bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold Versus Hot Snare Polypectomy for Colorectal Polyps
Authors: Abuelazm Mohamed , Mohamed Islam , Jaber Fouad S. , Katamesh Basant E. , Shaikhkhalil Hosam , Elzeftawy Mohamed A. , Mahmoud Abdelrahman , Afifi Ahmed M. , Abdelazeem Basel , Othman Mohamed 
Published: February 2023

Background and Objective:
Endoscopic polypectomy is an excellent tool for colon cancer prevention. With the innovation of novel resection techniques, the best method is still being investigated. Hence, we aim to evaluate the efficacy and safety of cold snare polypectomy (CSP) versus hot snare polypectomy (HSP) for colorectal polyp resection.

Methods:
A systematic review and meta-analysis synthesizing evidence from randomized controlled trials retrieved from PubMed, EMBASE, WOS, SCOPUS, and CENTRAL until July 16, 2022. We pooled dichotomous outcomes using risk ratio (RR) with the corresponding CI. This review’s protocol was prospectively registered in PROSPERO with ID: CRD42022347496.

Results:
We included 18 randomized controlled trials with a total of 4317 patients and 7509 polyps. Pooled RR favored HSP regarding the complete resection rate (RR: 0.96 with 95% CI: 0.95, 1, P = 0.03) and local recurrence incidence (RR: 5.74 with 95% CI: 1.27, 25.8, P = 0.02). Pooled RR favored CSP regarding the colonoscopy time (mean difference: −6.50 with 95% CI: −7.55, −5.44, P = 0.00001) and polypectomy time (mean difference: −57.36 with 95% CI: −81.74, −32.98, P = 0.00001). There was no difference regarding the incidence of immediate bleeding (P = 0.06) and perforation (P = 0.39); however, HSP was associated with more incidence of delayed bleeding (P = 0.01), abdominal pain (P = 0.007), and postresection syndrome (P = 0.02).

Discussion:
HSP is associated with a higher complete resection and lower recurrence rates; however, HSP is also associated with a higher incidence of adverse events. Therefore, improving the complete resection rate with CSP still warrants more innovation, giving the technique safety and shorter procedure duration.
An app for predicting patient dementia classes using convolutional neural networks (CNN) and artificial neural networks (ANN): Comparison of prediction accuracy in Microsoft Excel
Authors: Ho Sam Yu-Chieh , Chien Tsair-Wei , Lin Mei-Lien , Tsai Kang-Ting 
Published: February 2023

Background:
Dementia is a progressive disease that worsens over time as cognitive abilities deteriorate. Effective preventive interventions require early detection. However, there are no reports in the literature concerning apps that have been developed and designed to predict patient dementia classes (DCs). This study aimed to develop an app that could predict DC automatically and accurately for patients responding to the clinical dementia rating (CDR) instrument.

Methods:
A CDR was applied to 366 outpatients in a hospital in Taiwan, with assessments on 25 and 49 items endorsed by patients and family members, respectively. The 2 models of convolutional neural networks (CNN) and artificial neural networks (ANN) were applied to examine the prediction accuracy based on 5 classes (i.e., no cognitive decline, very mild, mild, moderate, and severe) in 4 scenarios, consisting of 74 (items) in total, 25 in patients, 49 in family, and a combination strategy to select the best in the aforementioned scenarios using the forest plot. Using CDR scores in patients and their families on both axes, patients were dispersed on a radar plot. An app was developed to predict patient DC.

Results:
We found that ANN had higher accuracy rates than CNN with a ratio of 3:1 in the 4 scenarios. The highest accuracy rate (=93.72%) was shown in the combination scenario of ANN. A significant difference was observed between the CNN and ANN in terms of the accuracy rate. An available ANN-based app for predicting DC in patients was successfully developed and demonstrated in this study.

