bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge, perceived needs of continuous professional’s development, and associated factors among healthcare workers in East Ethiopia: a multi-health facility-based cross-sectional study
Authors: Yadeta Tesfaye Assebe , Mohamed Ahmed , Behir Kerimo , Alemu Addisu , Balis Bikila , Debella Adera , Letta Shiferaw
Published: May 2024

Background

The Ethiopian Ministry of Health (EMOH) has recently introduced a Continuous Professional Development (CPD) program for healthcare workers to ensure they maintain the necessary competencies to meet the community’s health needs. However, there is limited information on healthcare workers’ knowledge and perceived need for CPD. This study aims to assess healthcare workers’ CPD knowledge, perceived needs, and factors associated with these in eastern Ethiopia.

Methods

A health facility-based cross-sectional quantitative study was conducted from September 1, 2022, to October 30, 2022. Health facilities and study participants were selected using a simple random sampling technique. A total of 731 healthcare professionals were randomly selected. Data was collected using a self-administered questionnaire developed from national CPD guidelines. Data analysis was performed using the STATA statistical package version 14. A logistic regression model was used to assess the association between predictors and the outcome variable. Adjusted odds ratios with 95% confidence intervals were calculated to determine the strength of the association. A p-value < 0.05 was considered statistically significant.

Results

In this study, 731 healthcare workers participated. Among them, 65.80% (95% CI: 62.35%, 69.24%) had knowledge of CPD, and 79.48% (CI95% 76.54, 82.41) expressed a strong perceived need for CPD. Female healthcare workers [AOR: 0.54 (95% CI: 0.37, 0.78)] and lack of internet access [AOR: 0.68 (95% CI: 0.47–0.97)] were predictors of knowledge of CPD. Age above 35 [AOR: 0.39 (95% CI: 0.17, 0.91)] and being female [AOR: 0.59 (95% CI: 0.40–0.87)] were predictors of a strong perceived need for CPD.

Conclusion

The study found that there was a low level of knowledge about Continuing Professional Development among healthcare workers. The perceived needs of healthcare workers varied. It is important for health sectors and stakeholders to prioritize developing strategies that address knowledge gaps, particularly among female healthcare workers, improve access to the Internet for CPD resources, and address the diverse needs of professionals for effective CPD implementation.
Early evidence of implementation of District Residency Programme: experiences and challenges of residents in Rajasthan, India
Authors: Raj Ankit , Singh Shalini , Rathore Monika
Published: May 2024

Background

District Residency Programme (DRP) was introduced by National Medical Commission as mandatory three-months training program for postgraduate residents. The program was for the first time implemented in April 2023 in Rajasthan. However, it ran into several teething problems, especially for residents. With a lack of any precedence, this study was planned to explore experiences and challenges of residents posted in DRP.

Methods

Cross-sectional study was conducted at 12 DRP sites attached to SMS Medical College, Jaipur between August-October 2023. A self-administered questionnaire was used to collect information from residents who had completed DRP. Questions were scored on a five-point Likert scale. Mann-Whitney U test and Kruskal-Wallis H test was used to show association.

Results

Only around 17% residents felt that the learning objectives of DRP were fulfilled and nearly 60% residents felt isolated from academic activities and parent department. Over half of the residents were never posted with their concerned specialty services. Around four-fifth residents felt concerned about safety at least sometimes and more than three-fourth residents were dissatisfied with basic amenities. Kruskal-Wallis and Mann-Whitney tests showed significant association of gender and specialisation strata with multiple outcome variables.

Conclusion

The study finds high degree of dissatisfaction among residents towards learning objectives, academic learning, and basic amenities during DRP. There was also a clear lack of specialty-exposure and high concerns of safety, especially for female residents. The study findings should alarm and inform policymakers and administrators to improve DRP implementation so as to better achieve laid objectives.
Ethics support for ethics support: the development of the Confidentiality Compass for dealing with moral challenges concerning (breaching) confidentiality in moral case deliberation
Authors: Ligtenberg Wieke , Stolper Margreet , Molewijk Bert
Published: May 2024

Background

Confidentiality is one of the central preconditions for clinical ethics support (CES). CES cases which generate moral questions for CES staff concerning (breaching) confidentiality of what has been discussed during CES can cause moral challenges. Currently, there seems to be no clear policy or guidance regarding how CES staff can or should deal with these moral challenges related to (not) breaching confidentiality within CES. Moral case deliberation is a specific kind of CES.

