bluuebunny/crossref_metadata_2025 huggingface dataset:
A Narrative Review of Novel Agents for Managing Heavily Treatment-Experienced People Living With HIV
Authors: Beran Christina , Duggan Joan M. , Sahloff Eric G.
Published: July 2024

Objective: The objective of this review is to compare ibalizumab, fostemsavir, and lenacapavir, present the clinical trials evaluating each agent, and provide guidance on their use in highly-treatment experienced (HTE) population living with HIV (PWH). Data sources: A search of PubMed and clinicaltrials.gov was conducted using the search terms: ibalizumab, fostemsavir, and lenacapavir. Study selection and data extraction: English-language, clinical publications were included. Data synthesis: Ibalizumab, fostemsavir, and lenacapavir, are each first-in-class agents, that have major differences in mechanism of action, route and frequency of administration, pharmacokinetic parameters, including elimination half-life, potential for drug-drug interactions, safety profiles, and cost. Each has been shown, when combined with an optimized background regimen (OBR) with at least one other active agent, to achieve virologic suppression in HTE-PWH. Conclusion: In HTE-patients, adding ibalizumab, fostemsavir, and/or lenacapavir to at least one other active agent can lead to virologic suppression in this difficult to treat population. Monotherapy with any of these agents is not recommended and will lead to a high likelihood of drug resistance. Selection of which agent(s) to include with an OBR will depend on other patient factors including concomitant medications, acceptance of formulations (oral vs. subcutaneous vs. intravenous infusion), and potential access (both insurance-based and transportation). Adherence to all agents in the regimen is paramount to successful outcomes.
A Review of the Potential Role of Sotagliflozin: A Dual SGLT2 and SGLT1 Inhibitor—in the Treatment of Heart Failure
Authors: Tran Bao Anh C. , White Raechel T. , Bullers Krystal , Cornelio Cyrille K.
Published: July 2024

Objective: This review provides an overview of the pharmacology, efficacy, and safety of sotagliflozin, a dual inhibitor of sodium-glucose cotransporters 1 and 2 (SGLT1 and SGLT2), to reduce the risk of cardiovascular death and hospitalization in those with heart failure. Data sources: A search of Embase via Elsevier, PubMed, Web of Science—All Databases, and The Cochrane Library for clinical trials in CENTRAL, as well as the MedRxiv and BioRxiv pre-print servers, was conducted from inception through December 1, 2023. Search terms included sotagliflozin, lx 4211, lp 802034, sar 439954, and (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol. Study selection and data extraction: Published phase 1, phase 2, and phase 3 clinical trials, meta-analyses, and systematic reviews. Studies were included if they were published in English and evaluated sotagliflozin pharmacology, pharmacokinetics, efficacy, or safety. Data synthesis: The Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure (SOLOIST-WHF) and Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) phase 3 trials compared sotagliflozin with placebo in patients with type 2 diabetes mellitus. In both the SCORED and SOLOIST-WHF trials, treatment with sotagliflozin resulted in a statistically significant reduction in the primary composite outcome of death from cardiovascular causes, hospitalizations due to heart failure (HF), and urgent visits for HF. Conclusions: Dual SGLT1 and SGLT2 inhibition with sotagliflozin is efficacious in reducing myocardial infarction (MI), stroke, and HF hospitalizations and urgent visits in the SCORED and SOLOIST-WHF trials. However, its impact on reducing cardiovascular mortality remains uncertain due to premature study discontinuation. Owing to these factors and lack of generalizability, further studies are needed to establish its role in renal protection and cardiovascular mortality in broader populations. At this time, more evidence is warranted to definitively establish sotagliflozin in HF.
Utilization of Glucagon-Like Peptide-1 Receptor Agonist and Dipeptidyl Peptidase-4 Inhibitors at the Veterans Health Administration
Authors: Krishnan Aditya , Suryanarayanan Sowmya K. , Mansi Ishak A.
Published: July 2024

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are incretin-based therapies commonly used in the management of type 2 diabetes. Public interest in GLP-1RA soared after discovering their ability to lower body weight in patients without diabetes. Objective: To examine recent trends in usage of GLP-1RA and DPP-4i in the Veterans Health Administration (VHA). Methods: We extracted GLP-1RA and DPP-4i use from the national VHA Corporate Data Workhouse (CDW) between fiscal years (FYs) 2011 to 2021, which encompass medication class, name, dosage, date of filled prescription, and patients’ characteristics. Results: A total of 3 037 006 prescriptions for DPP-4i and 2 183 294 prescriptions for GLP-1RA were filled during FY 2011 to 2021. More patients were prescribed DPP-4i (273 002 subjects) compared with GLP-1RA (157 209 subjects) from FY 2011 to 2021. Overall, 10.7% used DPP-4i for 90 days or less in comparison to 9.1% in GLP-1RA ( P < 0.001). The proportion of patients prescribed DPP-4i who were 75 years of age or older was relatively stable over the years 2011 to 2021 (mean proportion = 19%). However, the proportion of patients who were 75 years of age or older prescribed GLP-1RA increased from 4.2% in 2011 to 16.9% in 2021. Conclusions: Incretin-based therapies have become a well-established class of drugs within the VHA. Even though DPP-4i usage in older adults has remained stable over the past 10 years, prescriptions for GLP-1RA in older adults have increased multifold over the last few years, which might be attributed to recent trial evidence showing benefit in cardiovascular outcomes and weight reduction.
Effective type label-based synergistic representation learning for biomedical event trigger detection
Authors: Hao Anran , Yuan Haohan , Hui Siu Cheung , Su Jian
Published: July 2024

Background

Detecting event triggers in biomedical texts, which contain domain knowledge and context-dependent terms, is more challenging than in general-domain texts. Most state-of-the-art models rely mainly on external resources such as linguistic tools and knowledge bases to improve system performance. However, they lack effective mechanisms to obtain semantic clues from label specification and sentence context. Given its success in image classification, label representation learning is a promising approach to enhancing biomedical event trigger detection models by leveraging the rich semantics of pre-defined event type labels.