Conclusion:
On the basis of a combination strategy and a decision rule, a 74-item ANN model with 285 estimated parameters was developed and included. The development of an app that will assist clinicians in predicting DC in clinical settings is required in the near future.
A comparison of the efficacy of tocilizumab versus azathioprine for neuromyelitis optica spectrum disorder: A study protocol for systematic review and meta-analysis
Authors: Tang Qi , Yao Mengyuan , Huang Yuanyuan , Bian Jiangping , Wang Yupeng , Ji Wenbo 
Published: February 2023

Background:
Neuromyelitis optica spectrum disorder (NMOSD) is a chronic inflammatory disease of the nervous system, which is frequently accompanied by a pathological humoral immune response against aquaporin-4 water channel. The most common feature of the disorder is recurrent episodes of longitudinally extensive transverse myelitis and optic neuritis. Frequent relapse leads to the gradual accumulation of neurological dysfunction. Azathioprine (AZA) is an empirical attack -preventive immunotherapies drug to prevent the relapse of NMOSD, and tocilizumab (TCZ) has been also reported reduce the activity of NMOSD. Therefore, we designed this systematic review and meta-analysis to evaluate the efficacy between TCZ and AZA in the treatment of NMOSD patients.

Methods:
This study followed the PRISMA guidelines. We searched the English literature between 2000 and 2022 by using relevant medical subject heading and entry terms in PubMed, MEDLINE, Embase and CENTRAL databases. A meta-analysis of drug efficacy was performed using expanded disability status scale score and annualized relapse rate (ARR) as the primary outcome indicators.

Results:
The literature search found a total of 1546 articles about TCZ and AZA in the treatment of NMOSD, 27 of which were included in this study after a series of screening. 930 and 148 patients with NMOSD were enrolled, who had been treated with AZA and TCZ, respectively. The pooled standardized mean difference (SMD) of expanded disability status scale score before and after AZA treated was -0.40 (95%CI: -0.50, -0.30) (I2 = 65.4%, P < .001), before and after TCZ treated was -0.84 (95%CI: -1.08, -0.60) (I2 = 45.6%, P = .076). The SMD of ARR before and after AZA treated was -1.01 (95%CI: -1.12, -0.90) (I2 = 83.4%, P < .001), before and after TCZ treated was -1.27 (95%CI: -1.52, -1.03) (I2 = 52.7%, P = .039). In addition, TCZ reduce ARR more significantly compared with AZA (P = .031).

Conclusion:
The results of this study showed that the treatment of NMOSD patients with AZA and TCZ are associated with decreased number of relapses and disability improvement as well. In addition, compared with AZA, TCZ more significantly reduce ARR.
Clinical efficacy of overground powered exoskeleton for gait training in patients with subacute stroke: A randomized controlled pilot trial
Authors: Yoo Hyun-Joon , Bae Cho Rong , Jeong Hyeonsoon , Ko Myoung-Hwan , Kang Yoon-Kyoo , Pyun Sung-Bom 
Published: February 2023

Background:
To investigate the efficacy and usefulness of 12 sessions of overground robot-assisted gait training (RAGT) in subacute stroke patients.

Methods:
In this pilot study, 17 subacute stroke survivors were randomly assigned to the intervention (n = 9) and control (n = 8) groups. In addition to the conventional stroke neurorehabilitation program, the intervention group received 30 minutes of overground exoskeletal RAGT, while the control group received 30 minutes of conventional gait training by a physiotherapist. All interventions were performed in 12 sessions (3 times/week for 4 weeks). The primary aim was to assess ambulation ability using the functional ambulation category (FAC). The 10-m walk test, Berg Balance Scale, timed-up-and-go Timed-up-and-go, Fugl–Meyer assessment of lower extremity, pulmonary function test, the Korean version of the modified Barthel index, and Euro quality of life-5 dimensions (EQ-5D) were assessed. All outcomes were evaluated both before and after the intervention.

Results:
The Berg Balance Scale, Korean version of the modified Barthel index, and EQ-5D scores (P < .05) improved significantly in both groups. Only those in the RAGT group improved significantly in the FAC, timed-up-and-go, and 10-m walk test (P < .05). In the FAC and EQ-5D, the intervention group showed greater improvement than the control group (P < .05).

