bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with plans for early retirement among Ontario family physicians during the COVID-19 pandemic: a cross-sectional study
Authors: Walsh Rachel , Telner Deanna , Butt Debra A. , Krueger Paul , Fleming Karen , MacDonald Sarah , Pyakurel Aakriti , Greiver Michelle , Jaakkimainen Liisa 
Published: April 2024

Abstract
Background
Higher numbers of family physicians (FPs) stopped practicing or retired during the COVID-19 pandemic, worsening the family doctor shortage in Canada. Our study objective was to determine which factors were associated with FPs’ plans to retire earlier during the COVID-19 pandemic.

Methods
We administered two cross-sectional online surveys to Ontario FPs asking whether they were “planning to retire earlier” as a result of the pandemic during the first and third COVID-19 pandemic waves (Apr-Jun 2020 and Mar-Jul 2021). We used logistic regression to determine which factors were associated with early retirement planning, adjusting for age.

Results
The age-adjusted proportion of FP respondents planning to retire earlier was 8.2% (of 393) in the first-wave and 20.5% (of 454) in the third-wave. Planning for earlier retirement during the third-wave was associated with age over 50 years (50–59 years odds ratio (OR) 5.37 (95% confidence interval (CI):2.33–12.31), 60 years and above OR 4.18 (95% CI: 1.90-10.23)), having difficulty handling increased non-clinical responsibilities (OR 2.95 (95% CI: 1.79–4.94)), feeling unsupported to work virtually (OR 1.96 (95% CI: 1.19–3.23)) or in-person (OR 2.70 (95% CI: 1.67–4.55)), feeling unable to provide good care (OR 1.82 (95% CI: 1.10–3.03)), feeling work was not valued (OR 1.92 (95% CI: 1.15–3.23)), feeling frightened of dealing with COVID-19 (OR 2.01 (95% CI: 1.19–3.38)), caring for an elderly relative (OR 2.36 (95% CI: 1.69–3.97)), having difficulty obtaining personal protective equipment (OR 2.00 (95% CI: 1.16–3.43)) or difficulty implementing infection control practices in clinic (OR 2.10 (95% CI: 1.12–3.89)).

Conclusions
Over 20% of Ontario FP respondents were considering retiring earlier by the third-wave of the COVID-19 pandemic. Supporting FPs in their clinical and non-clinical roles, such that they feel able to provide good care and that their work is valued, reducing non-clinical (e.g., administrative) responsibilities, dealing with pandemic-related fears, and supporting infection control practices and personal protective equipment acquisition in clinic, particularly in those aged 50 years or older may help increase family physician retention during future pandemics.
Prenatal ultrasound findings and clinical outcomes of uniparental disomy: a retrospective study
Authors: Wu Cui-Yi , Zhou Yi , Yin Xia , Peng Ruan , Xie Hong-Ning 
Published: April 2024

Abstract
Background
Uniparental disomy is the inheritance of a homologous chromosome pair or part of homologous chromosomes from only one parent. However, the clinical significance of uniparental disomy and the difference among the prognosis of involvement of different chromosomes remain unclear.

Objective
To assess the associated prenatal ultrasound presentations and clinical outcomes of uniparental disomy on different chromosomes and to analyze the relationship between prenatal ultrasound markers and clinical outcomes.

Study design
We retrospectively analyzed data from fetuses with uniparental disomy diagnosed using chromosome microarray analysis with the Affymetrix CytoScan HD array at our institution between January 2013 and September 2022. The relationship between prenatal ultrasound findings, the involved chromosome(s), and clinical outcomes was evaluated.

Results
During the study period, 36 fetuses with uniparental disomy were diagnosed, and two cases were excluded for non-available postnatal data. Finally, 34 fetuses were included in our study, of which 30 (88.2%) had uniparental disomy occurring on a single chromosome, while four (11.8%) were identified with uniparental disomy on different chromosomes. The most frequently involved chromosomes were chromosomes 16, X and 2, which presented in 8 (23.5%), 5 (14.7%) and 4 (11.8%), respectively. Prenatal ultrasound abnormalities were detected in 21 fetuses, with the most common category being multiple abnormalities (12 (57.1%)). Fetal growth restriction was identified in 14 (41.2%) fetuses, all of which coexisted with other abnormal findings. The rate of adverse perinatal outcomes in patients with uniparental disomy and fetal abnormalities was significantly higher than those without abnormalities (76.2% versus 15.4%, P = 0.002). The incidence of fetal or neonatal death was significantly higher in fetuses with fetal growth restriction than those without (85.7% versus 30.0%, P = 0.004).

