950964

Metal Ions as the Third Component Coordinate with the Guest to Stereoscopically Enhance the Phosphorescence Properties of Doped Materials.

The construction of ponent doped systems is an important direction for the development of phosphorescence materials. Herein, benzophenone is selected as the host, phenylquinoline isomers are designed as guests, and seven metal ions are selected as the ponent (Al

35950963

Electron-Injection and Atomic-Interface Engineering toward Stabilized Defected 1T-Rich MoS

1T-phase MoS

35950965

Bubble Templated Flexible Ceramic Nanofiber Aerogels with Cascaded Resonant Cavities for High-Temperature Noise Absorption.

Aviation noise pollution has e a significant public health problem, especially with the endless improvement of flight speed and loading capacity. Existing aviation noise absorbers have fatal defects of large weight, weak high-temperature stability, and difficulty to achieve both good low-frequency (<1000 Hz) and high-frequency (up to 6000 Hz) noise absorption simultaneously. Herein, we report a robust strategy to create flexible ceramic nanofiber aerogels with cascaded resonant cavities by the air bubbles-assisted freeze-casting technology. The stable hinged resonance cavity structures coassembled by flexible ceramic nanofibers, soft montmorillonite nanosheets, and silica sol glue endow the aerogels with pressibility (from -196 to 1100 °C) and bendability. Moreover, prehensive advantages of cascaded resonance cavities and interconnected fibrous networks enable flexible ceramic nanofiber aerogels to have temperature-invariant full-frequency noise absorption performance (noise reduction coefficient up to 0.66 in 63-6300 Hz). The synthesis of this flexible ceramic nanofiber aerogel provides a versatile platform for the design of high-efficiency noise-absorbing material for various fields.

35950968

Who is essential in care? Reflections from the pandemic's backstage.

Since the beginning of the pandemic spread of the Coronavirus, societies have been reminded that the impact of Covid-19 and public health measures of infection containment reflect known gradients of inequality. Measures focusing only the (acknowledged) frontstage of the pandemic and neglecting its (unacknowledged) backstage-understood as those framework conditions indispensable for societies to thrive-have worsened the impact of social determinants of health on the most vulnerable, as shown by the deleterious effects of prolonged social isolation of residents of nursing homes. To reflect this phenomenon ethically, a framework is proposed which is inspired by the feminist philosopher Margret Little. At its core stands the assumption that caring for people and moral ends allows us to identify what is morally salient. This epistemological stance allows a critical look at the alleged dilemmas invoked to enforce brute, long-lasting policies of closing nursing homes in many places-especially in the light of their dubious effectiveness in preventing viral spread and the severe physical and psychological consequences for those affected. If moral salience is only fully perceived through the closeness of the caring relationship, the human suffering resulting from these policies reveals the utter inadequacy of the dilemma rhetoric used to justify them. This insight is illustrated by the personal experience of the author: He describes his role as an essential care partner of his mother living in a nursing home and forced into the role of a "visitor" who witnessed a constant deterioration of care. Based on an epistemological understanding of caring for making reliable moral judgments, potentially exclusionary effects of distinguishing essential from non-essential groups in care will be addressed together with the need to e strict boundaries between front- and backstage. Such efforts will strengthen the munity of persons needing care, professional care givers and essential care partners.

35950966

Association between the reflection magnitude and blood pressure in a multiethnic cohort: the Healthy Life in an Urban Setting study.

Reflection magnitude (RM), the ratio of the amplitudes of the backward and forward central arterial pressure waves, has been shown to predict cardiovascular events. However, the association with blood pressure (BP) and hypertension is unclear.

35950969

Boryl Radicals Enabled a Three-Step Sequence to Assemble All-Carbon Quaternary Centers from Activated Trichloromethyl Groups.

The construction of diversely substituted all-carbon quaternary centers has been a longstanding challenge in organic synthesis. Methods that add three alkyl substituents to a simple C(sp

35950970

Robotic colectomy with CME versus laparoscopic colon resection with or without CME for colon cancer: a systematic review and meta-analysis.