Results

In this paper, we propose the Biomedical Label-based Synergistic representation Learning (BioLSL) model, which effectively utilizes event type labels by learning their correlation with trigger words and enriches the representation contextually. The BioLSL model consists of three modules. Firstly, the Domain-specific Joint Encoding module employs a transformer-based, domain-specific pre-trained architecture to jointly encode input sentences and pre-defined event type labels. Secondly, the Label-based Synergistic Representation Learning module learns the semantic relationships between input texts and event type labels, and generates a Label-Trigger Aware Representation (LTAR) and a Label-Context Aware Representation (LCAR) for enhanced semantic representations. Finally, the Trigger Classification module makes structured predictions, where each label is predicted with respect to its neighbours. We conduct experiments on three benchmark BioNLP datasets, namely MLEE, GE09, and GE11, to evaluate our proposed BioLSL model. Results show that BioLSL has achieved state-of-the-art performance, outperforming the baseline models.

Conclusions

The proposed BioLSL model demonstrates good performance for biomedical event trigger detection without using any external resources. This suggests that label representation learning and context-aware enhancement are promising directions for improving the task. The key enhancement is that BioLSL effectively learns to construct semantic linkages between the event mentions and type labels, which provide the latent information of label-trigger and label-context relationships in biomedical texts. Moreover, additional experiments on BioLSL show that it performs exceptionally well with limited training data under the data-scarce scenarios.
Vaginal microbiome differences between patients with adenomyosis with different menstrual cycles and healthy controls
Authors: Pan Zangyu , Dai Jun , Zhang Ping , Ren Qianhui , Wang Xinyu , Yan Shumin , Sun Hao , Jiao Xue , Yuan Ming , Wang Guoyun
Published: July 2024

Background

Adenomyosis is a commonly observed benign gynecological disease that affects the quality of life and social psychology of women of childbearing age. However, because of the unknown etiology and incidence of adenomyosis, its pathophysiological mechanism remains unclear; further, because no noninvasive, accurate, and individualized diagnostic methods are available, treatment and efficacy evaluations are limited. Notably, the interaction between the changes in the microecological environment of the female reproductive tract and human immunity, endocrine, and other links leads to the occurrence and development of diseases. In addition, the vaginal microbiome differs in different menstrual cycles; therefore, assessing the differences between the microbiomes of patients with adenomyosis and healthy individuals in different menstrual cycles will improve the understanding of the disease and provide references for the search for noninvasive diagnosis and individualized precision treatment of adenomyosis. This study aimed to explored the data of individuals in different menstrual cycles.

Results

Differences in the vaginal microbiome between patients with adenomyosis and healthy individuals were observed. At phylum level, the relative abundance of Firmicutes in the adenomyosis group was higher than that in the control group, which contributed the most to the species difference between the two groups. At the genus level, Lactobacillus was the most dominant in both groups, Alpha-diversity analysis showed significant differences in the adenomyosis and control group during luteal phase (Shannon index, p = 0.0087; Simpson index, p = 0.0056). Beta-diversity index was significantly different between the two groups (p = 0.018). However, based on Weighted Unifrac analysis, significant differences were only observed throughout the luteal phase (p = 0.0146). Within the adenomyosis group, differences between women with different menstrual cycles were also observed. Finally, 50 possible biomarkers including were screened and predicted based on the random forest analyse.

Conclusions

The vaginal microbiome of patients with adenomyosis and healthy individuals differed during menstrual periods, especially during the luteal phase. These findings facilitate the search for specific biological markers within a limited range and provide a more accurate, objective, and individualized diagnostic and therapeutic evaluation method for patients with adenomyosis, compared to what is currently available.
Identification of quantitative trait loci and candidate genes for grain superoxide dismutase activity in wheat
Authors: Qu Kejia , Wang Jiqing , Cheng Yukun , Bai Bin , Xia Xianchun , Geng Hongwei
Published: July 2024

Background

Superoxide dismutase (SOD) can greatly scavenge reactive oxygen species (ROS) in plants. SOD activity is highly related to plant stress tolerance that can be improved by overexpression of SOD genes. Identification of SOD activity-related loci and potential candidate genes is essential for improvement of grain quality in wheat breeding. However, the loci and candidate genes for relating SOD in wheat grains are largely unknown. In the present study, grain SOD activities of 309 recombinant inbred lines (RILs) derived from the ‘Berkut’ × ‘Worrakatta’ cross were assayed by photoreduction method with nitro-blue tetrazolium (NBT) in four environments. Quantitative trait loci (QTL) of SOD activity were identified using inclusive composite interval mapping (ICIM) with the genotypic data of 50 K single nucleotide polymorphism (SNP) array.

