bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of global hepatitis E outbreaks to inform response and coordination initiatives
Authors: Al-Shimari Fatima H. , Rencken Camerin A. , Kirkwood Carl D. , Kumar Ramya , Vannice Kirsten S. , Stewart Barclay T.
Published: June 2023

Introduction

Hepatitis E virus (HEV) is the most common cause of acute hepatitis. While symptoms are generally mild and resolve within weeks, some populations (e.g., pregnant women, immunocompromised adults) are at high-risk of severe HEV-related morbidity and mortality. There has not been a recent comprehensive review of contemporary HEV outbreaks, which limits the validity of current disease burden estimates. Therefore, we aimed to characterize global HEV outbreaks and describe data gaps to inform HEV outbreak prevention and response initiatives.

Methods

We performed a systematic review of peer-reviewed (PubMed, Embase) and gray literature (ProMED) to identify reports of outbreaks published between 2011 and 2022. We included (1) reports with ≥ 5 cases of HEV, and/or (2) reports with 1.5 times the baseline incidence of HEV in a specific population, and (3) all reports with suspected (e.g., clinical case definition) or confirmed (e.g., ELISA or PCR test) cases if they met criterium 1 and/or 2. We describe key outbreak epidemiological, prevention and response characteristics and major data gaps.

Results

We identified 907 records from PubMed, 468 from Embase, and 247 from ProMED. We screened 1,362 potentially relevant records after deduplication. Seventy-one reports were synthesized, representing 44 HEV outbreaks in 19 countries. The populations at risk, case fatalities, and outbreak durations were not reported in 66% of outbreak reports. No reports described using HEV vaccines. Reported intervention efforts included improving sanitation and hygiene, contact tracing/case surveillance, chlorinating boreholes, and advising residents to boil water. Commonly missing data elements included specific case definitions used, testing strategy and methods, seroprevalence, impacts of interventions, and outbreak response costs. Approximately 20% of HEV outbreaks we found were not published in the peer-reviewed literature.

Conclusion

HEV represents a significant public health problem. Unfortunately, extensive data shortages and a lack of standardized reporting make it difficult to estimate the HEV disease burden accurately and to implement effective prevention and response activities. Our study has identified major gaps to guide future studies and outbreak reporting systems. Our results support the development of standardized reporting procedures/platforms for HEV outbreaks to ensure accurate and timely data distribution, including active and passive coordinated surveillance systems, particularly among high-risk populations.
Indonesia youth population norms for EQ-5D-Y-3 L, EQ-5D-Y-5 L and the PedsQL generic core scale: lower health related quality of life relates to high economic status and stress
Authors: Fitriana Titi Sahidah , Purba Fredrick Dermawan , Stolk Elly , Busschbach Jan J. V.
Published: June 2023

Background

The availability of population norms from generic health-related quality of life (HRQoL) instruments can support the interpretation of health outcomes. This study aimed to provide Indonesian youth population norms for the generic HRQoL measures: EQ-5D-Y-3 L, EQ-5D-Y-5 L, and the PedsQL Generic Core Scales. In addition the opportunity arising from the generation of a large representative sample was taken to explore the relationships between HRQoL, health, and socio-economic factors.

Methods

A representative sample of 1103 Indonesian children (aged 8–16 years) completed EQ-5D-Y-3 L, EQ-5D-Y-5 L, the PedsQL Generic Core Scales, and questions related to demographic data and self-reported health status. A stratified quota sampling design was used to represent Indonesian children in terms of residence, age, gender, and geographical area. Family expenses per capita per month were retrieved from parents to determine a child’s economic status.

Results

The total sample was representative of the Indonesian youth general population. The proportions of participants who reported problems were 43.35% (EQ-5D-Y-3 L), 44.10% (EQ-5D-Y-5 L), and 94.93% (PedsQL Generic), with 31.7% of children reporting health complaints. Older children (13–16 years) reported more problems than younger children (8–12 years). Children living in urban areas reported more problems than children living in rural areas. The lowest value health state reported was ‘12332’ (valued at 0.54), and the minimum EQ VAS score was 60.00. Moderate correlations were found between EQ-5D-Y-3 L values to EQ VAS scores and to PedsQL Total Score. Hierarchical regression analysis showed that females, older age, and having health complaints contributed to a lower level of HRQoL as measured by EQ-5D-Y-3 L values, EQ VAS, and PedsQL Total Score. Remarkably, children with high economic status had lower EQ VAS and PedsQL Total Scores. Among symptoms, ‘having stress’ had the largest influence with respect to lower EQ-5D-Y-3L values, EQ VAS, and PedsQL Total Score.

