bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-146b-5p regulates IL-23 receptor complex expression in chronic lymphocytic leukemia cells
Authors: Matis Serena , Grazia Recchia Anna , Colombo Monica , Cardillo Martina , Fabbi Marina , Todoerti Katia , Bossio Sabrina , Fabris Sonia , Cancila Valeria , Massara Rosanna , Reverberi Daniele , Emionite Laura , Cilli Michele , Cerruti Giannamaria , Salvi Sandra , Bet Paola , Pigozzi Simona , Fiocca Roberto , Ibatici Adalberto , Angelucci Emanuele , Gentile Massimo , Monti Paola , Menichini Paola , Fronza Gilberto , Torricelli Federica , Ciarrocchi Alessia , Neri Antonino , Fais Franco , Tripodo Claudio , Morabito Fortunato , Ferrarini Manlio , Cutrona Giovanna 
Published: July 2022

Abstract
Chronic lymphocytic leukemia (CLL) cells express the interleukin-23 receptor (IL-23R) chain, but the expression of the complementary IL-12Rβ1 chain requires cell stimulation via surface CD40 molecules (and not via the B-cell receptor [BCR]). This stimulation induces the expression of a heterodimeric functional IL-23R complex and the secretion of IL-23, initiating an autocrine loop that drives leukemic cell expansion. Based on the observation in 224 untreated Binet stage A patients that the cases with the lowest miR-146b-5p concentrations had the shortest time to first treatment (TTFT), we hypothesized that miR-146b-5p could negatively regulate IL-12Rβ1 side chain expression and clonal expansion. Indeed, miR-146b-5p significantly bound to the 3′-UTR region of the IL-12Rβ1 mRNA in an in vitro luciferase assay. Downregulation of miR-146b-5p with specific miRNA inhibitors in vitro led to the upregulation of the IL-12Rβ1 side chain and expression of a functional IL-23R complex similar to that observed after stimulation of the CLL cell through the surface CD40 molecules. Expression of miR-146b-5p with miRNA mimics in vitro inhibited the expression of the IL-23R complex after stimulation with CD40L. Administration of a miR-146b-5p mimic to NSG mice, successfully engrafted with CLL cells, caused tumor shrinkage, with a reduction of leukemic nodules and of IL-12Rβ1–positive CLL cells in the spleen. Our findings indicate that IL-12Rβ1 expression, a crucial checkpoint for the functioning of the IL-23 and IL-23R complex loop, is under the control of miR-146b-5p, which may represent a potential target for therapy since it contributes to the CLL pathogenesis. This trial is registered at www.clinicaltrials.gov as NCT00917540.
Risk factors, diagnosis and management of venous thromboembolic disease in pregnancy
Authors: Edebiri Osasere , Ní Áinle Fionnuala 
Published: July 2022

Venous thromboembolism (VTE) in pregnancy is a leading cause of maternal morbidity and mortality. However, despite the significant associated clinical burden and potentially devastating societal impact, there is still a paucity of data surrounding its prevention and management. Consequently, international guideline recommendations vary widely. Exclusion of pregnant women from clinical trials in the past has contributed to knowledge gaps. However, recently published and ongoing studies demonstrate that excellent clinical trials in pregnancy are achievable. This review will discuss prevention, diagnosis and treatment of VTE in pregnancy, and will also explore priorities for future research.Educational aimsTo gain an understanding of current knowledge on risk factors for pregnancy-associated venous thromboembolism (PA-VTE).To gain an understanding of the diagnosis of PA-VTE.To review up-to-date approaches to preventing and treating PA-VTE.To discuss possible limitations in current research and areas which require improvement.
Experimental and nonlinear finite-element analysis study on lateral push resistance of San-dou components perpendicular and parallel to grain in traditional timber buildings
Authors: Zhang Chengwen , Chun Qing , Lin Yijie , Wang Haoyu , Li Pan 
Published: July 2022