This systematic review with meta-analysis aimed pare the plete mesocolon excision (RCME) to laparoscopic colectomy (LC) with (LCME) or without CME (LC non-CME) in postoperative es, harvested lymph nodes and disease-free survival.

35950971

Sterically Shielded Hydrophilic Analogs of Indocyanine Green.

A modular synthetic process enables two or four shielding arms to be appended strategically over the fluorochromes of near-infrared cyanine heptamethine dyes to create hydrophilic analogs of clinically approved indocyanine green. A key synthetic step is the facile substitution of a heptamethine 4'-Cl atom by a phenol bearing two triethylene glycol chains. The pound is a heptamethine dye with four shielding arms, and a series parative spectroscopy studies showed that the shielding arms (a) increased dye photostability and chemical stability and (b) inhibited dye self-aggregation and association with albumin protein. In mice, the dye cleared from the blood primarily through the renal pathway rather than the biliary pathway for

35950972

A cross-sectional retrospective study comparing handwritten operation notes with electronic operation notes.

pleted medical notes have been shown to be superior in legibility pleteness to handwritten ones. Despite this, surgeons continue to use handwritten operation notes. This paper aims pare the quality of handwritten versus electronic operation notes.

35950973

Rapid Joule-Heating Synthesis for Manufacturing High-Entropy Oxides as Efficient Electrocatalysts.

High-entropy oxide (HEO) including multiple principal elements possesses great potential for various fields such as basic physics, mechanical properties, energy storage, and catalysis. However, the synthesis method of pounds through the traditional heating approach is not conducive to the rapid properties screening, and the current binations of HEO are also highly limited. Herein, we report a rapid synthesis method for HEO through the Joule-heating of nickel foil with dozens of seconds. High-entropy rocksalt oxides (HERSO) with the new bination, high-entropy spinel oxides (HESO), and high-entropy perovskite oxide (HEPO) have been synthesized through the Joule-heating. The synthesized HERSO with new binations proves to be a great promotion of OER activity due to the synergy of ponents and the continuous electronic structure experimentally and theoretically. The demonstrated synthesis approach and the bination of HERSO provide a broad platform for the development of high-entropy materials and catalysts.

35950974

Analysis of clinical characteristics and prognostic factors associated with EBV-associated HLH in children.

Purpose Our aim is to analyze the clinical characteristics and prognostic factors of Epstein-Barr (EB) virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children. Methods Children with newly diagnosed HLH were retrospectively analyzed. Results Finally, a total of 95 children with HLH were enrolled in this study, including 43 (45.3%) with EBV-HLH and 52 (54.7%) with non-EBV-HLH. Laboratory tests showed that the levels of absolute neutrophil count (ANC) decrease (

35950976

Mechanisms for blood pressure reduction following isometric exercise training: a systematic review and meta-analysis.

Isometric exercise training (IET) is established as an effective antihypertensive intervention. Despite this, the physiological mechanisms driving blood pressure (BP) reductions following IET are not well understood. Therefore, we aimed to perform the first meta-analysis of the mechanistic changes measured following IET.

35950975

Neutrophil extracellular traps accelerate vascular smooth muscle cell proliferation via Akt/CDKN1b/TK1 accompanying with the occurrence of hypertension.

Neutrophil extracellular traps (NETs) can trigger pathological changes in vascular cells or vessel ponents, which are vascular pathological changes of hypertension. Therefore, we hypothesized that NETs would be associated with the occurrence of hypertension.

35950978

Sequential Heck Cross-Coupling and Hydrothiolation Reactions Taking Place in the Ligand Sphere of a Chiral Dehydroalanine Ni(II) Complex: Asymmetric Route to β-Aryl Substituted Cysteines.

