bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive comparison of salivary collection, transportation, preparation, and storage methods: a systematic review
Authors: Mortazavi Hamed , Yousefi-Koma Amir-Ali , Yousefi-Koma Hannaneh 
Published: February 2024

Abstract
Background
Human saliva as a bodily fluid—similar to blood—is utilized for diagnostic purposes. Unlike blood sampling, collecting saliva is non-invasive, inexpensive, and readily accessible. There are no previously published systematic reviews regarding different collection, transportation, preparation, and storage methods for human saliva.

Design
This study has been prepared and organized according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines. This systematic review has been registered at PROSPERO (Registration ID: CRD42023415384). The study question according to the PICO format was as followed: Comparison of the performance (C) of different saliva sampling, handling, transportation, and storage techniques and methods (I) assessed for analyzing stimulated or unstimulated human saliva (P and O). An electronic search was executed in Scopus, Google Scholar, and PubMed.

Results
Twenty-three descriptive human clinical studies published between 1995 and 2022 were included. Eight categories of salivary features and biomarkers were investigated (i.e., salivary flow rate, total saliva quantity, total protein, cortisol, testosterone, DNA quality and quantity, pH and buffering pH). Twenty-two saliva sampling methods/devices were utilized. Passive drooling, Salivette®, and spitting were the most utilized methods. Sampling times with optimum capabilities for cortisol, iodine, and oral cancer metabolites are suggested to be 7:30 AM to 9:00 AM, 10:30 AM to 11:00 AM, and 14:00 PM to 20:00 PM, respectively. There were 6 storage methods. Centrifuging samples and storing them at -70 °C to -80 °C was the most utilized storage method. For DNA quantity and quality, analyzing samples immediately after collection without centrifuging or storage, outperformed centrifuging samples and storing them at -70 °C to -80 °C. Non-coated Salivette® was the most successful method/device for analyzing salivary flow rate.

Conclusion
It is highly suggested that scientists take aid from the reported categorized outcomes, and design their study questions based on the current voids for each method/device.
Exploring the potential link between MitoEVs and the immune microenvironment of periodontitis based on machine learning and bioinformatics methods
Authors: Yang Haoran , Zhao Anna , Chen Yuxiang , Cheng Tingting , Zhou Jianzhong , Li Ziliang 
Published: February 2024

Abstract
Background
Periodontitis is a chronic inflammatory condition triggered by immune system malfunction. Mitochondrial extracellular vesicles (MitoEVs) are a group of highly heterogeneous extracellular vesicles (EVs) enriched in mitochondrial fractions. The objective of this research was to examine the correlation between MitoEVs and the immune microenvironment of periodontitis.

Methods
Data from MitoCarta 3.0, GeneCards, and GEO databases were utilized to identify differentially expressed MitoEV-related genes (MERGs) and conduct functional enrichment and pathway analyses. The random forest and LASSO algorithms were employed to identify hub MERGs. Infiltration levels of immune cells in periodontitis and healthy groups were estimated using the CIBERSORT algorithm, and phenotypic subgroups of periodontitis based on hub MERG expression levels were explored using a consensus clustering method.

Results
A total of 44 differentially expressed MERGs were identified. The random forest and LASSO algorithms identified 9 hub MERGs (BCL2L11, GLDC, CYP24A1, COQ2, MTPAP, NIPSNAP3A, FAM162A, MYO19, and NDUFS1). ROC curve analysis showed that the hub gene and logistic regression model presented excellent diagnostic and discriminating abilities. Immune infiltration and consensus clustering analysis indicated that hub MERGs were highly correlated with various types of immune cells, and there were significant differences in immune cells and hub MERGs among different periodontitis subtypes.

