bluuebunny/crossref_metadata_2025_split huggingface dataset:
CrMP-Sol database: classification, bioinformatic analyses and comparison of cancer-related membrane proteins and their water-soluble variant designs
Authors: Ma Lina , Zhang Sitao , Liang Qi , Huang Wenting , Wang Hui , Pan Emily , Xu Ping , Zhang Shuguang , Tao Fei , Tang Jin , Qing Rui 
Published: September 2023

AbstractMembrane proteins are critical mediators for tumor progression and present enormous therapeutic potentials. Although gene profiling can identify their cancer-specific signatures, systematic correlations between protein functions and tumor-related mechanisms are still unclear. We present here the CrMP-Sol database (https://bio-gateway.aigene.org.cn/g/CrMP), which aims to breach the gap between the two. Machine learning was used to extract key functional descriptions for protein visualization in the 3D-space, where spatial distributions provide function-based predictive connections between proteins and cancer types. CrMP-Sol also presents QTY-enabled water-soluble designs to facilitate native membrane protein studies despite natural hydrophobicity. Five examples with varying transmembrane helices in different categories were used to demonstrate the feasibility. Native and redesigned proteins exhibited highly similar characteristics, predicted structures and binding pockets, and slightly different docking poses against known ligands, although task-specific designs are still required for proteins more susceptible to internal hydrogen bond formations. The database can accelerate therapeutic developments and biotechnological applications of cancer-related membrane proteins.
Highly sensitive and rapid point-of-care testing for HIV-1 infection based on CRISPR-Cas13a system
Authors: Li Xiaohui , Su Bin , Yang Lan , Kou Zhihua , Wu Hao , Zhang Tong , Liu Lifeng , Han Yao , Niu Mengwei , Sun Yansong , Li Hao , Jiang Taiyi 
Published: September 2023

Abstract
Background
Human immunodeficiency virus type one (HIV-1) is the leading cause of acquired immunodeficiency syndrome (AIDS). AIDS remains a global public health concern but can be effectively suppressed by life-long administration of combination antiretroviral therapy. Early detection and diagnosis are two key strategies for the prevention and control of HIV/AIDS. Rapid and accurate point-of-care testing (POCT) provides critical tools for managing HIV-1 epidemic in high-risk areas and populations.

Methods
In this study, a POCT for HIV-1 RNA was developed by CRISPR-Cas13a lateral flow strip combined with reverse transcriptase recombinase-aided amplification (RT-RAA) technology, the results can be directly observed by naked eyes.

Results
Moreover, with the degenerate base-binding CRISPR-Cas13a system was introduced into the RT-RAA primer designing, the technology developed in this study can be used to test majority of HIV-1 RNA with limit of detection (LOD) 1 copy/μL, while no obvious cross-reaction with other pathogens. We evaluated this method for detecting HIV-1 RNA of clinical samples, the results showed that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were 91.81% (85.03- 96.19%), 100% (92.60–100%), 100% (96.41–100%), 39.14% (25.59–54.60%) and 92.22% (86.89–95.88%), respectively. The lowest viral load detectable by this method was 112copies/mL.

Conclusion
Above all, this method provides a point-of-care detection of HIV-1 RNA, which is stable, simple and with good sensitivity and specificity. This method has potential to be developed for promoting early diagnosis and treatment effect monitoring of HIV patients in clinical.
Stroke epidemiology and outcomes of stroke patients in Nepal: a systematic review and meta-analysis
Authors: Paudel Raju , Tunkl Christine , Shrestha Shakti , Subedi Ram Chandra , Adhikari Ayush , Thapa Lekhjung , Gajurel Bikram Prasad , Chandra Avinash , Kharel Ghanashyam , Jalan Pankaj , Phuyal Subash , Pokharel Babu Ram , Acharya Subi , Bogati Kanchan , Jha Pinky , Kharbuja Naresh , Gumbinger Christoph 
Published: September 2023