A practically useful protocol for the asymmetric synthesis of artificial β-aryl-substituted cysteine derivatives was developed through sequential Pd(II)-catalyzed Heck cross-coupling with aryl iodides and hydrothiolation reaction with various alkyl thiols in the presence of triethylamine taking place in the ligand sphere of a robust and bench-stable chiral dehydroalanine plex. The subsequent acidic position of the single diastereomeric plexes led to the target enantiopure cysteine derivatives.

35950980

"Magic" Molecules and a New Look at Chemical Diversity of Hydrocarbons.

We address the question why among the multitude of imaginable C

35950981

Explicit-by-Implicit Treatment of Natural Orbital Occupations Using First- and Second-Order Optimization Algorithms: A Comparative Study.

To address the convergence issues in the natural occupation optimization of reduced density matrix functional theory (RDMFT), we recently proposed the explicit-by-implicit (EBI) idea to handle the ensemble

35950982

Interfacial Modulation on Co

Magnetic oxide films with a strong anomalous Hall effect (AHE) have attracted much attention due to their strong sensitivity and high polarization for magnetic sensor applications. However, the linearity of the anomalous Hall sensors still needs improving. In this work, we propose to use the interface regulation to improve the linearity of the AHE. We grow spinel ferrite Co

35950979

Diagnosis and management of hypertension in patients with Cushing's syndrome: a position statement and consensus of the Working Group on Endocrine Hypertension of the European Society of Hypertension.

Endogenous/exogenous Cushing's syndrome is characterized by a cluster of systemic manifestations of hypercortisolism, which cause increased cardiovascular risk. Its biological basis is glucocorticoid excess, acting on various pathogenic processes inducing cardiovascular damage. Hypertension is mon feature in Cushing's syndrome and may persist after normalizing hormone excess and discontinuing steroid therapy. In endogenous Cushing's syndrome, the earlier the diagnosis the sooner management can be employed to offset the deleterious effects of excess cortisol. Such management bined treatments directed against the underlying cause and tailored antihypertensive drugs aimed at controlling the consequences of glucocorticoid excess. Experts on endocrine hypertension and members of the Working Group on Endocrine Hypertension of the European Society of Hypertension (ESH) prepared this Consensus document, which summarizes the current knowledge in epidemiology, genetics, diagnosis, and treatment of hypertension in Cushing's syndrome.

35950985

Stage IIA Skin Melanoma Treatment With ECHO-7 Oncolytic Virus Rigvir.

Melanoma is a global problem due to the rising numbers of skin melanoma cases. Current treatment guidelines for patients with stage IIA melanoma mend only observation after surgery. In this report, the authors describe a patient with stage IIA skin melanoma treated with surgery and Rigvir virotherapy. Two years after the patient discovered a brown spot on the right cheek, surgery was indicated because the mass had started to ulcerate. Rigvir virotherapy was applied both before and after surgery. Observations made more than 7 years after surgery indicated no signs of disease progression. This case report illustrates an early treatment approach. Neoadjuvant treatment for early-stage melanoma is gaining more interest in both scientific and munities; therefore, the authors believe it is relevant to share their observations.

35950984

Occupational risk factors for hypertension.

The identification and characterization of the modifiable risk factors of hypertension is of great value for public health and clinical medicine to achieve primary prevention. A large amount of literature on the effects of occupational factors on blood pressure and hypertension has been published. In this review, I summarize current evidence regarding the role of occupational factors in hypertension. The results of this review suggest that there is sufficient evidence to support the association between increased risk of hypertension and job stress, shift work, occupational lead exposure, and noise exposure. The association of hypertension with physical inactivity, sedentary behavior, and occupational exposure to mercury, arsenic, cadmium, or carbon disulfide remains inconclusive, although several studies have reported this finding. This review will serve as a step toward future research and provide baseline information for developing strategic interventions to prevent hypertension in the working population.

35950986

Mediators of inflammation resolution and vasoactive eicosanoids in gestational diabetes and preeclampsia.

Women with gestational diabetes (GDM) have an increased risk of preeclampsia and postpartum diabetes. Inflammation associates with both GDM and preeclampsia. This study examined specialized proresolving mediators (SPM) that direct inflammation resolution and eicosanoids that are involved in inflammation, in relation to the development of preeclampsia and ongoing postpartum glucose intolerance in GDM.