Conclusions

Population norms for children’s HRQoL as measured by EQ-5D-Y-3 L, EQ-5D-Y-5 L, and the PedsQL Generic Scales are now available for Indonesia. Age, gender, economic status, and health complaints were related to children’s HRQoL. These results provide a basis for health studies and health policy for the youth population of Indonesia.
Promoting health and productivity among ageing workers: a longitudinal study on work ability, biological and cognitive age in modern workplaces (PROAGEING study)
Authors: Bonzini Matteo , Comotti Anna , Fattori Alice , Serra Daniele , Laurino Marco , Mastorci Francesca , Bufano Pasquale , Ciocan Catalina , Ferrari Luca , Bollati Valentina , Di Tecco Cristina
Published: June 2023

Background

Large changes in ageing population and in retirement age are increasing the number of older people in the workforce, raising many challenges for policymakers in promoting employment opportunities and health for older workers. In this respect, longitudinal assessments of workability, well-being perception and cognitive skills over time may allow to detect factors influencing workers’ health. Moreover, new available molecular markers permit the measurement of biological age and age-related changes. Most studies analysed one aspect at time (psychological, biological, labour productivity), without considering their interaction. Aims of the study are to evaluate the relationship between workability, cognitive skills, and biological age in a population of ageing workers; to conduct a cross-sectional analysis to assess the impact of occupational exposures on workability, cognitive skills, and biological age; to evaluate inter-individuals changes in a prospective analysis with a re-evaluation of each worker.

Methods

Our study plans to enrol 1000 full-time workers, aged over 50, undergoing the medical surveillance required by the current Italian Legislation. Data collection includes information about: (a) work ability and psychosocial risk factors (work ability index, HSE Management Standard-21 item, Utrecht Work Engagement Scale, World Health Organisation-Five, Well-Being Index, job satisfaction, general well-being, technostress); (b) cognitive skills (Stroop Color and Word test, Simon task, Corsi’s block-tapping test, Digit span test); (c) sleep habits and psychological well-being (Pittsburgh Sleep Quality Index, Insomnia Severity Index, Ford Insomnia Response to Stress Test; Symptom Check List 90, Psychological Well-Being Index, Profile of Mood State, Beck Depression Inventory, Beck Anxiety Inventory, Perceived Stress Scale, Brief COPE); (d) biological age (telomere length, DNA methylation) for 500 workers. All workers will repeat the evaluation after one year.

Discussion

This study aims to increase our knowledge about interactions between work ability, cognitive ability, well-being perception and psychological status also by including molecular markers, with a longitudinal and multidisciplinary approach. By bringing better insights into the relationship between risk factors and their impact on perceived and biological health, this study also aims at identifying possible interventions and protective measures to ensure aged workers’ well-being, consistent with all the eminent calls for actions promoted by key International and European labour organizations.
Sedentary behavior is associated with poor sleep quality during the COVID-19 pandemic, and physical activity mitigates its adverse effects
Authors: Menezes-Júnior Luiz Antônio Alves de , de Moura Samara Silva , Miranda Amanda Gonçalves , de Souza Andrade Amanda Cristina , Machado-Coelho George Luiz Lins , Meireles Adriana Lúcia
Published: June 2023

Background

We aimed to evaluate the association of sedentary behavior (SB) and moderate to vigorous leisure-time physical activity (MVPA) with sleep quality during the COVID-19 pandemic.

Methods

Cross-sectional, population-based study in adults, conducted from October to December 2020 in the Iron Quadrangle region, Brazil. The outcome was sleep quality, evaluated with the Pittsburgh Sleep Quality Index. SB was assessed by self-report of total sitting time, before and during the pandemic. Individuals with ≥ 9 h of total sitting time were classified as SB. In addition, the ratio of time spent in MVPA to time in SB was analyzed. A contrasted directed acyclic graph (DAG) model was constructed to adjust logistic regression models.

Results

A total of 1629 individuals were evaluated, the prevalence of SB before the pandemic was 11.3% (95%CI: 8.6–14.8), and during the pandemic 15.2% (95%CI: 12.1–18.9). In multivariate analysis, the chance of poor sleep quality was 77% higher in subjects with SB ≥ 9 h per day (OR: 1.77; 95% CI: 1.02–2.97). Furthermore, a one-hour increase in SB during the pandemic, increased the chance of poor sleep quality by 8% (OR: 1.08; 95%CI 1.01–1.15). In the analysis of the ratio of MVPA per SB in individuals with SB ≥ 9 h, practicing 1 min of MVPA per hour of SB reduces the chance of poor sleep quality by 19% (OR: 0.84; 95%CI: 0.73–0.98).

Conclusion

SB during the pandemic was a factor associated with poor sleep quality, and the practice of MVPA can reduce the effects of SB.

Graphical Abstract
Prediction of risk and clinical outcome of cuproptosis in lung squamous carcinoma
Authors: Zhang Yangyang , Zhou Jia , Li Hong , Liu Yaobang , Li Jinping
Published: June 2023

Background

Lung squamous cell carcinoma (LUSC) is an important subtype of non-small cell lung cancer. Its special clinicopathological features and molecular background determine the limitations of its treatment. A recent study published on Science defined a newly regulatory cell death (RCD) form – cuproptosis. Which manifested as an excessive intracellular copper accumulation, mitochondrial respiration-dependent, protein acylation-mediated cell death. Different from apoptosis, pyroptosis, necroptosis, ferroptosis and other forms of regulatory cell death (RCD). The imbalance of copper homeostasis in vivo will trigger cytotoxicity and further affect the occurrence and progression of tumors. Our study is the first to predict the prognosis and immune landscape of cuproptosis-related genes (CRGs) in LUSC.

