bluuebunny/crossref_metadata_2025_split huggingface dataset:
Examination of Risk Factors Affecting the Development of BSI and Mortality in Critically Ill COVID-19 Patients Hospitalized in Intensive Care Unit (ICU): A Single-Center Retrospective Study
Authors: Keskin Sarıtaş Çağla , Özsüt Halit , Benli Aysun , Başaran Seniha 
Published: December 2024

Background Various studies have shown that the incidence of BSI is greater in COVID-19 patients hospitalized in the intensive care unit (ICU). Aims Our study aimed to determine the risk factors for BSI, mortality rates, and factors affecting mortality in adult COVID-19 patients hospitalized in the ICU. Methods All COVID-19 patients who met the study criteria and stayed in intensive care for more than 2 days at a tertiary university hospital during the two-year pandemic period were included in the study. Logistic regression analysis was used to determine the risk factors for BSI and mortality. Results We found that respiratory rate (RR) ≥ 30 breaths per minute at the time of admission [OR: 2.342 (95% CI: 1.12-4.897)] and antibiotic use in the month before admission ICU [OR: 3.137 (95% CI: 1.321-7.451)] were independent risk factors for BSI in COVID-19 patients. Subanalysis was also performed according to the doses of immunomodulators such as anakinra, tocilizumab, and corticosteroids, and it was found that they had no effect on the BSI ( P > .05). The predominant causative pathogens were K. pneumoniae, A. baumannii and enterococci. The multidrug resistant rate among bacteria was 78%. Although their comorbidities and disease severity at the time of ICU admission were similar, patients with BSIs had a higher mortality rate (58.1 to 81.9%, P = .000). The SAPS-2 score at ICU admission [OR: 3.095 (95% CI: 1.969-4.865)] and mechanical ventilation requirement throughout the ICU admission [OR: 9.314 (95% CI: 3.878-22.37)] were found to be independent risk factors for mortality by multivariate analysis. BSI was not found to be a risk factor for mortality (> .05). Conclusions Antibiotic use in patients with severe COVID-19 significantly increases the risk of BSI; unnecessary antibiotic use should be avoided.
Effectiveness of Tuina massage combined with conventional treatment in improving post-stroke spasticity: A meta-analysis
Authors: Liu Di , Zhang Ding-ruo , Yu Tian-yuan , Guo Sheng , Xue Xiao-na , Hu Hui , Liu Jia-yue , Xu Yue , Na Ren-tuya 
Published: December 2024

Background Post-stroke spasticity (PSS) is a common complication that affects recovery and quality of life. Traditional rehabilitation approaches may benefit from complementary therapies. Objective This study aims to evaluate the efficacy of Tuina massage combined with conventional treatment for PSS through a meta-analysis, providing a scientific basis for clinical decision-making and future research directions. Method A literature search was conducted across both English-language (PubMed, Embase, Cochrane, Web of Science) and Chinese-language (CNKI, Wanfang, VIP) databases. Inclusion criteria were limited to randomized controlled trials. Data analysis was performed using Cochrane Collaboration's Review Manager 5.3 and Stata 12.0 software, with detailed inclusion and exclusion criteria and quality assessment using the Jadad scoring system. Results Eighteen studies met the inclusion criteria, involving 1937 patients treated with various Tuina techniques alone or in combination with other therapies. Results indicated that Tuina significantly improved symptoms and quality of life, with the Tuina treatment group outperforming the control group in the Modified Ashworth Scale (MAS), Modified Barthel Index (MBI), and Fugl–Meyer Assessment (FMA). Conclusion This meta-analysis demonstrates that Tuina massage combined with conventional treatment significantly reduces PSS severity and enhances functional abilities and quality of life, highlighting its potential integration into rehabilitation programs for comprehensive PSS management.
Shelters in Alpine Rescue: Can They Create a Comfortable Zone at the Deployment Site?
Authors: Troeger Willi , Winkler Manuel , Isser Markus , Lederer Wolfgang 
Published: December 2024