AbstractBackgroundWith an increasing burden of stroke, it is essential to minimize the incidence of stroke and improve stroke care by emphasizing areas that bring out the maximum impact. The care situation remains unclear in the absence of a national stroke care registry and a lack of structured hospital-based data monitoring. We conducted this systematic review and meta-analysis to assess the status of stroke care in Nepal and identify areas that need dedicated improvement in stroke care.MethodsA systematic literature review was conducted to identify all studies on stroke epidemiology or stroke care published between 2000 and 2020 in Nepal. Data analysis was done with Statistical Package for Social Sciences (SPSS) and Comprehensive Meta-analysis (CMA-3).ResultsWe identified 2533 studies after database searching, and 55 were included in quantitative and narrative synthesis. All analyses were done in tertiary care settings in densely populated central parts of Nepal. Ischemic stroke was more frequent (70.87%) than hemorrhagic (26.79%), and the mean age of stroke patients was 62,9 years. Mortality occurred in 16.9% (13-21.7%), thrombolysis was performed in 2.39% of patients, and no studies described thrombectomy or stroke unit care.ConclusionThe provision of stroke care in Nepal needs to catch up to international standards, and our systematic review demonstrated the need to improve access to quality stroke care. Dedicated studies on establishing stroke care units, prevention, rehabilitation, and studies on lower levels of care or remote regions are required.
Neutrophil-to-lymphocyte ratio is an independent predictor for neurological disability in patients with idiopathic transverse myelitis
Authors: Min Je Hong , Sohn Sung-Yeon , Lee Seung Yeon , Seo Sang Hyun , Kim Shin Yeop , Park Bumhee , Kim Seung Il , Joo In Soo 
Published: September 2023

Abstract
Introduction
The neutrophil-to-lymphocyte ratio (NLR) has been found to be useful in the prognostication of immune-mediated neurological disorders because it roughly reflects the systemic innate immune response compared to the adaptive immune response. However, studies on the validity of NLR in demyelinating disorders of the central nervous system have shown conflicting results. Therefore, we aimed to investigate NLR in the idiopathic transverse myelitis (ITM) cohort.

Methods
We retrospectively analyzed the cohort data of patients with ITM between January 2006 and February 2020. The medical data of all patients with myelitis were reviewed to exclude patients with disease-associated myelopathy according to predefined exclusion criteria. The relationship between the natural log-transformed NLR (lnNLR) and the clinical, paraclinical, and imaging data was evaluated. Factors associated with neurological disability were analyzed using a linear mixed-effects model. Predictive factors for moderate-to-severe neurological disability (Expanded Disability Status Scale [EDSS] score ≥ 4) were investigated.

Results
A total of 124 participants were included in the analysis. The lnNLR correlated with EDSS and lesion length. Linear mixed-effects analysis showed that age, lesion length, and lnNLR were independently associated with neurological disabilities. Multivariable logistic regression revealed that lnNLR (odds ratio [OR] = 4.266, 95% confidence interval [CI] = 1.220–14.912, p = 0.023) and lesion length (OR = 1.848, 95% CI = 1.249–2.734, p = 0.002) were independent predictive factors of the worst neurological disability.

Conclusion
NLR may be used as an independent prognostic factor for predicting poor neurological outcomes in patients with ITM.
ICD-11 and mental disorders: important changes, controversies, and future directions
Authors: Seemüller Florian 
Published: September 2023

AbstractAbout a year and a half after publishing ICD-11, we aim to gather initial feedback, comments, opinions, and even recent study results from experts in the relevant fields through this collection. We hope to facilitate a preliminary summary of whether the new classification truly represents progress, and how it has changed treatment, and research of mental illnesses.
Blood miRNA levels associated with ADHD traits in children across six European birth cohorts
Authors: Dypås Lene B. , Duale Nur , Olsen Ann-Karin , Bustamante Mariona , Maitre Lea , Escaramis Geòrgia , Julvez Jordi , Aguilar-Lacasaña Sofia , Andrusaityte Sandra , Casas Maribel , Vafeiadi Marina , Grazuleviciene Regina , Heude Barbara , Lepeule Johanna , Urquiza Jose , Wright John , Yang Tiffany C. , Vrijheid Martine , Gützkow Kristine B. 
Published: September 2023

Abstract
Background
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and highly heritable neurodevelopmental disorder of major societal concern. Diagnosis can be challenging and there are large knowledge gaps regarding its etiology, though studies suggest an interplay of genetic and environmental factors involving epigenetic mechanisms. MicroRNAs (miRNAs) show promise as biomarkers of human pathology and novel therapies, and here we aimed to identify blood miRNAs associated with traits of ADHD as possible biomarker candidates and further explore their biological relevance.