Conclusion:
We found that 4 weeks of overground RAGT combined with conventional training may improve walking independence and quality of life in patients with subacute stroke.
Research on the pathological mechanism of rectal adenocarcinoma based on DNA methylation
Authors: Pan Xiaoqiang , Yi Xingcheng , Lan Maozhuo , Su Xiaoyun , Zhou Fang , Wu Wei 
Published: February 2023

Colorectal cancer is one of the 3 most common cancers worldwide. In this study, a weighted network-based analysis method was proposed to explore the pathological mechanisms and prognostic targets of rectal adenocarcinoma (READ) at the deoxyribonucleic acid (DNA) methylation level.
In this study, we downloaded clinical information and DNA methylation data from The Cancer Genome Atlas database. Differentially methylated gene analysis was used to identify the differential methylated genes in READ. Canonical correlation analysis was used to construct the weighted gene regulatory network for READ. Multilevel analysis and association analyses between gene modules and clinical information were used to mine key modules related to tumor metastasis evaluation. Genetic significance analysis was used to identify methylation sites in key modules. Finally, the importance of these methylation sites was confirmed using survival analysis.
DNA methylation datasets from 90 cancer tissue samples and 6 paracancerous tissue samples were selected. A weighted gene regulatory network was constructed, and a multilevel algorithm was used to divide the gene co-expression network into 20 modules. From gene ontology enrichment analysis, characteristic M was related to biological processes such as the chemotaxis of fibroblast growth factors and the activation and regulation of immune cells etc and characteristic N was associated with the regulation of cytoskeleton formation, mainly microtubules and flagella, regulation of synapses, and regulation of cell mitosis. Based on the results of survival analysis, 7 key methylation sites were found closely correlated to the survival rate of READ, such as cg04441191 (microtubule-associated protein 4 [MAP4]), cg05658717 (KSR2), cg09622330 (GRIN2A), cg10698404 (YWHAG), cg17047993 (SPAG9), cg24504843 (CEP135), and cg24531267 (CEP250). Mutational and transcriptomic level studies revealed significant differences in DNA methylation, single nucleotide polymorphism, and transcript levels between YWHAG and MAP4 in normal tissues compared to tumor tissues, and differential expression of the 2 proteins in immunohistochemistry. Therefore, potential targeting drugs were screened for these 2 proteins for molecular docking, and artenimol was found to bind to MAP4 protein and 27-hydroxycholesterol to YWHAG.
Our study found that key methylation sites played an important role in tumor metastasis and were associated with the prognosis of READ. Mutations and methylation may jointly regulate the transcription and translation of related genes, which in turn affect cancer progression. This may provide some new potential therapeutic targets and thoughts for the prognosis of READ.
Predictions from standard epidemiological models of consequences of segregating and isolating vulnerable people into care facilities
Authors: Hickey Joseph , Rancourt Denis G. 
Published: February 2023

AbstractObjectivesSince the declaration of the COVID-19 pandemic, many governments have imposed policies to reduce contacts between people who are presumed to be particularly vulnerable to dying from respiratory illnesses and the rest of the population. These policies typically address vulnerable individuals concentrated in centralized care facilities and entail limiting social contacts with visitors, staff members, and other care home residents. We use a standard epidemiological model to investigate the impact of such circumstances on the predicted infectious disease attack rates, for interacting robust and vulnerable populations.DesignWe implement a general susceptible-infectious-recovered (SIR) compartmental model with two populations: robust and vulnerable. The key model parameters are the per-individual frequencies of within-group (robust-robust and vulnerable-vulnerable) and between-group (robust-vulnerable and vulnerable-robust) infectious-susceptible contacts and the recovery times of individuals in the two groups, which can be significantly longer for vulnerable people.ResultsAcross a large range of possible model parameters including degrees of segregation versus intermingling of vulnerable and robust individuals, we find that concentrating the most vulnerable into centralized care facilities virtually always increases the infectious disease attack rate in the vulnerable group, without significant benefit to the resistant group.ConclusionsIsolated care homes of vulnerable residents are predicted to be the worst possible mixing circumstances for reducing harm in epidemic or pandemic conditions.Strengths and limitations of this studyWe implement a simplest-possible sufficiently-realistic SIR model for an infectious respiratory disease with two interacting populations: robust and vulnerable.We investigate the predicted attack rates for a large range of parameters representing different degrees of segregation or isolation of the minority vulnerable population.We make broad-ranging conclusions about the consequences of segregation and isolation of vulnerable people, which apply to any epidemic model based on the SIR foundational assumptions.Large-parameter-range exploration is needed because the actual parameter values, especially the frequencies of infectious contacts, are not well delimited by empirical measurements and are often essentially unknown.
GATA1knockout in human pluripotent stem cells generates enhanced neutrophils to investigate extracellular trap formation
Authors: Harper Thomas C. , Oberlick Elaine M. , Smith Tomas J. , Nunes Duncan E. , Bray Mark A. , Park Seonmi , Driscoll Corey D. , Mowbray Sarah F. , Antczak Christophe 
Published: February 2023

