bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relative contributions of internal atmospheric variability and surface processes to the interannual variations in wintertime Arctic surface air temperatures
Authors: Wu Fengmin , Li Wenkai , Zhang Peng , Li Wei 
Published: June 2021

AbstractSuperimposed on a warming trend, Arctic winter surface air temperature (SAT) exhibits substantial interannual variability, whose underlying mechanisms are unclear, especially regarding the role of sea-ice variations and atmospheric processes. Here, atmospheric reanalysis data and idealized atmospheric model simulations are used to reveal the mechanisms by which sea-ice variations and atmospheric anomalous conditions affect interannual variations in wintertime Arctic SAT. Results show that near-surface interannual warming in the Arctic is accompanied by comparable warming throughout large parts of the Arctic troposphere and large-scale anomalous atmospheric circulation patterns. Within the Arctic, changes in large-scale atmospheric circulations due to internal atmospheric variability explain a substantial fraction of interannual variation in SAT and tropospheric temperatures, which lead to an increase in moisture and downward longwave radiation, with the rest likely coming from sea ice-related and other surface processes. Arctic winter sea-ice loss allows the ocean to release more heat and moisture, which enhances Arctic warming; however, this effect on SAT is confined to the ice-retreat area and has a limited influence on large-scale atmospheric circulations.
Development and external validation of a novel nomogram for screening Chinese Lynch syndrome: based on a multicenter, population study
Authors: Yang Mengyuan , Li Dan , Jiang Wu , Zhu Lizhen , Ju Haixing , Sun Yan , Shan Yuqiang , Yang Chunkang , Dong Jian , Wang Lin , Wu Baoping , Qiu Meng , Yin Xianli , Wang Xicheng , Xiong Bin , Yan Wei , Liu Tao , Liu Chenglin , Mao Xinru , Ding Kefeng , Zhang Suzhan , Zheng Shu , Xu Dong , Ding Peirong , Yuan Ying 
Published: June 2021

Background: This multicenter study aimed to reveal the genetic spectrum of colorectal cancer (CRC) with deficient mismatch repair (dMMR) and build a screening model for Lynch syndrome (LS). Methods: Through the immunohistochemical (IHC) screening of mismatch repair protein results in postoperative CRC patients, 311 dMMR cases, whose germline and somatic variants were detected using the ColonCore panel, were collected. Univariate and multivariate logistic regression analysis was performed on the clinical characteristics of these dMMR individuals, and a clinical nomogram, incorporating statistically significant factors identified using multivariate logistic regression analysis, was constructed to predict the probability of LS. The model was validated externally by an independent cohort. Results: In total, 311 CRC patients with IHC dMMR included 95 identified MMR germline variant (LS) cases and 216 cases without pathogenic or likely pathogenic variants in MMR genes (non-Lynch-associated dMMR). Of the 95 individuals, approximately 51.6%, 28.4%, 14.7%, and 5.3% cases carried germline MLH1, MSH2, MSH6, and PMS2 pathogenic or likely pathogenic variants, respectively. A novel nomogram was then built to predict the probability of LS for CRC patients with dMMR intuitively. The receiver operating characteristic (ROC) curve informed that this nomogram-based screening model could identify LS with a higher specificity and sensitivity with an area under curve (AUC) of 0.87 than current screening criteria based on family history. In the external validation cohort, the AUC of the ROC curve reached 0.804, inferring the screening model’s universal applicability. We recommend that dMMR-CRC patients with a probability of LS greater than 0.435 should receive a further germline sequencing. Conclusion: This novel screening model based on the clinical characteristic differences between LS and non-Lynch-associated dMMR may assist clinicians to preliminarily screen LS and refer susceptible patients to experienced specialists.
A genetic interaction of NRXN2 with GABRE, SYT1 and CASK in migraine patients: a case-control study
Authors: Alves-Ferreira Miguel , Quintas Marlene , Sequeiros Jorge , Sousa Alda , Pereira-Monteiro José , Alonso Isabel , Neto João Luís , Lemos Carolina 
Published: June 2021

Abstract
Background
Migraine is a multifactorial disorder that is more frequent (two to four times) in women than in men. In recent years, our research group has focused on the role of neurotransmitter release and its regulation. Neurexin (NRXN2) is one of the components of the synaptic vesicle machinery, responsible for connecting intracellular fusion proteins and synaptic vesicles.
Our aim was to continue exploring the role and interaction of proteins involved in the control and promotion of neurotransmission in migraine susceptibility.