AbstractDou-gong is an essential part of traditional timber buildings in East Asia, having a decoration function and a load transfer function. The San-dou component, which is vulnerable to the lateral push force of the Gong, Fang, and purlin, is a critical structural component in the Dou-gong. In San-dou components, there are two distinctive types of surfaces subjected to lateral push force, perpendicular to the grain and parallel to the grain. However, few investigation into the structural performance of these two types has been done. Considering this shortcoming in the literature, in the current study, tests were carried out to obtain elasticity and strength characteristics on 90 timber specimens of fir and larch. After the material property test, 24 San-dou specimens were prepared to investigate the lateral push resistance. Consequently, an elastic–plastic damage assessment model was developed to calculate the load–displacement curve and possible damage distribution region of San-dou component, using the nonlinear finite-element analysis. According to the analyses, the failure mode for the San-dou component perpendicular to the grain is a horizontal crack parallel to the Dou-ear. Besides, the failure mode of the San-dou component parallel to the grain is an oblique crack, which begins from the inner edge of the Dou-ear to the lower part of the San-dou component. In the case of the other factors being the same, the bearing capacity of the larch San-dou component is 49.64–55.78% stronger than the fir San-dou component. Besides that, the bearing capacity of the San-dou component perpendicular to the grain is 32.85–38.22% higher than the San-dou component parallel to the grain. The research findings are expected to give a theoretical foundation for the structural evaluation of the Dou-gong system in traditional timber buildings and a scientific basis for elucidating the differences in the construction of traditional timber buildings in East Asia.
Genotyping-by-Sequencing Based Investigation of Population Structure and Genome Wide Association Studies for Seven Agronomically Important Traits in a Set of 346 Oryza rufipogon Accessions
Authors: Malik Palvi , Huang Mao , Neelam Kumari , Bhatia Dharminder , Kaur Ramanjeet , Yadav Bharat , Singh Jasdeep , Sneller Clay , Singh Kuldeep 
Published: July 2022

AbstractBeing one of the most important staple dietary constituents globally, genetic enhancement of cultivated rice for yield, agronomically important traits is of substantial importance. Even though the climatic factors and crop management practices impact complex traits like yield immensely, the contribution of variation by underlying genetic factors surpasses them all. Previous studies have highlighted the importance of utilizing exotic germplasm, landraces in enhancing the diversity of gene pool, leading to better selections and thus superior cultivars. Thus, to fully exploit the potential of progenitor of Asian cultivated rice for productivity related traits, genome wide association study (GWAS) for seven agronomically important traits was conducted on a panel of 346 O. rufipogon accessions using a set of 15,083 high-quality single nucleotide polymorphic markers.
The phenotypic data analysis indicated large continuous variation for all the traits under study, with a significant negative correlation observed between grain parameters and agronomic parameters like plant height, culm thickness. The presence of 74.28% admixtures in the panel as revealed by investigating population structure indicated the panel to be very poorly genetically differentiated, with rapid LD decay. The genome-wide association analyses revealed a total of 47 strong MTAs with 19 SNPs located in/close to previously reported QTL/genic regions providing a positive analytic proof for our studies. The allelic differences of significant MTAs were found to be statistically significant at 34 genomic regions. A total of 51 O. rufipogon accessions harboured combination of superior alleles and thus serve as potential candidates for accelerating rice breeding programs. The present study identified 27 novel SNPs to be significantly associated with different traits. Allelic differences between cultivated and wild rice at significant MTAs determined superior alleles to be absent at 12 positions implying substantial scope of improvement by their targeted introgression into cultivars. Introgression of novel significant genomic regions into breeder’s pool would broaden the genetic base of cultivated rice, thus making the crop more resilient.
StackEPI: identification of cell line-specific enhancer–promoter interactions based on stacking ensemble learning
Authors: Fan Yongxian , Peng Binchao 
Published: July 2022

AbstractBackgroundUnderstanding the regulatory role of enhancer–promoter interactions (EPIs) on specific gene expression in cells contributes to the understanding of gene regulation, cell differentiation, etc., and its identification has been a challenging task. On the one hand, using traditional wet experimental methods to identify EPIs often means a lot of human labor and time costs. On the other hand, although the currently proposed computational methods have good recognition effects, they generally require a long training time.ResultsIn this study, we studied the EPIs of six human cell lines and designed a cell line-specific EPIs prediction method based on a stacking ensemble learning strategy, which has better prediction performance and faster training speed, called StackEPI. Specifically, by combining different encoding schemes and machine learning methods, our prediction method can extract the cell line-specific effective information of enhancer and promoter gene sequences comprehensively and in many directions, and make accurate recognition of cell line-specific EPIs. Ultimately, the source code to implement StackEPI and experimental data involved in the experiment are available athttps://github.com/20032303092/StackEPI.git.ConclusionsThe comparison results show that our model can deliver better performance on the problem of identifying cell line-specific EPIs and outperform other state-of-the-art models. In addition, our model also has a more efficient computation speed.
α-Gal antigen-deficient rabbits with GGTA1 gene disruption via CRISPR/Cas9
Authors: Wei Lina , Mu Yufeng , Deng Jichao , Wu Yong , Qiao Ying , Zhang Kun , Wang Xuewen , Huang Wenpeng , Shao Anliang , Chen Liang , Zhang Yang , Li Zhanjun , Lai Liangxue , Qu Shuxin , Xu Liming 
Published: July 2022

