bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of topologically associating domain callers over mammals at high resolution
Authors: Sefer Emre 
Published: April 2022

Abstract
Background
Topologically associating domains (TADs) are locally highly-interacting genome regions, which also play a critical role in regulating gene expression in the cell. TADs have been first identified while investigating the 3D genome structure over High-throughput Chromosome Conformation Capture (Hi-C) interaction dataset. Substantial degree of efforts have been devoted to develop techniques for inferring TADs from Hi-C interaction dataset. Many TAD-calling methods have been developed which differ in their criteria and assumptions in TAD inference. Correspondingly, TADs inferred via these callers vary in terms of both similarities and biological features they are enriched in.

Result
We have carried out a systematic comparison of 27 TAD-calling methods over mammals. We use Micro-C, a recent high-resolution variant of Hi-C, to compare TADs at a very high resolution, and classify the methods into 3 categories: feature-based methods, Clustering methods, Graph-partitioning methods. We have evaluated TAD boundaries, gaps between adjacent TADs, and quality of TADs across various criteria. We also found particularly CTCF and Cohesin proteins to be effective in formation of TADs with corner dots. We have also assessed the callers performance on simulated datasets since a gold standard for TADs is missing. TAD sizes and numbers change remarkably between TAD callers and dataset resolutions, indicating that TADs are hierarchically-organized domains, instead of disjoint regions. A core subset of feature-based TAD callers regularly perform the best while inferring reproducible domains, which are also enriched for TAD related biological properties.

Conclusion
We have analyzed the fundamental principles of TAD-calling methods, and identified the existing situation in TAD inference across high resolution Micro-C interaction datasets over mammals. We come up with a systematic, comprehensive, and concise framework to evaluate the TAD-calling methods performance across Micro-C datasets. Our research will be useful in selecting appropriate methods for TAD inference and evaluation based on available data, experimental design, and biological question of interest. We also introduce our analysis as a benchmarking tool with publicly available source code.
COX-2 strengthens the effects of acid and bile salts on human esophageal cells and Barrett esophageal cells
Authors: Jiangang Shen , Nayoung Kang , Hongfang Wang , Junda Li , Li Chen , Xuefeng Bai , Mingsong Li 
Published: April 2022

Abstract
Aims
Investigate the effect and mechanism of COX-2 on viability, intestinal metaplasia, and atypia in human esophageal squamous and Barrett esophageal cell lines.

Methods
Human esophageal squamous and Barrett esophageal cell lines were transfected with a COX-2 expression vector and a COX-2 siRNA, and then were treated with acid, bile salts, and a mixture of both. Cell viability, the expression of COX-2, NF-κB(p65), CDX-2, MUC2, c-myb, and BMP-4, and the morphology and microstructure of cells were then observed.

Results
The viability of COX-2 overexpressed cells was significantly higher than that of control cells, while the viability of COX-2 siRNA-treated cells was significantly lower than that of control cells. Intestinal metaplasia and atypia were observed in cells overexpressing COX-2. Acid, bile salts, and their mixture inhibited the viability of these two cell lines, but the inhibitory effect of the mixture was stronger than a single treatment in either. SiRNA mediated knockdown of COX-2 strengthened the antiproliferative effects of the mixture on HET-1A and BAR-T cells. The expression of p-p65, CDX-2, and BMP-4 was positively correlated with COX-2 expression, while the expression levels of p65, MUC2, and c-myb remained unchanged.

Conclusion
COX-2 may influence the viability, atypia, and intestinal metaplasia of human esophageal cells and Barrett esophageal cells. Activation of the p-p65, CDX-2, and BMP-4 signaling pathways by COX-2 may be part of this mechanism.
Standard rectal swabs as a surrogate sample for gut microbiome monitoring in intensive care
Authors: Schlebusch Sanmarié , Graham Rikki M. A. , Jennison Amy V. , Lassig-Smith Melissa M. , Harris Patrick N. A. , Lipman Jeffrey , Ó Cuív Páraic , Paterson David L. 
Published: April 2022