35950987

Inflammatory cytokines induce neutrophil extracellular traps interaction with activated platelets and endothelial cells exacerbate coagulation in moderate and severe essential hypertension.

Essential hypertension (EH) patients suffer from paradoxically thrombotic rather than haemorrhagic, although the exact mechanism remains elusive. Our aim is to explore whether and how neutrophil extracellular traps (NETs) play the procoagulant role in EH patients, as well as evaluated whether the NET releasing were triggered by inflammatory cytokines.

35950988

Hypertension, remnant cholesterol and cardiovascular disease: evidence from the China health and retirement longitudinal study.

Previous studies had reported the significant association between hypertension, remnant cholesterol (RC) and risk of cardiovascular disease (CVD). The aim of present study was to evaluate bined effect of hypertension and RC on the risk of CVD.

35950989

Dismantling Institutional Racism: The Role of Behavioral Science.

Institutionalized racism embeds our systems of healthcare delivery and medical education. This produces racial healthcare disparities which have been shown to severely impact both physical and behavioral health es. Efforts to address institutionalized racism often focus on individualized efforts directed towards the healthcare workforce. However, more effective system level approaches are emerging. The behavioral health sciences can play a role in dismantling institutionalized racism by providing the evidence needed to understand effects on individuals and develop targeted system level approaches.

35950990

Soy protein concentrate replacing animal protein supplements and its impacts on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, mucosa-associated microbiota, and growth performance of nursery pigs.

This study was to evaluate the effects of soy protein concentrate (SPC) supplementation replacing animal protein supplements on intestinal immune status, intestinal oxidative stress status, nutrient digestibility, mucosa-associated microbiota, and growth performance of nursery pigs. Thirty-two newly weaned pigs at 21 d of age with 6.4 ± 0.4 kg body weight (BW) were allotted to four treatments in a plete block design with initial BW and sex as blocks. Pigs were fed for 35 d in three phases. Dietary treatments were SPC 0% (diets with fish meal 4/2/1%, poultry meal 10/8/4%, blood plasma 4/2/1%, and crude protein 24.6/22.6/20.9% for phase 1/2/3, respectively), SPC 33%, SPC 66%, and SPC 100% (SPC 0% diets with SPC replacing 33/66/100% of animal protein supplements, respectively). Pigs were euthanized on day 35 to collect jejunal mucosa and tissues to evaluate intestinal immune status, intestinal oxidative stress status, intestinal morphology, and mucosa-associated microbiota in the jejunum. Titanium dioxide was added in phase three diets as an indigestible marker. Ileal digesta was collected to measure apparent ileal digestibility (AID) of nutrients. Data were analyzed using MIXED and NLMIXED procedures of SAS. Increasing SPC supplementation by replacing animal protein supplements linearly decreased (P < 0.05) the BW, ADG, and ADFI of pigs during the overall period, and linearly increased (P < 0.05) peptide tyrosine tyrosine (PYY) in jejunum. Increasing SPC supplementation linearly decreased (P < 0.05) feed cost per weight gain. In the exponential model, SPC can replace animal protein supplements up to 10.5% and 16.5% without reducing the ADG and ADFI of pigs, respectively. The SPC 100% decreased (P < 0.05) Helicobacteraceae, Campylobacteraceae, alpha diversity, and changed beta diversity of microbiota in the jejunal mucosa. In conclusion, SPC supplementation replacing animal protein supplements reduced growth performance by reducing feed intake, which might be related to increased PYY. However, 10.5% and 16.8% of animal protein supplements can be replaced by SPC without affecting BW gain and feed intake of nursery pigs, respectively. Complete removal of animal protein supplements by SPC supplementation modulated position of jejunal mucosa-associated microbiota by reducing Helicobacteraceae and Campylobacteraceae, whereas without affecting the intestinal immune status, intestinal oxidative stress status, intestinal morphology, and AID of nutrients in nursery pigs.