Method

Based on experiences and research into MCD facilitators’ needs for ethics support in this regard, we jointly developed an ethics support tool for MCD facilitators: the Confidentiality Compass. This paper describes the iterative developmental process, including our theoretical viewpoints and reflections on characteristics of CES tools in general.

Results

The content and goals of the ethics support tool, which contains four elements, is described. Part A is about providing information on the concept of confidentiality in MCD, part B is a moral compass with reflective questions, part C focuses on courses of action for careful handling of moral challenges related to confidentiality. Part D contains general lessons, best practices and tips for dealing with confidentiality in future cases.

Conclusions

This paper concludes with providing some lessons-learned related to developing ethics support tools and some reflections on issues of quality and normativity of ethics support tools.
Continuous patient state attention model for addressing irregularity in electronic health records
Authors: Chauhan Vinod Kumar , Thakur Anshul , O’Donoghue Odhran , Rohanian Omid , Molaei Soheila , Clifton David A.
Published: May 2024

Background

Irregular time series (ITS) are common in healthcare as patient data is recorded in an electronic health record (EHR) system as per clinical guidelines/requirements but not for research and depends on a patient’s health status. Due to irregularity, it is challenging to develop machine learning techniques to uncover vast intelligence hidden in EHR big data, without losing performance on downstream patient outcome prediction tasks.

Methods

In this paper, we propose Perceiver, a cross-attention-based transformer variant that is computationally efficient and can handle long sequences of time series in healthcare. We further develop continuous patient state attention models, using Perceiver and transformer to deal with ITS in EHR. The continuous patient state models utilise neural ordinary differential equations to learn patient health dynamics, i.e., patient health trajectory from observed irregular time steps, which enables them to sample patient state at any time.

Results

The proposed models’ performance on in-hospital mortality prediction task on PhysioNet-2012 challenge and MIMIC-III datasets is examined. Perceiver model either outperforms or performs at par with baselines, and reduces computations by about nine times when compared to the transformer model, with no significant loss of performance. Experiments to examine irregularity in healthcare reveal that continuous patient state models outperform baselines. Moreover, the predictive uncertainty of the model is used to refer extremely uncertain cases to clinicians, which enhances the model’s performance. Code is publicly available and verified at https://codeocean.com/capsule/4587224.

Conclusions

Perceiver presents a computationally efficient potential alternative for processing long sequences of time series in healthcare, and the continuous patient state attention models outperform the traditional and advanced techniques to handle irregularity in the time series. Moreover, the predictive uncertainty of the model helps in the development of transparent and trustworthy systems, which can be utilised as per the availability of clinicians.
Effectiveness of a family empowerment program on caregiving capacity and adverse mood in caregivers of children with acute leukemia: a quasi-experimental study
Authors: Guo Fang , Li Liangjian , Jiang Hao , Yu Jie , Wang Yueqi
Published: May 2024

Background

Family-centered empowerment programs have been widely used in the pediatric field. Therefore, the current study investigated the effectiveness of family empowerment programs on caregiving ability and adverse mood among caregivers of children with acute leukemia.

Objective

To evaluate the effect of a family empowerment program on the caregiving ability and adverse mood of caregivers of children with acute leukemia.

Methods

Sixty-eight children with acute leukemia and their family caregivers admitted to our hospital were selected for the study. The control group received routine care during hospitalization, and the family empowerment program was implemented in the intervention group to compare the changes in caregiving capacity (FCTI), illness uncertainty (PPUS) and anxiety(SAS)of the caregivers of the two groups.

Results

After 8 weeks of intervention, the FCTI score of the intervention group was significantly lower than that of the control group (P < 0.001), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the PPUS score of the intervention group was significantly lower than that of the control group (P < 0.05), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the SAS score of the intervention group was lower than that of the control group after intervention(P < 0.05), and the score difference before and after intervention was statistically significant (P < 0.001).

Conclusion

Family empowerment program is beneficial in improving caregiving capacity and reducing disease uncertainty and anxiety among caregivers of children with acute leukemia.