Abstract
Background
Previous studies have identified the carbohydrate epitope Galα1–3Galβ1–4GlcNAc-R (termed the α-galactosyl epitope), known as the α-Gal antigen as the primary xenoantigen recognized by the human immune system. The α-Gal antigen is regulated by galactosyltransferase (GGTA1), and α-Gal antigen-deficient mice have been widely used in xenoimmunological studies, as well as for the immunogenic risk evaluation of animal-derived medical devices. The objective of this study was to develop α-Gal antigen-deficient rabbits by GGTA1 gene editing with the CRISPR/Cas9 system.

Results
The mutation efficiency of GGTA1 gene-editing in rabbits was as high as 92.3% in F0 pups. Phenotype analysis showed that the α-Gal antigen expression in the major organs of F0 rabbits was decreased by more than 99.96% compared with that in wild-type (WT) rabbits, and the specific anti-Gal IgG and IgM antibody levels in F1 rabbits increased with increasing age, peaking at approximately 5 or 6 months. Further study showed that GGTA1 gene expression in F2-edited rabbits was dramatically reduced compared to that in WT rabbits.

Conclusions
α-Gal antigen-deficient rabbits were successfully generated by GGTA1 gene editing via the CRISPR/Cas9 system in this study. The feasibility of using these α-Gal antigen-deficient rabbits for the in situ implantation and residual immunogenic risk evaluation of animal tissue-derived medical devices was also preliminarily confirmed.
Effects of quadratus lumborum block on perioperative multimodal analgesia and postoperative outcomes in patients undergoing radical prostatectomy
Authors: Hu Zhen , Zhou Yingjie , Zhao Guohao , Zhang Xinxin , Liu Chunchun , Xing Huan , Liu Ji , Wang Fen 
Published: July 2022

Abstract
Background
This study aimed to investigate the effects of ultrasound-guided quadratus lumborum block (QLB) on perioperative multimodal analgesia and postoperative outcomes in patients undergoing radical prostatectomy.

Methods
A total of 80 patients undergoing radical prostatectomy were randomly divided into two groups: general anaesthesia with QLB (QLB group; n = 40) and general anaesthesia with sham QLB (normal saline [NS] group; n = 40). QLB or sham QLB was performed before the induction of anaesthesia. Sufentanil was intravenously administered for postoperative analgesia. The primary outcome was the pain score (measured using a numerical rating scale [NRS]) at different time points within 48 h postoperatively. Secondary outcomes included the cumulative dose of sufentanil within 48 h postoperatively, subjective comfort, grip strength, first time of exhaustion, first fluid intake time, time to get out of bed, length of postoperative hospital stay and overall satisfaction. The SPSS software, version 17.0, was used for all statistical analyses.

Results
Postoperative NRS at rest was significantly lower at 2 h (1.7 ± 1.1 versus 3.0 ± 2.1), 4 h (1.8 ± 1.2 versus 4.1 ± 2.3), 6 h (1.9 ± 2 versus 4.4 ± 2) and 12 h (3.5 ± 2.3 versus 5 ± 3.3) and was also lower when coughing at 2 h (2.3 ± 1.1 versus 4 ± 2.1), 4 h (2.3 ± 1. 1 versus 4.3 ± 2) and 6 h (2.4 ± 1.1 versus 5.9 ± 2.3) in the QLB than that in the NS group. The cumulative dose of sufentanil was significantly lower in the QLB than that in the NS group at 4 h, 6 h, 12 h, 24 h and 48 h. The nausea score was significantly lower in the QLB group at 24 h postoperatively, and the first time of exhaustion and time to get out of bed were significantly shorter (P < 0.05). The overall satisfaction score was significantly higher in the QLB than in the NS group (4 ± 0.7 versus 2.6 ± 0.9).

Conclusion
Ultrasound-guided bilateral QLB can provide effective postoperative analgesia for patients undergoing radical prostatectomy, reduce the need for sufentanil, facilitate comfort and improve postoperative outcomes. QLB can be a good component of multimodal analgesia.