35950991

Modified Biodegradation Behavior Induced Beneficial Microenvironments for Bone Regeneration by Low Addition of Gadolinium in Zinc.

Zinc (Zn) shows a great potential as a biodegradable material for bone implants after a decade of systematic research and development. However, uncontrollable biodegradation behavior and biphasic dose-response prevent Zn from fulfilling its essential role in facilitating bone regeneration. In this study, the low addition of gadolinium (Gd) modifies the intrinsic microstructure of Zn in terms of grain size distribution, grain boundary misorientation, and texture. Adding Gd refines grain size distribution and creates a stronger basal plane texture in Zn, consequently, changing the current density distribution and reducing the anode dissolution rate during corrosion. As a result, uniform degradation is more predominant in Zn-0.4Gd alloy implant, parison to localized degradation in pure Zn implant in bone environments. The modified biodegradation behavior of the Zn-0.4Gd alloy implant induces significantly better new bone formation and pared to the pure Zn implant. Therefore, Gd with trace amounts is able to tune the degradation behavior and improve the performance of Zn-based implants in promoting bone regeneration.

35950992

Management of intradialytic hypertension: current evidence and future perspectives.

Intradialytic hypertension (IDH), that is, a paradoxical rise in blood pressure (BP) during or immediately after a hemodialysis session, affects approximately 10-15% of the hemodialysis population. It is currently recognized as a phenomenon of major clinical significance as recent studies have shown that BP elevation extends to the whole interdialytic interval and associates with increased cardiovascular and all-cause mortality. The pathophysiology of IDH plex involving volume and sodium overload, endothelial dysfunction, excess renin-angiotensin-aldosterone system and sympathetic nervous system activation, and other mechanisms. For several years, there was a scarcity of studies regarding IDH treatment; recently, however, several attempts to examine the effect of nonpharmacological and pharmacological measures on BP levels in IDH are made. This review attempts to summarize this latest evidence in the field of management of IDH and discuss areas for future research.

35950994

Predictive power of 24-h ambulatory pulse pressure and its components for mortality and cardiovascular outcomes in 11 848 participants recruited from 13 populations.

The role of pulse pressure (PP) 'widening' at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of ponents: 'elastic PP' (elPP) and 'stiffening PP' (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP ('PP variables') with mortality posite cardiovascular events in different age classes.

35950995

Platelet-derived extracellular vesicles correlate with therapy-induced nocturnal blood pressure changes.

Elevated nocturnal blood pressure (BP) is closely associated with increased risk of cardiovascular (CV) events. Circulating extracellular vesicles (EVs) have been proposed as a potential CV risk biomarker and shown to correlate with BP. The present study aimed to assess whether a reduction in BP is paralleled by respective changes in EVs.

35950996

Temperature-Dependent Fracture Resistance of Silicon Nanopillars during Electrochemical Lithiation.

During the lithation of silicon anodes, the solid-state diffusion of lithium into Li

35950997

Functional Loop Dynamics and Characterization of the Inactive State of the NS2B-NS3 Dengue Protease due to Allosteric Inhibitor Binding.

Dengue virus, a flavivirus that causes dengue shock syndrome and dengue hemorrhagic fever, is currently prevalent worldwide. A ponent protease (NS2B-NS3) is essential for maturation, representing an important target for designing anti-flavivirus drugs. Previously, consideration has been centered on developing active-site inhibitors of NS2B-NS3pro. However, the flat and charged nature of its active site renders difficulties in developing inhibitors, suggesting an alternative strategy for identifying allosteric inhibitors. The allosterically sensitive site of the dengue protease is located near Ala125, between the 120s loop and 150s loop. Using atomistic molecular dynamics simulations, we have explored the protease's conformational dynamics upon binding of an allosteric inhibitor. Furthermore, characterization of the inherent flexible loops (71-75s loop, 120s loop, and 150s loop) is carried out for allosteric-inhibitor-bound wild-type and mutant A125C variants and parison is performed with its unbound state to extract the structural changes describing the inactive state of the protease. Our study reveals pared to the unliganded system, the inhibitor-bound system shows large structural changes in the 120s loop and 150s loop in contrast to the rigid 71-75s loop. The unliganded system shows a closed-state pocket in contrast to the open state for the plex that locks the protease into the open and inactive-state conformations. However, the plex fluctuates between open and closed states. Also, we tried to see how mutation and binding of an allosteric inhibitor perturb the connectivity in a protein structure network (PSN) at contact levels. Altogether, our study reveals the mechanism of conformational rearrangements of loops at the molecular level, locking the protein in an inactive conformation, which may be useful for developing allosteric inhibitors.