Conclusion
The periodontitis classification model based on MERGs shows excellent performance and can offer novel perspectives into the pathogenesis of periodontitis. The high correlation between MERGs and various immune cells and the significant differences between immune cells and MERGs in different periodontitis subtypes can clarify the regulatory roles of MitoEVs in the immune microenvironment of periodontitis. Future research should focus on elucidating the functional mechanisms of hub MERGs and exploring potential therapeutic interventions based on these findings.
Potentially burdensome care at the end-of-life for cancer decedents: a retrospective population-wide study
Authors: Mitchell Rebecca J , Delaney Geoffrey P , Arnolda Gaston , Liauw Winston , Phillips Jane L , Lystad Reidar P , Harrison Reema , Braithwaite Jeffrey 
Published: February 2024

Abstract
Background
Variation persists in the quality of end-of-life-care (EOLC) for people with cancer. This study aims to describe the characteristics of, and examine factors associated with, indicators of potentially burdensome care provided in hospital, and use of hospital services in the last 12 months of life for people who had a death from cancer.

Method
A population-based retrospective cohort study of people aged ≥ 20 years who died with a cancer-related cause of death during 2014–2019 in New South Wales, Australia using linked hospital, cancer registry and mortality records. Ten indicators of potentially burdensome care were examined. Multinominal logistic regression examined predictors of a composite measure of potentially burdensome care, consisting of > 1 ED presentation or > 1 hospital admission or ≥ 1 ICU admission within 30 days of death, or died in acute care.

Results
Of the 80,005 cancer-related deaths, 86.9% were hospitalised in the 12 months prior to death. Fifteen percent had > 1 ED presentation, 9.9% had > 1 hospital admission, 8.6% spent ≥ 14 days in hospital, 3.6% had ≥ 1 intensive care unit admission, and 1.2% received mechanical ventilation on ≥ 1 occasion in the last 30 days of life. Seventeen percent died in acute care. The potentially burdensome care composite measure identified 20.0% had 1 indicator, and 10.9% had ≥ 2 indicators of potentially burdensome care. Compared to having no indicators of potentially burdensome care, people who smoked, lived in rural areas, were most socially economically disadvantaged, and had their last admission in a private hospital were more likely to experience potentially burdensome care. Older people (≥ 55 years), females, people with 1 or ≥ 2 Charlson comorbidities, people with neurological cancers, and people who died in 2018–2019 were less likely to experience potentially burdensome care. Compared to people with head and neck cancer, people with all cancer types (except breast and neurological) were more likely to experience ≥ 2 indicators of potentially burdensome care versus none.

Conclusion
This study shows the challenge of delivering health services at end-of-life. Opportunities to address potentially burdensome EOLC could involve taking a person-centric approach to integrate oncology and palliative care around individual needs and preferences.
Association between drinking water quality and mental health and the modifying role of diet: a prospective cohort study
Authors: Zhou Shuduo , Su Mintao , Shen Peng , Yang Zongming , Chai Pengfei , Sun Shengzhi , Lin Hongbo , Shui Liming , Zhang Na , Xu Ming , Zheng Zhi-Jie , Wang Jianbing , Zhang Zhenyu , Chen Kun 
Published: February 2024

Abstract
Background
Environmental factors play an important role in developing mental disorders. This study aimed to investigate the associations of metal and nonmetal elements in drinking water with the risk of depression and anxiety and to assess whether diets modulate these associations.

Methods
We conducted a prospective cohort study including 24,285 participants free from depression and anxiety from the Yinzhou Cohort study in the 2016–2021 period. The exposures were measured by multiplying metal and nonmetal element concentrations in local pipeline terminal tap water samples and total daily drinking water intakes. Cox regression models adjusted for multi-level covariates were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (95%CIs).

