bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin Alleviates Sepsis-Associated Myocardial Injury by Enhancing AMP-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling Pathway–Mediated Autophagy
Authors: Gao Yu , Liu Jiao , Li Kemin , Li Tian , Li Ruihan , Zhang Wenlong , Zhang Xuanping , Wang Yan , Chen Min , Shi Ruizan , Cao Jing 
Published: July 2023

Abstract:
Sepsis-associated myocardial injury is one of the main causes of death in intensive care units, and current clinical treatments have not been satisfactory. Therefore, finding an effective intervention is an urgent requirement. Metformin, an anti–type 2 diabetes drug, has been reported to be an autophagic activator agent that confers protection in some diseases. However, it is unclear whether it can provide defense against sepsis-associated myocardial injury. In this study, we investigated the cardioprotective effects of metformin pretreatment against lipopolysaccharide (LPS)-induced myocardial injury in C57BL/6J mice or H9c2 cells and the possible underlying mechanisms. Metformin was administered at a dose of 100 mg/kg for a week before LPS intraperitoneal injection. Twenty-four hours after LPS intervention, echocardiographic evaluation, reactive oxygen species measurement, Hoechst staining, western blotting, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay were performed. Inhibitors of autophagy and AMP-activated protein kinase (AMPK) were used to further clarify the mechanisms involved. Metformin pretreatment effectively attenuated cardiac dysfunction, reduced the levels of myocardial enzymes, and alleviated cardiac hydroncus in LPS-treated mice. In addition, metformin restored the LPS-disrupted antioxidant defense and activated LPS-reduced autophagy by modulating the AMPK/mammalian target of rapamycin (AMPK/mTOR) pathway both in vivo and in vitro. The antioxidant effects of metformin on cardiomyocytes were abolished by the autophagy inhibitor 3-methyladenine (3-MA). Treatment with compound C, an AMPK inhibitor, reversed the metformin-induced autophagy in LPS-treated H9c2 cells. In conclusion, metformin pretreatment alleviates LPS-induced myocardial injury by activating AMPK/mTOR pathway–mediated autophagy.
Clinician Reasons for Stopping Clozapine
Authors: Grover Sandeep , Chaurasiya Nishtha , Chakrabarti Subho 
Published: July 2023

Abstract

Background
Little information is available on clozapine discontinuation rates in developing country settings.

Aim
The present study aimed to evaluate the incidence and reasons clinicians stopped clozapinine in patients after initiating treatment with the same. In addition, the study also aimed to assess the rechallenge rate, that is, restarting clozapine after a decision to discontinue the same by the clinicians.

Methodology
The treatment records of 859 patients started on clozapine were reviewed to identify the patients for whom the clinician stopped clozapine at least once because of any reason. The reasons for stopping clozapine were reviewed. In addition, the treatment records were also examined for rechallenge with clozapine at a later date.

Results
Clozapine was stopped by the clinicians in 44 of the 859 patients (5.12%). The most common reason for stopping clozapine was blood dyscrasias (n = 12), followed by poor adherence making the hematological monitoring difficult (n = 9), and intolerable sedation (n = 7). In half of the patients (n = 22), clozapine was restarted by the clinicians for further management of schizophrenia. Successful rechallenge was done in 58.33% of patients with blood dyscrasias, 44.44% with poor adherence, and 71.4% with intolerable sedation.

Conclusions
The present study suggests clinicians stop clozapine in only 5.14% of cases. The most common reasons for clozapine discontinuation by clinicians include blood dyscrasias, poor medication adherence making it challenging to monitor the hemogram, and sedation. However, in half of the patient's clozapine was rechallenged, and all the attempts of rechallenging were successful.
Evaluation of Virtual Assessment for a High Stakes' Clinical Examination—Physician Assistant Students' and Their Examiners' Perspectives
Authors: Joyce Pauline , Cassidy Dara , Kenna Laura 
Published: July 2023

Purpose
This case study emerged from the necessity to reschedule an in-person long case examination to an online platform for physician assistant students' final clinical examination during COVID-19 restrictions. The aim of this study was to evaluate the experiences of students and examiners for a high stakes' clinical examination online.

Methods
This was an evaluation research study using the Context, Input, Process, Product model, which provided a framework to establish the effectiveness and/or success of an online format for a high stakes' clinical examination. All students and examiners were invited to take part in virtual interviews.