AbstractBackgroundThe purpose of this study was to investigate the use of routinely available rectal swabs as a surrogate sample type for testing the gut microbiome and monitoring antibiotic effects on key gut microorganisms, of patients hospitalised in an intensive care unit. A metagenomic whole genome sequencing approach was undertaken to determine the diversity of organisms as well as resistance genes and to compare findings between the two sampling techniques.ResultsNo significant difference was observed in overall diversity between the faeces and rectal swabs and sampling technique was not demonstrated to predict microbial community variation. More human DNA was present in the swabs and some differences were observed only for a select few anaerobes and bacteria also associated with skin and/or the female genitourinary system, possibly reflecting sampling site or technique. Antibiotics and collections at different times of admission were both considered significant influences on microbial community composition alteration. Detection of antibiotic resistance genes between rectal swabs and faeces were overall not significantly different, although some variations were detected with a potential association with the number of human sequence reads in a sample.ConclusionTesting the gut microbiome using standard rectal swab collection techniques currently used for multi-resistant organism screening has been demonstrated to have utility in gut microbiome monitoring in intensive care. The use of information from this article, in terms of methodology as well as near equivalence demonstrated between rectal swabs and faeces will be able to support and potentially facilitate the introduction into clinical practice.
Plastome structure, phylogenomics and evolution of plastid genes in Swertia (Gentianaceae) in the Qing-Tibetan Plateau
Authors: Cao Qian , Gao Qingbo , Ma Xiaolei , Zhang Faqi , Xing Rui , Chi Xiaofeng , Chen Shilong 
Published: April 2022

Abstract
Background
The genus Swertia is of great medicinal importance and one of the most taxonomically challenging taxa within Gentianaceae, largely due to the morphological similarities of species within this genus and with its closely related genera. Previous molecular studies confirmed its polyphyly but suffered from low phylogenetic resolutions because only limited sequence loci were used. Thus, we conducted the structural, gene evolutionary, and phylogenetic analyses of 11 newly obtained plastomes of Swertia. Our result greatly improved the phylogenetic resolutions in Swertia, shed new light on the plastome evolution and phylogenetic relationships of this genus.

Results
The 11 Swertia plastomes together with the published seven species proved highly similar in overall size, structure, gene order, and content, but revealed some structural variations caused by the expansion and contraction of the IRb region into the LSC region, due to the heterogeneous length of the ψycf1. The gene rps16 was found to be in a state flux with pseudogenes or completely lost. Similar situation was also documented in other genera of Gentianaceae. This might imply loss of the gene in the common ancestor of Gentianaceae. The distribution plot of ENC vs. GC3 showed all these plastomes arranging very close in the Wright line with an expected ENC value (49–52%), suggesting the codon usage of Swertia was mainly constrained by a GC mutation bias. Most of the genes remained under the purifying selection, however, the cemA was identified under positive selection, possibly reflecting an adaptive response to low CO2 atmospheric conditions during the Late Miocene. Our phylogenomic analyses, based on 74 protein-coding genes (CDS), supported the polyphyly of Swertia with its close allies in the subtribe Swertiinae, presumably due to recent rapid radiation. The topology inferred from our phylogenetic analyses partly supported the current taxonomic treatment. Finally, several highly variable loci were identified, which can be used in future phylogenetic studies and accurate identification of medicinal genuineness of Swertia.

Conclusions
Our study confirmed the polyphyly of Swertia and demonstrated the power of plastome phylogenomics in improvement of phylogenetic resolution, thus contributing to a better understanding of the evolutionary history of Swertia.
Serum total bilirubin and long-term prognosis of patients with new-onset non-ST elevation myocardial infarction: a cohort study
Authors: Yang Yi , Wang Jun , Wai Si Ding A Ji Gu Li , Xu Yanan , Jiang Haibing , Ma Kezhong , Zhu Tongjian 
Published: April 2022

Abstract
Background
The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the potential predictive value of TBIL for long-term prognosis in patients with new-onset NSTEMI.

Methods
Patients with new-onset NSTEMI that underwent emergency coronary angiography in our department from June 2015 to March 2020 were included. Baseline TBIL was measured at admission. SYNTAX scores were used to indicate the severity of coronary lesions. The association between TBIL and SYNTAX scores was analyzed using multivariate logistic regression. The patients were followed for the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The association between TBIL and MACCEs was analyzed using Kaplan–Meier survival methods.