Results

Six QTL for SOD activity were mapped on chromosomes 1BL, 4DS, 5AL (2), and 5DL (2), respectively, explaining 2.2 ~ 7.4% of the phenotypic variances. Moreover, QSOD.xjau-1BL, QSOD.xjau-4DS, QSOD.xjau-5 A.1, QSOD.xjau-5 A.2, and QSOD.xjau-5DL.2 identified are likely to be new loci for SOD activity. Four candidate genes TraesCS4D01G059500, TraesCS5A01G371600, TraesCS5D01G299900, TraesCS5D01G343100LC, were identified for QSOD.xjau-4DS, QSOD.xjau-5AL.1, and QSOD.xjau-5DL.1 (2), respectively, including three SOD genes and a gene associated with SOD activity. Based on genetic effect analysis, this can be used to identify desirable alleles and excellent allele variations in wheat cultivars.

Conclusion

These candidate genes are annotated for promoting SOD production and inhibiting the accumulation of ROS during plant growth. Therefore, lines with high SOD activity identified in this study may be preferred for future wheat breeding.
Clinical efficacy of macrolide antibiotics in mycoplasma pneumoniae pneumonia carrying a macrolide-resistant mutation in the 23 S rRNA gene in pediatric patients
Authors: He Mengyuan , Xie Junfeng , Rui Pu , Li Xiaoyu , Lai Min , Xue Hongman , Chen Chun
Published: July 2024

Background

The global prospective surveillance data showed the re-emergence of mycoplasma pneumoniae pneumonia (MPP) in Europe and Asia after the coronavirus disease 2019 pandemic. We sought to observe the effect of macrolide antibiotics in the treatment of MPP carrying a macrolide-resistant mutation gene and the potential of targeted next-generation sequencing (tNGS) as a front-line diagnostic in MPP patients.

Methods

The baseline characteristics of 91 children with MPP hospitalized from January to October 2023 were retrospectively analyzed. They were divided into two groups according to whether carrying the macrolide-resistant mutation or not. The logistic and linear regression analyses were used to determine whether the mutation was a standalone predictive predictor of the duration of fever and hospital length of stay.

Results

First, no patients had a fever for ≥ 7 days after macrolide treatment. But length of stay and hormone concentration were significantly different between the two groups (P < 0.05). There were also no statistical association between the mutation and the duration of fever and hospital length of stay.

Conclusion

Macrolides can be administered to MPP children carrying a macrolide-resistant mutation. tNGS can be seen as a front-line diagnostic in MPP.
Risk-prediction nomogram for congenital heart disease in offspring of Chinese pregnant women
Authors: Qu Pengfei , Zhang Shutong , Chen Jie , Li Xiayang , Zhao Doudou , Liu Danmeng , Shen Mingwang , Yan Hong , Pei Leilei , Dang Shaonong
Published: July 2024

Background

The identification and assessment of environmental risks are crucial for the primary prevention of congenital heart disease (CHD). We were aimed to establish a nomogram model for CHD in the offspring of pregnant women and validate it using a large CHD database in Northwest China.

Methods

A survey was conducted among 29,204 women with infants born between 2010 and 2013 in Shaanxi province, Northwest China. Participants were randomly assigned to the training set and to the validation set at a ratio of 7:3. The importance of predictive variables was assessed using random forest. A multivariate logistic regression model was used to construct the nomogram for the prediction of CHD.

Results

Multivariate analyses revealed that the gravidity, preterm birth history, family history of birth defects, infection, taking medicine, tobacco exposure, pesticide exposure and singleton/twin pregnancy were significant predictive risk factors for CHD in the offspring of pregnant women. The area under the receiver operating characteristic curve for the prediction model was 0.716 (95% CI: 0.671, 0.760) in the training set and 0.714 (95% CI: 0.630, 0.798) in the validation set, indicating moderate discrimination. The prediction model exhibited good calibration (Hosmer-Lemeshow χ2 = 1.529, P = 0.910).

Conclusions

We developed and validated a predictive nomogram for CHD in offspring of Chinese pregnant women, facilitating the early prenatal assessment of the risk of CHD and aiding in health education.
Diagnostic performances of methylated septin9 gene, CEA, CA19-9 and platelet-to-lymphocyte ratio in colorectal cancer
Authors: Sun Qian , Long Lu
Published: July 2024

Background

This study was designed to compare the diagnostic efficacy of mSEPT9 to four blood markers (CEA, CA19-9, platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR)). In addition, we aimed to determine the combined diagnostic efficacy of mSEPT9, CEA, CA19-9, PLR and NLR in colorectal cancer.

Methods

A total of 567 participants were enrolled in the study, including 308 CRC patients, 61 colorectal polyp patients and 198 healthy subjects confirmed by colonoscopy and/or tissue biopsy. Plasma samples were collected for tests.

Results

The positive rate of mSEPT9 in CRC (71.8%) was markedly higher than that in either the colorectal polyps group (27.9%) or the healthy controls (6.1%) (P < 0.001). The levels of CEA, CA19-9, NLR and PLR in the CRC group were significantly higher than those in the non-CRC groups (P < 0.05). ROC curves comparison analyses showed that the diagnostic efficacy of mSEPT9 alone in CRC was significantly higher than CEA, CA19-9, NLR and PLR alone. The combination of mSEPT9 with CEA, CA19-9 and PLR showed superior diagnostic value. In addition, binary logistic regression was also used to build a better model for clinical diagnosis of CRC. On univariable analyses, age, mSEPT9, CEA, CA 19–9, PLR and NLR were independent predictors of CRC. When these covariates were fitted in multivariable models, the ones with positive detection of mSEPT9, CEA, CA 19–9 and PLR were more likely to have CRC.