Methods

The RNA-seq profiles and clinical data of LUSC patients were downloaded from TCGA and GEO databases and then combined into a novel cohort. R language packages are used to analyze and process the data, and CRGs related to the prognosis of LUSC were screened according to the differentially expressed genes (DEGs). After analyzed the tumor mutation burden (TMB), copy number variation (CNV) and CRGs interaction network. Based on CRGs and DEGs, cluster analysis was used to classify LUSC patients twice. The selected key genes were used to construct a CRGs prognostic model to further analyze the correlation between LUSC immune cell infiltration and immunity. Through the risk score and clinical factors, a more accurate nomogram was further constructed. Finally, the drug sensitivity of CRGs in LUSC was analyzed.

Results

Patients with LUSC were divided into different cuproptosis subtypes and gene clusters, showing different levels of immune infiltration. The risk score showed that the high-risk group had higher tumor microenvironment score, lower tumor mutation load frequency and worse prognosis than the low-risk group. In addition, the high-risk group was more sensitive to vinorelbine, cisplatin, paclitaxel, doxorubicin, etoposide and other drugs.

Conclusions

Through bioinformatics analysis, we successfully constructed a prognostic risk assessment model based on CRGs, which can not only accurately predict the prognosis of LUSC patients, but also evaluate the patient 's immune infiltration status and sensitivity to chemotherapy drugs. This model shows satisfactory predictive results and provides a reference for subsequent tumor immunotherapy.
Thai version of shortened Oral Impact on Daily Performances index for evaluating oral lichen planus patients
Authors: Yiemstan Sasirin , Piboonratanakit Pornpan , Krisdapong Sudaduang
Published: June 2023

Background

Patients’ perceptions and Oral Health-related Quality of life (OHRQoL) are important parts of dental treatment in all fields, including oral lichen planus (OLP) patients. A shortened version of the Oral Impact on Daily Performances (OIDP) might be more practical and feasible in clinical setting due to the busy nature of oral medicine clinics and staff availability to conduct the interview for data collection. The aim of the study was to develop a Thai version of shortened OIDP for assessing the OHRQoL in OLP patients.

Methods

Two types of shortened OIDP versions were tested in 69 OLP patients, one comprising the most commonly interfered with daily performances (OIDP-3 and OIDP-2) and another comprising either the highest frequency (OIDP frequency) or severity score (OIDP severity). The Numeric Rating Scale (NRS) and Thongprasom sign score were used to assess oral pain and clinical severity. Spearman rank-order correlation coefficients (rs) were used to demonstrate the associations between the shortened and original OIDP, pain, and clinical severity.

Results

OIDP-3 (Eating, Cleaning, and Emotional stability) and OIDP-2 (Eating and Emotional stability) were developed. The associations of the original OIDP with OIDP-3 and OIDP-2 (rs = 0.965 and 0.911) were significantly higher than those of the original OIDP with OIDP frequency and OIDP severity (rs = 0.768 and 0.880). The original OIDP, OIDP-3, and OIDP-2 were more significantly associated with pain compared with OIDP frequency and OIDP severity. The association between the clinical severity and oral impacts assessed by the original OIDP, OIDP-3, and OIDP-2 were similar and had higher correlation coefficients compared with those of OIDP frequency and OIDP severity.

Conclusion

OIDP-3 and OIDP-2 performed more similarly to the original OIDP than OIDP frequency and OIDP severity in assessing the OHRQoL of OLP patients.

Trial registration

The trial was registered at the Thai Clinical Trials Registry (TCTR identifier: TCTR 20190828002).
Which lecturers’ characteristics facilitate the learning process? A qualitative study on students’ perceptions in the rehabilitation sciences
Authors: Battista Simone , Furri Laura , Pellegrini Valeria , Giardulli Benedetto , Coppola Ilaria , Testa Marco , Dell’Isola Andrea
Published: June 2023

Background

In education, lecturers play a crucial role in facilitating students’ learning process. However, only a few studies explored which lecturers’ characteristics can facilitate this process in higher education for rehabilitation healthcare professionals. Starting from students’ perspectives, our qualitative study investigated the lecturers’ characteristics that facilitate students’ learning process in the rehabilitation sciences.

Methods

A qualitative interview study. We enrolled students attending the 2nd year of the Master of Science (MSc) degree in ‘Rehabilitation Sciences of Healthcare Professions’. Different themes were generated following a ‘Reflexive Thematic Analysis’.

Results

Thirteen students completed the interviews. From their analysis, we generated five themes. Specifically, a lecturer that facilitates students’ learning process should be: 1) ‘A Performer who Interacts with the Classroom’, 2) A Flexible Planner who Adopts Innovative Teaching Skills’, 3) ‘A Motivator who Embraces Transformational Leadership’, 4) ‘A Facilitator Who Encourages a Constructive Learning Context’ and 5) ‘A Coach who Devises Strategies to Reach Shared Learning Goals’.

