bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iam hiQ—a novel pair of accuracy indices for imputed genotypes
Authors: Rosenberger Albert , Tozzi Viola , Bickeböller Heike ,   the INTEGRAL-ILCCO consortium, Hung Rayjean J. , Christiani David C. , Caporaso Neil E. , Liu Geoffrey , Bojesen Stig E. , Le Marchand Loic , Albanes Demetrios , Aldrich Melinda C. , Tardon Adonina , Fernández-Tardón Guillermo , Rennert Gad , Field John K. , Davies Mike , Liloglou Triantafillos , Kiemeney Lambertus A. , Lazarus Philip , Haugen Aage , Zienolddiny Shanbeh , Lam Stephen , Schabath Matthew B. , Andrew Angeline S. , Duell Eric J. , Arnold Susanne M. , Brunnström Hans , Melander Olle , Goodman Gary E. , Chen Chu , Doherty Jennifer A. , Teare Marion Dawn , Cox Angela , Woll Penella J. , Risch Angela , Muley Thomas R. , Johansson Mikael , Brennan Paul , Landi Maria Teresa , Shete Sanjay S. , Amos Christopher I. 
Published: January 2022

Abstract
Background
Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand.

Results
Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2).

Conclusion
We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data.
Epigenetic landscape of drug responses revealed through large-scale ChIP-seq data analyses
Authors: Zou Zhaonan , Iwata Michio , Yamanishi Yoshihiro , Oki Shinya 
Published: January 2022

Abstract
Background
Elucidating the modes of action (MoAs) of drugs and drug candidate compounds is critical for guiding translation from drug discovery to clinical application. Despite the development of several data-driven approaches for predicting chemical–disease associations, the molecular cues that organize the epigenetic landscape of drug responses remain poorly understood.

Results
With the use of a computational method, we attempted to elucidate the epigenetic landscape of drug responses, in terms of transcription factors (TFs), through large-scale ChIP-seq data analyses. In the algorithm, we systematically identified TFs that regulate the expression of chemically induced genes by integrating transcriptome data from chemical induction experiments and almost all publicly available ChIP-seq data (consisting of 13,558 experiments). By relating the resultant chemical–TF associations to a repository of associated proteins for a wide range of diseases, we made a comprehensive prediction of chemical–TF–disease associations, which could then be used to account for drug MoAs. Using this approach, we predicted that: (1) cisplatin promotes the anti-tumor activity of TP53 family members but suppresses the cancer-inducing function of MYCs; (2) inhibition of RELA and E2F1 is pivotal for leflunomide to exhibit antiproliferative activity; and (3) CHD8 mediates valproic acid-induced autism.

Conclusions
Our proposed approach has the potential to elucidate the MoAs for both approved drugs and candidate compounds from an epigenetic perspective, thereby revealing new therapeutic targets, and to guide the discovery of unexpected therapeutic effects, side effects, and novel targets and actions.
Varia: a tool for prediction, analysis and visualisation of variable genes
Authors: Mackenzie Gavin , Jensen Rasmus W. , Lavstsen Thomas , Otto Thomas D. 
Published: January 2022

Abstract
Background
Parasites use polymorphic gene families to evade the immune system or interact with the host. Assessing the diversity and expression of such gene families in pathogens can inform on the repertoire or host interaction phenotypes of clinical relevance. However, obtaining the sequences and quantifying their expression is a challenge. In Plasmodium falciparum, the highly polymorphic var genes encode the major virulence protein, PfEMP1, which bind a range of human receptors through varying combinations of DBL and CIDR domains. Here we present a tool, Varia, to predict near full-length gene sequences and domain compositions of query genes from database genes sharing short sequence tags. Varia generates output through two complementary pipelines. Varia_VIP returns all putative gene sequences and domain compositions of the query gene from any partial sequence provided, thereby enabling experimental validation of specific genes of interest and detailed assessment of their putative domain structure. Varia_GEM accommodates rapid profiling of var gene expression in complex patient samples from DBLα expression sequence tags (EST), by computing a sample overall transcript profile stratified by PfEMP1 domain types.