Conclusions
The prognosis of fetuses with uniparental disomy combined with fetal abnormalities, especially fetal growth restriction, was much poorer than those without.
UBE2C promotes the proliferation of acute myeloid leukemia cells through PI3K/AKT activation
Authors: Wang Li , Zhao Shuqin , Wang Yongling , Liu Jianying , Wang Xiaoli 
Published: April 2024

AbstractThis study aims to investigate the role and mechanism of tubiquitin-conjugating enzyme E2 C (UBE2C) in acute myeloid leukemia (AML). Initially, UBE2C expression in leukemia was analyzed using the Cancer Genome Atlas database. Further, we silenced UBE2C expression using small-hairpin RNA (sh-RNA). UBE2C expression was detected via the quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blot analysis. Apoptotic events and reactive oxygen species (ROS) levels were detected by flow cytometry. A xenograft model of leukemia cells were established, and the protein levels of UBE2C, KI-67, and cleaved-caspase 3 were detected by immunohistochemistry. We reported an overexpression of UBE2C in leukemia patients and cell lines (HL60, THP-1, U937, and KG-1 cells). Moreover, a high expression level of UBE2C was correlated with a dismal prognosis in AML patients. UBE2C knockdown inhibited the viability and promoted apoptosis in AML cells by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Furthermore, UBE2C knockdown increased cellular Fe2+ and ROS levels, and enhanced erastin-induced ferroptosis in a proteasome-dependent manner. UBE2C knockdown also suppressed the tumor formation of AML cells in the mouse model. In summary, our findings suggest that UBE2C overexpression promotes the proliferation and inhibits ferroptosis in AML cells by activating the PI3K/AKT pathway.
Interstitial round needles should not be used for cervical cancer patient treated with intracavitary/ interstitial brachytherapy using a Venezia applicator : a case report
Authors: Takagawa Yoshiaki , Izumi Sachiko , Takahashi Eiichi , Kita Midori 
Published: April 2024

Abstract
Background
Image-guided adaptive brachytherapy (IGABT) demonstrates an excellent local control rate and low toxicity while treating cervical cancer. For intracavitary/interstitial (IC/IS) brachytherapy (BT), several applicators are commercially available. Venezia (Elekta, Sweden), an advanced gynecological applicator, is designed for IC/IS BT for treating locally advanced cervical cancer. There are two types of interstitial needles for the Venezia applicator: the round needle and sharp needle. Generally, a round needle is safer because it has less risk of damaging the organ at risk than a sharp needle. However, there is currently no evidence to suggest that a round needle is better than a sharp needle for the Venezia applicator in IC/IS BT. Herein, we documented our experience of using both round and sharp needles with the Venezia applicator in IC/IS BT for cervical cancer.

Case presentation
A 71-year-old woman was diagnosed with clinical stage T2bN0M0 and the International Federation of Gynecology and Obstetrics stage IIB cervical squamous cell carcinoma. Definitive therapy, including a high-dose-rate BT boost, was planned using a round needle with the Venezia applicator in IC/IS BT. After inserting four interstitial round needles during the first and second BT sessions, an unexpectedly large gap (1.5 cm) was detected between the cervix and ovoid. We therefore used a sharp needle with the Venezia applicator for IC/IS BT during the third and fourth BT sessions. Three sharp needles were firmly inserted during the third and fourth BT sessions.

Conclusions
The study findings suggest that the interstitial round needle should not be used for cervical cancer patients undergoing IC/IS BT using the Venezia applicator.
Development and application of a deep learning-based comprehensive early diagnostic model for chronic obstructive pulmonary disease
Authors: Zhu Zecheng , Zhao Shunjin , Li Jiahui , Wang Yuting , Xu Luopiao , Jia Yubing , Li Zihan , Li Wenyuan , Chen Gang , Wu Xifeng 
Published: April 2024

Abstract
Background
Chronic obstructive pulmonary disease (COPD) is a frequently diagnosed yet treatable condition, provided it is identified early and managed effectively. This study aims to develop an advanced COPD diagnostic model by integrating deep learning and radiomics features.

