bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating Length of Stay Patterns and Its Predictors in the South Wales Trauma Network
Authors: Wang Zihao , Rostami-Tabar Bahman , Haider Jane , Naim Mohamed , Haider Javvad 
Published: March 2024

Background: Length of stay (LOS) is frequently employed as a performance metric for trauma care. Following the establishment of the trauma network worldwide, the assessment and prediction of LOS in different levels of trauma centres have been extensively studied. However, assessing the total patient length of stay from a whole trauma network perspective is unclear. The objective of this study was to systematically analyse the overall Length of Stay (LOS) pattern within the SWTN before its establishment and in the immediate time after its foundation and, secondly, to assess the association between relevant impact factors and LOS. Methodology: A retrospective secondary analysis based on the trauma admission dataset from Trauma Audit and Research Network(TARN) dataset was conducted. The studied sample covered around 18000 patients admitted to trauma centres from South Wales Major trauma network between January 2012 and October 2021. The primary outcome is the total length of stay in the trauma network. Statistical tests were applied to examine the difference between normal and outlier LOS. Data visualisation was utilised to demonstrate the LOS patterns and potential association between LOS and relevant demographic and clinical predictors. Results: The distribution of length of stay in SWTN follows a right-skewed distribution with a median of 10 (IQR, 5–18) and a mean of 15.92 days. There were 1520 patients with outliers for LOS. A significant difference (p¡ 0.05) was found between the normal and outlier groups of LOS based on demographic (age, gender and residential information) and clinical characteristics(ward type, maximum of anatomically-based injury severity score(AIS) and probability of survival). Age group, maximum AIS score on specific injured region, ward type and its interaction effect with the number of admissions may associated with the LOS. Specifically, patients admitted to the geriatric ward exhibited notably prolonged LOS, and individuals with more than 2 admissions to long-term care and recovery-related wards such as neurosurgical rehabilitation, spinal injuries and burns wards also displayed elevated LOS. Conclusion: Our finding supports prior evidence indicating elderly people are vulnerable to longer stays. Moreover, concerning the types of admission wards, patients admitted to rehabilitation wards who underwent more than 2 hospitalisations also faced an increased risk of prolonged stay. Based on these results, policymakers and healthcare providers should contemplate expanding the allocation of medical resources to this demographic to mitigate the length of stay and optimise associated healthcare costs.
Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib
Authors: Moslehi Javid J. , Furman Richard R. , Tam Constantine S. , Salem Joe-Elie , Flowers Christopher R. , Cohen Aileen , Zhang Meng , Zhang Jun , Chen Lipeng , Ma Han , Brown Jennifer R. 
Published: March 2024

Abstract
First-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been associated with an increased risk of cardiovascular toxicities. Zanubrutinib is a more selective, next-generation BTK inhibitor. In this analysis, incidence rates of atrial fibrillation, symptomatic (grade ≥2) ventricular arrhythmia, and hypertension were evaluated in a pooled analysis of 10 clinical studies with zanubrutinib monotherapy in patients (N = 1550) with B-cell malignancies and a pooled analysis of head-to-head studies comparing zanubrutinib with ibrutinib (ASPEN cohort 1; ALPINE). Among the 10 studies, most patients (median age, 67 years) were male (66.3%) and had CLL/SLL (60.5%). Overall incidence and exposure-adjusted incidence rates (EAIR) for atrial fibrillation, symptomatic ventricular arrhythmia, and hypertension were lower with zanubrutinib than ibrutinib. Despite a similar prevalence of preexisting cardiovascular events in ASPEN and ALPINE, atrial fibrillation/flutter incidence rates (6.1% vs 15.6%) and EAIR (0.2 vs 0.64 persons per 100 person-months; P &lt; .0001) were lower with zanubrutinib than with ibrutinib. Symptomatic ventricular arrhythmia incidence was low for both zanubrutinib (0.7%) and ibrutinib (1.7%) with numerically lower EAIR (0.02 vs 0.06 persons per 100 person-months, respectively) for zanubrutinib. The hypertension EAIR was lower with zanubrutinib than ibrutinib in ASPEN but similar between treatment arms in ALPINE. The higher hypertension EAIR in ALPINE was inconsistent with other zanubrutinib studies. However, fewer discontinuations (1 vs 14) and deaths (0 vs 6) due to cardiac disorders occurred with zanubrutinib versus ibrutinib in ALPINE. These data support zanubrutinib as a treatment option with improved cardiovascular tolerability compared with ibrutinib for patients with B-cell malignancies in need of BTK inhibitors. These trials were registered at www.ClinicalTrials.gov as # NCT03053440, NCT03336333, NCT03734016, NCT04170283, NCT03206918, NCT03206970, NCT03332173, NCT03846427, NCT02343120, and NCT03189524.
Asymmetric voltage amplification using a capacitive load energy management circuit in a triboelectric nanogenerator
Authors: Jeong Jiwon , Ko Jiyoung , Kim Jinhee , Lee Jongjin 
Published: March 2024

