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36896846

Simulation workflows to predict the circular dichroism and circularly polarized luminescence of chiral materials.

Chiral materials are attracting considerable interest in various fields in view of their unique properties and optical activity. Indeed, the peculiar features of chiral materials to absorb and emit circularly polarized light enable their use in an extensive range of applications. Motivated by the interest in boosting the development of chiral materials characterized by enhanced chiroptical properties such as circular dichroism (CD) and circular polarized luminescence (CPL), we herein illustrate in this tutorial how theoretical simulations can be used for the predictions and interpretations of chiroptical data and for the identification of chiral geometries. We are focusing putational frameworks that can be used to investigate the theoretical aspects of chiral materials' photophysical and conformational characteristics. We will then illustrate ab initio methods based on density functional theory (DFT) and its time-dependent extension (TD-DFT) to simulate CD and CPL signals, and we will exemplify a variety of enhanced sampling techniques useful for an adequate sampling of the configurational space for chiral systems.

36896847

Total-factor energy efficiency of ten major global energy-consuming countries.

Improving energy efficiency is regarded as a key path to tackling global warming and achieving the Sustainable Development Goals (SDGs). In 2020, the energy consumption of the world's ten major energy-consuming countries accounted for 66.8% of the global total. This paper applied data envelopment analysis (DEA) to calculate these ten major energy-consuming countries' total-factor energy efficiency (TFEE) at national and sectoral levels from 2001-2020, and explored the influencing factors of total-factor energy efficiency with the Tobit regression model. The results showed significant difference in the ten countries' energy efficiency. The United States and Germany topped the list for total-factor energy efficiency, while China and India were at the bottom. Meanwhile, the energy efficiency of the industrial subsector has increased significantly over the past two decades, while that of the other subsectors has been relatively flat. The industrial structure upgrading, per capita GDP, energy consumption structure, and foreign direct investment had significant impacts on energy efficiency with national heterogeneity. Energy consumption structure and GDP per capita were determinative factors of energy efficiency.

36896848

Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients.

Metastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsible for the transport of drugs, e.g. P-glycoprotein (P-gp), the penetration of drugs into the CNS is insufficient. Until recently, the only method of CNS metastases treatment was radiotherapy and neurosurgery. The advancement of molecular biology allowed discover targets for molecularly targeted therapies. One of targets is abnormal anaplastic lymphoma kinase, which results from the rearrangement of the

36896849

Tuning a small electron polaron in FePO

Due to the existence of a small polaron, the intrinsic electronic conductivity of olivine-structured LiFePO

36896851

Regulatory requirements and optimization of multiple criteria decision analysis to quantify the benefit-risk assessment of medical devices.

Worldwide medical device regulatory authorities increasingly rely on the benefit-risk ratio for decision-making. However, current benefit-risk assessment (BRA) methods are mostly descriptive, not quantitative.

36896852

Co-encapsulation of curcumin and resveratrol in zein-bovine serum albumin nanoparticles using a pH-driven method.

In the present study, zein-bovine serum albumin posite nanoparticles (NPs) are produced with the use of a pH-driven method. The mass ratio of BSA to zein has a significant impact on the particle size, but exhibits a limited effect on the surface charge. With an optimal zein/BSA weight ratio of 1 : 2, zein-BSA core-shell NPs are fabricated for the single/co-loading of curcumin and resveratrol. The incorporation of curcumin or/and resveratrol into zein-BSA NPs changes the configuration of the proteins (zein and BSA), and zein NPs transform resveratrol and curcumin from the crystalline structure to the amorphous state. Compared with resveratrol, curcumin has higher binding strength with zein BSA NPs, showing higher encapsulation efficiency and storage stability. The co-encapsulation of curcumin is found to be an effective method to improve the encapsulation efficiency and shelf-stability of resveratrol. Through this co-encapsulation technology, curcumin and resveratrol are retained in different NP regions

36896854

Role of pre-operative embolization in carotid body tumor surgery according to Shamblin classification: A systematic review and meta-analysis.

Pre-operative embolization prior to surgical resection of carotid body tumors was meant to decrease intraoperative blood loss and operative time. Yet, potential confounders such as different Shamblin classes have never been analyzed. Aim of our meta-analysis was to investigate effectiveness of a pre-operative embolization according to different Shamblin classes.

36896855

Five New Phenolic Glycosides from Viburnum luzonicum.

Viburnum luzonicum is widely distributed in China. Its branch extracts showed potential α-amylase and α-glucosidase inhibitory activities. In order to discover new bioactive constituents, five undescribed phenolic glycosides, viburozosides A-E (1-5), were obtained by bioassay-guided isolation coupled with HPLC-QTOF-MS/MS analysis. Their structures were elucidated by spectroscopic analyses, including 1D NMR, 2D NMR, ECD, and ORD. pounds were tested for their α-amylase and α-glucosidase inhibitory potency. Compound 1 showed petitive inhibition against α-amylase (IC

36896856

Development of multiple AI pipelines that predict neoadjuvant chemotherapy response of breast cancer using H&E-stained tissues.

In recent years, the treatment of breast cancer has advanced dramatically and neoadjuvant chemotherapy (NAC) has e mon treatment method, especially for locally advanced breast cancer. However, other than the subtype of breast cancer, no clear factor indicating sensitivity to NAC has been identified. In this study, we attempted to use artificial intelligence (AI) to predict the effect of preoperative chemotherapy from hematoxylin and eosin images of pathological tissue obtained from needle biopsies prior to chemotherapy. Application of AI to pathological images typically uses a single machine-learning model such as support vector machines (SVMs) or deep convolutional neural networks (CNNs). However, cancer tissues are extremely diverse and learning with a realistic number of cases limits the prediction accuracy of a single model. In this study, we propose a novel pipeline system that uses three independent models each focusing on different characteristics of cancer atypia. Our system uses a CNN model to learn structural atypia from image patches and SVM and random forest models to learn nuclear atypia from fine-grained nuclear features extracted by image analysis methods. It was able to predict the NAC response with 95.15% accuracy on a test set of 103 unseen cases. We believe that this AI pipeline system will contribute to the adoption of personalized medicine in NAC therapy for breast cancer.

36896858

The Near-Death Experience and Suicidal Ideation.

The near-death experience (NDE) most generally refers to a state of altered consciousness with various features that can occur during real or presumed near-death circumstances and/or life-threatening incidents. Some NDEs are associated with a nonfatal suicide attempt. This paper discusses how a belief by suicide attempters that their NDEs are a true portrayal of objective spiritual reality can at least in some cases be positively associated with a persistence or increase of suicidal ideation and on occasion lead to further suicide attempts, while also exploring why at other times such a belief may reduce the risk of suicide. The formulation of suicidal ideation associated with NDEs among some of those who did not initially try to kill themselves is also explored. Various examples related to NDEs and suicidal ideation are provided and discussed. Furthermore, this paper also offers some theoretical insights related to this matter and points out some specific therapeutic concerns based on this discussion.

36896859

Disparities in 30-day readmission rates among Medicare enrollees with dementia.

Readmissions contribute to excessive care costs and burden for people living with dementia. Assessments of racial disparities in readmissions among dementia populations are lacking, and the role of social and geographic risk factors such as individual-level exposure to greater neighborhood disadvantage is poorly understood. We examined the association between race and 30-day readmissions in a nationally representative sample of Black and non-Hispanic White individuals with dementia diagnoses.

36896861

Clinical and immunological evaluation of peri-implant tissues around ultra-polished and conventionally-polished zirconia abutments. A 1-year follow-up randomized clinical trial.

This is a randomized clinical trial pare the clinical and immunological performance of ultrasmooth versus conventionally-smooth zirconia abutments placed subgingivally after a period of 1 year.

36896863

Pure spinal intraosseous arteriovenous fistula: A case report.

Spinal osseous arteriovenous fistula (AVF) is a rare disease with a characteristic angioarchitecture involving an intraosseous venous pouch (VP) of the vertebral body where the feeders are converging. Using spinal angiography alone, it is difficult to distinguish spinal osseous AVF from classical spinal epidural AVF (EDAVF) with fistulas in the epidural VP and bone erosion because both subtypes have an angiographically similar dilated VP appearance. Thus, spinal osseous AVF may be often misdiagnosed as spinal EDAVF. With advancing imaging techniques, it would be possible to determine the exact location of the fistula. Here, we present the case of a 37-year-old woman with a pure spinal thoracic osseous AVF and radiculopathy. She was diagnosed with spinal intraosseous AVF using high-resolution three-dimensional rotational angiography (3D-RA). The fistula was located in the Th1 lateral mass with a VP where multiple osseous feeders were converging. There was paravertebral venous drainage without intradural venous drainage. Transvenous embolization with Onyx and coils was performed through the azygos vein to the lateral epidural venous plexus, resulting plete obliteration. This case suggests that 3D-RA reconstructed images are essential for accurate diagnosis and successful treatment of this condition. It is important to occlude only intraosseous VPs by accurate subtype diagnosis. Transvenous embolization is a treatment option for spinal intraosseous AVF with paravertebral epidural venous drainage.

36896864

Prevalence and risk factors of phlebosclerosis in the great saphenous vein.