Results
Varia_VIP was tested querying sequence tags from all DBL domain types using different search criteria. On average 92% of query tags had one or more 99% identical database hits, resulting in the full-length query gene sequence being identified (> 99% identical DNA > 80% of query gene) among the five most prominent database hits, for ~ 33% of the query genes. Optimized Varia_GEM settings allowed correct prediction of > 90% of domains placed among the four most N-terminal domains, including the DBLα domain, and > 70% of C-terminal domains. With this accuracy, N-terminal domains could be predicted for > 80% of queries, whereas prediction rates of C-terminal domains dropped with the distance from the DBLα from 70 to 40%.

Conclusion
Prediction of var sequence and domain composition is possible from short sequence tags. Varia can be used to guide experimental validation of PfEMP1 sequences of interest and conduct high-throughput analysis of var type expression in patient samples.
Longitudinal SARS-CoV-2 seroepidemiological investigation among healthcare workers at a tertiary care hospital in Germany
Authors: Tomczyk Sara , Hönning Alexander , Hermes Julia , Grossegesse Marica , Hofmann Natalie , Michel Janine , Neumann Markus , Nitsche Andreas , Hoppe Berthold , Eckmanns Tim , Schmidt-Traub Hajo , Zappel Kristina 
Published: January 2022

Abstract
Background
SARS-CoV-2 cases in Germany increased in early March 2020. By April 2020, cases among health care workers (HCW) were detected across departments at a tertiary care hospital in Berlin, prompting a longitudinal investigation to assess HCW SARS-CoV-2 serostatus with an improved testing strategy and associated risk factors.

Methods
In May/June and December 2020, HCWs voluntarily provided blood for serology and nasopharyngeal/oropharyngeal (NP/OP) samples for real-time polymerase chain reaction (PCR) and completed a questionnaire. A four-tiered SARS-CoV-2 serological testing strategy including two different enzyme-linked immunosorbent assays (ELISA) and biological neutralization test (NT) was used. ELISA-NT correlation was assessed using Pearson’s correlation coefficient. Sociodemographic and occupational factors associated with seropositivity were assessed with multivariate logistic regression.

Results
In May/June, 18/1477 (1.2%) HCWs were SARS-CoV-2 seropositive, followed by 56/1223 (4.6%) in December. Among those tested in both, all seropositive in May/June remained seropositive by ELISA and positive by NT after 6 months. ELISA ratios correlated well with NT titres in May/June (R = 0.79) but less so in December (R = 0.41). Those seropositive reporting a past SARS-CoV-2 positive PCR result increased from 44.4% in May/June to 85.7% in December. HCWs with higher occupational risk (based on profession and working site), nurses, males, and those self-reporting COVID-19-like symptoms had significantly higher odds of seropositivity.

Conclusions
This investigation provides insight into the burden of HCW infection in this local outbreak context and the antibody dynamics over time with an improved robust testing strategy. It also highlights the continued need for effective infection control measures particularly among HCWs with higher occupational risk.
Replacing vaccine paper package inserts: a multi-country questionnaire study on the acceptability of an electronic replacement in different target groups
Authors: Bamberger Martina , De Loof Hans , Marstboom Charlotte , Oury Stéphanie , Bonanni Paolo , Launay Odile , Kojouharova Mira , Van Damme Pierre 
Published: January 2022

Abstract

Background

In the European Union it is mandatory to include paper package leaflets (PPL) with all medicines, including vaccines, to inform the recipient. However, it is difficult to meet the necessity for localized PPLs in each of the 24 official European languages. Replacing PPLs with electronic versions offers many advantages including redistribution across nations, reduced storage space, accessibility by the visually impaired, easily updated information or the addition of video content. We wanted to assess the attitudes of patients (vaccine recipients or their parents) to the potential of replacing PPL with electronic versions.