Results
During an average follow-up period of 4.72 and 4.68 years, 773 and 1334 cases of depression and anxiety were identified, respectively. A 1 standard deviation (SD) increase in manganese exposure reduced the incidence of depression by 8% (HR 0.92, 95%CI 0.88 to 0.97). In contrast, with a 1 SD increase in copper and cadmium exposure, the incidence of depression increased by 6% (HR 1.06, 95%CI 1.01 to 1.11) and 8% (HR 1.08, 95%CI 1.00 to 1.17), respectively. The incidence of anxiety increased by 39% (HR 1.39, 95%CI 1.20 to 1.62), 33% (HR 1.33, 95%CI 1.03 to 1.71), and 14% (HR 1.14, 95%CI 1.03 to 1.25) respectively for a 1 SD increase in manganese, iron, and selenium exposure. Diets have a moderating effect on the associations of metal and nonmetal elements with the risk of anxiety. Stronger associations were observed in older, low-income groups and low-education groups.

Conclusions
We found significant associations between exposure to metal and nonmetal elements and depression and anxiety. Diets regulated the associations to some extent.
From efficacy to effectiveness: a comprehensive framework for monitoring, evaluating and optimizing seasonal malaria chemoprevention programmes
Authors: de Cola Monica Anna , Chestnutt Elisabeth G. , Richardson Sol , Baudry Matthieu , Nnaji Chuks , Ibinaiye Taiwo , Moukénet Azoukalné , Rotimi Kunle , Sawadogo Benoît , Okafor Joshua , Compaoré Cheick Saïd , Oguoma Chibuzo , Rassi Christian , Roca-Feltrer Arantxa 
Published: February 2024

Abstract
Background
Seasonal Malaria Chemoprevention (SMC) is a highly effective intervention for preventing malaria, particularly in areas with highly seasonal transmission. Monitoring and evaluating (M&E) SMC programmes are complex due to the scale, time-sensitive delivery of the programme, and influence of external factors. This paper describes the process followed to develop a comprehensive M&E framework tailored specifically for the SMC context.

Methods
The Framework was developed through a literature and programme review, and stakeholder dialogues across three implementing countries—Burkina Faso, Chad, and Nigeria. Expert consultation further refined the Framework through an iterative approach drawing upon data collected through the three sources. The Framework was designed using the Logical Framework Approach incorporating external factors and intentionally aligned with global malaria M&E standards.

Results
An overall aim and seven programme objectives were developed measured by 70 indicators. The indicators also capture the causal links between the implementation and results of the programme. The Framework leverages the use of current data sources and existing mechanisms, ensuring efficient data use without requiring a significant increase in resources for overall programme optimization. It also promotes the use of data triangulation, and stratification for a more nuanced understanding of factors affecting programme performance and timely data informed decision-making.

Conclusions
The SMC M&E Framework presented here provides a standardized approach for programme implementers to enhance decision-making for optimal programme performance. This is an essential tool as the scope of SMC programmes expands to new geographies and target age groups.
Community-based mental health interventions in low- and middle-income countries: a qualitative study with international experts
Authors: Giebel Clarissa , Gabbay Mark , Shrestha Nipun , Saldarriaga Gabriel , Reilly Siobhan , White Ross , Liu Ginger , Allen Dawn , Zuluaga Maria Isabel 
Published: February 2024

Abstract
Background
Mental health services are scarce in low- and middle-income countries (LMICs), and designing and implementing effective interventions can be difficult. The aim of this international study was to explore the key lessons for developing, implementing, and evaluating community-based mental health and well-being interventions in LMICs, with an additional focus on older adults.

Methods
Research and clinical experts in developing and implementing psychosocial community-based interventions in LMICs were interviewed remotely between October 2021 and January 2022. Participants were recruited via existing global health networks and via published literature searches. Participants were asked about their experiences of developing and implementing interventions, and about key barriers and facilitators during the process. Interviews lasted up to 45 min, and data were analysed using combined inductive and deductive thematic analysis.

Results
Sixteen global mental health experts participated. Five themes with different sub-themes were generated: Mechanisms and contexts; Barriers; Facilitators; Public and stakeholder involvement; Looking through an ageing lens. The development and delivery of mental health interventions in LMICs are facilitated through integration into existing health infrastructures and working with existing job roles as delivery agents. Public and stakeholder involvement are crucial at all stages of development through to implementation to focus on meeting local needs and sustaining participant motivation. Logistical barriers of transport, resources, and location need to be addressed, emphasising local sustainability.