Phlebosclerosis is a fibrous degeneration of the vein wall, predominantly the intima, with or without calcification. The prevalence and etiology of phlebosclerosis of the great saphenous vein are not well documented. This study aimed to estimate the prevalence and define the risk factors of phlebosclerosis of the great saphenous vein.

36896865

Lymph Node Metastases in Papillary Thyroid Carcinoma can be Predicted by a Convolutional Neural Network: a Multi-Institution Study.

The presence of nodal metastases in patients with papillary thyroid carcinoma (PTC) has both staging and treatment implications. However, lymph nodes are often not removed during thyroidectomy. Prior work has demonstrated the capability of artificial intelligence (AI) to predict the presence of nodal metastases in PTC based on the primary tumor histopathology alone. This study aimed to replicate these results with multi-institutional data.

36896866

Discharge Disposition After Head and Neck Reconstruction: Effect on Adjuvant Therapy and Outcomes.

Head and neck cancer patients that require major reconstruction often have advanced-stage disease. Discharge disposition of patients can vary and impact time to adjuvant treatment. We sought to examine es in patients discharged to skilled nursing facilities pared to those discharged home, including the impact on adjuvant therapy initiation and treatment package time (TPT).

36896867

Trajectories of brain volumes in young children are associated with maternal education.

Brain growth in early childhood is reflected in the evolution of proportional cerebrospinal fluid volumes (pCSF), grey matter (pGM), and white matter (pWM). We study brain development as reflected in the relative fractions of these three tissues for a cohort of 388 children that were longitudinally followed between the ages of 18 and 96 months. We introduce statistical methodology (Riemannian Principal Analysis through Conditional Expectation, RPACE) that addresses major challenges that are of general interest for the analysis of longitudinal neuroimaging data, including the sparsity of the longitudinal observations over time and positional structure of the relative brain volumes. Applying the RPACE methodology, we find that longitudinal growth as reflected by position differs significantly for children of mothers with higher and lower maternal education levels.

36896868

Association Between Metabolic Syndrome and Outcomes in Complex Head and Neck Surgery.

We aim to evaluate the impact of MetS on the short-term postoperative es plex head and neck surgery patients.

36896869

Optic radiations representing different eccentricities age differently.

The neural pathways that carry information from the foveal, macular, and peripheral visual fields have distinct biological properties. The optic radiations (OR) carry foveal and peripheral information from the thalamus to the primary visual cortex (V1) through adjacent but separate pathways in the white matter. Here, we perform white matter tractometry using pyAFQ on a large sample of diffusion MRI (dMRI) data from subjects with healthy vision in the U.K. Biobank dataset (UKBB; N = 5382; age 45-81). We use pyAFQ to characterize white matter tissue properties in parts of the OR that transmit information about the foveal, macular, and peripheral visual fields, and to characterize the changes in these tissue properties with age. We find that (1) independent of age there is higher fractional anisotropy, lower mean diffusivity, and higher mean kurtosis in the foveal and macular OR than in peripheral OR, consistent with denser, more organized nerve fiber populations in foveal/parafoveal pathways, and (2) age is associated with increased diffusivity and decreased anisotropy and kurtosis, consistent with decreased density and tissue organization with aging. However, anisotropy in foveal OR decreases faster with age than in peripheral OR, while diffusivity increases faster in peripheral OR, suggesting foveal/peri-foveal OR and peripheral OR differ in how they age.

36896870

Spontaneous duodenal hematoma: a rare complication of triple antithrombotic therapy case report.

Triple therapy is defined as concurrent use of an anticoagulant and dual antiplatelet therapy. We aimed to review the clinical course of a patient who developed a spontaneous duodenal hematoma on triple therapy and appraise current guidelines regarding triple antithrombotic therapy use. A 59-year-old man presented with acute heart failure and an apical mural thrombus. After medical stabilization, the patient underwent elective coronary stent placement. He was placed on triple antithrombotic therapy and subsequently developed a spontaneous duodenal hematoma. This case describes a rare but potentially plication of triple therapy and underscores the importance of underutilizing this therapy. In conclusion, we report the clinical presentation and management of a rare plication in a patient on triple therapy.

36896871

Contrast-enhanced Ultrasound Combined With Elastography for the Evaluation of Muscle-invasive Bladder Cancer in Rats.

paring with the control group, we evaluated the usefulness of contrast-enhanced ultrasound bined with elastography for the assessment of muscle invasion by bladder cancer (MIBC) in a Sprague-Dawley (SD) rat model.

36896872

Individual Characteristics and Organizational Attributes: An Assessment of Probation Officer Burnout and Turnover Intent.

In recent years, Western and non-Western countries have experience increased reliance on probation services. However, prior research indicates that high job demands and ambiguous role responsibilities invoke feelings of stress and suggest the importance of understanding the relationship between stress and burnout and turnover. While past efforts largely focused on correctional officers (COs), less is known about how probation officers (POs) experience burnout and how organizational attributes may influence this relationship. Using survey data of federal POs (

36896873

The Effects of Nasal Surgery on Pulmonary Function: A Systematic Review and Meta-Analysis.

A deviated nasal septum (DNS) can result in an anatomical obstruction and impact lung function through prolonged suboptimal inspiration. Given the improvements in respiration reported by patients following septoplasty or septorhinoplasty (with or without inferior turbinate reduction), our study investigated the effect of these procedures on pulmonary function through a systematic review and meta-analysis.

36896874

Healthcare delivery research in older adults with cancer: A review of National Institutes of Health-funded projects.

Cancer is a disease of aging, and most people with cancer are older than 65. However, widespread uptake of evidence-based approaches that facilitate quality care delivery for older adults with cancer are lacking. This project aimed to review National Institutes of Health (NIH) grants funded in the last decade that focused on healthcare delivery in aging and older adults with cancer, and to examine grant-related characteristics, study designs, and scientific topics included.

36896875

Delivering effective combined treatments in mental health settings with difficult-to-treat patients: A bipolar case study illustrating the role of teamwork and other mediators.

Even in well-delivered treatments, a significant proportion of patients with severe diagnoses will not achieve sustained remission. For example, research demonstrates that in Bipolar II disorder, while psychological bined with pharmacotherapy yield much better results than pharmacotherapy alone, relapse rates remain very high. In this article, we show the successful treatment of Mrs. C., who was diagnosed with Bipolar II disorder and fell into the non-responders. The treatment integrated a novel approach grounded on a cognitive-behavioral theory with a systemic perspective. The psychotherapist, the psychiatrist, and a family posed the teamwork and delivered the treatment in three phases. In the first phase, the psychotherapist conjointly with the psychiatrist aimed at reducing symptoms. In the second phase, the psychotherapist and the family therapist addressed the dysfunctional relationship patterns that negatively reinforced emotional dysregulation. Finally, in the third phase, the aim was to consolidate the achievements, changes, and good es.

36896876

Intravascular Lithotripsy and Drug-Coated Balloon Angioplasty for Severely Calcified Common Femoral Artery Atherosclerotic Disease.

Intravascular lithotripsy (IVL) followed by drug-coated balloon (DCB) angioplasty might be a valuable alternative to surgery for mon femoral artery (CFA) atherosclerotic disease. Nonetheless, the 12 months performance of this treatment strategy remains unknown. This study reports on the 12 months es of IVL with adjunctive DCB angioplasty for calcified CFA lesions.

36896877

Postprocedural Management in Patients After Percutaneous Deep Venous Arterialization: An Expert Opinion.

After percutaneous deep venous arterialization (pDVA), the created arteriovenous circuit needs time to develop. Postprocedural care in patients after pDVA is essential in order to create optimal conditions for maturation of the circuit, and thus save the limb. However, current literature mainly focusses on the procedure itself, making postprocedural care an underexposed topic. Therefore, this study presents an overview of the available literature of postprocedural care of pDVA patients and provides mendations based on expert opinion when current knowledge is limited.

36896879

Therapeutic Interventions for Mental Wellness in Correctional Facilities: A Systematic Review.

The article includes a systematic review of therapeutic interventions being used to improve mental health of males and females incarcerated in U.S. jails and prisons. Using pertinent keywords, we searched the following databases: SocINDEX, CINAHL Complete, Medline Complete, PsychINFO, Psychology and Behavioral Sciences Collection, and Criminal Justice Abstracts with Full Text for studies published between 2010 and 2021. The initial search yielded 9,622 articles. After screening, 28 articles met the inclusion criteria and were reviewed. Review indicated use of a diverse range of interventions to address mental health es including, but not limited to, PTSD, depression, and anxiety. A few studies did not focus on specific mental health es, but rather on behavioral es such as distress, affect, mood, time spent in the hospital, number of acts of petency restoration, and wellbeing of the participants. The review includes implications for future research and practice.

36896878

Depressive and anxiety symptoms and illness perception among patients with acute coronary syndrome.

To evaluate the features of depressive and anxiety symptoms and illness perception and their associations in patients with acute coronary syndrome (ACS).

36896880

Association Between Hearing Impairment and Incident Depression: A Nationwide Follow-up Study.

Accumulating evidence suggests that hearing impairment is associated with the onset of depression. However, large-scale epidemiological studies are required to define this association more clearly. We aimed to investigate the risk of new-onset depression in Korean older adults with and without hearing impairment.

36896881

Bioinformatics analysis and verification of m6A related genes based on the construction of keloid diagnostic model.