Methods
We utilized a dataset comprising CT images from 2,983 participants, of which 2,317 participants also provided epidemiological data through questionnaires. Deep learning features were extracted using a Variational Autoencoder, and radiomics features were obtained using the PyRadiomics package. Multi-Layer Perceptrons were used to construct models based on deep learning and radiomics features independently, as well as a fusion model integrating both. Subsequently, epidemiological questionnaire data were incorporated to establish a more comprehensive model. The diagnostic performance of standalone models, the fusion model and the comprehensive model was evaluated and compared using metrics including accuracy, precision, recall, F1-score, Brier score, receiver operating characteristic curves, and area under the curve (AUC).

Results
The fusion model exhibited outstanding performance with an AUC of 0.952, surpassing the standalone models based solely on deep learning features (AUC = 0.844) or radiomics features (AUC = 0.944). Notably, the comprehensive model, incorporating deep learning features, radiomics features, and questionnaire variables demonstrated the highest diagnostic performance among all models, yielding an AUC of 0.971.

Conclusion
We developed and implemented a data fusion strategy to construct a state-of-the-art COPD diagnostic model integrating deep learning features, radiomics features, and questionnaire variables. Our data fusion strategy proved effective, and the model can be easily deployed in clinical settings.

Trial registration
Not applicable. This study is NOT a clinical trial, it does not report the results of a health care intervention on human participants.
Effects of quercetin on polycystic ovary syndrome in animal models: a systematic review and meta-analysis
Authors: Su Pingping , Chen Chao , Pang Liang , Wu Kai , Sun Yun 
Published: April 2024

Abstract
Background
Metformin is an insulin sensitizer that is widely used for the treatment of insulin resistance in polycystic ovary syndrome patients. However, metformin can cause gastrointestinal side effects.

Purpose
This study showed that the effects of quercetin are comparable to those of metformin. Therefore, this study aimed to systematically evaluate the efficacy of quercetin in treating PCOS.

Methods
The present systematic search of the Chinese National Knowledge Infrastructure (CNKI), Wanfang Data Information Site, Chinese Scientific Journals Database (VIP), SinoMed, Web of Science, and PubMed databases was performed from inception until February 2024. The methodological quality was then assessed by SYRCLE’s risk of bias tool, and the data were analyzed by RevMan 5.3 software.

Results
Ten studies were included in the meta-analysis. Compared with those in the model group, quercetin in the PCOS group had significant effects on reducing fasting insulin serum (FIS) levels (P = 0.0004), fasting blood glucose (FBG) levels (P = 0.01), HOMA-IR levels (P < 0.00001), cholesterol levels (P < 0.0001), triglyceride levels (P = 0.001), testosterone (T) levels (P < 0.00001), luteinizing hormone (LH) levels (P = 0.0003), the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio (P = 0.01), vascular endothelial growth factor (VEGF) levels (P < 0.00001), malondialdehyde (MDA) levels (P = 0.03), superoxide dismutase (SOD) levels (P = 0.01) and GLUT4 mRNA expression (P < 0.00001).

Conclusion
This meta-analysis suggested that quercetin has positive effects on PCOS treatment. Quercetin can systematically reduce insulin, blood glucose, cholesterol, and triglyceride levels in metabolic pathways. In the endocrine pathway, quercetin can regulate the function of the pituitary-ovarian axis, reduce testosterone and luteinizing hormone (LH) levels, and lower the ratio of LH to follicle-stimulating hormone (FSH). Quercetin can regulate the expression of the GLUT4 gene and has antioxidative effects at the molecular level.
Role of imbalanced gut microbiota in promoting CRC metastasis: from theory to clinical application
Authors: Fan Shiying , Zhou Lujia , Zhang Wenjie , Wang Daorong , Tang Dong 
Published: April 2024