Conclusions

This research revealed a significant association between mSEPT9 status and the clinicopathological characteristics of CRC patients, and the combination of mSEPT9, CEA, CA19-9 and PLR could significantly improve diagnostic efficacy in CRC.
Risk factors for acute complicated appendicitis in children aged three years and younger
Authors: Ju Jun-Jun , Zhang Tao , Cheng Yuan , Zhou Yu-Liang , Qi Shi-Qin , Zhang Zhen-Qiang , Shen Wei-Chen , Pan Zhu-Bin
Published: July 2024

Objective

The aim of this study is to identify risk factors associated with acute complicated appendicitis (CA) in children aged three years or younger, providing a theoretical foundation for the management and treatment of acute appendicitis (AA).

Methods

A retrospective analysis was conducted on 135 pediatric patients with AA, admitted to the Department of General Surgery at Anhui Children’s Hospital between December 2020 and December 2023, who underwent successful surgical treatment. Based on the intraoperative and postoperative pathological findings, patients were categorized into two groups: complicated appendicitis (CA) (n = 97 cases) and uncomplicated appendicitis (UA) (n = 38 cases). Clinical data including gender, age, weight, disease duration, preoperative white blood cell count (WCC), neutrophil granulocyte (NEUT) count, C-reactive protein (CRP) levels, total bilirubin (TBil) levels, procalcitonin (PCT) levels, calprotectin (Cal) levels, preoperative ultrasound results indicating the presence or absence of fecaliths, maximum appendix diameter, and pediatric appendicitis sore (PAS) were collected and analyzed. Comparative analysis was performed to investigate the differences between the groups and identify risk factors of CA.

Results

The CA group exhibited significantly higher values in disease duration, CRP levels, PCT, Cal, presence of appendiceal fecaliths, maximum appendix diameter, and PAS compared to the UA group (P < 0.05). Multivariate analysis identified CRP levels, maximum appendix diameter, and PAS as independent risk factors for CA. Specifically, differences in CRP level (OR = 1.045, 95% CI:1.024 ~ 1.067, P < 0.001), PAS (OR = 1.768, 95% CI:1.086 ~ 2.879, P = 0.022), and maximum appendix diameter (OR = 1.860, 95% CI:1.085 ~ 3.191, P = 0.024) were significant. The area under the receiver operating characteristic curve values were 0.6776 for the PAS, 0.7663 for CRP, and 0.5604 for the maximum appendix diameter.

Conclusion

CRP levels, PAS, and maximum appendix diameter are independent risk factors for CA in children under three years of age. These parameters are valuable for the early diagnosis of CA.
Meteorological gaps in audits of pedestrian environments: a scoping review
Authors: Drapeau H. F , Singh P. , Benyaminov F. , Wright K. , Spence J. C. , Nuzhat S. , Walsh A. , Islam K. , Azarm Z. , Lee K. K.
Published: July 2024

Background

Weather and season are determinants of physical activity. Therefore, it is important to ensure built environments are designed to mitigate negative impacts of weather and season on pedestrians to prevent these losses. This scoping review aims to identify built environment audits of pedestrian environments developed for use during a specific weather condition or season. Secondly, this review aims to investigate gaps in the inclusion of relevant weather mitigating built environment features in pedestrian environment audit tools.

Methods

Following a standard protocol, a systematic search was executed in CINAHL, Medline and Web of Science to identify built environment audit tools of pedestrian spaces. These databases were chosen since they are well-known to comprehensively cover health as well as multi-disciplinary research publications relevant to health. Studies were screened, and data were extracted from selected documents by two independent reviewers (e.g., psychometric properties and audit items included). Audit items were screened for the inclusion of weather mitigating built environment features, and the tool’s capacity to measure temperature, precipitation, seasonal and sustainability impacts on pedestrians was calculated.

Results

The search returned 2823 documents. After screening and full text review, 27 articles were included. No tool was found that was developed specifically for use during a specific weather condition or season. Additionally, gaps in the inclusion of weather mitigating items were found for all review dimensions (thermal comfort, precipitation, seasonal, and sustainability items). Poorly covered items were: (1) thermal comfort related (arctic entry presence, materials, textures, and colours of buildings, roads, sidewalk and furniture, and green design features); (2) precipitation related (drain presence, ditch presence, hazards, and snow removal features); (3) seasonal features (amenities, pedestrian scale lighting, and winter destinations and aesthetics); and (4) sustainability features (electric vehicle charging stations, renewable energy, car share, and bike share facilities).

Conclusions

Current built environment audit tools do not adequately include weather / season mitigating items. This is a limitation as it is important to investigate if the inclusion of these items in pedestrian spaces can promote physical activity during adverse weather conditions. Because climate change is causing increased extreme weather events, a need exists for the development of a new built environment audit tool that includes relevant weather mitigating features.
The implications of policy modeling assumptions for the projected impact of sugar-sweetened beverage taxation on body weight and type 2 diabetes in Germany
Authors: Emmert-Fees Karl M. F. , Felea Andreea , Staudigel Matthias , Ananthapavan Jaithri , Laxy Michael
Published: July 2024

Background

Evaluating sugar-sweetened beverage (SSB) taxation often relies on simulation models. We assess how assumptions about the response to SSB taxation affect the projected body weight change and subsequent health and economic impacts related to type 2 diabetes mellitus (T2DM) using Germany as an example.

