bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of lncRNA-m6A gene-mRNA regulatory network to identify m6A-related lncRNAs associated with the progression of lung adenocarcinoma
Authors: Zhang Jiangzhou , Bai Shuheng , Yan Yanli , Kang Haojing , Li Guangzu , Feng Zhaode , Ma Wen , Wang Xuan , Ren Juan 
Published: August 2023

Abstract
Background
We evaluated the prognostic value of m6A-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD).

Methods
The expression levels of lncRNAs and mRNAs in LUAD and normal adjacent tissues from The Cancer Genome Atlas dataset were analyzed using the limma package. m6A enzyme-related differentially expressed lncRNAs and mRNAs were identified and used to construct a regulatory network. Survival analysis was performed and the correlation between lncRNAs, m6A regulators, and mRNAs was analyzed; followed by functional enrichment analysis.

Results
A comparison of LUAD samples and normal tissues identified numerous differentially expressed lncRNAs and mRNAs, demonstrating that a comprehensive network was established. Two lncRNAs and six mRNAs were selected as prognosis related factors including SH3PXD2A-AS1, MAD2L1, CCNA2, and CDC25C. The pathological stage and recurrence status were identified as independent clinical factors (P < 0.05). The expression levels of these RNAs in the different clinical groups were consistent with those in the different risk groups. The interactions of m6A proteins, two lncRNAs, and six mRNAs were predicted, and functional analysis showed that m6A target mRNAs were involved in the cell cycle, progesterone-mediated oocyte maturation, and oocyte meiosis pathways.

Conclusions
These m6A target lncRNAs and mRNAs may be promising biomarkers for predicting clinical prognosis, and the lncRNA-m6A regulator-mRNA regulatory network could improve our understanding of m6A modification in LUAD progression.
Elevation of D-dimer levels are associated with early need for mechanical ventilation support in patients with COVID-19
Authors: Ali Asmaa , Liang Wu , Abdelhafiz Ahmed Samir , Saleh Mai M. , Salem Heba , Moazen Eman M. , Elmazny Maram I. , Rakha Mohammed Abdallah , Elfeky Seham Ezzat Fathy 
Published: August 2023

Abstract
Background
Severe COVID-19 disease is typically associated with an urgent need for supplemental oxygen therapy that may be successfully delivered through conventional methods or require invasive mechanical ventilation. Early prediction of the need for invasive mechanical ventilation could significantly improve outcomes of COVID-19 patients. Plasma levels of D-dimer and a number of inflammatory markers as well as values of complete blood counts, all measured in the first two days of hospital admission of COVID-19 patients, were evaluated for their significance as predictors of the eventual need for invasive mechanical ventilation support as well as their values as predictors of post-ventilation morbidly and mortality.

Methods
This retrospective cohort study was conducted at a single center and included data pertaining to 200 patients with previously confirmed moderate to severe COVID-19 disease in the period between May 2021 and the end of December 2022. Data were retrieved from medical records for further analysis.

Results
The mean (SD) age of patients stood at 59 (14) years of age, and with a majority of patients being male (77%). About 18% of cases, all of significantly older age, had been connected to invasive mechanical ventilation (IMV). Total leucocytic count (TLC), as well as levels of urea, creatinine, D-dimer, ferritin, and CRP in IMV patients were significantly higher than non-ventilated patients (p < 0.01 for all). In contrast, lymphocytic count, hemoglobin level, and platelet count were significantly lower in IMV patients (p < 0.001, 0.04, and 0.002, respectively). The mortality rate was significantly higher in IMV patients (p < 0.001). D-dimer independently predicted IMV demand (OR = 1, p = 0.001 in adjusted and unadjusted models). The utility of D-dimer was excellent; and the cutoff level of above 1415 µ/L showed sensitivity and specificity of about 92% and 76%, respectively. Also, the D-dimer level was very effective in predicting post-IMV survival; the AUC = 0.86, p = 0.02, and a cutoff value below 4558 µ/L was associated with 100% and 66% sensitivity and specificity, respectively.