Keloids are formed due to abnormal hyperplasia of the skin connective tissue. We explored the relationship between N6-methyladenosine (m6A)-related genes and keloids. The transcriptomic datasets (GSE44270 and GSE185309) of keloid and normal skin tissues samples were obtained from the Gene Expression Omnibus database. We constructed the m6A landscape and verified the corresponding genes using immunohistochemistry. We extracted hub genes for unsupervised clustering analysis using protein-protein interaction (PPI) network; gene ontology enrichment analysis was performed to determine the biological processes or functions affected by the differentially expressed genes (DEGs). We performed immune infiltration analysis to determine the relationship between keloids and the immune microenvironment using single-sample gene set enrichment analysis and CIBERSORT. Differential expression of several m6A genes was observed between the two groups; insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) was significantly upregulated in keloid patients. PPI analysis elucidated six genes with significant differences between the two keloid sample groups. Enrichment analysis revealed that the DEGs were mainly enriched in cell division, proliferation, and metabolism. Moreover, significant differences in immunity-related pathways were observed. Therefore, the results of this study will provide a reference for the elucidation of the pathogenesis and therapeutic targets of keloids.

36896882

Residential Instability and Suicidal Ideation Among Persons on Parole.

Parolees experience numerous barriers that may impact successful reintegration into society. Residential instability may further add to these obstacles, as there may be limited opportunities for housing given their criminal history. The present study aimed to examine the impact of residential instability on suicidal ideation among parolees. Results indicated that residentially stable and unstable individuals had similar risk factors which were significantly associated with suicidality, such as age and having perceived unmet mental health needs. Other risk factors differed among the two groups, highlighting the importance of treatment and preparation for re-entry into society while in the prison setting.

36896883

Could We Consider Ultrasound-Guided Minimally Invasive Autopsy as a Part of POCUS?

We present a 3-patient case series that support the use of ultrasound guided minimally invasive autopsy (MIA). This technique has a high diagnostic accuracy in specific clinical settings. It makes easier to diagnose pathologies once the patient has died, avoiding body deformation, with a notable reduction in sample processing pared to the open autopsy study and, therefore, a shorter overall diagnostic response time. MIA shows some similarities with point of care ultrasound (POCUS), like examination protocols or that they can be performed at the bedside.

36896884

Systematic Review and Meta-Analysis of Ex-Situ and In-Situ Fenestrated Stent-Grafts for Endovascular Repair of Aortic Arch Pathologies.

To gain insight into safety and efficacy of in situ and ex-situ fenestration techniques for total endovascular arch repair. The term ex-situ fenestration is referring to physician-modified stent-graft technique where fenestration is performed on a back table.

36896887

Narrowing the Divide: The Role of Telehealth in Type 1 Diabetes Care for Marginalized Communities.

Widespread uptake of telehealth in response to the COVID-19 pandemic has highlighted geographic, demographic, and economic disparities in access to virtual care. However, research studies and clinical programs that predate the pandemic demonstrate the potential for telehealth-based interventions to improve access to and es of type 1 diabetes (T1D) care for individuals in geographically or socially munities. In this mentary, we discuss telehealth-based care models that have been successful in improving care for marginalized T1D populations. We also outline the policy changes needed to expand access to such interventions to reduce established disparities in T1D care and promote better health equity among people living with T1D.

36896888

Juvenile Nasopharyngeal Angiofibroma: Outcomes Analysis Based Upon Hospital Volume.

To evaluate the management of juvenile nasopharyngeal angiofibroma (JNA) from a national perspective with parison based on hospital volume.

36896886

Health state utility estimation of

To obtain appropriate health state utility values for cost-effectiveness analyses of new

36896890

Structural and functional integrity of endocrine pancreas post administration of Karwinskia humboldtiana fruit to Wistar rats: a possible therapeutic application for cancer of exocrine origin.

Pancreatic adenocarcinoma represents a therapeutic challenge due to the high toxicity of antineoplastic treatments and secondary effects of pancreatectomy. T-514, a toxin isolated from Karwinskia humboldtiana (Kh) has shown antineoplastic activity on cell lines. In acute intoxication with Kh, we reported apoptosis on the exocrine portion of pancreas. One of the mechanisms of antineoplastic agents is the induction of apoptosis, therefore our main objective was to evidence structural and functional integrity of the islets of Langerhans after the administration of Kh fruit in Wistar rats.

36896891

Histone-lysine N-methyltransferase EHMT2 (G9a) inhibition mitigates tumorigenicity in Myc-driven liver cancer.

Hepatocellular carcinoma (HCC) is the third deadliest and sixth mon cancer in the world. Histone-lysine N-methyltransferase EHMT2 (also known as G9a) is a histone methyltransferase frequently overexpressed in many cancer types, including HCC. We showed that Myc-driven liver tumours have a unique H3K9 methylation pattern with corresponding G9a overexpression. This phenomenon of increased G9a was further observed in our c-Myc-positive HCC patient-derived xenografts. More importantly, we showed that HCC patients with higher c-Myc and G9a expression levels portend a poorer survival with lower median survival months. We demonstrated that c-Myc interacts with G9a in HCC and cooperates to regulate c-Myc-dependent gene repression. In addition, G9a stabilises c-Myc to promote cancer development, contributing to the growth and invasive capacity in HCC. bination therapy between G9a and synthetic-lethal target of c-Myc, CDK9, demonstrates strong efficacy in patient-derived avatars of Myc-driven HCC. Our work suggests that targeting G9a could prove to be a potential therapeutic avenue for Myc-driven liver cancer. This will increase our understanding of the underlying epigenetic mechanisms of aggressive tumour initiation and lead to improved therapeutic and diagnostic options for Myc-driven hepatic tumours.

36896893

Realizing Photoswitchable Mechanoluminescence in Organic Crystals Based on Photochromism.

Organic mechanoluminescent (ML) materials possessing photophysical properties that are sensitive to multiple external stimuli have shown great potential in many fields, including optic and sensing. Particularly, the photoswitchable ML property for these materials is fundamental to their applications but remains a formidable challenge. Herein, photoswitchable ML is successfully realized by endowing reversible photochromic properties to an ML molecule, namely 2-(1,2,2-triphenylvinyl) fluoropyridine (o-TPF). o-TPF shows both high-contrast photochromism with a distinct color change from white to purplish red, as well as bright blue ML (λ

36896894

Nanotechnology in hair growth: opportunities and challenges.

Tweetable abstract Nanotechnology and its role in hair growth by enhancing drug delivery for the management of alopecia #nanotechnology #hair #drug_delivery.

36896896

Preoperative Serum Albumin Level Predicts Length of Stay and Perioperative Adverse Events Following Vertebral Corpectomy and Posterior Stabilization for Metastatic Spine Disease.

Retrospective review of a prospectively collected national database.

36896895

Effects of COVID-19 vaccination during pregnancy on SARS-CoV-2 infection and maternal and neonatal outcomes: A systematic review and meta-analysis.

SARS-CoV-2 infection during pregnancy is associated with adverse maternal and neonatal es, but no systematic synthesis of evidence on COVID-19 vaccination during pregnancy against these es has been undertaken. Thus, we aimed to assess the collective evidence on the effects of COVID-19 vaccination during pregnancy on maternal and neonatal es. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched for articles published up to 1 November 2022. A systematic review and meta-analysis were performed to calculate pooled effects size and 95% confidence interval (CI). We evaluated 30 studies involving 862,272 individuals (308,428 vaccinated and 553,844 unvaccinated). Overall pooled analyses in pregnant women during pregnancy showed reduced risks of SARS-CoV-2 infection by 60% (41%-73%), COVID-19 hospitalisation during pregnancy by 53% (31%-69%), and COVID-19 intensive care unit (ICU) admission by 82% (12%-99%). Neonates of vaccinated women were 1.78 folds more likely to acquire SARS-CoV-2 infection during the first 2, 4 and 6 months of life during the Omicron period. The risk of stillbirth was reduced by 45% (17%-63%) in association with vaccination (vs. no vaccination) in pregnancy. A decrease of 15% (3%-25%), 33% (14%-48%), and 33% (17%-46%) in the odds of preterm births before 37, 32 and 28 weeks' gestation were associated with vaccination (vs. no vaccination) in pregnancy, respectively. The risk of neonatal ICU admission was significantly lower by 20% following COVID-19 vaccination in pregnancy (16%-24%). There was no evidence of a higher risk of adverse es including miscarriage, gestational diabetes, gestational hypertension, cardiac problems, oligohydramnios, polyhydramnios, unassisted vaginal delivery, cesarean delivery, postpartum haemorrhage, gestational age at delivery, placental abruption, Apgar score at 5 min below 7, low birthweight (<2500 g), very low birthweight (<1500 g), small for gestational age, and neonatal foetal abnormalities. COVID-19 vaccination during pregnancy is safe and highly effective in preventing maternal SARS-CoV-2 infection in pregnancy, without increasing the risk of adverse maternal and neonatal es, and is associated with a reduction in stillbirth, preterm births, and neonatal ICU admission. Importantly, maternal vaccination did not reduce the risk of neonatal SARS-CoV-2 infection during the first 6 months of life during the Omicron period.

