bluuebunny/crossref_metadata_2025_split huggingface dataset:
A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer
Authors: Shao Hanqiao , Zhao Mingye , Guan Ai-Jia , Shao Taihang , Zhou Dachuang , Yu Guo , Tang Wenxi 
Published: January 2024

AbstractBackgroundHormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 −) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis.MethodsRCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3–5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics.ResultsA total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings.ConclusionsCDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results’ uncertainty, further trials comparing these novel treatments are warranted.Trial registrationRegistration number: PROSPERO (CRD42022377431).
Therapeutic antibodies for the prevention and treatment of cancer
Authors: Kumar Mukesh , Jalota Akansha , Sahu Sushil Kumar , Haque Shabirul 
Published: January 2024

AbstractThe developments of antibodies for cancer therapeutics have made remarkable success in recent years. There are multiple factors contributing to the success of the biological molecule including origin of the antibody, isotype, affinity, avidity and mechanism of action. With better understanding of mechanism of cancer progression and immune manipulation, recombinant formats of antibodies are used to develop therapeutic modalities for manipulating the immune cells of patients by targeting specific molecules to control the disease. These molecules have been successful in minimizing the side effects instead caused by small molecules or systemic chemotherapy but because of the developing therapeutic resistance against these antibodies, combination therapy is thought to be the best bet for patient care. Here, in this review, we have discussed different aspects of antibodies in cancer therapy affecting their efficacy and mechanism of resistance with some relevant examples of the most studied molecules approved by the US FDA.
Measuring sustainability of opioid agonist therapy programs in the context of transition from Global Fund support
Authors: Stuikyte Raminta , Varentsov Ivan , Cook Catherine , Dvoriak Sergii 
Published: January 2024

Abstract
Background
Programmatic and financial sustainability of health responses dependent on donor funding has risen as a major concern. In the HIV field in particular, it generated a number of instruments and assessments on sustainability and processes related to donor transition planning. The authors aimed to develop an instrument specific to opioid agonist therapy (OAT) programs as they were addressed only marginally by the HIV-specific assessments.

Methods
The development of the OAT sustainability instrument used desk review of existing HIV sustainability concepts and tools, an International Advisory Board, and piloting to validate the instrument.

Results
The new OAT sustainability instrument is comprised of the three parts: the conceptual framework, methodological guidelines and a practical implementation tool for assessing the degree of OAT sustainability at the country level. It measures sustainability in the three broad areas for sustainability measuring–Policy & Governance; Finance & Resources; and Services. The selection of indicators and their composites for the three sustainability areas extensively used the United Nations and World Health Organization’s guidance on health system building blocks, on care and HIV and viral hepatitis prevention among people using opioids and for opioid dependence, and the definition of access to health framed by the United Nations Convent on Economic, Social and Cultural Rights. The instrument’s methodological guidelines require the engagement of a national consultant to conduct desk review, key informant interviews and focus groups for measuring discrete milestones and adding qualitative information for interpretation of the data, progress and opportunities. The guidelines advise engaging a country-specific multi-stakeholder advisory group for planning, validation and follow-up of the assessment. The pilot of the instrument in 3 countries in 2020 validated it and required minor adjustments in the instrument. By mid-2023, the instrument has been successfully applied in 5 countries.

Conclusions
The developed instrument enables a comprehensive review of the resilience of OAT programs and their ability to scale up and to inform a roadmap for improved sustainability. While developed in the context of Eastern Europe and Central Asia, it has been reviewed by a global advisory panel and could be easily adapted outside this regional context.
Long-term inhibition of ODC1 in APP/PS1 mice rescues amyloid pathology and switches astrocytes from a reactive to active state
Authors: Bhalla Mridula , Lee C. Justin 
Published: January 2024