Conclusions

The results of this study underscore the importance for lecturers in rehabilitation to cultivate a diverse set of skills drawn from the arts and performance, education, team building and leadership to facilitate students’ learning process. By developing these skills, lecturers can design lessons that are worth attending not only for their relevant content but also for their value in human experience.
Frequent hospital presenters’ use of health information during COVID-19: results of a cross-sectional survey
Authors: Jessup Rebecca L. , Bramston Cassandra , Putrik Polina , Haywood Cilla , Tacey Mark , Copnell Beverley , Cvetanovska Natali , Cao Yingting , Gust Anthony , Campbell Donald , Oldenburg Brian , Mehdi Hala , Kirk Michael , Zucchi Emiliano , Semciw Adam I. , Beauchamp Alison
Published: June 2023

Background

High-frequency hospital users often present with chronic and complex health conditions and are at increased risk of serious morbidity and mortality if they contract COVID-19. Understanding where high-frequency hospital users are sourcing their information, whether they understand what they find, and how they apply the information to prevent the spread of COVID-19 is essential for health authorities to be able to target communication approaches.

Methods

Cross-sectional survey of 200 frequent hospital users (115 with limited English proficiency) informed by the WHO’s “Rapid, simple, flexible behavioral insights on COVID-19”. Outcome measures were source of, and trust in information, and knowledge of symptoms, preventive strategies, restrictions, and identification of misinformation.

Results

The most frequently cited source of information was television (n = 144, 72%) followed by the internet (n = 84, 42%). One in four television users sought their information from overseas news outlets from their country of origin, while for those using the internet, 56% relied on Facebook and other forms of social media including YouTube and WeChat. Overall, 41.2% of those surveyed had inadequate knowledge about symptoms, 35.8% had inadequate knowledge about preventative strategies, 30.2% had inadequate knowledge about government-imposed restrictions, and 69% believed in misinformation. Half of the respondents (50%) trusted all information, and only one in five (20%) were uncertain or untrusting. English-speaking participants were almost three times more likely to have adequate knowledge about symptoms (OR 2.69, 95%CI 1.47;4.91) and imposed restrictions (OR 2.10 95%CI 1.06; 4.19), and 11 times more likely to recognize misinformation (OR 11.52 95%CI 5.39; 24.60) than those with limited English.

Conclusion

Within this population of high-frequency hospital users with complex and chronic conditions, many were sourcing their information from less trustworthy or locally relevant sources, including social media and overseas news outlets. Despite this, at least half were trusting all the information that they found. Speaking a language other than English was a much greater risk factor for having inadequate knowledge about COVID-19 and believing in misinformation. Health authorities must look for methods to engage diverse communities, and tailor health messaging and education in order to reduce disparities in health outcomes.
Glycemic variability and in-hospital death of critically ill patients and the role of ventricular arrhythmias
Authors: Su Yuhao , Fan Weiguo , Liu Yang , Hong Kui
Published: June 2023

Background

Abnormal glycemic variability is common in the intensive care unit (ICU) and is associated with increased in-hospital mortality and major adverse cardiovascular events, but little is known about whether adverse outcomes are partly mediated by ventricular arrhythmias (VA). We aimed to explore the association between glycemic variability and VA in the ICU and whether VA related to glycemic variability mediate the increased risk of in-hospital death.

Methods

We extracted all measurements of blood glucose during the ICU stay from The Medical Information Mart for Intensive Care IV (MIMIC-IV) database version 2.0. Glycemic variability was expressed by the coefficient of variation (CV), which was calculated by the ratio of standard deviation (SD) and average blood glucose values. The outcomes included the incidence of VA and in-hospital death. The KHB (Karlson, KB & Holm, A) is a method to analyze the mediation effect for nonlinear models, which was used to decompose the total effect of glycemic variability on in-hospital death into a direct and VA-mediated indirect effect.

Results

Finally, 17,756 ICU patients with a median age of 64 years were enrolled; 47.2% of them were male, 64.0% were white, and 17.8% were admitted to the cardiac ICU. The total incidence of VA and in-hospital death were 10.6% and 12.8%, respectively. In the adjusted logistic model, each unit increase in log-transformed CV was associated with a 21% increased risk of VA (OR 1.21, 95% CI: 1.11–1.31) and a 30% increased risk (OR 1.30, 95% CI: 1.20–1.41) of in-hospital death. A total of 3.85% of the effect of glycemic variability on in-hospital death was related to the increased risk of VA.