Results
In total 327 patients were included in this study. Patients were divided according to tertiles of TBIL (first tertile < 10.23 µmol/L, n = 109; second tertile 10.23–14.30 µmol/L, n = 109; and third tertile ≥ 14.30 µmol/L, n = 109). TBIL was independently associated with the severity of coronary lesions in patients with NSTEMI, with an adjusted odds ratio (OR) and 95% confidence interval (CI) for the third tertile and the second tertile compared with the first tertile of TBIL of 2.259 (1.197–4.263) and 2.167 (1.157–4.059), respectively (both p < 0.05). After a mean follow-up of 30.33 months, MACCE had occurred in 57 patients. TBIL was independently associated with the increased risk of MACCEs, with an adjusted hazard ratio (HR) and 95% CI for the third tertile and the second tertile compared with the first tertile of TBIL of 2.737 (1.161–6.450) and 3.272 (1.408–7.607), respectively (both p < 0.05).

Conclusions
Higher myocardial infarction admission TBIL might independently predict poor prognosis in patients with NSTEMI.
Association of serum creatinine with aortic arch calcification in middle-aged and elderly adults: an observational cross-sectional study from China
Authors: Zhang Feifei , Hao Nannan , Wang Lei , Sun Guoming , Feng Xiaoke , Li Chunjian , Tan Wenfeng , Wang Fang 
Published: April 2022

Abstract
Background and aims
Vascular calcification (VC) is a strong predictor of cardiovascular events and all-cause mortality in cardiovascular diseases (CVD). Renal dysfunction is closely related to VC. Serum creatinine, as an important indicator of renal function in chronic kidney disease (CKD), is closely associated with increased VC. Here, to explore the potential role of serum creatinine in CVD, we examined the association between serum creatinine level and aortic arch calcification (AAC) presence in a larger general population.

Methods
A total of 9067 participants aged > 45 years were included in this study. All participants underwent postero-anterior chest X-ray examination to diagnose AAC. According to the distribution characteristics, serum creatinine levels in male and female were divided into tertiles respectively. Univariate and multivariate logistic regression analysis were used to analyze the association between aortic calcification and serum creatinine.

Results
Participants included 3776 men and 5291 women, and 611 and 990 AAC were detected, respectively. Serum creatinine level in the female AAC group was significantly higher than that in the non-AAC group (p < 0.001), while there was no significant difference in male serum creatinine between the two groups (p = 0.241). After logistic regression analysis excluded confounding factors, with the first tertile of serum creatinine as the reference, multivariable-adjusted ORs and 95% CIs of the second and the highest tertile of female and male were 1.045 (0.856–1.276), 1.263 (1.036–1.539); 0.953 (0.761–1.193), 0.948 (0.741–1.198), respectively.

Conclusion
Elevated serum creatinine levels are independently associated with higher AAC incidence in female aged > 45 years old. Measuring serum creatinine levels may assist the early screening individuals at high risk of developing CVD. And higher attention should be given to female's serum creatinine levels in daily clinical practice.
Clinical factors associated with recent medical care visits in nursing homes: a multi-site cross-sectional study
Authors: Correia Rebecca H. , Mowbray Fabrice I. , Dash Darly , Katz Paul R. , Moser Andrea , Strum Ryan P. , Jones Aaron , von Schlegell Ahmad , Costa Andrew P. 
Published: April 2022

Abstract
Objectives
We examined which resident-level clinical factors influence the provision of a recent medical care visit in nursing homes (NHs).

Design
Multi-site cross-sectional.

Setting and participants
We extracted data on 3,556 NH residents from 18 NH facilities in Ontario, Canada, who received at minimum, an admission and first-quarterly assessment with the Resident Assessment Instrument Minimum Data Set (MDS) 2.0 between November 1, 2009, and October 31, 2017.

Methods
We conducted a secondary analysis of routinely collected MDS 2.0 data. The provision of a recent medical care visit by a physician (or authorized clinician) was assessed in the 14-day period preceding a resident’s first-quarterly MDS 2.0 assessment. We utilized best-subset multivariable logistic regression to model the adjusted associations between resident-level clinical factors and a recent medical care visit.