36896898

Advances in Drug Delivery Systems Based on Red Blood Cells and Their Membrane-Derived Nanoparticles.

Red blood cells (RBCs) and RBC membrane-derived nanoparticles have been historically developed as bioinspired drug delivery systems bat the issues of premature clearance, toxicity, and immunogenicity of synthetic nanocarriers. RBC-based delivery systems possess characteristics including patibility, biodegradability, and long circulation time, which make them suited for systemic administration. Therefore, they have been employed in designing optimal drug formulations in various preclinical models and clinical trials to treat a wide range of diseases. In this review, we provide an overview of the biology, synthesis, and characterization of drug delivery systems based on RBCs and their membrane including whole RBCs, RBC membrane-camouflaged nanoparticles, RBC-derived extracellular vesicles, and RBC hitchhiking. We also highlight conventional and latest engineering strategies, along with various therapeutic modalities, for enhanced precision and effectiveness of drug delivery. Additionally, we focus on the current state of RBC-based therapeutic applications and their clinical translation as drug carriers, as well as discussing opportunities and challenges associated with these systems.

36896901

Role of Supplements in the Management of COVID-19 - A Comprehensive Review.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) and patients with COVID-19 may be treated primarily with SARS CoV- 2-targeting drugs and the therapeutic agents assisting in the management of plications. This review focuses on the supplements like vitamins, minerals, herbal constituents, and others that help prevent or manage negative es among COVID-19 patients. The literature was searched in databases such as Medline/PubMed Central/PubMed, Google Scholar, Science Direct, EBSCO, Scopus, EMBASE, the Directory of Open Access Journals (DOAJ), and reference lists to identify relevant articles. The vitamins, including vitamin C, and vitamin D, minerals such as zinc, selenium, and copper, herbal constituents like thymoquinone, curcumin, naringenin, quercetin, and glycyrrhizin, and other supplements, including N-acetylcysteine and melatonin. Melatonin have been identified as having the potential to manage patients with COVID-19 along with standard care. Some of the ongoing clinical trials are investigating the effectiveness of different supplements among COVID-19 patients.

36896902

DihydrofolateReductase (DHFR) Inhibitors: A Comprehensive Review.

Dihydrofolate reductase (DHFR) is an indispensable enzyme required for the survival of most prokaryotic and eukaryotic cells as it is involved in the biosynthesis of essential ponents. DHFR has attracted a lot of attention as a molecular target for various diseases like cancer, bacterial infection, malaria, tuberculosis, dental caries, trypanosomiasis, leishmaniasis, fungal infection, influenza, Buruli ulcer, and respiratory illness. Various teams of researchers have reported different DHFR inhibitors to explore their therapeutic efficacy. Despite all the progress made, there is a strong need to find more novel leading structures, which may be used as better and safe DHFR inhibitors, especially against the microorganisms which are resistant to the developed drug candidates.

36896903

Computational Analysis to Predict Drug Targets for the Therapeutic Management of

Mycobacterium avium sp. paratuberculosis (MAP) is a pathogen, which causes paratuberculosis in animals; it has also been found to be associated with a number of autoimmune disorders in humans. The emergence of drug resistance has also been found in this bacillus during disease management.

36896904

Anxiety, Depression, Body Mass Index, Physical Activity in Nomophobic Italian Nurses: A Chronic Latent Inflammation?

To investigate which risk factors are strictly connected to nomophobia in Italian nurses, according to socio-demographic characteristics, Body Mass Index scores, physical activity habits, anxiety, and depression.

36896905

Formulation and Development of Hyaluronic Acid based Gel with Ketoconazole-Loaded Nanostructured Lipid Carriers in Fungal Infection.

Ketoconazole is an imidazole ring containing antifungal agent used in the treatment of systemic fungal infections. It acts by blocking the synthesis of ergosterol, an ponent of the fungal cell membrane.

36896906

Insulin Glargine in Type 1 Diabetes Mellitus: A Review of Clinical Trials and Real-world Evidence Across Two Decades.

Over the past two decades, insulin glargine 100 U/mL (Gla-100) has emerged as the "standard of care" basal insulin for the management of type 1 diabetes mellitus (T1DM). Both formulations, insulin glargine 100 U/mL (Gla-100) and glargine 300 U/mL (Gla-300) have been extensively studied against parator basal insulins across various clinical and real-world studies. In prehensive article, we reviewed the evidence on both insulin glargine formulations in T1DM across clinical trials and real-world studies.

36896908

Bleeding Complications in a Patient After the Unexpected Interaction between Valproic Acid and Phenprocoumon.

Phenprocoumon is a vitamin K antagonist that is widely prescribed in Europe and Latin America for the prophylaxis and treatment of thromboembolic events.

36896909

General histological woes: Encore. Tissues, please.

In a previous essay, we wrote about the ings of the four basic tissue dogma of histology - miscellaneous tissues lumped under the ill-fitting name "connective tissues" and the existence of human tissues that are not recognized as subtypes of any of the four "basic types". A provisional reclassification of human tissues was constructed to improve the precision pleteness of the tissue taxonomy. Here, we address criticisms from a recent paper that claims that the four basic tissue dogma is more useful than that revised classification in medical education and in clinical practice. Some of the criticism appears to arise from mon misconception of a tissue as simply an array of similar cells.

36896910

PK/PD modeling to characterize placebo and treatment effect of omalizumab for chronic spontaneous urticaria.

The pharmacokinetic (PK) characteristics of omalizumab and its pharmacodynamic (PD) effect in patients has yet to be fully characterized in chronic spontaneous urticaria, which could elucidate its pathogenesis and treatment response. This study has two objectives; (1) characterize the population PK of omalizumab and its PD effect on IgE, and (2) develop a drug effect model of omalizumab in urticaria (via change in weekly itch severity score). The target-mediated population of PK/PD model incorporating omalizumab-IgE binding and turnover adequately described PK and PD of omalizumab. The partment model and linear drug effect and additive placebo response adequately described placebo and treatment effects of omalizumab. Several baseline covariates were identified for PK/PD and drug effect models. The developed model has the potential to aid in understanding variability in PK/PD as well as response to omalizumab treatment.

36896911

A Text-Mining Analysis to Examine Dominant Sources of Online Information and Content on Continuous Glucose Monitors.

The purpose of this study is to use text-mining methods to examine the dominant sources of online information and content about continuous glucose monitors (CGMs). Because the internet is the most popular source for health information, it is important to understand what is being said about CGMs in online sources of information.

36896912

A mitochondrial SCF-FBXL4 ubiquitin E3 ligase complex degrades BNIP3 and NIX to restrain mitophagy and prevent mitochondrial disease.

Mitophagy is a fundamental quality control mechanism of mitochondria. Its regulatory mechanisms and pathological implications remain poorly understood. Here, via a mitochondria-targeted genetic screen, we found that knockout (KO) of FBXL4, a mitochondrial disease gene, hyperactivates mitophagy at basal conditions. Subsequent counter screen revealed that FBXL4-KO hyperactivates mitophagy via two mitophagy receptors BNIP3 and NIX. We determined that FBXL4 functions as an integral outer-membrane protein that forms an SCF-FBXL4 ubiquitin E3 plex. SCF-FBXL4 ubiquitinates BNIP3 and NIX to target them for degradation. Pathogenic FBXL4 mutations disrupt SCF-FBXL4 assembly and impair substrate degradation. Fbxl4

36896914

Experimental approaches to study evolutionary cell biology using yeasts.

The past century has witnessed tremendous advances in understanding how cells function. Nevertheless, how cellular processes have evolved is still poorly understood. Many studies have highlighted surprising molecular diversity in how cells from diverse species execute the same processes, and advances parative genomics are likely to reveal much more molecular diversity than was believed possible until recently. Extant cells remain therefore the product of an evolutionary history that we vastly ignore. Evolutionary cell biology has emerged as a discipline aiming to address this knowledge gap bining evolutionary, molecular, and cellular biology thinking. Recent studies have shown how even essential molecular processes, such as DNA replication, can undergo fast adaptive evolution under certain laboratory conditions. These developments open new lines of research where the evolution of cellular processes can be investigated experimentally. Yeasts naturally find themselves at the forefront of this research line. Not only do they allow the observation of fast evolutionary adaptation, but they also provide numerous genomic, synthetic, and cellular biology tools already developed by a munity. Here we propose that yeasts can serve as an "evolutionary cell lab" to test hypotheses, principles, and ideas in evolutionary cell biology. We discuss various experimental approaches available for this purpose, and how biology at large can benefit from them.

36896915

Large symptomatic esophageal diverticulum.

A 72 years-old woman derived to Gastroenterology Department from Primary Care due to pyrosis and sometimes dysphagia with 8 years evolution, showing isolated episodes of regurgitation without any other alarms signs, and currently asymptomatic treated with omeprazole. She had a gastroscopy performed diagnosing dilated oesophageal lumen and food rests which were not able to reach gastric cavity being thus suspected of achalasia. She were performed a pHmetry without pathologic reflux sign, oesophageal manometry showing no presence of oesophageal motor alterations, and oesophagogastric transit perceiving a diverticulum in the posterior wall of the oesophageal lower third (Figure 1 and 2) with food content and neither additional alterations nor achalasia signs. Given these findings, patient had gastroscopy performed again, then detecting a large diverticulum (4-5 cm of size) in the distal oesophageal third occupying 50% of the oesophageal lumen and plenty of semi-liquid food rests. After the diverticulum aspiration, whitish mucous mass was observed with erythematous areas around and 1.5 cm sliding hiatal hernia, progressing to second duodenal section without alterations yet. Therefore, due to clinical findings and symptomatology, patient was derived to Surgery Department to assess diverticulectomy.

