bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of lncRNA CBR3-AS1 for patients with cancer: A meta-analysis
Authors: Peng Jun , Wang Daidong , Liu Shixue 
Published: November 2024

Background:
Several studies have shown that the long noncoding RNA (lncRNA) CBR3-AS1 is overexpressed in various cancers and is playing an oncogene role. This meta-analysis aims to elucidate the relationship between lncRNA CBR3-AS1 expression and the prognosis and clinicopathological features of cancer patients.

Methods:
A comprehensive and systematic search was conducted in PubMed, Web of Science, Cochrane Library, and EMBASE database. Pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were employed to evaluate the association between lncRNA CBR3-AS1 expression and clinical outcomes and clinicopathological features in cancer patients.

Results:
This meta-analysis finally enrolled 9 studies comprising 800 cancer patients. The combined results indicated that lncRNA CBR3-AS1 overexpression was significantly associated with shorter overall survival (pooled hazard ratios = 1.69, 95% CI 1.28–2.21, P < .001). Furthermore, elevated lncRNA CBR3-AS1 expression was closely correlated with larger tumor size (large vs small OR = 2.17, 95% CI: 1.50–3.14, P < .0001), lymph node metastasis (yes vs no OR = 2.75, 95% CI: 1.67–4.51, P < .0001), distant metastasis (yes vs no OR = 3.08, 95% CI: 1.82–5.23, P < .0001), and advanced tumour, node, metastasis stage (III/IV vs I/II OR = 2.82, 95% CI: 1.68–4.75, P < .0001).

Conclusion:
Upregulated expression of lncRNA CBR3-AS1 showed significant association with unfavorable survival and indicated worse clinicopathological outcomes in multiple kinds of human cancer, and therefore might serve as a promising prognosis biomarker and therapeutic target for cancers.
Safety of baricitinib 24 weeks 4 mg or 2 mg for the treatment of rheumatoid arthritis: A meta-analysis of randomized controlled trials
Authors: Shi Zhihua , Cai Junlong , Yang Ling , Tang Lizhi , She Lang 
Published: November 2024

Backgrounds:
Baricitinib, an oral selective inhibitor of Janus kinase 1 and 2, is approved for moderate and severe rheumatoid arthritis (RA) with insufficient response to conventional synthetic disease-modifying antirheumatic drugs. The study evaluated the safety of baricitinib 24 weeks 4 mg or 2 mg for the treatment of RA.

Methods:
The net change (least squares mean [LSM]) of alanine aminotransferase (ALT), creatinine, low-density lipoprotein cholesterol (LDL-C) levels from baseline with the comparison of baricitinib versus placebo was pooled, respectively. The risk ratios (RR) of serious advanced events (SAEs), major cardiovascular events (MACEs), infection, serious infection, and advanced events (AEs) at the end of treatment across groups were compared.

Results:
Five randomized controlled trials with 2901 patients were included in the summary analysis. Results showed that baricitinib 4 mg significantly increased ALT and creatinine levels, the net LSM change was respectively 3.59 U/L with 95% confidence interval (CI) (1.75–5.43), 4.25 µmol/L with 95% CI (3.38–5.12), however, baricitinib 2 mg of ALT and creatinine levels were not significantly different. Baricitinib 4 mg and 2 mg significantly increased LDL-C levels, the net LSM change was respectively 11.44 mg/dL with 95% CI (6.08–16.80), 8.70 mg/dL with 95% CI (4.19–13.20). Baricitinib 4 mg significantly increased the incidence of infection, the pooled RR (95% CI) was 1.29 (1.13–1.47), and baricitinib 2 mg was not significantly different. However, the pooled RRs of SAEs, MACEs, and serious infection were not statistically significant across groups. The pooled RRs of AEs were not statistically significant between baricitinib 4 mg and 2 mg.

Conclusions:
This study confirmed that patients with RA taking 4 mg baricitinib increased levels of ALT, creatinine, as well as an increased risk of infections, compared with those taking 2 mg baricitinib. Both 2 mg and 4 mg also increased the level of LDL-C, but it increased the most severely at 4 mg baricitinib. However, the incidence of SAEs, MACEs, and serious infection was not significantly different in patients treated with baricitinib 4 mg and 2 mg compared with placebo, the incidence of AEs was not significantly different between baricitinib 4 mg and 2 mg.
Platelet-rich plasma: A bibliometric and visual analysis from 2000 to 2022
Authors: Du Kai , Li Ao , Zhang Chen-Yu , Guo Ren , Li Shu-Ming 
Published: November 2024

Background:
Platelet-rich plasma (PRP) is an integral biotherapeutic modality with evolving significance in the medical domain. Despite its expanding applications, a comprehensive bibliometric evaluation is essential to understand its development and impact.