AbstractAlzheimer’s disease (AD) is characterized by the loss of memory due to aggregation of misphosphorylated tau and amyloid beta (Aβ) plaques in the brain, elevated release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and reactive oxygen species from astrocytes, and subsequent neurodegeneration. Recently, it was found that enzyme Ornithine Decarboxylase 1 (ODC1) acts as a bridge between the astrocytic urea cycle and the putrescine-to-GABA conversion pathway in the brain of AD mouse models as well as human patients. In this study, we show that the long-term knockdown of astrocytic Odc1 in APP/PS1 animals was sufficient to completely clear Aβ plaques in the hippocampus while simultaneously switching the astrocytes from a detrimental reactive state to a regenerative active state, characterized by proBDNF expression. Our experiments also reveal an effect of astrocytic ODC1 inhibition on the expression of genes involved in synapse pruning and organization, histone modification, apoptotic signaling and protein processing. These genes are previously known to be associated with astrocytic activation and together create a neuroregeneration-supportive environment in the brain. By inhibiting ODC1 for a long period of 3 months in AD mice, we demonstrate that the beneficial amyloid-clearing process of astrocytes can be completely segregated from the systemically harmful astrocytic response to insult. Our study reports an almost complete clearance of Aβ plaques by controlling an endogenous degradation process, which also modifies the astrocytic state to create a regeneration-supportive environment in the brain. These findings present the potential of modulating astrocytic clearance of Aβ as a powerful therapeutic strategy against AD.
Niche-DE: niche-differential gene expression analysis in spatial transcriptomics data identifies context-dependent cell-cell interactions
Authors: Mason Kaishu , Sathe Anuja , Hess Paul R. , Rong Jiazhen , Wu Chi-Yun , Furth Emma , Susztak Katalin , Levinsohn Jonathan , Ji Hanlee P. , Zhang Nancy 
Published: January 2024

AbstractExisting methods for analysis of spatial transcriptomic data focus on delineating the global gene expression variations of cell types across the tissue, rather than local gene expression changes driven by cell-cell interactions. We propose a new statistical procedure called niche-differential expression (niche-DE) analysis that identifies cell-type-specific niche-associated genes, which are differentially expressed within a specific cell type in the context of specific spatial niches. We further develop niche-LR, a method to reveal ligand-receptor signaling mechanisms that underlie niche-differential gene expression patterns. Niche-DE and niche-LR are applicable to low-resolution spot-based spatial transcriptomics data and data that is single-cell or subcellular in resolution.
Proteomic differences between extracellular vesicles and extracellular vesicle-depleted excretory/secretory products of barber’s pole worm
Authors: Wu Fei , Chen Xueqiu , Du Zhendong , Chen Yanqiong , Tong Danni , Zhang Jingju , Yang Yi , Ma Guangxu , Du Aifang 
Published: January 2024

Abstract
Background
Components of excretory/secretory products (ESPs) of helminths have been proposed as vaccine targets and shown to play a role in modulating host immune responses for decades. Such research interest is further increased by the discovery of extracellular vesicles (EVs) in the ESPs of parasitic worms. Although efforts have been made to reveal the cargos of EVs, little is known about the proteomic differences between EVs and canonical ESPs released by parasitic worms from animals.

Methods
The total ESPs of Haemonchuscontortus (barber’s pole worm) were obtained by short-term in vitro culturing of young adult worms, and small EVs were isolated from ESPs using an ultracentrifugation method. Data-dependent acquisition (DDA) label-free Nano-LC–MS/MS was used to quantify the proteomic difference between small EVs and EV-depleted ESPs of H.contortus. Functional annotation and enrichment of the differential proteins were performed regarding cellular components, molecular functions, pathways, and/or biological processes.

Results
A total of 1697 proteins were identified in small EVs and EV-depleted ESPs of H.contortus adult worms, with 706 unique proteins detected in the former and 597 unique proteins in the latter. It was revealed that proteins in small EVs are dominantly cytoplasmic, whereas proteins in EV-depleted ESPs are mainly extracellular; canonical ESPs such as proteases and small GTPases were abundantly detected in small EVs, and SCP/TAP-, DUF-, and GLOBIN domain-containing proteins were mainly found in EV-depleted ESPs. Compared with well-characterised proteins in small EVs, about 50% of the proteins detected in EV-depleted ESPs were poorly characterised.

Conclusions
There are remarkable differences between small EVs and EV-depleted ESPs of H.contortus in terms of protein composition. Immune modulatory effects caused by nematode ESPs are possibly contributed mainly by the proteins in small EVs.

Graphical Abstract
The effect of using a sports application on the quality of sleep in patients with heart failure: a randomized clinical trial study
Authors: Arezomand Mohsen , Dehghan Mahlagha , Rigi Zahra Ebrahimi , Fatehi Farhad , Shahrbabaki Parvin Mangolian 
Published: January 2024

Abstract
Background
Patients with heart failure often suffer from sleep disorders. Due to the side effects of medications used to treat this disorder, non-pharmacological methods may be used to improve these patients’ sleep quality. This study aimed to determine the effect of a sports application on sleep quality in patients with heart failure.

