bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and clinical impact of frailty in COPD：A Systematic Review and Meta-analysis
Authors: Wang Lina , Zhang Xiaolin , Liu Xinmin 
Published: February 2023

Abstract
Background: Frailty has been increasingly identified as a risk factor of adverse outcomes in chronic obstructive pulmonary disease (COPD). The prevalence and impact of frailty on health outcomes in people with COPD require clarification.
Methods: PubMed, Embase, The Cochrane Library and Web of Science (January 1, 2002, to July 1, 2022) were comprehensively searched to identify studies related to frailty and COPD. Comparisons were made between people who did and did not have frailty for pulmonary function, dyspnea severity, 6-minute walking distance, activities of daily life, and mortality.
Results: Twenty studies (8 cross-sectional, 6 prospective, 5 retrospective cohort,1 clinical trial) from Europe (9), Asia (6), and North and South America (4), Oceania (1) involving 11, 620 participants were included. The prevalence of frailty ranged from 6.43% to 71.7% based on the frailty tool used. Overall sarcopenia prevalence varied from 32.07% (95% confidence interval (CI) 26.64–37.49). People with frailty had lower predicted forced expiratory volume in the first second (mean difference -5.06%; 95%CI -6.70 to -3.42%)，shorter 6-minute walking distance (mean difference -90.23 meter; 95%CI -124.70 to -55.76), poorer activities of daily life (standardized mean difference -0.99; 95%CI -1.35 to -0.62) , higher CAT score(mean difference 6.2; 95%CI 4.43 to 7.96) and mMRC grade (mean difference 0.93; 95%CI 0.85 to 1.02) compared with those who did not (P < 0.001 for all). Meta-analysis showed that frailty was associated with an increased risk of long-term all-cause mortality (HR 1.68; 95% CI 1.37-2.05; I2=0%, p < 0.00, Tau-squared=0).
Conclusion: Frailty is prevalent in people with COPD and associates with negative clinical outcomes including pulmonary function, dyspnea severity, exercise capacity, quality of life and mortality.
Protocol for an observational study of working conditions and musculoskeletal health in Swedish online retail warehousing from the perspective of gender and race/ethnicity
Authors: Jackson Jennie A. , Mathiassen Svend Erik , Rydström Klara , Johansson Kristina 
Published: February 2023

Abstract
Background
Disparate occupational health outcomes are evident both between men and women and between domestic- and foreign-born workers in Sweden, Europe, and internationally. Current European and International sustainable development agendas target the reduction of such inequalities in working conditions and work-related health. Major growth in online retail has increased occupational opportunities in warehousing which are more accessible to foreign-born workers than traditional retail work. The rapid change has left research on working conditions, i.e., employment conditions, facility design (including digital tool use), work organization, physical and psychosocial work environment conditions, and worker health lagging. Further, to date, no known studies have considered patterns of inequality related to these factors. The overall aim of this 3-year study is to describe working conditions and musculoskeletal health in online retail warehousing, determine the extent to which differences exist related to gender and race/ethnicity, and to examine factors at the organisational and individual levels to provide a deeper understanding of why any differences may exist.
Methods
Three online retail warehouses, each employing approximately 50-150 employees performing receiving, order picking, order packing and dispatching tasks, will be recruited in Sweden. Warehouses will, to the extent possible, differ in their extent of digital technology use. Employment conditions, facility design (including digital tool use), work organization, physical and psychosocial work environment conditions and worker health will be assessed by survey, interview and technical measurements, the latter over five consecutive days. Analysis stratified by gender and place of birth will consider the extent to which inequalities exist. Focus group interviews with operations employees and in-depth interviews with managers, union and health and safety representatives will be conducted to assess how employee working conditions and musculoskeletal health are related to inequality regimes of gender and/or race/ethnicity in organizational processes and practices in online retail warehousing.
Discussion
This study will describe working conditions and health in online retail warehouse production workers and consider the extent to which patterns of inequality exist based on gender and race/ethnicity.
Trial registration: The study is pre-registered with the Open Science Framework
A novel RBBP8 (c.841G&gt;T) germline mutation is a predisposition mutation in familial hereditary cancer syndrome
Authors: Yan Jinhua , Wu Jinzheng , Wang Yang , Di Xiaotang , Jiang Hao , Wen Doudou , Li Duo , Zhang Shubing 
Published: February 2023