Conclusion

High glycemic variability was an independent risk factor for in-hospital death in ICU patients, and the effect was caused in part by an increased risk of VA.
Development of a biomarker panel for assessing cardiovascular risk in diabetic patients with chronic limb-threatening ischemia (CLTI): a prospective study
Authors: Nardella Elisabetta , Biscetti Federico , Rando Maria Margherita , Cecchini Andrea Leonardo , Nicolazzi Maria Anna , Rossini Enrica , Angelini Flavia , Iezzi Roberto , Eraso Luis H. , Dimuzio Paul J. , Pitocco Dario , Massetti Massimo , Gasbarrini Antonio , Flex Andrea
Published: June 2023

Background

Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), High-Mobility Group Box-1 (HMGB-1), Osteoprotegerin (OPG), Sortilin and Omentin-1- at baseline, with cardiovascular outcomes (MACE and MALE) after LER in diabetic patients with CLTI.

Methods

In this prospective non-randomized study, 264 diabetic patients with CLTI undergoing endovascular revascularization were enrolled. Serum levels of each biomarker were collected before revascularization and outcomes’ incidence was evaluated after 1, 3, 6 and 12 months.

Results

During the follow-up period, 42 cases of MACE and 81 cases of MALE occurred. There was a linear association for each biomarker at baseline and incident MACE and MALE, except Omentin-1 levels that were inversely related to the presence of MACE or MALE. After adjusting for traditional cardiovascular risk factors, the association between each biomarker baseline level and outcomes remained significant in multivariable analysis. Receiver operating characteristics (ROC) models were constructed using traditional clinical and laboratory risk factors and the inclusion of biomarkers significantly improved the prediction of incident events.

Conclusions

Elevated IL-1, IL-6, CRP, TNF-α, HMGB-1, OPG and Sortilin levels and low Omentin-1 levels at baseline correlate with worse vascular outcomes in diabetic patients with CLTI undergoing LER. Assessment of the inflammatory state with this panel of biomarkers may support physicians to identify a subset of patients more susceptible to the procedure failure and to develop cardiovascular adverse events after LER.
Normal-weight visceral obesity promotes a higher 10-year atherosclerotic cardiovascular disease risk in patients with type 2 diabetes mellitus–a multicenter study in China
Authors: Zheng Jia , Hu Ye , Xu Hanwen , Lei Yu , Zhang Jieji , Zheng Qidong , Li Li , Tu Weiping , Chen Riqiu , Guo Qiongyao , Zang Xunxiong , You Qiaoying , Xu Zhiyong , Zhou Qiang , Wu Xiaohong
Published: June 2023

Background

Visceral obesity is associated with high cardiovascular events risk in type 2 diabetes mellitus (T2DM). Whether normal-weight visceral obesity will pose a higher atherosclerotic cardiovascular disease (ASCVD) risk than body mass index (BMI)-defined overweight or obese counterparts with or without visceral obesity remains unclear. We aimed to explore the relationship between general obesity and visceral obesity and 10-year ASCVD risk in patients with T2DM.

Methods

Patients with T2DM (6997) who satisfied the requirements for inclusion were enrolled. Patients were considered to have normal weight when 18.5 kg/m2 ≤ BMI < 24 kg/m2; overweight when 24 kg/m2 ≤ BMI < 28 kg/m2; and obesity when BMI ≥ 28 kg/m2. Visceral obesity was defined as a visceral fat area (VFA) ≥ 100 cm2. Patients were separated into six groups based on BMI and VFA. The odd ratios (OR) for a high 10-year ASCVD risk for different combinations of BMI and VFA were analysed using stepwise logistic regression. Receiver operating characteristic (ROC) curves for diagnosing the high 10-year ASCVD risk were constructed, and areas under the ROC curves were estimated. Potential non-linear relationships between VFA levels and high 10-year ASCVD risk were examined using restricted cubic splines (knot = 4). Multilinear regression was used to identify factors affecting VFA in patients with T2DM.

Results

In patients with T2DM, subjects with normal-weight visceral obesity had the highest 10-year ASCVD risk among the six groups, which had more than a 2-fold or 3-fold higher OR than those who were overweight or obese according to BMI but did not have visceral obesity (all P < 0.05). The VFA threshold for high 10-year ASCVD risk was 90 cm2. Multilinear regression showed significant differences in the effect of age, hypertension, drinking, fasting serum insulin, fasting plasma glucose, 2 h postprandial C-peptide, triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol on VFA in patients with T2DM (all P < 0.05).

Conclusions

T2DM patients with normal-weight visceral obesity had a higher 10-year ASCVD risk than BMI-defined overweight or obese counterparts with or without visceral obesity, which should initiate standardised management for ASCVD primary prevention.
Evolution of carbapenem resistance in klebsiella pneumoniae and escherichia coli carrying blaNDM−1 gene: imipenem exposure results in sustained resistance memory of strains in vitro
Authors: Zhao Qiong , Sha Longhua , Wu Zhaomeng , Meng Lixue , Yang Feixiang , Wu Lingling , Yu Chunfang , Zhang Hua , Yu Jingdan , Jin Zhixiong
Published: June 2023

Background

Antibiotics exert an outstanding selective pressure on bacteria, forcing their chromosomal gene mutations and drug resistance genes to spread. The objective of this study is to evaluate the expression of the New Delhi Metallo-β-Lactamase-1 gene (blaNDM−1) in the clinical isolate (Klebsiella pneumoniae TH-P12158), transformant strains Escherichia coli BL21 (DE3)-blaNDM−1, and Escherichia coli DH5α- blaNDM−1 when exposed to imipenem.