Methods
We surveyed vaccinees or their parents in four European countries—Belgium, Italy, Bulgaria and France—for their actual use of vaccine PPLs and their opinions about switching to an electronic package leaflet. Our survey was conducted online because of the COVID-19 pandemic and resulted in 2518 responses to a questionnaire targeted at three specific groups with particular information needs: parents of young children, pregnant women and the elderly (≥ 60 years).

Results
Our main findings are that currently vaccine PPLs are rarely used and frequently unavailable for the vaccinee. Across the four countries surveyed 55–82% of vaccinees would accept an electronic version, as did 64% when there was an option to request a printout of the leaflet.

Conclusions
We found that switching to electronic versions of vaccine PPLs is an acceptable alternative for the public, potentially increasing the quality and amount of information reaching vaccinees while eliminating some barriers to redistribution of vaccines between countries.
Reproductive and hormonal risk factors for sarcoidosis: a nested case–control study
Authors: Dehara Marina , Sachs Michael C. , Kullberg Susanna , Grunewald Johan , Blomberg Anders , Arkema Elizabeth V. 
Published: January 2022

Abstract
Background
Sarcoidosis incidence peaks in females around the fifth decade of life, which coincides with menopause, suggesting hormonal factors play a role in disease development. We investigated whether longer exposure to reproductive and hormonal factors is associated with reduced sarcoidosis risk.

Methods
We conducted a matched case–control study nested within the Mammography Screening Project. Incident sarcoidosis cases were identified via medical records and matched to controls on birth and questionnaire date (1:4). Information on hormonal factors was obtained through questionnaires prior to sarcoidosis diagnosis. Multilevel modelling was used to estimate adjusted odds ratios with 95% credible intervals (OR; 95% CI).

Results
In total, 32 sarcoidosis cases and 124 controls were included. Higher sarcoidosis odds were associated with older age at menarche (OR 1.19: 95% CI 0.92–1.55), natural menopause versus non-natural (OR 1.53: 95% CI 0.80–2.93), later age at first pregnancy (OR 1.11: 95% CI 0.76–1.63) and ever hormone replacement therapy (HRT) use (OR 1.40: 95% CI 0.76–2.59). Lower odds were associated with older age at menopause (OR 0.90: 95% CI 0.52–1.55), longer duration of oral contraceptive use (OR 0.70: 95% CI 0.45–1.07), longer duration of HRT use (OR 0.61: 95% CI 0.22–1.70), ever local estrogen therapy (LET) use (OR 0.83: 95% CI 0.34–2.04) and longer duration of LET use (OR 0.78: 95% CI 0.21–2.81). However, the CIs could not rule out null associations.

Conclusion
Given the inconsistency and modest magnitude in our estimates, and that the 95% credible intervals included one, it still remains unclear whether longer estrogen exposure is associated with reduced sarcoidosis risk.
Identifying palliative care needs of patients with non-communicable diseases in Indonesia using the SPICT tool: a descriptive cross-sectional study
Authors: Effendy Christantie , Silva Jony Francisco Dos Santos , Padmawati Retna Siwi 
Published: January 2022

AbstractBackgroundIn Indonesia, Non-Communicable Diseases (NCD) are a contributing factor to mortality with most cases involving heart disease, cancer, chronic lung disease and diabetes. Accordingly, the identification of palliative care needs is very important as a first step in providing palliative care for these patients with NCD. However, currently there is no national standardized tool nor guidance system for identifying palliative care needs of NCD patients in Indonesia. The Supportive and Palliative Care Indicators Tool (SPICT) has been used worldwide for screening palliative care needs. This study aimed to identify palliative care needs in NCD patients using the SPICT tool.MethodsThis descriptive study used a cross-sectional design. Sampling technique used convenience sampling with a total sample of 124 adult patients with NCD in Dr. Sardjito Hospital Yogyakarta. Data collection used the Indonesian version of the SPICT. Data analyses used descriptive statistics and chi-square tests withp < 0,05 set as significant. Additionally, the prevalence of patients requiring palliative care was also calculated.ResultsThe patients with NCD requiring palliative care who were screened using the SPICT tool were 61.3%. The nurses identified only 17.7%, while the physicians identified only 9.7%. The overall agreement of the clinician’s assessments to the researchers was < 32%. Meanwhile, agreement with nurses was 31 and 25% with the physicians.ConclusionsThese results highlight that by using the SPICT tool, recognition of hospitalized patients with NCD needing palliative care increased from 10 to 18% to > 61%. The Indonesian version of the SPICT tool can help the clinicians to reach meet agreement in identifying hospitalized patients who need palliative care as the first step in addressing palliative interventions for patients with NCD. It can provide several benefits in screening patients with NCD from the beginning of diagnosis.
Remote interpreting in primary care settings: a feasibility trial in Germany
Authors: Fiedler Jonas , Pruskil Susanne , Wiessner Christian , Zimmermann Thomas , Scherer Martin 
Published: January 2022