AbstractMetastasis poses a major challenge in colorectal cancer (CRC) treatment and remains a primary cause of mortality among patients with CRC. Recent investigations have elucidated the involvement of disrupted gut microbiota homeostasis in various facets of CRC metastasis, exerting a pivotal influence in shaping the metastatic microenvironment, triggering epithelial-mesenchymal transition (EMT), and so on. Moreover, therapeutic interventions targeting the gut microbiota demonstrate promise in enhancing the efficacy of conventional treatments for metastatic CRC (mCRC), presenting novel avenues for mCRC clinical management. Grounded in the “seed and soil” hypothesis, this review consolidates insights into the mechanisms by which imbalanced gut microbiota promotes mCRC and highlights recent strides in leveraging gut microbiota modulation for the clinical prevention and treatment of mCRC. Emphasis is placed on the considerable potential of manipulating gut microbiota within clinical settings for managing mCRC.
The development of chimeric antigen receptor T-cells against CD70 for renal cell carcinoma treatment
Authors: Xiong Qinghui , Wang Haiying , Shen Qiushuang , Wang Yan , Yuan Xiujie , Lin Guangyao , Jiang Pengfei 
Published: April 2024

AbstractIn this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.
Discovery of a novel and highly selective JAK3 inhibitor as a potent hair growth promoter
Authors: Hossain Md Mehedi , Khalid Arfan , Akhter Zaheen , Parveen Sabra , Ayaz Mir Owais , Bhat Aadil Qadir , Badesra Neetu , Showket Farheen , Dar Mohmmad Saleem , Ahmed Farhan , Dhiman Sumit , Kumar Mukesh , Singh Umed , Hussain Razak , Keshari Pankaj , Mustafa Ghulam , Nargorta Amit , Taneja Neha , Gupta Somesh , Mir Riyaz A. , Kshatri Aravind Singh , Nandi Utpal , Khan Nooruddin , Ramajayan P. , Yadav Govind , Ahmed Zabeer , Singh Parvinder Pal , Dar Mohd Jamal 
Published: April 2024

AbstractJAK-STAT signalling pathway inhibitors have emerged as promising therapeutic agents for the treatment of hair loss. Among different JAK isoforms, JAK3 has become an ideal target for drug discovery because it only regulates a narrow spectrum of γc cytokines. Here, we report the discovery of MJ04, a novel and highly selective 3-pyrimidinylazaindole based JAK3 inhibitor, as a potential hair growth promoter with an IC50 of 2.03 nM. During in vivo efficacy assays, topical application of MJ04 on DHT-challenged AGA and athymic nude mice resulted in early onset of hair regrowth. Furthermore, MJ04 significantly promoted the growth of human hair follicles under ex-vivo conditions. MJ04 exhibited a reasonably good pharmacokinetic profile and demonstrated a favourable safety profile under in vivo and in vitro conditions. Taken together, we report MJ04 as a highly potent and selective JAK3 inhibitor that exhibits overall properties suitable for topical drug development and advancement to human clinical trials.
Mesothelin-based CAR-T cells exhibit potent antitumor activity against ovarian cancer
Authors: Guo Jing , Zeng Xiaozhu , Zhu Yongjie , Yang Dong , Zhao Xudong 
Published: April 2024

Abstract
Background
Ovarian cancer (OC) is characterized by its rapid growth and spread which, accompanied by a low 5-year survival rate, necessitates the development of improved treatments. In ovarian cancer, the selective overexpression of Mucin-16 (MUC16, CA125) in tumor cells highlights its potential as a promising target for developing anti-tumor therapies. However, the potential effectiveness of CAR-T cell therapy that targets MUC16 in ovarian cancer cells is unknown.

Methods
The expression of MUC16 in viable OC cells was detected using immunofluorescence and flow cytometry techniques. A MSLN-CAR construct, comprising the MUC16-binding polypeptide region of mesothelin (MSLN), a CD8 hinge spacer and transmembrane domain, 4-1BB, and CD3ζ endo-domains; was synthesized and introduced into T cells using lentiviral particles. The cytotoxicity of the resultant CAR-T cells was evaluated in vitro using luciferase assays. Cytokine release by CAR-T cells was measured using enzyme-linked immunosorbent assays. The anti-tumor efficacy of the CAR-T cells was subsequently assessed in mice through both systemic and local administration protocols.

Results
MSLN-CAR T cells exhibited potent cytotoxicity towards OVCAR3 cells and their stem-like cells that express high levels of MUC16. Also, MSLN-CAR T cells were inefficient at killing SKOV3 cells that express low levels of MUC16, but were potently cytotoxic to such cells overexpressing MUC16. Moreover, MSLN-CAR T cells delivered via tail vein or peritoneal injection could shrink OVCAR3 xenograft tumors in vivo, with sustained remission observed following peritoneal delivery of MSLN-CAR T cells.