Methods

β-Lactamase genes (blaSHV, blaTEM−1, blaCTX−M−9, blaIMP, blaNDM−1, blaKPC, blaOXA, blaGES, and blaDHA) from randomly selected carbapenems-sensitive K.pneumoniae (n = 20) and E.coli (n = 20) strains were amplified by PCR. The recombinant plasmid of pET-28a harboring blaNDM−1 was transformed into E.coli BL21 (DE3) and E.coli DH5α by electroporation. The resistance phenotype and higher blaNDM−1 expression in K.pneumoniae TH-P12158, transformant E.coli BL21 (DE3)-blaNDM−1, and E.coli DH5α-blaNDM−1 were observed when exposed to imipenem with grade increasing, decreasing, and canceling doses, respectively.

Results

After being exposed to different doses of imipenem, the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of antimicrobial drugs and blaNDM−1 expression of strains increased, which was positively correlated with doses of imipenem. On the contrary, with the decrease or cancellation of imipenem doses, the blaNDM−1 expression was deteriorated, while the MIC and MBC values remained relatively stable. These results demonstrated that low doses of imipenem (˂MIC) could press blaNDM−1 positive strains producing stable drug resistance memory and altered blaNDM−1 expression.

Conclusions

Low doses of imipenem could press blaNDM−1 positive strains producing sustained resistance memory and altered blaNDM−1 expression. In particular, the positive correlation between the resistance genes expression and antibiotics exposure shows promising guiding significance for clinical medication.
Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology, molecular docking, and experimental validation
Authors: Chen Shengnan , Li Bo , Chen Lei , Jiang Hongli
Published: June 2023

Background

Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited.

Methods

Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins.

Results

After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR.

Conclusions

RES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.
Establishment of a potent weighted risk model for determining the progression of diabetic kidney disease
Authors: Zhang Tianxiao , Wang Xiaodan , Zhang Yueying , Yang Ying , Yang Congying , Wei Huiyi , Zhao Qingbin
Published: June 2023

Background

Diabetic kidney disease (DKD) is a severe complication of diabetes. Currently, no effective measures are available to reduce the risk of DKD progression. This study aimed to establish a weighted risk model to determine DKD progression and provide effective treatment strategies.

Methods

This was a hospital-based, cross-sectional study. A total of 1104 patients with DKD were included in this study. The random forest method was used to develop weighted risk models to assess DKD progression. Receiver operating characteristic curves were used to validate the models and calculate the optimal cutoff values for important risk factors.

Results

We developed potent weighted risk models to evaluate DKD progression. The top six risk factors for DKD progression to chronic kidney disease were hemoglobin, hemoglobin A1c (HbA1c), serum uric acid (SUA), plasma fibrinogen, serum albumin, and neutrophil percentage. The top six risk factors for determining DKD progression to dialysis were hemoglobin, HbA1c, neutrophil percentage, serum albumin, duration of diabetes, and plasma fibrinogen level. Furthermore, the optimal cutoff values of hemoglobin and HbA1c for determining DKD progression were 112 g/L and 7.2%, respectively.

Conclusion

We developed potent weighted risk models for DKD progression that can be employed to formulate precise therapeutic strategies. Monitoring and controlling combined risk factors and prioritizing interventions for key risk factors may help reduce the risk of DKD progression.
Three-year outcomes for women newly initiated on lifelong antiretroviral therapy during pregnancy – Malawi option B+
Authors: Chagomerana Maganizo B. , Harrington Bryna J. , DiPrete Bethany L. , Wallie Shaphil , Maliwichi Madalitso , Wesevich Austin , Phulusa Jacob N. , Kumwenda Wiza , Jumbe Allan , Hosseinipour Mina C.
Published: June 2023

Introduction

Antiretroviral therapy (ART) is very effective in preventing vertical transmission of HIV but some women on ART experience different virologic, immunologic, and safety profiles. While most pregnant women are closely monitored for short-term effects of ART during pregnancy, few women receive similar attention beyond pregnancy. We aimed to assess retention in care and clinical and laboratory-confirmed outcomes over 3 years after starting ART under Malawi’s Option B + program.

Methods

We conducted a prospective cohort study of pregnant women newly diagnosed with HIV who started tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/3TC/EFV) for the first time at Bwaila Hospital in Lilongwe, Malawi between May 2015 and June 2016. Participants were followed for 3 years. We summarized demographic characteristics, pregnancy outcomes, and clinical and laboratory adverse events findings using proportions. Log-binomial regression models were used to estimate the overall risk ratios (RR) and the corresponding 95% confidence interval (CI) for the association between index pregnancy (i.e. index pregnancy vs. subsequent pregnancy) and preterm birth, and index pregnancy and low birthweight.