36896916

The effect of a lifestyle intervention program using a mobile application versus the effect of a program using a booklet for adults with metabolic syndrome: A three-arm randomized controlled trial.

The research aimed to examine the effect of a lifestyle intervention program using mobile application versus booklet for adults with metabolic syndrome in Hong Kong. The prised body weight (primary e), exercise amount, improvement of cardiometabolic risk factors, cardiovascular endurance, perceived stress scale, and exercise self-efficacy.

36896917

Diversification in the inositol tris/tetrakisphosphate kinase (ITPK) family: crystal structure and enzymology of the outlier AtITPK4.

Myo-inositol tris/tetrakisphosphate kinases (ITPKs) catalyze diverse phosphotransfer reactions with myo-inositol phosphate and myo-inositol pyrophosphate substrates. However, the lack of structures of nucleotide-coordinated plant ITPKs thwarts a rational understanding of phosphotransfer reactions of the family. Arabidopsis possesses a family of four ITPKs of which two isoforms, ITPK1 and ITPK4, control inositol hexakisphosphate and inositol pyrophosphate levels directly or by provision of precursors. Here, we describe the specificity of Arabidopsis ITPK4 to pairs of enantiomers of diverse inositol polyphosphates and show how substrate specificity differs from Arabidopsis ITPK1. Moreover, we provide a description of the crystal structure of ATP-coordinated AtITPK4 at 2.11 Å resolution that, along with a description of the enantiospecificity of the enzyme, affords a molecular explanation for the diverse phosphotransferase activity of this enzyme. That Arabidopsis ITPK4 has a KM for ATP in the tens of micromolar range, potentially explains how, despite the large-scale abolition of InsP6, InsP7 and InsP8 synthesis in Atitpk4 mutants, Atitpk4 lacks the phosphate starvation responses of Atitpk1 mutants. We further demonstrate that Arabidopsis ITPK4 and its homologues in other plants possess an N-terminal haloacid dehalogenase-like fold not previously described. The structural and enzymological information revealed will guide elucidation of ITPK4 function in diverse physiological contexts, including InsP8-dependent aspects of plant biology.

36896918

Chaetocin disrupts the SUV39H1-HP1 interaction independent of SUV39H1 methyltransferase activity.

Chemical tools to control the activities and interactions of ponents have broad impact on our understanding of cellular and disease processes. It is important to accurately identify their molecular effects to inform clinical efforts and interpretations of scientific studies. Chaetocin is a widely used chemical that decreases H3K9 methylation in cells. It is frequently attributed as a specific inhibitor of the histone methyltransferase activities of SUV39H1/SU(VAR)3-9, although prior observations showed chaetocin likely inhibits methyltransferase activity through covalent mechanisms involving its epipolythiodixopiperazine disulfide 'warhead' functionality. The continued use of chaetocin in scientific studies may derive from the net effect of reduced H3K9 methylation, irrespective of a direct or indirect mechanism. However, there may be other molecular impacts of chaetocin on SUV39H1 besides inhibition of H3K9 methylation levels that could confound the interpretation of past and future experimental studies. Here, we test a new hypothesis that chaetocin may have an additional downstream impact aside from inhibition of methyltransferase activity. Using bination of truncation mutants, a yeast two-hybrid system, and direct in vitro binding assays, we show that the human SUV39H1 chromodomain (CD) and HP1 chromoshadow domain (CSD) directly interact. Chaetocin inhibits this binding interaction through its disulfide functionality with some specificity by covalently binding with the CD of SUV39H1, whereas the histone H3-HP1 interaction is not inhibited. Given the key role of HP1 dimers in driving a feedback cascade to recruit SUV39H1 and to establish and stabilize constitutive heterochromatin, this additional molecular consequence of chaetocin should be broadly considered.

36896920

An improved method for evaluating LINAC isocenter.

The traditional approach to medical linear accelerator (LINAC) isocenter quality assurance is pare the radius of the LINAC isocenter, determined via analysis of Winston-Lutz (WL) dataset, to a threshold in order to approve the LINAC for clinical use. This scalar metric provides little insight into beam-to-target accuracy with gantry and couch motion.

36896921

Intestinal obstruction secondary to Brunner's glands hyperplasia.

Brunner's gland hyperplasia constitutes 10.6% of benign tumors of the duodenum, with an incidence of 0.008%. It is usually an incidental finding during endoscopy or imaging tests as they are small and asymptomatic. In the case of symptomatic tumors, resection of the lesion is indicated. In lesions ≤2 cm, endoscopic resection can be chosen, reserving surgery for larger lesions or endoscopically inaccessible ones. We present the case of a patient with a history of vomiting and hyporexia of months of evolution who presented peptic ulcer perforation and underwent surgery. During follow-up, she presented intestinal obstruction due to pyloric stenosis. Given the impossibility of ruling out a neoplastic process with certainty in diagnostic tests, surgical resection (antrectomy) was decided with an anatomopathological finding of Brunner's gland hyperplasia.

36896922

Does the ARRIVE trial merit changing obstetric practice? Some reflections four-year postrelease.

It has been 4 years since the release of the study Labor Induction versus Expectant Management in Low-Risk Nulliparous Women, also known as the ARRIVE trial. As researchers and speakers who frequently present to the United States and international audiences about models of care and strategies to support normal physiologic labor and birth, we have had ample opportunity to engage with practitioners who consistently ask about our perspectives on the ARRIVE trial's findings and methods. Many note the marked increase in pressure they feel to induce at 39 weeks since the study's publication in 2018.

36896923

Factors associated with poor prognosis of hip arthritis in juvenile idiopathic arthritis: Data from the JIR cohort.

Hip involvement remains a predictor of severe juvenile idiopathic arthritis (JIA) course and carries a high risk of disability. This study aims to determine the factors of poor prognosis of hip involvement in patients with JIA and to assess the treatment response.

36896924

Carcinoid syndrome and somatostatin analogues.

Clinical experience is herein reported with somatostatin analogues (octreotide and lanreotide) in the management of 10 CS out of a series of 14 collected cases of carcinoid syndrome (CS).

36896925

Time trends and endoscopic management of foreign body ingestion in the upper GI tract: a retrospective analysis of 1,152 cases in China.

foreign body ingestions are encountered in the clinical practice and sometimes require endoscopic management. However, time trends and epidemiology of these cases have not been fully clarified. Whether seasons and festivals have an effect on the occurrence has been poorly described.

36896926

Enhanced Cell Penetration and Pluripotency Maintenance of hiPSCs in 3D Natural Chitosan Scaffolds.

Human-induced pluripotent stem cells (hiPSCs) cultured in 3D matrices hold great promise in disease modeling, drug discovery, and tissue regeneration. Uniform cell distribution in a 3D structure is critical to the growth and function of hiPSCs, yet cell seeding in 3D matrices often remains superficial, leading to limited cell proliferation promised pluripotency. Here, an approach to improve cell penetration depth of hiPSCs in 3D scaffolds modified with hiPSCs conditioned medium (CM) is reported. It is shown that extracellular ponents are successfully deposited onto the scaffold wall surface after CM treatment and promoted homogeneous cell adhesion during initial seeding. Compared to plain, unmodified scaffolds, the CM treated scaffold improves spatial cell distribution uniformity and upregulates pluripotency markers. Notably, the expression of 29 genes associated with 11 signaling pathways participated in the pluripotency maintenance of hiPSCs exhibits >2-fold change in hiPSCs grown in the CM treated scaffolds than 2D counterparts, demonstrating that CM treated scaffolds can support a more primitive and undifferentiated phenotype of hiPSCs. This study introduces a simple and effective method to enhance cell penetration and maintain cell pluripotency in 3D matrices.

36896927

Hepatic splenosis, description of an unusual behavior at contrast-enhanced ultrasonography (CEUS).

The case was a 47-year-old male, asymptomatic, with a personal history of splenectomy in childhood. He was referred to our outpatient clinic plete the study of space-occupying liver lesion. The initial diagnostic suspicion was liver adenoma, given its behavior on magnetic resonance imaging and the absence of previous liver disease. We performed an intravascular contrast-enhanced ultrasound (CEUS) (SonoVue©). The lesion showed rapid centripetal enhancement, remaining enhanced in the portal phase with dim washout in the late venous phase. Given the therapeutic implications of the diagnosis of a hepatic adenoma, an ultrasound-guided percutaneous biopsy with an 18-gauge core needle was performed. The anatomopathological study confirmed the presence of hepatic splenosis. Hepatic splenosis can present as isolated or multiple foci (1). There is little published information on the behavior of hepatic splenosis in CEUS (2, 3, 4), which prevents any behavior from being generalized. The most frequently described behavior is hyperenhancement in the arterial phase without subsequent washout, not a specific behavior that can lead to the misdiagnosis of other entities such as hemangioma. In our case, it was caused by an isolated focus of splenosis that did not show the most frequent described behavior at CEUS, since it presented a faint washout in the venous phase, making it necessary to rule out malignancy.

