bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing HOXC13 exerts anti-prostate cancer effects by inducing DNA damage and activating cGAS/STING/IRF3 pathway
Authors: Li Maozhang , Bai Guangwei , Cen Yi , Xie Qitong , Chen Jiahong , Chen Jia , Chen Qingbiao , Zhong Weide , Zhou Xiaobo 
Published: December 2023

Abstract
Background
Advanced prostate cancer (PCa) will develop into castration-resistant prostate cancer (CRPC) and lead to poor prognosis. As the primary subtype of CRPC, CRPC-AR accounts for the major induction of PCa heterogeneity. CRPC-AR is mainly driven by 25 transcription factors (TFs), which we speculate may be the key factors driving PCa toward CRPC. Therefore, it is necessary to clarify the key regulator and its molecular mechanism mediating PCa progression.

Methods
Firstly, we downloaded transcriptomic data and clinical information from TCGA-PRAD. The characteristic gene cluster was identified by PPI clustering, GO enrichment, co-expression correlation and clinical feature analyses for 25 TFs. Then, the effects of 25 TFs expression on prognosis of PCa patients was analyzed using univariate Cox regression, and the target gene was identified. The expression properties of the target gene in PCa tissues were verified using tissue microarray. Meanwhile, the related mechanistic pathway of the target gene was mined based on its function. Next, the target gene was silenced by small interfering RNAs (siRNAs) for cellular function and mechanistic pathway validation. Finally, CIBERSORT algorithm was used to analyze the infiltration levels of 22 immune cells in PCa patients with low and high expression of target gene, and validated by assaying the expression of related immunomodulatory factor.

Results
We found that HOX family existed independently in 25 TFs, among which HOXC10, HOXC12 and HOXC13 had unique clinical features and the PCa patients with high HOXC13 expression had the worst prognosis. In addition, HOXC13 was highly expressed in tumor tissues and correlated with Gleason score and pathological grade. In vitro experiments demonstrated that silencing HOXC13 inhibited 22RV1 and DU145 cell function by inducing cellular DNA damage and activating cGAS/STING/IRF3 pathway. Immune infiltration analysis revealed that high HOXC13 expression suppressed infiltration of γδ T cells and plasma cells and recruited M2 macrophages. Consistent with these results, silencing HOXC13 up-regulated the transcriptional expression of IFN-β, CCL2, CCL5 and CXCL10.

Conclusion
HOXC13 regulates PCa progression by mediating the DNA damage-induced cGAS/STING/IRF3 pathway and remodels TIME through regulation of the transcription of the immune factors IFN-β, CCL2, CCL5 and CXCL10.
GATA6-AS1 suppresses epithelial–mesenchymal transition of pancreatic cancer under hypoxia through regulating SNAI1 mRNA stability
Authors: Zhou Yunhui , Zhou Xinyi , Ben Qiwen , Liu Ningning , Wang Jiahui , Zhai Yongpeng , Bao Yichen , Zhou Lin 
Published: December 2023

AbstractPancreatic ductal adenocarcinoma (PDAC) is characterized by a hypoxic microenvironment, a high rate of heterogeneity as well as a high likelihood of recurrence. Mounting evidence has affirmed that long non-coding RNAs (lncRNAs) participate in the carcinogenesis of PDAC cells. In this study, we revealed significantly decreased expression of GATA6-AS1 in PDAC based on the GEO dataset and our cohorts, and showed that low GATA6-AS1 expression was linked to unfavorable clinicopathologic characteristics as well as a poor prognosis. Gain- and loss-of-function studies demonstrated that GATA6-AS1 suppressed the proliferation, invasion, migration, and epithelial–mesenchymal transition (EMT) process of PDAC cells under hypoxia. In vivo data confirm the suppressive roles of GATA6-AS1/SNAI1 in tumor growth and lung metastasis of PDAC. Mechanistically, hypoxia-driven E26 transformation-specific sequence-1 (ETS1), as an upstream modulatory mechanism, was essential for the downregulation of GATA6-AS1 in PDAC cells. GATA6-AS1 inhibited the expression of fat mass and obesity-associated protein (FTO), an N6-methyladenosine (m6A) eraser, and repressed SNAI1 mRNA stability in an m6A-dependent manner. Our data suggested that GATA6-AS1 can inhibit PDAC cell proliferation, invasion, migration, EMT process and metastasis under hypoxia, and disrupting the GATA6-AS1/FTO/SNAI1 axis might be a viable therapeutic approach for refractory hypoxic pancreatic cancers.
RUNX1 knockdown induced apoptosis and impaired EMT in high-grade serous ovarian cancer cells
Authors: Chen Yuanzhi , He Zhicheng , Yang Shuting , Chen Cheng , Xiong Wenyong , He YingYing , Liu Shubai 
Published: December 2023

