bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of prescription benzodiazepines and related drugs in family caregivers: a nation-wide register-based study
Authors: Mikkola Tuija M , Mänty Minna , Kautiainen Hannu , von Bonsdorff Mikaela B , Koponen Hannu , Kröger Teppo , Eriksson Johan G 
Published: December 2022

Abstract

Background
objective indicators of sleep and mental health problems in family caregivers have rarely been reported.

Objective
to study the use of prescription benzodiazepines and related drugs (BZDRD) in Finnish family caregivers and matched controls.

Design
prospective follow-up in 2012–17.

Setting
nationwide register-linkage study.

Subjects
all individuals who received family caregiver’s allowance in Finland in 2012 (N = 42,256; mean age 67 years; 71% women) and controls matched for age, sex and municipality of residence (N = 83,618).

Methods
information on purchases of prescription BZDRD, including the number of defined daily doses (DDDs), between 2012 and 2017 was obtained from the Dispensations Reimbursable under the National Health Insurance Scheme register. Background information was obtained from national registers.

Results
more caregivers than controls used BZDRD, both among women (users per 100 person-years: 17.2 versus 15.2, P &lt; 0.001) and men (14.6 versus 11.8, P &lt; 0.001). These differences were largely explained by hypnotic BZDRD use. There were also more long-term BZDRD users per 100 person-years among caregivers than controls, both among women (5.0 versus 4.3, P = 0.001) and men (5.3 versus 3.8, P &lt; 0.001). Use of hypnotic BZDRD in number of DDDs was higher in caregivers than in controls, particularly among men above 50 years. Caregivers used more anxiolytic BZDRD than controls from middle age to 75 years but less in the oldest age groups.

Conclusions
higher level of BZDRD use among caregivers indicates that caregivers have more sleep and mental health problems than non-caregivers. Adequate treatment of these problems and support for caregiving should be ensured for caregivers.
Asymptomatic orthostatic hypotension and risk of falls in community-dwelling older people
Authors: Claffey Paul , Pérez-Denia Laura , Lavan Amanda , Kenny Rose Anne , Finucane Ciarán , Briggs Robert 
Published: December 2022

Abstract

Introduction
Many older people with orthostatic hypotension (OH) may not report typical symptoms of dizziness, light-headedness or unsteadiness. However, the relationships between OH and falls in the absence of typical symptoms are not yet established.

Methods
Continuous orthostatic blood pressure (BP) was measured during active stand using a Finometer at Wave 1 of The Irish Longitudinal Study on Ageing in participants aged ≥ 70 years.
OH, with and without dizziness, was defined as a sustained drop in systolic BP ≥ 20 and/or diastolic BP ≥ 10 mm Hg at 30, 60 and 90 seconds post-standing.
The association between symptoms of dizziness and orthostatic BP was assessed with multi-level mixed-effects linear regression; logistic regression models assessed the longitudinal relationship between OH and falls at 6-year follow-up (Waves 2–5).

Results
Almost 11% (n = 934, mean age 75 years, 51% female) had OH, two-thirds of whom were asymptomatic.
Dizziness was not associated with systolic BP drop at 30 (β = 1.54 (−1.27, 4.36); p = 0.256), 60 (β = 2.64 (−0.19, 5.47); p = 0.476) or 90 seconds (β = 2.02 (−0.91, 4.95); p = 0.176) after standing in adjusted models.
Asymptomatic OH was independently associated with unexplained falls (odds ratio 2.01 [1.11, 3.65]; p = 0.022) but not explained falls (OR 0.93 [0.53, 1.62]; p = 0.797) during follow-up.

Conclusions
Two-thirds of older people with OH did not report typical symptoms of light-headedness. Dizziness or unsteadiness after standing did not correlate with the degree of orthostatic BP drop or recovery. Participants with asymptomatic OH had a significantly higher risk of unexplained falls during follow-up, and this has important clinical implications for the assessment of older people with falls.
Is a seasonally reduced growth potential a convergent strategy to survive drought and frost in plants?
Authors: Volaire Florence , Barkaoui Karim , Grémillet David , Charrier Guillaume , Dangles Olivier , Lamarque Laurent J , Martin-StPaul Nicolas , Chuine Isabelle 
Published: December 2022

Abstract

Background
Plants have adapted to survive seasonal life-threatening frost and drought. However, the timing and frequency of such events are impacted by climate change, jeopardizing plant survival. Understanding better the strategies of survival to dehydration stress is therefore timely and can be enhanced by the cross-fertilization of research between disciplines (ecology, physiology), models (woody, herbaceous species) and types of stress (drought, frost).