Abstract
Background
Global migration trends have led to a more diverse population in health care services everywhere, which in turn has set off a paradigm shift away from medical paternalism toward more patient autonomy. Consequently, physicians need to provide a more precise patient-centred healthcare. Professional interpreting appears to play a crucial part in tackling the challenges of language barriers adequately. The aim of this study was to conduct process evaluation through the implementing of video remote interpreting (VR) and telephone remote interpreting (TR) within primary care facilities in the northern German metropolis of Hamburg.

Methods
We conducted a three-armed exploratory pilot trial, which compared VR to TR and to a control group (CG) in different primary care settings. We assessed feasibility of implementation, as well as the acceptance of interpreting tools among their users. In addition, we compared the quality of communication as perceived by patients and physicians, as well as the enabling of patient-centred medicine over all three study groups using quantitative questionnaires.

Results
13 practices (7 GPs, 3 Gynaecologists, 3 Paediatricians) took part in this trial. 183 interpreting calls were documented, 178 physicians as well as 127 patients answered their respective questionnaires. The implementation of the VR- und TR-tools went smoothly and they were broadly accepted by their users. However, the tools were used significantly less often than we had anticipated. With regards to quantitative questionnaires, VR scored significantly better than the control group in terms of the perceived quality of communication by both, patients and physicians and enabled of patient-centred medicine.

Conclusion
Our main findings were the discrepancy between the assumed high demand of professional interpreting solutions on the one hand and the low willingness of practices to participate on the other. The rather low utilisation rates were also noteworthy. This discrepancy indicates a lack of awareness concerning the adverse effects of using informal or no interpreter in medical settings, which needs to be rectified. Due to the small sample size, all statistical results must be viewed with caution. However, our results show that remote interpreting represents a promising approach to tackling language barriers in primary care settings.
Equal access to healthcare in national legislations: how do Croatia, Germany, Poland, and Slovenia counteract discrimination in healthcare?
Authors: Bielińska Katarzyna , Chowaniec Anna , Doričić Robert , Nowak Marianne , Orzechowski Marcin , Ramšak Mojca , Łuków Paweł , Muzur Amir , Zupanič-Slavec Zvonka , Steger Florian 
Published: January 2022