AbstractOvarian cancer is the leading cause of death from gynecologic illnesses worldwide. High-grade serous ovarian cancer (HGSOC) is a gynecological tumor that accounts for roughly 70% of ovarian cancer deaths in women. Runt-related transcription factor 1(RUNX1) proteins were identified with overexpression in the HGSOC. However, the roles of RUNX1 in the development of HGSOC are poorly understood. In this study, combined with whole-transcriptome analysis and multiple research methods, RUNX1 was identified as vital in developing HGSOC. RUNX1 knockdown inhibits the physiological function of ovarian cancer cells and regulates apoptosis through the FOXO1-Bcl2 axis. Down-regulated RUNX1 impairs EMT function through the EGFR-AKT-STAT3 axis signaling. In addition, RUNX1 knockdown can significantly increase the sensitivity to clinical drug therapy for ovarian cancer. It is strongly suggested that RUNX1 work as a potential diagnostic and therapeutic target for HGSOC patients with better prognoses and treatment options. It is possible to generate novel potential targeted therapy strategies and translational applications for serous ovarian carcinoma patients with better clinical outcomes.
Nicotinamide mononucleotide as a therapeutic agent to alleviate multi-organ failure in sepsis
Authors: Cao Ting , Ni Rui , Ding Weimin , Ji Xiaoyun , Fan Guo-Chang , Zhang Zhuxu , Peng Tianqing 
Published: December 2023

Abstract
Background
Sepsis-caused multi-organ failure remains the major cause of morbidity and mortality in intensive care units with limited therapeutics. Nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), has been recently reported to be protective in sepsis; however, its therapeutic effects remain to be determined. This study sought to investigate the therapeutic effects of NMN in septic organ failure and its underlying mechanisms.

Methods
Sepsis was induced by feces-injection-in-peritoneum in mice. NMN was given after an hour of sepsis onset. Cultured neutrophils, macrophages and endothelial cells were incubated with various agents.

Results
We demonstrate that administration of NMN elevated NAD+ levels and reduced serum lactate levels, oxidative stress, inflammation, and caspase-3 activity in multiple organs of septic mice, which correlated with the attenuation of heart dysfunction, pulmonary microvascular permeability, liver injury, and kidney dysfunction, leading to lower mortality. The therapeutic effects of NMN were associated with lower bacterial burden in blood, and less ROS production in septic mice. NMN improved bacterial phagocytosis and bactericidal activity of macrophages and neutrophils while reducing the lipopolysaccharides-induced inflammatory response of macrophages. In cultured endothelial cells, NMN mitigated mitochondrial dysfunction, inflammation, apoptosis, and barrier dysfunction induced by septic conditions, all of which were offset by SIRT3 inhibition.

Conclusion
NAD+ repletion with NMN prevents mitochondrial dysfunction and restrains bacterial dissemination while limiting inflammatory damage through SIRT3 signaling in sepsis. Thus, NMN may represent a therapeutic option for sepsis.
An engineered Fc fusion protein that targets antigen-specific T cells and autoantibodies mitigates autoimmune disease
Authors: Janakiraman Mathangi , Leliavski Alexei , Varadarajulu Jeeva , Jenne Dieter , Krishnamoorthy Gurumoorthy 
Published: December 2023