35950998

The effects of hypertension on the prognosis of coronavirus disease 2019: a systematic review and meta-analysis on the interactions with age and antihypertensive treatment.

Hypertension and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) have been reported to be associated with the prognosis of COVID-19, but the findings remain controversial. Here, we conducted a systematic review to summarize the current evidence.

35950999

Variability of aldosterone, renin and the aldosterone-to-renin ratio in hypertensive patients without primary aldosteronism.

The aldosterone-to-renin ratio (ARR) monly used in the screening of primary aldosteronism. However, limited information is available with regard to the intra-patient variability in this ratio. Our objective is to determine whether ARR measurements are reliably consistent over both the short- and long-term.

35951001

Impact of Levy noise on a stochastic Norovirus epidemic model with information intervention.

In this article, we study the dynamics of Norovirus infection by developing a stochastic epidemic model having Levy noise. The study shows that Levy noise and informative interventions have more influence on the said dynamics. Firstly, we show that the model has a unique global positive solution. After this, we formulated a stochastic threshold value as a necessary condition for the extinction and persistence in the mean of the proposed epidemic model. Finally, numerical simulation are drawn to verify our obtained results of the dynamics. The perturbed stochastic approach may affect the dynamical properties of the model and large noises will be greatly significant to minimize its transmission.

35951002

SDGCCA: Supervised Deep Generalized Canonical Correlation Analysis for Multi-Omics Integration.

Integration of multi-omics data provides opportunities for revealing biological mechanisms related to certain phenotypes. We propose a novel method of multi-omics integration called supervised deep generalized canonical correlation analysis (SDGCCA) for modeling correlation structures between nonlinear multi-omics manifolds that aims at improving the classification of phenotypes and revealing the biomarkers related to phenotypes. SDGCCA addresses the limitations of other canonical correlation analysis (CCA)-based models (such as deep CCA, deep generalized CCA) by plex/nonlinear cross-data correlations between multiple (

35951003

Elevated expression of TAM receptor tyrosine kinase in synovial fluid and synovial tissue of rheumatoid arthritis.

To investigate the expression and roles of TAM (Tyro3/Axl/Mer) receptor tyrosine kinases (TK) in synovial fluid and synovial tissue of patients with rheumatoid arthritis (RA). The expression of TAM TKs in the synovial fluid and synovial tissues of RA and osteoarthritis (OA) patients was measured by ELISA and immunohistochemistry. The relationships between soluble TAM TKs (sTAM TKs) levels and the clinical features, laboratory parameters and disease activity were analyzed in RA. The concentrations of sTAM TK in the synovial fluids of RA patients were increased parison to those of OA patients. Compared with OA patients, the expression of membrane Tyro3 TK (mTyro3 TK) and mMer TK in RA patient synovial tissue were significantly increased, which may partly explain the possible mechanism of elevated levels of sTAM TK in RA patient synovial fluid. sAxl TK levels were decreased in RA patients under sulfasalazine treatment and elevated in patients under Iguratimod treatment. Furthermore, sTyro3 TK levels were positively correlated with erythrocyte sedimentation rate (ESR) and negatively correlated with white blood cells (WBCs), red blood cells (RBCs), and hemoglobin (HB) in RA patients. The levels of sMer TK were positively associated with disease duration and rheumatoid factor (RF) and negatively correlated with plement 3 (C3), and C4. Taken together, TAM TKs might be involved in RA synovial tissue inflammation.