Methods
Our study population consisted of 1126 children (aged 5–12 years, 46% female) from the Human Early Life Exposome study, a study spanning six ongoing population-based European birth cohorts. Expression profiles of miRNAs in whole blood samples were quantified by microarray and tested for association with ADHD-related measures of behavior and neuropsychological functions from questionnaires (Conner’s Rating Scale and Child Behavior Checklist) and computer-based tests (the N-back task and Attention Network Test).

Results
We identified 29 miRNAs significantly associated (false discovery rate < .05) with the Conner’s questionnaire-rated trait hyperactivity, 15 of which have been linked to ADHD in previous studies. Investigation into their biological relevance revealed involvement in several pathways related to neurodevelopment and function, as well as being linked with other neurodevelopmental or psychiatric disorders known to overlap with ADHD both in symptomology, genetic risk, and co-occurrence, such as autism spectrum disorder or schizophrenia. An additional three miRNAs were significantly associated with Conner’s-rated inattention. No associations were found with questionnaire-rated total ADHD index or with computer-based tests.

Conclusions
The large overlap of our hyperactivity-associated miRNAs with previous studies on ADHD is intriguing and warrant further investigation. Though this study should be considered explorative and preliminary, these findings contribute towards identifying a set of miRNAs for use as blood-based biomarkers to aid in earlier and easier ADHD diagnosis.
Microvesicle-associated and circulating microRNAs in diabetic dyslipidemia: miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 have biomarker potential
Authors: Nemecz Miruna , Stefan Diana Simona , Comarița Ioana Karla , Constantin Alina , Tanko Gabriela , Guja Cristian , Georgescu Adriana 
Published: September 2023

Abstract
Background
Circulating MicroRNAs (miRNAs) carried by microvesicles (MVs) have various physiological and pathological functions by post-transcriptional regulation of gene expression being considered markers for many diseases including diabetes and dyslipidemia. We aimed to identify new common miRNAs both in MVs and plasma that could be predictive biomarkers for diabetic dyslipidemia evolution.

Methods
For this purpose, plasma from 63 participants in the study (17 type 2 diabetic patients, 17 patients with type 2 diabetes and dyslipidemia, 14 patients with dyslipidemia alone and 15 clinically healthy persons without diabetes or dyslipidemia) was used for the analysis of circulating cytokines, MVs, miRNAs and MV-associated miRNAs.

Results
The results uncovered three miRNAs, miR-218, miR-132 and miR-143, whose expression was found to be significantly up-regulated in both circulating MVs and plasma from diabetic patients with dyslipidemia. These miRNAs showed significant correlations with important plasma markers, representative of this pathology. Thus, MV/plasma miR-218 was negatively correlated with the levels of erythrocyte MVs, plasma miR-132 was positively connected with MV miR-132 and negatively with uric acid and erythrocyte plasma levels, and plasma miR-143 was negatively related with creatinine levels and diastolic blood pressure. Also, three miRNAs common to MV and plasma, namely miR-21, miR-122, and miR-155, were identified to be down-regulated and up-regulated, respectively, in diabetic dyslipidemia. In addition, MV miR-21 was positively linked with cholesterol plasma levels and plasma miR-21 with TNFα plasma levels, MV miR-122 was negatively correlated with LDL-c levels and plasma miR-122 with creatinine and diastolic blood pressure and positively with MV miR-126 levels, MV miR-155 was positively associated with cholesterol and total MV levels and negatively with HDL-c levels, whereas plasma miR-155 was positively correlated with Il-1β plasma levels and total MV levels and negatively with MV miR-223 levels.

