bluuebunny/crossref_metadata_2025_split huggingface dataset:
Broad synergistic antiviral efficacy between a novel elite controller-derived dipeptide and antiretrovirals against drug-resistant HIV-1
Authors: Giammarino Federica , Sönnerborg Anders , Ceña-Diez Rafael 
Published: June 2024

IntroductionThe naturally occurring dipeptide Tryptophylglycine (WG) is enhanced in human immunodeficiency virus (HIV-1) infected Elite Controllers (EC). We have shown that this dipeptide has an anti-HIV-1 effect and evaluated now its synergistic antiretroviral activity, in combination with current antiretrovirals against multi-drug resistant HIV-1 isolates.MethodsDrug selectivity assay with WG-am and ARVs agains HIV-1 resistant isolates were carried out. Subsequently, two methods, Chou-Talalay’s Combination Index (CI) and ZIP synergy score (SS), were used to quantify the synergism.ResultsWG-am had a moderate/strong synergism with the four tested antiretrovirals: raltegravir, tenofovir, efavirenz, darunavir. WG-am:TDF had strong synergism at ED50, ED75, ED90 (CI: &lt;0.2) in isolates resistant to protease inhibitors or integrase strand inhibitors (INSTI), and a slightly less synergism in isolates resistant to non-nucleoside or nucleotide reverse transcriptase inhibitors. WG-am combined with each of the four drugs inhibited all drug-resistant isolates with over 95% reduction at maximum concentration tested. The highest selectivity indexes (CC50/ED50) were in INSTI-resistant isolates.ConclusionOur data suggest that WG, identified as occurring and enhanced in Elite Controllers has a potential to become a future treatment option in patients with HIV-1 strains resistant to any of the four major categories of anti-HIV-1 compounds.
Case Report: unexpected cause of cyanosis in an infant after acute exposure to high altitude—severe tricuspid regurgitation secondary to tricuspid valve prolapse
Authors: Cui Yaru , Yang Lixia , Wu Ping , Shao Shuran , Luo Shuhua , Zhou Kaiyu , Liu Xiaoliang , Wang Chuan , Duan Hongyu 
Published: June 2024

BackgroundSevere tricuspid regurgitation (TR) causing cyanosis with patent foramen ovale (PFO) and right-to-left atrial shunting requires a precise diagnosis for optimal therapy. Tricuspid valve prolapse (TVP) can lead to TR and is sometimes overlooked, especially in complex cases with factors like pulmonary hypertension (PH). We present an infant with cyanosis and profound TR after high-altitude exposure, initially misattributed to PH but found to be primarily due to spontaneous chordae tendineae rupture and TVP. This case underscores the challenges in diagnosing TR-induced cyanosis.Case presentationThe 3-month-old infant rapidly developed cyanosis, hypoxemia, right atrial enlargement, severe tricuspid regurgitation (TR), and patent foramen ovale (PFO) shunting after high-altitude exposure. Although echocardiography revealed tricuspid valve prolapse (TVP), initial consideration linked TR and right-to-left shunting to pulmonary hypertension (PH) due to the temporal correlation with rapid altitude exposure. Despite hemodynamic stability and the absence of respiratory distress after respiratory support and combined PH medication therapy, the persistent hypoxemia did not reverse as expected. This treatment outcome and repeated echocardiograms reminded us that TR was primarily caused by TVP rather than PH alone. Intraoperative exploration confirmed that TVP was caused by a rupture of TV chordae tendineae and anterior papillary muscle head, and the chordae tendineae/papillary muscle connection was reconstructed. After surgery, this patient was noncyanotic with an excellent long-term prognosis, a trivial TR with normal TV function being observed echocardiographically.ConclusionsTR-induced cyanosis can be not only a consequence of PH and right-sided heart dilation but also a primary condition. Repetitive reassessment should be undertaken with caution, particularly when patients are not improving on therapy in the setting of conditions known to predisposition to secondary TR. Since TVP caused by rupture of the chordae or papillary muscles is rare but fatal in children, early diagnosis is clinically substantial to proper management and satisfactory long-term outcomes.
Changes of cardiac function: cardiac adaptation in patients with hypothyroidism assessed by cardiac magnetic resonance-a meta-analysis
Authors: Yang Yucheng , Xue Chen , Zhao Junyu , Zhang Laozhui , Wang Yanwei , Ouyang Meixiang , Li Ju , Wang Haipeng , Wang Cuiyan 
Published: June 2024

