bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic and reproductive outcomes in women who had uterine myomas removed during cesarean section and sutured using different techniques
Authors: Dai Qiao-Hong , Zhang Lu , Chen An-Er
Published: January 2024

Background

In this study, the prognostic and reproductive outcomes of women who underwent excision of uterine myomas and were sutured using different techniques while undergoing a cesarean section were investigated.

Methods

A total of 299 females who underwent cesarean section between January 2015 and June 2022 due to a scarred uterus were enrolled in this study. These participants were segregated into two categories: the experimental group (comprising 155 cases) in which uterine myoma (single lesion) was excised during the cesarean procedure, and the control group (consisting of 144 cases) in which only the cesarean section was conducted. A comparison between the two groups was carried out based on the following parameters: volume of intraoperative bleeding (mL), additional measures taken for intraoperative hemostasis (n, %), percentage (%) of patients experiencing postoperative fever, duration required for the passage of gas (hours [h]), length of hospital stay (days [d]), weight of newborns (kg) and their Apgar scores, and the reproductive outcomes of the experimental group assessed two years after the surgical procedure.

Results

In the experimental group, the amount of bleeding during surgery, occurrence of postoperative fever among women, time taken for patients to resume passing gas, and length of hospital stay were 540.65 ± 269.12 mL, 9.03%, 15.99 ± 4.68 h, and 5.08 ± 1.18 days, respectively. In contrast, the control group had values of 409.03 ± 93.24 mL, 2.77%, 16.24 ± 4.92, and 4.47 ± 0.70 days, respectively (P < 0.05). No notable increase was observed in the need for additional intraoperative hemostasis measures, and there was no significant difference in the time it took for patients to pass gas after the surgery. All newborns had positive health status. In the experimental group, 25 patients underwent subsequent pregnancies, and 15 of them successfully reached full-term deliveries, all of which had positive outcomes.

Conclusion

Combining myomectomy with various suture methods during cesarean delivery did not cause excessive bleeding and resulted in healthy newborns. This approach offers the advantage of avoiding additional surgeries under anesthesia and can be considered a viable option. Subsequent pregnancies after myomectomy were considered high-risk.
Deep learning prediction of esophageal squamous cell carcinoma invasion depth from arterial phase enhanced CT images: a binary classification approach
Authors: Wu Xiaoli , Wu Hao , Miao Shouliang , Cao Guoquan , Su Huang , Pan Jie , Xu Yilun
Published: January 2024

Background

Precise prediction of esophageal squamous cell carcinoma (ESCC) invasion depth is crucial not only for optimizing treatment plans but also for reducing the need for invasive procedures, consequently lowering complications and costs. Despite this, current techniques, which can be invasive and costly, struggle with achieving the necessary precision, highlighting a pressing need for more effective, non-invasive alternatives.

Method

We developed ResoLSTM-Depth, a deep learning model to distinguish ESCC stages T1-T2 from T3-T4. It integrates ResNet-18 and Long Short-Term Memory (LSTM) networks, leveraging their strengths in spatial and sequential data processing. This method uses arterial phase CT scans from ESCC patients. The dataset was meticulously segmented by an experienced radiologist for effective training and validation.

Results

Upon performing five-fold cross-validation, the ResoLSTM-Depth model exhibited commendable performance with an accuracy of 0.857, an AUC of 0.901, a sensitivity of 0.884, and a specificity of 0.828. These results were superior to the ResNet-18 model alone, where the average accuracy is 0.824 and the AUC is 0.879. Attention maps further highlighted influential features for depth prediction, enhancing model interpretability.

Conclusion

ResoLSTM-Depth is a promising tool for ESCC invasion depth prediction. It offers potential for improvement in the staging and therapeutic planning of ESCC.
Effectiveness of mobile application interventions for stroke survivors: systematic review and meta-analysis
Authors: Cao Wenjing , Kadir Azidah Abdul , Tang Wenzhen , Wang Juan , Yuan Jiamu , Hassan Intan Idiana
Published: January 2024

Background

Although smartphone usage is ubiquitous, and a vast amount of mobile applications have been developed for chronic diseases, mobile applications amongst stroke survivors remain unclear.

Objective

This systematic review and meta-analysis aimed to determine the effectiveness of mobile applications on medication adherence, functional outcomes, cardiovascular risk factors, quality of life and knowledge on stroke in stroke survivors.

Methods

A review of the literature was conducted using key search terms in PubMed, EMBASE, Cochrane and Web of Science databases until 16 March 2023 to identify eligible randomized controlled trials (RCTs) or controlled clinical trial (CCTs) of mobile application interventions among stroke survivors. Two reviewers independently screened the literature in accordance with the eligibility criteria and collected data from the articles included. Outcomes included medication adherence,functional outcomes,cardiovascular risk factors, quality of life,and knowledge of stroke.

