bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparisons of lifetime exposures between differently polluted areas and years of life lost due to all-cause mortality attributable to air pollution
Authors: Machaczka Ondřej , Jiřík Vítězslav , Janulková Tereza , Michalík Jiří , Siemiatkowski Grzegorz , Osrodka Leszek , Krajny Ewa , Topinka Jan
Published: August 2023

Background

Lifetime (or long-term) exposure to air pollution has been linked to an increased risk of premature death. This association might persist even at low air pollutant concentrations level. The objective was to describe and compare lifetime exposures to PM10, PM2.5, NO2, benzene, and benzo(a)pyrene in two differently polluted localities and quantify years of life lost due to all-cause mortality attributable to PM10, PM2.5, NO2.

Methods

The study population was selected from two differently polluted localities of the Czech Republic from the period 2000–2017. For determination of lifetime exposures specially developed methodology for historical air pollutants time series concentrations estimation was used. Estimated lifetime exposures, new WHO air quality guideline levels and relative risks were used to quantify years of life lost due to all-cause mortality attributable to air pollutants.

Results

Significant differences in lifetime exposures of air pollutants between study areas were found. Average lifetime exposure to PM10, PM2.5, NO2, benzene and B(a)P was 45.6 μg/m3, 34.9 μg/m3, 18.1 μg/m3, 2.1 μg/m3and 2.6 ng/m3, respectively, in high-polluted area, against 24.9 μg/m3, 19.4 μg/m3, 13.3 μg/m3, 0.8 μg/m3, 0.4 ng/m3 in low-polluted area. All-cause mortality and years of life lost due to all-cause mortality (non-external) were higher in high-polluted area. The highest contribution was found for PM2.5, when the population attributable fraction was at the 23% level for the high polluted area and at the 14% level for the low polluted area. The highest losses of 35,776 years per 100,000 men or 131 days per 1 man were achieved in the high polluted area and in a case of PM2.5 exposure, namely for men in the age category of 80–84 years. Additionally, the results were expressed per number of deaths. The average value for the number of deaths attributable to PM2.5 exposure was 4.75 years per1 death man, or 3.51 years per 1 death woman in a high-polluted area.

Conclusions

Expression of years of life lost due to all-cause mortality attributable to air pollution per number of deaths can be more appropriate for communication about health risks or in the field of public health protection.
MCL-DTI: using drug multimodal information and bi-directional cross-attention learning method for predicting drug–target interaction
Authors: Qian Ying , Li Xinyi , Wu Jian , Zhang Qian
Published: August 2023

Background

Prediction of drug–target interaction (DTI) is an essential step for drug discovery and drug reposition. Traditional methods are mostly time-consuming and labor-intensive, and deep learning-based methods address these limitations and are applied to engineering. Most of the current deep learning methods employ representation learning of unimodal information such as SMILES sequences, molecular graphs, or molecular images of drugs. In addition, most methods focus on feature extraction from drug and target alone without fusion learning from drug–target interacting parties, which may lead to insufficient feature representation.

Motivation

In order to capture more comprehensive drug features, we utilize both molecular image and chemical features of drugs. The image of the drug mainly has the structural information and spatial features of the drug, while the chemical information includes its functions and properties, which can complement each other, making drug representation more effective and complete. Meanwhile, to enhance the interactive feature learning of drug and target, we introduce a bidirectional multi-head attention mechanism to improve the performance of DTI.

Results

To enhance feature learning between drugs and targets, we propose a novel model based on deep learning for DTI task called MCL-DTI which uses multimodal information of drug and learn the representation of drug–target interaction for drug–target prediction. In order to further explore a more comprehensive representation of drug features, this paper first exploits two multimodal information of drugs, molecular image and chemical text, to represent the drug. We also introduce to use bi-rectional multi-head corss attention (MCA) method to learn the interrelationships between drugs and targets. Thus, we build two decoders, which include an multi-head self attention (MSA) block and an MCA block, for cross-information learning. We use a decoder for the drug and target separately to obtain the interaction feature maps. Finally, we feed these feature maps generated by decoders into a fusion block for feature extraction and output the prediction results.

Conclusions

MCL-DTI achieves the best results in all the three datasets: Human, C. elegans and Davis, including the balanced datasets and an unbalanced dataset. The results on the drug–drug interaction (DDI) task show that MCL-DTI has a strong generalization capability and can be easily applied to other tasks.
Genome-wide identification and bioinformatics analysis of the WD40 transcription factor family and candidate gene screening for anthocyanin biosynthesis in Rhododendron simsii
Authors: Wang Cheng , Tang Yafang , Li Yan , Hu Chao , Li Jingyi , Lyu Ang
Published: August 2023