Trial registration

Chinese Clinical Trial Registry ChiCTR2300073476 2023-07-12 Retrospectively registered.
Developing a typology of interventions to support doctors’ mental health and wellbeing
Authors: Pearson Alison , Carrieri Daniele , Melvin Anna , Bramwell Charlotte , Scott Jessica , Hancock Jason , Papoutsi Chrysanthi , Pearson Mark , Wong Geoff , Mattick Karen
Published: May 2024

Background

The problem of mental ill-health in doctors is complex, accentuated by the COVID-19 pandemic, and impacts on healthcare provision and broader organisational performance. There are many interventions to address the problem but currently no systematic way to categorise them, which makes it hard to describe and compare interventions. As a result, implementation tends to be unfocussed and fall short of the standards developed for implementing complex healthcare interventions. This study aims to develop: 1) a conceptual typology of workplace mental health and wellbeing interventions and 2) a mapping tool to apply the typology within research and practice.

Methods

Typology development was based on iterative cycles of analysis of published and in-practice interventions, incorporation of relevant theories and frameworks, and team and stakeholder group discussions.

Results

The newly developed typology and mapping tool enable interventions to be conceptualised and/or mapped into different categories, for example whether they are designed to be largely preventative (by either improving the workplace or increasing personal resources) or to resolve problems after they have arisen. Interventions may be mapped across more than one category to reflect the nuance and complexity in many mental health and wellbeing interventions. Mapping of interventions indicated that most publications have not clarified their underlying assumptions about what causes outcomes or the theoretical basis for the intervention.

Conclusion

The conceptual typology and mapping tool aims to raise the quality of future research and promote clear thinking about the nature and purpose of interventions, In doing so it aims to support future research and practice in planning interventions to improve the mental health and wellbeing of doctors.
A survey on the implementation of clinical medication reviews in community pharmacies within a multidisciplinary setting
Authors: Hogervorst S. , Adriaanse M.C. , Vervloet M. , Teichert M. , Beckeringh J.J. , van Dijk L. , Hugtenburg J.G.
Published: May 2024

Background

Polypharmacy is common in chronic medication users, which increases the risk of drug related problems. A suitable intervention is the clinical medication review (CMR) that was introduced in the Netherlands in 2012, but the effectiveness might be hindered by limited implementation in community pharmacies. Therefore our aim was to describe the current implementation of CMRs in Dutch community pharmacies and to identify barriers to the implementation.

Methods

An online questionnaire was developed based on the Consolidated Framework for Implementation Research (CFIR) and consisted of 58 questions with open ended, multiple choice or Likert-scale answering options. It was sent out to all Dutch community pharmacies (n = 1,953) in January 2021. Descriptive statistics were used.

Results

A total of 289 (14.8%) community pharmacies filled out the questionnaire. Most of the pharmacists agreed that a CMR has a positive effect on the quality of pharmacotherapy (91.3%) and on medication adherence (64.3%). Pharmacists structured CMRs according to available selection criteria or guidelines (92%). Pharmacists (90%) believed that jointly conducting a CMR with a general practitioner (GP) improved their mutual relationship, whereas 21% believed it improved the relationship with a medical specialist. Lack of time was reported by 43% of pharmacists and 80% (fully) agreed conducting CMRs with a medical specialist was complicated. Most pharmacists indicated that pharmacy technicians can assist in performing CMRs, but they rarely do in practice.

Conclusions

Lack of time and suboptimal collaboration with medical specialists are the most important barriers to the implementation of CMRs.
Swd2/Cps35 determines H3K4 tri-methylation via interactions with Set1 and Rad6
Authors: Oh Junsoo , Park Shinae , Kim Jueun , Yeom Soojin , Lee Ji Min , Lee Eun-Jin , Cho Yong-Joon , Lee Jung-Shin
Published: May 2024

Background

Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation.

Results

We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5ʹ region and 3ʹ region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5ʹ region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5ʹ region was impaired and rather increased in the 3ʹ region.

Conclusions

This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2’s binding to the transcribed genes and Set1 redistributes the Swd2 to the 5ʹ region for accomplishments of H3K4me3 in the genome-wide level.
Development of novel Streptococcus equi vaccines with an assessment of their immunizing potentials and protective efficacies
Authors: Soliman Rafik , Yousef Mohamed , gelil Sara Abdel , Aboul-Ella Hassan
Published: May 2024