Results

Twenty-three studies involving 2983 participants across nine countries were included in this review. Sixteen trials involved health care professionals in app use, and seven trials reported measures to ensure app-based intervention adherence. Mobile applications targeting stroke survivors primarily encompassed three areas: rehabilitation, education and self-care. The participants in the studies primarily included young and middle-aged stroke survivors. Meta-analysis results demonstrated that mobile application intervention significantly improved trunk control ability (mean differences [MD] 3.00, 95% CI [1.80 to 4.20]; P < 0.00001), Fugl–Meyer assessment of upper extremity (MD 9.81, 95% CI [8.72 to 10.90]; P < 0.00001), low-density lipoprotein cholesterol (MD − 0.33, 95% CI [− 0.54 to − 0.11]; P = 0.003) and glycosylated haemoglobin A1c (HbA1c)<7 levels (MD 1.95, 95% CI [1.17 to 3.25]; P = 0.01). However, the mobile application intervention did not differ significantly in medication adherence, 10-min walk test (10 MWT), Barthel index, systolic blood pressure, diastolic blood pressure, high-density lipoprotein cholesterol, body mass index, smoking, health-related quality of life and knowledge of stroke.

Conclusion

Our study suggested that mobile application interventions may have a potential benefit to stroke survivors, but clinical effectiveness should be established. More studies using rigorous designs are warranted to understand their usefulness. Future research should also involve more older adult stroke survivors.
Process evaluation of the 90-90-90 targets of surge project in Addis Ababa, Ethiopia: a case study evaluation
Authors: Eshetu Belete Kefyalew , Tafere Tesfahun Zemene , Asrade Geta , Haile Tsegaye Gebremedhin
Published: January 2024

Background

Human Immunodeficiency Virus (HIV) is a major public health problem that continues to pose an enormous challenge to mankind’s survival worldwide. In urban Ethiopia, the HIV prevalence among adults aged 15–49 years is 2.9%, while in Addis Ababa, it is 3.4%. To take the edge off, the Ethiopian government has been implementing the 90-90-90 strategy also known as the surge project, in urban cities. However, the implementation of the program has not been evaluated. Thus, we evaluated the process of the 90-90-90 targets of the surge project in Addis Ababa, Ethiopia.

Methods

We conducted a case study with concurrent mixed-methods evaluation. We used indicator-driven evaluation dimensions –availability and accommodation dimensions from the health services access and compliance and fidelity from implementation fidelity frameworks to test the program process theory with a total of 52 indicators. We interviewed a total of 419 clients and 210 healthcare providers and reviewed 417 clients’ cards and 17 registries. We also conducted 30 key informant interviews and resource inventory. A binary logistic regression analysis was done to identify factors associated with clients’ satisfaction. We transcribed and translated the qualitative data and analysed thematically. Finally, we judged the overall process of the surge project based on the pre-seated judgmental criteria as; needs urgent improvement, needs improvement and well implemented.

Results

We found that 90% of the project process was as per the program process theory measured by the availability of resources (95.8%), compliance (88.0%), fidelity (84.7%), and accommodation of services (89.3%). We found a shortage of human power, test kits, and viral load testing machines. The commitment of health care providers, provider-client interaction, and clients’ satisfaction with the service at card rooms were found to be poor. Moreover, being aged 15–24, being married and government government-employed were negatively associated with clients’ satisfaction with antiretroviral therapy services.

Conclusion

The process of the surge project needs improvement. Moreover, the achievements of the first two 90–90 targets were poor. Therefore, implementers need to take intensified action for the availability of resources and to improve the commitment of healthcare providers through refreshment training.
Interpregnancy interval and early infant neurodevelopment: the role of maternal–fetal glucose metabolism
Authors: Ma Ruirui , Wang Peng , Yang Qiaolan , Zhu Yuanyuan , Zhang Lei , Wang Yuhong , Sun Lijun , Li Wenxiang , Ge Jinfang , Zhu Peng
Published: January 2024

Background

Interpregnancy interval (IPI) is associated with a variety of adverse maternal and infant outcomes. However, reports of its associations with early infant neurodevelopment are limited and the mechanisms of this association have not been elucidated. Maternal–fetal glucose metabolism has been shown to be associated with infant neurodevelopmental. The objective of this study was to determine whether this metabolism plays a role in the relationship between IPI and neurodevelopment.