Introduction Lightweight shelters made of water- and windproof polyester are frequently used by mountain rescue, but information on physical and psychological stress during their use is scarce. Methods A prospective observational study was conducted with 48 experienced rescuers who performed cardiopulmonary resuscitation training on a manikin in a shelter in alpine terrain. The objective parameters of air temperature, moisture, and concentrations of carbon dioxide and oxygen were measured inside the shelter. The subjective experience of the rescuers regarding stress, moisture, noise, air draft, convenience, spatial confinement, brightness, room temperature, and air quality was assessed using a questionnaire. Results During 15 min of cardiopulmonary resuscitation, the median temperature in the shelter rose by >15°C (Δ t, 15.9°C; interquartile range, 14.3–16.5°C; P=0.018). Carbon dioxide concentrations increased to 0.97 vol% maximum. Bag valve mask ventilation was established with and without the use of supplemental oxygen, which showed significantly different oxygen shelter concentrations (21.1 vol% with oxygen, 20.6 vol% without oxygen; P<0.001). Most participants rated the physical comfort and spatial conditions inside the shelter as convenient. Conclusions In this study, the use of shelters in alpine terrain improved physical comfort while carrying out a rescue. Most participants gave high ratings for the working conditions in the shelter.
Healthcare providers’ use of dashboards with patient reported outcomes reinforces patients to fill out patient reported outcome measures
Authors: Pasma Annelieke , van Lint Céline , Hollander Monique Ardon-den , Bruinsma Sophie M. , Peters Ingrid A. 
Published: December 2024

Background Patient reported outcomes are used to assess the impact of medical interventions on perceived health in both clinical trials and daily care. Further, patient-reported outcome measures (PROMs) optimize the consultation. However, patient completion of PROMs before their consultation, and healthcare provider's (HCP) use of PROMs in their consultation are suboptimal. In this cross-sectional study, we examined whether viewing a PROM dashboard before or during consultation consecutively resulted in higher patient completion of PROMs. Methods As part of regular care, patients were asked to fill out PROMs prior their consultation. HCPs’ dashboard views were logged. A chi-square test was performed on dashboard viewed (yes/no) with consecutively filling out PROMs (yes/no). The odds ratio (OR) of consecutively filling out PROMs after a dashboard view was calculated. Results 38.016 consecutive appointments were linked to a previous appointment in which a dashboard could be viewed. In 2740 cases, a dashboard was viewed by the HCP, against 35.276 cases in which a dashboard was not viewed. Follow-up adherence in completing PROMs was 49%. The chi-square test showed statistical significance of p < .001. The OR of filling out a consecutive PROM when a dashboard was viewed was 3.16 ( p < .001, 95% CI [2.9–3.5]). Discussion Patients are more likely to complete PROMs for their follow-up appointment when an HCP has viewed PROMs during or before consultation. HCPs should be aware of their responsibility in addressing PROMs, because using PROMs in consultation does not only have a positive effect on communication, but also on patient completion of PROMs.
Clinical concept annotation with contextual word embedding in active transfer learning environment
Authors: Abbas Asim , Lee Mark , Shanavas Niloofer , Kovatchev Venelin 
Published: December 2024

Objective The study aims to present an active learning approach that automatically extracts clinical concepts from unstructured data and classifies them into explicit categories such as Problem, Treatment, and Test while preserving high precision and recall and demonstrating the approach through experiments using i2b2 public datasets. Methods Initially labeled data are acquired from a lexical-based approach in sufficient amounts to perform an active learning process. A contextual word embedding similarity approach is adopted using BERT base variant models such as ClinicalBERT, DistilBERT, and SCIBERT to automatically classify the unlabeled clinical concept into explicit categories. Additionally, deep learning and large language model (LLM) are trained on acquiring label data through active learning. Results Using i2b2 datasets (426 clinical notes), the lexical-based method achieved precision, recall, and F1-scores of 76%, 70%, and 73%. SCIBERT excelled in active transfer learning, yielding precision of 70.84%, recall of 77.40%, F1-score of 73.97%, and accuracy of 69.30%, surpassing counterpart models. Among deep learning models, convolutional neural networks (CNNs) trained with embeddings (BERTBase, DistilBERT, SCIBERT, ClinicalBERT) achieved training accuracies of 92–95% and testing accuracies of 89–93%. These results were higher compared to other deep learning models. Additionally, we individually evaluated these LLMs; among them, ClinicalBERT achieved the highest performance, with a training accuracy of 98.4% and a testing accuracy of 96%, outperforming the others. Conclusions The proposed methodology enhances clinical concept extraction by integrating active learning and models like SCIBERT and CNN. It improves annotation efficiency while maintaining high accuracy, showcasing potential for clinical applications.
Predictors and Early Treatment of Knee Arthrofibrosis After Arthroscopic Knee Ligament Reconstruction Surgery in Adolescent Patients
Authors: Marquez-Lara Alejandro , Padget William , Wall Eric J. , Parikh Shital N. 
Published: December 2024

