bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and utilization of copy number information for correcting Hi-C contact map of cancer cell lines
Authors: Khalil Ahmed Ibrahim Samir , Muzaki Siti Rawaidah Binte Mohammad , Chattopadhyay Anupam , Sanyal Amartya 
Published: November 2020

AbstractBackgroundHi-C and its variant techniques have been developed to capture the spatial organization of chromatin. Normalization of Hi-C contact map is essential for accurate modeling and interpretation of high-throughput chromatin conformation capture (3C) experiments. Hi-C correction tools were originally developed to normalize systematic biases of karyotypically normal cell lines. However, a vast majority of available Hi-C datasets are derived from cancer cell lines that carry multi-level DNA copy number variations (CNVs). CNV regions display over- or under-representation of interaction frequencies compared to CN-neutral regions. Therefore, it is necessary to remove CNV-driven bias from chromatin interaction data of cancer cell lines to generate a euploid-equivalent contact map.ResultsWe developed the HiCNAtra framework to compute high-resolution CNV profiles from Hi-C or 3C-seq data of cancer cell lines and to correct chromatin contact maps from systematic biases including CNV-associated bias. First, we introduce a novel ‘entire-fragment’ counting method for better estimation of the read depth (RD) signal from Hi-C reads that recapitulates the whole-genome sequencing (WGS)-derived coverage signal. Second, HiCNAtra employs a multimodal-based hierarchical CNV calling approach, which outperformed OneD and HiNT tools, to accurately identify CNVs of cancer cell lines. Third, incorporating CNV information with other systematic biases, HiCNAtra simultaneously estimates the contribution of each bias and explicitly corrects the interaction matrix using Poisson regression. HiCNAtra normalization abolishes CNV-induced artifacts from the contact map generating a heatmap with homogeneous signal. When benchmarked against OneD, CAIC, and ICE methods using MCF7 cancer cell line, HiCNAtra-corrected heatmap achieves the least 1D signal variation without deforming the inherent chromatin interaction signal. Additionally, HiCNAtra-corrected contact frequencies have minimum correlations with each of the systematic bias sources compared to OneD’s explicit method. Visual inspection of CNV profiles and contact maps of cancer cell lines reveals that HiCNAtra is the most robust Hi-C correction tool for ameliorating CNV-induced bias.ConclusionsHiCNAtra is a Hi-C-based computational tool that provides an analytical and visualization framework for DNA copy number profiling and chromatin contact map correction of karyotypically abnormal cell lines. HiCNAtra is an open-source software implemented in MATLAB and is available athttps://github.com/AISKhalil/HiCNAtra.
Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation
Authors: Gottwald Dorian , Putz Florian , Hohmann Nora , Büttner-Herold Maike , Hecht Markus , Fietkau Rainer , Distel Luitpold 
Published: November 2020

Abstract

Background
Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally.

Results
Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival.

Conclusion
Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.
Avian phenotypic convergence is subject to low genetic constraints based on genomic evidence
Authors: Chen Yu-Chi , Kuo Hao-Chih , Lo Wen-Sui , Hung Chih-Ming 
Published: November 2020