36896929

Gastric calcinosis ulcer in a renal transplanted patient.

A 53-year-old lady with dysfunctional renal transplant and post-surgical hypoparathyroidism with phosphocalcic metabolism impairment was admitted to hospital because of long-lasting epigastric pain and nausea. An esophagogastroduodenoscopy was performed, visualising a nodular lesion of 1 cm diameter with a depressed and ulcerated base. Microscopically the lesion was in relation with a metastatic calcinosis ulcer. Pantoprazole was initiated and serum phosphocalcic levels adjusted, achieving symptom remission. In the follow-up esophagogastroduodenoscopy, the lesion was healing with a fibrinous base and the histopathological report diagnosed superficial gastritis.

36896928

Methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility: an updated meta-analysis.

Widely regarded as one of the most prevalent malignancies worldwide, gastric cancer (GC) is mon clinical condition of the digestive system. Reviewing 14 meta-analyses that evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and GC risk, we observed inconsistent results, and the credibility of the significant correlation between the statistical results was ignored. With the aim of further exploring the association between MTHFR C677T and A1298C and the risk of GC, we searched electronic databases, pooling 43 relevant studies and calculating odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for each of the five genetic models. Subgroup and regression analyses were performed to look for sources of heterogeneity and publication bias was assessed by funnel plots. To assess the plausibility of statistically significant associations, we used the FPRP test and the Venice criteria. Overall data analysis showed that MTHFR C677T polymorphism was significantly associated with GC risk, especially in Asians, while MTHFR A1298C polymorphism was not associated with GC risk. However, in subgroup analysis by hospital-based controls, we found that MTHFR A1298C might be a protective factor for GC. After credibility assessment, the statistical association between MTHFR C677T and GC susceptibility study was classified as 'less credible positive result', while the result of MTHFR A1298C was considered unreliable. In summary, the present study strongly suggests that MTHFR C677T and A1298C polymorphisms are not significantly associated with the GC risk.

36896930

Colonic perforation after esophagogastroduodenoscopy: complications with self-expanding metallic stents.

An 83-year-old man was admitted to the emergency room with abdominal pain and bloating. puted tomography (CT) revealed a sigmoid colon obstruction caused by colonic carcinoma involving a short segment with circumferential luminal narrowing. The patient underwent endoscopy with colonic self-expanding metallic stent (SEMS) placement as a bridge to surgery. Six days after SEMS placement, the patient was prepared for esophagogastroduodenoscopy for screening. Although screening revealed plications, 8 h later, the plained of sudden abdominal pain. Emergency abdominal CT revealed that the SEMS was about to burst out of the colon. An emergency operation with sigmoidectomy and colostomy was performed, and operative findings revealed a colonic perforation by the SEMS at the proximal side of the tumor. The patient was discharged from the hospital without major problems. This case is a very plication of colonic SEMS insertion. It is possible that increased intraluminal bowel movement and/or CO2 pressure during the esophagogastroduodenoscopy caused colonic perforation. Endoscopic placement of a SEMS is an effective alternative to surgical pression for treating colon obstruction. To avoid unexpected and unnecessary perforations, tests that could increase the intraluminal pressure within the intestine after SEMS insertion should be avoided.

36896931

CircRBM23 regulates the switch between osteogenesis and adipogenesis of mesenchymal stem cells via sponging miR-338-3p.

The disruption of the balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in bone marrow contributes to the adipocytes accumulation and bone loss, which leads to the development of osteoporosis (OP). The circular RNA (circRNA), circRBM23, was generated from the RNA binding motif protein 23 (RBM23) gene. It was reported that circRBM23 was down-regulated in OP patients, but it remains unknown whether its down-regulation is involved in the lineage switch of MSCs.

36896932

Efficacy and safety of mesenchymal stem cells in the treatment of perianal fistulas in Crohn's disease: a meta-analysis of randomized controlled trials.

Local mesenchymal stem cell (MSC) therapy for perianal fistulas in Crohn's disease (CD) has yielded promising results, but it still remains controversial. In this study, we aimed to conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of MSC therapy for perianal CD (pCD).

36896933

Retractions relevant to COVID-19: does the retraction rate jump during the pandemic?

Since the outbreak of Coronavirus Disease 2019, the munity has acted promptly before many publications appeared in the scientific literature. It posed a question of whether the expedited research and publication process would impair the research integrity, further leading to the rise in retractions. Hence in this study, we aimed to examine the characteristics of retracted articles related to COVID-19 and provide some insight into the scientific publishing of COVID-19 literature.

36896935

Suppressive Strong Metal-Support Interactions on Ruthenium/TiO

Strong metal-support interactions (SMSI) have gained great attention in the heterogeneous catalysis field, but its negative role in regulating light-induced electron transfer is rarely explored. Herein, we describe how SMSI significantly restrains the activity of Ru/TiO

36896936

Barriers and Facilitators to Home- and Community-Based Services Access for Persons With Dementia and Their Caregivers.

The United States has seen increasing shifts toward home- munity-based services (HCBS) in place of institutional care for long-term services and supports. However, research has neglected to assess whether these shifts have improved access to HCBS for persons with dementia. This paper identifies HCBS access barriers and facilitators, and discusses how barriers contribute to disparities for persons with dementia living in rural areas and exacerbate disparities for minoritized populations.

36896939

Strategies to improve the experience of patients with brain tumors in the inpatient rehabilitation setting: development of a care coordination checklist.

To develop a checklist to facilitate coordination of care munication of patients with brain tumors and assess the benefit of the checklist using a quality improvement survey.

36896934

Efficacy of

The significance of

36896940

Use of Sotrovimab in a cohort of pregnant women with a high risk of COVID 19 progression: a single-center experience.

Neutralizing monoclonal antibodies (mAbs) have been shown to reduce disease progression in patients with underlying predisposing conditions. Unfortunately, there is no evidence on the use of Sotrovimab in pregnant women. Herein we present a case series of pregnant women who received mAbs with Sotrovimab following the Italian Drug Agency (AIFA) indications. Since February 1, 2022 all pregnant women - regardless of gestational age - admitted to Obstetrics & Gynaecology of Policlinico University of Bari, with positive nasopharyngeal NAAT for SARS-CoV-2 were screened according to the AIFA indications for Sotrovimab and, if eligible, were proposed for treatment. Data on COVID-19, pregnancy, delivery, newborn es, and adverse events were collected. From February 1 to May 15, 2022, 58 pregnant women were screened. Fifty (86%) patients were eligible, 19 of them (32.7%) denied their consent, in 18 cases (31%), the drug was temporarily unavailable, and the remaining 13 (22%) were treated with Sotrovimab. Out of these 13 patients, 6 (46%) were in the 3rd and 7 (54%) in the 2nd trimester of pregnancy. None of the 13 patients experienced adverse reactions due to Sotrovimab and all had a good clinical e. Furthermore, evaluating pre- and post-infusion clinical status and hematochemical profile, a reduction in D-dimers and an increase in SARS-CoV-2 antibodies (p < 0.01) during the 72 h following the infusion were observed. Our data, the first on the use of Sotrovimab in pregnant women, showed the safety and efficacy drug profile and its potential crucial role in preventing COVID-19 disease progression.

36896941

Stress, depression, and hippocampus: from biochemistry to electrophysiology.

Major depressive disorder is a mon serious mental illness with increasing prevalence in the population. Its pathology includes biochemical, morphological, and electrophysiological changes in various brain areas. In spite of decades of extensive research pathophysiology of depression is still not sufficiently understood. When depression occurs just before or during pregnancy, it may have a detrimental effect on perinatal and/or postnatal brain development, affecting the offspring's behavior. An important role in the pathology of depression is the hippocampus as a center for cognition and memory. Here we review changes in morphology, biochemical, and electrical signaling caused by depression in first and second generation identified in various animal models.

36896942

Construction of a novel lncRNA-miRNA-mRNA competing endogenous RNA network in muscle in response to exercise training.

Physical inactivity has evidently been a hazard factor for many diseases, including cardiovascular disease, diabetes, cancer, etc. Rising evidence indicates that RNA, petitive endogenous RNA (ceRNA), plays an important role in adaptive changes in skeletal muscle in response to exercise training. Although the effects of exercise-induced fitness on skeletal muscle have been well established, the mechanisms underlying are not fully understood. The purpose of this study is to construct a novel ceRNA network in skeletal muscle in response to exercise training. Skeletal muscle gene expression profiles were downloaded from the GEO database. Then, we identified differentially expressed lncRNAs, miRNAs, and mRNAs between the pre-exercise and post-exercise samples. Subsequently, we constructed lncRNA-miRNA-mRNA regulatory networks based on the ceRNA theory. 1153 mRNAs (687 upregulated and 466 downregulated), 7 miRNAs (3 upregulated and 4 downregulated), and 5 lncRNAs (3 upregulated and 2 downregulated) were identified as differentially expressed genes. 3 lncRNAs, 5 miRNAs and 227 mRNAs were obtained to build miRNA-mediated ceRNA networks. We constructed a novel ceRNA regulatory network in muscle in response to exercise training, which provides insights into molecular mechanisms underlying the health benefits brought by physical activity.