Background: Postoperative knee arthrofibrosis after arthroscopic ligament reconstruction is a serious complication. Among adolescents, risk factors for postoperative arthrofibrosis are not well characterized and the effectiveness of early manipulation under anesthesia (MUA) is not well established. Purposes: To identify risk factors for arthrofibrosis after arthroscopic knee ligament reconstruction in adolescent patients and to evaluate the safety and effectiveness of early MUA. Study Design: Case-control study; Level of evidence, 3. Methods: The charts of all adolescent patients (<19 years of age) who underwent early MUA (<3 months) for knee stiffness after anterior cruciate ligament (ACL) or medial patellofemoral ligament (MPFL) reconstructions between 2008 and 2021 were retrospectively reviewed. Patients were matched 2:1 with patients without MUA from the same study period. The primary outcome was the final range of motion (ROM) after MUA. Logistic regression analysis was performed to identify predictors of MUA. Results: A total of 25 patients (10 with ACL reconstruction and 15 with MPFL reconstruction) with a mean age of 14.8 ± 2.6 years were included for analysis. Overall, 44% were skeletally immature. Patients underwent MUA at a mean of 63.3 ± 19.5 days after the index surgery. The mean ROM improved significantly from 96.3°± 20.5° to 135°± 9.7° after MUA after a median follow-up of 8.1 months (interquartile range, 5.4-15.0 months). There were no complications associated with MUA, but 2 patients (8.0%) had MUA treatment failure. There were no differences in body mass index, type and frequency of associated procedures, or patellar height on lateral radiographs between the cohorts. The MUA cohort had statistically significant increased operative time, decreased preoperative motion, decreased ROM at 6 weeks postoperatively, and increased pain at 6 weeks postoperatively when compared with the non-MUA cohort. Regression analysis demonstrated that ROM at 6 weeks (OR: 0.83, 95% CI, 0.69-0.98, p = .034) was significantly associated with the need for MUA. Conclusion: The findings of this study suggest that early (<3 months) MUA is safe and effective in treating knee arthrofibrosis in adolescent patients. MUA is a treatment alternative for patients with restricted ROM at 6 weeks that may help them recover full ROM.
Beneficial effects of mineral water with human-like electrolytic content in a pre-clinical model of vascular inflammaging
Authors: Benvenuti Laura , D’Antongiovanni Vanessa , Di Salvo Clelia , Valdiserra Giulia , Masi Stefano , Mengozzi Alessandro , Duranti Emiliano , Pellegrini Carolina , Fornai Matteo , Antonioli Luca 
Published: December 2024

Background The term “inflammaging” has been introduced to describe the chronic, low-grade inflammatory process associated with the increase in age and the senescence of the immune system, that confers susceptibility to suffering age-related pathologies. In this context, previous studies have already demonstrated that the regular consumption of mineral water can be a valuable tool for detoxifying the body from reactive oxygen species (ROS) and for mitigating the systemic inflammation. Objective Herein, we tested the beneficial effects of a mineral water with human-like electrolytic content (San Carlo® water) in a pre-clinical model of vascular inflammaging and investigated the mechanisms underlying this effect. San Carlo® water was administered ad libitum to both young (10-week old) and aged rats (40-week old) for 3 months. Methods Vascular functionality, oxidative stress (fluorescent dye dihydroethidium assay, levels of MDA, and levels of 8-isoprostanes in the urine), and systemic inflammation (levels of IL-1β and TNF) were assessed. Results San Carlo® water ingestion mitigated the inflammation by reducing TNF plasma levels and improved endothelial-dependent vasorelaxation, acting against ROS production. Conclusion The present study suggests that the use of San Carlo® water can effectively counteract the low-grade inflammation typically associated with age and the related vascular dysfunction, likely through both antioxidant and anti-inflammatory properties.
A Phase 2, Double-blind, Randomized, Placebo-Controlled Study to Assess Collagenase Clostridium Histolyticum vs Placebo in Patients With Plantar Fibromatosis
Authors: James Anderson C. , Gottlieb Ira , Levy Jason , El-Amin Saadiq , Suttle Sara , Tursi James , Jones Nigel , Ortega Luis A. , Zhou Gongfu , Caporusso Joseph 
Published: December 2024