WD40 transcription factors (TFs) constitute a large gene family in eukaryotes, playing diverse roles in cellular processes. However, their functions in the major ornamental plant, Rhododendron simsii, remain poorly understood. In this study, we identified 258 WD40 proteins in the R. simsii genome, which exhibited an uneven distribution across chromosomes. Based on domain compositions and phylogenetic analysis, we classified these 258 RsWD40 proteins into 42 subfamilies and 47 clusters. Comparative genomic analysis suggested that the expansion of the WD40 gene family predates the divergence of green algae and higher plants, indicating an ancient origin. Furthermore, by analyzing the duplication patterns of RsWD40 genes, we found that transposed duplication played a major role in their expansion. Notably, the majority of RsWD40 gene duplication pairs underwent purifying selection during evolution. Synteny analysis identified significant orthologous gene pairs between R. simsii and Arabidopsis thaliana, Oryza sativa, Vitis vinifera, and Malus domestica. We also investigated potential candidate genes involved in anthocyanin biosynthesis during different flower development stages in R. simsii using RNA-seq data. Specifically, we identified 10 candidate genes during the bud stage and 7 candidate genes during the full bloom stage. GO enrichment analysis of these candidate genes revealed the potential involvement of the ubiquitination process in anthocyanin biosynthesis. Overall, our findings provide a valuable foundation for further investigation and functional analysis of WD40 genes, as well as research on the molecular mechanisms underlying anthocyanin biosynthesis in Rhododendron species.
Effects of the COVID-19 pandemic on trauma-related emergency medical service in older people: a retrospective cohort study
Authors: Sabbaghi Mohammadreza , Miri Kheizaran , Namazinia Mohammad
Published: August 2023

Introduction

The ever-increasing human life expectancy has currently resulted in a noticeable rise in the world’s older population. Addressing the healthcare needs of the older people has become a significant concern for many countries. Moreover, the older people are particularly vulnerable to traumatic events. This study aimed to examine the impact of the COVID-19 pandemic on prehospital care provided by Emergency Medical Services (EMS) for trauma-related cases among the older people in Iran.

Methods

This retrospective cohort study involved analyzing the medical records of 1,111 older people aged above 60 who experienced traumatic injuries and received pre-hospital emergency services from March 2018 to March 2022. In order to collect the data, the checklist made by the researcher was used and data analysis in SPSS16 was done using the Chi-square test and Fisher’s exact test.

Results

The age group of 60–74 received the highest number of services both before and after the COVID-19 pandemic. The older men experienced more traumatic events compared to women throughout the study period. The majority of the traumatic events occurred between 8 a.m. and 12 p.m. both before and after the COVID-19 pandemic.

Conclusions

The high prevalence rate of geriatric traumas can be primarily attributed to their physical problems and no control over movements caused by old age, as well as unsafe living conditions. To address these issues, it is suggested that facilities be provided to assist with mobility problems. Moreover, constructing suitable pedestrian bridges and regularly checking neighborhoods and surroundings to identify potential risk factors should be prioritized. Once these risk factors are identified, efforts can be made to adjust and eliminate them, thereby minimizing traumatic events and enhancing a safe and friendly environment for the older people.
Correlation of toxicities and efficacies of pemetrexed with clinical factors and single-nucleotide polymorphisms: a prospective observational study
Authors: Takeda Yuichiro , Naka Go , Katsuya Yuki , Kobayashi Konomi , Suzuki Manabu , Hashimoto Masao , Hirano Satoshi , Uemura Yukari
Published: August 2023

Background

Pemetrexed is an efficacious multi-targeted antifolate with acceptable toxicity for non-squamous non-small cell lung cancer (non-Sq NSCLC) and malignant pleural mesothelioma. Vitamin B12 and folic acid as premedication can reduce the frequency of severe toxicities of pemetrexed chemotherapy. However, adverse effects are frequent in clinical settings. In this study, we aimed to identify the clinical factors and single-nucleotide polymorphisms (SNPs) associated with the toxicity and efficacy of pemetrexed chemotherapy.

Methods

This observational study was conducted from October 2012 to December 2019; we evaluated the toxicities and efficacies of pemetrexed chemotherapy using multivariate logistic or Cox regression analysis. In total, 106 patients received pemetrexed chemotherapy. SNPs were analyzed for four patients with malignant pleural mesothelioma and 67 with non-Sq NSCLC.

Results

The median progression-free survival (PFS) and overall survival of 63 patients with non-Sq NSCLC, excluding four in the adjuvant setting, were 6.8 and 33.3 months, respectively. Per propensity-score-adjusted multivariate Cox analyses, favorable factors for PFS were folic acid level ≥ 9.3 ng/mL before premedication, platinum combination, bevacizumab combination, vitamin B12 level < 1136 pg/mL before chemotherapy, A/A + A/G of BHMT (742 G > A), and A/A + A/C of DHFR (680 C > A). Favorable prognostic factors included good performance status, low smoking index, body mass index ≥ 20.66 kg/m2, folic acid level ≥ 5.55 ng/mL before premedication, higher retinol-binding protein before chemotherapy, and A/G of MTRR (66 A > G). Among the 71 patients who were analyzed for SNPs, the frequencies of hematologic toxicities and non-hematologic toxicities in Grades 3–4 were 38% and 36.6%, respectively. Per propensity-score-adjusted multivariate logistic analyses, risk factors for Grades 3–4 hematologic toxicities were vitamin B12 level < 486 pg/mL before premedication, leucocyte count < 6120 /µL before chemotherapy, folic acid level < 15.8 ng/mL before chemotherapy, status with a reduced dose of chemotherapy, and C/T + T/T of MTHFR (677 C > T). Risk factors for Grades 2–4 non-hematologic toxicities were homocysteine levels ≥ 11.8 nmol/mL before premedication, transthyretin level < 21.5 mg/dL before chemotherapy, C/C + T/T of MTHFR (677 C > T), and A/A + G/G of SLC19A1 [IVS2 (4935) G > A].