Methods
In this single-blinded randomized clinical trial, 60 patients aged 30–70 referred to Shafa Hospital in Kerman were randomly assigned to control (n = 30) and intervention (n = 30) groups based on convenience sampling. The intervention group used the sports application for eight consecutive weeks. Data was collected using a demographic questionnaire and the Pittsburgh Sleep Quality Index (PSQI). An independent t-test and a Mann-Whitney U test were used for comparisons between groups and paired t-tests and Wilcoxon tests were used for comparisons within groups.

Results
The data analysis revealed a significant difference in sleep quality scores between the two groups after the intervention, meaning that the intervention group had better sleep quality than the control group (P < 0.05).

Conclusions
As a result of the study, it was found that the sport application improved the quality of sleep in patients with heart failure. Our recommendation is for healthcare providers to use this sports application to present educational content related to physical activity and improve the sleep quality of patients.

Trial registration
Iranian Registry of Clinical Trials: IRCT. 2019123045475N1.” Registered 16 December 2019.
Prevalence of female genital mutilation and associated factors among women and girls in Africa: a systematic review and meta-analysis
Authors: Ayenew Asteray Assmie , Mol Ben W. , Bradford Billie , Abeje Gedefaw 
Published: January 2024

Abstract
Background
Female genital mutilation (FGM) has zero health benefits. It can lead to short- and long-term risks and complications, including physical, sexual, and mental health and well-being of girls and women. It is a worldwide public health issue with more than 80% prevalence in Africa. It is a global imperative to strengthen work for the elimination, and the United Nations Sustainable Development Goal (SDG) strives to eliminate FGM and monitor the progress made. However, one of a challenge in tracking progress is establishing baseline prevalence data within regions and countries. Therefore, this review aimed to pool the prevalence of FGM in Africa and identify the promoting factors among women and girls.

Methods
This review was conducted according to the PRISMA checklist guideline. Both published and unpublished studies conducted from 2012 onwards were eligible. Studies written in non-English languages were excluded. To retrieve relevant studies; PubMed/Medline, Google Scholar, Science Direct, African Journals Online databases, and African Index Medicus (AIM) were searched using a combination of searching terms. The Newcastle-Ottawa Assessment Scale (NOS) tool was used to assess the quality of each included study. The Cochran’s Q chi-square and I2 statistical tests were used to evaluate the heterogeneity of the included studies. The Funnel plot and Egger's regression test (p value < 0.05) were used to evaluate meh publication bias. We used STATA for analysis and the overall and subgroup pooled effect size was estimated using the random effect model with DerSimonian and Laired pooled effect method. The overall prevalence of FGM and the adjusted odds ratio (AOR) with 95%CI (confidence interval) for contributing factors were calculated and presented using a forest plot.

Result
This study included 155 primary studies conducted on the prevalence and/or factors associated with FGM in Africa. The pooled prevalence of FGM was 56.4% (95%CI 49.7–63.6). The primary factors promoting the practice of FGM were family history of circumcision (AOR = 13.71, 95%CI 9.11−20.62), being a Muslim religion follower (AOR = 3.51, 95%CI 2.61−4.71), poor wealth index (AOR = 1.38, 95%CI1.27−1.51), higher age (AOR = 2.95, 95%CI 2.49−3.38), not attending formal education (AOR = 3.28, 95%CI 2.62−4.12), and rural residency (AOR = 2.27, 95%CI 1.84−2.80).

Conclusion
The prevalence of FGM in Africa was found to be high. This study also observed a variation in FGM prevalence across regions and countries and a slight temporal decline over the study period. As the global community enters the final decade dedicated to eliminating FGM, there remains much to be done to achieve the elimination goal.
The synthetic cannabinoids menace: a review of health risks and toxicity
Authors: Alzu’bi Ayman , Almahasneh Fatimah , Khasawneh Ramada , Abu-El-Rub Ejlal , Baker Worood Bani , Al-Zoubi Raed M. 
Published: January 2024