AbstractWe investigated the polarity dependence of a capacitive energy management circuit in a triboelectric nanogenerator (TENG) power system. In a half-wave rectifying circuit, the Simulation Program with Integrated Circuit Emphasis and analytical models show that the charge dump to the load varied depending on the polarity of the rectifying circuit even with the same charge output from TENG. Depending on the polarity of the rectifying circuit, a fast saturation of the direct current (DC) output voltage or a high DC output voltage was obtained. Experiments with a half-wave rectifier and Bennet doubler confirmed our simulation and theoretical results. The charge dump from the minimum capacitance of the separated TENG to the load capacitance and the charge dump from the maximum capacitance of the contacted TENG to the load resulted in asymmetric charging behavior. We concluded that it is necessary to analyze the TENG and the capacitive energy management circuit as a single system rather than considering them as independent units in the rectifying circuit of the TENG. This work can provide insights for the design of triboelectric energy harvesting systems.
RNA-binding proteins potentially regulate the alternative splicing of apoptotic genes during knee osteoarthritis progression
Authors: Zhang Zheng , Dong Limei , Tao Hai , Dong Yusong , Xiang Wei , Tao Fenghua , Zhao Yingchun 
Published: March 2024

Abstract
Background
Alternative splicing (AS) is a principal mode of genetic regulation and one of the most widely used mechanisms to generate structurally and functionally distinct mRNA and protein variants. Dysregulation of AS may result in aberrant transcription and protein products, leading to the emergence of human diseases. Although considered important for regulating gene expression, genome-wide AS dysregulation, underlying mechanisms, and clinical relevance in knee osteoarthritis (OA) remain unelucidated. Therefore, in this study, we elucidated and validated AS events and their regulatory mechanisms during OA progression.

Results
In this study, we identified differentially expressed genes between human OA and healthy meniscus samples. Among them, the OA-associated genes were primarily enriched in biological pathways such as extracellular matrix organization and ossification. The predominant OA-associated regulated AS (RAS) events were found to be involved in apoptosis during OA development. The expression of the apoptosis-related gene BCL2L13, XAF1, and NF2 were significantly different between OA and healthy meniscus samples. The construction of a covariation network of RNA-binding proteins (RBPs) and RAS genes revealed that differentially expressed RBP genes LAMA2 and CUL4B may regulate the apoptotic genes XAF1 and BCL2L13 to undergo AS events during OA progression. Finally, RT-qPCR revealed that CUL4B expression was significantly higher in OA meniscus samples than in normal controls and that the AS ratio of XAF1 was significantly different between control and OA samples; these findings were consistent with their expected expression and regulatory relationships.

Conclusions
Differentially expressed RBPs may regulate the AS of apoptotic genes during knee OA progression. XAF1 and its regulator, CUL4B, may serve as novel biomarkers and potential therapeutic targets for this disease.
Association between triglyceride-glucose index and hypertension: a cohort study based on the China Health and Nutrition Survey (2009–2015)
Authors: Wang Su , Wang Qian , Yan Xianliang 
Published: March 2024

Abstract
Aim
Insulin resistance (IR) may participate in the pathogenesis of hypertension by mediating low-grade systemic inflammation. The triglycerides-glucose (TyG) index has recently been suggested as a reliable alternative biochemical marker of IR compared with traditional methods. Herein, we speculated TyG index may also be associated with hypertension.

