bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quartet DNA reference materials and datasets for comprehensively evaluating germline variant calling performance
Authors: Ren Luyao , Duan Xiaoke , Dong Lianhua , Zhang Rui , Yang Jingcheng , Gao Yuechen , Peng Rongxue , Hou Wanwan , Liu Yaqing , Li Jingjing , Yu Ying , Zhang Naixin , Shang Jun , Liang Fan , Wang Depeng , Chen Hui , Sun Lele , Hao Lingtong ,   The Quartet Project Team, Scherer Andreas , Nordlund Jessica , Xiao Wenming , Xu Joshua , Tong Weida , Hu Xin , Jia Peng , Ye Kai , Li Jinming , Jin Li , Hong Huixiao , Wang Jing , Fan Shaohua , Fang Xiang , Zheng Yuanting , Shi Leming 
Published: November 2023

Abstract
Background
Genomic DNA reference materials are widely recognized as essential for ensuring data quality in omics research. However, relying solely on reference datasets to evaluate the accuracy of variant calling results is incomplete, as they are limited to benchmark regions. Therefore, it is important to develop DNA reference materials that enable the assessment of variant detection performance across the entire genome.

Results
We established a DNA reference material suite from four immortalized cell lines derived from a family of parents and monozygotic twins. Comprehensive reference datasets of 4.2 million small variants and 15,000 structural variants were integrated and certified for evaluating the reliability of germline variant calls inside the benchmark regions. Importantly, the genetic built-in-truth of the Quartet family design enables estimation of the precision of variant calls outside the benchmark regions. Using the Quartet reference materials along with study samples, batch effects are objectively monitored and alleviated by training a machine learning model with the Quartet reference datasets to remove potential artifact calls. Moreover, the matched RNA and protein reference materials and datasets from the Quartet project enables cross-omics validation of variant calls from multiomics data.

Conclusions
The Quartet DNA reference materials and reference datasets provide a unique resource for objectively assessing the quality of germline variant calls throughout the whole-genome regions and improving the reliability of large-scale genomic profiling.
Single-cell multiomics of the human retina reveals hierarchical transcription factor collaboration in mediating cell type-specific effects of genetic variants on gene regulation
Authors: Wang Jun , Cheng Xuesen , Liang Qingnan , Owen Leah A. , Lu Jiaxiong , Zheng Yiqiao , Wang Meng , Chen Shiming , DeAngelis Margaret M. , Li Yumei , Chen Rui 
Published: November 2023

Abstract
Background
Systematic characterization of how genetic variation modulates gene regulation in a cell type-specific context is essential for understanding complex traits. To address this question, we profile gene expression and chromatin accessibility in cells from healthy retinae of 20 human donors through single-cell multiomics and genomic sequencing.

Results
We map eQTL, caQTL, allelic-specific expression, and allelic-specific chromatin accessibility in major retinal cell types. By integrating these results, we identify and characterize regulatory elements and genetic variants effective on gene regulation in individual cell types. The majority of identified sc-eQTLs and sc-caQTLs display cell type-specific effects, while the cis-elements containing genetic variants with cell type-specific effects are often accessible in multiple cell types. Furthermore, the transcription factors whose binding sites are perturbed by genetic variants tend to have higher expression levels in the cell types where the variants exert their effects, compared to the cell types where the variants have no impact. We further validate our findings with high-throughput reporter assays. Lastly, we identify the enriched cell types, candidate causal variants and genes, and cell type-specific regulatory mechanism underlying GWAS loci.

Conclusions
Overall, genetic effects on gene regulation are highly context dependent. Our results suggest that cell type-dependent genetic effect is driven by precise modulation of both trans-factor expression and chromatin accessibility of cis-elements. Our findings indicate hierarchical collaboration among transcription factors plays a crucial role in mediating cell type-specific effects of genetic variants on gene regulation.
RCC2 promotes prostate cancer cell proliferation and migration through Hh/GLI1 signaling pathway and cancer stem-like cells
Authors: Wang Shenghan , Lei Zhentao , Liu Wei , Xiong Jie , Shi Yuqiang , Yang Lin , Gao Qiang , Le Kai , Zhang Bao 
Published: November 2023

Abstract
Background
Regulator of chromosome condensation 2 (RCC2) was a telophase disk-binding protein on mitosis, and functions as an oncogene in many human cancers. However, its role on prostate cancer (PCa) was unknown. The goal of this study is to explore the function of RCC 2 on PCa development.

Methods
The expression of RCC2 and its methylation level, its correlation with lymph node metastasis or disease-free survival (DFS) was analyzed using TCGA database. The effect of RCC2 on PCa cell proliferation, migration and invasion were detected using CCK-8, cell colony formation, Transwell and wood healing assays. RNA-seq and GSEA analysis were used to search the downstream genes and pathways of RCC2 in mediated PCa progression. Western blot was used to detect the proteins in PCa cells transfected with indicated siRNAs or plasmids.