ObjectiveThe meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance.Research methods and proceduresDatabases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114.ResultsSix studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls.ConclusionHypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function.Systematic review registrationhttps://inplasy.com, identifier (INPLASY202440114).
Levels of asymmetric dimethylarginine in plasma and aqueous humor: a key risk factor for the severity of fibrovascular proliferation in proliferative diabetic retinopathy
Authors: Guo Xinyang , Jin Wei , Xing Yiqiao 
Published: June 2024

IntroductionProliferative diabetic retinopathy (PDR) is a common diabetes complication, significantly impacting vision and quality of life. Previous studies have suggested a potential link between arginine pathway metabolites and diabetic retinopathy (DR). Connective tissue growth factor (CTGF) plays a role in the occurrence and development of fibrovascular proliferation (FVP) in PDR patients. However, the relationship between arginine pathway metabolites and FVP in PDR remains undefined. This study aimed to explore the correlation between four arginine pathway metabolites (arginine, asymmetric dimethylarginine[ADMA], ornithine, and citrulline) and the severity of FVP in PDR patients.MethodsIn this study, plasma and aqueous humor samples were respectively collected from 30 patients with age-related cataracts without diabetes mellitus (DM) and from 85 PDR patients. The PDR patients were categorized as mild-to-moderate or severe based on the severity of fundal FVP. The study used Kruskal-Wallis test to compare arginine, ADMA, ornithine, and citrulline levels across three groups. Binary logistic regression identified risk factors for severe PDR. Spearman correlation analysis assessed associations between plasma and aqueous humor metabolite levels, and between ADMA and CTGF levels in aqueous humor among PDR patients.ResultsADMA levels in the aqueous humor were significantly greater in patients with severe PDR than in those with mild-to-moderate PDR(P=0.0004). However, the plasma and aqueous humor levels of arginine, ornithine, and citrulline did not significantly differ between mild-to-moderate PDR patients and severe PDR patients (P&gt;0.05). Binary logistic regression analysis indicated that the plasma (P=0.01) and aqueous humor (P=0.006) ADMA levels in PDR patients were risk factors for severe PDR. Furthermore, significant correlations were found between plasma and aqueous humor ADMA levels (r=0.263, P=0.015) and between aqueous humor ADMA and CTGF levels (r=0.837, P&lt;0.001).ConclusionElevated ADMA levels in plasma and aqueous humor positively correlate with the severity of FVP in PDR, indicating ADMA as a risk factor for severe PDR.
Early marriage, education and mental health: experiences of adolescent girls in Mozambique
Authors: Nhampoca Joaquim M. , Maritz Jeanette E. 
Published: June 2024

Introduction and backgroundEarly marriage and maternity represent a violation of human rights and a barrier to achieving gender equality in education. Studies conducted across various regions and countries, including Mozambique, have highlighted the negative consequences of early marriage and maternity, particularly on adolescent girls' physical, educational and mental health. Adolescent girls who marry before the age of 18 are more prone to a broad spectrum of mood, anxiety, and other psychiatric disorders. In the districts of Maganja da Costa and Morrumbala in Zambézia Province, Mozambique, high rates of early marriage persist despite government policies and interventions.Purpose statementThis study aims to understand early marriage's socio-cultural, economic, and psychological drivers and impacts on adolescent girls' lives, focusing on education, mental health, and well-being.Design and methodsThis paper used a qualitative research design. We employed a life-story approach and used purposeful sampling to identify participants. Semi-structured interviews were conducted with 25 participants and the data were analysed using Tesch's thematic analysis approach.ResultsElements contributing to early marriage and pregnancy are intricately linked with socio-cultural elements. These include the induction into specific societal roles, the affirmation of childbearing, the perceived importance of dowry, the impact of rite-of-passage ceremonies, and the cultural significance associated with a girl's initial menstruation. School dropout often originates from geographical and transportation challenges, nudging adolescent girls towards early marriage. In some instances, termination of pregnancy was viewed as a solution, while engaging in sexual activities was seen as a means to inject purpose into their lives or as a response to poverty. Positive changes and emotions were evident, yet regrettably, the ramifications of early pregnancy and marriage were primarily detrimental. These influenced the adolescent girls' interpersonal connections, educational and career opportunities, emotional well-being, and access to support networks.ConclusionsThe modern perspective, which advocates for equal educational rights for boys and girls and posits that marriage should occur after the age of 18, contradicts the socio-cultural perspective of adulthood.ContributionThis study adds to the ongoing efforts to prevent and combat early marriage and maternity in Africa.
Elucidating sleep disorders: a comprehensive bioinformatics analysis of functional gene sets and hub genes
Authors: Lin Junhan , Liu Changyuan , Hu Ende 
Published: June 2024