Methods
Data of adults were extracted from the China Health and Nutrition Survey (CHNS) in 2009–2015 in this retrospective cohort study. The TyG index was calculated using the formula: TyG = Ln [fasting triglycerides (mg/dL) ×fasting glucose (mg/dL)/2]. Associations between TyG index and hypertension were evaluated by univariate and multivariate logistic regression analyses with odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup analyses of age and gender were also performed. In addition, we assessed the interaction effect between TyG index and body mass index (BMI) on hypertension in participants with different age and gender.

Results
Among 3,413 eligible participants, 1,627 (47.67%) developed hypertension. The average TyG index in hypertension group and non-hypertension group was 8.58 and 8.39 respectively. After adjusting for covariates, we found that compared with participants with TyG index ≤ 8.41 (median value), those who had higher TyG index seemed to have higher odds of hypertension [OR = 1.17, 95%CI: (1.01–1.37)]. Similarly, this association was also discovered in participants who aged ≤ 65 years old [OR = 1.19, 95%CI: (1.01–1.39)] or were female [OR = 1.35, 95%CI: (1.10–1.65)]. Additionally, there was a potential additive interaction effect between obesity and TyG index on hypertension.

Conclusion
High TyG index was associated with high odds of hypertension in general population in China, but the causal relationship between them needed further exploration.
Facilitators and barriers to home blood pressure monitoring among pregnant women in Ghana: a mixed-methods analysis of patient perspectives
Authors: Newman Noah , Beyuo Titus K. , Nartey Betty A. , Segbedzi-Rich Elorm , Pangori Andrea , Moyer Cheryl A. , Lori Jody R. , Oppong Samuel A. , Lawrence Emma R. 
Published: March 2024

Abstract
Background
The benefit of home blood pressure monitoring during pregnancy and in low-resource settings is incompletely understood. The objective of this study was to explore the experiences, barriers, and facilitators of home blood pressure monitoring among pregnant women in Ghana.

Methods
This concurrent triangulation mixed-methods study was conducted at an urban tertiary hospital in Ghana. Participants were recruited from adult pregnant women presenting for routine antenatal care. Upon enrollment, participants’ demographics and history were collected. At the next study visit, participants received audiovisual and hands-on training on using an automatic blood pressure monitor; they then monitored and logged their blood pressure daily at home for 2–4 weeks. At the final study visit, verbally administered surveys and semi-structured interviews assessed participant’s experiences. Quantitative data were analyzed using R version 4.2.2, and frequencies and descriptive statistics were calculated. Qualitative data were imported into DeDoose 9.0.78 for thematic analysis.

Results
Of 235 enrolled participants, 194 completed surveys; of those, 33 completed in-depth interviews. Participants’ mean age was 31.6 (SD 5.3) years, 32.1% had not previously given birth, and 31.1% had less than a senior high school education. On a 4-point Likert scale, the majority reported they “definitely” were able to remember (n = 134, 69.1%), could find the time (n = 124, 63.9%), had the energy (n = 157, 80.9%), could use the blood pressure monitor without problems (n = 155, 79.9%), and had family approval (n = 182, 96.3%) while engaging in home blood pressure monitoring. 95.88% (n = 186) believed that pregnant women in Ghana should monitor their blood pressure at home. Qualitative thematic analysis demonstrated that most participants liked home blood pressure monitoring because of increased knowledge of their health during pregnancy. While most participants found measuring their blood pressure at home doable, many faced challenges. Participants’ experiences with five key factors influenced how easy or difficult their experience was: 1) Time, stress, and daily responsibilities; 2) Perceived importance of BP in pregnancy; 3) Role of family; 4) Capability of performing monitoring; 5) Convenience of monitoring.

Conclusions
Among pregnant women in urban Ghana, home blood pressure monitoring was perceived as positive, important, and doable; however, challenges must be addressed.
Prognostic marker CD27 and its micro-environmental in multiple myeloma
Authors: Wang Xinya , Luo Keyang , Xu Qiuting , Chi Liqun , Guo Yiwei , Jia Chuiming , Quan Lina 
Published: March 2024

Abstract
Background
The Cluster of Differentiation 27 (CD27) is aberrantly expressed in multiple myeloma (MM) -derived. This expression facilitates the interaction between tumor and immune cells within TME via the CD27-CD70 pathway, resulting in immune evasion and subsequent tumor progression. The objective of this study is to investigate the correlation between CD27 expression and the prognosis of MM, and to elucidate its potential relationship with the immune microenvironment.

