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35950522 | Desirable Difficulty: Theory and application of intentionally challenging learning. | Health professions trainees must acquire a vast amount of clinical knowledge and skills, and a deliberate instructional design approach is needed to provide trainees with effective learning strategies. One powerful yet counterintuitive strategy that facilitates long-term learning is incorporating intentional difficulties during the learning process. Difficulties that require more effort from learners may impede short-term learning but are ultimately beneficial for long-term learning and are therefore termed Desirable Difficulties. |
35950521 | Pain and Reorganization after Amputation: Is Interoceptive Prediction a Key? | There is an ongoing discussion on the relevance of brain reorganization following amputation for phantom limb pain. Recent attempts to provide explanations for seemingly controversial findings-specifically, maladaptive plasticity versus persistent functional representation as plementary process-acknowledged that reorganization in the primary somatosensory cortex is not sufficient to explain phantom limb pain satisfactorily. Here we provide theoretical considerations that might help integrate the data reviewed and suppose a possible additional driver of the development of phantom limb pain-namely, an error in interoceptive predictions to somatosensory sensations and movements of the missing limb. Finally, we derive empirically testable consequences based on our considerations to guide future research. |
35950518 | Interaction of the insecticide bioallethrin with human hemoglobin: biophysical, | Bioallethrin is an insecticide that is widely used in households resulting in human exposure. Bioallethrin is cytotoxic to human erythrocytes. Here we have studied the interaction of bioallethrin with human hemoglobin (Hb) using |
35950524 | Tractable Bayes of skew-elliptical link models for correlated binary data. | Correlated binary response data with covariates are ubiquitous in longitudinal or spatial studies. Among the existing statistical models, the most well-known one for this type of data is the multivariate probit model, which uses a Gaussian link to model dependence at the latent level. However, a symmetric link may not be appropriate if the data are highly imbalanced. Here, we propose a multivariate skew-elliptical link model for correlated binary responses, which includes the multivariate probit model as a special case. Furthermore, we perform Bayesian inference for this new model and prove that the regression coefficients have a closed-form unified skew-elliptical posterior with an elliptical prior. The new methodology is illustrated by an application to COVID-19 data from three different counties of the state of California, USA. By jointly modeling extreme spikes in weekly new cases, our results show that the spatial dependence cannot be neglected. Furthermore, the results also show that the skewed latent structure of our proposed model improves the flexibility of the multivariate probit model and provides a better fit to our highly imbalanced dataset. |
35950525 | Health technology assessment: A matter of facts and values. | The unique task and contribution of health technology assessment (HTA) is to help identify those health technologies and their uses that are most likely to preserve and restore a population's health in a way that is consonant with its values, including, for example, equity and access to high-quality care (1). Such a task is challenging for at least two reasons. First, because of the vast and constantly evolving number and diversity of health technologies and their applications. Second, because of the usual wide variety peting views munities and their stakeholders regarding what strategies are likely to be conducive to the goal of preserving and restoring population health. Although perhaps tempting, it would be a grave mistake to hold that the controversies that result from peting views can be resolved by taking recourse to the facts only. For such controversies are usually fueled by different notions of health and disease and different specifications of values such as equity and individual and collective responsibility for health. For this reason, they cannot be resolved in a satisfactory way without also addressing those normative issues and their interplay with empirical analysis. |
35950526 | [Community health nursing in urban setting (CoSta): Development of a care concept for people with chronic conditions in primary care]. | Community health nursing in urban setting (CoSta): Development of a care concept for people with chronic conditions in primary care |
35950527 | A review of sugar beet pectin-stabilized emulsion: extraction, structure, interfacial self-assembly and emulsion stability. | In recent years, sugar beet pectin as a natural emulsifier has shown great potential in food and pharmaceutical fields. However, the emulsification performance depends on the molecular structure of sugar beet pectin, and the molecular structure is closely related to the extraction method. This review summarizes the extraction methods of pectin, structure characterization methods and the current research status of sugar beet pectin-stabilized emulsions. The structural characteristics of sugar beet pectin (such as degree of methylation, degree of acetylation, degree of blockiness, molecular weight, ferulic acid content, protein content, neutral sugar side chains, etc.) are of great significance to the emulsifying activity and stability of sugar beet pectin. Compared with traditional hot acid extraction method, ultrasonic-assisted extraction, microwave-assisted extraction, subcritical water-assisted extraction, induced electric field-assisted extraction and enzyme-assisted extraction can improve the yield of sugar beet pectin. At the same pared with harsh extraction conditions (too high temperature, too strong acidity, too long extraction time, etc.), mild extraction conditions can better preserve these emulsifying groups in sugar beet pectin molecules, which are beneficial to improve the emulsifying properties of sugar beet pectin. In addition, the interfacial self-assembly behavior of sugar beet pectin induced by the molecular structure is crucial to the long-term stability of the emulsion. This review provides a direction for extracting or modifying sugar beet pectin with specific structure and function, which is instructive for finding alternatives to gum arabic. |
35950528 | Do Salient Social Norms Moderate Mortality Salience Effects? A (Challenging) Meta-Analysis of Terror Management Studies. | Terror management theory postulates that mortality salience (MS) increases the motivation to defend one's cultural worldviews. How that motivation is expressed may depend on the social norm that is momentarily salient. Meta-analyses were conducted on studies that manipulated MS and social norm salience. Results based on 64 effect sizes for the hypothesized interaction between MS and norm salience revealed a small-to-medium effect of |
35950532 | Editorial: Environmental conditions for growing healthy children. | The deleterious developmental effects of exposure to early adversity have been well documented in the scientific literature. The finding that poverty in early childhood is among the most robust predictors of a range of poor developmental es has been well known for decades. More recently, evidence that early experiences of poverty and related forms of adversity negatively impact the function and structure of the developing brain have also emerged. Retrospective studies linking poor physical health es to adverse childhood experiences (ACES) highlighted the more global nature of these risk factors to wellbeing and follow-up prospective studies have since confirmed these findings (Brown et al., 2009). Alternatively, it has e increasingly clear that early experiences of stimulation, nurturance, and caregiver support promote positive development es with emerging evidence for tangible impacts on neurodevelopment in humans (Luby et al., 2021). However, the scientific and public munity has yet to synthesize these related bodies of data and develop a plan of action related to their over-reaching and global importance to protecting and promoting childhood health and development more generally despite numerous calls to do just that (Farah, 2018; Luby et al., 2020). |
35950531 | Functional and safety characterization of beneficial vaginal lactic acid bacteria for the design of vaginal hygiene products. | The aim was plement the evaluation of functional and safety properties of beneficial vaginal lactic acid bacteria to select the most adequate strains as potential probiotics for their inclusion in a vaginal probiotic formula. |
35950523 | Molecular insights into the structural and dynamical changes of calcium channel TRPV6 induced by its interaction with phosphatidylinositol 4,5-bisphosphate. | Transient receptor potential vanilloid subfamily member 6 (TRPV6) is an epithelial calcium channel that regulates the initial step of the transcellular calcium transport pathway. TRPV6 is expressed in the kidney, intestine, placenta, and other tissues, and the dysregulation of the channel is implicated in several human cancers. It has been reported that phosphatidylinositol 4,5-bisphosphate (PIP |
35950535 | Potent preclinical activity of FLT3-directed chimeric antigen receptor T-cell immunotherapy against | Chimeric antigen receptor (CAR) T-cell immunotherapies targeting CD19 or CD22 induce remissions in the majority of patients with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL), although relapse due to target antigen loss or downregulation has emerged as a major clinical dilemma. Accordingly, great interest exists in developing CAR T cells directed against alternative leukemia cell surface antigens that may help to e immunotherapeutic resistance. The fms-like tyrosine kinase 3 receptor (FLT3) is constitutively activated via FLT3 mutation in acute myeloid leukemia (AML) or wild-type FLT3 overexpression in KMT2A (lysine-specific methyltransferase 2A)-rearranged ALL, which are associated with poor clinical es in children and adults. We developed monovalent FLT3-targeted CAR T cells (FLT3CART) and bispecific CD19xFLT3CART and assessed their anti-leukemia activity in preclinical models of FLT3-mutant AML and KMT2A-rearranged infant ALL. We report robust in vitro FLT3CART-induced cytokine production and cytotoxicity against AML and ALL cell lines with minimal cross-reactivity against normal hematopoietic and non-hematopoietic tissues. We also observed potent in vivo inhibition of leukemia proliferation in xenograft models of both FLT3-mutant AML and KMT2A-rearranged ALL, including a post-tisagenlecleucel ALL-to-AML lineage switch patient-derived xenograft model pairing. We further demonstrate significant in vitro and in vivo activity of bispecific CD19xFLT3CART against KMT2Arearranged ALL and posit that this additional approach might also diminish potential antigen escape in these high-risk leukemias. Our preclinical data credential FLT3CART as a highly effective immunotherapeutic strategy for both FLT3- mutant AML and KMT2A-rearranged ALL which is poised for further investigation and clinical translation. |