Conclusions
Collectively, these results suggested that MSLN-CAR T cells could potently eliminate MUC16- positive ovarian cancer tumor cells both in vitro and in vivo, thereby providing a promising therapeutic intervention for MUC16-positive patients.
Microbiota-derived acetate attenuates neuroinflammation in rostral ventrolateral medulla of spontaneously hypertensive rats
Authors: Yin Xiaopeng , Duan Changhao , Zhang Lin , Zhu Yufang , Qiu Yueyao , Shi Kaiyi , Wang Sen , Zhang Xiaoguang , Zhang Huaxing , Hao Yinchao , Yuan Fang , Tian Yanming 
Published: April 2024

Abstract
Background
Increased neuroinflammation in brain regions regulating sympathetic nerves is associated with hypertension. Emerging evidence from both human and animal studies suggests a link between hypertension and gut microbiota, as well as microbiota-derived metabolites short-chain fatty acids (SCFAs). However, the precise mechanisms underlying this gut-brain axis remain unclear.

Methods
The levels of microbiota-derived SCFAs in spontaneously hypertensive rats (SHRs) were determined by gas chromatography-mass spectrometry. To observe the effect of acetate on arterial blood pressure (ABP) in rats, sodium acetate was supplemented via drinking water for continuous 7 days. ABP was recorded by radio telemetry. The inflammatory factors, morphology of microglia and astrocytes in rostral ventrolateral medulla (RVLM) were detected. In addition, blood-brain barrier (BBB) permeability, composition and metabolomics of the gut microbiome, and intestinal pathological manifestations were also measured.

Results
The serum acetate levels in SHRs are lower than in normotensive control rats. Supplementation with acetate reduces ABP, inhibits sympathetic nerve activity in SHRs. Furthermore, acetate suppresses RVLM neuroinflammation in SHRs, increases microglia and astrocyte morphologic complexity, decreases BBB permeability, modulates intestinal flora, increases fecal flora metabolites, and inhibits intestinal fibrosis.

Conclusions
Microbiota-derived acetate exerts antihypertensive effects by modulating microglia and astrocytes and inhibiting neuroinflammation and sympathetic output.
Targeting brain-peripheral immune responses for secondary brain injury after ischemic and hemorrhagic stroke
Authors: Duan Mingxu , Xu Ya , Li Yuanshu , Feng Hua , Chen Yujie 
Published: April 2024

AbstractThe notion that the central nervous system is an immunologically immune-exempt organ has changed over the past two decades, with increasing evidence of strong links and interactions between the central nervous system and the peripheral immune system, both in the healthy state and after ischemic and hemorrhagic stroke. Although primary injury after stroke is certainly important, the limited therapeutic efficacy, poor neurological prognosis and high mortality have led researchers to realize that secondary injury and damage may also play important roles in influencing long-term neurological prognosis and mortality and that the neuroinflammatory process in secondary injury is one of the most important influences on disease progression. Here, we summarize the interactions of the central nervous system with the peripheral immune system after ischemic and hemorrhagic stroke, in particular, how the central nervous system activates and recruits peripheral immune components, and we review recent advances in corresponding therapeutic approaches and clinical studies, emphasizing the importance of the role of the peripheral immune system in ischemic and hemorrhagic stroke.
Massive retroperitoneal hematoma caused by intercostal artery bleeding after blunt trauma: a case report
Authors: Zhu Ran , Liu Xiangtian , Li Xiaoli , Ye Liping 
Published: April 2024

Abstract
Background
The occurrence of massive retroperitoneal hematoma caused by intercostal artery bleeding is exceedingly uncommon.

Case presentation
A middle-aged male presented to the hospital after a fall. Computed tomography scan revealed a massive retroperitoneal hematoma without any evidence of organ or major vessel rupture. The angiogram revealed extravasation from a branch of the twelfth intercostal artery, and successful transcatheter arterial embolization was performed on this specific artery.

Conclusions
The possibility of intercostal artery rupture should be considered in cases of retroperitoneal hematomas, and accurate diagnosis can be achieved through imaging studies. Transcatheter arterial embolization represents an effective treatment modality.