Conclusions
In conclusion, miR-218, miR-132, miR-143, and miR-21, miR-122, miR-155 show potential as biomarkers for diabetic dyslipidemia, but there is a need for more in-depth studies. These findings bring new information regarding the molecular biomarkers specific to diabetic dyslipidemia and could have important implications for the treatment of patients affected by this pathology.
A fine-tuned yeast surface-display/secretion platform enables the rapid discovery of neutralizing antibodies against Clostridioides difficile toxins
Authors: Sun Ying , Zhang Yongrong , Yu Hua , Saint Fleur Ashley , Yu Di , Yang Zhiyong , Feng Hanping 
Published: September 2023

Abstract
Background
Neutralizing antibody plays a key role in protecting hosts from invasive pathogens and their virulent components. Current high-throughput assays for antibody screening are based on binding activities. However, those antibodies with high affinity may not have neutralizing activities. Subsequent functionality assays are necessary to identify neutralizing antibodies from binders with high affinity to their target antigens, which is laborious and time-consuming. Therefore, a versatile platform that can rapidly identify antibodies with both high binding affinity and neutralizing activity is desired to curb future pandemics like COVID-19.

Results
In this proof-of-concept study, we adapted Saccharomyces cerevisiae to either display human antibodies on the yeast surface or secrete soluble antibodies into the cultivation supernatant under a controllable ‘switch’ through different carbon source induced promoters. Initially, an engineered chimeric-bispecific Fab antibody, derived from humanized nanobodies against both Clostridioides difficile toxin A and B (TcdA and TcdB), was successfully expressed either on the yeast cell surface or in the culture medium with intact bioactivity, suggesting the applicability of our system in antibody display and secretion. Next, a combinatorial Fab library was constructed from B cells isolated from a convalescent patient with a high serological neutralizing titer against TcdB. Following three rounds of magnetic bead enrichment and one round of flow cytometry sorting, antibodies against TcdB were enriched efficiently. We then sorted out single binders with high binding affinity and induced them to express soluble antibodies in culture medium. The neutralizing activity of culture supernatant was analyzed using cell-based assay immediately. This way, we rapidly identified two unique neutralizers (out of seven binders) that can neutralize the cytotoxicity of TcdB.

Conclusion
The antibody screening platform described here simplifies the neutralizing antibody discovery procedure and will be an attractive alternative for screening functional antibodies against infectious diseases.
A survey of Transformer applications for histopathological image analysis: New developments and future directions
Authors: Atabansi Chukwuemeka Clinton , Nie Jing , Liu Haijun , Song Qianqian , Yan Lingfeng , Zhou Xichuan 
Published: September 2023

AbstractTransformers have been widely used in many computer vision challenges and have shown the capability of producing better results than convolutional neural networks (CNNs). Taking advantage of capturing long-range contextual information and learning more complex relations in the image data, Transformers have been used and applied to histopathological image processing tasks. In this survey, we make an effort to present a thorough analysis of the uses of Transformers in histopathological image analysis, covering several topics, from the newly built Transformer models to unresolved challenges. To be more precise, we first begin by outlining the fundamental principles of the attention mechanism included in Transformer models and other key frameworks. Second, we analyze Transformer-based applications in the histopathological imaging domain and provide a thorough evaluation of more than 100 research publications across different downstream tasks to cover the most recent innovations, including survival analysis and prediction, segmentation, classification, detection, and representation. Within this survey work, we also compare the performance of CNN-based techniques to Transformers based on recently published papers, highlight major challenges, and provide interesting future research directions. Despite the outstanding performance of the Transformer-based architectures in a number of papers reviewed in this survey, we anticipate that further improvements and exploration of Transformers in the histopathological imaging domain are still required in the future. We hope that this survey paper will give readers in this field of study a thorough understanding of Transformer-based techniques in histopathological image analysis, and an up-to-date paper list summary will be provided athttps://github.com/S-domain/Survey-Paper.
Factors that influence evidence-informed meso-level regional primary health care planning: a qualitative examination and conceptual framework
Authors: Windle Alice , Javanparast Sara , Freeman Toby , Baum Fran 
Published: September 2023

Abstract
Background
Evidence-informed primary health care (PHC) planning in decentralised, meso-level regional organisations has received little research attention. In this paper we examine the factors that influence planning within this environment, and present a conceptual framework.