35950534 | Molecular monitoring of T-cell kinetics and migration in severe neurotoxicity after real-world CD19-specific chimeric antigen receptor T cell therapy. | CD19-specific chimeric antigen receptor (CD19-CAR) T-cell therapies mediate durable responses in late-stage B-cell malignancies, but can plicated by a potentially severe immune effector cell-associated neurotoxicity syndrome (ICANS). Despite broad efforts, the precise mechanisms of ICANS are not entirely known, and resistance to current ICANSdirected therapies (especially corticosteroids) has been observed. Recent data suggest that inflammatory cytokines and/or targeting of cerebral CD19-expressing pericytes can disrupt the blood-brain barrier and facilitate influx of immune cells, including CAR T cells. However, specific tools for CD19-CAR T-cell analysis within often minute samples of cerebrospinal fluid (CSF) are not broadly available. Here, we applied our recently developed digital polymerase chain reaction assays to monitor CD19-CAR T-cell kinetics in CSF and blood in real-world patients with neurotoxicity. Consistently, we observed a CAR T-cell enrichment within CSF in ICANS patients with further progressive accumulation despite intense corticosteroid- containing immuno-chemotherapies in a subset of patients with prolonged and therapy-resistant grade 3-4 neurotoxicity. We used next-generation T-cell receptor-b sequencing to assess the repertoire of treatment-refractory cells. Longitudinal analysis revealed a profound skewing of the T-cell receptor repertoire, which at least partly reflected selective expansion of infused T-cell clones. Interestingly, a major fraction of eventually dominating hyperexpanded T-cell clones were of non-CAR T-cell derivation. These findings hint to a role of therapy-refractory T-cell clones in severe ICANS development and prompt future systematic research to determine if CAR T cells may serve as 'door openers' and to further characterize both CAR-positive and non-CAR T cells to interrogate the transcriptional signature of these possibly pathologic T cells. |
35950533 | Osteoprogenitor SFRP1 prevents exhaustion of hematopoietic stem cells via PP2A-PR72/130-mediated regulation of p300. | Remodeling of the bone marrow microenvironment in chronic inflammation and in aging reduces hematopoietic stem cell (HSC) function. To assess the mechanisms of this functional decline of HSC and find strategies to counteract it, we established a model in which the Sfrp1 gene was deleted in Osterix+ osteolineage cells (OS1Δ/Δ mice). HSC from these mice showed severely diminished repopulating activity with associated DNA damage, enriched expression of the reactive oxygen species pathway and reduced single-cell proliferation. Interestingly, not only was the protein level of Catenin beta-1 (bcatenin) elevated, but so was its association with the phosphorylated co-activator p300 in the nucleus. Since these two proteins play a key role in promotion of differentiation and senescence, we inhibited in vivo phosphorylation of p300 through PP2A-PR72/130 by administration of IQ-1 in OS1Δ/Δ mice. This treatment not only reduced the b-catenin/phosphop300 association, but also decreased nuclear p300. More importantly, in vivo IQ-1 treatment fully restored HSC repopulating activity of the OS1Δ/Δ mice. Our findings show that the osteoprogenitor Sfrp1 is essential for maintaining HSC function. Furthermore, pharmacological downregulation of the nuclear b-catenin/phospho-p300 association is a new strategy to restore poor HSC function. |
35950537 | Efficacy of | Patients undergoing chemotherapy suffer from taste disorders that affect the quality of life (QOL). In this study, a randomized, double-blind, placebo-controlled trial was conducted to explore the effectiveness of AHCC |
35950538 | Prognostic value of right atrial pressure-corrected cardiac power index in cardiogenic shock. | The pulmonary artery catheter (PAC)-derived cardiac power index (CPI) has been found of prognostic value in cardiogenic shock (CS) patients. The original CPI equation included the right atrial pressure (RAP), accounting for heart filling pressure as a determinant of systolic myocardial work, but this term was subsequently omitted. We hypothesized that the original CPI formula (CPI |
35950530 | Giloy: a potential anti-COVID-19 herb with propitious pharmacological attributes: a short review. | Plant-based medicine actually restores the balance in the body instead of treating the source of the disease. The strain of coronavirus (SAR-CoV-2) going to be more serious due to the lack of a reliable treatment option. Holistic treatment for this disease is in the form of Ayurveda as traditional medicine. As the infection of coronavirus is spreading like a wildfire, so the one way to fight is 'immunity'. Building immunity is the only way to stay safe and healthy and prepared themselves for the ongoing pandemic. In the current scenario, good immunity safeguard us from disease progression and prevention from this deadly virus. Giloy herb came into the limelight after the start of the COVID-19 pandemic due to its immunomodulatory and antiviral activity. The genome sequencing of Giloy is proved to be a breakthrough for controlling the COVID-19.Communicated by Ramaswamy H. Sarma. |
35950539 | Predicting tubular heat exchanger efficiency reduction caused by marine biofilm adhesion using CFD simulations. | A novel efficiency reduction model to tubular heat exchanger based on heat transfer losses by biofilm adhesion is proposed, which included a modified equation based on the real data-dependent time, seawater, hydrodynamics and heat transfer resistance putational fluid dynamics (CFD). The biofilm growth model based on Verhulst model and experimental data has been obtained and simulated in a CFD software tool to analyze the tubular heat exchanger performance prediction cooled by seawater. The biofilm CFD model with appropriate fit, and the correlation coefficient (R2) values are between 0.97 and 0.99, was validated by experimental data obtained at different flow velocity. The final results of in/outlet difference temperatures were from 3.9 °C to 2.2 °C for different flow velocity with R2 > 0.97. The simulation results demonstrate that the novel CFD model is capable of predicting the efficiency losses during the development period of biofilm growth in in open-loop cooling seawater systems. |
35950540 | Fifteen Years after a 10-year Retrospective: The State of Health Mass Mediated Campaigns. | In 2006, a 10-year retrospective of successful mass mediated munication campaigns reviewed the field and highlighted strategies for successful campaigns. In the 15 years since the retrospective, there have been dramatic changes in the media environment and advances in munication research. In this article, we describe changes in the munication media landscape and in our understanding of mass mediated munication campaigns in the 15 years since the retrospective. Although the media environment has shifted, we argue that effective principles of munication have remained relatively constant. We note significant advances in technology since the previous retrospective that can further advance munication campaigns, with new technologies offering promise as channels for munication campaigns as well as for campaign planning. We also mend that campaign researchers report in detail on their use of theory, audience segmentation, channel selection, and the role of formative research when describing campaign efforts; municators continue to develop frameworks that integrate principles of effective campaign design; and that additional research focus on understanding how technology can be effectively incorporated into campaign planning, distribution, and evaluation. |
35950541 | Sleep regularity in athletes: Comparing sex, competitive level and sport type. | This study aims to describe the athletes' sleep regularity using the Sleep Regularity Index (SRI) and determine whether factors, such as petitive level and sport type, could affect the sleep/wake rhythm. It is a descriptive, cross-sectional study consisting of 172 athletes (25 ± 7 y old; 45 women). peted in team sports and 99 in individual sports. Furthermore, peted in the international level, 95 in the national and 21 in the regional. We recorded the SRI values for at least 5 d via continuous actigraphy. We recorded a mean SRI value of 73 ± 12. We found no significant differences between athletes' sleep parameters in relation to sleep regularity. Furthermore, SRI data showed no correlations (Spearman's |
35950542 | Measuring a Patient's understanding of their prognosis: An exploratory analysis. | In patients with cancer across the illness trajectory, treatment decisions are often influenced by one's perception of their prognosis (i.e., curability of disease, life expectancy, quality of life). However, research on how patients understand their prognosis (i.e., prognostic understanding) has been limited by simplistic measurement tools that fail to capture plexity of the construct. This study describes the initial development of a measure of prognostic understanding: the Prognostic Understanding Perceptions Scale (PUPS) for use in patients with advanced cancer. |
35950543 | Remote blood pressure monitoring with a wearable photoplethysmographic device in patients undergoing coronary angiography: the senbiosys substudy. | The purpose of this study is to evaluate the accuracy of the Senbiosys device in measuring blood pressure (BP) by photoplethysmography (PPG) in patients undergoing coronary angiography. |