Methods
In this research, CD27 expression in T cells within the 82 newly diagnosed MM microenvironment was assessed via flow cytometry. We then examined the association between CD27 expression levels and patient survival. Subsequent a series of bioinformatics and in vitro experiments were conducted to reveal the role of CD27 in MM.

Results
Clinical evidence suggests that elevated CD27 expression in T cells within the bone marrow serves as a negative prognostic marker for MM survival. Data analysis from the GEO database has demonstrated a strong association between MM-derived CD27 and the immune response, as well as the hematopoietic system. Importantly, patients with elevated levels of CD27 expression were also found to have an increased presence of MDSCs and macrophages in the bone marrow microenvironment. Furthermore, the PERK-ATF4 signaling pathway has been implicated in mediating the effects of CD27 in MM.

Conclusions
We revealed that CD27 expression levels serve as an indicative marker for the prognosis of MM patients. The CD27- PERK-ATF4 is a promising target for the treatment of MM.
Assessing colposcopy competencies in medically underserved communities: a multi-center study in China
Authors: Cui Xiaoli , Wang Huike , Chen Mingyang , Seery Samuel , Xue Peng , Qiao Youlin , Shang Yuhong 
Published: March 2024

Abstract
Background
Colposcopy plays an essential role in diagnosing cervical lesions and directing biopsy; however, there are few studies of the capabilities of colposcopists in medically underserved communities in China. This study aims to fill this gap by assessing colposcopists’ competencies in medically underserved communities of China.

Methods
Colposcopists in medically underserved communities across China were considered eligible to participate. Assessments involved presenting participants with 20 cases, each consisting of several images and various indications. Participants were asked to determine transformation zone (TZ) type, colposcopic diagnoses and to decide whether biopsy was necessary. Participants are categorized according to the number of colposcopic examinations, i.e., above or below 50 per annum.

Results
There were 214 participants in this study. TZ determination accuracy was 0.47 (95% CI 0.45,0.49). Accuracy for colposcopic diagnosis was 0.53 (95% CI 0.51,0.55). Decision to perform biopsies was 0.73 accurate (95% CI 0.71,0.74). Participants had 0.61 (95% CI 0.59,0.64) sensitivity and a 0.80 (95% CI 0.79,0.82) specificity for detecting high-grade lesions. Colposcopists who performed more than 50 cases were more accurate than those performed fewer across all indicators, with a higher sensitivity (0.66 vs. 0.57, p = 0.001) for detecting high-grade lesions.

Conclusions
In medically underserved communities of China, colposcopists appear to perform poorly at TZ identification, colposcopic diagnosis, and when deciding to biopsy. Colposcopists who undertake more than 50 colposcopies each year performed better than those who perform fewer. Therefore, colposcopic practice does improve through case exposure although there is an urgent need for further pre-professional and clinical training.
NanoLuc Binary Technology as a methodological approach: an important new tool for studying the localization of androgen receptor and androgen receptor splice variant V7 homo and heterodimers
Authors: Guzman Juan , Weigelt Katrin , Neumann Angela , Tripal Philipp , Schmid Benjamin , Winter Zoltán , Palmisano Ralph , Culig Zoran , Cronauer Marcus V. , Muschler Paul , Wullich Bernd , Taubert Helge , Wach Sven 
Published: March 2024

Abstract
Background
The androgen/androgen receptor (AR)-signaling axis plays a central role in prostate cancer (PCa). Upon androgen-binding the AR dimerizes with another AR, and translocates into the nucleus where the AR-dimer activates/inactivates androgen-dependent genes. Consequently, treatments for PCa are commonly based on androgen deprivation therapy (ADT). The clinical benefits of ADT are only transitory and most tumors develop mechanisms allowing the AR to bypass its need for physiological levels of circulating androgens. Clinical failure of ADT is often characterized by the synthesis of a constitutively active AR splice variant, termed AR-V7. AR-V7 mRNA expression is considered as a resistance mechanism following ADT. AR-V7 no longer needs androgenic stimuli for nuclear entry and/or dimerization.

Methods
Our goal was to mechanistically decipher the interaction between full-length AR (AR-FL) and AR-V7 in AR-null HEK-293 cells using the NanoLuc Binary Technology under androgen stimulation and deprivation conditions.