Results
RCC2 had high expression and low promoter methylation level in PCa, and its expression was correlated with regional node metastasis and disease-free survival. Cell proliferation, migration, invasion and EMT of PCa cells in vitro were greatly enhanced after RCC2 overexpression, while the RCC2 knockdown suppressed these processes. RNA-seq and GSEA results showed the Hedgehog signaling regulator Gli1 and Gli3 were involved in RCC2 knockdown DU145 cells. Gli1 was also a marker of cancer stem-like cells (CSCs). Mechanistically, RCC2 induced cell growth, EMT, CSCs markers through Gli1; inhibiting Gli1 expression using siGli1 or GLI inhibitor suppressed cell progression in vitro and tumor growth in vivo.

Conclusion
In summary, RCC2 promoted PCa development through Hh/Gli1 signaling pathway via regulating EMT and CSCs.
The efficacy of a blended intervention to improve physical activity and protein intake for optimal physical recovery after oncological gastrointestinal and lung cancer surgery, the Optimal Physical Recovery After Hospitalization (OPRAH) trial: study protocol for a randomized controlled multicenter trial
Authors: de Leeuwerk Marijke , de Groot Vincent , Dam Suzanne ten , Kruizenga Hinke , Weijs Peter , Geleijn Edwin , van der Leeden Marike , van der Schaaf Marike ,   on behalf of the OPRAH consortium, Dickhoff Chris , Besselink Marc G. , Tuynman Jurriaan B. , van Berge Henegouwen Mark I. , Erdmann Joris I. , Huijsmans Rosalie J. , van der Ploeg Hidde P. , Eskes Anne M. , Pijnappels Mirjam A. G. M. , van Leeuwen Liesbeth Schuijs , Smits Anke B. , van Dijk Jasmijn , Grimbergen Eva 
Published: November 2023

Abstract
Background
Improving physical activity, especially in combination with optimizing protein intake, after surgery has a potential positive effect on recovery of physical functioning in patients after gastrointestinal and lung cancer surgery. The aim of this randomized controlled trial is to evaluate the efficacy of a blended intervention to improve physical activity and protein intake after hospital discharge on recovery of physical functioning in these patients.

Methods
In this multicenter single-blinded randomized controlled trial, 161 adult patients scheduled for elective gastrointestinal or lung cancer surgery will be randomly assigned to the intervention or control group. The purpose of the Optimal Physical Recovery After Hospitalization (OPRAH) intervention is to encourage self-management of patients in their functional recovery, by using a smartphone application and corresponding accelerometer in combination with coaching by a physiotherapist and dietician during three months after hospital discharge. Study outcomes will be measured prior to surgery (baseline) and one, four, eight, and twelve weeks and six months after hospital discharge. The primary outcome is recovery in physical functioning six months after surgery, and the most important secondary outcome is physical activity. Other outcomes include lean body mass, muscle mass, protein intake, symptoms, physical performance, self-reported limitations in activities and participation, self-efficacy, hospital readmissions and adverse events.

Discussion
The results of this study will demonstrate whether a blended intervention to support patients increasing their level of physical activity and protein intake after hospital discharge improves recovery in physical functioning in patients after gastrointestinal and lung cancer surgery.

Trial registration
The trial has been registered at the International Clinical Trials Registry Platform at 14–10-2021 with registration number NL9793. Trial registration data are presented in Table 1.
Analgesic effect of nitrous oxide during manual therapy after anterior cruciate ligament reconstruction: a study protocol for a randomized controlled trial
Authors: Wang Ziyang , Wang Fei , Li Yuxiang , Xing Yihui , Jiang Xiaochen , Li Cui , Ding Zhiguo , Tang Lu 
Published: November 2023

Abstract
Background
Many patients during manual therapy after anterior ligament reconstruction will experience severe pain, which has a negative impact on their rehabilitation. However, there is rarely an analgesic method for these patients during rehabilitation. Nitrous oxide with rapid analgesic and sedative effects is often used to relieve pain in minor procedures. The purpose of this study is to determine whether or not nitrous oxide analgesia decreases pain compared to oxygen during manual therapy after anterior ligament reconstruction.