35950544 | Lethal toxicity induced by combined ingestion of dietary acetic acid and carbamazepine. | Acetic acid is an organic acid that can be used in the food industry, which normally has an insignificant rate of adverse reactions when used rationally. However, irrational use can cause serious toxic effects and even death. In this context, the case of a death of a 52-year-old woman, involving the suspected voluntary use of food acetic acid, is presented, while toxicological and histopathological aspects were addressed for death mechanism elucidation. In this case, the pH value of 6.75 in blood, has shown severe metabolic acidosis after the ingestion of the large quantity of dietary acetic acid - about a liter. Also, the victim suffers from mental illness, carbamazepine being one of the treatment drugs. Liver damage, demonstrated by histopathological examination may be a consequence of both massive accumulation of carbamazepine in the liver and toxicity of food acetic acid. In conclusion, the hepatotoxicity induced by high level of carbamazepine was suspected of increasing the risk of multiple organ failure, in the context of acetic acid acute toxicity, highlighting the particularities of the case. |
35950547 | Association of left atrial enlargement and increased left ventricular wall thickness with arrhythmia recurrence after cryoballoon ablation for atrial fibrillation. | Left atrial enlargement (LAE) predicts atrial fibrillation (AF) recurrence after cryoballoon-based pulmonary vein isolation (CB). Increased left ventricular wall thickness (LVWT) is pathophysiologically associated with LAE and atrial arrhythmias. |
35950546 | The First Class of Small Molecules Potently Disrupting the YAP-TEAD Interaction by Direct Competition. | Inhibition of the YAP-TEAD protein-protein interaction is an attractive therapeutic concept under intense investigation with the objective to treat cancers associated with a dysregulation of the Hippo pathway. However, owing to the very extended surface of interaction of the two proteins, the identification of small drug-like molecules able to efficiently prevent YAP from binding to TEAD by petition has been elusive so far. We disclose here the discovery of the first class of small molecules potently inhibiting the YAP-TEAD interaction by binding at one of the main interaction sites of YAP at the surface of TEAD. These inhibitors, providing a path forward to pharmacological intervention in the Hippo pathway, evolved from a weakly active virtual screening hit advanced to high potency by structure-based design. |
35950545 | The prevalence of psychological disorders among cancer patients during the COVID-19 pandemic: A meta-analysis. | We aimed to assess the prevalence rate (PR) of depression, anxiety, posttraumatic stress disorder (PTSD), insomnia, distress, and fear of cancer progression/recurrence among patients with cancer during the COVID-19 pandemic. |
35950548 | Ribbon-Type Boron-Doped Polycyclic Aromatic Hydrocarbons: Conformations, Dynamic Complexation and Electronic Properties. | Molecular ribbons (MRs), one-dimentional topological polycyclic aromatic hydrocarbons (PAHs), are of importance for synthetic chemistry and material sciences. Herein, we disclose an effective strategy to develop boron-doped MRs, i.e. photochemical cyclization on conjugated organoboranes for rapid π-extension. A series of ribbon-type boron-doped PAHs that own multiple cove edges were synthesized using Mallory photoreaction in solution. Two of them feature isomeric C |
35950549 | Toughened Hydrogels for 3D Printing of Soft Auxetic Structures. | Materials with negative Poisson's ratio have attracted considerable attention and offered high potential applications as biomedical devices due to their ability to expand in every direction when stretched. Although negative Poisson's ratio has been obtained in various base materials such as metals and polymers, there are very limited works on hydrogels due to their intrinsic brittleness. Herein, we report the use of methacrylated cellulose nanocrystals (CNCMAs) as a macro-cross-linking agent in poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels for 3D printing of auxetic structures. Our developed CNCMA-pHEMA hydrogels exhibit significant improvements in mechanical properties, which is attributed to the coexistence of multiple chemical and physical interactions between the pHEMA and CNCMAs. Structures printed by using CNCMA-pHEMA hydrogels show auxetic behavior with greatly enhanced toughness and pared to the hydrogel with a traditional cross-linking agent. Such strong and tough auxetic hydrogels would contribute toward establishing advanced flexible implantable devices such as biodegradable oesophageal self-expandable stents. |
35950550 | Understanding Type 2 Diabetes Self-Management in Racial/Ethnic Minorities: Application of the Extended Parallel Processing Model and Sensemaking Theory in a Qualitative Study. | The purpose of the study was to understand the role of perceived disease threat and self-efficacy in type 2 diabetes (T2DM) patients' self-management by using the extended parallel processing model (EPPM) and sensemaking theory. |
35950552 | Optimized Reconstruction Procedure of Photoacoustic Imaging for Reflection Artifacts Reduction. | Photoacoustic (PA) imaging technology is of some value in medical diagnoses such as breast cancer detection, vasculature imaging, and surgery navigating. While as most imaging objects are bounded, the received RF signals consist of the direct-arrived signals (DAS) from the PA sources and the boundary-reflected signals (BRS). The undesired BRS will severely impair the quality during the image reconstruction. They will bring in many artifacts and confuse the actual shape and location of the PA sources. We improved the reconstruction procedure by removing the BRS before the regular reconstruction process to suppress those artifacts. To verify our proposed method, pared the results of the conventional and optimized procedures experimentally. In terms of qualitative observation, the reconstructed images by the optimized procedure illustrate fewer artifacts and more accurate shapes of the PA sources. To quantitatively evaluate the traditional and the optimized imaging procedure, we calculated the Distribution Relative Error (DRE) between each experiment result and its standard drawing of the phantoms. For both phantoms and the ex-vivo sample, the DREs of reconstruction result by the optimized reconstruction procedure decrease significantly. The results suggest that the optimized reconstruction process can effectively suppress the reflection artifacts and improve the shape accuracy of the PA sources. |
35950554 | Cytotoxic effect and induction of apoptosis in human cervical cancer cells by a wood extract from | Cervical cancer ranks fourth in incidence among women worldwide. Cisplatin is currently the first-line drug of treatment for cervical cancer; however, it causes serious adverse effects. Therefore, it is crucial to explore natural products for cervical cancer treatment. |
35950553 | Comparing the effect of administering gelatin-low dose albumin versus albumin on renal function in liver transplantation: A randomized clinical trial. | Acute kidney injury (AKI) is plication after liver transplantation (LT) that is independently associated with an increased risk of morbidity and mortality. This study aimed to evaluate the effects of administering gelatin-low dose albumin versus albumin on renal function and other early es in LT. |
35950558 | Race/Ethnicity and Relationship Stereotypes in Child Sex Abuse Cases. | Child sex abuse (CSA) is a specific category of crime for which the presumption of guilt may be particularly high, especially for defendant categories stereotypically associated with the crime. The current study utilized survey methodology to examine the magnitude of the presumption of guilt for CSA, as well as stereotypes associating perpetrator race and relationship to the victim with likelihood of CSA. Participants ( |
35950555 | Delay in the initiation of adjuvant chemotherapy in patients with breast cancer with mastectomy with or without immediate breast reconstruction. | Patients with breast cancer undergoing mastectomy should be offered the option of immediate breast reconstruction (IBR). The aim of this retrospective study was to assess whether there is a delay in the initiation of adjuvant chemotherapy in patients undergoing mastectomy with or without IBR. |
35950556 | Efficacy of PET/CT in diagnosis of regional lymph node metastases in patients with colorectal cancer: retrospective cohort study. | Endoscopic and transanal local resection without lymph node dissection are treatment options for patients with a low risk of lymph node metastasis; however, some patients might have undiagnosed lymph node metastases before surgery. This retrospective study aimed to evaluate the efficacy of preoperative PET/CT for diagnosing regional lymph node metastasis. |
35950559 | Conformer Selection Upon Dilution with Water: The Fascinating Case of Liquid Ethylene Glycol Studied via Molecular Dynamics Simulations. | The aqueous solution of ethylene glycol (EG) is a binary liquid mixture that displays rich conformational and structural behaviour, which has not yet been adequately explored through atomistic molecular dynamics simulations. Herein, employing an accurate force field for EG, several physical properties of this solution are calculated to be in quantitative agreement with experimental data. While 79 % of molecules in neat liquid EG exist with their central OCCO dihedral in the gauche state, this fraction increases to 89 % in the dilute aqueous solution, largely in response to the increase in the static dielectric constant of the solution from that of neat liquid EG. The increase in gauche conformers increases the mean dipole moment of EG molecules in the solution which is additionally contributed by specific conformational states of the two terminal HOCC dihedral angles. |