Methods
A case-control study was performed comprising 183 migraineurs (148 females and 35 males) and 265 migraine-free controls (202 females and 63 males). Tagging single nucleotide polymorphisms of NRXN2 were genotyped to assess the association between NRXN2 and migraine susceptibility. The χ2 test was used to compare allele frequencies in cases and controls and odds ratios were estimated with 95% confidence intervals. Haplotype frequencies were compared between groups. Gene-gene interactions were analysed using the Multifactor Dimensionality Reduction v2.0.

Results
We found a statistically significant interaction model (p = 0.009) in the female group between the genotypes CG of rs477138 (NRXN2) and CT of rs1158605 (GABRE). This interaction was validated by logistic regression, showing a significant risk effect [OR = 4.78 (95%CI: 1.76–12.97)] after a Bonferroni correction. Our data also supports a statistically significant interaction model (p = 0.011) in the female group between the GG of rs477138 in NRXN2 and, the rs2244325's GG genotype and rs2998250’s CC genotype of CASK. This interaction was also validated by logistic regression, with a protective effect [OR = 0.08 (95%CI: 0.01–0.75)]. A weak interaction model was found between NRXN2-SYT1. We have not found any statistically significant allelic or haplotypic associations between NRXN2 and migraine susceptibility.

Conclusions
This study unravels, for the first time, the gene-gene interactions between NRXN2, GABRE - a GABAA-receptor - and CASK, importantly it shows the synergetic effect between those genes and its relation with migraine susceptibility.
These gene interactions, which may be a part of a larger network, can potentially help us in better understanding migraine aetiology and in development of new therapeutic approaches.
Do standards of care and early outcomes of periprosthetic fractures change during the COVID-19 pandemic? A multicentre study
Authors: Zagra Luigi , D’Apolito Rocco , Guindani Nicola , Zatti Giovanni , Rivera Fabrizio , Ravasi Flavio , Mosconi Mario , Momoli Alberto , Massè Alessandro , Franceschini Massimo , D’Angelo Fabio , Dallari Dante , Catani Fabio , Casiraghi Alessandro , Bove Federico , Castelli Claudio Carlo 
Published: June 2021

Abstract
Background
Periprosthetic fractures (PPFs) are a growing matter for orthopaedic surgeons, and patients with PPFs may represent a frail target in the case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The purpose of this study is to investigate whether hospital reorganisations during the most severe phase of the SARS-CoV-2 pandemic affected standards of care and early outcomes of patients treated for PPFs in Northern Italy.

Materials and methods
Data were retrieved from a multicentre retrospective orthopaedics and traumatology database, including 14 hospitals. The following parameters were studied: demographics, results of nasopharyngeal swabs, prevalence of coronavirus disease 2019 (COVID-19), comorbidities, general health status (EQ-5D-5L Score), frailty (Clinical Frailty Scale, CFS), pain (visual analogue scale, VAS), anaesthesiologic risk (American Society of Anaesthesiology Score, ASA Score), classification (unified classification system, UCS), type of operation and anaesthesia, in-hospital and early complications (Clavien–Dindo Classification, CDC), and length of stay (LOS). Data were analysed by means of descriptive statistics. Out of 1390 patients treated for any reason, 38 PPFs were included.

Results
Median age was 81 years (range 70–96 years). Twenty-three patients (60.5%) were swabbed on admission, and two of them (5.3%) tested positive; in three patients (7.9%), the diagnosis of COVID-19 was established on a clinical and radiological basis. Two more patients tested positive post-operatively, and one of them died due to COVID-19. Thirty-three patients (86.8%) presented a proximal femoral PPF. Median ASA Score was 3 (range, 1–4), median VAS score on admission was 3 (range, 0–6), median CFS was 4 (range, 1–8), median EQ-5D-5L Score was 3 in each one of the categories (range, 1–5). Twenty-three patients (60.5%) developed post-operative complications, and median CDC grade was 3 (range, 1–5). The median LOS was 12.8 days (range 2–36 days), and 21 patients (55.3%) were discharged home.

Conclusions
The incidence of PPFs did not seem to change during the lockdown. Patients were mainly elderly with comorbidities, and complications were frequently recorded post-operatively. Despite the difficult period for the healthcare system, hospitals were able to provide effective conventional surgical treatments for PPFs, which were not negatively influenced by the reorganisation. Continued efforts are required to optimise the treatment of these frail patients in the period of the pandemic, minimising the risk of contamination, and to limit the incidence of PPFs in the future.