Results
Our data point toward a hypothesis that AR-FL/AR-FL homodimers form in the cytoplasm, whereas AR-V7/AR-V7 homodimers localize in the nucleus. However, after androgen stimulation, all the AR-FL/AR-FL, AR-FL/AR-V7 and AR-V7/AR-V7 dimers were localized in the nucleus.

Conclusions
We showed that AR-FL and AR-V7 form heterodimers that localize to the nucleus, whereas AR-V7/AR-V7 dimers were found to localize in the absence of androgens in the nucleus.
ART1 knockdown decreases the IL-6-induced proliferation of colorectal cancer cells
Authors: Lin Ting , Zhang Shuxian , Tang Yi , Xiao Ming , Li Ming , Gong Hanjuan , Xie Hailun , Wang Yalan 
Published: March 2024

AbstractColorectal cancer (CRC) is a worldwide health concern. Chronic inflammation is a risk factor for CRC, and interleukin-6 (IL-6) plays a pivotal role in this process. Arginine-specific mono-ADP-ribosyltransferase-1 (ART1) positively regulates inflammatory cytokines. ART1 knockdown reduces the level of glycoprotein 130 (gp130), a key transducer in the IL-6 signalling pathway. However, the relationship between ART1 and IL-6 and the resulting effects on IL-6-induced proliferation in CRC cells remain unclear. The aims of this study were to investigate the effects of ART1 knockdown on IL-6-induced cell proliferation in vitro and use an in vivo murine model to observe the growth of transplanted tumours. The results showed that compared with the control, ART1-sh cancer cells induced by IL-6 exhibited reduced viability, a lower rate of colony formation, less DNA synthesis, decreased protein levels of gp130, c-Myc, cyclin D1, Bcl-xL, and a reduced p-STAT3/STAT3 ratio (P < 0.05). Moreover, mice transplanted with ART1-sh CT26 cells that had high levels of IL-6 displayed tumours with smaller volumes (P < 0.05). ART1 and gp130 were colocalized in CT26, LoVo and HCT116 cells, and their expression was positively correlated in human CRC tissues. Overall, ART1 may serve as a promising regulatory factor for IL-6 signalling and a potential therapeutic target for human CRC.
Renal toxicity of ifosfamide in children with cancer: an exploratory study integrating aldehyde dehydrogenase enzymatic activity data and a wide-array urinary metabolomics approach
Authors: Febvey-Combes Olivia , Guitton Jérôme , Marec-Berard Perrine , Faure-Conter Cécile , Blanc Ellen , Chabaud Sylvie , Conjard-Duplany Agnès , Schell Matthias , Derain Dubourg Laurence 
Published: March 2024

Abstract
Background
Ifosfamide is a major anti-cancer drug in children with well-known renal toxicity. Understanding the mechanisms underlying this toxicity could help identify children at increased risk of toxicity.

Methods
The IFOS01 study included children undergoing ifosfamide-based chemotherapy for Ewing sarcoma or rhabdomyosarcoma. A fully evaluation of renal function was performed during and after chemotherapy. Proton nuclear magnetic resonance (NMR) and conventional biochemistry were used to detect early signs of ifosfamide-induced tubulopathy. The enzymatic activity of aldehyde dehydrogenase (ALDH) was measured in the peripheral blood lymphocytes as a marker of ifosfamide-derived chloroacetaldehyde detoxification capacity. Plasma and urine concentrations of ifosfamide and dechloroethylated metabolites were quantified.

Results
The 15 participants received a median total ifosfamide dose of 59 g/m2 (range: 24–102), given over a median of 7 cycles (range: 4–14). All children had acute proximal tubular toxicity during chemotherapy that was reversible post-cycle, seen with both conventional assays and NMR. After a median follow-up of 31 months, 8/13 children presented overall chronic toxicity among which 7 had decreased glomerular filtration rate. ALDH enzymatic activity showed high inter- and intra-individual variations across cycles, though overall activity looked lower in children who subsequently developed chronic nephrotoxicity. Concentrations of ifosfamide and metabolites were similar in all children.

Conclusions
Acute renal toxicity was frequent during chemotherapy and did not allow identification of children at risk for long-term toxicity. A role of ALDH in late renal dysfunction is possible so further exploration of its enzymatic activity and polymorphism should be encouraged to improve the understanding of ifosfamide-induced nephrotoxicity.