Methods

This prospective birth cohort study included 2599 mother-infant pairs. The IPI was calculated by subtracting the gestational age of the current pregnancy from the interval at the end of the previous pregnancy. Neurodevelopmental outcomes at 12 months in infants were assessed by the Ages and Stages Questionnaire Edition 3 (ASQ-3). Maternal fasting venous blood was collected at 24–28 weeks and cord blood was collected at delivery. The association between IPI and neurodevelopment was determined by logistic regression. Mediation and sensitivity analyses were also conducted.

Results

In our cohort, 14.0% had an IPI < 12 months. IPI < 12 months increased the failure of the communication domain, fine motor domain, and personal social domain of the ASQ (relative risks (RRs) with 95% confidence interval (CI): 1.73 [1.11,2.70]; 1.73 [1.10,2.72]; 1.51 [1.00,2.29]). Maternal homeostasis model assessment of insulin resistance (HOMA-IR) and cord blood C-peptide was significantly associated with failure in the communication domain [RRs with 95% CI: 1.15 (1.02, 1.31); 2.15 (1.26, 3.67)]. The proportion of the association between IPI and failure of the communication domain risk mediated by maternal HOMA-IR and cord blood C-peptide was 14.4%.

Conclusions

IPI < 12 months was associated with failing the communication domain in infants. Maternal–fetal glucose metabolism abnormality may partially explain the risk of neurodevelopmental delay caused by short IPI.
Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial
Authors: Liu Moqi , Jiao Xueqiao , Li Rui , Li Jialu , Wang Lu , Wang Liyan , Wang Yishu , Lv Chunmei , Huang Dan , Wei Ran , Wang Liming , Ji Xunming , Guo Xiuhai
Published: January 2024

Background

We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS).

Methods

This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms.

Results

The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07–0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3− 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS.

Conclusions

The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS.

Trial registration

ClinicalTrials.gov NCT05023941.
Genetic proxies for antihypertensive drugs and mental disorders: Mendelian randomization study in European and East Asian populations
Authors: Fan Bohan , Zhao Jie V.
Published: January 2024

Background

Mental disorders are among the top causes of disease burden worldwide. Existing evidence regarding the repurposing of antihypertensives for mental disorders treatment is conflicting and cannot establish causation.

Methods

We used Mendelian randomization to assess the effects of angiotensin-converting-enzyme inhibitors (ACEIs), beta blockers (BBs), and calcium channel blockers (CCBs) on risk of bipolar disorder (BD), major depression disorder (MDD), and schizophrenia (SCZ). We used published genetic variants which are in antihypertensive drugs target genes and correspond to systolic blood pressure (SBP) in Europeans and East Asians, and applied them to summary statistics of BD (cases = 41,917; controls = 371,549 in Europeans), MDD (cases = 170,756; controls = 329,443 in Europeans and cases = 15,771; controls = 178,777 in East Asians), and SCZ (cases = 53,386; controls = 77,258 in Europeans and cases = 22,778; controls = 35,362 in East Asians) from the Psychiatric Genomics Consortium. We used inverse variance weighting with MR-Egger, weighted median, weighted mode, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. We performed gene-specific analysis and utilized various methods to address potential pleiotropy.

Results

After multiple testing correction, genetically proxied ACEIs were associated with an increased risk of SCZ in Europeans (odds ratio (OR) per 5 mmHg lower in SBP 2.10, 95% CI 1.54 to 2.87) and East Asians (OR per 5 mmHg lower in SBP 2.51, 95% CI 1.38 to 4.58). Genetically proxied BBs were not associated with any mental disorders in both populations. Genetically proxied CCBs showed no benefits on mental disorders.

Conclusions

Antihypertensive drugs have no protection for mental disorders but potential harm. Their long-term use among hypertensive patients with, or with high susceptibility to, psychiatric illness needs careful evaluation.
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

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

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

In 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

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

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

Background

Persons 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.

Methods

The 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.

Results

Access 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.

Conclusions

The 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

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

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

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

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

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.
A WHO-led global strategy to control greenhouse gas emissions: a call for action
Authors: Chersich Matthew F , Brink Nicholas , Craig Marlies H , Maimela Gloria , Scorgie Fiona , Luchters Stanley
Published: January 2024

Background

Climate change, driven by anthropogenic greenhouse gas emissions, is among the greatest threats to human health. The World Health Organisation (WHO), has led global efforts to respond to emerging public health threats including the control of hazardous substances such as tobacco, alcohol, lead and asbestos, with remarkable health gains.