Strangles is a highly contagious disease of the equine upper respiratory tract caused by Streptococcus equi subspecies. Streptococcus equi subsp. equi (S. equi) and Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) was isolated, as local, hot, and field strains, from horses clinically suffering from respiratory distress. The isolated Streptococci were identified using bacteriological and molecular techniques. Four formulations of inactivated S. equi vaccines were developed and evaluated. The first formulation was prepared using the S. equi isolates, adjuvanted with MONTANIDE GEL adjuvant, while the second formulation was adjuvanted with MONTANIDE ISA-70 adjuvant. The other 2 formulations were inactivated combined vaccines prepared from both S. equi and S. zooepidemicus isolates. The 3rd formulation was the combined isolates adjuvanted with MONTANIDE GEL while the 4th formulation was the combined isolates adjuvanted with MONTANIDE ISA-70. The developed vaccines’ physical properties, purity, sterility, safety, and potency were ensured. The immunizing efficacy was determined in isogenic BALB/c mice and white New Zealand rabbits using the passive hemagglutination test. Also, the antibodies’ titer of the combined S. equi and S. zooepidemicus vaccine adjuvanted with MONTANIDE ISA-70 in foals was tracked using an indirect enzyme-linked immunosorbent assay. The protective efficacy of the developed vaccines was determined using a challenge test in both laboratory and field animal models, where a 75% protection rate was achieved. The combined vaccine proved to be more efficacious than the monovalent vaccine. Also, the MONTANIDE ISA-70 adjuvant provided significant protective efficacy than the MONTANIDE GEL. The current work is introducing a very promising mitigative and strategic controlling solution for strangles.
Analyzing the expression and clinical significance of CENPE in gastric cancer
Authors: Wang Jing , Li Xiaofei , Qiang Xihui , Yin Xueqing , Guo Lianyi
Published: May 2024

Background

Gastric cancer (GC) is a prevalent type of malignant gastrointestinal tumor. Many studies have shown that CENPE acts as an oncogene in some cancers. However, its expression level and clinical value in GC are not clear.

Methods

Obtaining clinical data information on gastric adenocarcinoma from TCGA and GEO databases. The gene expression profiling interaction analysis (GEPIA) was used to evaluate the relationship between prognosis and CENPE expression in gastric cancer patients. Utilizing the UALCAN platform, the correlation between CENPE expression and clinical parameters was examined. Functions and signaling pathways of CENPE were analyzed using the Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). The association between immunological infiltrating cells and CENPE expression was examined using TIMER2.0. Validation was performed by real-time quantitative PCR (qPT-PCR) and immunohistochemical analysis.

Results

According to the analysis of the GEPIA database, the expression of CENPE is increased in gastric cancer tissues compared to normal tissues. It was also found to have an important relationship with the prognosis of the patient (p<0.05). The prognosis was worse and overall survival was lower in individuals with increased expression of CENPE. In line with the findings of the GEPIA, real-time fluorescence quantitative PCR (qPT-PCR) confirmed that CENPE was overexpressed in gastric cancer cells. Furthermore, It was discovered that H. pylori infection status and tumor grade were related to CENPE expression. Enrichment analysis revealed that CENPE expression was linked to multiple biological functions and tumor-associated pathways. CENPE expression also correlated with immune-infiltrating cells in the gastric cancer microenvironment and was positively connected to NK cells and mast cells. According to immunohistochemical examination, paracancerous tissues had minimal expression of CENPE, but gastric cancer showed significant expression of the protein.

Conclusions

According to our findings, CENPE is substantially expressed in GC and may perhaps contribute to its growth. CENPE might be a target for gastric cancer therapy and a predictor of a bad prognosis.
Charting the cellular landscape of pulmonary arterial hypertension through single-cell omics
Authors: Tang Brian , Vadgama Arjun , Redmann Bryce , Hong Jason
Published: May 2024

This review examines how single-cell omics technologies, particularly single-cell RNA sequencing (scRNAseq), enhance our understanding of pulmonary arterial hypertension (PAH). PAH is a multifaceted disorder marked by pulmonary vascular remodeling, leading to high morbidity and mortality. The cellular pathobiology of this heterogeneous disease, involving various vascular and non-vascular cell types, is not fully understood. Traditional PAH studies have struggled to resolve the complexity of pathogenic cell populations. scRNAseq offers a refined perspective by detailing cellular diversity within PAH, identifying unique cell subsets, gene networks, and molecular pathways that drive the disease. We discuss significant findings from recent literature, summarizing how scRNAseq has shifted our understanding of PAH in human, rat, and mouse models. This review highlights the insights gained into cellular phenotypes, gene expression patterns, and novel molecular targets, and contemplates the challenges and prospective paths for research. We propose ways in which single-cell omics could inform future research and translational efforts to combat PAH.
Ion channel Piezo1 activation aggravates the endothelial dysfunction under a high glucose environment
Authors: Zhang Xiaoyu , Leng Shaoqiu , Liu Xinyue , Hu Xiang , Liu Yan , Li Xin , Feng Qi , Guo Wei , Li Nailin , Sheng Zi , Wang Shuwen , Peng Jun
Published: May 2024

Background

Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear.