Methods

In the main analysis, we estimated changes in energy intake by age and sex under a 20% value-added tax on SSBs in Germany using marginal price elasticities (PE) and applied an energy equilibrium model to predict body weight changes. We then quantified the impact of several assumption modifications: SSB own-PE adjusted for consumption (M1)/based on alternative meta-analysis (M2); SSB consumption adjusted for underreporting (M3); substitution via marginal (M4a) or adjusted (M4b) cross-PE/as % of calorie change (M4c). We also assessed scenarios with alternative tax rates of 10% (S1) or 30% (S2) and including fruit juice (S3). We calculated overweight and obesity rates per modification and scenario. We simulated the impact on T2DM, associated healthcare costs, and disability-adjusted life years (DALYs) over the lifetime of the 2011 German adult population with a Markov model. Data included official demographics, national surveys, and meta-analyses.

Results

A 20% value-added tax in Germany could reduce the number of men and women with obesity by 210,800 [138,800; 294,100] and 80,800 [45,100; 123,300], respectively. Over the population’s lifetime, this would lead to modest T2DM-related health and economic impacts (76,700 DALYs [42,500; 120,600] averted; €2.37 billion [1.33; 3.71] costs saved). Policy impacts varied highly across modifications (all in DALYs averted): (M1) 94,800 [51,500; 150,700]; (M2) 164,200 [99,500; 243,500]; (M3) 52,600 [22,500; 91,100]; (M4a) -18,100 [-111,500; 68,300]; (M4b) 25,800 [-31,400; 81,500]; (M4c) 46,700 [25,300; 77,200]. The variability in policy impact related to modifications was similar to the variability between alternative policy scenarios (all in DALYs averted): (S1) 26,400 [9,300; 47,600]; (S2) 126,200 [73,600; 194,500]; (S3) 342,200 [234,200; 430,400].

Conclusions

Predicted body weight reductions under SSB taxation are sensitive to assumptions by researchers often needed due to data limitations. Because this variability propagates to estimates of health and economic impacts, the resulting structural uncertainty should be considered when using results in decision-making.
Prevalence, response and associated factors of needlestick injury among health care workers in Orotta National Referral Hospital, Eritrea
Authors: Negash Feven Beletse , Hailemichael Amanuel , Haileslassie Enabi , Hawaz Eyob , Zerai Samuel , Tesfamariam Zerabruk , Lebahati Laban
Published: July 2024

Background

Healthcare workers are at risk of occupational exposure to blood and other body fluids after sustaining needlestick injury which constitutes a risk for transmission of blood-borne pathogens such as Hepatitis B virus, Hepatitis C virus or Human Immune-deficiency Virus.

Objectives

To assess the prevalence, response, and associated factors of needlestick injury by medical sharps among healthcare workers in Orotta National Referral Hospital, Asmara, Eritrea.

Methods

Cross sectional study was conducted between September and December 2017 among healthcare workers. This was a census study whereby a total of 383 healthcare workers who had contact with sharp medical equipment were taken as study population. An aided self-administered questionnaire, checklist and key informant interviews were used as data collection tools. Analysis was done using Statistical Package for Social Sciences, version 22. Bivariate and binary logistic regression analyses were carried out and the level of significance was set at P < .05.

Results

The prevalence of needlestick injury 12 months preceding the study was 37.1% (134/361). Midwives had the highest occurrence (45%) among others while adult intensive care unit were found to have higher prevalence of needlestick injury (61.5%) as compared to the other sections. As an immediate response to needlestick injury, only 15.7% washed the injured part with soap and water. The factors associated with needlestick injury include age > 40 years (AOR = .314, p = .05), marital status (married (AOR = 0.595, p = .05)), additional duty that made healthcare workers rush during working hours (AOR = 2.134, p = .002) and back bone problem (AOR = 2.239, p = .002).

Conclusion

The overall finding of the study indicated that there was a great risk of contracting blood-borne infections among the healthcare workers especially midwives. Therefore, there is need for adequate supply of safety engineered devices, Hepatitis B vaccine, better reporting, and surveillance of needlestick injury cases at the hospital. Moreover, further research on assessment of the knowledge, attitude, and practice of healthcare workers toward occupational safety and health, particularly needlestick injury, is necessary.
Optimised stress – intensification of pyocyanin production with zinc oxide nanoparticles
Authors: Honselmann genannt Humme Joanna , Dubrowska Kamila , Grygorcewicz Bartłomiej , Gliźniewicz Marta , Paszkiewicz Oliwia , Głowacka Anna , Musik Daniel , Story Grzegorz , Rakoczy Rafał , Augustyniak Adrian
Published: July 2024

Background

Pyocyanin is a blue pigment produced by Pseudomonas aeruginosa. Due to its unique redox properties over the last decade, it has gained more and more interest as a utile chemical. Nevertheless, it remains a rather costly reagent. It was previously shown that the production of pyocyanin can be enhanced by employing various methods. Among them are using statistical methods for planning the experiments or exposing bacterial cultures to stressors such as nanoparticles dosed in sublethal concentrations, e.g. zinc oxide nanoparticles.