Results
Two thousand eight hundred fifty nine (80.4%) NH residents had one or more medical care visits prior to their first-quarterly MDS 2.0 assessment. Six clinically relevant factors were identified to be associated with recent medical care visits in the final model: exhibiting wandering behaviours (OR = 1.34, 95% CI 1.09 – 1.63), presence of a pressure ulcer (OR = 1.37, 95% CI 1.05 – 1.78), a urinary tract infection (UTI) (OR = 1.52, 95% CI 1.06 – 2.18), end-stage disease (OR = 9.70, 95% CI 1.32 – 71.02), new medication use (OR = 1.31, 95% CI 1.09 – 1.57), and analgesic use (OR = 1.24, 95% CI 1.03 – 1.49).

Conclusions and implications
Our findings suggest that resident-level clinical factors drive the provision of medical care visits following NH admission. Clinical factors associated with medical care visits align with the minimum competencies expected of physicians in NH practice, including managing safety risks, infections, medications, and death. Ensuring that NH physicians have opportunities to acquire and strengthen these competencies may be transformative to meet the ongoing needs of NH residents.
A novel technique using ultrasonography in upper airway management after anterior cervical decompression and fusion
Authors: Murata Shizumasa , Iwasaki Hiroshi , Oka Hiroyuki , Hashizume Hiroshi , Yukawa Yasutsugu , Minamide Akihito , Tsutsui Shunji , Takami Masanari , Nagata Keiji , Taiji Ryo , Kozaki Takuhei , Yamada Hiroshi 
Published: April 2022

Abstract
Background
Airway complications are the most serious complications after anterior cervical decompression and fusion (ACDF) and can have devastating consequences if their detection and intervention are delayed. Plain radiography is useful for predicting the risk of dyspnea by permitting the comparison of the prevertebral soft tissue (PST) thickness before and after surgery. However, it entails frequent radiation exposure and is inconvenient. Therefore, we aimed to overcome these problems by using ultrasonography to evaluate the PST and upper airway after ACDF and investigate the compatibility between X-ray and ultrasonography for PST evaluation.

Methods
We included 11 radiculopathy/myelopathy patients who underwent ACDF involving C5/6, C6/7, or both segments. The condition of the PST and upper airway was evaluated over 14 days. The Bland–Altman method was used to evaluate the degree of agreement between the PST values obtained using radiography versus ultrasonography. The Pearson correlation coefficient was used to determine the relationship between the PST measurement methods. Single-level and double-level ACDF were performed in 8 and 3 cases, respectively.

Results
PST and upper airway thickness peaked on postoperative day 3, with no airway complications. The Bland–Altman bias was within the prespecified clinically nonsignificant range: 0.13 ± 0.36 mm (95% confidence interval 0.04–0.22 mm). Ultrasonography effectively captured post-ACDF changes in the PST and upper airway thickness and detected airway edema.

Conclusions
Ultrasonography can help in the continuous assessment of the PST and the upper airway as it is simple and has no risk of radiation exposure risk. Therefore, ultrasonography is more clinically useful to evaluate the PST than radiography from the viewpoint of invasiveness and convenience.
Serum-based measurements of stromal activation through ADAM12 associate with poor prognosis in colorectal cancer
Authors: ten Hoorn Sanne , Waasdorp Cynthia , van Oijen Martijn G. H. , Damhofer Helene , Trinh Anne , Zhao Lan , Smits Lisanne J. H. , Bootsma Sanne , van Pelt Gabi W. , Mesker Wilma E. , Mol Linda , Goey Kaitlyn K. H. , Koopman Miriam , Medema Jan Paul , Tuynman Jurriaan B. , Zlobec Inti , Punt Cornelis J. A. , Vermeulen Louis , Bijlsma Maarten F. 
Published: April 2022

Abstract
Background
Recently it has been recognized that stromal markers could be used as a clinically relevant biomarker for therapy response and prognosis. Here, we report on a serum marker for stromal activation, A Disintegrin and Metalloprotease 12 (ADAM12) in colorectal cancer (CRC).

Methods
Using gene expression databases we investigated ADAM12 expression in CRC and delineated the source of ADAM12 expression. The clinical value of ADAM12 was retrospectively assessed in the CAIRO2 trial in metastatic CRC with 235 patients (31% of total cohort), and an independent rectal cancer cohort (n = 20).