Methods

Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation.

Results

Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1.

Conclusion

In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.
Statistical design and analysis of controlled human malaria infection trials
Authors: Tian Xiaowen , Janes Holly E. , Kublin James G.
Published: May 2024

Background

Malaria is a potentially life-threatening disease caused by Plasmodium protozoa transmitted by infected Anopheles mosquitoes. Controlled human malaria infection (CHMI) trials are used to assess the efficacy of interventions for malaria elimination. The operating characteristics of statistical methods for assessing the ability of interventions to protect individuals from malaria is uncertain in small CHMI studies. This paper presents simulation studies comparing the performance of a variety of statistical methods for assessing efficacy of intervention in CHMI trials.

Methods

Two types of CHMI designs were investigated: the commonly used single high-dose design (SHD) and the repeated low-dose design (RLD), motivated by simian immunodeficiency virus (SIV) challenge studies. In the context of SHD, the primary efficacy endpoint is typically time to infection. Using a continuous time survival model, five statistical tests for assessing the extent to which an intervention confers partial or full protection under single dose CHMI designs were evaluated. For RLD, the primary efficacy endpoint is typically the binary infection status after a specific number of challenges. A discrete time survival model was used to study the characteristics of RLD versus SHD challenge studies.

Results

In a SHD study with the continuous time survival model, log-rank test and t-test are the most powerful and provide more interpretable results than Wilcoxon rank-sum tests and Lachenbruch tests, while the likelihood ratio test is uniformly most powerful but requires knowledge of the underlying probability model. In the discrete time survival model setting, SHDs are more powerful for assessing the efficacy of an intervention to prevent infection than RLDs. However, additional information can be inferred from RLD challenge designs, particularly using a likelihood ratio test.

Conclusions

Different statistical methods can be used to analyze controlled human malaria infection (CHMI) experiments, and the choice of method depends on the specific characteristics of the experiment, such as the sample size allocation between the control and intervention groups, and the nature of the intervention. The simulation results provide guidance for the trade off in statistical power when choosing between different statistical methods and study designs.
Repurposing of anti-malarial drugs for the treatment of tuberculosis: realistic strategy or fanciful dead end?
Authors: Hanscheid Thomas , del Portal Luyten Claire Ruiz , Hermans Sabine M. , Grobusch Martin P.
Published: May 2024

Background

Drug repurposing offers a strategic alternative to the development of novel compounds, leveraging the known safety and pharmacokinetic profiles of medications, such as linezolid and levofloxacin for tuberculosis (TB). Anti-malarial drugs, including quinolones and artemisinins, are already applied to other diseases and infections and could be promising for TB treatment.

Methods

This review included studies on the activity of anti-malarial drugs, specifically quinolones and artemisinins, against Mycobacterium tuberculosis complex (MTC), summarizing results from in vitro, in vivo (animal models) studies, and clinical trials. Studies on drugs not primarily developed for TB (doxycycline, sulfonamides) and any novel developed compounds were excluded. Analysis focused on in vitro activity (minimal inhibitory concentrations), synergistic effects, pre-clinical activity, and clinical trials.

Results

Nineteen studies, including one ongoing Phase 1 clinical trial, were analysed: primarily investigating quinolones like mefloquine and chloroquine, and, to a lesser extent, artemisinins. In vitro findings revealed high MIC values for anti-malarials versus standard TB drugs, suggesting a limited activity. Synergistic effects with anti-TB drugs were modest, with some synergy observed in combinations with isoniazid or pyrazinamide. In vivo animal studies showed limited activity of anti-malarials against MTC, except for one study of the combination of chloroquine with isoniazid.