Results
The results suggest that both students (n = 5) and examiners (n = 7) agree that, although the stress of a face-to-face examination was lessened for the student, this was balanced by a new stressor of potential Internet problems. All agreed that a virtual setting for a high stakes' assessment is not transferable, with both groups citing the lack of opportunities to “read the patient” and “showcase their physical examination skills” as challenging.

Conclusion
Our study suggests that, in the context of balancing the risks of the pandemic with graduating health care professionals, the online clinical examination format met the required assessment criteria. Recommendations suggest that the long case could be planned so that students and patients are in the same setting to perform a physical examination, confirming the finding that questions on “how to” examine a patient are no substitute for “doing.”
Characteristics of Hybrid Learning Among Health Professions Programs: A Mixed-Methods Study
Authors: Gordes Karen L. , Kulo Violet , Cawley James F. , Kayingo Gerald 
Published: July 2023

PurposeTo characterize current trends in hybrid education within the physician assistant (PA) profession, specifically program design, drivers, and outcomes in comparison with physical therapy hybrid education.MethodsThis was a mixed-methods study involving secondary data analysis and focused interviews with stakeholders to triangulate the data.ResultsCompared with traditional PA programs, hybrid programs have similar admission requirements, higher cost of tuition, larger class size, and higher attrition rate than national mean. Physician Assistant National Certifying Exam outcome data are in line or slightly lower than national scores. Technological advancements and need for faculty/learner flexibility by time and location are frequently cited driving forces.ConclusionsThere is a growing trend toward hybrid education among health professions. Other than cost, attrition rate, and immersion experiences, characteristics of hybrids are similar to traditional programs. It is relevant for PA educators to understand how this educational design may shape the future of PA graduates. Long-term impact should be evaluated with future studies.
Diagnosis of Acute Pancreatitis Using Postmortem Computed Tomography and Postmortem Magnetic Resonance Imaging
Authors: Chen Xin , Zhang Hui-mao , Zhou Dan-dan , Chen Zhi-ming , Wang Bo , Wang Zhuo , Bai Xiao 
Published: July 2023

Abstract
Acute pancreatitis (AP) is inflammation of the pancreas, which may be due to a wide variety of etiologies that share a final common pathway of premature activation of pancreatic enzymes and resultant autodigestion of pancreatic parenchyma. Acute pancreatitis is easy to diagnose clinically, with the presence of at least 2 of the 3 criteria (upper abdominal pain, serum amylase or lipase level greater than 3 times the upper limit of normal, or characteristic findings on imaging studies) of the revised Atlanta classification. However, postmortem imaging examinations of pancreatitis are extremely rare, and very few successful cases have been reported. Here, we present a case report of a single patient who underwent autopsy and postmortem imaging. Postmortem computed tomography (PMCT) and postmortem magnetic resonance imaging (PMMRI) showed peripancreatic inflammation and acute peripancreatic fluid collection in the left anterior pararenal space, which is consistent with the examination by autopsy. The advantages of PMMRI in AP have also been demonstrated. Our study also confirmed the advantage of PMCT angiography in the diagnosis of AP. To the best of our knowledge, this is the first report of PMCT and PMMRI combined with postmortem pathology in the diagnosis of AP.
Clinical and Magnetic Resonance Imaging Radiomics–Based Survival Prediction in Glioblastoma Using Multiparametric Magnetic Resonance Imaging
Authors: Bathla Girish , Soni Neetu , Ward Caitlin , Pillenahalli Maheshwarappa Ravishankar , Agarwal Amit , Priya Sarv 
Published: July 2023

Introduction
Survival prediction in glioblastoma remains challenging, and identification of robust imaging markers could help with this relevant clinical problem. We evaluated multiparametric magnetic resonance imaging–derived radiomics to assess prediction of overall survival (OS) and progression-free survival (PFS).

Methodology
A retrospective, institutional review board–approved study was performed. There were 93 eligible patients, of which 55 underwent gross tumor resection and chemoradiation (GTR-CR). Overall survival and PFS were assessed in the entire cohort and the GTR-CR cohort using multiple machine learning pipelines. A model based on multiple clinical variables was also developed. Survival prediction was assessed using the radiomics-only, clinical-only, and the radiomics and clinical combined models.