Results

The Design of Experiment (DoE) methodology allowed for calculating the optimal process temperature and nanoparticle concentration to intensify pyocyanin production. Low concentrations of the nanoparticles (6.06 µg/mL) and a temperature of 32℃ enhanced pyocyanin production, whereas higher concentrations of nanoparticles (275.75 µg/mL) and higher temperature stimulated biomass production and caused the abolishment of pyocyanin production. Elevated pigment production in zinc oxide nanoparticles-supplemented media was sustained in the scaled-up culture. Conducted analyses confirmed that observed stimulation of pyocyanin production is followed by higher membrane potential, altered gene expression, generation of reactive oxygen species, and accumulation of zinc in the cell’s biomass.

Conclusions

Pyocyanin production can be steered using ZnO nanoparticles. Elevated production of pyocyanin due to exposure to nanoparticles is followed by the number of changes in physiology of bacteria and is a result of the cellular stress. We showed that the stress response of bacteria can be optimised using statistical methods and result in producing the desired metabolite more effectively.
TGFBI promotes proliferation and epithelial–mesenchymal transition in renal cell carcinoma through PI3K/AKT/mTOR/HIF-1α pathway
Authors: Zhan Shanzhi , Bai Xiaojie , Zhao Yiqiao , Tuoheti Kuerban , Yisha Zuhaer , Zuo Yingtong , Lu Peixiang , Liu Tongzu
Published: July 2024

Background

Renal cell carcinoma (RCC) is presently recognized as the most prevalent kidney tumor. However, the role and underlying mechanism of action of the conversion factor-inducible protein (TGFBI), an extracellular matrix protein, in RCC remain poorly understood.

Methods

In this study, we employed Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), and immunohistochemistry techniques to assess the expression of TGFBI in RCC tissues or cells. Furthermore, we analyzed the proliferation and migration of RCC cells using CCK8, cloning, scratching, and migration assays. Additionally, we examined apoptosis and cell cycle progression through flow cytometry, analysis. Lastly, we employed gene set enrichment analysis (GSEA) to investigate the biological processes associated with TGFBI, which were subsequently validated.

Results

The findings indicate that TGFBI exhibits significantly elevated expression levels in both renal cell carcinoma (RCC) tissues and cells. Furthermore, the knockdown of TGFBI in SiRNA transfected cells resulted in the inhibition of RCC cell proliferation, migration, invasiveness, apoptosis, and alteration of the cell cycle. Additionally, TGFBI was found to impede the epithelial-mesenchymal transition (EMT) process in RCC cells. Bioinformatics analysis suggests that TGFBI may exert its influence on various biological processes in RCC through the tumor immune microenvironment. Moreover, our study demonstrates that TGFBI promotes RCC progression by activating the PI3K/AKT/mTOR/HIF-1α.

Conclusions

Our research indicates that TGFBI exhibits high expression in RCC and facilitate RCC progression and metastasis through various molecular mechanisms. Hence, TGFBI has the potential to be a novel therapeutic target for the diagnosis and treatment of RCC in the future.
Patterns and predictors of malaria among head porters: a mobile population in Ghana
Authors: Mintah-Agyeman Eunice , Adomako Boakye-Yiadom , Adu George Asumah , Oteng Benjamin , Duvor Fergusson , Abubakari Ihsan , Kommey Mildred , Asamoah Alexander , Peprah Nana Yaw , Malm Keziah L.
Published: July 2024

Background

Head porters popularly known as ‘Kayayeis in Ghana, face challenges in accessing essential health care services due to the mobile nature of their trade, low formal education, poor settlements, low-income among others. Kayayeis are predominantly females and form part of the mobile population who are at increased risk of malaria infection. Despite their increased risk of malaria, mobile populations are difficult to target for malaria interventions, hence serving as potential drivers of transmission even if malaria in the general population is controlled. The study, therefore, assessed the patterns and predictors of malaria among the Kayayei population in Ghana to inform policy decisions.

Methods

A mixed methods study was conducted among Head-porters and their leaders in the three main hubs of Head-porters in Ghana; namely Accra, Kumasi, and Tamale. Blood samples were collected from participants and tested for malaria parasites using Rapid Diagnostic Test (RDT). Additionally, data including socio-demographics, malaria knowledge, attitude and practice were collected using a semi-structured questionnaire. Associations between malaria status and participants characteristics were determined by logistic regression (p < 0.05). Thematic analysis was used to analyse transcripts from the key informant interviews.

Results

Out of 754 head porters studied, 10.48% (79) tested positive for malaria. The majority 43.10% (325/754) of the head porters were twenty years and below, and most 67.11% (506/754) had no formal education. Nearly half (50.4%) were not on any health insurance. Receiving malaria education in the past 6 months [AOR = 0.48, (0.26–0.88), p-value 0.02], and having poor knowledge of malaria [AOR = 2.23, (1.26–4.27), p < 0.02], were the factors significantly associated with malaria infection.