AbstractBackgroundPhenotypic convergence between distinct species provides an opportunity to examine the predictability of genetic evolution. Unrelated species sharing genetic underpinnings for phenotypic convergence suggests strong genetic constraints, and thus high predictability of evolution. However, there is no clear big picture of the genomic constraints on convergent evolution. Genome-based phylogenies have confirmed many cases of phenotypic convergence in birds, making them a good system for examining genetic constraints in phenotypic convergence. In this study, we used hierarchical genomic approaches to estimate genetic constraints in three convergent avian traits: nocturnality, raptorial behavior and foot-propelled diving.ResultsPhylogeny-based hypothesis tests and positive selection tests were applied to compare 16 avian genomes, representing 14 orders, and identify genes with strong convergence signals. We found 43 adaptively convergent genes (ACGs) associated with the three phenotypic convergence cases and assessed genetic constraints in all three cases, from (amino acid) site mutations to genetic pathways. We found that the avian orders shared few site mutations in the ACGs that contributed to the convergent phenotypes, and that these ACGs were not enriched in any genetic pathways. In addition, different pairs of orders with convergent foot-propelled diving or raptorial behaviors shared few ACGs. We also found that closely related orders that shared foot-propelled diving behavior did not share more ACGs than did distinct orders, suggesting that convergence among these orders could not be explained by their initial genomic backgrounds.ConclusionsOur analyses of three avian convergence events suggest low constraints for phenotypic convergence across multiple genetic levels, implying that genetic evolution is unpredictable at the phylogenetic level of avian order. Ours is one of first studies to apply hierarchical genomic examination to multiple avian convergent cases to assess the genetic constraints in life history trait evolution.
Effect of acute noise trauma on the gene expression profile of the hippocampus
Authors: Lee Chang Ho , Kim Kyung Woon , Lee So Min , Kim So Young 
Published: November 2020

AbstractBackgroundThis study aimed to investigate the changes in the expression of hippocampal genes upon acute noise exposure.MethodsThree-week-old Sprague–Dawley rats were assigned to control (n = 15) and noise (n = 15) groups. White noise (2–20 kHz, 115 dB sound pressure level [SPL]) was delivered for 4 h per day for 3 days to the noise group. All rats were sacrificed on the last day of noise exposure, and gene expression in the hippocampus was analyzed using a microarray. Pathway analyses were conducted for genes that showed differential expression ≥ 1.5-fold andP ≤ 0.05 compared to the control group. The genes included in the putative pathways were measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).ResultsThirty-eight upregulated genes and 81 downregulated genes were identified. The pathway analyses revealed that upregulated genes were involved in the cellular responses to external stimuli and immune system pathways. qRT-PCR confirmed the upregulation of the involved genes. The downregulated genes were involved in neuronal systems and synapse-related pathways, and qRT-PCR confirmed the downregulation of the involved genes.ConclusionsAcute noise exposure upregulated the expression of immune-related genes and downregulated the expression of neurotransmission-related genes in the hippocampus.
Social participation needs of older adults living in a rural regional county municipality: toward reducing situations of isolation and vulnerability
Authors: Levasseur Mélanie , Routhier Sonia , Clapperton Irma , Doré Chantal , Gallagher Frances 
Published: November 2020

AbstractBackgroundSocial participation is restricted for approximately half the older adult population but is critical in fostering community vitality, promoting health, and preventing disabilities. Although targeted through interventions by community organizations, healthcare professionals and municipalities, little is known about the needs of older adults to participate socially, especially in rural areas. This study thus aimed to identify and prioritize the social participation needs of older adults living in a rural regional county municipality.MethodsA participatory action research was conducted in a rural regional county municipality (RCM) in Quebec, Canada, with a convenience sample of 139 stakeholders, including older adults, caregivers, healthcare and community organization managers, healthcare and community organization workers, community partners and key informants.ResultsFacilitators and barriers to social participation are related to personal factors (e.g., health, interests, motivation), the social environment (e.g., availability of assistance or volunteers) and the physical environment (e.g., distance to resources, recreational facilities and social partners). Nine older adults’ needs emerged and were prioritized as follows: 1) having access to and being informed about transportation options, 2) being informed about available activities and services, 3) having access to activities, including volunteering opportunities, suited to their interests, schedule, cost, language and health condition, 4) being accompanied to activities, 5) having access to meeting places near home and adapted to their health condition, and 6–9 (no preferred order) being reached when isolated, being personally invited and welcomed to activities, having a social support network, and being valued and recognized. Differences emerged when prioritizing needs of older adults with disabilities (greater need for assistance, accessibility and adapted activities) and older adults living in a rural area (greater need for transportation).ConclusionsTo promote active participation in the community, the social participation needs of older women and men living in rural areas must be addressed, especially in regard to transportation, information, adapted activities, assistance and accessibility. The first part of this action research will be followed by community selection and implementation of initiatives designed to ultimately foster their social participation.
The prevalence of malnutrition and impact on patient outcomes among older adults presenting at an Irish emergency department: a secondary analysis of the OPTI-MEND trial
Authors: Griffin Anne , O’Neill Aoife , O’Connor Margaret , Ryan Damien , Tierney Audrey , Galvin Rose 
Published: November 2020