Results
ADAM12 is expressed by activated CRC associated fibroblasts. In the CAIRO2 trial cohort, ADAM12 serum levels were prognostic (ADAM12 low versus ADAM12 high; median OS 25.3 vs. 17.1 months, HR 1.48 [95% CI 1.11–1.96], P = 0.007). The prognostic potential was specifically high for metastatic rectal cancer (HR 1.78 [95% CI 1.06–3.00], P = 0.030) and mesenchymal subtype tumors (HR 2.12 [95% CI 1.25–3.60], P = 0.004). ADAM12 also showed potential for predicting recurrence in an exploratory analysis of non-metastatic rectal cancers.

Conclusions
Here we describe a non-invasive marker for activated stroma in CRC which associates with poor outcome, especially for primary cancers located in the rectum.
Genetic and RNA-related molecular markers of trastuzumab-chemotherapy-associated cardiotoxicity in HER2 positive breast cancer: a systematic review
Authors: Lunardi Mattia , Al-Habbaa Ahmed , Abdelshafy Mahmoud , Davey Matthew G. , Elkoumy Ahmed , Ganly Sandra , Elzomor Hesham , Cawley Christian , Sharif Faisal , Crowley James , Kerin Michael , Wijns William , Lowery Aoife , Soliman Osama 
Published: April 2022

AbstractCancer-therapy related cardiotoxicity (CTRCT) is a significant and frequent complication of monoclonal antibody directed therapy, especially Trastuzumab, for human epidermal growth factor receptor 2 (HER2) overexpressing breast cancers. Reliable, clinically available molecular predictive markers of CTRCT have not yet been developed. Identifying specific genetic variants and their molecular markers, which make the host susceptible to this complication is key to personalised risk stratification. A systematic review was conducted until April 2021, using the Medline, Embase databases and Google Scholar, to identify studies genetic and RNA-related markers associated with CTRCT in HER2 positive breast cancer patients. So far, researchers have mainly focused on HER2 related polymorphisms, revealing codons 655 and 1170 variants as the most likely SNPs associated with cardiotoxicity, despite some contradictory results. More recently, new potential genetic markers unrelated to the HER2 gene, and linked to known cardiomyopathy genes or to genes regulating cardiomyocytes apoptosis and metabolism, have been detected. Moreover, microRNAs are gaining increasing recognition as additional potential molecular markers in the cardio-oncology field, supported by encouraging preliminary data about their relationship with cardiotoxicity in breast cancers. In this review, we sought to synthesize evidence for genetic variants and RNA-related molecular markers associated with cardiotoxicity in HER2-positive breast cancer.
Risk factors for cut-outs in geriatric intertrochanteric fractures with cephalomedullary nailing after obtaining acceptable reduction: a case–control study
Authors: Huang Jian-wen , Gao Xiao-sheng , Yang Yun-fa 
Published: April 2022

Abstract
Background
It is irresponsible if we disregard reduction quality to talk about cut-outs in intertrochanteric fractures (ITF) with internal fixation. The aim of this study is to analyze the risk-factors for cut-outs in geriatric ITF with cephalomedullary nailing after obtaining acceptable reduction.

Methods
In order to investigate the risk-factors for cut-outs in geriatric ITF after obtaining acceptable reduction, we retrospectively reviewed 367 patients who underwent cephalomedullary nail for ITF in our department between September 2016 and December 2021. Potential variables including demographic data and radiological parameters (namely the fracture type, Singh index, lateral wall fracture, cephalic nail position, Parker’s ratio index, tip-apex-distance (TAD), and calcar-referenced TAD (CalTAD)) were collected. Logistic regression analysis was performed to identify the significant risk factors for cut-outs.

Results
One hundred twenty-one patients were suitable for this study. Of the 121 cases, nine cases (7.4%) were observed with cut-out or pending cut-out. We found that Age (adjusted odds ratio (OR) 1.158, 95% confidence interval (CI) 1.016 to 1.318, p = 0.028), lateral wall fracture (adjusted OR 11.07, 95%CI 1.790 to 68.380, p = 0.01), and CalTAD (adjusted OR 1.277, 95%CI 1.005 to 1.622, p = 0.045) were independent risk-factors for cut-outs.

Conclusions
Age, lateral wall fracture and CalTAD are independent risk-factors for cut-outs in geriatric ITF with cephalomedullary nailing after obtaining acceptable reduction. In order to avoid cut-outs, an optimal CalTAD is necessary even obtaining acceptable reduction, especially in the over-aged patients with lateral wall fracture.