Abstract
Background: Screening tumor susceptibility genes will be found powerful biomarkers for hereditary cancer monitoring, prevention and diagnosis, which providing opportunities for understanding the potential molecular mechanism and biomarker for precise treatment of hereditary cancer syndromes.
Methods: Whole blood exon sequencing and bioinformatics analysis uncovers a novel RBBP8 (c.841G>T) germline mutation in this familial hereditary cancer syndrome, and verified by sanger sequencing. Cell proliferation, clone formation, cell migration, in vivo tumorigenesis were investigated by CCK8, clone formation assays, transwell, in vivo xenograft. The protein localization and interaction were detected by immunofluorescence, nuclear and cytoplasmic protein extraction kit and Co-IP .
Results: A new heterozygous germline mutation of RBBP8 (c.841G>T) gene was associated with familial hereditary cancer syndrome. Unlike RBBP8-WT is mainly detected in the nucleus and could interact with BRCA1. Opposite, RBBP8(c.841G>T) is mainly located in the cytoplasm and lost interact with BRCA1, which may gain some new functions in the cytoplasm to promote breast cancer proliferation, in vivo tumorigenesis and migration. Meanwhile, patients with RBBP8(c.841G>T) germline mutation maybe benefit from PARP inhibitors (Olaparib) and platinum (Cisplatin).
Conclusions: A de novo RBBP8 (c.841G>T) germline mutation was identified from familial hereditary cancer syndrome. RBBP8 (c.841G>T) lost its ability to enter the nucleus and the BRCA1 binding motif, which may gain some new functions to promote tumorigeneses in the cytoplasm. RBBP8 (c.841G>T) is a tumor susceptibility gene and candidate precision medicine biomarker in this familial hereditary cancer syndrome.
Identification of Bromelain Subfamily Proteases Encoded in the Pineapple Genome
Authors: Yow Ashley G. , Bostan Hamed , Young Roberto , Valacchi Giuseppe , Gillitt Nicholas , Perkins-Veazie Penelope , Xiang Qiu-Yun (Jenny) , Iorizzo Massimo 
Published: February 2023

Abstract
Papain (aka C1A) family proteases, including bromelain enzymes, are widespread across the plant kingdom and play critical regulatory functions in protein turnover during development. The proteolytic activity exhibited by papain family proteases has led to their increased usage for a wide range of cosmetic, therapeutic, and medicinal purposes. Bromelain enzymes, or bromelains in short, are members of the papain family that are specific to the bromeliad plant family. The only major commercial extraction source of bromelain is pineapple. The importance of C1A family and bromelain subfamily proteases in pineapple development and their increasing economic importance led several researchers to utilize available genomic resources to identify protease-encoding genes in the pineapple genome. To date, studies are lacking in screening bromelain genes for targeted use in applied science studies. In addition, the bromelain genes coding for the enzymes present in commercially available bromelain products have not been identified and their evolutionary origin has remained unclear. Here, using the newly developed MD2 v2 pineapple genome, we aimed to identify bromelain-encoding genes and elucidate their evolutionary origin. Orthologous and phylogenetic analyses of all papain-family proteases encoded in the pineapple genome revealed a single orthogroup (189) and phylogenetic clade (XIII) containing the bromelain subfamily. Duplication mode and synteny analyses provided insight into the origin and expansion of the bromelain subfamily in pineapple. Proteomic analysis identified four bromelain enzymes present in two commercially available bromelain products derived from pineapple stem, corresponding to products of four putative bromelain genes. Gene expression analysis using publicly available transcriptome data showed that 31 papain-family genes identified in this study were up-regulated in specific tissues, including stem, fruit, and floral tissues. Some of these genes had higher expression in earlier developmental stages of different tissues. Similar expression patterns were identified by RT-qPCR analysis with leaf, stem, and fruit. Our results provide a strong foundation for future applicable studies on bromelain, such as transgenic approaches to increase bromelain content in pineapple, development of bromelain-producing bioreactors, and studies that aim to determine the medicinal and/or therapeutic viability of individual bromelain enzymes.
End-user acceptability of a prototype digital stethoscope to diagnose childhood pneumonia- A qualitative exploration from Sylhet, Bangladesh
Authors: Joarder Taufique , Tune Samiun Nazrin Bente Kamal , Islam Ashraful , Islam Arifa , Roy Arunangshu Dutta , McCollum Eric D. , Nair Harish , Cunningham Steven , McLane Ian , Shahidullah Mohammod , Baqui Abdullah H. , Ahmed Salahuddin 
Published: February 2023