Methods:
The Web of Science core collection subject search identified articles pertinent to PRP applications. Analytical tools, including CiteSpace, VOSviewer, Bibliometrix (R-Tool for R-Studio), TBtools, SCImago Graphica, Origin, and Excel, facilitated the bibliometric scrutiny. This examination spanned dimensions ranging from geographical and institutional contributions to thematic shifts and keyword prevalence.

Results:
A corpus of 5167 publications was analyzed, with the United States, particularly the Hospital for Special Surgery, emerging as major contributors. The American Journal of Sports Medicine was identified as the primary journal, and Anitua Eduardo as the leading author in the domain. Keyword analysis highlighted evolving research themes, with a shift from traditional applications in orthopedics and dentistry to emerging areas such as dermatology, aesthetics, and chronic pain management.

Conclusion:
The bibliometric analysis of PRP research reveals a multifaceted array of applications across various medical disciplines and highlights areas requiring further exploration, particularly in standardization, personalization, and safety. Future advancements in PRP research will necessitate innovative exploration, ethical considerations, and rigorous scientific validation to fully harness the therapeutic potential of PRP and related therapies.
The National Emergency Department Overcrowding Scale and Perceived Staff Workload
Authors: McKinley Kenneth W. , Bregstein Joan S. , Perotte Rimma , Fenster Daniel , Kwok Maria , Rose Jake , Nye Megan , Sonnett Meridith , Kessler David O. 
Published: November 2024

Objective
The aim of the study is to determine if there is a correlation between perceived staff workload, measured by the NASA Task Load Index (TLX), and the National Emergency Department Overcrowding Scale (NEDOCS) in a pediatric ED.

Methods
We collected staff questionnaires in a large, urban pediatric ED to assess perceived workload on each of six different TLX subscales, which we weighted evenly to create an overall estimate of workload. We evaluated the correlation between individual TLX responses and NEDOCS overall and by staff subgroup. Additionally, we analyzed: (1) the correlation between mean TLX responses and NEDOCS within a given hour and (2) the performance of a logistic regression model, using TLX as a predictor for “severely overcrowded,” as measured by NEDOCS.

Results
Four hundred one questionnaires between 6/2018 and 1/2019 demonstrated significant variation between concurrently collected TLX responses and an overall poor correlation between perceived workload and NEDOCS (R
2 0.096 [95% confidence interval, 0.048–0.16]). TLX responses by subgroups of fellows (n = 4, R
2 0.96) and patient financial advisors (n = 15, R
2 0.58) demonstrated the highest correlation with NEDOCS. Taking mean TLX responses within a given hour, during periods with NEDOCS >60 (extremely busy or overcrowded), a polynomial trend line matched the data best (R
2 0.638). On logistic regression, the TLX predicts “severely overcrowded” with an area under the curve of the receiver operating characteristic of 0.731.

Conclusions
NEDOCS does not have a strong correlation with individual responses on questionnaires of perceived workload for staff in a pediatric ED. NEDOCS, as a measure of overcrowding, may be better correlated with perceived workload during periods with elevated crowding or when interpreted categorically as yes/no “severely overcrowded”.
Immune Reconstitution After Total Parathyroidectomy and Forearm Transplantation in Chronic Renal Failure
Authors: Ren Tingting , Zhong Tao , Yang Fuhua , Liao Xuesong , Yang Mei , Ji Lingling , Guo Zonglin , Huang Jun 
Published: November 2024

Objective:
To investigate the immune reconstitution after total parathyroidectomy and forearm transplantation in chronic renal failure.

Method:
Forty-three patients, accompanied with chronic renal failure and secondary hyperparathyroidism (SHPT) that hospitalized during January 2019 to 2021 and underwent total thyroidectomy and forearm transplantation were enrolled as observation group. Forty hemodialysis patients with chronic renal failure but without SHPT were selected as the hemodialysis group. In addition, fifty volunteers who underwent physical examination within the same period were chosen as a control group. The parathyroid hormone (iPTH), blood phosphorus, blood calcium, th22, Treg cells, and inflammatory factors were detected in the three groups.

