bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioinformatic identification and experiment validation reveal 6 hub genes, promising diagnostic and therapeutic targets for Alzheimer’s disease
Authors: Cao Wenyuan , Ji Zhangge , Zhu Shoulian , Wang Mei , Sun Runming 
Published: January 2024

Abstract
Background
Alzheimer’s disease (AD) is a progressive neurodegenerative disease that can cause dementia. We aim to screen out the hub genes involved in AD based on microarray datasets.

Methods
Gene expression profiles GSE5281 and GSE28146 were retrieved from Gene Expression Omnibus database to acquire differentially expressed genes (DEGs). Gene Ontology and pathway enrichment were conducted using DAVID online tool. The STRING database and Cytoscape tools were employed to analyze protein-protein interactions and identify hub genes. The predictive value of hub genes was assessed by principal component analysis and receiver operating characteristic curves. AD mice model was constructed, and histology was then observed by hematoxylin-eosin staining. Gene expression levels were finally determined by real-time quantitative PCR.

Results
We obtained 197 overlapping DEGs from GSE5281 and GSE28146 datasets. After constructing protein-protein interaction network, three highly interconnected clusters were identified and 6 hub genes (RBL1, BUB1, HDAC7, KAT5, SIRT2, and ITGB1) were selected. The hub genes could be used as basis to predict AD. Histological abnormalities of brain were observed, suggesting successful AD model was constructed. Compared with the control group, the mRNA expression levels of RBL1, BUB1, HDAC7, KAT5 and SIRT2 were significantly increased, while the mRNA expression level of ITGB1 was significantly decreased in AD groups.

Conclusion
RBL1, BUB1, HDAC7, KAT5, SIRT2 and ITGB1 are promising gene signatures for diagnosis and therapy of AD.
Development and validation of a disulfidptosis and disulfide metabolism-related risk index for predicting prognosis in lung adenocarcinoma
Authors: Zhong Leqi , Chang Wuguang , Luo Bin , Gao Wuyou , He Huanhuan , Fang Mouxiang , Li Hongmu , Wen Zhesheng , Chen Youfang 
Published: January 2024

Abstract
Background
Disulfidptosis is a recently proposed novel cell death mode in which cells with high SLC7A11 expression induce disulfide stress and cell death in response to glucose deficiency. The purpose of the research was to explore the function of disufidptosis and disulfide metabolism in the progression of lung adenocarcinoma (LUAD).

Methods
The RNA-seq data from TCGA were divided into high/low expression group on the base of the median expression of SLC7A11, and the characteristic of differentially expressed disulfide metabolism-related genes. Least absolute shrinkage and selection operator (LASSO) algorithm was conducted the disulfidptosis and disulfide metabolism risk index. The tumor mutation burden (TMB), mechanism, pathways, tumor microenvironment (TME), and immunotherapy response were assessed between different risk groups. The role of TXNRD1 in LUAD was investigated by cytological experiments.

Results
We established the risk index containing 5 genes. There are significant differences between different risk groups in terms of prognosis, TMB and tumor microenvironment. Additionally, the low-risk group demonstrated a higher rate of response immunotherapy in the prediction of immunotherapy response. Experimental validation suggested that the knockdown of TXNRD1 suppressed cell proliferation, migration, and invasion of LUAD.

Conclusion
Our research highlights the enormous potential of disulfidptosis and disulfide metabolism risk index in predicting the prognosis of LUAD. And TXNRD1 has great clinical translational ability.
Expanding the roles of community health workers to sustain programmes during malaria elimination: a meeting report on operational research in Southeast Asia
Authors: Dysoley Lek , Callery James J. , Bunreth Voeurng , Vanna Moul , Davoeung Chan , Sovann Yok , You Sles , Ol Sam , Tripura Rupam , Chew Rusheng , Chandna Arjun , Christiansen-Jucht Céline , Hughes Jayme , Sokomar Nguon , Sophornarann Top , Rideout Jeanne , Veyvath Tat , Sarith Oum , Puthy Thaung , Sothearoth Hay , An Sen Sam , Zaman Sazid Ibna , von Seidlein Lorenz , Vanthy Lim , Sodavuth Preap , Vannak Chrun , Dondorp Arjen M. , Lubell Yoel , Maude Richard J. , Peto Thomas J. , Adhikari Bipin 
Published: January 2024