Abstract
Background: Considering the high frequency of respiratory infections among children in low- and middle-income countries (LMICs), the World Health Organization (WHO) developed a pragmatic guideline for managing pneumonia in low-resource settings. The guideline’s low specificity leads to many false-positive pneumonia cases receiving antibiotic treatment. Integrating diagnostic technology to incorporate lung sounds into WHO guidelines could improve childhood pneumonia diagnosis and management. This qualitative study aimed to explore the acceptability of a prototype digital stethoscope device among potential end-users in Bangladesh.
Methods: We conducted four focus group discussions (FGDs) with beneficiaries and service providers who used a 2018 digital stethoscope prototype. The data collection was conducted in November 2020. The study was carried out at Zakiganj Upazila (sub-district) of Sylhet district of Bangladesh. A total of 34 respondents, including parents of under-5 children, Community Health Care Providers (CHCPs), and community leaders were enrolled. Two researchers (TJ and another researcher) conducted the FGD. Verbatim transcripts were prepared, and translations were completed. Coding was executed in Microsoft Excel, and relevant quotes were extracted to ascertain the emerging themes. To ensure validity, two researchers coded the dataset independently and inconsistencies were resolved through discussion.
Findings: Mothers were more aware of the digital stethoscope than fathers. Except for the female community leaders, male leaders were unaware of the stethoscopes. Most CHCPs had positive perceptions of the digital stethoscope. They appreciated stethoscope training as they learned about new technology and diagnostic approaches. The users mentioned several technical shortcomings of the prototype device. A few stakeholders expressed dissatisfaction with the level of community involvement and information sharing from the study. The use of the device plummeted during the COVID-19 pandemic for fear of infection, to counteract which the CHCPs cleaned the device with chlorhexidine after every application as a precaution.
Conclusion:
Overall, device use was supported by stakeholders despite perceptions that the prototype had some technological limitations, community engagement was suboptimal, and the COVID-19 pandemic caused disruptions. Stronger community engagement, addressing technological issues, and further research on its health systems application would improve the acceptability and effective use of the digital stethoscope.
Repetitive transcranial magnetic stimulation alleviates glial activation through suppressing HMGB1/TLR4 pathway in a rat model of Parkinson’s disease
Authors: Han Chao , Zhang Xue , Dou Kaixin , Yao Weichao , Yao Minyi , Wan Qi , Xie Anmu 
Published: February 2023