Conclusions
High D-dimer levels independently correlated with the need for invasive mechanical ventilation. Low levels of this marker could evidently predict post-IMV survival of mechanically ventilated COVID-19 patients. Measuring D-dimer levels during routine follow up of those patients would thus be useful in predicting patient outcomes.
Prognostic value of triglyceride glucose index in population at high cardiovascular disease risk
Authors: Cai Xiao-ling , Xiang Yi-fei , Chen Xiao-fang , Lin Xue-qin , Lin Bi-ting , Zhou Geng-yu , Yu Lin , Guo Yan-song , Lin Kai-yang 
Published: August 2023

Abstract
Background
Early identification of populations at high cardiovascular disease (CVD) risk and improvement of risk factors can significantly decrease the probability of CVD development and improve outcomes. Insulin resistance (IR) is a CVD risk factor. The triglyceride glucose (TyG) index is a simple and reliable index for evaluating IR. However, no clinical studies on the prognostic value of the TyG index in a high risk CVD population have been conducted. This study evaluated the relationship between the TyG index and prognosis in a high risk CVD population.

Methods
This study enrolled 35,455 participants aged 35–75 years who were at high CVD risk and visited selected health centers and community service centers between 2017 and 2021. Their general clinical characteristics and baseline blood biochemical indicators were recorded. The TyG index was calculated as ln[fasting triglyceride (mg/dl)× fasting blood glucose (mg/dl)/2]. The endpoints were all-cause death and cardiovascular death during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the TyG index and endpoints.

Results
In the overall study population, the mean age of all participants was 57.9 ± 9.6 years, 40.7% were male, and the mean TyG index was 8.9 ± 0.6. All participants were divided into two groups based on the results of the RCS analysis, with a cut-off value of 9.83. There were 551 all-cause deaths and 180 cardiovascular deaths during a median follow-up time of 3.4 years. In the multivariate Cox proportional hazard model, participants with a TyG index ≥ 9.83 had a higher risk of all-cause death (Hazard ratio [HR] 1.86, 95% Confdence intervals [CI] 1.37–2.51, P<0.001) and cardiovascular death (HR 2.41, 95%CI 1.47–3.96, P = 0.001) than those with a TyG index < 9.83. Subgroup analysis revealed that there was no interaction between the TyG index and variables in all subgroup analyses.

Conclusions
The high TyG index was associated with an increased risk of all-cause death and cardiovascular death in people at high risk of CVD. This finding demonstrates the value of the TyG index in the primary prevention of CVD.

Trial registration
retrospectively registered, the registration number is K2022-01-005 and the date is 2022.01.30.
Measuring quality of facility-based ITN distribution in Ghana
Authors: Nuñez Luigi , Skjefte Malia , Asamoah Obed E. , Owusu Prince , Malm Keziah L. , Miller Jane E. 
Published: August 2023

Abstract
Background
Continuous distribution channels are effective methods to deliver malaria interventions such as insecticide treated nets (ITNs) to pregnant women attending antenatal care clinics and children under five attending immunization visits. Facility-based and provider-based checklists were used during supportive supervision visits to measure the quality of facility-based services and interventions. This study looks at ITN distributions at health facilities in Ghana, with the aim of providing insights on how quality can be measured and monitored.

Methods
Various quality improvement approaches for malaria services occur in Ghana. Selected indicators were analysed to highlight the similarities and differences of how the approaches measured how well the channel was doing. Generally, the approaches assessed (1) service data management, (2) logistics data management, and (3) observation of service provision (ITN issuance, malaria education, ITN use and care education). Two approaches used a binary (Yes/No) scale, and one used a Likert scale.

Results
Results showed that most data reported to the national HMIS is accurate. Logistics data management remained an issue at health facilities, as results showed scores below average across facility stores, antenatal care, and immunization. Though the supervision approaches differed, overall results indicated that almost all eligible clients received ITNs, data were recorded accurately and reported on-time, and logistics was the largest challenge to optimal distribution through health facilities.