BackgroundSleep disorders (SD) are known to have a profound impact on human health and quality of life although their exact pathogenic mechanisms remain poorly understood. MethodsThe study first accessed SD datasets from the GEO and identified DEGs. These DEGs were then subjected to gene set enrichment analysis. Several advanced techniques, including the RF, SVM-RFE, PPI networks, and LASSO methodologies, were utilized to identify hub genes closely associated with SD. Additionally, the ssGSEA approach was employed to analyze immune cell infiltration and functional gene set scores in SD. DEGs were also scrutinized in relation to miRNA, and the DGIdb database was used to explore potential pharmacological treatments for SD. Furthermore, in an SD murine model, the expression levels of these hub genes were confirmed through RT-qPCR and Western Blot analyses.ResultsThe findings of the study indicate that DEGs are significantly enriched in functions and pathways related to immune cell activity, stress response, and neural system regulation. The analysis of immunoinfiltration demonstrated a marked elevation in the levels of Activated CD4+ T cells and CD8+ T cells in the SD cohort, accompanied by a notable rise in Central memory CD4 T cells, Central memory CD8 T cells, and Natural killer T cells. Using machine learning algorithms, the study also identified hub genes closely associated with SD, including IPO9, RAP2A, DDX17, MBNL2, PIK3AP1, and ZNF385A. Based on these genes, an SD diagnostic model was constructed and its efficacy validated across multiple datasets. In the SD murine model, the mRNA and protein expressions of these 6 hub genes were found to be consistent with the results of the bioinformatics analysis.ConclusionIn conclusion, this study identified 6 genes closely linked to SD, which may play pivotal roles in neural system development, the immune microenvironment, and inflammatory responses. Additionally, the key gene-based SD diagnostic model constructed in this study, validated on multiple datasets showed a high degree of reliability and accuracy, predicting its wide potential for clinical applications. However, limited by the range of data sources and sample size, this may affect the generalizability of the results.
Elevated extracellular particle concentration in plasma predicts in-hospital mortality after severe trauma
Authors: Becker Nils , Franz Niklas , Eguchi Akiko , Wagner Alessa , Sturm Ramona , Rinderknecht Helen , Kobayashi Yoshinao , Iwasa Motoh , Weber Birte , Marzi Ingo , Relja Borna 
Published: June 2024

BackgroundExtracellular particles (EPs), particularly extracellular vesicles, play a crucial role in regulating various pathological mechanisms, including immune dysregulations post-trauma. Their distinctive expression of cell-specific markers and regulatory cargo such as cytokines or micro-ribonucleic acid suggests their potential as early biomarkers for organ-specific damage and for identifying patients at risk for complications and mortality. Given the critical need for reliable and easily assessable makers to identify at-risk patients and guide therapeutic decisions, we evaluated the early diagnostic value of circulating EPs regarding outcomes in severely injured multiple-trauma patients.MethodsPlasma samples were collected from 133 severely injured trauma patients (Injury Severity Score (ISS) ≥16) immediately upon arrival at the emergency department (ED). Patients were categorized into survivors and non-survivors. Injury characteristics and outcomes related to sepsis, pneumonia, or early (&lt;1 day after admission) and late mortality were assessed. Circulating EPs, cytokine profiles, and blood counts of platelets and leukocytes were determined. Receiver operating characteristic analyses were conducted.ResultsDespite no significant differences in injury pattern or severity, non-survivors exhibited significantly elevated counts of circulating EPs compared to survivors. The optimal cut-off for EPs &lt;200 nm indicating non-survivors was 17380/µl plasma, with a sensitivity of 77% and a specificity of 61% in predicting in-hospital mortality. Later non-survivors received significantly higher numbers of units of packed red blood cells [8.54 ± 5.45 vs. 1.29 ± 0.36 units], had higher serum lactate [38.00 ± 7.51 vs. 26.98 ± 1.58 mg/dL], significantly lower platelet counts [181.30 ± 18.06 vs. 213.60 ± 5.85 *10³/µL] and lower heart rates [74.50 ± 4.93 vs. 90.18 ± 2.06 beats/minute] upon arrival at the ED compared to survivors.ConclusionOur results demonstrate the high diagnostic potential of elevated concentrations of circulating EPs &lt;200 nm for identifying patients at risk of mortality after severe trauma. This parameter shows comparable sensitivity to established clinical predictors. Early evaluation of EPs concentration could complement assessment markers in guiding early therapeutic decisions.
Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study
Authors: Liang Liu-dan , Li Sheng , Huang Mei-jin , Peng Hui-xin , Lu Zi-jun , Zhang Zhuo-hua , Su Li-ye , Sooranna Suren R. , Liu Yan , Huang Zhao-he 
Published: June 2024