AbstractIn Southeast Asia malaria elimination is targeted by 2030. Cambodia aims to achieve this by 2025, driven in large part by the urgent need to control the spread of artemisinin-resistant falciparum malaria infections. Rapid elimination depends on sustaining early access to diagnosis and effective treatment. In much of Cambodia, rapid elimination will rely on a village malaria worker (VMW) network. Yet as malaria declines and is no longer a common cause of febrile illness, VMWs may become less popular with febrile patients, as VMWs do not diagnose or treat other conditions at present. There is a risk that VMWs become inactive and malaria rebounds before the complete interruption of transmission is achieved.During 2021–23 a large-scale operational research study was conducted in western Cambodia to explore how a VMW network could be sustained by including health activities that cover non-malarial illnesses to encourage febrile patients to continue to attend. 105 VMWs received new rapid diagnostic tests (including dengue antigen–antibody and combined malaria/C-reactive protein tests), were trained in electronic data collection, and attended health education packages on hygiene and sanitation, disease surveillance and first aid, management of mild illness, and vaccination and antenatal care.In August 2023 the National Malaria Control Programme of Cambodia convened a stakeholder meeting in Battambang, Cambodia. Findings from the study were reviewed in the context of current malaria elimination strategies. The discussions informed policy options to sustain the relevance of the VMW network in Cambodia, and the potential for its integration with other health worker networks. This expansion could ensure VMWs remain active and relevant until malaria elimination is accomplished.
Limited threat of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletion to the utility of HRP2-based malaria RDTs in Northern Uganda
Authors: Agaba Bosco B. , Smith David , Travis Jye , Pasay Cielo , Nabatanzi Monica , Arinaitwe Emmanuel , Ssewanyana Isaac , Nabadda Susan , Cunningham Jane , Kamya Moses R. , Cheng Qin 
Published: January 2024

Abstract
Background
Rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein-2 (PfHRP2) are exclusively deployed in Uganda, but deletion of the pfhrp2/3 target gene threatens their usefulness as malaria diagnosis and surveillance tools.

Methods
A cross-sectional survey was conducted at 40 sites across four regions of Uganda in Acholi, Lango, W. Nile and Karamoja from March 2021 to June 2023. Symptomatic malaria suspected patients were recruited and screened with both HRP2 and pan lactate dehydrogenase (pLDH) detecting RDTs. Dried blood spots (DBS) were collected from all patients and a random subset were used for genomic analysis to confirm parasite species and pfhrp2 and pfhrp3 gene status. Plasmodium species was determined using a conventional multiplex PCR while pfhrp2 and pfhrp3 gene deletions were determined using a real-time multiplex qPCR. Expression of the HRP2 protein antigen in a subset of samples was further assessed using a ELISA.

Results
Out of 2435 symptomatic patients tested for malaria, 1504 (61.8%) were positive on pLDH RDT. Overall, qPCR confirmed single pfhrp2 gene deletion in 1 out of 416 (0.2%) randomly selected samples that were confirmed of P. falciparum mono-infections.

Conclusion
These findings show limited threat of pfhrp2/3 gene deletions in the survey areas suggesting that HRP2 RDTs are still useful diagnostic tools for surveillance and diagnosis of P. falciparum malaria infections in symptomatic patients in this setting. Periodic genomic surveillance is warranted to monitor the frequency and trend of gene deletions and its effect on RDTs.
Cycling using functional electrical stimulation therapy to improve motor function and activity in post-stroke individuals in early subacute phase: a systematic review with meta-analysis
Authors: Galvão Wagner Rodrigues , Castro Silva Luana Karoline , Formiga Magno Ferreira , Thé George André Pereira , Faria Christina Danielli Coelho de Morais , Viana Ramon Távora , Lima Lidiane Andréa Oliveira 
Published: January 2024

Abstract
Background
Stroke necessitates interventions to rehabilitate individuals with disabilities, and the application of functional electrical stimulation therapy (FEST) has demonstrated potential in this regard. This study aimed to analyze the efficacy and effectiveness of cycling using FEST to improve motor function and lower limb activity in post-stroke individuals.