Level of evidence
IV.
Increased peak detection accuracy in over-dispersed ChIP-seq data with supervised segmentation models
Authors: Liehrmann Arnaud , Rigaill Guillem , Hocking Toby Dylan 
Published: June 2021

AbstractBackgroundHistone modification constitutes a basic mechanism for the genetic regulation of gene expression. In early 2000s, a powerful technique has emerged that couples chromatin immunoprecipitation with high-throughput sequencing (ChIP-seq). This technique provides a direct survey of the DNA regions associated to these modifications. In order to realize the full potential of this technique, increasingly sophisticated statistical algorithms have been developed or adapted to analyze the massive amount of data it generates. Many of these algorithms were built around natural assumptions such as the Poisson distribution to model the noise in the count data. In this work we start from these natural assumptions and show that it is possible to improve upon them.ResultsOur comparisons on seven reference datasets of histone modifications (H3K36me3 & H3K4me3) suggest that natural assumptions are not always realistic under application conditions. We show that the unconstrained multiple changepoint detection model with alternative noise assumptions and supervised learning of the penalty parameter reduces the over-dispersion exhibited by count data. These models, implemented in the R packageCROCS(https://github.com/aLiehrmann/CROCS), detect the peaks more accurately than algorithms which rely on natural assumptions.ConclusionThe segmentation models we propose can benefit researchers in the field of epigenetics by providing new high-quality peak prediction tracks for H3K36me3 and H3K4me3 histone modifications.
Vocal cord granuloma after transoral thyroidectomy using oral endotracheal intubation: two case reports
Authors: Liang Tsung-Jung , Wang Nai-Yu , Liu Shiuh-Inn , Chen I-Shu 
Published: June 2021

Abstract
Background
Transoral thyroidectomy can be performed using nasal or oral intubation. Recently, we encountered two cases of vocal cord granuloma that were suspected to result from intraoperative compression by the oral endotracheal tube.

Cases presentation
Two women underwent transoral endoscopic thyroidectomy with oral endotracheal tubes fixed at the mouth angle. Their initial postoperative recovery was uneventful, but they developed hoarseness 2 months after the surgery. Subsequent strobolaryngoscopy revealed vocal cord granulomas at the side of contact of the endotracheal tube. One patient received medication and voice therapy, and her granuloma shrank significantly one month later. The other patient underwent granuloma resection. Thereafter, the symptoms improved in both the patients.

Conclusions
Oral intubation with tube placement at the mouth angle might result in the formation of vocal cord granulomas. Therefore, we suggest positioning the tube at the midline to avoid excessive irritation on one side of the vocal cord.
Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study
Authors: Schellhorn Till , Zucknick Manuela , Askim Torunn , Munthe-Kaas Ragnhild , Ihle-Hansen Hege , Seljeseth Yngve M. , Knapskog Anne-Brita , Næss Halvor , Ellekjær Hanne , Thingstad Pernille , Wyller Torgeir Bruun , Saltvedt Ingvild , Beyer Mona K. 
Published: June 2021

AbstractBackgroundChronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences.MethodsThis prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex.ResultsPatients’ (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5,p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1,p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2;p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9;p = 0.3).ConclusionsPre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI.Trial registrationNCT02650531, date of registration: 08.01.2016.
Three transmission events of Vibrio cholerae O1 into Lusaka, Zambia
Authors: Mwaba John , Debes Amanda K. , Murt Kelsey N. , Shea Patrick , Simuyandi Michelo , Laban Natasha , Kazimbaya Katayi , Chisenga Caroline , Li Shan , Almeida Mathieu , Meisel Jacquelyn S. , Shibemba Aaron , Kantenga Timothy , Mukonka Victor , Kwenda Geoffrey , Sack David A. , Chilengi Roma , Stine O. Colin 
Published: June 2021

Abstract
Background
Cholera has been present and recurring in Zambia since 1977. However, there is a paucity of data on genetic relatedness and diversity of the Vibrio cholerae isolates responsible for these outbreaks. Understanding whether the outbreaks are seeded from existing local isolates or if the outbreaks represent separate transmission events can inform public health decisions.

Results
Seventy-two V. cholerae isolates from outbreaks in 2009/2010, 2016, and 2017/2018 in Zambia were characterized using multilocus variable number tandem repeat analysis (MLVA) and whole genome sequencing (WGS). The isolates had eight distinct MLVA genotypes that clustered into three MLVA clonal complexes (CCs). Each CC contained isolates from only one outbreak. The results from WGS revealed both clustered and dispersed single nucleotide variants. The genetic relatedness of isolates based on WGS was consistent with the MLVA, each CC was a distinct genetic lineage and had nearest neighbors from other East African countries. In Lusaka, isolates from the same outbreak were more closely related to themselves and isolates from other countries than to isolates from other outbreaks in other years.