Results:
The preoperative iPHT, serum phosphorus, and calcium levels in the observation group were higher than those in the control group and hemodialysis group (P<0.05), and the index values of the observation group at each time point after surgery were remarkably lower than those in pre-surgery (P<0.05). The preoperative Th22 and Th22/Treg in the observation group were higher, and Treg was lower than those in the control group and hemodialysis group (P<0.05); The levels of Th22 and Th22/Treg in the observation group at each time point in post-operation were lower than those in pre-operation (P<0.05), whereas Treg cells in observation group at each time point postoperatively were higher than those prior-operation (P<0.05). The preoperative serum TNF-α, IL-6, TGF-β, and IL-22 in the observation group were notably higher than those in the control group and hemodialysis group (P<0.05); And TNF-α, IL-6, TGF-β, and IL-22 in observation group at each time point in post-operation were lower than those in pre-surgery(P<0.05).

Conclusion:
For chronic renal failure patients complicated with SHPT, total parathyroidectomy and forearm transplantation can effectively improve their clinical symptoms, reduce the inflammatory state of the body, and beneficial for immune reconstruction.
Competency, Proficiency, and Mastery
Authors: Müller Philip C. , Kuemmerli Christoph , Billeter Adrian T. , Shen Baiyong , Jin Jiabin , Nickel Felix , Guidetti Cristiano , Kauffmann Emanuele , Purchla Julia , Tschuor Christoph , Krohn Paul Suno , Burgdorf Stefan K. , Jonas Jan Philipp , Bussmann Felix J. , Saint-Marc Olivier , Iben-khayat Abdallah , Andel Paul C.M. , Molenaar Izaak Quintus , Wellner Ulrich , Keck Tobias , Moeckli Beat , Toso Christian , Di Benedetto Fabrizio , Valle Valentina , Giulianotti Pier , Roulin Didier , Martinie John B. , Rama Martina , Lavu Harish , Yeo Charles , Mavani Parit T. , Shah Mihir M. , Kooby David A. , He Jin , Boggi Ugo , Hackert Thilo , Borel-Rinkes Inne H.M. , Müller Beat P. , Clavien Pierre-Alain 
Published: November 2024

Objective:
The aim of this study was to evaluate the different phases of the learning curve for robotic distal pancreatectomy (RDP) in international expert centers.

Summary Background Data:
RDP is an emerging minimally invasive approach; however, only limited, mostly single center data are available on its safe implementation, including the learning curve.

Methods:
Consecutive patients undergoing elective RDP from 16 expert centers across three continents were included to assess the learning curve. Based on the first 100 RDPs at each center, three cutoffs were used to define the learning curve: operative time for competency, major complications (Clavien–Dindo grade ≥III) for proficiency, and textbook outcome for mastery. Clinical outcomes before and after the cutoffs were compared.

Results:
The learning curve analysis was conducted on 1109 of 2403 RDPs. Competency, proficiency, and mastery, respectively, were reached after 46, 63, and 73 RDP procedures. After competency, operative time decreased from 245 to 235 minutes (P=0.002). Attaining proficiency was reflected by a reduction in the rate of major complications from 20% to 15% (P=0.012), and mastery was associated with a higher proportion of patients with textbook outcome (71% vs. 63%; P=0.028). The postoperative pancreatic fistula rate remained stable along the learning curve, ranging between 18.5% and 21.5%. Previous laparoscopic experience accelerated the learning process by virtue of reduced operative time and an earlier decrease in major complications.

Conclusion:

Competency, proficiency, and mastery for RDP were reached after 46, 63, and 73 procedures, respectively, at international expert centers. The findings highlight that the learning curves for intraoperative parameters are completed earlier; however, extensive experience is needed to master RDP.
Exploring the druggability of the UEV domain of human TSG101 in search for broad-spectrum antivirals
Authors: Montero Fernando , Parra-López Marisa , Rodríguez-Martínez Alejandro , Murciano-Calles Javier , Buzon Pedro , Han Ziying , Lin L.-Y. , Ramos Maria C. , Ruiz-Sanz Javier , Martinez Jose C. , Radi Marco , Moog Christiane , Diederich Sandra , Harty Ronald N. , Pérez-Sánchez Horacio , Vicente Francisca , Castillo Francisco , Luque Irene 
Published: November 2024