Scope
We build upon the ‘growth–stress survival’ trade-off, which underpins the identification of global plant strategies across environments along a ‘fast–slow’ economics spectrum. Although phenological adaptations such as dormancy are crucial to survive stress, plant global strategies along the fast–slow economic spectrum rarely integrate growth variations across seasons. We argue that the growth–stress survival trade-off can be a useful framework to identify convergent plant ecophysiological strategies to survive both frost and drought. We review evidence that reduced physiological activity, embolism resistance and dehydration tolerance of meristematic tissues are interdependent strategies that determine thresholds of mortality among plants under severe frost and drought. We show that complete dormancy, i.e. programmed growth cessation, before stress occurrence, minimizes water flows and maximizes dehydration tolerance during seasonal life-threatening stresses. We propose that incomplete dormancy, i.e. the programmed reduction of growth potential during the harshest seasons, could be an overlooked but major adaptation across plants. Quantifying stress survival in a range of non-dormant versus winter- or summer-dormant plants, should reveal to what extent incomplete to complete dormancy could represent a proxy for dehydration tolerance and stress survival.

Conclusions
Our review of the strategies involved in dehydration stress survival suggests that winter and summer dormancy are insufficiently acknowledged as plant ecological strategies. Incorporating a seasonal fast–slow economics spectrum into global plant strategies improves our understanding of plant resilience to seasonal stress and refines our prevision of plant adaptation to extreme climatic events.
Interpretable artificial intelligence model for accurate identification of medical conditions using immune repertoire
Authors: Zhao Yu , He Bing , Xu Zhimeng , Zhang Yidan , Zhao Xuan , Huang Zhi-An , Yang Fan , Wang Liang , Duan Lei , Song Jiangning , Yao Jianhua 
Published: December 2022

Abstract
Underlying medical conditions, such as cancer, kidney disease and heart failure, are associated with a higher risk for severe COVID-19. Accurate classification of COVID-19 patients with underlying medical conditions is critical for personalized treatment decision and prognosis estimation. In this study, we propose an interpretable artificial intelligence model termed VDJMiner to mine the underlying medical conditions and predict the prognosis of COVID-19 patients according to their immune repertoires. In a cohort of more than 1400 COVID-19 patients, VDJMiner accurately identifies multiple underlying medical conditions, including cancers, chronic kidney disease, autoimmune disease, diabetes, congestive heart failure, coronary artery disease, asthma and chronic obstructive pulmonary disease, with an average area under the receiver operating characteristic curve (AUC) of 0.961. Meanwhile, in this same cohort, VDJMiner achieves an AUC of 0.922 in predicting severe COVID-19. Moreover, VDJMiner achieves an accuracy of 0.857 in predicting the response of COVID-19 patients to tocilizumab treatment on the leave-one-out test. Additionally, VDJMiner interpretively mines and scores V(D)J gene segments of the T-cell receptors that are associated with the disease. The identified associations between single-cell V(D)J gene segments and COVID-19 are highly consistent with previous studies. The source code of VDJMiner is publicly accessible at https://github.com/TencentAILabHealthcare/VDJMiner. The web server of VDJMiner is available at https://gene.ai.tencent.com/VDJMiner/.
Matrix reconstruction with reliable neighbors for predicting potential MiRNA–disease associations
Authors: Feng Hailin , Jin Dongdong , Li Jian , Li Yane , Zou Quan , Liu Tongcun 
Published: December 2022