AbstractBackgroundMalnutrition is common among older adults and is associated with adverse outcomes but remains undiagnosed on healthcare admissions. Older adults use emergency departments (EDs) more than any other age group. This study aimed to determine the prevalence and factors associated with malnutrition on admission and with adverse outcomes post-admission among older adults attending an Irish ED.MethodsSecondary analysis of data collected from a randomised controlled trial exploring the impact of a dedicated team of health and social care professionals on the care of older adults in the ED. Nutritional status was determined using the Mini Nutritional Assessment- short form. Patient parameters and outcomes included health related quality of life, functional ability, risk of adverse health outcomes, frailty, hospital admissions, falls history and clinical outcomes at index visit, 30-day and 6-month follow up. Aggregate anonymised participant data linked from index visit to 30-days and 6-month follow-up were used for statistical analysis.ResultsAmong 353 older adults (mean age 79.6 years (SD = 7.0); 59.2% (n = 209) female) the prevalence of malnutrition was 7.6% (n = 27) and ‘risk of malnutrition’ was 28% (n = 99). At baseline, those who were malnourished had poorer quality of life scores, functional ability, were more frail, more likely to have been hospitalised or had a fall recently, had longer waiting times and were more likely to be discharged home from the ED than those who had normal nutrition status. At 30-days, those who were malnourished were more likely to have reported another hospital admission, a nursing home admission, reduced quality of life and functional decline than older adults who had normal nutrition status at the baseline ED visit. Differences between the MNA SF and 6-month outcomes were similar but not statistically significant.ConclusionOver one-third of older adults admitted to an Irish ED are either malnourished or at risk of malnourishment. Malnutrition was associated with a longer stay in the ED, functional decline, poorer quality of life, increased risk of hospital admissions and a greater likelihood of admission to a nursing home at 30 days.Trial registrationProtocol registered in ClinicalTrials.gov, ID:NCT03739515, first posted November 13, 2018.
Inflammatory indexes are not associated with sarcopenia in Chinese community-dwelling older people: a cross-sectional study
Authors: Tang Tianjiao , Xie Lingling , Tan Lingling , Hu Xiaoyi , Yang Ming 
Published: November 2020

Abstract

Background
Inflammatory indexes (platelet-to-lymphocyte ratio [PLR], neutrophil-to-lymphocyte ratio [NLR], and lymphocyte-to-monocyte ratio [LMR]) are recently supposed to be the biomarkers of sarcopenia. We aimed to validate the association between these inflammatory indexes and sarcopenia in Chinese community-dwelling older people.

Methods
We consecutively recruited community-dwelling older adults aged 60 years or older. The neutrophil, lymphocyte, monocyte, and platelet counts, and C-reactive protein (CRP) were tested using standard methods. Sarcopenia was defined according to different criteria: the Asian Working Group for Sarcopenia (AWGS), the updated version of AWGS (AWGS 2019), the European Working Group on Sarcopenia in Older People (EWGSOP), the updated version of EWGSOP (EWGSOP2), the International Working Group on Sarcopenia (IWGS), and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). Multiple logistic regression analysis was performed.

Results
We included 384 participants. A total of 61 participants (15.9%) were diagnosed with sarcopenia according to the AWGS criteria. There was no significant difference in PLR, NLR, LMR, and CRP between the sarcopenia group and the non-sarcopenia group regardless of the diagnostic criteria. No significant association between PLR, NLR, LMR, and AWGS-defined sarcopenia was found (PLR per 1- standard deviation [SD]: adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.82 to 1.45; NLR per 1-SD: adjusted OR 0.96, 95% CI 0.71 to 1.30; LMR per 1-SD: adjusted OR 1.01, 95% CI 0.74 to 1.38). Similar results were found when sarcopenia was defined by different criteria and when PLR, NLR, LMR were treated as categorical variables.