Results
For all patients combined, the clinical feature–derived model outperformed the best radiomics model for both OS (C-index, 0.706 vs 0.597; P < 0.0001) and PFS prediction (C-index, 0.675 vs 0.588; P < 0.001). Within the GTR-CR cohort, the radiomics model showed nonstatistically improved performance over the clinical model for predicting OS (C-index, 0.638 vs 0.588; P = 0.4). However, the radiomics model outperformed the clinical feature model for predicting PFS in GTR-CR cohort (C-index, 0.641 vs 0.550; P = 0.004). Combined clinical and radiomics model did not yield superior prediction when compared with the best model in each case.

Conclusions
When considering all patients, regardless of therapy, the radiomics-derived prediction of OS and PFS is inferior to that from a model derived from clinical features alone. However, in patients with GTR-CR, radiomics-only model outperforms clinical feature–derived model for predicting PFS.
Efficacy and Safety of Tofacitinib in Anti–Melanoma Differentiation–Associated 5 Gene Antibody–Positive Dermatomyositis
Authors: Li Shanshan , Li Sizhao , Wang Jinping , Zhang Ling , Duan Jianghui , Lu Xin , Zhang Lu , Wang Guochun 
Published: July 2023

Objectives
This study aimed to evaluate the efficacy and safety of tofacitinib for the treatment of anti–melanoma differentiation–associated 5 gene (anti-MDA5) antibody–positive dermatomyositis (DM).

Methods
This study included 52 patients with anti-MDA5 antibody–positive DM (MDA5+DM) who were treated with tofacitinib and followed up. Clinical and laboratory data of these patients were recorded between January 2019 and June 2022. SPSS was used for all statistical analyses.

Results
The mean age of patients with MDA5+DM was 45 ± 12.4 years, and the median disease duration was 6.5 months (range, 3–13 months). The mean dosage of glucocorticoids was 34.7 ± 20.9 mg/d at the initiation of tofacitinib therapy. Overall, 47 patients were followed up for a mean duration of 7.8 ± 6.2 months. We found that the clinical symptoms of 28 patients (59.6%) were improved, but 1 patient (2.1%) died because of severe infection. Moreover, complications occurred in 25 patients (53.2%), among whom 19 patients had infections. Older age and C-reactive protein levels close to the upper value in reference range at the initial treatment were found to be the potential risk factors of infection. Furthermore, patients with cutaneous ulcers were found to have a lower risk of infection.

Conclusion
Tofacitinib can be used as a potential therapeutic option for MDA5+DM. The occurrence of infection requires special attention during treatment, particularly in patients with older age and C-reactive protein levels close to the upper value in reference range.
An Objective Computer-Assisted Measurement of Sonographic Renal Cortical Echogenicity
Authors: Beutler Bryce D. , El-Sabawi Bassim , Walker Daphne K. , Cen Steven , Tchelepi Hisham 
Published: July 2023

AbstractRenal cortical echogenicity represents a marker of renal function. However, evaluation of the renal echotexture is subjective and thus disposed to error and interrater variability. Computer-aided image analysis may be used to objectively assess renal cortical echogenicity by comparing the echogenicity of the left kidney to that of the spleen; the resultant ratio is referred to as the splenorenal index (SRI). We performed a retrospective review of all adult patients who received a renal ultrasound over a 45-day period at our institution. Demographic data and kidney function laboratory values were documented for each patient. Regions of interest (ROIs) were selected in the left renal cortex and spleen using ImageJ software. The SRI was calculated as a ratio of the mean pixel brightness of the left kidney cortex ROI to the mean pixel brightness of the spleen ROI. The SRI was then correlated with serum creatinine, blood urea nitrogen, and estimated glomerular filtration rate. We found that among the 94 patients included in the study, the SRI had a significant positive correlation with serum creatinine (r= 0.43,P <0.001) and serum blood urea nitrogen (r= 0.45,P <0.001) and negative correlation with estimated glomerular filtration rate (r= −0.47,P< 0.001). Our data indicate that SRI may serve as a valuable tool for sonographic evaluation of renal parenchymal disease.
Persistent High Long-term Excess Mortality after Elective AAA Repair Especially in Women
Authors: Bulder Ruth M.A. , van der Vorst Joost R. , van Schaik Jan , Bedene Ajda , Lijfering Willem M. , Bastiaannet Esther , Hamming Jaap F. , Lindeman Jan H.N. 
Published: July 2023

Objective:
The aim of this time-trend analysis is to estimate long-term excess-mortality and associated cardiovascular risk for abdominal aortic aneurysm (AAA) patients after elective repair, while addressing the changes in AAA management and patient selection over time.