AbstractThe ubiquitin E2 variant domain of TSG101 (TSG101-UEV) plays a pivotal role in protein sorting and virus budding by recognizing PTAP motifs within ubiquitinated proteins. Disruption of TSG101-UEV/PTAP interactions has emerged as a promising strategy for the development of host-oriented broad-spectrum antivirals with low susceptibility to resistance. TSG101 is a challenging target characterized by an extended and flat binding interface, low affinity for PTAP ligands, and complex binding energetics. Here, we assess the druggability of the TSG101-UEV/PTAP binding interface by searching for drug-like inhibitors and evaluating their ability to block PTAP recognition, impair budding, and inhibit viral proliferation. A discovery workflow was established combining in vitro miniaturized HTS assays and a set of cell-based activity assays including high-content bimolecular complementation, virus-like particle release measurement, and antiviral testing in live virus infection. This approach has allowed us to identify a set of chemically diverse molecules that block TSG101-UEV/PTAP binding with IC50s in the low μM range, and able to disrupt the interaction between full-length TSG101 and viral proteins in human cells and inhibit viral replication. State-of-the-art molecular docking studies reveal that the active compounds exploit binding hotspots at the PTAP binding site, unlocking the full binding potential of the TSG101-UEV binding pockets. These inhibitors represent promising hits for the development of novel broad-spectrum antivirals through targeted optimization and are also valuable tools for investigating the involvement of ESCRT in the proliferation of different virus families and study the secondary effects induced by the disruption of ESCRT/virus interactions.ImportanceMany viruses rely on the interaction between TSG101 and viral proteins containing PTAP motifs for their proliferation. Here we show that these interactions can be efficiently blocked by drug-like compounds that impair budding and replication of viruses from different families. We have also provided valuable insights into the determinants of high affinity for these small molecule inhibitors that open new avenues for developing the identified candidates into broad-spectrum antivirals with low susceptibility to resistance.
WITHDRAWN: Significantly enhancing antiviral efficacy by computational optimization and structural engineering of grafted nanobodies
Authors: Huo Liyun , Qin Qin , Tian Tian , Zhang Xing , He Xiaoming , Cao Yuhui , Zhang Tianfu , Xu Yanqin , Huang Qiang 
Published: November 2024

Withdrawal StatementThe authors have withdrawn this manuscript because of incorrect figure legends and some typos in the main text. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Physically Interpretable Performance Metrics for Clustering
Authors: Mondal Kinjal , Klauda Jeffery B. 
Published: November 2024

AbstractClustering is a type of machine learning (ML) technique which is used to group huge amounts of data based on their similarity into separate groups or clusters. Clustering is a very important task which is nowadays used to analyze the huge and diverse amount of data coming out of molecular dynamics (MD) simulations. Typically, the data from the MD simulations in terms of their various frames in the trajectory are clustered into different groups and a representative element from each group is studied separately. Now a very important question coming in this process is what is the quality of the clusters that are obtained. There are several performance metrics that are available in literature like Silhouette index and Davies-Bouldin Index that are often used to analyze the quality of clustering. However, most of these metrics focus on the overlap or the similarity of the clusters in the reduced dimension that is used for clustering and do not focus on the physically important properties or the parameters of the system. To address this issue, we have developed two physically interpretable scoring metrics that focus on the physical parameters of the system that we are analyzing. We have used and tested our algorithm on three different systems (1) Ising model, (2) peptide folding and unfolding of WT HP35, (3) a protein-ligand trajectory of an enzyme and substrate and (4) a protein-ligand dissociated trajectory. We show that the scoring metrics provide us clusters that match with our physical intuition about the systems.
Phenome-wide causal proteomics enhance systemic lupus erythematosus flare prediction: A study in Asian populations
Authors: Chen Liying , Deng Ou , Fang Ting , Chen Mei , Zhang Xvfeng , Cong Ruichen , Lu Dingqi , Zhang Runrun , Jin Qun , Wang Xinchang 
Published: November 2024

AbstractObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by unpredictable flares. This study aimed to develop a novel proteomics-based risk prediction model specifically for Asian SLE populations to enhance personalized disease management and early intervention.MethodsA longitudinal cohort study was conducted over 48 weeks, including 139 SLE patients monitored every 12 weeks. Patients were classified into flare (n = 53) and non-flare (n = 86) groups. Baseline plasma samples underwent data-independent acquisition (DIA) proteomics analysis, and phenome-wide Mendelian randomization (PheWAS) was performed to evaluate causal relationships between proteins and clinical predictors. Logistic regression (LR) and random forest (RF) models were used to integrate proteomic and clinical data for flare risk prediction.ResultsFive proteins (SAA1, B4GALT5, GIT2, NAA15, and RPIA) were significantly associated with SLE Disease Activity Index-2K (SLEDAI-2K) scores and 1-year flare risk, implicating key pathways such as B-cell receptor signaling and platelet degranulation. SAA1 demonstrated causal effects on flare-related clinical markers, including hemoglobin and red blood cell counts. A combined model integrating clinical and proteomic data achieved the highest predictive accuracy (AUC = 0.769), surpassing individual models. SAA1 was highlighted as a priority biomarker for rapid flare discrimination.ConclusionThe integration of proteomic and clinical data significantly improves flare prediction in Asian SLE patients. The identification of key proteins and their causal relationships with flare-related clinical markers provides valuable insights for proactive SLE management and personalized therapeutic approaches.Graphical Abstract
A PRDM16-CtBP1/2 Complex Interacts with HDAC1/2 to Regulate Transcriptional Programs of Neurogenesis and Guide Cortical Neuron Migration
Authors: Warren Sophie , Farran Bader El , Kang Sungyun , Choudhuri Adhyeta , Xiong Sen , Brendel Volker P. , Baizabal José-Manuel 
Published: November 2024

ABSTRACTChromatin regulation of transcriptional enhancers plays a central role in cell fate specification and differentiation. However, how the coordinated activity of transcription factors and chromatin-modifying enzymes regulates enhancers in neural stem cells (NSCs) and dictates subsequent stages of neuronal differentiation and migration is not well understood. The histone methyltransferase PRDM16 is expressed in NSCs of the developing mouse and human cerebral cortex and is essential for determining the position of upper-layer cortical neurons. Here, we report that PRDM16 interacts with C-terminal binding protein 1 (CtBP1) and CtBP2 to control the transcriptional programs of cortical neurogenesis and regulate upper-layer neuron migration. PRDM16 and CtBP1/2 co-regulate enhancers by interacting with histone deacetylase 1 (HDAC1) and HDAC2, and lysine-specific demethylase 1 (LSD1). In addition, our results suggest that the CCCTC-binding factor CTCF plays a key role in recruiting CtBP1/2 to cortical enhancers. These findings underscore that reduced interactions between PRDM16 and ubiquitous chromatin regulators may contribute to neurodevelopmental deficits in patients withPRDM16haploinsufficiency.
Advancing Remote and Low-Resource Healthcare Delivery with Microbiopsy Skin Sample mRNA Housekeeping Gene Stability Analysis Across Various Temperatures
Authors: Nataren Nathalie , Gunnell Lucy , Prow Tarl W , Yamada Miko 
Published: November 2024

AbstractIn the clinical dermatology setting, conventional skin sampling methods such as punch, shave, or excision biopsy are invasive, requiring local anesthesia and after-procedure care. These methods also necessitate immediate processing and cold storage to preserve high-quality nucleic acid, limiting their use in remote and low-resource regions. The microbiopsy, a minimally invasive device designed for sub-millimetre skin sampling, offers an alternative that may overcome these limitations by providing genetic profiles from the viable epidermis.We examined skin patient samples (5 microbiopsies, 3 individuals) stored across five conditions temperature conditions expected to be encountered during commercial shipping. RNA was extracted for TaqMan assay Real-Time PCR on the Fluidgim Dynamic Array targeting three housekeeping genes (ACTB, GAPDH, and RPLP0). Housekeeping genes were successfully detected at comparable levels in samples across non-control conditions, contrasting with positive control samples which showed a trend toward lower gene expression detection.In conclusion, we have established that microbiopsy samples stored in the RNA preservation agent can withstand uncontrolled temperatures likely to be encountered during commercial shipping. This could have a significant impact on enabling access to molecular diagnostic testing in an era of increasing personalized medicine and to address the long-standing need to improve remote healthcare delivery.