Methods
We performed a systematic review according to the recommendations of the PRISMA checklist, searching MEDLINE, Cochrane, EMBASE, LILACS, and PEDro databases by July 2022, without any date or language limitations. Studies were selected using the following terms: stroke, electrical stimulation therapy, cycling, and clinical trials. Randomized or quasi-randomized clinical trials that investigated the effectiveness of cycling using FEST combined with exercise programs and cycling using FEST alone for motor function and activity in subacute post-stroke individuals were included. The quality of included trials was assessed using the PEDro scores. Outcome data were extracted from eligible studies and combined in random-effects meta-analyses. The quality of evidence was determined according to the Grading of Recommendations Assessment, Development, and Evaluation system.

Results
Five randomized clinical trials involving 187 participants were included. Moderate-quality evidence indicates that cycling using FEST combined with exercise programs promotes relevant benefits in trunk control (MD 9 points, 95% CI 0.36–17.64) and walking distance (MD 94.84 m, 95% CI 39.63–150.05, I = 0%), the other outcomes had similar benefits. Cycling using FEST alone compared to exercise programs promotes similar benefits in strength, balance, walking speed, walking distance, and activities of daily living.

Conclusion
This systematic review provides low- to moderate-quality evidence that cycling using FEST may be an effective strategy to consider in improving motor function and activity outcomes for post-stroke individuals in the early subacute phase.
Review registration: PROSPERO (CRD42022345282).
Mapping a research-advocacy-policy agenda on human rights and albinism: a mixed methods project
Authors: Reimer-Kirkham Sheryl , Astle Barbara , Ero Ikponwosa , Beaman Lori , Ibhawoh Bonny , Imafidon Elvis , Sawatzky Richard , Tettey Wisdom , Buyco Meghann , Strobell Emma 
Published: January 2024

AbstractBackgroundPersons with albinism face challenges to their wellbeing, safety, and security, ranging from vision impairment and skin cancer to stigma and discrimination. In some regions, they also face human rights atrocities including mutilation and murder. Research on human rights and albinism is a relatively new field that has gained momentum since the United Nations appointment of an Independent Expert on the enjoyment of human rights by persons with albinism. In this paper, we present the results of a mixed methods study undertaken to identify priorities for research, advocacy, and policy on albinism and human rights.MethodsThe first component was a synthesis of peer-reviewed and grey literatures at the nexus of albinism, spiritual/cultural beliefs and practices, and human rights. We then conducted a priority-setting survey, informed by Delphi methods, on extant knowledge-practice gaps and research, advocacy, and policy priorities. Inclusion criteria included demonstrated expertise in the field (e.g., peer-reviewed publications, funded research), membership on national or international associations, or advocacy (civil society organizations) of more than 2 years in albinism and human rights. Thereafter, we gathered leading researchers, policy-makers, and civil society stakeholders for a Roundtable to gain consensus on these priorities.ResultsAccess to skin and vision care, and education were not deemed high priority for research, likely because the evidence supporting the need for these is well established. However, they were priorities for advocacy and policy: what is needed is mobilization of this evidence through advocacy and implementation of such services (policy). Other social determinants of health (rurality, poverty, and gender equality) are present as subtext in the findings, more so than priorities for research, advocacy, or policy, despite their preponderance in the lives of persons with albinism. Research was prioritized on stigma and discrimination; advocacy; and witchcraft, but with some differentiation between Global North and Global South priorities. Priorities for research, advocacy, and policy vary in keeping with the explanatory frameworks at play, including how harmful practices and witchcraft are viewed.ConclusionsThe lived experience of albinism is profoundly shaped by the social determinants of health (SDOH). Threats to the security and well-being of persons with albinism should be viewed through a human rights lens that encompasses the explanatory frameworks at play.
Tumor immune escape: extracellular vesicles roles and therapeutics application
Authors: Ahmadi Mahdi , Abbasi Reza , Rezaie Jafar 
Published: January 2024

Abstract
Background
Immune escape, a process by which tumor cells evade immune surveillance, remains a challenge for cancer therapy. Tumor cells produce extracellular vesicles (EVs) that participate in immune escape by transferring bioactive molecules between cells.

The main body of the abstract
EVs refer to heterogeneous vesicles that participate in intercellular communication. EVs from tumor cells usually carry tumor antigens and have been considered a source of tumor antigens to induce anti-tumor immunity. However, evidence also suggests that these EVs can accelerate immune escape by carrying heat shock proteins (HSPs), programmed death-ligand 1 (PD-L1), etc. to immune cells, suppressing function and exhausting the immune cells pool. EVs are progressively being evaluated for therapeutic implementation in cancer therapies. EVs-based immunotherapies involve inhibiting EVs generation, using natural EVs, and harnessing engineering EVs. All approaches are associated with advantages and disadvantages. The EVs heterogeneity and diverse physicochemical properties are the main challenges to their clinical applications.