Summary Background Data:
Despite the intensification of endovascular aneurysm repair (EVAR) and cardiovascular risk management (CVRM), Swedish population data suggest that AAA patients retain a persistently high long-term mortality after elective repair. The question is whether this reflects sub-optimal treatment, a changing patient population over time, or a national phenomenon.

Methods:
Nationwide time-trend analysis including 40730 patients (87% men) following elective AAA repair between 1995-2017. Three timeframes were compared, each reflecting changes in the use of EVAR and intensification of CVRM. Relative survival analyses were used to estimate disease-specific excess-mortality. Competing risk of death analysis evaluated the risk of cardiovascular versus non-cardiovascular death. Sensitivity analysis evaluated the impact of changes in patient selection over time.

Results:
Short-term excess-mortality significantly improved over time. Long-term excess-mortality remained high with a doubled mortality risk for women (RER 1.87 (95%CI 1.73–2.02)). Excess-mortality did not differ between age-categories. The risk of cardiovascular versus non-cardiovascular death remained similar over time, with a higher risk of cardiovascular death for women. Changes in patient population (i.e. older and more comorbid patients in the latter period) marginally impacted excess-mortality (2%).

Conclusions:
Despite changes in AAA care, patients retain a high long-term excess-mortality after elective repair with a persistent high cardiovascular mortality risk. In this a clear sex- but no age disparity stands out.
Immunohistochemical expression of TFF1 is a new prognostic marker in retinoblastoma
Authors: Aschero Rosario , Ganiewich Daiana , Lamas Gabriela , Restrepo-Perdomo Camilo A , Ottaviani Daniela , Zugbi Santiago , Camarero Sandra , Néspoli Ezequiel , Vilanova Maria Cuadrado , Perez-Jaume Sara , Pascual-Pasto Guillem , Sampor Claudia , Grigorovski Nathalia , Salas Beatriz , Suñol Mariona , Carcaboso Angel M. , Mora Jaume , de Dávila María T G , Doz François , Radvanyi François , Abramson David H , Llera Andrea S , Schaiquevich Paula S , Lubieniecki Fabiana , Chantada Guillermo L 
Published: July 2023

ABSTRACTIntroductionThe risk of relapse in retinoblastoma is currently determined by the presence of high-risk histopathologic factors in the enucleated eye. However, the probability of developing metastatic disease is heterogeneous among these patients. Evaluating a biological marker to identify high-risk patients could be useful in clinical setting. This study aims to evaluate whether the expression of TFF1, a surrogate for subtype 2 retinoblastoma, is a prognostic marker for relapse and death.MethodsThis multicenter cohort study included 273 patients, 48 of whom had extraocular disease. Immunohistochemical staining were performed for CRX, ARR3, TFF1 and Ki67. Tumors were classified as histological subtype 1 (HS1) if they had low or no expression of TFF1 (quick score (QS) ≤ 50) and as histological subtype 2 (HS2) if they expressed TFF1 diffusely (QS > 50). We studied the association between HS classification and outcome.ResultsOf 273 patients, 35.9% were classified as HS1, 59.3% as HS2 and 4.8% were not evaluable. In multivariate analysis, patients with HS2 tumors had a higher probability of relapse and death than those with HS1 (P< 0.0001 andP= 0.00020, respectively). We identified a higher-risk subgroup among HS2 tumors, presenting non-mutually exclusive expression of ARR3 and TFF1 and had an increased risk of relapse and death compared to tumors that displayed mutually exclusive expression (P= 0.012 andP= 0.027, respectively).ConclusionsExpression of TFF1, especially when it is not-mutually exclusive with ARR3, is an independent prognostic marker of poor outcome in retinoblastoma.
Validating an Approach for Estimating Appropriate Black Participation in Clinical Trials
Authors: Berg Jeremy M. , Celedón Juan C. , Jonassaint Naudia N. 
Published: July 2023