AbstractHuman pluripotent stem cell (hPSC)-derived tissues can be used to model diseases and validate targets in cell types that are challenging to harvest and study at-scale, such as neutrophils. Neutrophil dysregulation, specifically unbalanced neutrophil extracellular trap (NET) formation, plays a critical role in the prognosis and progression of multiple diseases, including COVID-19. hPSCs can provide a limitless supply of neutrophils (iNeutrophils) to study these processes and discover and validate targetsin vitro. However, current iNeutrophil differentiation protocols are inefficient and generate heterogeneous cultures consisting of different granulocytes and precursors, which can confound the study of neutrophil biology. Here, we describe a method to dramatically improve iNeutrophils’ yield, purity, functionality, and maturity through the deletion of the transcription factorGATA1. GATA1knockout (KO) iNeutrophils are nearly identical to primary neutrophils in cell surface marker expression, morphology, and host defense functions. Unlike wild type (WT) iNeutrophils,GATA1KO iNeutrophils generate NETs in response to the physiologic stimulant lipopolysaccharide (LPS), suggesting they could be used as a more accurate model when performing small-molecule screens to find NET inhibitors. Furthermore, through CRSPR/Cas9 deletion ofCYBBwe demonstrate thatGATA1KO iNeutrophils are a powerful tool in quickly and definitively determining involvement of a given protein in NET formation.
Truncated titin is integrated into the human dilated cardiomyopathic sarcomere
Authors: Kellermayer Dalma , Tordai Hedvig , Kiss Balázs , Török György , Péter Dániel M. , Sayour Alex Ali , Pólos Miklós , Hartyánszky István , Szilveszter Bálint , Labeit Siegfried , Gángó Ambrus , Bedics Gábor , Bödör Csaba , Radovits Tamás , Merkely Béla , Kellermayer Miklós S.Z. 
Published: February 2023

AbstractHeterozygous (HET) truncating mutations in the TTN gene (TTNtv) encoding the giant titin protein are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations induce DCM are controversial. Here we investigated 127 clinically identified DCM human cardiac samples with next-generation sequencing (NGS), high-resolution gel electrophoresis, Western blot analysis and super-resolution microscopy in order to dissect the structural and functional consequences of TTNtv mutations. The occurrence of TTNtv was found to be 15% in the DCM cohort. Truncated titin proteins matching, by molecular weight, the gene-sequence predictions were detected in the majority of the TTNtv samples. The total amount of expressed titin, which includes the truncated fragments, was comparable in the TTNtv+ and TTNtv-samples, indicating that titin haploinsufficiency is not the leading cause of the molecular pathogenesis. Proteomic analysis of washed cardiac myofibrils and Stimulated Emission Depletion (STED) super-resolution microscopy of myocardial sarcomeres labeled with sequence-specific anti-titin antibodies revealed that truncated titin is structurally integrated in the sarcomere. Sarcomere lengthdependent anti-titin epitope position, shape and intensity analysis pointed at structural defects in the I/A junction and the M-band of TTNtv+ sarcomeres, which may contribute, via faulty mechanosensor function, to the development of manifest DCM.
Cytokine-Mediated Degradation of the Transcription Factor ERG Impacts the Pulmonary Vascular Response to Systemic Inflammatory Challenge
Authors: Schafer Christopher M. , Martin-Almedina Silvia , Kurylowicz Katarzyna , Dufton Neil , Osuna-Almagro Lourdes , Wu Meng-Ling , Johnson Charmain F. , Shah Aarti V. , Haskard Dorian O. , Buxton Andrianna , Willis Erika , Wheeler Kate , Turner Sean , Chlebicz Magdalena , Scott Rizaldy P. , Kovats Susan , Cleuren Audrey , Birdsey Graeme M. , Randi Anna M. , Griffin Courtney T. 
Published: February 2023