AbstractNumerous experimental studies have indicated that alteration and dysregulation in mircroRNAs (miRNAs) are associated with serious diseases. Identifying disease-related miRNAs is therefore an essential and challenging task in bioinformatics research. Computational methods are an efficient and economical alternative to conventional biomedical studies and can reveal underlying miRNA–disease associations for subsequent experimental confirmation with reasonable confidence. Despite the success of existing computational approaches, most of them only rely on the known miRNA–disease associations to predict associations without adding other data to increase the prediction accuracy, and they are affected by issues of data sparsity. In this paper, we present MRRN, a model that combines matrix reconstruction with node reliability to predict probable miRNA–disease associations. In MRRN, the most reliable neighbors of miRNA and disease are used to update the original miRNA–disease association matrix, which significantly reduces data sparsity. Unknown miRNA–disease associations are reconstructed by aggregating the most reliable first-order neighbors to increase prediction accuracy by representing the local and global structure of the heterogeneous network. Five-fold cross-validation of MRRN produced an area under the curve (AUC) of 0.9355 and area under the precision-recall curve (AUPR) of 0.2646, values that were greater than those produced by comparable models. Two different types of case studies using three diseases were conducted to demonstrate the accuracy of MRRN, and all top 30 predicted miRNAs were verified.
ASTER: accurately estimating the number of cell types in single-cell chromatin accessibility data
Authors: Chen Shengquan , Wang Rongxiang , Long Wenxin , Jiang Rui 
Published: December 2022

Abstract

Summary
Recent innovations in single-cell chromatin accessibility sequencing (scCAS) have revolutionized the characterization of epigenomic heterogeneity. Estimation of the number of cell types is a crucial step for downstream analyses and biological implications. However, efforts to perform estimation specifically for scCAS data are limited. Here, we propose ASTER, an ensemble learning-based tool for accurately estimating the number of cell types in scCAS data. ASTER outperformed baseline methods in systematic evaluation on 27 datasets of various protocols, sizes, numbers of cell types, degrees of cell-type imbalance, cell states and qualities, providing valuable guidance for scCAS data analysis.

Availability and implementation
ASTER along with detailed documentation is freely accessible at https://aster.readthedocs.io/ under the MIT License. It can be seamlessly integrated into existing scCAS analysis workflows. The source code is available at https://github.com/biox-nku/aster.

Supplementary information
Supplementary data are available at Bioinformatics online.
Identification of novel NFKB1 and ICOS frameshift variants in patients with CVID
Authors: Liu Anli , Liu Qiang , Leng Shaoqiu , Zhang Xiaoyu , Feng Qi , Peng Jun , Feng Gege 
Published: December 2022

AbstractCommon variable immunodeficiency (CVID) is a ‘late-onset’ primary immunodeficiency characterized by variable manifestations and genetic heterogeneity. A monogenic cause of CVID has been reported in 10% of patients. In this study, we identified two novel pathogenic variants implicated in monogenic CVID by whole exome sequencing (WES) analysis: a heterozygous nuclear factor κB subunit 1 (NFKB1) p.G686fs mutation and a homozygous inducible T-cell co-stimulator (ICOS) p.L96Sfs mutation. The predicted crystal models indicated premature truncation of the two mutated proteins. Both variants were demonstrated as loss-of-function mutations and were associated with overlapped manifestations of respiratory fungal infection and splenomegaly. We further performed a detailed assessment of immunologic phenotypes and impaired lymphocyte functions in patients. Moreover, we discovered an association between monoclonal T-large granular lymphocyte proliferation and ICOS-deficient CVID for the first time. These observations lead to a new perspective on the underlying genetic heterogeneity of CVID.
Reproductive biology of harvestmen (Arachnida: Opiliones): a review of a rapidly evolving research field
Authors: Machado Glauco , Burns Mercedes 
Published: December 2022

Abstract
Harvestmen are a major arachnid order that has experienced a dramatic increase in biological knowledge in the 21st century. The publication of the book Harvestmen: The Biology of Opiliones in 2007 stimulated the development of many behavioral studies. Although the book is relatively recent, our understanding of the reproductive biology of harvestmen is already outdated due to the fast accumulation of new data. Our goal is to provide an updated review of the subject to serve as a benchmark for the following years. In the pre-copulatory phase, we explore the evolution of facultative parthenogenesis, the factors that may affect the types of mating system, and the role of nuptial gifts in courtship. Regarding the copulatory phase, harvestmen are unique arachnids because they have aflagellate spermatozoa and a penis with complex morphology. We discuss the implications of these two features for sperm competition and cryptic female choice. In the post-copulatory phase, we connect oviposition site selection and climate conditions to the widespread occurrence of resource defense polygyny, alternative reproductive tactics, and sexual dimorphism in several clades of tropical harvestmen. Finally, we present the different forms of parental care in the order, and discuss the benefits and costs of this behavior, which can be performed either by females or males. Throughout the review, we indicate gaps in our knowledge and subjects that deserve further studies. Hopefully, the information synthesized here will stimulate researchers worldwide to embrace harvestmen as a study system and to improve our effort to unravel the mysteries of their reproductive biology.
Value of 96-hour ambulatory esophageal pH monitoring in the assessment of patients with refractory acid reflux symptoms and their response to anti-reflux diet
Authors: Triadafilopoulos George , Kamal Afrin , Clarke John O 
Published: December 2022