Conclusions
Our study did not support the utility of the inflammatory indexes (NLR, PLR, and LMR) as the biomarkers of sarcopenia in Chinese community-dwelling older people. However, considering the inflammatory indexes can be simply calculated from a routine blood test, further studies in different populations remain warranted.
Impact of daily versus weekly service of infectious diseases consultation on hospital antimicrobial consumption: a retrospective study
Authors: Cona Andrea , Gazzola Lidia , Viganò Ottavia , Bini Teresa , Marchetti Giulia Carla , d’Arminio Monforte Antonella 
Published: November 2020

Abstract

Background
To verify whether a daily service of Infectious Diseases consultation (ID-cons) is more effective than a weekly service in reducing antibiotic (ATB) consumption without worsening of clinical outcomes.

Methods
Two-year observational analysis of the ID-cons provided in a hospital setting in Milan, Italy. ID-cons resulted in: start-of-ATB; no-ATB; confirmation; modification-of-ATB. The impact of a weekly (September 1, 2016 - August 31, 2017 versus a daily (September 1, 2017 – September 30, 2018) service of ID-cons was evaluated in terms of: time-from-admission-to-first-ID-cons, type of ATB-intervention and number-of-ID-cons per 100 bed-days (bd). Primary outcomes: reduction of hospital ATB consumption overall and by department and classes expressed as Defined Daily Dose (DDD)/100bd (by Wilcoxon test for paired data). Secondary outcomes: overall and sepsis-related in-hospital annual mortality rates (as death/patient’s admissions).

Results
Overall 2552 ID-cons in 1111 patients (mean, 2.3 ID-cons per patient) were performed (18.6% weekly vs 81.4% daily). No differences in patient characteristics were observed. In the daily-service, compared to the weekly-service, patients were seen by the ID-consultant earlier (time-from-admission-to-ID-cons: 6 days (IQR 2–13) vs 10 days (IQR 6–19), p < 0.001) and ATB was more often started by the ID-consultant (Start-of-ATB: 11.6% vs 8%, p = 0.02), rather than treating physicians. After switching to daily-service, the number-of-ID-cons increased from 0.4/100bd to 1.5/100bd (p = 0.01), with the greatest increase in the emergency department (1.5/100bd vs 6.7/100bd, p < 0.001). Total ATB consumption decreased from 64 to 60 DDD/100bd. As for the number-of-cons, the consumption of ATB decreased mainly in the emergency area. According to ATB classes, glycopeptides consumption was reduced from 3.1 to 2.1 DDD/100bd (p = 0.02) while carbapenem use decreased from 3.7 to 3.1 DDD/100bd (p = 0.07). No changes in overall mortality (5.2% vs 5.2%) and sepsis-related mortality (19.3% vs 20.9%; p = 0.7) were observed among the two time-period.

Conclusions
Daily-ID-cons resulted in a more comprehensive management of the infected patient by the ID-consultant, especially in the emergency area where we also observed the highest rate of reduction of ATB-usage. No change in mortality was observed.
“Summer hypokalemia” as an initial presentation of cystic fibrosis in a morbidly obese African American adult: case report
Authors: Cao Yangming , Donaldson Rachel , Lee David 
Published: November 2020