Conclusions
This study provides important insights for how the development, implementation, and evaluation of community-based mental health and well-being interventions in LMICs can be optimised, and can complement general guidance into complex interventions developments.
Ten-eleven translocation-2-mediated macrophage activation promotes liver regeneration
Authors: Chen Yiyuan , Meng Lijun , Xu Nan , Chen Huan , Wei Xuyong , Lu Di , Wang Shuai , Xu Xiao 
Published: February 2024

Abstract
Background
The remarkable regenerative capacity of the liver enables recovery after radical Hepatocellular carcinoma (HCC) resection. After resection, macrophages secrete interleukin 6 and hepatocyte growth factors to promote liver regeneration. Ten-eleven translocation-2 (Tet2) DNA dioxygenase regulates pro-inflammatory factor secretion in macrophages. In this study, we explored the role of Tet2 in macrophages and its function independent of its enzymatic activity in liver regeneration.

Methods
The model of liver regeneration after 70% partial hepatectomy (PHx) is a classic universal model for studying reparative processes in the liver. Mice were euthanized at 0, 24, and 48 h after PHx. Enzyme-linked immunosorbent assays, quantitative reverse transcription-polymerase chain reaction, western blotting, immunofluorescence analysis, and flow cytometry were performed to explore immune cell infiltration and liver regenerative capability. Molecular dynamics simulations were performed to study the interaction between Tet2 and signal transducer and activator of transcription 1 (Stat1).

Results
Tet2 in macrophages negatively regulated liver regeneration in the partial hepatectomy mice model. Tet2 interacted with Stat1, inhibiting the expression of proinflammatory factors and suppressing liver regeneration. The Tet2 inhibitor attenuated the interaction between Stat1 and Tet2, enhanced Stat1 phosphorylation, and promoted hepatocyte proliferation. The proliferative function of the Tet2 inhibitor relied on macrophages and did not affect hepatocytes directly.

Conclusion
Our findings underscore that Tet2 in macrophages negatively regulates liver regeneration by interacting with Stat1. Targeting Tet2 in macrophages promotes liver regeneration and function after a hepatectomy, presenting a novel target to promote liver regeneration and function.

Graphical Abstract
Tet2 interacts with Stat1 in the cytoplasm and suppresses IFN-γ-induced macrophage activation. Tet2 inhibitor decreases the combination of Stat1 and Tet2, activating the macrophages through the Jak-Stat pathway. The activation of macrophages increases the transcription and translation of the IL-6 and promotes liver regeneration.
Women's voices and meanings of empowerment for reproductive decisions: a qualitative study in Mozambique
Authors: Castro Lopes Sofia , Constant Deborah , Fraga Sílvia , Harries Jane 
Published: February 2024

Abstract
Background
Women in Mozambique are often disempowered when it comes to making decisions concerning their lives, including their bodies and reproductive options. This study aimed to explore the views of women in Mozambique about key elements of empowerment for reproductive decisions and the meanings they attach to these elements.

Methods
Qualitative in-depth interviews were undertaken with 64 women of reproductive age (18–49 years) in two provinces in Mozambique. Participants were recruited through convenience sampling. Data collection took place between February and March 2020 in Maputo city and Province, and during August 2020 in Nampula Province. A thematic analysis was performed.

Results
Women described crucial elements of how power is exerted for reproductive choices. These choices include the ability to plan the number and timing of pregnancies and the ability either to negotiate with sexual partners by voicing choice and influencing decisions, or to exercise their right to make decisions independently. They considered that women with empowerment had characteristics such as independence, active participation and being free. These characteristics are recognized key enablers for the process of women’s empowerment.