Methods/design
This single-center, randomized, double-blind and controlled trial will recruit 120 patients. Patients ≥ 18 years old undergoing manual therapy after anterior ligament reconstruction (1 month post-operative) with acute pain (VAS ≥ 4) are included. The main exclusion criteria included the following: pulmonary embolism, intestinal obstruction, pneumothorax. Patients will be randomly allocated to the intervention group (A) and the control group (B) in a ratio of 1:1. Doctors, therapists, patients, and data collectors are all blind to the study. The manual therapy will be performed by therapists. Nurses who implemented the intervention handed the doctors envelopes containing the patients’ codes and allocation of A or B. Group A will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesic) given as 30-min treatment sessions, once daily, and group B will receive oxygen plus conventional treatment (no analgesic) under the same conditions. Assessments will be taken 2 min before the intervention (T0), 5 min after the beginning of the intervention (T1), and 5 min after the intervention finished (T2). The primary outcome is pain score. Secondary outcomes include vital signs, side effects, joint range of motion, adjuvant analgesia need, therapist and patient satisfaction, and whether willing to receive the same gas again.

Expected outcomes
We expect nitrous oxide inhalation to have a beneficial effect on the pain of patients who receive manual therapy after anterior ligament reconstruction.

Discussion
If this treatment appears beneficial, it could improve patients’ satisfaction and quality of life potentially and even be implemented widely in hospital and rehabilitation settings.

Trial registration
ClinicalTrials.gov identifier, ChiCTR2200061175 (Version 2.0 June 15, 2022), https://www.chictr.org.cn.
Effects of a single dose of amisulpride on functional brain changes during reward- and motivation-related processing using task-based fMRI in healthy subjects and patients with major depressive disorder — study protocol for a randomized clinical trial
Authors: Carstens Luisa , Popp Margot , Keicher Christian , Hertrampf Rita , Weigner David , Meiering Marvin S. , Luippold Gerd , Süssmuth Sigurd D. , Beckmann Christian F. , Wunder Andreas , Grimm Simone 
Published: November 2023

Abstract
Background
Anhedonia and other deficits in reward- and motivation-related processing in psychiatric patients, including patients with major depressive disorder (MDD), represent a high unmet medical need. Neurobiologically, these deficits in MDD patients are mainly associated with low dopamine function in a frontostriatal network. In this study, alterations in brain activation changes during reward processing and at rest in MDD patients compared with healthy subjects are explored and the effects of a single low dose of the dopamine D2 receptor antagonist amisulpride are investigated.

Methods
This is a randomized, controlled, double-blind, single-dose, single-center parallel-group clinical trial to assess the effects of a single dose of amisulpride (100 mg) on blood-oxygenation-level-dependent (BOLD) responses during reward- and motivation-related processing in healthy subjects (n = 60) and MDD patients (n = 60). Using functional magnetic resonance imaging (fMRI), BOLD responses are assessed during the monetary incentive delay (MID) task (primary outcome). Exploratory outcomes include BOLD responses and behavioral measures during the MID task, instrumental learning task, effort-based decision-making task, social incentive delay task, and probabilistic reward task as well as changes in resting state functional connectivity and cerebral blood flow.

Discussion
This study broadly covers all aspects of reward- and motivation-related processing as categorized by the National Institute of Mental Health Research Domain Criteria and is thereby an important step towards precision psychiatry. Results regarding the immediate effects of a dopaminergic drug on deficits in reward- and motivation-related processing not only have the potential to significantly broaden our understanding of underlying neurobiological processes but might eventually also pave the way for new treatment options.

Trial registration
ClinicalTrials.gov NCT05347199. April 12, 2022.
Effects of a physical activity and endometriosis-based education program delivered by videoconference on endometriosis symptoms: the CRESCENDO program (inCRease physical Exercise and Sport to Combat ENDOmetriosis) protocol study
Authors: Escriva-Boulley Géraldine , Philip Charles-André , Warembourg Sophie , Lenotre Lionel , Flore Patrice , Faure Patrice , Michy Thierry , Letouzey Vincent , Arnold Carole , Piluso Claire , Chalmel Loic , Kacem Ramzi , Blum Georges Fabrice , Detayrac Renaud , Trocmé Candice , Brigaud Isabelle , Herbach Ulysse , Branche Patricia , Faller Emilie , Chalabaev Aïna 
Published: November 2023

Abstract
Background
Endometriosis is a chronic disease characterized by growth of endometrial tissue outside the uterine cavity which could affect 200 million women (The term “woman” is used for convenience. Individuals gendered as man or as nonbinary can also suffer from this disease) worldwide. One of the most common symptoms of endometriosis is pelvic chronic pain associated with fatigue. This pain can cause psychological distress and interpersonal difficulties. As for several chronic diseases, adapted physical activity could help to manage the physical and psychological symptoms. The present study will investigate the effects of a videoconference-based adapted physical activity combined with endometriosis-based education program on quality of life, pain, fatigue, and other psychological symptoms and on physical activity.