35950560 | The Roles of Busyness and Daily Routine in Medication Management Behaviors Among Older Adults. | Busyness (the density of activities) and daily routine (patterns of organizing time) are two understudied factors that likely impact medication-taking behaviors. We examined the association between busyness and routine with medication adherence (MA) in 405 older adults with adequate cognition using multivariable models. The final model included an interaction term between daily routine and busyness. MA scores (measured by the ASK-12, higher scores mean more barriers to adherence) were higher for individuals reporting low and moderate levels of daily routine versus those with high daily routine. MA scores were higher for individuals reporting moderate and high busyness versus those reporting low busyness. The busyness/routine interaction term was significant for MA; among highly busy individuals, those with high daily routine had lower MA scores than those with low routine. A daily routine may be a modifiable factor for improving MA among older adults, particularly among those with busy lives. |
35950562 | Structure-guided approach on the role of substitution on amide-linked bipyrazoles and its effect on their anti-inflammatory activity. | A structure-guided modelling approach using COX-2 as a template was used to investigate the effect of replacing the chloro atom located at the chlorophenyl ring of amide-linked bipyrazole moieties, aiming at attaining better anti-inflammatory effect with a good safety profile. Bromo, fluoro, nitro, and methyl groups were revealed to be ideal candidates. Consequently, new bipyrazole derivatives were synthesised. The |
35950561 | Investigation of the Second Harmonic Generation at the Water-Vacuum Interface by Using Multi-Scale Modeling Methods. | The Sequential Quantum Mechanics/Molecular Mechanics scheme has been enacted to perform a systematic investigation of the polarizability (α) and first hyperpolarizability (β) responses at the water-vacuum interface. After performing classical molecular dynamics simulations to provide snapshots of the structures, quantum chemistry calculations of the linear and nonlinear optical responses have been performed for clusters of five water molecules at the time-dependent DFT level bination with different embedding schemes, ranging from point charges to polarizable point charges, with and without local field effects. When going from the bulk to the interface, the main observations of these calculations pass i) a modest increase of the average polarizability but an increase by about a factor of two of its anisotropy, ii) an increase by about 20 % of the β |
35950563 | Flexible Pressure Sensors with Combined Spraying and Self-Diffusion of Carbon Nanotubes. | High-performance wearable sensors are required for applications in medical health and human-machine interaction, but their application has limited owing to the trade-off between sensitivity, pressure range, and durability. Herein, we propose bined spraying and self-diffusion process of carbon nanotubes (CNTs) to balance and improve these parameters with the CNTs spontaneously diffusing into the film surface before the film curing. The obtained sensor not only achieves high sensitivity (155.54 kPa |
35950564 | Myocardial injury in stress echocardiography: Comparison of dobutamine, dipyridamole and dynamic stressors-single center study. | In stress echocardiography (SE), dipyridamole (DIP) and dynamic stress (ExSE) are reported as being safer than dobutamine stress echocardiography (DSE). We investigated whether monly used stressors cause myocardial injury, measured by high sensitivity troponin T (hsTnT). |
35950565 | A Sandwich-Type Electrochemical Immunosensor for Insulin Detection Based on Au-Adhered Cu | Rapid, accurate, and sensitive insulin detection is crucial for managing and treating diabetes. A simple sandwich-type electrochemical immunosensor is engineered using gold nanoparticle (AuNP)-adhered metal-organic framework-derived copper-zinc hollow porous carbon nanocubes (Au@Cu |
35950566 | LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA | Selpercatinib, a first-in-class, highly selective and potent central nervous system-active RET kinase inhibitor demonstrated clinically meaningful activity with manageable toxicity in pretreated and treatment-naive advanced/metastatic |
35950568 | CD 4 | P-type atypical lymphocytes may play important roles in the aetiology and therapy of schizophrenia. However, there is merely a direct immunological characterisation of it. The aim of this study is to explore the surface antigens of these cells and parative ultrastructure in schizophrenia. |
35950567 | 3-Arylcoumarin inhibits vascular calcification by inhibiting the generation of AGEs and anti-oxidative stress. | This work aims to screen drugs for preventing and treating vascular calcification. |
35950570 | Clomiphene citrate priming increases sensitivity during ovarian stimulation in poor ovarian responders undergoing | This single-centre retrospective cohort study aimed to investigate whether a clomiphene citrate (CC) priming protocol could increase ovarian sensitivity in poor ovarian responders. It included 294 patients (374 ovarian stimulation cycles). Of these, 193 cycles were treated by a CC priming antagonist protocol (study group) and 181 by the classical flexible gonadotropin-releasing hormone antagonist protocol (control group). Stimulation data and laboratory and clinical es pared between the groups. The results showed that in the study group, total gonadotropin dosage and dosage per follicle were considerably lower, the follicle-to-oocyte index was significantly higher, and the gonadotropin duration was shorter. After adjusting for potential confounders, multivariate regression analysis showed that cumulative ongoing pregnancy parable between the groups (adjusted odds ratio: 0.761, 95% confidence interval: 0.300-1.933, |
35950569 | Development of a predictive model for bovine leukemia virus proviral load. | There is currently mercially available method in Canada to identify bovine leukemia virus (BLV)-positive cows with high proviral load (PVL). |
35950572 | Colorectal Cancer and Microbiota Modulation for Clinical Use. A Systematic Review. | Colorectal cancer (CRC) is one of the top contributors to the global burden of cancer incidence and mortality, with both genetic and environmental factors contributing to its etiology. Environmental factors may be the cause of up to 60% of the risk of developing CRC, with gut microbiota being a crucial modifiable risk factor. The microbial ecosystem plays a vital role in CRC prevention and antitumoral response through modulation of the immune system and production of short-chain fatty acids. Numerous approaches have been followed to modify the gut microbiota in order to reduce the risk of cancer development, improve treatment efficacy, and reduce side effects. This study aims to perform a systematic analysis of the published literature to elucidate whether microbiota modulation through pre-, pro-, and symbiotic treatment and/or nutritional intervention can be beneficial for patients diagnosed with CRC. Our analysis finds that some prebiotics, mainly in the form of oligo- and polysaccharides, probiotics such as lactic strain producers of short-chain fatty acids, and consumption of a Mediterranean plant-based diet may be beneficial for patients diagnosed with CRC. However, there is a need for clinical data which evaluate the modulation of gut microbiota in a safe and effective manner. |
35950573 | Responses of the public towards the government in times of crisis. | We experimentally investigate how and when the public responds to government actions during times of crisis. Public reactions are shown to follow different processes, depending on whether government performs in exemplary or unsatisfactory ways to the COVID-19 pandemic. The 'how' question is addressed by proposing that negative moral emotions mediate public reactions to bad government actions, and positive moral emotions mediate reactions to good government actions. Tests of mediation are conducted while taking into account attitudes and trust in the government as rival hypotheses. The 'when' question is studied by examining self-regulatory moderators governing the experience of moral emotions and their effects. These include conspiracy beliefs, political ideology, attachment coping styles and collective values. A total of 357 citizens of a representative sample of adult Norwegians were randomly assigned to two experimental groups and a control group, plaining, putting pressure on the government pliance to Covid-19 policies were dependent variables. The findings show that negative moral emotions mediate the effects of government doing badly plaining and pressuring the government, with conspiracy beliefs moderating the experience of negative moral emotions and attachment coping moderating the effects of negative moral emotions. The results also show that positive moral emotions mediate the effects of government doing well pliance with COVID-19 regulations, with political ideology moderating the experience of positive moral emotions and collective values moderating the effects of positive moral emotions. |
35950574 | Could serum endocannabinoid and N-acylethanolamine levels be important in bipolar disorder? | The endocannabinoid system (ECS) is a critical important neuromodulatory system that interacts with many neurohormonal and neurotransmitter systems in the brain. It plays a pivotal role in emotional responses and mood regulation. The ECS is related with psychotic disorders, depression, anxiety and autism. In this study, we aimed to investigate whether there is any relationship between endocannabinoid and N-acylethanolamine levels with bipolar disorder. |
35950575 | Precarity and preparedness during the SARS-CoV-2 pandemic: A qualitative service evaluation of maternity healthcare professionals. | The SARS-CoV-2 pandemic has devastated populations, posing unprecedented challenges for healthcare services, staff and service-users. In the UK, rapid reconfiguration of maternity healthcare service provision changed the landscape of antenatal, intrapartum and postnatal care. This study aimed to explore the experiences of maternity services staff who provided maternity care during the SARS-CoV-2 pandemic to inform future improvements in care. |