Conclusion
The supervision approaches provided valuable insights into the quality of facility-based ITN distribution. Ghana should continue to implement supportive supervision in their malaria agenda, with additional steps needed to improve reporting of collected data and increase the number of facilities visited for supportive supervision and the frequency. There were various supervision approaches used with no clear guidance on how to measure quality of facility-based ITN distribution, so there is also need for the global community to agree on standardized indicators and approaches to measuring quality of facility-based ITN distribution. Additionally, future studies can review the effect of multiple rounds of supervision visits on the quality of ITN distribution as well as understand the facilitators and barriers to scaling up supervision of facility-based ITN distribution.
Receptor tyrosine kinases Tyro3, Axl, and Mertk differentially contribute to antibody-induced arthritis
Authors: Gao Liang , He Chao , Yang Aizhen , Zhou Haibin , Lu Qingxian , Birge Raymond B. , Wu Yi 
Published: August 2023

AbstractTyro3, Axl, and Mertk (abbreviated TAMs) comprise a family of homologous type 1 receptor tyrosine kinases (RTKs) that have been implicated as inhibitory receptors that dampen inflammation, but their roles in the pathogenesis of rheumatoid arthritis remains understudied. Here, to investigate TAMs in an inflammatory arthritis model, antibody-induced arthritis in single TAM-deficient mice (Tyro3- KO, Axl-KO, Mertk-KO) was induced by K/BxN serum injection. Subsequently, joint inflammation and cytokine levels, as well as the expression of Fcγ Rs and complement receptors were assessed in WT and TAM-deficient mice. Compared with littermate control mice, Axl−/− and Mertk−/− mice developed more severe antibody-induced arthritis, while in contrast, Tyro3−/− mice showed diminished joint inflammation. Concomitantly, the levels of cytokines in joints of Axl−/− and Mertk−/− mice were also significantly increased, while cytokines in the Tyro3−/− joint tissues were decreased. At the molecular and cellular level, TAMs showed distinct expression patterns, whereby monocytes expressed Axl and Mertk, but no Tyro3, while neutrophils expressed Axl and Tyro3 but little Mertk. Moreover, expression of Fcγ receptors and C5aR showed different patterns with TAMs expression, whereby FcγRIV was higher in monocytes of Axl−/− and Mertk−/− mice compared to wild-type mice, while Tyro3−/− neutrophils showed lower expression levels of FcγRI, FcγRIII and FcγRIV. Finally, expression of C5aR was increased in Mertk−/− monocytes, and was decreased in Tyro3−/− neutrophils. These data indicate that Axl, Mertk and Tyro3 have distinct functions in antibody-induced arthritis, due in part to the differential regulation of cytokines production, as well as expression of FcγRs and C5aR.
GSG2 facilitates the progression of human breast cancer through MDM2-mediated ubiquitination of E2F1
Authors: Tang Yu , Dai Gaosai , Yang Yupeng , Liu Huantao 
Published: August 2023

Abstract
Background
Breast cancer (BC) has posed a great threat to world health as the leading cause of cancer death among women. Previous evidence demonstrated that germ cell-specific gene 2 (GSG2) was involved in the regulation of multiple cancers. Thus, the clinical value, biological function and underlying mechanism of GSG2 in BC were investigated in this study.

Methods
The expression of GSG2 in BC was revealed by immunohistochemistry (IHC), qPCR and western blotting. Secondly, the biological function of GSG2 in BC was evaluated by MTT assay, flow cytometry, Transwell assay and wound healing assay. Furthermore, the potential molecular mechanism of GSG2 regulating the progression of BC by co-immunoprecipitation (Co-IP) and protein stability detection.

Results
Our data indicated that GSG2 was frequently overexpressed in BC. Moreover, there was a significant correlation between the GSG2 expression and the poor prognosis of BC patients. Functionally, GSG2 knockdown inhibited the malignant progression of BC characterized by reduced proliferation, enhanced apoptosis and attenuated tumor growth. Migration inhibition of GSG2 knockdown BC cells via epithelial-mesenchymal transition (EMT), such as downregulation of Vimentin and Snail. In addition, E2F transcription factor 1 (E2F1) was regarded as a target protein of GSG2. Downregulation of E2F1 attenuated the promoting role of GSG2 on BC cells. Mechanistically, knockdown of GSG2 accelerated the ubiquitination of E2F1 protein, which was mediated by E3 ubiquitin ligase MDM2.