35951000

Genetic basis of growth reaction to drought stress differs in contrasting high-latitude treeline ecotones of a widespread conifer.

Climate change is increasing the frequency and intensity of drought events in many boreal forests. Trees are sessile organisms with a long generation time, which makes them vulnerable to fast climate change and hinders fast adaptations. Therefore, it is important to know how forests cope with drought stress and to explore the genetic basis of these reactions. We investigated three natural populations of white spruce (Picea glauca) in Alaska, located at one drought-limited and two cold-limited treelines with a paired plot design of one forest and one treeline plot. We obtained individual increment cores from 458 trees and climate data to assess dendrophenotypes, in particular the growth reaction to drought stress. To explore the genetic basis of these dendrophenotypes, we genotyped the individual trees at 3000 single nucleotide polymorphisms in candidate genes and performed genotype-phenotype association analysis using linear mixed models and Bayesian sparse linear mixed models. Growth reaction to drought stress differed in contrasting treeline populations. Therefore, the populations are likely to be unevenly affected by climate change. We identified 40 genes associated with dendrophenotypic traits that differed among the treeline populations. Most genes were identified in the drought-limited site, paratively strong selection pressure of drought-tolerant phenotypes. Contrasting patterns of drought-associated genes among sampled sites and parison to Canadian populations in a previous study suggest that drought adaptation acts on a local scale. Our results highlight genes that are associated with wood traits which in turn are critical for the establishment and persistence of future forests under climate change.

35951004

Longitudinal Mediating Effect of Depression on the Relationship between Excessive Daytime Sleepiness and Activities of Daily Living in Parkinson's Disease.

Whether depression affects activities of daily living (ADLs) in patients with Parkinson's disease (PD) via excessive daytime sleepiness (EDS) remains unclear; moreover, few longitudinal studies have been conducted.

35951005

Heterozygous variants in SIX3 and POU1F1 cause pituitary hormone deficiency in mouse and man.

Congenital hypopituitarism is a genetically heterogeneous condition that is part of a spectrum disorder that can include holoprosencephaly. Heterozygous mutations in SIX3 cause variable holoprosencephaly in humans and mice. We identified two children with neonatal hypopituitarism and thin pituitary stalk who were doubly heterozygous for rare, likely deleterious variants in the transcription factors SIX3 and POU1F1. We used genetically engineered mice to understand the disease pathophysiology. Pou1f1 loss-of-function heterozygotes are unaffected; Six3 heterozygotes have pituitary gland dysmorphology and pletely ossified palate; and the Six3+/-; Pou1f1+/dw double heterozygote mice have a pronounced phenotype, including pituitary growth through the palate. The interaction of Pou1f1 and Six3 in mice supports the possibility of digenic pituitary disease in children. Disruption of Six3 expression in the oral pletely ablated anterior pituitary development, and deletion of Six3 in the neural ectoderm blocked the development of the pituitary stalk and both anterior and posterior pituitary lobes. Six3 is required in both oral and neural ectodermal tissues for the activation of signaling pathways and transcription factors necessary for pituitary cell fate. These studies clarify the mechanism of SIX3 action in pituitary development and provide support for a digenic basis for hypopituitarism.

35951007

Population genomics of an emergent tri-species hybrid zone.