35950576 | THALASSEMIA in ASIA 2021: Thalassemia in Guangxi Province, People's Republic of China. | Guangxi Province is located in the southwest of the People's Republic of China (PRC). The province has a population of 50.12 million with a birth rate of 13.31%. Thalassemia is a major health problem in Guangxi Province. About 20.0-25.0% of the population carries thalassemia genes, which is acknowledged to be the highest prevalence in China. National and provincial programs for thalassemia prevention and control have been introduced. Premarital screening and prenatal diagnosis (PND) for the prevention of thalassemic fetuses are available. Blood transfusions, iron chelation therapy, and stem cell transplantation are also available for transfusion-dependent thalassemic patients. |
35950577 | Thalassemia in Malaysia. | Malaysia is a multi-ethnic prising of Malays and other indigenous groups (67.4%), Chinese (24.6%), Indians (7.3%) and others (0.7%). Thalassemia, which includes α- and β-thalassemia (α- and β-thal), is one of the mon genetic disease in Malaysia. Between 4.5 and 5.0% of the Malaysian population were reported to be carriers of this disease and 3.0-40.0% were Hb E (c.79G>A) carriers. In 2013, the Malaysian Thalassaemia Registry reported a total of 5712 registered thalassemia patients, of which 1847 had Hb E/β-thal and 2329 had β-thal major (β-TM). Out of the total number of registered thalassemia patients, prise 62.0%, Chinese 13.0% and Kadazan-Dusun 13.0%. There were mon deletions and mutations of the α-thal gene, including three double gene deletions, two single gene deletions, and three nondeletional mutations. The five types of β-thal mutations generally found in the Malay ethnic group were codon 19 (A>G) (or Hb Malay ( |
35950578 | Thalassemia in Viet Nam. | The population of Viet Nam, is 96.2 million, of which 13.8% are carriers of thalassemia genes. Thalassemia/hemoglobinopathies carriers exist at different frequencies in all 54 ethnic groups of the country. Gene carrier rate and globin gene mutation rate varies ethnically and topographically. The ethnic groups in the Northern Highland region have high rates of α |
35950579 | Current Status of Thalassemia in Lao People's Democratic Republic. | Thalassemia is a major public health and economical burden in Lao People's Democratic Republic (Lao PDR). This study is aiming to elaborate the current situation of Thalassemia in Laos. α- and β-thalassemia (α- and β-thal) includes mon Hb S ( |
35950580 | Thalassemia in Indonesia. | Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry β-thalassemia (β-thal) and 2.6-11.0% of the population carry α-thalassemia (α-thal). It is estimated that around 2500 babies are born with β-thal major (β-TM) each year. At present, the cornerstone of treatment for β-TM in Indonesia remains supportive, including blood transfusions and iron chelation therapy. Hemovigilance systems in some cities are poor and it increases the risk of transfusion-transmitted infections and transfusion reactions. The availability of iron chelators remains uncertain, even in some rural areas, iron chelators do not exist. The poor adherence to iron chelation therapy and maintaining pretransfusion hemoglobin (Hb) levels above 9.0 g/dL are still a major issue in Indonesia. The cost of blood transfusion and iron chelation are covered by national health insurance. In line with the rise of life expectancy, the financial burden of thalassemia in Indonesia is increasing sharply. Thus, optimizing preventive programs may be the most suitable option for the current thalassemia condition in Indonesia. |
35950581 | Thalassemia in the Philippines. | For an archipelago that has a rich history of trade with overseas merchants and colonial rule, the Philippine Islands are models of ethnic and cultural diversity, including hereditary blood disorders such as hemoglobinopathies. Pending a prehensive national screening program, available cluster data provides evidence of the prevalence of thalassemia in the country. The National Blood Services Act of 1994 was enacted to promote voluntary blood donation to address the supply of blood products but falls short in addressing the immense blood transfusion requirements of the munity. Iron overload monitoring and management is a considerable challenge due to high cost of laboratory tests and iron chelators on top of minimal health insurance coverage for the majority of Filipino patients with thalassemia. Continuous engagement with the thalassemia munity and multi sectoral efforts are the means to ensure sustained improvement in the delivery of care. |
35950582 | Thalassemia in Pakistan. | The estimated population of Pakistan is approximately 225,633,392 (225 million). The healthcare delivery system of Pakistan plex because it includes healthcare subsystems operated by both the federal government and the provincial government. In Pakistan β-thalassemia (β-thal) trait frequency ranges between 5.0-7.0%, thus, there are more than 10 million carriers in the country; and every year, around 5000 children are diagnosed to carry β-thal major (β-TM) in Pakistan. No standard management protocols exist and blood transfusion remains the mainstay of management. Most of the population belong to the lower socioeconomic strata, family units are large and therefore cannot afford to pay for treatment and management of their thalassemic child. Currently in Pakistan, at the national level, not a single thalassemia prevention program is available to counter this disease. However, at the provincial level some initiatives have been taken, legislation has been approved for premarital screening in Sindh, Khyber Pakhtunkhwa (KPK) and Baluchistan, but implementation remains the issue. |
35950584 | Thalassemia Status in Cambodia. | The population of Cambodia (in 2019) was approximately 16 million with an annual growth rate of 1.4% in which the prevalence of hemoglobinopathies was estimated at about 40.0% (range 30.0-50.0%) to be carriers, and 2240 annual births for β-thalassemia major (β-TM). The overall prevalence of β-thalassemia (β-thal) and α-thalassemia (α-thal) were 40.9 and 39.6%, respectively. Currently, the specific epidemiological data regarding the abnormal gene frequency/mutations among different ethnic groups is unknown. In 2011, national guidelines for the Clinical Management of Patients with Thalassemia in Cambodia were developed and published by the Ministry of Health (MoH). Packed red cells (PRCs) are available at most referral hospitals (provincial hospitals). Oral iron chelators [deferiprone (DFP) and deferasirox (DFX)] are only available from a private pany. The future needs for Cambodia are to develop a national policy on the prevention or control of β-thal and α-thal, and a national registry of patients with thalassemia, to determine the gene frequency of α- and β-thal in different regions of the country, and to place the iron chelators on the list of essential medicines. |
35950585 | Thalassemia in Asia 2021 Overview of Thalassemia and Hemoglobinopathies in Bangladesh. | Bangladesh is a country with a population of 160 million with a gross national e per capita of US$1580.00. The major health problems in Bangladesh include acute respiratory infection, pneumonia, dengue fever, malaria and water-borne diseases. The health care system in Bangladesh is divided into primary secondary and tertiary levels, with each level having their own breakdown of available hospital beds and other treatment facilities. Thalassemia is a major health problem in Bangladesh. There are two types of thalassemia in Bangladesh: β-thalassemia (β-thal) and Hb E ( |
35950586 | Thalassemia in Sri Lanka. | The island nation of Sri Lanka with 22 million people (in 2020) has an estimated 2000 patients with severe thalassemia. The majority have β-thalassemia (β-thal) major (β-TM), and Hb E ( |
35950587 | Thalassemia in India. | Management and control of hemoglobinopathies are a challenge in India where 67.0% of people reside in rural regions. The GDP spent on health is one of the lowest (1.3%) resulting in high out-of-pocket expenses. The β-thalassemias are prevalent with an estimated 7500-12000 new births each year. Hb S ( |
35950588 | Clinical Severity of β-Thalassemia Pediatric Patients in Myanmar. | β-Thalassemia (β-thal) is highly prevalent in Myanmar, but limited data are available on the molecular basis and the clinical manifestations in Myanmar patients. In this study, we investigated the clinical features and β-globin gene abnormalities in 15 homozygous β-thal and 60 Hb E ( |
35950589 | Thalassemia in Asia 2021 Thalassemia in Brunei Darussalam. | Acknowledging and understanding the extent of thalassemia and hemoglobinopathy issues in a country is crucial for the benefit of implementing a national preventive and control program to reduce its prevalence. In order to obtain reliable prevalence data, the gene frequencies of the thalassemias and other hemoglobinopathies should be investigated. Molecular studies on thalassemia have yet to be done for Brunei's population. It was estimated that carriers of thalassemia or hemoglobinopathies in Brunei is approximately 5.0% or less of the overall population. There are about 200 current cases of thalassemia and other hemoglobinopathies including adults and children reported across all four districts of Brunei. Blood parameter analysis, microscopy, hemoglobin (Hb) electrophoresis and high performance liquid chromatography (HPLC) are the mon methods of investigation in aiding diagnosis in the hospital laboratory. Genotyping analysis conducted in an overseas laboratory has been employed to confirm some diagnosis. Compiled data from 2009-2017 at the Hematology Laboratory of the Raja Isteri Pengiran Anak Saleha Hospital, Jalan Putera Al-Muhtadee Billah, Bandar Seri Begawan, Brunei Darussalam, showed that the most reported diagnoses are α-thalassemia (α-thal) trait, β-thalassemia (β-thal) trait, heterozygous Hb E ( |
35950590 | Thalassemia in Thailand. | Thailand has a population of 66.2 million with 30.0-40.0% of them carrying thalassemia genes. Interaction of these thalassemia genes lead to more than 60 genotypes with a wide spectrum of clinical severity from asymptomatic to lethal. Estimation based on gene frequencies and number of babies born each year, there will be about 1.2% babies born with severe cases of thalassemia each year. Further estimation revealed that 1.0% of the Thai population have thalassemia disease, which is a big health problem for the country. Thalassemia prevention and control programs were introduced using post conception screening in couples and prenatal diagnosis (PND) for the prevention of new thalassemic births. Moreover, the majority of existing cases are undergoing supportive treatment with regular blood transfusions and iron chelation. Curative treatment by hematopoietic stem cell transplantation (HSCT) is available but is limited to a minority of the patients. |