AbstractBackgroundMost patients with cystic fibrosis (CF) present with respiratory or digestive symptoms. About 3% of patients have electrolyte disturbances at the time of diagnosis, but most of the described cases presenting with this manifestation have been in children. Only 3 adult patients are identified in the literature who first presented with hypokalemia. We describe a morbidly obese African American adult who presented with severe hypokalemia and metabolic alkalosis, which eventually led to the diagnosis of CF after multiple hospitalizations over 4 consecutive summers. Besides being the first African American adult with this presentation, he had the highest BMI, lowest serum potassium, highest pH, and highest bicarbonate level.Case presentationIn the summer of 2015, a 26 year-old African American man presented to the hospital for generalized weakness. His BMI was 54 kg/M2, and he had been on a special diet for a few months with a weight loss of 50 pounds. He sweated profusely while working as a chef. Laboratory tests showed severe hypokalemia and metabolic alkalosis. Further work-up pointed toward extrarenal losses of potassium. He was treated with intravenous normal saline and potassium chloride. After discharge, his potassium level remained normal through the winter while the potassium was tapered off. However, over the following three summers, he repeatedly presented to hospitals for the same problems. Cystic fibrosis was suspected and confirmed by an abnormal pilocarpine sweat test. Gene test revealed two mutations of cystic fibrosis transmembrane conductance regulator (CFTR). Thereafter, his potassium level remained normal with potassium replacement during summertime. Unexpectedly, however, his BMI rose to 83 kg/M2after he stopped the special diet for weight reduction. The reason for the delayed diagnosis is discussed.ConclusionWe present an exceedingly rare case of CF in a morbidly obese African American adult male whose only manifestation of CF was hypokalemia and metabolic alkalosis. Clinicians should keep an open mind to the diagnosis of CF in ethnically diverse populations, even if it seems unlikely at first glance. For “summer hypokalemia”, consider cystic fibrosis.
A case report of late-onset cerebellar ataxia associated with a rare p.R342W TGM6 (SCA35) mutation
Authors: Manini Arianna , Bocci Tommaso , Migazzi Alice , Monfrini Edoardo , Ronchi Dario , Franco Giulia , De Rosa Anna , Sartucci Ferdinando , Priori Alberto , Corti Stefania , Comi Giacomo Pietro , Bresolin Nereo , Basso Manuela , Di Fonzo Alessio 
Published: November 2020

Abstract

Background
Mutations in TGM6 gene, encoding for transglutaminase 6 (TG6), have been implicated in the pathogenesis of spinocerebellar ataxia type 35 (SCA35), a rare autosomal dominant disease marked by cerebellar degeneration and characterized by postural instability, incoordination of gait, features of cerebellar dysfunction and pyramidal signs.

Case presentation
Here we report the case of an Italian patient with late-onset, slowly progressive cerebellar features, including gait ataxia, scanning speech and ocular dysmetria and pyramidal tract signs. Whole exome sequencing revealed the rare heterozygous c.1024C > T (p.R342W) variant of TGM6, located at a highly evolutionary conserved position and predicted as pathogenic by in silico tools. Expression of TG6-R342W mutant in HEK293T cells led to a significant reduction of transamidase activity compared to wild-type TG6.

Conclusion
This finding extends SCA35 genetic landscape, highlighting the importance of TGM6 screening in undiagnosed late-onset and slowly progressive cerebellar ataxias.
Hypertrophic olivary degeneration concomitant with bilateral middle cerebellar peduncles Wallerian degeneration following unilateral pontine infarction
Authors: Bao Bing , Wu Xiangbin , Xia Zhongbin , Shen Yaoyao 
Published: November 2020

Abstract

Background
Wallerian degeneration (WD) can occur in different projecting systems, such as corticospinal tract, dentate-rubro-olivary pathway, and corticopontocerebellar tract. However, the co-occurrence of hypertrophic olivary degeneration (HOD) and middle cerebellar peduncles (MCPs) degeneration secondary to unilateral pontine infarction in a single patient is extremely rare.

Case presentation
A 71-year-old man presented with acute onset of dizzness, slurred speech, and right-sided weakness. On the next day, his previous neurologic deficits deteriorated. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke of the left pons. After treatment with thrombolysis, antiplatelets, and rehabilitation training, his speaking and motor function improved moderately. At the 3-month follow-up, the MRI showed hyperintensity in the left medulla oblongata and bilateral MCPs on T2-weighted and FLAIR images, suggesting HOD as well as MCPs degeneration.

Conclusions
It is of great importance for us to know the anatomic knowledge of dentate-rubro-olivary and corticopontocerebellar pathways.