Trial registration
The clinical trial is registered in the Chinese Clinical Trial Registry (ChiCTR). Current Controlled Trials:ChiCTR1900022009. the date of registration:2019/03/20.
Variation by default: cesarean section discharge opioid prescription patterns and outcomes in Military Health System hospitals: a retrospective longitudinal cohort study
Authors: Highland Krista B. , Robertson Ian , Lutgendorf Monica , Herrera Germaine F. , Velosky Alexander G. , Costantino Ryan C. , Patzkowski Michael S. 
Published: July 2022

Abstract
Background
To examine factors associated with post-Cesarean section analgesic prescription variation at hospital discharge in patients who are opioid naïve; and examine relationships between pre-Cesarean section patient and care-level factors and discharge morphine equivalent dose (MED) on outcomes (e.g., probability of opioid refill within 30 days) across a large healthcare system.

Methods
The Walter Reed Institutional Review Board provided an exempt determination, waiver of consent, and waiver of HIPAA authorization for research use in the present retrospective longitudinal cohort study. Patient records were included in analyses if: sex assigned in the medical record was “female,” age was 18 years of age or older, the Cesarean section occurred between January 2016 to December 2019 in the Military Health System, the listed TRICARE sponsor was an active duty service member, hospitalization began no more than three days prior to the Cesarean section, and the patient was discharged to home < 4 days after the Cesarean section.

Results
Across 57 facilities, 32,757 adult patients had a single documented Cesarean section procedure in the study period; 24,538 met inclusion criteria and were used in analyses. Post-Cesarean section discharge MED varied by facility, with a median MED of 225 mg and median 5-day supply. Age, active duty status, hospitalization duration, mental health diagnosis, pain diagnosis, substance use disorder, alcohol use disorder, gestational diabetes, discharge opioid type (combined vs. opioid-only medication), concurrent tubal ligation procedure, single (vs. multiple) births, and discharge morphine equivalent dose were associated with the probability of an opioid prescription refill in bivariate analyses, and therefore were included as covariates in a generalized additive mixed model (GAMM). Generalized additive mixed model results indicated that non-active duty beneficiaries, those with mental health and pain conditions, those who received an opioid/non-opioid combination medication, those with multiple births, and older patients were more likely to obtain an opioid refill, relative to their counterparts.

Conclusion
Significant variation in discharge pain medication prescriptions, as well as the lack of association between discharge opioid MED and probability of refill, indicates that efforts are needed to optimize opioid prescribing and reduce unnecessary healthcare variation.
Coding linguistic elements in clinical interactions: a step-by-step guide for analyzing communication form
Authors: Stortenbeker Inge , Salm Lisa , olde Hartman Tim , Stommel Wyke , Das Enny , van Dulmen Sandra 
Published: July 2022

AbstractBackgroundThe quality of communication between healthcare professionals (HCPs) and patients affects health outcomes. Different coding systems have been developed to unravel the interaction. Most schemes consist of predefined categories that quantify the content of communication (thewhat). Though the form (thehow) of the interaction is equally important, protocols that systematically code variations in form are lacking. Patterns of form and how they may differ between groups therefore remain unnoticed. To fill this gap, we present CLECI, Coding Linguistic Elements in Clinical Interactions, a protocol for the development of a quantitative codebook analyzing communication form in medical interactions.MethodsAnalyzing with a CLECI codebook is a four-step process, i.e. preparation, codebook development, (double-)coding, and analysis and report. Core activities within these phases are research question formulation, data collection, selection of utterances, iterative deductive and inductive category refinement, reliability testing, coding, analysis, and reporting.Results and conclusionWe present step-by-step instructions for a CLECI analysis and illustrate this process in a case study. We highlight theoretical and practical issues as well as the iterative codebook development which combines theory-based and data-driven coding. Theory-based codes assess how relevant linguistic elements occur in natural interactions, whereas codes derived from the data accommodate linguistic elements to real-life interactions and contribute to theory-building. This combined approach increases research validity, enhances theory, and adjusts to fit naturally occurring data. CLECI will facilitate the study of communication form in clinical interactions and other institutional settings.
Comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study using routine data of faecal calprotectin testing for inflammatory bowel disease
Authors: Freeman Karoline , Willis Brian H. , Ryan Ronan , Taylor-Phillips Sian , Clarke Aileen 
Published: July 2022

Abstract
Background
Meta-analyses of test accuracy studies may provide estimates that are highly improbable in clinical practice. Tailored meta-analysis produces plausible estimates for the accuracy of a test within a specific setting by tailoring the selection of included studies compatible with a specific setting using information from the target setting. The aim of this study was to validate the tailored meta-analysis approach by comparing outcomes from tailored meta-analysis with outcomes from a setting specific test accuracy study.