AbstractSynthetic cannabinoids (SCs) are chemically classified as psychoactive substances that target the endocannabinoid system in many body organs. SCs can initiate pathophysiological changes in many tissues which can be severe enough to damage the normal functionality of our body systems. The majority of SCs-related side effects are mediated by activating Cannabinoid Receptor 1 (CB1R) and Cannabinoid Receptor 2 (CB2R). The activation of these receptors can enkindle many downstream signalling pathways, including oxidative stress, inflammation, and apoptosis that ultimately can produce deleterious changes in many organs. Besides activating the cannabinoid receptors, SCs can act on non-cannabinoid targets, such as the orphan G protein receptors GPR55 and GPR18, the Peroxisome Proliferator-activated Receptors (PPARs), and the Transient receptor potential vanilloid 1 (TRPV1), which are broadly expressed in the brain and the heart and their activation mediates many pharmacological effects of SCs. In this review, we shed light on the multisystem complications found in SCs abusers, particularly discussing their neurologic, cardiovascular, renal, and hepatic effects, as well as highlighting the mechanisms that intermediate SCs-related pharmacological and toxicological consequences to provide comprehensive understanding of their short and long-term systemic effects.
Graphical Abstract
Investigation of offshore landslides impact on bucket foundations using a coupled SPH–FEM method
Authors: Wang Zehao , Zheng Defeng , Guo Xingsen , Gu Zhongde , Shen Yueqiang , Nian Tingkai 
Published: January 2024

Abstract
Background
As the exploitation of marine resources intensifies, the impact of submarine landslides on underwater structures has become a significant issue. Existing research primarily focuses on the impact on pipelines, often neglecting the actual deformation and mechanical response of underwater structures under impact loads in numerical simulations, thus complicating the evaluation of the reliability of these engineering structures in extreme conditions. Moreover, the dynamic response of bucket foundations, a common form of underwater base, under the effect of submarine landslide impacts remains unclear.

Methods
To address this knowledge gap, we have developed a fluid-structure coupling system that employs the coupled Smoothed Particle Hydrodynamics (SPH)-Finite Element Method (FEM) to investigate a single impact process and analyze the displacement response of bucket foundations within a water-offshore landslide-bucket foundationsubgrade context. The accuracy of this developed method has been systematically verified through comparisons with previous experimental and numerical results.

Results
During a submarine landslide impact event, the impact force demonstrates a distinct decrease followed by stabilization, and the displacement response of the bucket foundation exhibits a rebound effect after reaching its maximum value. Furthermore, we conducted an extensive analysis of different impact angles for underwater data centers equipped with multi-bucket foundations. Our study revealed that group-bucket foundations experience a combined translation-turnover failure when subjected to submarine landslide impacts, and the most unfavorable scenario for such impact is identified. The research introduces a novel numerical simulation approach for investigating the impact of submarine landslides on complex underwater structures.
Detection of low urine output by measuring urinary biomarkers
Authors: Hahn Robert G. 
Published: January 2024

Abstract
Background
Urine output < 1 L per 24 h is a clinical warning sign that requires attention from hospital staff, who should determine whether the low flow is due to low habitual intake of water or disease-induced dehydration. The incidence of this condition is unclear.

Methods
A cohort of 20 healthy volunteers (mean age 42 years, range 23–62 years) recorded their food and water intakes daily for 8 days. They also collected and measured all urine and delivered first morning urine samples for analysis of osmolality and creatinine. Optimal cutoffs for these biomarkers to indicate urine output of < 1 L or 15 mL/kg during the preceding 24 h were applied with and without correction for age to cross-sectional data from 1,316 subjects in various clinical settings, including healthy volunteers, preoperative patients, patients seeking acute care at a hospital, and patients receiving institutional geriatric care.

Results
The urine output amounted to < 1 L during 22 of the 159 evaluable study days and was indicated by urine osmolality > 760 mosmol/kg or urine creatinine > 13 mmol/L, which had sensitivity and specificity of approximately 80%. Days with urine output < 1 L were associated with significantly less intake of both water (–41%) and calories (–22%) compared to other days. Application of age-corrected biomarker cutoffs to the 1,316 subjects showed a stronger dependency of low urine output on age than the clinical setting, occurring in 44% of the 72 participants aged 15–30 years and 18% of the 62 patients aged 90–104 years.

Conclusion
Biomarkers measured in morning urine of young and middle-aged volunteers indicated urine output of < 1 L with good precision, but the cutoffs should be validated in older age groups to yield reliable results.

Trial registrations
ISRCTN12215472 at http://www.isrctn.com; NCT01458678 at ClinicalTrials.gov, and ChiCTR-TNRC-14,004,479 at the chictr.org/en.