Conclusion

The prevalence of malaria among ‘Kayayei’s was estimated at 10.46%. A majority of them sleeps outside and in structures without mosquito screens. Receiving malaria education in the past 6 months reduced the odds of malaria infection whilst poor knowledge of malaria increased the odds of malaria infection among the porters. The authors recommend that the National Malaria Elimination Programme and partners should provide long-lasting insecticidal nets (LLIN) and other outdoor interventions for use by this special group. Designated state institutions should arrange free National Health Insurance Scheme (NHIS) registration for ‘Kayayeis’ to narrow the health access gap.
Decoding the spatiotemporal heterogeneity of tumor-associated macrophages
Authors: Chu Xiangyuan , Tian Yu , Lv Chao
Published: July 2024

Tumor-associated macrophages (TAMs) are pivotal in cancer progression, influencing tumor growth, angiogenesis, and immune evasion. This review explores the spatial and temporal heterogeneity of TAMs within the tumor microenvironment (TME), highlighting their diverse subtypes, origins, and functions. Advanced technologies such as single-cell sequencing and spatial multi-omics have elucidated the intricate interactions between TAMs and other TME components, revealing the mechanisms behind their recruitment, polarization, and distribution. Key findings demonstrate that TAMs support tumor vascularization, promote epithelial-mesenchymal transition (EMT), and modulate extracellular matrix (ECM) remodeling, etc., thereby enhancing tumor invasiveness and metastasis. Understanding these complex dynamics offers new therapeutic targets for disrupting TAM-mediated pathways and overcoming drug resistance. This review underscores the potential of targeting TAMs to develop innovative cancer therapies, emphasizing the need for further research into their spatial characteristics and functional roles within the TME.
Brief communication: temporal trends of chronic diseases medications prescriptions among HIV-infected patients in Belgium: a 4-year population-based study using pharmacy claims data
Authors: Ilboudo Dieudonné , Ngwasiri Calypse , Savoye Isabelle , Sommet Agnès , Beckhoven Dominique Van , Yombi Jean Cyr , Kirakoya-Samadoulougou Fati
Published: July 2024

The Objective of this study was to examine change over time of prevalence of chronic diseases medications (CDM) prescriptions among People living with HIV (PLWH) in Belgium, using Pharmanet database from 2018 to 2021. We identified 13,570, 14,175, 14,588 and 14,813 PLWH in 2018, 2019, 2020 and 2021, respectively. Prescriptions of cardiovascular diseases (CVD) medications (31.7–37.2%) and antidiabetics (7.4–9.0%), increased significantly (p for trend < 0.001 for all), while the prescription of neurological and mental disorders medications (18.0–19.3%) remained stable (p for trend = 0.11) and the prescription of chronic respiratory diseases (CRD) medications decreased from 12.2 to 10.6% (p for trend < 0.001), between 2018 and 2021. It is imperative to ensure that these medications are used appropriately.
The current global threat of weapons of mass destruction to humanity and public health
Authors: Ahmed Darya Rostam , Al Diab Al Azzawi Mohammad
Published: July 2024

Weapons of mass destruction (WMDs) have profoundly shaped global conflict and security landscapes throughout history. From the nuclear bombings of Hiroshima and Nagasaki to the chemical attack in Halabja, these catastrophic events underscored the devastating potential of WMDs on health, humanity, ecosystems, and international stability. This study explored the immediate and long-term impacts of WMDs, analyzing historical precedents and current global conflicts to highlight ongoing risks. Emphasizing the urgent need for international disarmament and non-proliferation efforts, the study aimed to raise awareness of the humanitarian, psychological, and ecological consequences of WMD use. By examining the geopolitical hotspots and the humanitarian crises they generated, it called for proactive crisis prevention strategies and enhanced global cooperation to mitigate the catastrophic effects of WMDs and protect global security.
Starch phosphorylation—A needle in a haystack
Authors: Compart Julia , Apriyanto Ardha , Fettke Joerg
Published: July 2024

Phosphoesterification is the only naturally occurring covalent starch modification identified to date, and it has a major impact on overall starch metabolism. The incorporation of phosphate groups mediated by dikinases [α-glucan, water dikinase (GWD), EC 2.7.9.4; phosphoglucan, water dikinase (PWD), EC 2.7.9.5] massively alters the starch granule properties; however, previous studies did not determine whether the starch-related dikinases bind the phosphate to the glucosyl units within the amylopectin molecules in a specific pattern or randomly. In order to answer this challenging question, a number of approaches were initially pursued until a protocol could be established that enabled a massive step forward in the in vitro analysis of phosphorylated glucan chains obtained from starch. For this purpose, phosphorylation by GWD was investigated, including the final state of phosphorylation i.e., the state of substrate saturation when GWD lacks further free hydroxyl groups at OH-C6 for the catalysis of monophosphate esters. Since the separated phosphorylated glucan chains were required for the analysis, isoamylase digestion was performed to cleave the α-1,6-glycosidic bonds and to allow for the removal of the huge number of existing neutral chains by means of anion exchange chromatography. Via Matrix-Assisted Laser Desorption/Ionization–Time of Flight (MALDI-TOF) MS and MALDI-MS/MS, the phosphorylated α-glucan chains were analysed, and the position of the phosphate group within the chain in relation to the reducing end was determined. Here, we demonstrate a protocol that enables the analysis of phosphorylated oligosaccharides, even in small quantities.
Developing a simple and rapid method for cell-specific transcriptome analysis through laser microdissection: insights from citrus rind with broader implications
Authors: Mei Xuehan , Zhu Kaijie , Yan Danni , Jia Huihui , Luo Wangyao , Ye Junli , Deng Xiuxin
Published: July 2024

Background

With the rapid development of single-cell sequencing technology, histological studies are no longer limited to conventional homogenized tissues. Laser microdissection enables the accurate isolation of specific tissues or cells, and when combined with next-generation sequencing, it can reveal important biological processes at the cellular level. However, traditional laser microdissection techniques have often been complicated and time-consuming, and the quality of the RNA extracted from the collected samples has been inconsistent, limiting follow-up studies. Therefore, an improved, simple, and efficient laser microdissection method is urgently needed.