Conclusions
Our observations are consistent with i) the presence of random mutation and alternative mechanisms of nucleotide variation, and ii) three separate transmission events of V. cholerae into Lusaka, Zambia. We suggest that locally, case-area targeted invention strategies and regionally, well-coordinated plans be in place to effectively control future cholera outbreaks.
Diagnostic tools for neurosyphilis: a systematic review
Authors: Boog Gustavo Henrique Pereira , Lopes João Vitor Ziroldo , Mahler João Vitor , Solti Marina , Kawahara Lucas Tokio , Teng Andre Kakinoki , Munhoz João Victor Taba , Levin Anna S. 
Published: June 2021

Abstract
Purpose
Increasing incidences of syphilis highlight the preoccupation with the occurrence of neurosyphilis. This study aimed to understand the current diagnostic tools and their performance to detect neurosyphilis, including new technologies and the variety of existing methods.

Methods
We searched databases to select articles that reported neurosyphilis diagnostic methods and assessed their accuracy, presenting sensitivity and specificity values. Information was synthesized in tables. The risk of bias was examined using the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy recommendations.

Results
Fourteen studies were included. The main finding was a remarkable diversity of tests, which had varied purposes, techniques, and evaluation methodologies. There was no uniform criterion or gold standard to define neurosyphilis. The current basis for its diagnosis is clinical suspicion and cerebrospinal fluid analysis. There are new promising tests such as PCR tests and chemokine measurement assays.

Conclusions
The diagnosis of neurosyphilis is still a challenge, despite the variety of existing and developing tests. We believe that the multiplicity of reference standards adopted as criteria for diagnosis reveals the imprecision of the current definitions of neurosyphilis. An important next step for the scientific community is to create a universally accepted diagnostic definition for this disease.
Identification of novel hub genes associated with gastric cancer using integrated bioinformatics analysis
Authors: Lu Xiao-Qing , Zhang Jia-Qian , Zhang Sheng-Xiao , Qiao Jun , Qiu Meng-Ting , Liu Xiang-Rong , Chen Xiao-Xia , Gao Chong , Zhang Huan-Hu 
Published: June 2021

Abstract
Background
Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy.

Methods
Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytohubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs.

Results
Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients.

Conclusions
We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.
Surgical and functional outcomes and survival following Colon Cancer surgery in the aged: a study protocol for a prospective, observational multicentre study
Authors: Niemeläinen Susanna , Huhtala Heini , Ehrlich Anu , Kössi Jyrki , Jämsen Esa , Hyöty Marja 
Published: June 2021

Abstract
Background
The number of colorectal cancer patients increases with age. The decision to go through major surgery can be challenging for the aged patient and the surgeon because of the heterogeneity within the older population. Differences in preoperative physical and cognitive status can affect postoperative outcomes and functional recovery, and impact on patients’ quality of life.

Methods / design
A prospective, observational, multicentre study including nine hospitals to analyse the impact of colon cancer surgery on functional ability, short-term outcomes (complications and mortality), and their predictors in patients aged ≥80 years. The catchment area of the study hospitals is 3.88 million people, representing 70% of the population of Finland. The data will be gathered from patient baseline characteristics, surgical interventional data, and pre- and postoperative patient-questionnaires, to an electronic database (REDCap) especially dedicated to the study.

Discussion
This multicentre study provides information about colon cancer surgery’s operative and functional outcomes on older patients. A further aim is to find prognostic factors which could help to predict adverse outcomes of surgery.

Trial registration
ClinicalTrials.gov (NCT03904121). Registered on 1 April 2019.
Parental risk factors for congenital diaphragmatic hernia – a large German case-control study
Authors: Schulz Felicitas , Jenetzky Ekkehart , Zwink Nadine , Bendixen Charlotte , Kipfmueller Florian , Rafat Neysan , Heydweiller Andreas , Wessel Lucas , Reutter Heiko , Mueller Andreas , Schaible Thomas 
Published: June 2021

Abstract
Background
Evidence for periconceptional or prenatal environmental risk factors for the development of congenital diaphragmatic hernia (CDH) is still scarce. Here, in a case-control study we investigated potential environmental risk factors in 199 CDH patients compared to 597 healthy control newborns.

Methods
The following data was collected: time of conception and birth, maternal BMI, parental risk factors such as smoking, alcohol or drug intake, use of hairspray, contact to animals and parental chronic diseases. CDH patients were born between 2001 and 2019, all healthy control newborns were born in 2011. Patients and control newborns were matched in the ratio of three to one.

Results
Presence of CDH was significantly associated with maternal periconceptional alcohol intake (odds ratio = 1.639, 95% confidence interval 1.101–2.440, p = 0.015) and maternal periconceptional use of hairspray (odds ratio = 2.072, 95% confidence interval 1.330–3.229, p = 0.001).

Conclusion
Our study suggests an association between CDH and periconceptional maternal alcohol intake and periconceptional maternal use of hairspray. Besides the identification of novel and confirmation of previously described parental risk factors, our study underlines the multifactorial background of isolated CDH.