BackgroundSome recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis.MethodsThis study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p &lt; 1.0 × 10–5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran’s Q and the leave-one-out tests were carried out to assess the robustness of our findings.ResultsOur study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66–1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66–0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07–1.67, p = 0.011).ConclusionThis two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.
Inhibition of phosphorus removal performance in activated sludge by Fe(III) exposure: transitions in dominant metabolic pathways
Authors: Hong Yiyihui , Cheng Hong , Huangfu Xiaoliu , Li Lin , He Qiang 
Published: June 2024

IntroductionSimultaneous chemical phosphorus removal process using iron salts (Fe(III)) has been widely utilized in wastewater treatment to meet increasingly stringent discharge standards. However, the inhibitory effect of Fe(III) on the biological phosphorus removal system remains a topic of debate, with its precise mechanism yet to be fully understood.MethodsBatch and long-term exposure experiments were conducted in six sequencing batch reactors (SBRs) operating for 155 days. Synthetic wastewater containing various Fe/P ratios (i.e., Fe/P = 1, 1.2, 1.5, 1.8, and 2) was slowly poured into the SBRs during the experimental period to assess the effects of acute and chronic Fe(III) exposure on polyphosphate-accumulating organism (PAO) growth and phosphorus metabolism.ResultsExperimental results revealed that prolonged Fe(III) exposure induced a transition in the dominant phosphorus removal mechanism within activated sludge, resulting in a diminished availability of phosphorus for bio-metabolism. In Fe(III)-treated groups, intracellular phosphorus storage ranged from 3.11 to 7.67 mg/g VSS, representing only 26.01 to 64.13% of the control. Although the abundance of widely reported PAOs (Candidatus Accumulibacter) was 30.15% in the experimental group, phosphorus release and uptake were strongly inhibited by high dosage of Fe(III). Furthermore, the abundance of functional genes associated with key enzymes in the glycogen metabolism pathway increased while those related to the polyphosphate metabolism pathway decreased under chronic Fe(III) stress.DiscussionThese findings collectively suggest that the energy generated from polyhydroxyalkanoates oxidation in PAOs primarily facilitated glycogen metabolism rather than promoting phosphorus uptake. Consequently, the dominant metabolic pathway of communities shifted from polyphosphate-accumulating metabolism to glycogen-accumulating metabolism as the major contributor to the decreased biological phosphorus removal performance.
Case report: Endoscopic endonasal transposterior clinoid approach for resection of posterior clinoid process meningioma: technical notes and literature review
Authors: Awyono Steven , Takeuchi Kazuhito , Ito Eiji , Nagata Yuichi , Golden Nyoman , Mahadewa Tjokorda Gde Bagus , Saito Ryuta 
Published: June 2024

BackgroundPosterior clinoid process (PCP) meningioma is an exceedingly rare entity. It remains the most challenging skull base lesion for neurosurgeons due to its treacherous location that insinuates amongst critical neurovascular structures. This article will describe the technical notes using the endoscopic endonasal approach that provide the earliest devascularization and detachment of the tumor PCP meningioma.MethodsWe are introducing the surgical implementation of an endoscopic endonasal approach to removing PCP meningioma. Furthermore, we perform a literature review of posterior clinoid process meningioma that undergoes surgical intervention, then summarize the benefits and limitations of each approach.ResultsWe present a case of right PCP meningioma that was removed using an endoscopic endonasal approach through the transposterior clinoid corridor in a 52-year-old-woman. We describe the technical notes in performing this approach to have the earliest devascularization and detachment of the tumor by performing posterior clinoidectomy. Safe tumor removal is performed with a wide and clear view of the surrounding neurovascular structure. Based on our database search, we found nine articles reported on the surgical management of PCP meningiomas, with a total number of 15 cases. All of the reported cases performed the tumor removal using the transcranial approach.ConclusionThe endoscopic endonasal transposterior clinoid approach circumvents all disadvantages faced by the traditional transcranial approach, providing the earliest approach to devascularized and detaching the tumor from its attachment at PCP. This approach demonstrates safety and efficacy, making it an acceptable alternative for PCP meningioma resections.