Conclusions
GSG2 facilitated the development and progression of BC through MDM2-mediated ubiquitination of E2F1, which may be a promising candidate target with potential therapeutic value.
Lived experiences of pregnant and parenting adolescents in Africa: A scoping review
Authors: Ajayi Anthony Idowu , Athero Sherine , Muga Winstoun , Kabiru Caroline W. 
Published: August 2023

Abstract
Background
Previous studies have not synthesized existing literature on the lived experiences of pregnant and parenting adolescents (aged 10–19) in Africa. Such evidence synthesis is needed to inform policies, programs, and future research to improve the well-being of the millions of pregnant or parenting adolescents in the region. Our study fills this gap by reviewing the literature on pregnant and parenting adolescents in Africa. We mapped existing research in terms of their substantive focus, and geographical distribution. We synthesized these studies based on thematic focus and identified gaps for future research.

Methods
We used a three-step search strategy to find articles, theses, and technical reports reporting primary research published in English between January 2000 and June 2021 in PubMed, Jstor, AJOL, EBSCO Host, and Google Scholar. Three researchers screened all articles, including titles, abstracts, and full text, for eligibility. Relevant data were extracted using a template designed for the study. Overall, 116 studies met the inclusion criteria and were included in the study. Data were analyzed using descriptive and thematic analyses.

Results
Research on pregnant and parenting adolescents is limited in volume and skewed to a few countries, with two-fifths of papers focusing on South Africa (41.4%). Most of the studies were African-led (81.9%), received no funding (60.3%), adopted qualitative designs (58.6%), and were published between 2016 and 2021 (48.3%). The studies highlighted how pregnancy initiates a cycle of social exclusion of girls with grave implications for their physical and mental health and social and economic well-being. Only 4.3% of the studies described an intervention. None of these studies employed a robust research design (e.g., randomized controlled trial) to assess the intervention’s effectiveness. Adolescent mothers' experiences (26.7%) and their education (36.2%) were the most studied topics, while repeat pregnancy received the least research attention.

Conclusion
Research on issues affecting pregnant and parenting adolescents is still limited in scope and skewed geographically despite the large burden of adolescent childbearing in many African countries. While studies have documented how early pregnancy could result in girls' social and educational exclusion, few interventions to support pregnant and parenting adolescents exist. Further research to address these gaps is warranted.
The impact of bleeding event frequency on health-related quality of life and work productivity outcomes in a European cohort of adults with haemophilia A: insights from the CHESS II study
Authors: Young Lisa , Chen Yong , Alvir José , Burke Tom , Ferri Grazzi Enrico , Winburn Ian 
Published: August 2023

Abstract
Background
Haemophilia A carries a substantial healthcare burden, affecting health-related quality of life (HRQoL). The Cost of Haemophilia in Men: a Socioeconomic Survey II (CHESS II), a retrospective real-world study, characterised the burden of haemophilia and its impact on HRQoL and work productivity. The current analysis explored the impact of bleeding events on HRQoL and work productivity in Europe. This analysis focused on data collected from males aged 18 to 64 years with haemophilia A without inhibitors who were receiving replacement factor products or a monoclonal antibody and were not participating in a clinical trial at the time of study recruitment. Descriptive statistics were analysed using scores from EuroQoL’s EQ-5D-5L index and EQ-VAS analogue scale and the Work Productivity and Activity Index Specific Health Problem (WPAI:SHP) percentage scores stratified by the number of annual bleeding events (ABs) 0, 1, 2, 3–4, or ≥ 5.

Results
Of 918 males with haemophilia A in CHESS II, 318 met inclusion criteria and had data available for HRQoL measures; mean age (SD) was 33.8 (12.1) years and 96% were White. Mean (SD) ABs of 2.7 (2.9) occurred over the preceding 12 months: 20% had 3 or 4 ABs; 17% had ≥ 5 ABs. Mean EQ-5D-5L index scores for patients with 0, 1, 2, 3–4, or ≥ 5 ABs were 0.92, 0.76, 0.76, 0.71, and 0.56, respectively. Mean (SD) EQ-VAS scores were 86.9 (13.6), with 0 ABs versus 69.5 (19.1) for 3 or 4 ABs and 61.2 (17.2) for ≥ 5 ABs. Mean percentage of overall work productivity loss on the WPAI:SHP questionnaire ranged from 9.70 to 0 ABs to 47.65 for ≥ 5 ABs.