Short conclusion
Although EVs are criminal; they can be useful for overcoming immune escape. This review discusses the latest knowledge on EVs population and sheds light on the function of tumor-derived EVs in immune escape. It also describes EVs-based immunotherapies with a focus on engineered EVs, followed by challenges that hinder the clinical translation of EVs that are essential to be addressed in future investigations.
Modulation of apoptosis and Inflammasome activation in chondrocytes: co-regulatory role of Chlorogenic acid
Authors: Kulyar Muhammad Fakhar-e-Alam , Mo Quan , Yao Wangyuan , Li Yan , Nawaz Shah , Loon Kyein San , Ahmed Ahmed Ezzat , Alsaegh Aiman A. , Al Syaad Khalid M. , Akhtar Muhammad , Bhutta Zeeshan Ahmad , Li Jiakui , Qi Desheng 
Published: January 2024

Abstract
Background
The B-cell lymphoma 2 (Bcl-2) protein regulates programmed cell death throughout the disease conditions by upholding apoptotic pathways. However, the mechanism by which it’s expressed in chondrocytes still needs to be studied in chondrocyte-related disorders. Additionally, exploring the potential therapeutic role of Chlorogenic acid (CGA) in confluence with Bcl-2 modulation is of significant interest.

Methods
In vivo and in vitro studies were performed according to our previous methodologies. The chondrocytes were cultured in specific growth media under standard conditions after expression verification of different microRNAs through high-throughput sequencing and verification of Bcl-2 involvement in tibial growth plates. The effect of Bcl-2 expression was investigated by transfecting chondrocytes with miR-460a, siRNA, and their negative controls alone or in combination with CGA. The RNA was extracted and subjected to a reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blot analysis and immunofluorescence assays were performed to visualize the intracellular localization of Bcl-2 and associated proteins related to apoptotic and inflammasome pathways. Moreover, apoptosis through flow cytometry was also performed to understand the modulation of concerning pathways.

Results
The suppression of Bcl-2 induced higher apoptosis and mitochondrial dysfunction, leading to IL-1β maturation and affecting the inflammasome during chondrocyte proliferation. Conversely, overexpression attenuated the activation, as evidenced by reduced caspase activity and IL-1β maturation. In parallel, CGA successfully reduced siRNA-induced apoptosis by decreasing Cytochrome C (Cyto C) release from the mitochondria to the cytoplasm, which in turn decreased Caspase-3 and Caspase-7 cleavage with Bcl-2-associated X protein (Bax). Furthermore, siBcl-2 transfection and CGA therapy increased chondrocyte proliferation and survival. The CGA also showed a promising approach to maintaining chondrocyte viability by inhibiting siRNA-induced apoptosis.

Conclusions
Targeting Bcl-2-mediated regulation might be a possible treatment for chondrocyte-related conditions. Moreover, these results add knowledge of the complicated processes underlying chondrocyte function and the pathophysiology of related diseases, highlighting the significance of target specific therapies.
Enhancement of targeted therapy in combination with metformin on human breast cancer cell lines
Authors: Mahmoudi Ghazal , Ehteshaminia Yahya , Kokhaei Parviz , Jalali Seyedeh Farzaneh , Jadidi-Niaragh Farhad , Pagheh Abdol Sattar , Enderami Seyed Ehsan , Kenari Saeid Abedian , Hassannia Hadi 
Published: January 2024

Abstract
Background
Breast cancer remains a primary global health concern due to its limited treatment options, frequent disease recurrence, and high rates of morbidity and mortality. Thereby, there is a need for more effective treatment approaches. The proposal suggests that the combination of targeted therapy with other antitumoral agents could potentially address drug resistance. In this study, we examined the antitumoral effect of combining metformin, an antidiabetic drug, with targeted therapies, including tamoxifen for estrogen receptor-positive (MCF-7), trastuzumab for HER2-positive (SKBR-3), and antibody against ROR1 receptor for triple-negative breast cancer (MDA-MB-231).