Isolating barriers that drive speciation monly studied in the context of two-species hybrid zones. There is, however, evidence that plex introgressive relationships mon in nature. Here, we use field observations and genomic analysis, including the sequencing and assembly of a novel reference genome, to study an emergent hybrid zone involving two colliding hybrid zones of three woodpecker species: red-breasted, red-naped, and yellow-bellied sapsuckers (Sphyrapicus ruber, S. nuchalis, and S. varius). Surveys of the area surrounding Prince George, British Columbia, Canada, show that all three species are sympatric, and Genotyping-by-Sequencing identifies hybrids from each species pair and birds with ancestry from all three species. Observations of phenotypes and genotypes of mated pairs provide evidence for assortative mating, though there is some heterospecific pairing. Hybridization is more extensive in this tri-species hybrid zone than in two di-species hybrid zones. However, there is no evidence of a hybrid swarm and admixture is constrained to contact zones, so we classify this region as a tension zone and invoke selection against hybrids as a likely mechanism maintaining species boundaries. Analysis of sapsucker age classes does not show disadvantages in hybrid survival to adulthood, so we speculate the selection upholding the tension zone may involve hybrid fecundity. Gene flow among all sapsuckers in di-species hybrid zones suggests introgression probably occurred before the formation of this tri-species hybrid zone, and might result from bridge hybridization, vagrancies, or other three-species interactions.

35951008

Bovine pericardium leaflet damage during transcatheter aortic valve crimping: a study of the mechanisms.

Leaflet damage has been documented to occur while deploying a transcatheter aortic valve (TAV) due to mechanical loads during the crimping procedures. In this study, the impact pressive stress on folded leaflets was measured to investigate the mechanism of traumatic leaflet tissue damage. Numerical simulation of TAV crimping procedure was adapted to calculate stress magnitude and distribution of leaflets. A 20 mm balloon expanding short stent TAV with 0.25 mm thickness leaflets was used in the simulation. Then the calculated stresses were applied on leaflet material (bovine pericardium) samples by loading experiments. Mechanical properties bined with histological and microscopy observation were used to investigate the tissue damage. The elastic modulus and the tensile strength of the tissue began to decrease significantly at 2 MPa stress and 2.5 MPa stress, respectively. No significant differences were observed at 0-1.5 MPa stress. When the TAV was crimped to 14 Fr and 12 Fr, the 2 MPa greater areas on leaflets increased from 18.17% to 76.96%. pressive stress might be the threshold value for leaflet damage. The TAV crimping size should be paid attention to avoid pressive stress higher than 2 MPa.

35951010

Teaching Second-Year Medical Students How to Counsel Pediatric Patients With Unhealthy Body Mass Index.

Obesity affects the health and well-being of children globally. Despite mendations to routinely screen children for obesity starting at age 6 years, physicians do not consistently address weight or provide effective weight-management counseling. We developed an interactive session for second-year medical students with foundational knowledge and munication skills around partnership and discussion of pediatric healthy weight management. Students were administered a pre-/post-Likert survey to self-assess fort, and confidence in counseling patients and caregivers about weight management. Students' related counseling skills were assessed during a standardized patient encounter of a teen with rapid weight gain. The session successfully increased students' self-assessed fort, and confidence, and resulted in successful application of weight management skills in a simulated patient encounter. Utilization of empathy skills requires continued coaching. We propose incorporation of similar sessions into medical school curricula to address the pediatric obesity epidemic.

35951009

Environmental Persistence of Monkeypox Virus on Surfaces in Household of Person with Travel-Associated Infection, Dallas, Texas, USA, 2021.

In July 2021, we conducted environmental sampling at the residence of a person in Dallas, Texas, USA, who had travel-associated human West African monkeypox virus (MPXV-WA). Targeted environmental swab sampling was conducted 15 days after the person who had monkeypox left the household. Results indicate extensive MPXV-WA DNA contamination, and viable virus from 7 samples was successfully isolated in cell culture. There was no statistical difference (p = 0.94) between MPXV-WA PCR positivity of porous (9/10, 90%) vs. nonporous (19/21, 90.5%) surfaces, but there was a significant difference (p<0.01) between viable virus detected in cultures of porous (6/10, 60%) vs. nonporous (1/21, 5%) surfaces. These findings indicate that porous surfaces (e.g., bedding, clothing) may pose more of a MPXV exposure risk than nonporous surfaces (e.g., metal, plastic). Viable MPXV was detected on household surfaces after at least 15 days. However, low titers (<10