36896938

Microbiota-directed biotherapeutics: considerations for quality and functional assessment.

Mounting evidence points to causative or correlative roles of gut microbiome in the development of a myriad of diseases ranging from gastrointestinal diseases, metabolic diseases to neurological disorders and cancers. Consequently, efforts have been made to develop and apply therapeutics targeting the human microbiome, in particular the gut microbiota, for treating diseases and maintaining wellness. Here we summarize the current development of gut microbiota-directed therapeutics with a focus on novel biotherapeutics, elaborate the need of advanced -omics approaches for evaluating the microbiota-type biotherapeutics, and discuss the clinical and regulatory challenges. We also discuss the development and potential application of

36896943

Testicular cytoprotective effect of glucagon like peptide-1 in diabetic rats involves inhibition of apoptosis, endoplasmic reticulum stress and activation of autophagy.

This study aimed to explore the possible cytoprotective effects of exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in the testicles of diabetic rats. Exenatide has numerous advantageous properties in addition to its hypoglycemic effect. However, its impact on testicular tissue in diabetes needs more clarification. Therefore, rats were divided into control, exenatide-treated, diabetic and exenatide-treated diabetic groups. Blood glucose and serum levels of insulin, testosterone, pituitary gonadotropins and kisspeptin-1 were measured. Real-time PCR for beclin-1, p62, mammalian target of rapamycin (mTOR), and AMP-activated protein kinase (AMPK), were estimated in testicular tissue in addition to markers of oxidative stress, inflammation, and endoplasmic reticulum stress. Also, immuno-expression of protein P53, nuclear erythroid factor2 (Nrf2) and vimentin was conducted. Exenatide was able to attenuate diabetic toxic changes and enhance autophagy in testicular tissue. These results indicate the protective effect of exenatide against diabetic testicular dysfunction.

36896944

Hypoxic cardiomyocyte-derived exosomes regulate cardiac fibroblast activation, apoptosis, migration and ferroptosis through miR-208a/b.

Studies have found that cardiomyocytes and cardiac fibroblasts (CFs) municate through exosomes, thereby affecting each other's biological functions, but there are few studies on the mechanism. miR-208a/b are specifically expressed in the heart and highly expressed in exosomes derived from various myocardial diseases. Hypoxia induced cardiomyocytes to secrete exosomes (H-Exo) with high expression of miR-208a/b. When H-Exo were added to CFs for co-culture, it was found that CFs took up exosomes, thereby upregulating the expression of miR-208a/b. H-Exo significantly promoted the viability and migration of CFs, enhanced the expression of α-SMA, collagen I and III, and promoted the secretion of collagen I and III. miR-208a or/and miR-208b inhibitors significantly attenuated the effects of H-Exo on CF biological functions. miR-208a/b inhibitors significantly enhanced the levels of apoptosis and caspase-3 activity in CFs, while H-Exo significantly attenuated the pro-apoptotic effects of miR-208a/b inhibitors. Further treatment of CFs with ferroptosis inducer Erastin found that H-Exo further enhanced the accumulation of ROS, MDA and Fe2+, the main indicators of ferroptosis, and inhibited the expression of GPX4, a key regulator of ferroptosis. miR-208a or/and miR-208b inhibitors significantly attenuated the effects of Erastin and H-Exo on ferroptosis. In conclusion, hypoxic cardiomyocyte-derived exosomes can regulate the biological functions of CFs through highly expressed miR-208a/b.

36896945

Bioinformatic analysis and validation of cardiac hypertrophy-related genes.

In this study, we have screened genes involved in myocardial hypertrophy (MH) using a mice model pensatory stress overload (transverse aortic constriction, TAC) and bioinformatics. Microarrays were downloaded, and according to the Venn diagram, three groups of data intersections were obtained. Gene function was analyzed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), whereas protein-protein interactions (PPI) were analyzed using the STRING database. A mouse aortic arch ligation model was established to verify and screen the expression of hub genes. A total of 53 (DEGs) and 32 PPI genes were screened out. GO analysis showed DEGs mainly involved in cytokine and peptide inhibitor activity. KEGG analysis focused on ECM receptor interaction and osteoclast differentiation. Expedia co-expression gene network analysis showed that Serpina3n, Cdkn1a, Fos, Col5a2, Fn1 and Timp1 participated in the occurrence and development of MH. RT-qPCR verified that all the other 9 hub genes except Lox were highly expressed in TAC mice. This study lays a foundation for further study on the molecular mechanism of MH and for screening of molecular markers.

36896946

Protective effects of NF-κB inhibitor and continuous perfusion of pulmonary arteries on pulmonary injury in piglet models of deep hypothermia low flow.

Deep hypothermia with low flow perfusion (DHLF) is mon cardiopulmonary bypass (CPB) technique. The associated lung ischemia/reperfusion injury is a major cause of postoperative morbidity and mortality in patients undergoing DHLP; we aimed to investigate the effects of nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC) with continuous perfusion of pulmonary arteries (CPP) on DHLF-induced lung injury and the related molecular mechanisms. Twenty-four piglets were randomly divided into the DHLF (control), CPP (with DHLF), or CPP+PDTC (intravenous PDTC before CPP with DHLF) groups. Lung injury was evaluated by respiratory function measurement, lung immunohistochemistry, and serum levels of TNF, IL-8, IL-6, and NF-κB before CPB, at pletion, and at 1 h post-CPB. Western blot was used to detect NF-κB protein expression in lung tissues. After CPB, decreased parcial pressure of oxygen (PaO2) and increased parcial pressure of carbon dioxide (PaCO2) and serum levels of TNF, IL-8, IL-6, and NF-κB were observed in the DHLF group. Both CPP and CPP+PDTC groups showed better indices of lung function, decreased levels of TNF, IL-8, and IL-6, and less severe pulmonary edemas and injuries. PDTC with CPP further improved pulmonary function and mitigated pulmonary injury than did CPP alone. PDTC with CPP better attenuates DHLF-induced lung injury than does CPP alone.

36896947

The role of NOS3 (rs2070744) and GNB3 (rs5443) genes' polymorphisms in endothelial dysfunction pathway and carotid intima-media thickness in hypertensive patients.

The mechanisms orchestrating the balance between nitric oxide and endothelium-derived contracting factors, and genetic predisposition to endothelial dysfunction in hypertensive patients remain to be determined. One-hundred hypertensive patients participated in the case-control study to clarify the risk of endothelial dysfunction and carotid "intima media" thickness (IMT) changes depending on NOS3 (rs2070744) and GNB3 (rs5443) genes' polymorphisms. It is found that presence of NOS3 gene's С-allele significantly elevates the risk of atherosclerotic plaques on carotid arteries (OR95%CI: 1.24-11.20; р = 0.019) and the probability of low NOS3 gene expression (OR95%CI: 17.72-520.0; р < 0.001). Homozygous carriage of С-allele of GNB3 gene is protective and corresponds to the lowest chances of the carotid IMT increase, atherosclerotic plaques formation and sVCAM-1 elevation (OR = 0.10-0.34; OR95%CI: 0.03-0.95; р ≤ 0.035-0.001). Vice versa, Т-allele of GNB3 gene significantly augments the risk of the carotid IMT increase (OR95%CI: 1.09-7.74; р = 0.027) including development of atherosclerotic plaques, associating GNB3 (rs5443) with cardiovascular pathology.

36896948

Silencing of long non-coding RNA SOX2-overlapping transcript relieves myocardial ischemia/reperfusion injury through up-regulating miRNA-146a-5p.

Long non-coding RNAs (lncRNAs) are involved in the development of myocardial ischemia/reperfusion injury (MIRI). In this study, we aimed to explore the regulatory effect and mechanism of lncRNA SOX2-overlapping transcript (SOX2-OT) in MIRI. The viability of oxygen and glucose deprivation/reperfusion (OGD/R)-treated H9c2 cells was detected by MTT assay. The levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), and superoxide dismutase (SOD) were measured by ELISA. The target relationship between SOX2-OT and miR-146a-5p was predicted by LncBase, and subsequently confirmed by Dual luciferase reporter assay. The effects of SOX2-OT silencing on myocardial apoptosis and function were further validated in MIRI rats. The expression of SOX2-OT was increased in OGD/R-treated H9c2 cells and myocardial tissues of MIRI rats. Silencing of SOX2-OT increased the viability and inhibited the inflammation and oxidative stress of OGD/R-treated H9c2 cells. SOX2-OT negatively regulated its target miR-146a-5p. Silencing of miR-146a-5p reversed the effects of sh-SOX2-OT on OGD/R-treated H9c2 cells. In addition, silencing of SOX2-OT also alleviated myocardial apoptosis and improved myocardial function in MIRI rats. Silencing of SOX2-OT relieved the apoptosis, inflammation, and oxidative stress of myocardial cells via up-regulating miR-146a-5p, contributing to the remission of MIRI.

36896949

Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats.

Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.

36896950

Ivabradine curbs isoproterenol-induced kidney fibrosis.