Results

Of the 299 pregnant women who were enrolled in the study, 255 (85.3%) were retained in care. There were 340 total pregnancies with known outcomes during the 36-month study period, 280 index pregnancies, and 60 subsequent pregnancies. The risks of delivering preterm (9.5% for index pregnancy and13.5% for subsequent pregnancy: RR = 0.70; 95% CI: 0.32–1.54), or low birth weight infant (9.8% for index pregnancy and 4.2% for subsequent pregnancy: RR = 2.36; 95% CI: 0.58–9.66) were similar between index and subsequent pregnancies. Perinatally acquired HIV was diagnosed in 6 (2.3%) infants from index pregnancies and none from subsequent pregnancies. A total of 50 (16.7%) women had at least one new clinical adverse event and 109 (36.5%) women had at least one incident abnormal laboratory finding. Twenty-two (7.3%) women switched to second line ART: of these 64.7% (8/17) had suppressed viral load and 54.9% (6/17) had undetectable viral load at 36 months.

Conclusion

Most of the women who started TDF/3TC/EFV were retained in care and few infants were diagnosed with perinatally acquired HIV. Despite switching, women who switched to second line therapy continued to have higher viral loads suggesting that additional factors beyond TDF/3TC/EFV failure may have contributed to the switch. Ongoing support during the postpartum period is necessary to ensure retention in care and prevention of vertical transmission.
Angiotensin-converting enzyme 2 (ACE2) polymorphisms and susceptibility of severe SARS-CoV-2 in a subset of Pakistani population
Authors: Sidhwani Santosh Kumar , Mirza Talat , Khatoon Ambrina , Shaikh Fouzia , Khan Rizma , Shaikh Omer Ahmed , Nashwan Abdulqadir J.
Published: June 2023

Science is digging for the varied presentation of COVID-19 patients exposed to the same risk factors, and medical conditions may be influenced by the presence of polymorphic genetic variants. This study investigated the link between ACE2 gene polymorphisms and the severity of SARS-CoV-2. This cross-sectional study recruited COVID-19 PCR-positive patients by consecutive sampling from Ziauddin Hospital from April to September 2020. DNA was extracted from whole blood, followed by gene amplification and Sanger’s sequencing. Most of the patients, 77: 53.8%, were serious. Males were higher (80; 55.9%) with age more than 50 years (106: 74.1%). We found 22 ACE2 SNPs. rs2285666 SNP was most prevalent with 49.2% CC, 45.2% TT, 4.8% CT heterozygosity, and 0.8% AA genotypes. Variants with multiple genotypes were also insignificantly associated with the severity of COVID-19 in the analysis of the dominant model. Only rs2285666 had a significant statistical link with gender (p-value 0.034, OR; 1.438, CI; 1.028–2.011) while rs768883316 with age groups (p-value 0.026, OR; 1.953, CI; 1.085–3.514). Haplotypes ATC of three polymorphisms (rs560997634, rs201159862, and rs751170930) commonly found in 120 (69.77%) and TTTGTAGTTAGTA haplotype consisting of 13 polymorphisms (rs756737634, rs146991645, rs1601703288, rs1927830489, rs1927831624, rs764947941, rs752242172, rs73195521, rs781378335, rs756597390, rs780478736, rs148006212, rs768583671) in 112 (90.32%) had statistically significant association with the severity having p = value 0.029 and 0.001 respectively. Males of old age and diabetics are found to have more severe COVID-19 infection in the current study. We also found that common ACE2 polymorphism rs2285666 influences the susceptibility of acquiring the severe SARS-CoV-2 infection.
Detect Acute Porphyrias in Emergency Departments (DePorED) – a pilot study
Authors: Diehl-Wiesenecker Eva , Blaschke Sabine , Wohmann Nils , Kubisch Ilja , Stauch Thomas , Mainert Mona , Helm Franziska , von Wegerer Sabine , Pittrow David , Frank Jorge , Stölzel Ulrich , Somasundaram Rajan
Published: June 2023

Background

Acute porphyrias (APs) are a group of rare metabolic diseases related to a disturbed heme biosynthesis. Symptoms may first occur as life threatening attacks, comprising abdominal pain and/or variable neuro-psychiatric symptoms, thus leading to presentation in emergency departments (ED) first. Due to the low prevalence, diagnosis of AP is often missed, even after readmission to the ED. Therefore, strategies are needed to consider APs in ED patients with unexplained abdominal pain, especially since early and adequate treatment will avoid an unfavorable clinical course. Aim of this prospective study was to investigate the prevalence of APs in ED patients and thus, addressing feasibility of screening for rare diseases, such as APs in the real life setting.

Methods

From September 2019 to March 2021, patients presenting to the ED of three German tertiary care hospitals with moderate to severe prolonged abdominal pain (Visual Analog Scale, VAS > 4 out of 10 points) not otherwise explained were screened and prospectively enrolled. In addition to standard of care (SOC) diagnostics a blood and urine sample for plasma fluorescence scan and biochemical porphyrin analysis were sent to a certified German porphyria laboratory.