Category: Midfoot/Forefoot; Basic Sciences/Biologics Introduction/Purpose: Collagenase clostridium histolyticum (CCH), a nonsurgical treatment approved for Peyronie’s disease and Dupuytren’s contracture, is being investigated for plantar fibromatosis (PFI), or Ledderhose disease, a rare disorder characterized by benign, slow-growing, collagen-containing nodules along the foot’s medial or central plantar fascia. Here, we report on safety and efficacy results of a multicenter phase 2b randomized, placebo-controlled trial (NCT05152173). Methods: Multicenter patients with PFI, at least one “moderately firm” to “hard” nodule causing pain were randomized 1:1 to CCH treatment or placebo. The primary endpoint was mean change in pain from baseline to Day 57 via the Foot Function Index (FFI)-Pain subscale. Secondary outcomes included the Clinical Global Impression of Change (CGIC) scale and changes in nodule hardness (by durometer) and consistency (firmness by palpation). Outcomes were analyzed by ANCOVA and MMRM from baseline to Day 57. Results: A total of 166 subjects (83 CCH, 83 placebo) completed the study. At Day 57, the mean FFI-Total subscale Pain score trended toward improvement in both groups; however, the difference was not statistically significant (Figure-1a) (least squares mean [LSM] difference, -1.427; 95% CI -3.985 to 1.131; P=0.274). The CGIC showed there were 14.8% more responders in the CCH group vs placebo (P=0.044). Also, statistically significant improvements occurred in nodule hardness (Figure-1b) (LSM difference, -5.877; P=0.020) and consistency (22.4% more responders; P=0.002) between the CCH group and placebo, favoring CCH treatment. Similar to other approved CCH indications, common treatment-related or -emergent adverse events (AEs) were injection site pain, bruising, and swelling. There were no deaths, serious AEs, or study withdrawals in the CCH treatment group. Conclusion: As this trial demonstrated a trend in treatment effect for the primary endpoint with some secondary endpoints illustrating a significant treatment benefit versus placebo, an appropriately powered pivotal phase 3 trial is underway. Figure 1. Mean Change From Baseline to Day 57 on FFI-Total Pain Subscale Score (a) and Nodular Hardness by Durometer (b).
A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies
Authors: Davids Matthew S. , Brander Danielle M. , Alvarado-Valero Yesid , Diefenbach Catherine S. , Egan Daniel N. , Dinner Shira N. , Javidi-Sharifi Nathalie , Al Malki Monzr M. , Begna Kebede H. , Bhatt Vijaya Raj , Abedin Sameem , Cook Rachel J. , Collins Mary C. , Roleder Carly , Dominguez Edward C. , Rajagopalan Prabhu , Wiley Sandra E. , Ghalie Richard G. , Danilov Alexey V. 
Published: December 2024

Abstract
The antiapoptotic protein, myeloid cell leukemia-1 (Mcl-1), contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models. This dose escalation study evaluated voruciclib in patients with previously treated hematologic malignancies. Initially, voruciclib was administered daily, continuously, on a 28-day cycle (group 1). After 2 patients with prior allogeneic stem cell transplantation had a dose-limiting toxicity (DLT) of interstitial pneumonitis at 100 mg, voruciclib administration was changed to days 1 to 14 of a 28-day cycle (group 2). Forty patients, 21 with AML and 19 with B-cell malignancies, were enrolled. Patients had a median of 3 prior lines of therapy (range, 1-8). Dose escalation in group 2 was stopped at 200 mg, a dose that achieved plasma concentrations sufficient for target inhibition, without DLTs observed. The most common adverse events were diarrhea (30%), nausea (25%), anemia (22%), fatigue (22%), constipation (17%), dizziness (15%), and dyspnea (15%). In AML, 1 patient achieved a morphologic leukemia-free state, and 2 had stable disease. Voruciclib treatment led to a decrease in MCL1 messenger RNA expression, downregulation of myelocytomatosis (MYC) and NF-κB transcriptional gene sets, and reduced phosphorylation of RNA polymerase 2. Voruciclib on intermittent dosing was well tolerated, with no DLTs, paving the way for evaluation of the combination of voruciclib with venetoclax for patients with previously treated AML. This trial was registered at www.clinicaltrials.gov as #NCT03547115.
CGREF1 modulates osteosarcoma proliferation by regulating the cell cycle through the Wnt/β-catenin signaling pathway
Authors: Wei Zicheng , Xia Kezhou , Liu Wenda , Huang Xinghan , Wei Zhun , Guo Weichun 
Published: December 2024

Abstract
Background
Osteosarcoma, the most prevalent primary bone malignancy in children and adolescents, exhibits high heterogeneity. The CGREF1 gene encodes a novel 301 amino acid classical secreted protein that contains the presumed N-terminal signaling peptide and EF hand motif. However, its role in osteosarcoma remains unclear.