Body

Despite WHO’s clear messaging on the enormous and growing health risks of climate change, greenhouse gases are not yet classified as hazardous substances, requiring control through a global strategy or framework. Additionally, WHO has not classified disease attributable to climate change as a result of the promulgation of these hazards as a Public Health Emergency of International Concern (PHEIC), despite the serious and preventable health risks it poses globally. Several historical precedents set the stage for WHO to declare excess greenhouse gases as health hazards, including the control of ozone-depleting substances and breast-milk substitutes where the public benefit of control exceeded the potential benefit of their promulgation. In addition, WHO’s undertaking within the International Health Regulations to protect global health, providing imperative to declare climate change a PHEIC, with Tedros Adhanom Ghebreyesus, director-general of WHO, declaring: “The climate crisis is a health crisis, fuelling outbreaks, contributing to higher rates of noncommunicable diseases, and threatening to overwhelm our health workforce and health infrastructure”. Importantly, the health sector, perhaps more than other sectors, has successfully overcome formidable, vested interests in combatting these threats to health.

Conclusion

It is thus imperative that WHO make full use of their credibility and influence to establish a global framework for the control of greenhouse gases through the declaration of excess greenhouse gas emissions as a hazardous substance, and declaring climate change a PHEIC. Who else is better placed to drive the considerable societal transformation needed to secure a liveable future?
Adjunctive duration-doubled transcranial direct current stimulation for the treatment of depressive patients with suicidal ideation: study protocol for a double-blind, randomized, sham-controlled trial
Authors: Chen Yiming , Lyu Dongbin , Wang Fan , Huang Qinte , Yang Weichieh , Zhang Mengke , Wei Zheyi , Shi Shuxiang , Kong Shuqi , Chen Shentse , He Shuang , Yang Vivien , Fang Yiru , Douiri Abdel , Hong Wu
Published: January 2024

Background

The problem of suicide has become increasingly common in individuals with major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) is an effective treatment for MDD with 2 milliamperes (mA) for at least 30 min per day for 2 weeks. This study aims to investigate the efficacy of daily duration-doubled tDCS as an adjunctive intervention for rapidly reducing suicidal ideation and improving depression in MDD patients.

Methods

In this double-blind, randomized, sham-controlled study, 76 MDD patients with suicidal ideation are randomly assigned to either active (n=38) or sham (n=38) tDCS group. The anode and cathode are placed over the scalp areas corresponding to left and right dorsolateral prefrontal cortex (DLPFC), respectively, and each stimulation lasts for 60 min. The primary outcome is defined as change of Beck Scale for Suicide Ideation (BSI) after 5 and 10 sessions. The change of other clinical assessments, blood biomarkers related to suicidal ideation and depressive sumptoms are defined as secondary outcomes. Blood biomarkers related to suicidal ideation are collected at baseline and after 10 sessions.

Discussion

This study suggests the adjunctive duration-doubled tDCS might be a novel method to rapidly reduce suicidal ideation and improve depressive symptom. The variation of biomarkers could be potential predictive models of suicide risk.

Trial registration

The trial protocol is registered with ClinicalTrials.gov under protocol registration number NCT05555927. Registered on September 25, 2022.
Preoperative supine time for adrenal venous sampling: a prospective randomized controlled trial
Authors: He Minzhi , Zhang Yuhao , Song Xiaoxiao , Zhang Tianyue , Yu Hailan , Ji Yongli , Gong Siyuan , Chai Peifei , Chen Jinyi , Wang Siwei , Chen Bing , Xu Xiaohong , Liu Zhenjie
Published: January 2024

Background

Primary aldosteronism (P.A.) is the most common form of secondary hypertension, accounting for 5% of hypertensive patients and 17–23% of patients with resistant hypertension. Compared to primary hypertension, P.A. is more prone to cause severe organ damage and even early death. Adrenal venous sampling (AVS) is a practical confirmatory test for subtyping aldosterone-producing adenoma and bilateral adrenal hyperplasia, helping physicians to make an accurate decision between surgery or medication. According to guidelines, supine in bed before AVS is recommended for a desirable result of AVS. However, investigations about the most optimal preoperative supine time before AVS are lacking.

Methods/design

This is a multi-center prospective randomized controlled study. One hundred twenty patients diagnosed as P.A. and willing for AVS examination will be included. Participants will be randomly allocated to a 15-min supine time group or 2-h supine time group. The primary outcome is the degree of biochemical remission (serum potassium and orthostatic ARR). The secondary outcomes are degrees of clinical remission (blood pressure, type and dose of antihypertensive drugs), the technical success rate, and the adverse event of AVS (selective index ≥ 2 is considered successful surgery without corticotropin stimulation).

Discussion

P.A. is an intractable public health problem, and many techniques including AVS have been developed to identify this disease correctly. This study will help to understand whether the length of preoperative supine time would affect the diagnostic efficacy of AVS and thus help to formulate a more reasonable AVS procedure.

Trial registration

ClinicalTrials.gov NCT05658705. Registered on 10 September 2022.