This study investigated whether chronic isoproterenol administration could induce kidney alterations and whether ivabradine, a heart rate (HR)-reducing substance exerting cardiovascular protection, is able to attenuate potential kidney damage. Twenty-eight Wistar rats were divided into non-diseased controls, rats treated with ivabradine, rats treated with isoproterenol, and rats treated with isoproterenol plus ivabradine. Six weeks of isoproterenol administration was associated with decreased systolic blood pressure (SBP) (by 25%) and glomerular, tubulointerstitial and vascular/perivascular fibrosis due to enhanced type I collagen volume (7-, 8-, and 4-fold, respectively). Ivabradine reduced HR (by 15%), partly prevented SBP decline (by 10%) and site-specifically mitigated kidney fibrosis by decreasing type I collagen volume in all three sites investigated (by 69, 58, and 67%, respectively) and the ratio of type I collagen-to-type III collagen in glomerular and vascular/perivascular sites (by 79 and 73%, respectively). We conclude that ivabradine exerts protection against kidney remodelling in isoproterenol-induced kidney damage.

36896952

Cost-effectiveness of an adjuvanted recombinant zoster vaccine in adults with inflammatory bowel disease.

binant zoster vaccine (RZV) is mended for all adults ≥19 years of age who are at increased risk for HZ, including patients with inflammatory bowel disease (IBD).

36896953

Deep Learning Radiomics for the Assessment of Telomerase Reverse Transcriptase Promoter Mutation Status in Patients With Glioblastoma Using Multiparametric MRI.

Studies have shown that magnetic resonance imaging (MRI)-based deep learning radiomics (DLR) has the potential to assess glioma grade; however, its role in predicting telomerase reverse transcriptase (TERT) promoter mutation status in patients with glioblastoma (GBM) remains unclear.

36896955

Protein phosphorylation database and prediction tools.

Protein phosphorylation, one of the main protein post-translational modifications, is required for regulating various life activities. Kinases and phosphatases that regulate protein phosphorylation in humans have been targeted to treat various diseases, particularly cancer. High-throughput experimental methods to discover protein phosphosites are laborious and time-consuming. The burgeoning databases and predictors provide essential infrastructure to the munity. To date, >60 publicly available phosphorylation databases and predictors each have been developed. In this review, we prehensively summarized the status and applicability of major online phosphorylation databases and predictors, thereby helping researchers rapidly select tools that are most suitable for their projects. Moreover, the organizational strategies and limitations of these databases and predictors have been highlighted, which may facilitate the development of better protein phosphorylation predictors in silico.

36896956

Cellulose Nanocrystal-Based All-3D-Printed Pyro-Piezoelectric Nanogenerator for Hybrid Energy Harvesting and Self-Powered Cardiorespiratory Monitoring toward the Human-Machine Interface.

Biomaterials with spontaneous piezoelectric property are highly emerging in recent times for the generation of electricity from mechanical energy sources that are amply available in nature. In this context, pyroelectricity, an integral property of piezoelectric materials, might be an interesting tool in harvesting thermal energy from the fluctuations of temperature. On the other hand, respiration and heart pulse are the significant human vital signs that can be used for early detection and prevention of cardiorespiratory diseases. Here, we report an all-three-dimensional (3D)-printed pyro-piezoelectric nanogenerator (Py-PNG) based on the most abundant pletely biodegradable biopolymer on earth, i.e., cellulose nanocrystal (CNC) for hybrid (mechanical as well as thermal) energy harvesting, and interestingly, the NG could be used as an e-skin sensor for application in self-powered noninvasive cardiorespiratory monitoring for personal healthcare. Notably, the CNC-based device will be patible and economically advantageous due to its biomaterial-based supremacy and huge availability. This is an original approach with 3D geometrical advancement in designing a NG/sensor, where the unique all-3D-printed manner is adopted, and certainly, it has promising potential in reducing the number of processing steps to required equipment during the multilayer fabrication. The all-3D-printed NG/sensor shows outstanding mechano-thermal energy harvesting performance along with sensitivity and is capable of accurate detection of heart pulse as well as respiration, whenever and whichever required without the need of any battery or an external power supply. In addition, we have also extended its application in demonstrating a smart mask-based breath monitoring system. Thus, the real-time cardiorespiratory monitoring provides notable and fascinating information in medical diagnosis, stepping toward biomedical device development and human-machine interface.

36896957

Co-designing a shared book reading environment at a community hub.

Community hubs often provide support to families in areas of high vulnerability and can provide unique opportunities for delivering early literacy programs. This study used a co-design process to engage families, staff, munity partners within munity hub to design an environment that supported shared book reading.

36896954

The Sapienza count-down for a healthy and sustainable diet.

The prevalence of obesity and of other municable diseases related to overnutrition is significantly increasing in the past few years. Policy makers are called to counteract this pandemic, orienting consumers towards a healthier and more sustainable diet. Most of the proposed initiatives are dedicated to the content of nutrients with "unfavourable" effects but, in fact, focusing the attention only or mainly on single foods or nutrients is not effective in decreasing the incidence/prevalence of municable diseases. Whole dietary patterns play by far a more important role than specific ponents in promoting health and modulating survival; and the adherence to eating patterns like the Mediterranean diet reduces the risk of municable diseases. The challenge is therefore to be able to transmit information relating to a healthy eating pattern through positive messages in a few simple indications which in turn represent the nutritional, but also the socio-cultural, environmental and economic characteristics of a healthy and sustainable dietary model. The Mediterranean Diet is normally proposed through a graphic depiction that represents a pyramid which is a simple and effective representation but not of immediate impact. For this reason, we are proposing to adopt the "Sapienza Count-down for a Healthy and Sustainable Diet" that will integrate the pyramid with a more immediate approach.

36896958

Nanodrug delivery systems for metabolic chronic liver diseases: advances and perspectives.

Nanomedicines are revolutionizing healthcare as recently demonstrated by the Pfizer/BioNTech and Moderna COVID-2019 vaccines, with billions of doses administered worldwide in a safe manner. Nonalcoholic fatty liver disease is the mon municable chronic liver disease, posing a major growing challenge to global public health. However, due to unmet diagnostic and therapeutic needs, there is great interest in the development of novel translational approaches. Nanoparticle-based approaches offer novel opportunities for efficient and specific drug delivery to liver cells, as a step toward precision medicines. In this review, the authors highlight recent advances in nanomedicines for the generation of novel diagnostic and therapeutic tools for nonalcoholic fatty liver disease and related liver diseases.

36896959

A Moderated Mediation Analysis to Further Examine the Role of Verbal Intelligence in the Association Between Psychopathic Personality and Crime.

The current study examined the association between psychopathy, criminal behavior, and the role of verbal intelligence. One promising approach is to examine alternative links between psychopathic traits and criminality like moderation and mediation effects by considering the potential relevance of verbal intelligence as a possible moderating variable. We hypothesized that psychopathic traits linearly predict antisocial behavior (ASB) but that a conviction because of ASB is moderated by verbal intelligence. To test a path model of this hypothesis,

36896960

Immediate-delayed lymphatic reconstruction after axillary lymph nodes dissection for locally advanced breast cancer-related lymphedema prevention: Report of two cases.

Approximately 60%-70% of breast cancer patients in Indonesia are diagnosed in the locally advanced stage. The stage carries a higher risk of lymph node metastasis which increases susceptibility to lymph obstruction. Hence, breast cancer-related lymphedema (BCRL) could present before axillary lymph node dissection (ALND). The purpose of this case report is to describe immediate-delayed lymphatic reconstructions with lymphaticovenous anastomosis in two subclinical lymphedema cases that present before ALND. There were 51 and 58 years old breast cancer patients with stage IIIC and IIIB, respectively. Both had no arm lymphedema symptoms, but arm lymphatic vessel abnormalities were found during preoperative indocyanine green (ICG) lymphography. Mastectomy and ALND were performed and proceeded with lymphaticovenous anastomoses (LVA) in both cases. One LVA at the axilla (isotopic) was done in the first patient. On the second patient, 3 LVAs at the affected arm (ectopic) and 3 isotopic LVAs were created. The patients were discharged on the second day plications during the follow-up. The intensity of dermal backflow was reduced, and no subclinical lymphedema progression occurred during 11 and 9 months follow-up, respectively. Based on these cases, BCRL screening might be mended for the locally advanced stage before cancer treatment. Once diagnosed, immediate lymphatic reconstruction after ALND should be mended to cure or prevent BCRL progression.

36896962

Interim monitoring of sequential multiple assignment randomized trials using partial information.

The sequential multiple assignment randomized trial (SMART) is the gold standard trial design to generate data for the evaluation of multistage treatment regimes. As with conventional (single-stage) randomized clinical trials, interim monitoring allows early stopping; however, there are few methods for principled interim analysis in SMARTs. Because SMARTs involve multiple stages of treatment, a key challenge is that not all enrolled participants will have progressed through all treatment stages at the time of an interim analysis. Wu et al. (2021) propose basing interim analyses on an estimator for the mean e under a given regime that uses data only from participants who pleted all treatment stages. We propose an estimator for the mean e under a given regime that gains efficiency by using partial information from enrolled participants regardless of their progression through treatment stages. Using the asymptotic distribution of this estimator, we derive associated Pocock and O'Brien-Fleming testing procedures for early stopping. In simulation experiments, the estimator controls type I error and achieves nominal power while reducing expected sample size relative to the method of Wu et al. (2021). We present an illustrative application of the proposed estimator based on a recent SMART evaluating behavioral pain interventions for breast cancer patients.