Methods
Tumor Immune Estimation Resource (TIMER), The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized for bioinformatics analysis. Western blot and immunohistochemistry (IHC) techniques were employed to detect the expression of relevant proteins. siRNA, lentivirus, and plasmid technologies were applied to modulate gene expression. The downstream pathway of CGREF1 was identified through RNA sequencing analysis. Cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, wound healing assay, and Transwell assay were conducted for in vitro functional experiments. In vivo experiments involved subcutaneous tumor formation in nude mice.

Results
Our analysis of public databases and clinical samples revealed that CGREF1 is highly expressed in osteosarcoma and is associated with poor prognosis. Knockdown of CGREF1 impeded cell cycle progression and suppressed the proliferation of osteosarcoma cells. Conversely, upregulation of CGREF1 exhibited an opposing pattern. The RNA-seq data from 143B cells was subjected to analysis, revealing that the differentially expressed genes were predominantly enriched in the Wnt signaling pathway. Further experimental results demonstrated that CGREF1 affects activation of the Wnt pathway by regulating GSK3/β-catenin signaling, thereby affecting proliferation ability of osteosarcoma cells. Finally, experiments using subcutaneous transplanted tumor models in nude mice showed that CGREF1 knockdown inhibited tumor growth in vivo by inhibiting the Wnt/β-catenin signaling pathway.

Conclusion
The expression of CGREF1 was significantly upregulated in osteosarcoma and correlated with unfavorable prognosis. CGREF1 exerted a regulatory effect on the proliferation of osteosarcoma cells both in vitro and in vivo through modulation of the wnt/β-catenin signaling pathway. In the future, targeting CGREF1 could potentially offer a novel therapeutic strategy for treating osteosarcoma.
CXCL4 deficiency limits M4 macrophage infiltration and attenuates hyperoxia-induced lung injury
Authors: Yu Bingrui , Jia Siyuan , Chen Yu , Guan Rong , Chen Shuyu , Tang Wanwen , Bao Tianping , Tian Zhaofang 
Published: December 2024

Abstract
Background
Bronchopulmonary dysplasia (BPD), a chronic lung disease prevalent among premature infants, significantly impacts lifelong respiratory health. Macrophages, as key components of the innate immune system, play a role in lung tissue inflammation and injury, exhibiting diverse and dynamic functionalities. The M4 macrophage, a distinctive subtype primarily triggered by chemokine (C-X-C motif) ligand 4 (CXCL4), has been implicated in pulmonary inflammatory and fibrotic processes. Nonetheless, its contribution to the pathophysiology of BPD remains uncertain.

Objective
This study aimed to elucidate the involvement of CXCL4 in hyperoxia-induced neonatal lung injury and fibrosis, with a particular focus on its influence on M4 macrophages.

Methods
A BPD model in neonatal mice was established through continuous exposure to 95% O2 for 7 days. Comparative analyses of lung damage and subsequent regeneration were conducted between wild-type (WT) and CXCL4 knockout (KO) mice. Lung tissue inflammation and fibrosis were assessed using histological and immunofluorescence staining, enzyme-linked immunosorbent assay, Western blot, and real-time quantitative polymerase chain reaction. Differentiation of M0 and M4 macrophages was performed in vitro using macrophage colony-stimulating factor and CXCL4, while expressions of S100A8 and MMP7, along with migration assays, were evaluated.

Results
Elevated CXCL4 levels and M4 macrophage activation were identified in the lung tissue of BPD model mice. CXCL4 deficiency conferred protection to alveolar type 2 epithelial cells, reduced sphingosine-1-phosphate metabolic activity, mitigated pulmonary fibrosis, and limited M4 macrophage progression. This deletion further enhanced lung matrix remodeling during recovery. In vitro, CXCL4 promoted M4 macrophage differentiation and increased macrophage migration via chemokine (C-C motif) receptor 1.

Conclusion
CXCL4 contributes to hyperoxia-induced lung injury and fibrosis through modulation of cytokine release, alveolar cell proliferation, lipid metabolism, and the regulation of macrophage phenotype and function.