35950592 | Electrochemically stimulated protein release from pH-switchable electrode-immobilized nitroavidin-biotin and avidin-iminobiotin systems. | Bovine serum albumin (BSA), used as a model protein, was immobilized on a buckypaper electrode by formation of covalent bonds with avidin/iminobiotin or plexes. pH-sensitive affinity interactions between avidin and iminobiotin or between nitroavidin and biotin allowed splitting of the affinity bonds upon pH variation, thus resulting in BSA release. Local (interfacial) pH was changed electrochemically. The pH was decreased upon electrochemical oxidation of ascorbate or increased upon electrochemical reduction of O |
35950594 | Quantitation of RhoA activation: differential binding to downstream effectors. | The small GTPase RhoA controls many important cellular processes through its ability to activate multiple downstream effector pathways. Most RhoA effectors contain a Rho-binding domain (RBD), and interaction between active RhoA and the RBD typically induces a conformational change in effectors that stimulates their recruitment or activity. Isolated GTPase binding domains fused to GST have been widely used in so-called pulldown assays to measure the activation state of other GTPases in cell lysates. Similarly, GST fusions containing the RBD of the RhoA effector Rhotekin have been widely adopted as a standardized tool for the measurement of RhoA activation. RBDs have also been used to generate fluorescent reporter constructs to localize sites of GTPase activation in intact cells. In this report, we demonstrate that not all forms of active RhoA are capable of interacting with the Rhotekin RBD. A constitutively active RhoA-G14V mutant, which interacted with the RBDs of ROCK2 and mDIA1, was unable to bind the Rhotekin RBD as evidenced by both conventional GST pulldown assay and our newly established BRET assay. Furthermore, active RhoA induced by different stimuli in cells also displayed binding preference for its diverse effectors. Our data demonstrate that RhoA may undergo effector-specific activation for differential regulation of its downstream pathways, and that RhoA activation should not be defined solely by its interaction with Rhotekin. |
35950593 | Human 1PN and 3PN zygotes recapitulate all morphokinetic events of normal fertilization but reveal novel developmental errors. | Does mono- (1PN) and tri-pronuclear (3PN) fertilization recapitulate the morphokinetic changes of normal bi-pronuclear (2PN) fertilization? |
35950596 | Randomized Controlled Trial of Group Exercise Intervention for Fall Risk Factors Reduction in Nursing Home Residents. | The aim of this study was to assess the effectiveness of a multidimensional exercise intervention on improving fall risk deterrent factors, such as overall strength and flexibility in nursing home residents. |
35950595 | Maternal high-fat diet modifies epigenetic marks H3K27me3 and H3K27ac in bone to regulate offspring osteoblastogenesis in mice. | Studies from both humans and animal models indicated that maternal chronic poor-quality diet, especially a high fat diet (HFD), is significantly associated with reduced bone density and childhood fractures in offspring. When previously studied in a rat model, our data suggested that maternal HFD changes epigenetic marks such as DNA methylation and histone modifications to control osteoblast metabolism. In mouse embryonic and postnatal offspring bone samples, a ChIP-sequencing (ChIP-Seq)-based genome-wide method was used to locate the repressive histone mark H3K27me3 (mediated via the b histone methyltransferase, |
35950597 | Rapid generation of genetically engineered T cells for the treatment of virus-related cancers. | Adoptive transfer of T cell receptor (TCR)-engineered T cells targeting viral epitopes represents a promising approach for treating virus-related cancers. However, the efficient identification of epitopes for T cells and the corresponding TCR remains challenging. Here, we report a workflow permitting the rapid generation of human papillomavirus (HPV)-specific TCR-T cells. Six epitopes of viral proteins belonged to HPV16 or HPV18 were predicted to have high affinity to A11:01 according to bioinformatic analysis. Subsequently, CTL induction were performed with these six antigen peptides separately, and antigen-specific T cells were sorted by FACS. TCR clonotypes of these virus-specific T cells were determined using next-generation sequencing. To improve the efficiency of TCRαβ pair validation, a lentiviral vector library containing 116 TCR constructs was generated that consisted of predominant TCRs according to TCR repertoire analysis. Later, TCR library transduced T cells were simulated with peptide pool-pulsed antigen-presenting cells, then CD137-positive cells were sorted and subjected to TCR repertoire analysis. The top-hit TCRs and corresponding antigen peptides were deduced and validated. Through this workflow, a TCR targeting the E6 |
35950600 | Improvement of Antibacterial and Antifouling Properties of a Cellulose Acetate Membrane by Surface Grafting Quaternary Ammonium Salt. | Through etherification reaction, epoxy propyl dimethyl dodecyl ammonium chloride (EPDMDAC) was grafted onto the surface of a cellulose acetate (CA) membrane to prepare a stable nonleaching antibacterial antifouling membrane (QCA- |
35950601 | Bioequivalence and Pharmacokinetic Study of 2 Edoxaban Tablets in Healthy Chinese Subjects. | The aim was to investigate the bioequivalence of 2 orally administered edoxaban 60-mg tablets and the food effects on the pharmacokinetics of edoxaban. Sixty-four healthy Chinese subjects participated in this open-label, randomized, 2-sequence, 4-period, crossover study. All subjects randomly received 60-mg generic (test) or branded (reference) edoxaban tablet in each period. Plasma edoxaban concentrations were determined using liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters maximum concentration (C |
35950598 | Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity: State of the art and research gaps. | Maternal diabetes and/or obesity in pregnancy are undoubtedly associated with later disease-risk in the offspring. The placenta, interposed between the mother and the foetus, is a potential mediator of this risk through epigenetic mechanisms, including DNA methylation. In recent years, multiple studies have identified differentially methylated CpG sites in the placental tissue DNA in plicated by diabetes and obesity. We reviewed all published original research relevant to this topic and analysed our findings with the focus of identifying overlaps, contradictions, and gaps. Most studies focused on the association of gestational diabetes and/or hyperglycaemia in pregnancy and DNA methylation in placental tissue at term. We identified overlaps in results related to specific candidate genes, but also observed a large research gap of pregnancies affected by type 1 diabetes. Other unanswered questions relate to analysis of specific placental cell types and the timing of DNA methylation change in response to diabetes and obesity during pregnancy. Maternal metabolism is altered already in the first trimester involving structural and functional changes in the placenta, but studies into its effects on placental DNA methylation during this period are lacking and urgently needed. Foetal sex is also an important determinant of pregnancy e, but only few studies have taken this into account. Collectively, we provide a reference work for researchers working in this large and evolving field. Based on the results of the literature review, we formulate suggestions for future focus of placental DNA methylation studies in plicated by diabetes and obesity. |
35950599 | Epigenetic Aging Mediates the Association between Pain Impact and Brain Aging in Middle to Older Age Individuals with Knee Pain. | Chronic musculoskeletal pain is a health burden that may accelerate the aging process. Accelerated brain aging and epigenetic aging have separately been observed in those with chronic pain. However, it is unknown whether these biological markers of aging are associated with each other in those with chronic pain. We aimed to explore the association of epigenetic aging and brain aging in middle-to-older age individuals with varying degrees of knee pain. Participants (57.91 ± 8.04 y) with low impact knee pain (n = 95), high impact knee pain (n = 53), and pain-free controls pleted self-reported pain, a blood draw, and an MRI scan. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge), the subsequent difference of predicted epigenetic and brain age from chronological age (DNAmGrimAge-Difference and Brain-PAD, respectively). There was a significant main effect for pain impact group ( |
35950603 | BETA PRIME: Phase I study of AdAPT-001 as monotherapy and combined with a checkpoint inhibitor in superficially accessible, treatment-refractory solid tumors. | AdAPT-001 is an investigational therapy consisting of a replicative type 5 adenovirus armed with a TGF-β receptor-immunoglobulin Fc fusion trap, designed to neutralize isoforms 1 and 3 of the profibrotic and immunosuppressive cytokine, TGF-β. In preclinical studies with an petent mouse model, AdAPT-001 eradicated directly treated 'cold' tumors as well as distant untreated tumors, and, from its induction of systemic CD8 |
35950602 | A comparative study on roles of natural killer T cells in two diet-induced non-alcoholic steatohepatitis-related fibrosis in mice. | Immune responses are important in the progression of non-alcoholic fatty liver disease (NAFLD). Natural killer T (NKT) cells are ponents of the innate immune system that modulate immunity. However, the role of NKT cells in NAFLD remains controversial. |