AbstractRepresentation of different groups at appropriate levels in clinical trials is of great importance. Factors affecting what appropriate levels include the demographics at the trial sites and the prevalence of the condition under study in different populations. We examined 359 trials published in New England Journal of Medicine, Journal of the American Medical Association (JAMA), and the Lancet in 2020 for information about Black participation rates. Sufficient information for analysis was available in 58 trials. Simulations including both site demographics and prevalence factors revealed that observed Black participation rates were reasonably well correlated with estimated potential Black participation rates, but that actual participation rates were lower than potential rates in 47 out of 58 trials. This approach could be used to estimate appropriate participation rates prior to trial initiation and for analysis of trials upon completion. Promotion of such transparency standards will aid future analyses and should help drive improvements in representation over time.Clinical trials represent important opportunities to test potential interventions in groups of individuals who can provide meaningful data and who represent populations who might benefit from the trial results. This has been described and highlighted by the recent report “Improving Representation in Clinical Trials and Research: Building Research Equity for Women and Underrepresented Groups” from the United States National Academy of Sciences1. One of the overarching conclusions from this report is:
A parametric finite element model of leg campaniform sensilla inDrosophilato study CS location and arrangement
Authors: Saltin Brian D. , Haustein Moritz , Büschges Ansgar , Blanke Alexander 
Published: July 2023

AbstractCampaniform sensilla (CS) are mechanosensors embedded within the cuticle of many insects at key locations such as nearby leg segment joints or halters. CS located at leg segments were found to respond to cuticle bending which can be induced by walking or jumping movements or by the underlying tensile forces of the muscles. ForDrosophilait is unclear how CS location and material property variation influence stress levels within and around CS but this information is crucial to understand how flies might use CS input to adjust walking behaviour. Here, we designed a parametric model of the femoral CS field forDrosophilato allow for a systematic testing of the influence of CS location, orientation and material property variation on stress levels. The model consists of 7 changeable parameters per CS and 12 which can be changed for the CS field. Simulations of leg bending are in line with general beam bending theory: At the specific proximal CS field location nearby the trochantero-femoral leg joint, displacements are smaller than distal, while stresses are higher. When changing CS location towards more distal leg parts the situation changes towards more displacement and less stress. Changes in material property values for CS substructures or whole CS fields have a very low influence on stress or displacement magnitudes (regarding curve shape and amplitude) at the CS caps to which the nerve cells attach. Taken together, our simulation results indicate that for CS fields located at proximal leg parts, the displacements induced by other sources such as muscle tensile forces might be more relevant stimuli than the overall leg bending induced by typical locomotion scenarios. Future parametric finite element models should contain experimentally validated information on the anisotropic and viscoelastic properties of materials contained in this sensory system to further our understanding of CS activation patterns.
Identification of consensus head and neck cancer-associated microbiota signatures: a meta-analysis of 16S rRNA and The Cancer Microbiome Atlas datasets
Authors: Yeo Kenny , Li Runhao , Wu Fangmeinuo , Bouras George , Mai Linh T.H. , Smith Eric , Wormald Peter-John , Valentine Rowan , Psaltis Alkis James , Vreugde Sarah , Fenix Kevin 
Published: July 2023

AbstractObjectiveMultiple reports have attempted to describe the tumour microbiota in head and neck cancer. However, these have failed to produce a consistent microbiota signature which may undermine understanding the importance of bacterial-mediated effects in head and neck cancer. The aim of this study is to consolidate these datasets and identify a consensus microbiota signature in head and neck cancer.MethodsWe analysed 11 published head and neck cancer 16S ribosomal RNA microbial datasets collected from cancer, cancer-adjacent and non-cancer tissue to generate a consensus microbiota signature. These signatures were then validated using The Cancer Microbiome Atlas database.ResultsWe identified unique bacteria enrichment within tissue types and correlated it with possible functional and clinical outcomes.ConclusionsOur meta-analysis demonstrates a consensus microbiota signature for head and neck cancer, highlighting its potential importance in this disease.HighlightsThe first meta-analysis of tissue microbiome in head and neck cancer containing eleven 16S ribosomal RNA and The Cancer Microbiome Atlas dataset.Microbiome from head and neck tissues were able to distinguish tissue types (cancer, cancer-adjacent, non-cancer) using 16S rRNA sequencing and whole genome sequencing datasets.Specific bacterial genera correlate with different tumour microenvironment phenotypes.High abundanceFusobacteriumin tumour tissue correlates with better overall survival.