Methods
This multicentric randomized-controlled trial will propose to 200 patients with endometriosis to be part of a trial which includes a 6-month program with 45 min to more than 120 min a week of adapted physical activity and/or 12 sessions of endometriosis-based education program. Effects of the program will be compared to a control group in which patients will be placed on a waiting list. All participants will be followed up 3 and 6 months after the intervention. None of the participants will be blind to the allocated trial arm. The primary outcome measure will be quality of life. Secondary outcomes will include endometriosis-related perceived pain, fatigue, physical activity, and also self-image, stereotypes, motivational variables, perceived support, kinesiophobia, basic psychological need related to physical activity, and physical activity barriers. General linear models and multilevel models will be performed. Predictor, moderator, and mediator variables will be investigated.

Discussion
This study is one of the first trials to test the effects of a combined adapted physical activity and education program for improving endometriosis symptoms and physical activity. The results will help to improve care for patients with endometriosis.

Trial registration
ClinicalTrials.gov, NCT05831735. Date of registration: April 25, 2023
Home-based rehabilitation training with human key point detection for chronic low back pain patients: a randomized controlled trial protocol
Authors: Fuming Zheng , Zhicheng Li , Huanjie Huang , Xinna Zhang , Rong Chen , Jiahui Peng , Liming Yang , Xi Chen , Chuhuai Wang 
Published: November 2023

Abstract
Background
Core stability exercise (CSE) is a globally acknowledged intervention for managing chronic low back pain. However, the sustained adherence of patients with chronic low back pain to CSE can be challenging, mainly due to the absence of supervision and guidance from physical therapists during home-based exercise sessions. Consequently, exercise compliance tends to decline, resulting in suboptimal long-term effectiveness of the intervention. In this trial, our primary aim is to evaluate the potential therapeutic equivalence between home-based rehabilitation training employing key point identification technology and exercise guidance administered in a hospital setting.

Methods
In this trial, we will randomly assign 104 adults with chronic low back pain (CLBP) to either an intervention or control group, with 52 participants in each group. Both interventions will consist of three weekly 0.5-h sessions of core stability exercise (CSE). The intervention group will engage in home rehabilitation training utilizing key identification technology for movement, while the control group will perform supervised exercises in a hospital setting. Outcome assessments will be conducted at 4 weeks and 16 weeks after randomization. The primary outcome measure will be the change in pain intensity based on numeric rating scale (NRS scores) from baseline to 4 weeks. Secondary outcomes will include changes in physical function (measured by the Oswestry Disability Index (ODI)) and lumbar spine mobility as well as activity participation and treatment satisfaction.

Discussion
If home-based rehabilitation method is demonstrated to be non-inferior or even superior to traditional face-to-face exercise guidance, it could significantly advance the adoption of digital medical care and contribute to improving the overall health of the population.

Trial registration
NCT05998434. Registered on 16 August 2023.
Comparison of amiodarone and esmolol for prevention of reperfusion ventricular fibrillation in individuals undergoing heart valve or aortic surgery: a study protocol for a randomized controlled clinical trial
Authors: Zhu Dan , Li Yu , Tian A-yong , Wang Hong-nan 
Published: November 2023

Abstract
Background
Amiodarone and esmolol can help to prevent and treat post-cardiac surgery reperfusion ventricular fibrillation. However, the relative efficacies of these two drugs remain unknown. The aim of the current trial is to compare the performances of amiodarone and esmolol for preventing reperfusion ventricular fibrillation following open heart surgery.

Methods/design
This is a single-center, prospective, double-blind, controlled clinical trial. A total of 260 patients undergoing heart valve or aortic surgery will be assigned randomly to treatment with prophylactic esmolol (intervention group) or amiodarone (control group). The main outcome is the incidence of reperfusion ventricular fibrillation following aortic opening during extracorporeal circulation. The secondary outcomes are the rate of automatic cardiac resuscitation, energy and frequency of electrical defibrillation, number of electrical defibrillations, and pacemaker use in the two groups of patients. Information on the patients’ general condition and the durations of anesthesia, extracorporeal circulation, aortic occlusion, and operation time will be recorded. We will also compare the heart rate, mean arterial pressure, and central venous pressure between the two groups of patients at induction of anesthesia (T1), start of surgery (T2), start of extracorporeal circulation (T3), aortic block (T4), aortic opening (T5), after opening for 10 (T6), 20 (T7), and 30 min (T8), at cessation of extracorporeal circulation (T9), and at the end of surgery (T10) and compare blood gas analysis results at T1, T5, T9, and T10.

Discussion
This study will determine if prophylactic esmolol is more effective than amiodarone for reducing the incidence of reperfusion ventricular fibrillation in patients undergoing heart valve or aortic surgery.

Trial registration
China Clinical Trials Registry ChiCTR1900026429. Registered on 2019.10.9.