Conclusions

The repurposing of anti-malarials for TB treatment is limited by high MIC values, poor synergy, and minimal in vivo effects. Concerns about potential toxicity at effective dosages and the risk of antimicrobial resistance, especially where TB and malaria overlap, further question their repurposing. These findings suggest that focusing on novel compounds might be both more beneficial and rewarding.
Urinary volatile organic compound metabolites and COPD among US adults: mixture, interaction and mediation analysis
Authors: Wang Ying , Meng Zhaowei , Wei Sen , Li Xuebing , Su Zheng , Jiang Yong , Wu Heng , Pan Hongli , Wang Jing , Zhou Qinghua , Qiao Youlin , Fan Yaguang
Published: May 2024

Background

Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample.

Methods

We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin.

Results

In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers.

Conclusions

Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.
Engineered nanoparticles promote cardiac tropism of AAV vectors
Authors: Switala Lauren , Di Lin , Gao Huiyun , Asase Courteney , Klos Matthew , Rengasamy Palanivel , Fedyukina Daria , Maiseyeu Andrei
Published: May 2024

Cardiac muscle targeting is a notoriously difficult task. Although various nanoparticle (NP) and adeno-associated viral (AAV) strategies with heart tissue tropism have been developed, their performance remains suboptimal. Significant off-target accumulation of i.v.-delivered pharmacotherapies has thwarted development of disease-modifying cardiac treatments, such as gene transfer and gene editing, that may address both rare and highly prevalent cardiomyopathies and their complications. Here, we present an intriguing discovery: cargo-less, safe poly (lactic-co-glycolic acid) particles that drastically improve heart delivery of AAVs and NPs. Our lead formulation is referred to as ePL (enhancer polymer). We show that ePL increases selectivity of AAVs and virus-like NPs (VLNPs) to the heart and de-targets them from the liver. Serotypes known to have high (AAVrh.74) and low (AAV1) heart tissue tropisms were tested with and without ePL. We demonstrate up to an order of magnitude increase in heart-to-liver accumulation ratios in ePL-injected mice. We also show that ePL exhibits AAV/NP-independent mechanisms of action, increasing glucose uptake in the heart, increasing cardiac protein glycosylation, reducing AAV neutralizing antibodies, and delaying blood clearance of AAV/NPs. Current approaches utilizing AAVs or NPs are fraught with challenges related to the low transduction of cardiomyocytes and life-threatening immune responses; our study introduces an exciting possibility to direct these modalities to the heart at reduced i.v. doses and, thus, has an unprecedented impact on drug delivery and gene therapy. Based on our current data, the ePL system is potentially compatible with any therapeutic modality, opening a possibility of cardiac targeting with numerous pharmacological approaches.

Graphical Abstract
Physiologic oxygen responses to smoking opioids: an observational study using continuous pulse oximetry at overdose prevention services in British Columbia, Canada
Authors: Moe Jessica , Buxton Jane A. , Wang Yueqiao Elle , Chavez Tamara , Feldman-Kiss Damian , Marr Charotte , Purssell Roy A. , Otterstatter Michael
Published: May 2024

Background

In British Columbia, Canada, smoking is the most common modality of drug use among people who die of opioid toxicity. We aimed to assess oxygen saturation (SpO2) while people smoked opioids during a pilot study that introduced continuous pulse oximetry at overdose prevention services (OPS) sites.

Methods

This was an observational cohort study, using a participatory design. We implemented our monitoring protocol from March to August 2021 at four OPS. We included adults (≥ 18 years) presenting to smoke opioids. A sensor taped to participants’ fingers transmitted real-time SpO2 readings to a remote monitor viewed by OPS staff. Peer researchers collected baseline data and observed the timing of participants’ inhalations. We analyzed SpO2 on a per-event basis. In mixed-effects logistic regression models, drop in minimum SpO2 ≤ 90% in the current minute was our main outcome variable. Inhalation in that same minute was our main predictor. We also examined inhalation in the previous minute, cumulative inhalations, inhalation rate, demographics, co-morbidities, and substance use variables.

Results

We recorded 599 smoking events; 72.8% (436/599) had analyzable SpO2 data. Participants’ mean age was 38.6 years (SD 11.3 years) and 73.1% were male. SpO2 was highly variable within and between individuals. Drop in SpO2 ≤ 90% was not significantly associated with inhalation in that same minute (OR: 1.2 [0.8–1.78], p = 0.261) or inhalation rate (OR 0.47 [0.20–1.10], p = 0.082). There was an association of SpO2 drop with six cumulative inhalations (OR 3.38 [1.04–11.03], p = 0.043); this was not maintained ≥ 7 inhalations. Demographics, co-morbidities, and drug use variables were non-contributory.