Results

Overall, of 653 screened patients, 68 patients (36 females; mean age 36 years) were included for biochemical porphyrin analysis. No patient with AP was detected. The most frequent discharge diagnoses included “abdominal and digestive symptoms” (n = 22, 32%), “gastrooesophageal diseases” (n = 18, 27%), “infectious bowel disease” (n = 6, 9%) and “biliopancreatic diseases” (n = 6, 9%). Although not primarily addressed, we observed an increase in knowledge of the ED staffs at all study sites regarding our screening algorithm and thus, awareness for APs.

Conclusions

To the best of our knowledge, we performed the first prospective screening project for APs in the ED. Although we detected no patient with AP in this study, we demonstrated the feasibility of a multicenter screening process for APs by building up a well-working infrastructure comprising laboratory testing as well as data management. This enables the set-up of a larger scale revised follow-up study with a central focus on structured education, thus, possibly acting as blueprint for other rare diseases.
B4GALT1 promotes immune escape by regulating the expression of PD-L1 at multiple levels in lung adenocarcinoma
Authors: Cui Yanan , Li Jun , Zhang Pengpeng , Yin Dandan , Wang Ziyu , Dai Jiali , Wang Wei , Zhang Erbao , Guo Renhua
Published: June 2023

Background

Invasive adenocarcinoma (IAC), which is typically preceded by minimally invasive adenocarcinoma (MIA), is the dominant pathological subtype of early-stage lung adenocarcinoma (LUAD). Identifying the molecular events underlying the progression from MIA to IAC may provide a crucial perspective and boost the exploration of novel strategies for early-stage LUAD diagnosis and treatment.

Methods

Transcriptome sequencing of four pairs of MIA and IAC tumours obtained from four multiple primary lung cancer patients was performed to screen out beta-1,4-galactosyltransferase1 (B4GALT1). Function and mechanism experiments in vitro and in vivo were performed to explore the regulatory mechanism of B4GALT1-mediated immune evasion by regulating programmed cell death ligand 1 (PD-L1).

Results

B4GALT1, a key gene involved in N-glycan biosynthesis, was highly expressed in IAC samples. Further experiments revealed that B4GALT1 regulated LUAD cell proliferation and invasion both in vitro and in vivo and was related to the impaired antitumour capacity of CD8 + T cells. Mechanistically, B4GALT1 directly mediates the N-linked glycosylation of PD-L1 protein, thus preventing PD-L1 degradation at the posttranscriptional level. In addition, B4GALT1 stabilized the TAZ protein via glycosylation, which activated CD274 at the transcriptional level. These factors lead to lung cancer immune escape. Importantly, inhibition of B4GALT1 increased CD8 + T-cell abundance and activity and enhanced the antitumour immunity of anti-PD-1 therapy in vivo.

Conclusion

B4GALT1 is a critical molecule in the development of early-stage LUAD and may be a novel target for LUAD intervention and immunotherapy.
Influence of alcohol consumption and alcohol metabolism variants on breast cancer risk among Black women: results from the AMBER consortium
Authors: Young Kristin L. , Olshan Andrew F. , Lunetta Kathryn , Graff Mariaelisa , Williams Lindsay A. , Yao Song , Zirpoli Gary R. , Troester Melissa , Palmer Julie R.
Published: June 2023

Background

Moderate to heavy alcohol consumption is associated with an increased risk of breast cancer. The etiologic role of genetic variation in genes involved in ethanol metabolism has not been established, with little information available among women of African ancestry.

Methods

Our analysis from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium included 2889 U.S. Black women who were current drinkers at the time of breast cancer diagnosis (N cases = 715) and had available genetic data for four ethanol metabolism genomic regions (ADH, ALDH, CYP2E1, andALDH2). We used generalized estimating equations to calculate genetic effects, gene* alcohol consumption (≥ 7drinks/week vs. < 7/week) interactions, and joint main plus interaction effects of up to 23,247 variants in ethanol metabolism genomic regions on odds of breast cancer.

Results

Among current drinkers, 21% of cases and 14% of controls reported consuming ≥ 7 drinks per week. We identified statistically significant genetic effects for rs79865122-C inCYP2E1with odds of ER- breast cancer and odds of triple negative breast cancer, as well as a significant joint effect with odds of ER- breast cancer (≥ 7drinks per week OR = 3.92, < 7 drinks per week OR = 0.24,pjoint = 3.74 × 10−6). In addition, there was a statistically significant interaction of rs3858704-A inALDH2with consumption of ≥ 7 drinks/week on odds of triple negative breast cancer (≥ 7drinks per week OR = 4.41, < 7 drinks per week OR = 0.57,pint = 8.97 × 10–5).

Conclusions

There is a paucity of information on the impact of genetic variation in alcohol metabolism genes on odds of breast cancer among Black women. Our analysis of variants in four genomic regions harboring ethanol metabolism genes in a large consortium of U.S. Black women identified significant associations between rs79865122-C inCYP2E1and odds of ER- and triple negative breast cancer. Replication of these findings is warranted.