Conclusions
In this European sample of adult men with haemophilia A, HRQoL and work productivity scores were lower among those reporting more AB events. Bleeding burden appears to affect HRQoL and productivity; however, this cross-sectional analysis limits the ability to draw firm conclusions on causality.
Intrathecal magnesium delivery for Mg++-insensitive NMDA receptor activity due to GRIN1 mutation
Authors: Lewis Sara A. , Shetty Sheetal , Gamble Sean , Heim Jennifer , Zhao Ningning , Stitt Gideon , Pankratz Matthew , Mangum Tara , Marku Iris , Rosenberg Robert B. , Wilfong Angus A. , Fahey Michael C. , Kim Sukhan , Myers Scott J. , Appavu Brian , Kruer Michael C. 
Published: August 2023

Abstract
Background
Mutations in the NMDA receptor are known to disrupt glutamatergic signaling crucial for early neurodevelopment, often leading to severe global developmental delay/intellectual disability, epileptic encephalopathy, and cerebral palsy phenotypes. Both seizures and movement disorders can be highly treatment-refractory.

Results
We describe a targeted ABA n-of-1 treatment trial with intrathecal MgSO4, rationally designed based on the electrophysiologic properties of this gain of function mutation in the GRIN1 NMDA subunit.

Conclusion
Although the invasive nature of the trial necessitated a short-term, non-randomized, unblinded intervention, quantitative longitudinal neurophysiologic monitoring indicated benefit, providing class II evidence in support of intrathecal MgSO4 for select forms of GRIN disorders.
CD20 × CD3 bispecific antibodies for lymphoma therapy: latest updates from ASCO 2023 annual meeting
Authors: Liu Xinyuan , Zhao Juanjuan , Guo Xiangqian , Song Yongping 
Published: August 2023

AbstractMultiple bispecific antibodies (bsAbs) have been approved for cancer immunotherapy. Several CD20 × CD3 bsAbs have demonstrated significant anti-B-cell non-Hodgkin lymphoma (NHL) activity by engaging T cells to target CD20+ NHL cells in clinical trials. Mosunetuzumab, epcoritamab and glofitamab have been approved recently for B-cell NHL therapy. In this study, we summarized several latest reports on CD20 × CD3 bsAbs for the therapy of B-cell NHL from the ASCO 2023 annual meeting (ASCO2023).
Progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with anti-glycine receptor antibodies and urothelial carcinoma: a case report
Authors: Ali Amanuel Hassen , Benterud Anna , Holmøy Trygve , Myro Aija Zuleron 
Published: August 2023

Abstract
Background
Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological condition with paraneoplastic etiology in about 20% of cases, usually presenting before or shortly after the oncological diagnosis is established. PERM associated with anti-glycine receptor antibodies is not previously reported in a patient with bladder cancer.

Case presentation
A 72-years-old Caucasian male was admitted with acute onset of dysarthria, dysphagia and trismus three years after initial surgical treatment for bladder cancer. The condition was initially diagnosed as tetanus and treated accordingly, but the diagnosis was reconsidered because of progression despite adequate treatment. Diagnostic workup on readmission revealed lung and paraaortal metastases from bladder cancer and anti-glycine receptor (anti-GlyR) antibodies both in the cerebrospinal fluid and in serum, which supplemented with the clinical presentation led to the diagnosis of PERM, presumably related to bladder cancer. The patient showed improvement and stabilization after treatment with intravenous immunoglobulin and chemotherapy against metastatic bladder cancer.

Conclusion
To the best of our knowledge, this is the first reported case of anti-GlyR antibody positive PERM related to urothelial carcinoma. The symptoms mimicked tetanus, and responded to chemotherapy and immunotherapy.
Variational inequality arising from variable annuity with mean reversion environment
Authors: Jeon Junkee , Kim Geonwoo 
Published: August 2023

AbstractIn this paper, we study a variational inequality arising from variable annuity (VA) to find the optimal surrender strategy for a VA investor when the underlying asset follows a mean reverting process. We formulate the problem as a free boundary partial differential equation (PDE) to obtain the optimal strategy. The PDE is solved analytically by the Mellin transform approach. Using the Mellin transform, we derive the integral equations for the value of the VA and the optimal surrender boundary. Since the solutions are obtained as the integral equations, we use the recursive integration method to determine the optimal surrender strategy. Finally, we provide the optimal surrender boundaries and values of VA with respect to some significant parameters to show the impacts of mean reversion.