Results

We omitted the sample fixation and cryoprotectant addition steps. Instead, fresh samples were embedded in Optimal Cutting Temperature medium within 1.5 ml centrifuge tube caps, rapidly frozen with liquid nitrogen, and immediately subjected to cryosectioning. A series of section thicknesses of citrus rind were tested for RNA extraction, which showed that 18 μm thickness yielded the highest quality RNA. By shortening the dehydration time to one minute per ethanol gradient and omitting the tissue clearing step, the resulting efficient dehydration and preserved morphology ensured high-quality RNA extraction. We also propose a set of laser microdissection parameters by adjusting the laser power to optimal values, reducing the aperture size, and lowering the pulse frequency. Both the epidermal and subepidermal cells from the citrus rind were collected, and RNA extraction was completed within nine hours. Using this efficient method, the transcriptome sequencing of the isolated tissues generated high-quality data with average Q30 values and mapping rates exceeding 91%. Moreover, the transcriptome analysis revealed significant differences between the cell layers, further confirming the effectiveness of our isolation approach.

Conclusions

We developed a simple and rapid laser microdissection method and demonstrated its effectiveness through a study based on citrus rind, from which we generated high-quality transcriptomic data. This fast and efficient method of cell isolation, combined with transcriptome sequencing not only contributes to precise histological studies at the cellular level in citrus but also provides a promising approach for cell-specific transcriptome analysis in a broader range of other plant tissues.
The influence of operation time for hip hemiarthroplasty on complication rates and mortality in patients with femoral neck fracture: a retrospective data analysis: Letter to Editor
Authors: Vaishya Raju , Vaish Abhishek
Published: July 2024

Ramadanov et al.‘s study highlights the importance of minimizing operative time in HHA for femoral neck fractures. Future prospective studies are needed to explore causality and refine strategies for achieving shorter, yet safe, procedures.
Statistical considerations for the platform trial in COVID-19 vaccine priming and boosting
Authors: Dymock Michael , McLeod Charlie , Richmond Peter , Snelling Tom , Marsh Julie A. ,   On behalf of the PICOBOO Investigator Team
Published: July 2024

The Platform trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, adaptive platform trial designed to generate evidence of the immunogenicity, reactogenicity, and cross-protection of different booster vaccination strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, specific for the Australian context. The PICOBOO trial randomises participants to receive one of three COVID-19 booster vaccine brands (Pfizer, Moderna, Novavax) available for use in Australia, where the vaccine brand subtypes vary over time according to the national vaccine roll out strategy, and employs a Bayesian hierarchical modelling approach to efficiently borrow information across consecutive booster doses, age groups and vaccine brand subtypes. Here, we briefly describe the PICOBOO trial structure and report the statistical considerations for the estimands, statistical models and decision making for trial adaptations. This paper should be read in conjunction with the PICOBOO Core Protocol and PICOBOO Sub-Study Protocol 1: Booster Vaccination. PICOBOO was registered on 10 February 2022 with the Australian and New Zealand Clinical Trials Registry ACTRN12622000238774.
A zebrafish gephyrinb mutant distinguishes synaptic and enzymatic functions of Gephyrin
Authors: Brennan Emma J. , Monk Kelly R. , Li Jiaxing
Published: July 2024

Gephyrin is thought to play a critical role in clustering glycine receptors at synapses within the central nervous system (CNS). The main in vivo evidence for this comes from Gephyrin (Gphn)-null mice, where glycine receptors are depleted from synaptic regions. However, these mice die at birth, possibly due to impaired molybdenum cofactor (MoCo) synthesis, an essential role Gephyrin assumes throughout an animal. This complicates the interpretation of synaptic phenotypes in Gphn-null mice and raises the question whether the synaptic and enzymatic functions of Gephyrin can be investigated separately. Here, we generated a gephyrinb zebrafish mutant, vo84, that almost entirely lacks Gephyrin staining in the spinal cord. gephyrinbvo84 mutants exhibit normal gross morphology at both larval and adult stages. In contrast to Gphn-null mice, gephyrinbvo84 mutants exhibit normal motor activity and MoCo-dependent enzyme activity. Instead, gephyrinbvo84 mutants display impaired rheotaxis and increased mortality in late development. To investigate what may mediate these defects in gephyrinbvo84 mutants, we examined the cell density of neurons and myelin in the spinal cord and found no obvious changes. Surprisingly, in gephyrinbvo84 mutants, glycine receptors are still present in the synaptic regions. However, their abundance is reduced, potentially contributing to the observed defects. These findings challenge the notion that Gephyrin is absolutely required to cluster glycine receptors at synapses and reveals a new role of Gephyrin in regulating glycine receptor abundance and rheotaxis. They also establish a powerful new model for studying the mechanisms underlying synaptic, rather than enzymatic, functions of Gephyrin.