Conclusions

Continuous pulse oximetry SpO2 monitoring is a safe adjunct to monitoring people who smoke opioids at OPS. Our data reflect challenges of real-world monitoring, indicating that greater supports are needed for frontline responders at OPS. Inconsistent association between inhalations and SpO2 suggests that complex factors (e.g., inhalation depth/duration, opioid tolerance, drug use setting) contribute to hypoxemia and overdose risk while people smoke opioids.
Surgical management of right hepatectomy after coronary artery bypass grafting using the right gastroepiploic artery: a case report and literature review
Authors: Kawaguchi Nao , Kizawa Shun , Daimon Masahiro , Minami Hiroki , Ueda Yasuhiko , Tomioka Atsushi , Komeda Koji , Asakuma Mitsuhiro , Tomiyama Hideki , Lee Sang-Woong
Published: May 2024

Background

Coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) is a well-established, safe procedure. However, problems with RGEA grafts in subsequent abdominal surgeries can lead to fatal complications. This report presents the first case of right hepatectomy for hepatocellular carcinoma after CABG using the RGEA.

Case presentation

We describe a case in which a right hepatectomy for an 81-year-old male patient with hepatocellular carcinoma was safely performed after CABG using a RGEA graft. Preoperatively, three-dimensional computed tomography (3D- CT) images were constructed to confirm the run of the RGEA graft. The operation was conducted with the standby of a cardiovascular surgeon if there was a problem with the RGEA graft. The RGEA graft had formed adhesions with the hepatic falciform ligament, necessitating meticulous dissection. After the right hepatectomy, the left hepatic lobe descended into the vacated space, exerting traction on the RGEA. However, this traction was mitigated by suturing the hepatic falciform ligament to the abdominal wall, ensuring stability of the RGEA. There were no intraoperative or postoperative complications.

Conclusion

It is crucial to confirm the functionality and anatomy of the RGEA graft preoperatively, handle it gently intraoperatively, and collaborate with cardiovascular surgeons.
Built and natural environment correlates of physical activity of adults living in rural areas: a systematic review
Authors: Müller Christina , Paulsen Lisa , Bucksch Jens , Wallmann-Sperlich Birgit
Published: May 2024

Background

According to social-ecological models, the built and natural environment has the potential to facilitate or hinder physical activity (PA). While this potential is well researched in urban areas, a current systematic review of how the built and natural environment is related to PA in rural areas is lacking.

Methods

We searched five databases and included studies for adults (18–65 years) living in rural areas. We included quantitative studies investigating the association between any self-reported or objectively measured characteristic of the built or natural environment and any type of self-reported or objectively measured PA, and qualitative studies that reported on features of the built or natural environment perceived as barriers to or facilitators of PA by the participants. Screening for eligibility and quality assessment (using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields) were done in duplicate. We used a narrative approach to synthesize the results.

Results

Of 2432 non-duplicate records, 51 quantitative and 19 qualitative studies were included. Convincing positive relationships were found between the availability and accessibility of places for exercise and recreation and leisure-time PA as well as between the overall environment and leisure-time PA. Possible positive associations were found between the overall environment and total and transport-related PA, between greenness/natural environment and total PA, between cycling infrastructure and aesthetics and MVPA, and between pedestrian infrastructure and total walking. A possible negative relationship was found between safety and security and total walking. Qualitative studies complemented several environmental facilitators (facilities for exercise and recreation, sidewalks or streets with low traffic, attractive natural environment) and barriers (lack of facilities and destinations, lack of sidewalks, speeding traffic and high traffic volumes, lack of street lighting).

Conclusions

Research investigating the relationship between the built and natural environment and PA behaviors of adults living in rural areas is still limited and there is a need for more high-quality and longitudinal studies. However, our most positive findings indicate that investing in places for exercise and recreation, a safe infrastructure for active transport, and nature-based activities are possible strategies that should be considered to address low levels of PA in rural adults.