Summary
Ambulatory esophageal pH monitoring is a diagnostic tool in patients with heartburn and regurgitation. The aim of this study is to evaluate 96-hour esophageal pH monitoring in patients with gastroesophageal reflux disease (GERD), at baseline and under diet that impedes GER. We hypothesized that diet would potentially reduce pathologic acid exposure time (AET). Retrospective series of 88 patients with GERD undergoing wireless 96-hour pH monitoring. Two-day (48 hours) tandem periods, one on liberal, followed by another on restricted diet assessed esophageal AET. Primary end point was &gt;30% reduction in AET while on anti-GER diet. Of the 88 patients, 16 were excluded because of probe migration. Endoscopy and biopsies assessed erosive esophagitis (EE) and Barrett’s esophagus (BE), or normal esophagus. Abnormal AET (% pH &lt; 4.0 ≥ 6) further defined nonerosive reflux disease (NERD), whereas normal AET (% pH &lt; 4.0 &lt; 6) with normal endoscopy defined patients as functional heartburn (FH). There were 6 patients with EE (n = 5) and BE (n = 1), 23 with NERD and 43 with FH. Anti-GER diet led to &gt;30% reduction in AET in EE and NERD patients, but not in those with FH. Most patients (n = 43/72; 60%) had FH and could have avoided acid suppression. Furthermore, (14/23; 61%) of patients with NERD completely normalized AET with diet, potentially negating acid suppression. Ninety-six-hour esophageal pH distinguishes GERD patients from those with FH. Fifty percent of EE/BE patients and 61% of those with NERD completely normalize AET with diet. If pathologic AET occurs despite diet, acid suppression is indicated.
Mass-Cytometry-Based Quantification of Global Histone Post-Translational Modifications at Single-Cell Resolution Across Peripheral Immune Cells in IBD
Authors: Bai Lawrence , Dermadi Denis , Kalesinskas Laurynas , Dvorak Mai , Chang Sarah E , Ganesan Ananthakrishnan , Rubin Samuel J S , Kuo Alex , Cheung Peggie , Donato Michele , Utz Paul J , Habtezion Aida , Khatri Purvesh 
Published: December 2022

Abstract

Background and Aims
Current understanding of histone post-translational modifications [histone modifications] across immune cell types in patients with inflammatory bowel disease [IBD] during remission and flare is limited. The present study aimed to quantify histone modifications at a single-cell resolution in IBD patients during remission and flare and how they differ compared to healthy controls.

Methods
We performed a case-control study of 94 subjects [83 IBD patients and 11 healthy controls]. IBD patients had either ulcerative colitis [n = 38] or Crohn’s disease [n = 45] in clinical remission or flare. We used epigenetic profiling by time-of-flight [EpiTOF] to investigate changes in histone modifications within peripheral blood mononuclear cells from IBD patients.

Results
We discovered substantial heterogeneity in histone modifications across multiple immune cell types in IBD patients. They had a higher proportion of less differentiated CD34+ haematopoietic progenitors, and a subset of CD56bright natural killer [NK] cells and γδ T cells characterized by distinct histone modifications associated with gene transcription. The subset of CD56bright NK cells had increases in several histone acetylations. An epigenetically defined subset of NK cells was associated with higher levels of C-reactive protein in peripheral blood. CD34+ monocytes from IBD patients had significantly decreased cleaved H3T22, suggesting they were epigenetically primed for macrophage differentiation.