AbstractCurrent effective therapies for autoimmune diseases rely on systemic immunomodulation that broadly affects all T and/or B cell responses. An ideal therapeutic approach would combine autoantigen-specific targeting of both T and B cell effector functions, including efficient removal of pathogenic autoantibodies. Albeit multiple strategies to induce T cell tolerance in an autoantigen-specific manner have been proposed, therapeutic removal of autoantibodies remains a significant challenge. Here, we devised an approach to target both autoantigen-specific T cells and autoantibodies by producing a central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG)-Fc fusion protein. We demonstrate that MOG-Fc fusion protein has significantly higher bioavailability than monomeric MOG and is efficient in clearing anti-MOG autoantibodies from circulation. We also show that MOG-Fc promotes T cell tolerance and protects mice from MOG-induced autoimmune encephalomyelitis. This multipronged targeting approach may be therapeutically advantageous in the treatment of autoimmunity.
Coagulation parameters correlate to venous thromboembolism occurrence during the perioperative period in patients with spinal fractures
Authors: Jiao Yong , Mu Xiaohong 
Published: December 2023

Abstract
Background
Venous thromboembolism (VTE) is one of the leading causes of mortality in hospitalized patients. However, whether the coagulation-related parameters of the hospitalized patients could be used to predict the occurrence of VTE in patients with spinal injury surgery remained unclear.

Method
The patients with spinal fractures who met the inclusion and exclusion criteria were enrolled to be analyzed using a retrospective analysis approach. The association of risk factors of enrolled patients and operations to VTE occurrence were analyzed. The activated partial thromboplastin time, prothrombin time, thrombin time, D-dimer (D-D), fibrinogen (FIB) and fibrinogen degradation products (FDP) were detected. ROC and HR analysis were applied to evaluate the correlation of coagulation-related parameters and other parameters to VTE occurrence.

Result
The indicators of D-D, FIB and FDP were significantly elevated in VTE patients compared to non-VTE patients. The multivariate analysis of OR showed that six risk factors, including age ≥ 60, spinal cord injury, postoperative bedtime over 5 days, plasma D-dimer ≥ 0.54 mg/L, plasma fibrinogen ≥ 3.75 g/L and plasma FDP ≥ 5.19 mg/L, were positively correlated to VTE.

Conclusion
The six risk factors, including D-D, FIB, FDP, age ≥ 60, spinal cord injury, and postoperative bedtime over 5 days, could be used to predict the occurrence of VTE.
The effect of extracorporeal shock wave on joint capsule fibrosis based on A2AR-Nrf2/HO-1 pathway in a rat extending knee immobilization model
Authors: Yuan Hai , Wang Kui , Zhang Quan-Bing , Wang Feng , Zhou Yun 
Published: December 2023

AbstractJoint capsule fibrosis, a common complication of joint immobilization, is mainly characterized by abnormal collagen deposition. The present study aimed to investigate the effect of extracorporeal shock wave therapy (ESWT) on reduced collagen deposition in the joint capsule during immobilization-induced joint capsule fibrosis. Additionally, the potential involvement of the adenosine A2A receptor (A2AR)-Neurotrophic factor e2-related factor 2 (Nrf2)/Haem oxygenase-1 (HO-1) pathway was explored. Thirty 3-month-old male Sprague–Dawley rats were randomly assigned to five groups: control (C), immobilization model (IM), natural recovery (NR), ESWT intervention (EI), and ESWT combined with A2AR antagonist SCH 58261 intervention (CI). After the left knee joints of rats in the IM, NR, EI and CI groups were immobilized using a full-extension fixation brace for 4 weeks, the EI and CI groups received ESWT twice a week for 4 weeks. The CI group was also treated with ESWT following intraperitoneal injection of SCH 58261 (0.01 mg/kg) for 4 weeks. The range of motion of the left knee joint was measured, and the protein levels of collagens I and III, A2AR, phosphorylated-protein kinase A/protein kinase A (p-PKA/PKA), p-Nrf2/Nrf2, and HO-1 were analysed by Western blotting. The IM and NR groups showed significantly greater arthrogenic contracture than the C group (P < 0.05). Compared to the NR group, the EI and CI groups exhibited significant improvement in arthrogenic contracture (P < 0.05). Conversely, the EI group showed lower contracture than the CI group (P < 0.05). Similar results were observed for collagen deposition and the protein levels of collagens I and III. The intervention groups (EI and CI groups) showed higher levels of p-Nrf2/Nrf2 and HO-1 than the NR group (P < 0.05). Moreover, the EI group exhibited higher levels of p-PKA/PKA, p-Nrf2/Nrf2, and HO-1 than the CI group (P < 0.05). However, no significant difference was found in the A2AR levels among the five groups (P > 0.05). ESWT may activate A2AR, leading to the phosphorylation of PKA. Subsequently, Nrf2 may be activated, resulting in the upregulation of HO-1, which then reduces collagen deposition and alleviates immobilization-induced joint capsule fibrosis.
Pneumocystis jirovecii with high probability detected in bronchoalveolar lavage fluid of chemotherapy-related interstitial pneumonia in patients with lymphoma using metagenomic next-generation sequencing technology
Authors: Jin Dian , Le Jing , Yang Qianqian , Cai Qianqian , Dai Hui , Luo Liufei , Tong Jiaqi , Shu Wenxiu 
Published: December 2023