Methods
We employed mixed methods: case studies of five Australian Primary Health Networks (PHNs), involving 29 primary interviews and secondary analysis of 38 prior interviews; and analysis of planning documents from all 31 PHNs. The analysis was informed by a WHO framework of evidence-informed policy-making, and institutional theory.

Results
Influential actors included federal and state/territory governments, Local Health Networks, Aboriginal Community Controlled Health Organisations, local councils, public hospitals, community health services, and providers of allied health, mental health and aged care services. The federal government was most influential, constraining PHNs’ planning scope, time and funding. Other external factors included: the health service landscape; local socio-demographic and geographic characteristics; (neoliberal) ideology; interests and politics; national policy settings and reforms; and system reorganisation. Internal factors included: organisational structure; culture, values and ideology; various capacity factors; planning processes; transition history; and experience. The additional regional layer of context adds to the complexity of planning.

Conclusions
Like national health policy-making, meso-level PHC planning occurs in a complex environment, but with additional regional factors and influences. We have developed a conceptual framework of the meso-level PHC planning environment, which can be employed by similar regional organisations to elucidate influential factors, and develop strategies and tools to promote transparent, evidence-informed PHC planning for better health outcomes.
“It’s important to foster open discussion about the topic”: development, implementation, and evaluation of an ethics of abortion independent learning module for second year medical students
Authors: McCarty Catherine A. , Hutto Sarah L. , Shaw Aubie K. 
Published: September 2023

Abstract
Purpose
Despite the frequency of abortions, one-third of medical schools in the US and Canada did not include coverage of that topic, according to a survey conducted in 2002–2005. The purpose of this project was to develop, implement, and evaluate a module for second year medical students related to the ethics of abortion.

Methods
The module was designed as Independent Learning Time (ILT). The stated purpose was for students to consider some of the recent debate in the ethics literature related to conscientious objection and abortion and how personal views may influence future practice. The ILT included readings and Power Points to view. Students were asked to write a one-page reflection on one of three writing prompts.

Results
The most commonly selected writing prompt in three classes was on personal values in relation to abortion (56.5%), followed by information about nearest provider of reproductive services to rural preceptor site (34.7%), followed by conscientious objection (23.3%). We received many positive comments about the ILT, including: “First, I would like to acknowledge my gratitude for this assignment and its subject. I believe it is very important that future physicians learn the entirety of women’s reproductive health care, including abortion and contraception, but unfortunately this is not always the case in medical training”.

Conclusions
There has been an extremely positive response to the ILT. With the exception of the prompt specific to our regional campus mission that includes rural preceptorships during the preclinical years, this module could be implementable at other medical schools.
Well-being is associated with cortical thickness network topology of human brain
Authors: Li Yubin , Li Chunlin , Jiang Lili 
Published: September 2023

Abstract
Background
Living a happy and meaningful life is an eternal topic in positive psychology, which is crucial for individuals’ physical and mental health as well as social functioning. Well-being can be subdivided into pleasure attainment related hedonic well-being or emotional well-being, and self-actualization related eudaimonic well-being or psychological well-being plus social well-being. Previous studies have mostly focused on human brain morphological and functional mechanisms underlying different dimensions of well-being, but no study explored brain network mechanisms of well-being, especially in terms of topological properties of human brain morphological similarity network.

Methods
Therefore, in the study, we collected 65 datasets including magnetic resonance imaging (MRI) and well-being data, and constructed human brain morphological network based on morphological distribution similarity of cortical thickness to explore the correlations between topological properties including network efficiency and centrality and different dimensions of well-being.

Results
We found emotional well-being was negatively correlated with betweenness centrality in the visual network but positively correlated with eigenvector centrality in the precentral sulcus, while the total score of well-being was positively correlated with local efficiency in the posterior cingulate cortex of cortical thickness network.

Conclusions
Our findings demonstrated that different dimensions of well-being corresponded to different cortical hierarchies: hedonic well-being was involved in more preliminary cognitive processing stages including perceptual and attentional information processing, while hedonic and eudaimonic well-being might share common morphological similarity network mechanisms in the subsequent advanced cognitive processing stages.