Abstract
Background: Repetitive transcranial magnetic stimulation (rTMS) has been demonstrated to be effective in Parkinson’s disease (PD), but whether rTMS treatment has a relieving effect on neuroinflammation remains to be investigated. In this article, we explored the effects of rTMS on forelimb use asymmetry and neuroinflammation-related mechanisms in a 6-hydroxydopamine (6-OHDA)-induced PD rat model.
Methods and Results: Rats in the 6-OHDA+rTMS group received 10 Hz rTMS daily for 4 weeks. Behavioral tests (the cylinder test) were performed at the 3rd and 7th weeks after the operation. Astrocyte and microglia activation and protein levels of tyrosine hydroxylase (TH), high-mobility group box 1(HMGB1) and toll-like receptors 4(TLR4) were investigated by immunohistochemistry and Western blot analyses, respectively. After 4 weeks of treatment，forelimb use asymmetry was ameliorated in the 6-OHDA+rTMS group. Consistent with the behavioral tests, rTMS increased TH in the substantia nigra (SN) of PD rats. High glial activation and HMGB1/TLR4 expression were observed in the 6-OHDA group, while rTMS alleviated these changes.
Conclusions: This study showed that rTMS might be a promising method for alleviating neuroinflammation in PD rat models, and the effects might be mediated through the downregulation of the HMGB1/TLR4 pathway.
Application of Facial Expression Recognition Based on Domain Adapted Convolutional Neural Network in English Smart Teaching System
Authors: Liu Lilin 
Published: February 2023

Abstract
The application of the facial expression recognition system in the human-computer interaction system refers to the recognition of human facial expressions through the human-computer interaction system in the real society, so as to be able to feel the specific situation of recognizing people. This is also one of the main directions of human-computer interaction system research. In this paper, the facial expression recognition system is designed by the algorithm that combines the expressions of the students in the classroom teaching with the system environment, so that the recognition of the facial expressions of the students in the classroom environment is more accurate. This article elaborates on the identification method of the system, and conducts detailed experimental analysis on the specific functions of other modules in the system. The experimental results show that the security and stability of the system are very high. At the same time, the accuracy of the system in the classroom teaching environment is also very high in the recognition of student facial expressions. This is a modern intelligent face recognition system that enters education and teaching. Provide a strong theoretical basis and technical support during the work.
Cooperative function of oncogenic MAPK signaling and the loss of Pten for melanoma migration through the formation of lamellipodia
Authors: Yokoyama Satoru , Yasuta Yutaka , Nagai Shutaro , Mouri Shuto , Kaminaka Ryuya , Ishida Katsuya , Tanaka Akihiro , Zhou Yue , Sakurai Hiroaki 
Published: February 2023

Abstract
The combination of oncogenes and tumor suppressors overcomes selective pressure from host immune systems for cancer development; however, it is still unknown whether their combination plays a critical role in cancer metastasis. We herein investigated whether genetic combinations affected cell migration ability by establishing the immortalized melanocytes, melan-a cells, with an oncogene, either BRAFV600E or GNA11Q209L, and the loss of mouse Pten. The loss of mouse Pten or human PTEN increased the cell migration ability of our established cells and human melanoma cell lines with oncogenic MAPK signaling and the BRAFV600E or NRASQ61R background, but not with the GNA11Q209L background or no oncogenes. Although increased migration was not related to PI3K-AKT activation, those migration is regulated by the induction of some components in the WAVE regulatory complex, resulting in a higher rate of the formation of lamellipodia. On the other hand, BRAFV600E induced EphA2 phosphorylation at Serine 897 through RSK and was also required for cell migration and the formation of lamellipodia. Therefore, the oncogenic MAPK pathway and loss of Pten in melanoma were important for cell migration through the formation of lamellipodia, suggesting the significance of an appropriate combination of genetic alterations not only in cancer development, but also cancer metastasis.
No cause-effect relationships between psychiatric disorders and amyotrophic lateral sclerosis: a bidirectional Mendelian randomization study
Authors: Huang Zhilin , Wen Yutong , Tian Yueqin , Zou Haiqiang , Chen Aimin , Chen Jian , Xie Haiting , Chen Jingyi , Xiong Fu , Gao Xiaoya 
Published: February 2023