Abstract
Background
Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF).

Methods
Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared.

Results
Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids.

Conclusion
Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.
Impact of the COVID-19 pandemic on mental health care and people with mental health conditions in Ethiopia: the MASC mixed-methods study
Authors: Mihretu Awoke , Fekadu Wubalem , Alemu Azeb Asaminew , Amare Beakal , Assefa Dereje , Misganaw Eleni , Ayele Abebaw , Esleman Ousman , Assefa Zewdu , Alem Atalay , Thornicroft Graham , Hanlon Charlotte 
Published: December 2023

Abstract
Background
The COVID-19 pandemic has had far-reaching effects on the mental health of populations around the world, but there has been limited focus on the impact on people with existing mental health conditions in low-income countries. The aim of this study was to examine impact of the pandemic on mental health care and people with mental health conditions in Ethiopia.

Methods
A convergent mixed methods study was conducted. We systematically mapped information from publicly available reports on impacts of the pandemic on mental health care. Monthly service utilisation data were obtained from Amanuel Mental Specialised Hospital, the main psychiatric hospital, and analysed using segmented Poisson regression (2019 vs. 2020). In-depth interviews were conducted with 16 purposively selected key informants. Framework analysis was used for qualitative data. Findings from each data source were integrated.

Results
In the early stages of the pandemic, participants indicated a minimal response towards the mental health aspects of COVID-19. Mental health-related stigma and discrimination was evident. Scarce mental health service settings were diverted to become COVID-19 treatment centres. Mental health care became narrowly biomedical with poorer quality of care due to infrequent follow-up. Households of people with pre-existing mental health conditions in the community reported worsening poverty and decreased access to care due to restricted movement, decreased availability and fear. Lack of reliable medication supplies increased relapse and the chance of becoming chained at home, abandoned or homeless. Caregiver burden was exacerbated. Within mental health facilities, prisons and residential units, infection control procedures did not adequately safeguard those with mental health conditions. Meanwhile, the needs of people with mental health conditions in COVID-19 quarantine and treatment facilities were systematically neglected. Only late in the day were integrated services developed to address both physical and mental health needs.

Conclusions
The COVID-19 pandemic had substantial negative impacts on the lives of people with mental health conditions in Ethiopia. Future emergency response should prioritise the human rights, health, social and economic needs of people with mental health conditions. Integration of mental and physical health care would both expand access to care and increase resilience of the mental health system.
Prenatal diagnosis of mosaic chromosomal aneuploidy and uniparental disomy and clinical outcomes evaluation of four fetuses
Authors: Qin Shengfang , Wang Xueyan , Wang Jin , Xi Na , Yan Mengjia , He Yuxia , Ye Mengling , Zhang Zhuo , Yin Yan 
Published: December 2023

Abstract
Background
Few co-occurrence cases of mosaic aneuploidy and uniparental disomy (UPD) chromosomes have been reported in prenatal periods. It is a big challenge for us to predict fetal clinical outcomes with these chromosome abnormalities because of their highly heterogeneous clinical manifestations and limited phenotype attainable by ultrasound.

Methods
Amniotic fluid samples were collected from four cases. Karyotype, chromosome microarray analysis, short tandem repeats, and whole exome sequencing were adopted to analyze fetal chromosomal aneuploidy, UPD, and gene variation. Meanwhile, CNVseq analysis proceeded for cultured and uncultured amniocytes in case 2 and case 4 and MS-MLPA for chr11 and chr15 in case 3.