Trial registration

PROSPERO: CRD42021283508.
Tribulations and future opportunities for artificial intelligence in precision medicine
Authors: Carini Claudio , Seyhan Attila A.
Published: May 2024

Upon a diagnosis, the clinical team faces two main questions: what treatment, and at what dose? Clinical trials' results provide the basis for guidance and support for official protocols that clinicians use to base their decisions. However, individuals do not consistently demonstrate the reported response from relevant clinical trials. The decision complexity increases with combination treatments where drugs administered together can interact with each other, which is often the case. Additionally, the individual's response to the treatment varies with the changes in their condition. In practice, the drug and the dose selection depend significantly on the medical protocol and the medical team's experience. As such, the results are inherently varied and often suboptimal. Big data and Artificial Intelligence (AI) approaches have emerged as excellent decision-making tools, but multiple challenges limit their application. AI is a rapidly evolving and dynamic field with the potential to revolutionize various aspects of human life. AI has become increasingly crucial in drug discovery and development. AI enhances decision-making across different disciplines, such as medicinal chemistry, molecular and cell biology, pharmacology, pathology, and clinical practice. In addition to these, AI contributes to patient population selection and stratification. The need for AI in healthcare is evident as it aids in enhancing data accuracy and ensuring the quality care necessary for effective patient treatment. AI is pivotal in improving success rates in clinical practice. The increasing significance of AI in drug discovery, development, and clinical trials is underscored by many scientific publications. Despite the numerous advantages of AI, such as enhancing and advancing Precision Medicine (PM) and remote patient monitoring, unlocking its full potential in healthcare requires addressing fundamental concerns. These concerns include data quality, the lack of well-annotated large datasets, data privacy and safety issues, biases in AI algorithms, legal and ethical challenges, and obstacles related to cost and implementation. Nevertheless, integrating AI in clinical medicine will improve diagnostic accuracy and treatment outcomes, contribute to more efficient healthcare delivery, reduce costs, and facilitate better patient experiences, making healthcare more sustainable. This article reviews AI applications in drug development and clinical practice, making healthcare more sustainable, and highlights concerns and limitations in applying AI.
Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets
Authors: Xu Mengchen , Hou Yiming , Li Na , Yu Wenqian , Chen Lei
Published: May 2024

The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients.

Graphical Abstract
Immune checkpoint inhibitors induce acute interstitial nephritis in mice with increased urinary MCP1 and PD-1 glomerular expression
Authors: Martinez Valenzuela Laura , Gómez-Preciado Francisco , Guiteras Jordi , Antón Pampols Paula , Gomà Montserrat , Fulladosa Xavier , Cruzado Josep Maria , Torras Joan , Draibe Juliana
Published: May 2024

Introduction

Immune checkpoint inhibitors (ICIs) induce acute interstitial nephritis (AIN) in 2–5% of patients, with a clearly higher incidence when they are combined with platinum derivatives. Unfortunately, suitable disease models and non-invasive biomarkers are lacking. To fill this gap in our understanding, we investigated the renal effects of cisplatin and anti-PD-L1 antibodies in mice, assessing PD-1 renal expression and cytokine levels in mice with AIN, and then we compared these findings with those in AIN-diagnosed cancer patients.

Methods

Twenty C57BL6J mice received 200 µg of anti-PD-L1 antibody and 5 mg/kg cisplatin intraperitoneally and were compared with those receiving cisplatin (n = 6), anti-PD-L1 (n = 7), or saline (n = 6). After 7 days, the mice were euthanized. Serum and urinary concentrations of TNFα, CXCL10, IL-6, and MCP-1 were measured by Luminex. The kidney sections were stained to determine PD-1 tissue expression. Thirty-nine cancer patients with AKI were enrolled (AIN n = 33, acute tubular necrosis (ATN) n = 6), urine MCP-1 (uMCP-1) was measured, and kidney sections were stained to assess PD-1 expression.

Results

Cisplatin and anti PD-L1 treatment led to 40% AIN development (p = 0.03) in mice, accompanied by elevated serum creatinine and uMCP1. AIN-diagnosed cancer patients also had higher uMCP1 levels than ATN-diagnosed patients, confirming our previous findings. Mice with AIN exhibited interstitial PD-1 staining and stronger glomerular PD-1 expression, especially with combination treatment. Conversely, human AIN patients only showed interstitial PD-1 positivity.

Conclusions

Only mice receiving cisplatin and anti-PDL1 concomitantly developed AIN, accompanied with a more severe kidney injury. AIN induced by this drug combination was linked to elevated uMCP1, consistently with human AIN, suggesting that uMCP1 can be potentially used as an AIN biomarker.