35950606 | The road ahead of dietary restriction on anti-aging: focusing on personalized nutrition. | Dietary restriction (DR), including caloric restriction (CR), intermittent fasting (IF), and restriction of specific positions, can delay aging, and the main mechanisms include regulation of nutrient-sensing pathways and gut microbiota. However, the effects of DR regimens on longevity remain controversial, as some studies have demonstrated that IF, rather than CR or position, influences longevity, while other studies have shown that the restricted-carbohydrate or -protein diets, rather than CR, determine health and longevity. Many factors, including DR-related factors (carbohydrate or position, degree and duration of DR), and individual differences (health status, sex, genotype, and age of starting DR), would be used to explain the controversial anti-aging effects of DR, thus highlighting the necessity of precise DR intervention for anti-aging. Personalized DR intervention in humans is challenging because of the lack of accurate aging molecular biomarkers and vast individual variability. Using machine learning to build a predictive model based on the data set of clinical features, gut microbiome and metabolome, may be a good method to achieve precise DR intervention. Therefore, this review analyzed the anti-aging effects of various DR regimens, summarized their mechanisms and influencing factors, and proposed a future research direction for achieving personalized DR regimens for slowing aging. |
35950605 | Engaging White parents to address their White children's racial biases in the Black-White context. | Multiple studies (n = 1065 parents, 625 females, 437 males, 3 nonbinary, 99.06% White; n = 80, 5 to 7-year-old children, 35 girls, 45 boys, 87.50% White; data collection September 2017-January 2021) investigated White U.S. parents' thinking about White children's Black-White racial biases. In Studies 1-3, parents reported that their own and other children would not express racial biases. When predicting children's social preferences for Black and White children (Study 2), parents underestimated their own and other children's racial biases. Reading an article about the nature, prevalence, and consequences of White children's racial biases (Study 3) increased parents' awareness of, concern about, and motivation to address children's biases (relative to a control condition). The findings have implications for engaging White parents to address their children's racial biases. |
35950607 | Shifting gears to differentiation agents in acute promyelocytic leukemia with resource constraints-a cohort study. | Treatment of acute promyelocytic leukaemia has emerged as a major success in hemato-oncology. While literature from the developed world boasts of outstanding es, there is a paucity of data from the developing world. This study aimed to plications and es of acute promyelocytic leukaemia in a resource-constrained setting. |
35950608 | Study Evaluating Self-Collected Specimen Return for HIV, Bacterial STI, and Potential Pre-Exposure Prophylaxis Adherence Testing Among Sexual Minority Men in the United States. | Web-based HIV and sexually transmitted infection (STI) prevention studies are increasingly requesting gay, bisexual, and other men who have sex with men (GBMSM) to return self-collected specimens for laboratory processing. Some studies have solicited self-collected extragenital swabs for gonorrhea and chlamydia testing, but to date, none have solicited self-collected hair samples for pre-exposure prophylaxis (PrEP) adherence testing. Project Caboodle! offered 100 racially/ethnically diverse GBMSM aged 18 to 34 years residing across the United States a choice to self-collect at home and return by mail any of the following: a finger-stick blood sample (for HIV testing), a pharyngeal swab, a rectal swab and a urine specimen (for gonorrhea and chlamydia testing), and a hair sample (to visually assess its adequacy for PrEP drug level testing). Despite not incentivizing specimen return, 51% mailed back at least one type of specimen within 6 weeks (1% returned three specimens, 11% returned four specimens and 39% returned all five specimens). The majority of returned specimens were adequate for laboratory processing. Significantly more participants without a college education ( |
35950611 | Risk of neonatal hypothyroidism in newborns from mothers exposed to CTPA during pregnancy: Ancillary data from a prospective outcome study. | Neonatal hypothyroidism is often raised as a potential concern for the use puted tomography pulmonary angiography (CTPA) in pregnant women with suspected pulmonary embolism (PE). |
35950609 | Prostate Cancer Drug Therapy: What Have Clinicians Missed During the COVID-19 Pandemic. | Due to the COVID-19 pandemic, major congresses and many teaching opportunities as well as the usual visits from medical advisors of pharmaceutical firms have been postponed and canceled. The major trials of prostate cancer in the last 5 years in each state are shortly discussed providing a panoramic overview of the available evidence and data on prostate cancer treatment. Apalutamide, enzalutamide, and darolutamide have proven to have clinical benefits when added to androgen deprivation therapy for patients with nonmetastatic castration-resistant prostate cancer. In patients in the metastatic hormone-sensitive setting, next to docetaxel, abiraterone, enzalutamide, and apalutamide have been shown to significantly improve overall survival and progression-free survival parison to standard hormone therapy. In addition, docetaxel abiraterone and enzalutamide are widely used in the metastatic setting. For second-line therapy of metastasized prostate cancer patients who have received either docetaxel or abiraterone or enzalutamide, olaparib, cabazitaxel, radium, and lutetium therapy have been shown to be beneficial in selected patient groups. |
35950612 | Clinical and metabolic imaging features of late-onset and early-onset posterior cortical atrophy. | Late-onset (LO) and early-onset (EO) dementia show neurobiological and clinical differences. Clinical and |
35950615 | Development and External Validation of a Machine Learning Model for the Early Prediction of Doses of Harmful Intracranial Pressure in Patients with Severe Traumatic Brain Injury. | Treatment and prevention of elevated intracranial pressure (ICP) is crucial in patients with severe traumatic brain injury (TBI). Elevated ICP is associated with secondary brain injury, and both intensity and duration of an episode of intracranial hypertension, often referred to as "ICP dose," are associated with worse es. Prediction of such harmful episodes of ICP dose could allow for a more proactive and preventive management of TBI, with potential implications on patients' es. The goal of this study was to develop and validate a machine-learning (ML) model to predict potentially harmful ICP doses in patients with severe TBI. The prediction target was defined based on previous studies and included a broad range of doses of elevated ICP that have been associated with poor long-term neurological es. The ML models were used, with minute-by-minute ICP and mean arterial blood pressure signals as inputs. Harmful ICP episodes were predicted with a 30 min forewarning. Models were developed in a multi-center dataset of 290 adult patients with severe TBI and externally validated on 264 patients from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) dataset. The external validation of the prediction model on the CENTER-TBI dataset demonstrated good discrimination and calibration (area under the curve: 0.94, accuracy: 0.89, precision: 0.87, sensitivity: 0.78, specificity: 0.94, calibration-in-the-large: 0.03, calibration slope: 0.93). The proposed prediction model provides accurate and timely predictions of harmful doses of ICP on the development and external validation dataset. A future interventional study is needed to assess whether early intervention on the basis of ICP dose predictions will result in improved es. |
35950613 | Technological Breakthroughs in Chip Fabrication, Transfer, and Color Conversion for High-Performance Micro-LED Displays. | The implementation of high-efficiency and high-resolution displays has been the focus of considerable research interest. Recently, micro light-emitting diodes (micro-LEDs), which are inorganic light-emitting diodes of size <100 µm |
35950614 | Epitope Fine Mapping by Mass Spectrometry: Investigations of Immune Complexes Consisting of Monoclonal Anti-HpTGEKP Antibody and Zinc Finger Protein Linker Phospho-Hexapeptides. | Accurate formation of plexes has been relied on in both, multitudes of scientific projects and ample therapeutic and diagnostic applications. Mass spectrometrically determined dissociation behavior of plexes with the anti-HpTGEKP antibody revealed that the ten most frequently occurring phospho-hexapeptide linker sequences from C2H2 zinc finger proteins could be divided into two classes: orthodox binders, where strong noncovalent interactions developed as anticipated, and unorthodox binders with deviating structures and weaker binding. Phosphorylation of threonine pulsory for antibody binding in an orthodox manner. Gas phase dissociation energy determinations of seven C2H2 zinc finger protein linker phospho-hexapeptides with orthodox binding properties revealed a bipolar binding motif of the antibody paratope. Epitope peptides, which in addition to the negatively charged phospho-threonine residue were C-terminally flanked by positively charged residues provided stronger binding, i. e. dissociation was endothermic, than peptides with acidic amino acid residues at these positions, for which dissociation was exothermic. |
35950618 | Endobronchial tuberculosis in children: Defining the role of interventional bronchoscopy. | Endobronchial tuberculosis (EBTB) can lead to plications when diagnosis is delayed. Bronchoscopic treatment in children can be challenging due to small airway size. We report our experience treating children with EBTB. |