Abstract
Background
Previous reports have been inconsistent about the associations between amyotrophic lateral sclerosis (ALS) and psychiatric disorders. More importantly, it needs to be elucidated whether these associations are causal or confounded.
Objective
We aimed to determine the presence of cause-effect relationships between ALS and four psychiatric disorders (schizophrenia; bipolar disorder; anxiety, nerves, tension or depression disorders (ADD); and neuroticism) using a bidirectional Mendelian randomization (BDMR) analysis based on gene associations.
Methods
First, we extracted genome-wide association studies (GWAS) summaries for the four psychiatric disorders and ALS from the Integrative Epidemiology Unit (IEU) and the Psychiatric Genomics Consortium (PGC) GWAS database. We then identified single-nucleotide polymorphisms (SNPs) that are strongly associated with exposure, are independent of confounders, and are related to exposure-outcome, as instrumental variables (IVs) for Mendelian randomization (MR) analyses. In the MR analysis, the cause-effect relationships were analyzed using psychiatric disorders as the exposure variable and ALS as the outcome, with six methods (primary inverse-variance weighted (IVW), MR-Egger, weighted median estimator, simple mode, weighted mode, and robust adjusted profile score (RAPS)analyses). Moreover, the results were subjected to sensitivity analyses, namely, IVW and MR-Egger analyses (for potential heterogeneity and horizontal pleiotropy) and MR leave-one-out analysis (to determine whether one SNP drove the causal signal). Finally, reverse MR analyses were conducted using ALS as the exposure variable and four psychiatric disorders as outcome variables; sensitivity was assessed.
Results
After extracting the GWAS summaries, we established IVs, including 147, 13, 37, and 105 SNPs for schizophrenia, bipolar disorder, ADD, and neuroticism, respectively. Subsequently, the MR analyses conducted using the six methods revealed no cause-effect relationships of the four psychiatric disorders with ALS. Moreover, we set up six SNPs as IVs for ALS in reverse MR analyses. Finally, no statistically significant cause-effect relationship of ALS with the four psychiatric disorders was found. These associations were robust as shown by the sensitivity analyses.
Conclusions
BDMR analyses revealed no significant genetic evidence for a cause-effect relationship between ALS and four psychiatric disorders.
The Role of Plasmids in Carbapenem Resistant E. coli in Alameda County, California
Authors: Walas Nikolina , Slown Samuel , Amato Heather K. , Lloyd Tyler , Bender Monica , Varghese Vici , Pandori Mark , Graham Jay P. 
Published: February 2023

Abstract
Background: Antimicrobial resistant infections continue to be a leading global public health crisis. Mobile genetic elements, such as plasmids, have been shown to play a major role in the dissemination of antimicrobial resistance genes. Despite its ongoing threat to human health, surveillance in the United States is often limited to phenotypic resistance. Genomic analyses are important to better understand the underlying resistance mechanisms, assess risk, and implement appropriate prevention methods. This study aimed to investigate the extent of plasmid mediated antimicrobial resistance that can be inferred from short read sequences of carbapenem resistant E. coli (CR-Ec) in Alameda County, California. E. coli isolates from healthcare locations in Alameda County were sequenced using an Illumina MiSeq and assembled with Unicycler. Genomes were categorized according to predefined multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) schemes. Resistance genes were identified and corresponding contigs were predicted to be plasmid-borne or chromosome-borne using two bioinformatic tools (MOB-suite and mlplasmids).
Results: Among 82 of CR-Ec identified between 2017 and 2019, twenty-five sequence types (STs) were detected. ST131 was the most prominent (n=17) followed closely by ST405 (n=12). blaCTX-M were the most common ESBL genes and just over half (18/30) of these genes were predicted to be plasmid-borne by both MOB-suite and mlplasmids. Three genetically related groups of E. coli isolates were identified with cgMLST. One of the groups contained an isolate with a chromosome-borne blaCTX-M-15 gene and an isolate with a plasmid-borne blaCTX-M-15 gene.
Conclusions: This study provides insights into the dominant clonal groups driving carbapenem resistant E. coli infections in Alameda County, CA, USA clinical sites and highlights the relevance of whole-genome sequencing in routine local genomic surveillance. The finding of multi-drug resistant plasmids harboring high-risk resistance genes is of concern as it indicates a risk of dissemination to previously susceptible clonal groups in the community, potentially complicating clinical and public health intervention.