AbstractBackgroundThe aim of the study was a comparative analysis of legislative measures against discrimination in healthcare on the grounds of a) race and ethnicity, b) religion and belief, and c) gender identity and sexual orientation in Croatia, Germany, Poland and Slovenia.MethodsWe conducted a search for documents in national legal databases and reviewed legal commentaries, scientific literature and official reports of equality bodies. We integrated a comparative method with text analysis and the critical interpretive approach. The documents were examined in their original languages: Croatian, German, Polish, and Slovenian.ResultsAll examined states prohibit discrimination and guarantee the right to healthcare on the constitutional level. However, there are significant differences among them on the statutory level, regarding both anti-discriminatory legal measures and other legislation affecting access to healthcare for groups of diverse race or ethnicity, religion or belief, sexual orientation or gender identity. Croatia and Slovenia show the most comprehensive legislation concerning non-discrimination in healthcare in comparison to Germany and even more Poland. Except for Slovenia, explicit provisions protecting equal access for members of the abovementioned groups are insufficiently represented in healthcare legislation.ConclusionsThe study identified legislative barriers to access to healthcare for persons of diverse race or ethnicity, religion or belief, sexual orientation or gender identity in Croatia, Germany, Poland and Slovenia. The discrepancies in the level of implementation of anti-discriminatory measures among these states show that there is a need for comprehensive EU-wide regulations, which would implement the principle of equal treatment in the specific context of healthcare. General anti-discrimination regulations should be strengthened by inclusion of anti-discrimination provisions directly into national legislation relating specifically to the area of healthcare.
Genotyping of Chlamydia abortus using multiple loci variable number of tandem repeats analysis technique
Authors: Barati Sara , Bakhtiari Naghmeh Moori , Shokoohizadeh Leili , Ghorbanpoor Masoud , Momtaz Hassan 
Published: January 2022

AbstractBackgroundThe correlation between various factors (geographical region, clinical incidence, and host type) and the genomic heterogeneity has been shown in several bacterial strains includingChlamydia abortus.MethodsThe aim of this study was to survey the predominant types ofC. abortusstrains isolated from ruminants in Iran by the multiple loci variable number of tandem repeats (VNTR) analysis (MLVA) method.C. abortusinfection was evaluated in a total of 117 aborted fetuses by real-time PCR. The isolation was done via the inoculation of the positive samples in chicken embryo and the L929 cell line. Genotyping was carried out by MLVA typing technique.ResultsForty samples (34.2%) were detected withC. abortusinfection; however, chlamydial infection in ruminants of Charmahal/Bakhtiari (3 bovines and 35 sheep) was higher than that of Khuzestan (2 sheep). All MLVA types (MT1-MT8) were detected in the collected samples from Charmahal/Bakhtiari but only 2 types (MT1 and MT3) were reported in samples from Khuzestan. The main MT type was MT1 (32% of aborted fetuses). Although in this study only 9 cow samples were investigated, they possessed similar clusters to those obtained from sheep (MT1 and MT6).Variation of type in sheep samples (MT1 to MT8) was more than that of bovine samples (MT1, and MT6).ConclusionBy this research revealed thatC.abortuswas responsible for a significant percentage of ruminant abortion in two studied regions. The main MT type was MT1 (32% of aborted fetuses) and also 7 different genotypes were involved in infections. So it is concluded that diversity inC.abortusgenotyping is high in two regions.
Case–control study on TP73 rs1801173 C > T gene polymorphism and susceptibility to gastric cancer in a Chinese Han population
Authors: Pan Huiwen , Gu Xuyu , Wang Xiaoyan , Gao Zhenjun , Ding Guowen , Zou Chen , Fan Yu 
Published: January 2022

Abstract
Background
This study investigated the role of TP73 gene polymorphism, rs1801173on risk of gastric cancer.

Methods
We conducted a case-controlled study including 577 primary gastric cancer and 678 normal control cases. The target gene fragment was amplified using PCR using blood samples collected from patients. Allele analysis and genotyping were performed using snapshot method.

Results
The findings showed that the control group had consistent genotype frequency distribution and presented Hardy–Weinberg equilibrium. The results showed no significant differences in sex, drinking history and age distributions between subjects with the polymorphism and subjects in the control group. Smoking status was correlated with incidence of gastric cancer (P = 0.006). The rs1801173 locus of TP73 gene contained 3 genotypes including: TT, CT, and CT. Logistic regression analysis showed that distribution of recessive model and dominant model was comparable between the two groups before (P = 0.688; 0.937) or after (P = 0.703; 0.990) adjusting for confounders. The distribution frequency in case group was not significantly different relative to that of the control group (P = 0.763).

Conclusion
Smoking can independently influence the risk of gastric cancer. TP73 gene rs1801173 polymorphism was not significantly correlated with risk of gastric cancer.