35950617 | Progress report on new antiepileptic drugs: A summary of the Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI): II. Drugs in more advanced clinical development. | The Sixteenth Eilat Conference on New Antiepileptic Drugs and Devices (EILAT XVI) was held in Madrid, Spain on May 22-25, 2022 and was attended by 157 delegates from 26 countries representing basic and clinical science, regulatory agencies, and pharmaceutical industries. One day of the conference was dedicated to sessions presenting and discussing pounds under development for the treatment of seizures and epilepsy. The current progress report summarizes recent findings and current knowledge for seven of pounds in more advanced clinical development for which either novel preclinical or patient data are available. pounds include bumetanide and its derivatives, darigabat, ganaxolone, lorcaserin, soticlestat, STK-001, and XEN1101. Of these, ganaxolone was approved by the US Food and Drug Administration in March 2022 for the treatment of seizures associated with cyclin-dependent kinase-like 5 deficiency disorder in patients 2 years of age and older. |
35950623 | Specific Brain Gray Matter Volume Changes in Pediatric Complete Spinal Cord Injury without Fracture or Dislocation Using Voxel-Based Morphometry Analysis: Preliminary Results. | This study aims to investigate the brain gray matter volume (GMV) alterations of plete thoracolumbar spinal cord injury (SCI) without fracture or dislocation (SCIWOFD) using voxel-based morphometry (VBM) analysis and assess the sensitive neuroimaging biomarkers that may be surrogate targets to enhance brain plasticity. A total of 52 pediatric subjects (age range, 6-12 years), including 25 pediatric SCIWOFD patients and 27 typically developing (TD) children were recruited. An independent two-sample |
35950625 | Use of a Novel Standardized Administration Protocol Reduces Agitation Pro Re Nata (PRN) Medication Requirements: The Birmingham Agitation Management (BAM) Initiative. | Agitation management is a principal challenge on inpatient psychiatric units. Overreliance mon prescribing strategies of pro re nata (PRN) medication administration is problematic, given the tendencies to have overlapping or unclear indications. |
35950624 | Long transient response of vegetation dynamics after four millennia of anthropogenic impacts in an island ecosystem. | Agents of global monly have a higher impact on island ecosystem dynamics. In the Mediterranean region, those dynamics have historically been influenced by anthropogenic impacts, for example, the introduction of invasive species and overharvesting of resources. Here, we analysed the spatio-temporal dynamics of vegetation in sa Dragonera island, which experienced a large environmental change ca. 4000 years ago by the arrival of humans. Anthropogenic impacts, such as herbivory by goats and over-logging, ended in the 1970s, while in 2011 the site became the largest Mediterranean island where rats were eradicated. Invasive rats and goats played the ecological role of two endemic species, the cave goat and the giant dormouse, which inhabited the island for more than 5 million years and were rapidly extinct by humans. We used Landsat imagery to explore NDVI as a proxy of vegetation productivity over the years 1984-2021, orthophotos to assess changes in land and vegetation covers and historical plant inventories to study the dynamics in plant diversity. Results showed that those indicators steadily increased both in spring and in summer, while the noise around the trends was partially explained by climate variability. The regime shifts in the temporal dynamics of vegetation productivity suggested a transient from a perturbed to a non-perturbed stable state. Trends in successional dynamics, spatial self-organization and plant diversity also showed the same type of transient dynamics. Historical perturbations related to harvesting (mainly the synergies between goat browsing, burning and forest over-logging) were more important than rat eradication or the influence of climate to explain the vegetation dynamics. Our study shows the transient nature of this small island ecosystem after 4000 years of perturbations and its current path towards vegetation dynamics more controlled by ecological interactions lacking large herbivores and omnivores, drought dynamics and the carrying capacity of the island. |
35950627 | Creating age-friendly nursing homes: The time is now. | The current global age-friendly movement supports older adults by promoting different policies and services. However, there is a dearth of attention to nursing home (NH) residents as part of age-friendly movements. The pioneering idea of an age-friendly health system, i.e., the "4 Ms" model is significant for NHs and formative for further developments; however, it does not identify ponents of NH care. This article aims to identify specific aspects of person-centered care in the literature to advance the development of a standardized conceptual framework. Along with residents, NH staff and administrators are integral parts of NHs. Incorporating the central role of caregivers, this study proposes a new "8 Ms" framework to describe the age-friendly NH. The traditional 4 Ms model notes that everything related to care matters to residents, along with care related to |
35950629 | Semi-Synthetic Glycoconjugate Vaccine Lead Against Acinetobacter baumannii 17978. | Acinetobacter baumannii is a opportunistic bacterial pathogen responsible for serious ial infections that is ing increasingly resistant against antibiotics. Capsular polysaccharides (CPS) that cover A. baumannii are a major virulence factor that play an important role in pathogenesis, are used to assign serotypes and provide the basis for vaccine development. Synthetic oligosaccharides resembling the CPS of A. baumannii 17978 were printed onto microarray slides and used to screen sera from patients infected with A. baumannii as well as a monoclonal mouse antibody (mAb C8). A synthetic oligosaccharide emerged from glycan array screening as lead for the development of a vaccine against A. baumannii 17978. Tetrasaccharide 20 is a key epitope for recognition by an antibody and is a vaccine lead. |
35950631 | Rates of Emotional Disturbance Among Children in Foster Care: Comparing Federal Child Welfare Data and Medicaid Records in Two States. | The purpose of this study is to estimate the rate of emotional disturbance (ED) among children in foster care and assess the validity of the national foster care census data (AFCARS) measure of ED. This study used linked child protection and Medicaid records from 2014 and 2015, for the states of California and Wisconsin, as well as data from AFCARS, a federal population census of children in foster care which states are mandated to contribute to. ED is defined by AFCARS and includes an array of mental and behavioral health diagnoses. According to AFCARS, 13% of CA children in foster care and 15% of WI children in foster care had an ED, whereas Medicaid claims produce rates of 45% and 48%, respectively. Rates of ED among children in congregate care were underestimated by 43-46 percentage points, with substantial proportions having diagnoses of disruptive behavioral disorders. Despite the AFCARS ED measure being cited in congressional testimonies and its wide use in research, results from this study suggest that the AFCARS ED estimates are an unreliable metric for use in research, policy, or practice. |
35950632 | Clinical Characteristics and Outcomes of Chronic Kidney Disease in People Living with HIV in a Resource-Limited Center of Central China. | Clinical management and optimal treatment are essential to improving es for people living with HIV (PLWH). We assessed trends and es of chronic kidney disease (CKD) in PLWH in a resource-limited center of central China. All PLWH who were followed up in a tertiary referral center in Wuhan, China, from July 2016 to June 2021 were evaluated. CKD was defined as glomerular filtration rate (GFR) <60 mL/min/1.73 m |
35950635 | Food traceability 4.0 as part of the fourth industrial revolution: key enabling technologies. | Food Traceability 4.0 (FT 4.0) is about tracing foods in the era of the fourth industrial revolution (Industry 4.0) with techniques and technologies reflecting this new revolution. Interest in food traceability has gained momentum in response to, among others events, the outbreak of the COVID-19 pandemic, reinforcing the need for digital food traceability that prevents food fraud and provides reliable information about food. This review will briefly summarize the mon conventional methods available to determine food authenticity before highlighting examples of emerging techniques that can be used bat food fraud and improve food traceability. A particular focus will be on the concept of FT 4.0 and the significant role of digital solutions and other relevant Industry 4.0 innovations in enhancing food traceability. Based on this review, a possible new research topic, namely FT 4.0, is encouraged to take advantage of the rapid digitalization and technological advances occurring in the era of Industry 4.0. The main FT 4.0 enablers are blockchain, the Internet of things, artificial intelligence, and big data. Digital technologies in the age of Industry 4.0 have significant potential to improve the way food is traced, decrease food waste and reduce vulnerability to fraud opening new opportunities to achieve smarter food traceability. Although most of these emerging technologies are still under development, it is anticipated that future research will e current limitations making large-scale applications possible. |
35950636 | Elevated apoptosis and abnormal apoptosis signaling of regulatory T cells in patients with systemic lupus erythematosus. | In systemic lupus erythematosus (SLE), immune tolerance is influenced by defects in naturally occurring T cells (Tregs). To investigate the apoptosis rate of Tregs and their suppressive activity in patients with SLE and then to recognize the genes and signaling pathways that cause Treg apoptosis. FACS was used to assess the frequency and apoptosis rates of Tregs in 48 SLE patients and 28 normal controls (NCs). Coculture of Tregs with CD4 |
35950637 | Primary implant stability based on alternative site preparation techniques: A systematic review and meta-analysis. | To evaluate the effect of special implant site preparation methods in improving primary implant stability in low-density bone. |
35950638 | Cognitive Function and Olfactory Impairment in Community-Dwelling Older Adults Attending a Salon. | Early detection, treatment, and care are important for the prevention of dementia. Though olfactory impairment has been reported to be associated with mild cognitive impairment (MCI), there are few reports munity-dwelling older adults with no difficulty in daily life in Japan. |