Results
All four fetuses showed mosaic chromosomal aneuploidy and UPD simultaneously. The results were: Case 1: T2(7%) and UPD(2)mat(12%). Case 2: T15(60%) and UPD(15)mat(40%). Case 3: 45,X(13%) and genome-wide paternal UPD(20%). Case 4: <10% of T20 and > 90% UPD(20)mat in uncultured amniocyte. By analyzing their formation mechanism of mosaic chromosomal aneuploidy and UPD, at least two adverse genetic events happened during their meiosis and mitosis. The fetus of case 1 presented a benign with a normal intrauterine phenotype, consistent with a low proportion of trisomy cells. However, the other three fetuses had adverse pregnancy outcomes, resulting from the UPD chromosomes with imprinted regions involved or a higher level of mosaic aneuploidy.

Conclusion
UPD is often present with mosaic aneuploidy. It is necessary to analyze them simultaneously using a whole battery of analyses for these cases when their chromosomes with imprinted regions are involved or known carriers of a recessive allele. Fetal clinical outcomes were related to the affected chromosomes aneuploidy and UPD, mosaic levels and tissues, methylation status, and homozygous variation of recessive genes on the UPD chromosome. Genetic counseling for pregnant women with such fetuses is crucial to make informed choices.
Reconstruction of private genomes through reference-based genotype imputation
Authors: Mosca Matthew J. , Cho Hyunghoon 
Published: December 2023

AbstractBackgroundGenotype imputation is an essential step in genetic studies to improve data quality and statistical power. Public imputation servers are widely used by researchers to impute their data using otherwise access-controlled reference panels of high-fidelity genomes held by these servers.ResultsWe report evidence against the prevailing assumption that providing access to panels only indirectly via imputation servers poses a negligible privacy risk to individuals in the panels. To this end, we present algorithmic strategies for adaptively constructing artificial input samples and interpreting their imputation results that lead to the accurate reconstruction of reference panel haplotypes. We illustrate this possibility on three reference panels of real genomes for a range of imputation tools and output settings. Moreover, we demonstrate that reconstructed haplotypes from the same individual could be linked via their genetic relatives using our Bayesian linking algorithm, which allows a substantial portion of the individual’s diploid genome to be reassembled. We also provide population genetic estimates of the proportion of a panel that could be linked when an adversary holds a varying number of genomes from the same population.ConclusionsOur results show that genomes in imputation server reference panels can be vulnerable to reconstruction, implying that additional safeguards may need to be considered. We suggest possible mitigation measures based on our findings. Our work illustrates the value of adversarial algorithms in uncovering new privacy risks to help inform the genomics community towards secure data sharing practices.
A blueprint for a multi-disease, multi-domain Bayesian adaptive platform trial incorporating adult and paediatric subgroups: the Staphylococcus aureus Network Adaptive Platform trial
Authors: Mahar Robert K. , McGlothlin Anna , Dymock Michael , Lee Todd C. , Lewis Roger J. , Lumley Thomas , Mora Jocelyn , Price David J. , Saville Benjamin R. , Snelling Tom , Turner Rebecca , Webb Steven A. , Davis Joshua S. , Tong Steven Y. C. , Marsh Julie A. ,   on behalf of the SNAP Global Trial Steering Committee, Bowen Asha , Cheng Matthew , Daneman Nick , Davis Joshua , Goodman Anna , Heriot George , Lee Todd C. , Lewis Roger , Lye David , Marsh Julie , McGlothlin Anna , McQuilten Zoe , Mora Jocelyn , Morpeth Susan , Paterson David , Price David , Roberts Jason , Robinson Owen , Scarborough Matthew , Tong Steven , van Hal Sebastiaan , Walls Genevieve , Webb Steve , Whiteway Lynda , Yahav Dafna 
Published: December 2023

AbstractThe Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a multifactorial Bayesian adaptive platform trial that aims to improve the way that S. aureus bloodstream infection, a globally common and severe infectious disease, is treated. In a world first, the SNAP trial will simultaneously investigate the effects of multiple intervention modalities within multiple groups of participants with different forms of S. aureus bloodstream infection. Here, we formalise the trial structure, modelling approach, and decision rules that will be used for the SNAP trial. By summarising the statistical principles governing the design, our hope is that the SNAP trial will serve as an adaptable template that can be used to improve comparative effectiveness research efficiency in other disease areas.Trial registrationNCT05137119. Registered on 30 November 2021.