Conclusions
This study’s findings contribute to an expanded conceptualization and operationalization of women’s sexual and reproductive empowerment by unveiling key elements that need to be considered in future research and approaches to women’s empowerment. Furthermore, it gave women the central role and voice in the research of empowerment's conceptualization and measurement where women’s views and meanings are seldom considered.
Accelerating drug development for amyotrophic lateral sclerosis: construction and application of a disease course model using historical placebo group data
Authors: Cai Ruifen , Yang Juan , Wu Lijuan , Liu Yixiao , Wang Xinrui , Zheng Qingshan , Li Lujin 
Published: February 2024

Abstract
Background
Amyotrophic lateral sclerosis (ALS) is an irreversible degenerative disease. Placebo-controlled randomized trials are currently the main trial design to assess the clinical efficacy of drugs for ALS treatment. The aim of this study was to establish models to quantitatively describe the course of ALS, explore influencing factors, and provide the necessary information for ALS drug development.

Methods
We conducted a comprehensive search of PubMed and the Cochrane Library Central Register for placebo-controlled trials that evaluated treatments for ALS. From these trials, we extracted the clinical and demographic characteristics of participants in the placebo group, as well as outcome data, which encompassed overall survival (OS) and Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) scores, at various time points.

Results
In total, 47 studies involving 6118 participants were included. Disease duration and the proportion of patients receiving riluzole were identified as significant factors influencing OS in the placebo group. Specifically, the median OS was 35.5 months for a disease duration of 9 months, whereas it was 20.0 months for a disease duration of 36 months. Furthermore, for every 10% increase in the proportion of patients treated with riluzole (100 mg daily), there was an association with a median OS extension of approximately 0.4 months. The estimated time for the ALSFRS-R score in the placebo group to decrease to 50% of its maximum effect from baseline level was approximately 17.5 months, and the time to reach a plateau was about 40 months.

Conclusions
The established disease course model of the historical placebo group is valuable in the decision-making process for the clinical development of ALS drugs. It serves not only as an external control to evaluate the efficacy of the tested drug in single-arm trials but also as prior information that aids in accurately estimating the posterior distribution of the disease course in the placebo group during small-sample clinical trials.
Mapping the functional impact of non-coding regulatory elements in primary T cells through single-cell CRISPR screens
Authors: Alda-Catalinas Celia , Ibarra-Soria Ximena , Flouri Christina , Gordillo Jorge Esparza , Cousminer Diana , Hutchinson Anna , Sun Bin , Pembroke William , Ullrich Sebastian , Krejci Adam , Cortes Adrian , Acevedo Alison , Malla Sunir , Fishwick Carl , Drewes Gerard , Rapiteanu Radu 
Published: February 2024

Abstract
Background
Drug targets with genetic evidence are expected to increase clinical success by at least twofold. Yet, translating disease-associated genetic variants into functional knowledge remains a fundamental challenge of drug discovery. A key issue is that the vast majority of complex disease associations cannot be cleanly mapped to a gene. Immune disease-associated variants are enriched within regulatory elements found in T-cell-specific open chromatin regions.

Results
To identify genes and molecular programs modulated by these regulatory elements, we develop a CRISPRi-based single-cell functional screening approach in primary human T cells. Our pipeline enables the interrogation of transcriptomic changes induced by the perturbation of regulatory elements at scale. We first optimize an efficient CRISPRi protocol in primary CD4+ T cells via CROPseq vectors. Subsequently, we perform a screen targeting 45 non-coding regulatory elements and 35 transcription start sites and profile approximately 250,000 T -cell single-cell transcriptomes. We develop a bespoke analytical pipeline for element-to-gene (E2G) mapping and demonstrate that our method can identify both previously annotated and novel E2G links. Lastly, we integrate genetic association data for immune-related traits and demonstrate how our platform can aid in the identification of effector genes for GWAS loci.

Conclusions
We describe “primary T cell crisprQTL” — a scalable, single-cell functional genomics approach for mapping regulatory elements to genes in primary human T cells. We show how this framework can facilitate the interrogation of immune disease GWAS hits and propose that the combination of experimental and QTL-based techniques is likely to address the variant-to-function problem.