ABSTRACTBackgroundDuring infectious diseases, pro-inflammatory cytokines transiently destabilize interactions between adjacent vascular endothelial cells (ECs) to facilitate the passage of immune molecules and cells into tissues. However, in the lung the resulting vascular hyperpermeability can lead to organ dysfunction. Previous work identified the transcription factor ERG as a master regulator of endothelial homeostasis. Here we investigate whether the sensitivity of pulmonary blood vessels to cytokine-induced destabilization is due to organotypic mechanisms affecting the ability of endothelial ERG to protect lung ECs from inflammatory injury.MethodsCytokine-dependent ubiquitination and proteasomal degradation of ERG was analyzed in cultured Human Umbilical Vein ECs (HUVECs). Systemic administration of TNFα or the bacterial cell wall component lipopolysaccharide (LPS) was used to cause a widespread inflammatory challenge in mice; ERG protein levels were assessed by immunoprecipitation, immunoblot, and immunofluorescence. MurineErgdeletion was genetically induced in ECs (Ergfl/fl;Cdh5(PAC)CreERT2), and multiple organs were analyzed by histology, immunostaining, and electron microscopy.ResultsIn vitro, TNFα promoted the ubiquitination and degradation of ERG in HUVECs, which was blocked by the proteasomal inhibitor MG132. In vivo, systemic administration of TNFα or LPS resulted in a rapid and substantial degradation of ERG within lung ECs, but not ECs of the retina, heart, liver, or kidney. Pulmonary ERG was also downregulated in a murine model of influenza infection.Ergfl/fl;Cdh5(PAC)-CreERT2mice spontaneously recapitulated aspects of inflammatory challenges, including lung-predominant vascular hyperpermeability, immune cell recruitment, and fibrosis. These phenotypes were associated with a lung-specific decrease in the expression ofTek, a gene target of ERG previously implicated in maintaining pulmonary vascular stability during inflammation.ConclusionsCollectively, our data highlight a unique role for ERG in pulmonary vascular function. We propose that cytokine-induced ERG degradation and subsequent transcriptional changes in lung ECs play critical roles in the destabilization of pulmonary blood vessels during infectious diseases.
Genetic Predictors of Blood Pressure Traits are Associated with Preeclampsia
Authors: Jasper Elizabeth A. , Hellwege Jacklyn N. , Breeyear Joseph H. , Xiao Brenda , Jarvik Gail P. , Stanaway Ian B. , Leppig Kathleen A. , Chittoor Geetha , Hayes M. Geoffrey , Dikilitas Ozan , Kullo Iftikhar J. , Holm Ingrid A. , Verma Shefali Setia , Edwards Todd L. , Velez Edwards Digna R. 
Published: February 2023

AbstractBackgroundPreeclampsia, a pregnancy complication characterized by hypertension after 20 gestational weeks, is a major cause of maternal and neonatal morbidity and mortality. The mechanisms leading to preeclampsia are unclear; however, there is evidence that preeclampsia is highly heritable. We evaluated the association of polygenic risk scores (PRS) for blood pressure traits and preeclampsia to assess whether there is shared genetic architecture.MethodsParticipants were obtained from Vanderbilt University’s BioVU, the Electronic Medical Records and Genomics network, and the Penn Medicine Biobank. Non-Hispanic Black and White females of reproductive age with indications of pregnancy and genotype information were included. Preeclampsia was defined by ICD codes. Summary statistics for diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) PRS were obtained from Giri et al 2019. Associations between preeclampsia and each PRS were evaluated separately by race and study population before evidence was meta-analyzed. Prediction models were developed and evaluated using 10-fold cross validation.ResultsIn the 3,504 Black and 5,009 White individuals included, the rate of preeclampsia was 15.49%. The DBP and SBP PRSs were associated with preeclampsia in Whites but not Blacks. The PP PRS was significantly associated with preeclampsia in Blacks and Whites. In trans-ancestry meta-analysis, all PRSs were associated with preeclampsia (ORDBP=1.10, 95% CI=1.02-1.17,p=7.68×10−3; ORSBP=1.16, 95% CI=1.09-1.23,p=2.23×10−6; ORPP=1.14, 95% CI=1.07-1.27,p=9.86×10−5). However, addition of PRSs to clinical prediction models did not improve predictive performance.ConclusionsGenetic factors contributing to blood pressure regulation in the general population also predispose to preeclampsia.