Methods
Once the expression of relevant receptors on each cell line was confirmed and appropriate drug concentrations were selected through cytotoxicity assays, the antitumor effects of both monotherapy and combination therapy on colony formation, migration, invasion were assessed in in vitro as well as tumor area and metastatic potential in ex ovo Chick chorioallantoic membrane (CAM) models.

Results
The results exhibited the enhanced effects of tamoxifen when combined with targeted therapy. This combination effectively inhibited cell growth, colony formation, migration, and invasion in vitro. Additionally, it significantly reduced tumor size and metastatic potential in an ex ovo CAM model.

Conclusions
The findings indicate that a favorable strategy to enhance the efficacy of breast cancer treatment would be to combine metformin with targeted therapies.

Graphical Abstract
Causal effects of gut microbiota on sepsis and sepsis-related death: insights from genome-wide Mendelian randomization, single-cell RNA, bulk RNA sequencing, and network pharmacology
Authors: Yang Sha , Guo Jing , Kong Zhuo , Deng Mei , Da Jingjing , Lin Xin , Peng Shuo , Fu Junwu , Luo Tao , Ma Jun , Yin Hao , Liu Lin , Liu Jian , Zha Yan , Tan Ying , Zhang Jiqin 
Published: January 2024

Abstract
Background
Gut microbiota alterations have been implicated in sepsis and related infectious diseases, but the causal relationship and underlying mechanisms remain unclear.

Methods
We evaluated the association between gut microbiota composition and sepsis using two-sample Mendelian randomization (MR) analysis based on published genome-wide association study (GWAS) summary statistics. Sensitivity analyses were conducted to validate the robustness of the results. Reverse MR analysis and integration of GWAS and expression quantitative trait loci (eQTL) data were performed to identify potential genes and therapeutic targets.

Results
Our analysis identified 11 causal bacterial taxa associated with sepsis, with increased abundance of six taxa showing positive causal relationships. Ten taxa had causal effects on the 28-day survival outcome of septic patients, with increased abundance of six taxa showing positive associations. Sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis did not provide evidence of reverse causality. Integration of GWAS and eQTL data revealed 76 genes passing the summary data-based Mendelian randomization (SMR) test. Differential expression of these genes was observed between sepsis patients and healthy individuals. These genes represent potential therapeutic targets for sepsis. Molecular docking analysis predicted potential drug-target interactions, further supporting their therapeutic potential.

Conclusion
Our study provides insights for the development of personalized treatment strategies for sepsis and offers preliminary candidate targets and drugs for future drug development.
Effects of riboflavin deficiency and high dietary fat on hepatic lipid accumulation: a synergetic action in the development of non-alcoholic fatty liver disease
Authors: Wang Yanxian , Bian Xiangyu , Wan Min , Dong Weiyun , Gao Weina , Yao Zhanxin , Guo Changjiang 
Published: January 2024

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Riboflavin, one of water soluble vitamins, plays a role in lipid metabolism and antioxidant function. However, the effects of riboflavin deficiency on NAFLD development have not yet to be fully explored.

Methods
In the present study, an animal model of NAFLD was induced by high fat diet feeding in mice and a cellular model of NAFLD was developed in HepG2 cells by palmitic acid (PA) exposure. The effects of riboflavin deficiency on lipid metabolism and antioxidant function were investigated both in vivo and in vitro. In addition, the possible role of peroxisome proliferator-activated receptor gamma (PPARγ) was studied in HepG2 cells using gene silencing technique.

Results
The results showed that riboflavin deficiency led to hepatic lipid accumulation in mice fed high fat diet. The expressions of fatty acid synthase (FAS) and carnitine palmitoyltransferase 1 (CPT1) were up-regulated, whereas that of adipose triglyceride lipase (ATGL) down-regulated. Similar changes in response to riboflavin deficiency were demonstrated in HepG2 cells treated with PA. Factorial analysis revealed a significant interaction between riboflavin deficiency and high dietary fat or PA load in the development of NAFLD. Hepatic PPARγ expression was significantly upregulated in mice fed riboflavin deficient and high fat diet or in HepG2 cells treated with riboflavin deficiency and PA load. Knockdown of PPARγ gene resulted in a significant reduction of lipid accumulation in HepG2 cells exposed to riboflavin deficiency and PA load.

Conclusions
There is a synergetic action between riboflavin deficiency and high dietary fat on the development of NAFLD, in which PPARγ may play an important role.