Methods
A retrospective cohort study of primary care electronic health records provided setting-specific data on the test positive rate and disease prevalence. This was used to tailor the study selection from a review of faecal calprotectin testing for inflammatory bowel disease for meta-analysis using the binomial method and the Mahalanobis distance method. Tailored estimates were compared to estimates from a study of test accuracy in primary care using the same routine dataset.

Results
Tailoring resulted in the inclusion of 3/14 (binomial method) and 9/14 (Mahalanobis distance method) studies in meta-analysis. Sensitivity and specificity from tailored meta-analysis using the binomial method were 0.87 (95% CI 0.77 to 0.94) and 0.65 (95% CI 0.60 to 0.69) and 0.98 (95% CI 0.83 to 0.999) and 0.68 (95% CI 0.65 to 0.71), respectively using the Mahalanobis distance method. The corresponding estimates for the conventional meta-analysis were 0.94 (95% CI 0.90 to 0.97) and 0.67 (95% CI 0.57 to 0.76) and for the FC test accuracy study of primary care data 0.93 (95%CI 0.89 to 0.96) and 0.61 (95% CI 0.6 to 0.63) to detect IBD at a threshold of 50 μg/g. Although the binomial method produced a plausible estimate, the tailored estimates of sensitivity and specificity were not closer to the primary study estimates than the estimates from conventional meta-analysis including all 14 studies.

Conclusions
Tailored meta-analysis does not always produce estimates of sensitivity and specificity that lie closer to the estimates derived from a primary study in the setting in question. Potentially, tailored meta-analysis may be improved using a constrained model approach and this requires further investigation.
Hepatitis C treatment outcomes for Australian First Nations Peoples: equivalent SVR rate but higher rates of loss to follow-up
Authors: Clark Paul J. , Valery Patricia C. , Ward James , Strasser Simone I. , Weltman Martin , Thompson Alexander , Levy Miriam T. , Leggett Barbara , Zekry Amany , Rong Julian , Angus Peter , George Jacob , Bollipo Steven , McGarity Bruce , Sievert William , Macquillan Gerry , Tse Edmund , Nicoll Amanda , Wade Amanda , Chu Geoff , Harding Damian , Cheng Wendy , Farrell Geoff , Roberts Stuart K. 
Published: July 2022

AbstractBackgroundFirst Nations Peoples of Australia are disproportionally affected by hepatitis C (HCV) infection. Through a prospective study we evaluated the outcome of direct-acting antiviral (DAA) therapy among First Nations Peoples with HCV infection.MethodsAdults who initiated DAA therapy at one of 26 hospitals across Australia, 2016–2019 were included in the study. Clinical data were obtained from medical records and the Pharmaceutical and Medicare Benefits Schemes. Outcomes included sustained virologic response (SVR) and loss to follow-up (LTFU). A multivariable analysis assessed factors associated with LTFU.ResultsCompared to non-Indigenous Australians (n = 3206), First Nations Peoples (n = 89) were younger (p < 0.001), morel likely to reside in most disadvantaged (p = 0.002) and in regional/remote areas (p < 0.001), and had similar liver disease severity. Medicines for mental health conditions were most commonly dispensed among First Nations Peoples (55.2% vs. 42.8%;p = 0.022). Of 2910 patients with follow-up data, both groups had high SVR rates (95.3% of First Nations Peoples vs. 93.2% of non-Indigenous patients;p = 0.51) and ‘good’ adherence (90.0% vs. 86.9%, respectively;p = 0.43). However, 28.1% of First Nations Peoples were LTFU vs. 11.2% of non-Indigenous patients (p < 0.001). Among First Nations Peoples, younger age (adj-OR = 0.93, 95% CI 0.87–0.99) and treatment initiation in 2018–2019 vs. 2016 (adj-OR = 5.14, 95% CI 1.23–21.36) predicted LTFU, while higher fibrosis score was associated with better engagement in HCV care (adj-OR = 0.71, 95% CI 0.50–0.99).ConclusionsOur data showed that First Nations Peoples have an equivalent HCV cure rate, but higher rates of LTFU. Better strategies to increase engagement of First Nations Peoples with HCV care are needed.