Conclusion
We describe the first systems-level quantification of histone modifications across immune cells from IBD patients at a single-cell resolution, revealing the increased epigenetic heterogeneity that is not possible with traditional ChIP-seq profiling. Our data open new directions in investigating the association between histone modifications and IBD pathology using other epigenomic tools.
Smartphone-activated volunteer responders and bystander defibrillation for out-of-hospital cardiac arrest in private homes and public locations
Authors: Andelius Linn , Malta Hansen Carolina , Jonsson Martin , Gerds Thomas A , Rajan Shahzleen , Torp-Pedersen Christian , Claesson Andreas , Lippert Freddy , Tofte Gregers Mads Chr , Berglund Ellinor , Gislason Gunnar H , Køber Lars , Hollenberg Jacob , Ringh Mattias , Folke Fredrik 
Published: December 2022

Abstract

Aims
To investigate the association between the arrival of smartphone-activated volunteer responders before the Emergency Medical Services (EMS) and bystander defibrillation in out-of-hospital cardiac arrest (OHCA) at home and public locations.

Methods and results
This is a retrospective study (1 September 2017–14 May 2019) from the Stockholm Region of Sweden and the Capital Region of Denmark. We included 1271 OHCAs, of which 1029 (81.0%) occurred in private homes and 242 (19.0%) in public locations. The main outcome was bystander defibrillation. At least one volunteer responder arrived before EMS in 381 (37.0%) of OHCAs at home and 84 (34.7%) in public. More patients received bystander defibrillation when a volunteer responder arrived before EMS at home (15.5 vs. 2.2%, P &lt; 0.001) and in public locations (32.1 vs. 19.6%, P = 0.030). Similar results were found among the 361 patients with an initial shockable heart rhythm (52.7 vs. 11.5%, P &lt; 0.001 at home and 60.0 vs. 37.8%, P = 0.025 in public). The standardized probability of receiving bystander defibrillation increased with longer EMS response times in private homes. The 30-day survival was not significantly higher when volunteer responders arrived before EMS (9.2 vs. 7.7% in private homes, P = 0.41; and 40.5 vs. 35.4% in public locations, P = 0.44).

Conclusion
Bystander defibrillation was significantly more common in private homes and public locations when a volunteer responder arrived before the EMS. The standardized probability of bystander defibrillation increased with longer EMS response times in private homes. Our findings support the activation of volunteer responders and suggest that volunteer responders could increase bystander defibrillation, particularly in private homes.
Tumour location predicts occult N1 nodal metastasis in clinical stage I non-small-cell lung cancer
Authors: Kawamoto Nobutaka , Tsutani Yasuhiro , Kamigaichi Atsushi , Ohsawa Manato , Mimae Takahiro , Miyata Yoshihiro , Okada Morihito 
Published: December 2022

Abstract

OBJECTIVES
Pathological lymph node metastases are often observed in patients with clinical N0 lung cancer. Identifying preoperative predictors of occult hilar nodal metastasis (OHNM) is important in determining the surgical procedure in patients with clinical stage I non-small-cell lung cancer. This study aimed to determine the frequency and predictors of OHNM by tumour location in these patients.

METHODS
Between April 2007 and May 2019, data of patients who underwent lobectomy or segmentectomy for clinical stage I pure-solid non-small-cell lung cancer were retrospectively reviewed. The ratio of the distance from the pulmonary hilum to the proximal side of the tumour to the distance from the pulmonary hilum to the visceral pleural surface through the centre of the tumour, named ‘distance ratio (DR)’, was calculated. The relationship of the DR with clinicopathological findings and prognosis was discussed.

RESULTS
A total of 357 patients were enrolled. OHNM frequency was 14.6%. Patients were divided into 2 groups based on whether the DR was ≤0.67 (central type) or &gt;0.67 (peripheral type). The frequency of OHNM was significantly higher in the DR ≤0.67 group (21.5% vs 7.4%; P &lt; 0.001). Multivariable analysis revealed that DR was the only independent preoperative predictor of OHNM (odds ratio, 3.63; 95% confidence interval, 1.83–7.18; P &lt; 0.001).

CONCLUSIONS
The frequency of OHNM was significantly lower in peripheral-type lung cancer; therefore, tumour location was the most important preoperative predictor of OHNM.