Conclusion

The information on metabolites and SNPs of the folate and methionine cycle will help predict the toxicities and efficacies of pemetrexed.

Trial registration

This trial was retrospectively registered with the University hospital Medical Information Network (UMIN000009366) on November 20, 2012.
Development and validation of a nomogram based on common biochemical indicators for survival prediction of children with high-risk neuroblastoma: A valuable tool for resource-limited hospitals
Authors: Wu Ruohao , Li Xiaohui , Chen Zhishan , Shao Qiong , Zhang Xiao , Tang Wenting , Hu Bo
Published: August 2023

Background

Despite multiple attempts have been made to develop risk stratification within high-risk neuroblastoma (NB) patients (age of diagnosis ≥ 18 month-old with metastatic NB), the definition of “ultra high-risk NB” is still lack of consensus, and indicators for identifying this subgroup are still unclear. This study aimed to develop a nomogram based on easy-to-obtain blood-derived biofactors for identifying ultra high-risk NB patients with highest risk of death within 3 or 5 years.

Methods

One hundred sixty-seven NB patients who treated at Sun Yat-sen University Cancer Center between 2015 and 2023 were recruited and clustered randomly into training and validation cohorts (116 and 51 cases, respectively). Univariate and multivariate Cox analysis were performed in training set to screen independent prognostic indicators for constructing nomogram model of predicting 1-, 3- and 5-year overall survival (OS). The discrimination power of the nomogram in training and validation sets were assessed by concordance index (C-index) and calibration plot. Based on the risk score obtained from nomogram model, the prognostic accuracy of 1-, 3- and 5-year OS rates in training and validation cohorts were further evaluated using the area under receiver operating characteristic (ROC) curves (AUC).

Results

Through univariate and multivariate Cox analysis, independent prognostic indicators, including serum lactate dehydrogenase (LDH) and albumin (ALB), were identified in training set, and used to establish a nomogram model. The model showed good discrimination power with C-index in training cohort being 0.706 (95%CI: 0.633—0.788). According to the cut-point calculated based on the established nomogram, patients with a nomogram score > 34 points could be stratified to ultra high-risk NB subgroup, and this subgroup had poorer OS than those in non-ultra one (p < 0.001). AUC values of ROC curves for 3- and 5-year OS rates in the training set were 0.758 and 0.756, respectively. Moreover, based on the cut-point score (34 points) developed in training set, The model also showed good discrimination power with C-index of 0.773 (95%CI: 0.664—0.897) and powerful prognostic accuracy of AUC for 3- and 5-year OS rates being 0.825 and 0.826, respectively, in validation cohort.

Conclusions

We developed a simple-to-use nomogram based on common laboratory indicators to identify the subgroup of ultra high-risk NB before treatment, providing these children even from developing countries or regions access to intensified multimodal treatments earlier and thus improving their long-term outcome.
Factors associated with in-hospital recurrence of intestinal intussusception in children
Authors: Zhang Jing , Dong Qi , Su Xiaoxia , Long Junshan
Published: August 2023

Background

A minority of children experience in-hospital recurrence of intestinal intussusception after treatment. This study investigated the factors associated with in-hospital recurrence of intussusception in pediatric patients in China.

Methods

This retrospective study included patients aged 0–18 years-old with intestinal intussusception treated at Hainan Women and Children’s Medical Center between January 2019 and December 2019. Demographic and clinical characteristics were extracted from the medical records. Factors associated with in-hospital recurrence of intussusception were identified by logistic regression analysis.

Results

The analysis included 624 children (400 boys) with a median age of 1.8 years (range, 2 months and 6 days to 9 years). Seventy-three children (11.7%) had in-hospital recurrence of intussusception after successful reduction with air enema. Multivariate logistic regression analysis identified age > 1 year-old (odds ratio [OR]: 7.65; 95% confidence interval [95%CI]: 2.70–21.71; P < 0.001), secondary intestinal intussusception (OR: 14.40; 95%CI: 4.31–48.14; P < 0.001) and mesenteric lymph node enlargement (OR: 1.90; 95%CI: 1.13–3.18; P = 0.015) as factors independently associated with in-hospital recurrence of intussusception.

Conclusions

Age > 1 year-old, secondary intussusception and mesenteric lymph node enlargement were independently associated with increased odds of in-hospital recurrence of intussusception after successful reduction with air enema.
Ignored and distressed: a cross-sectional study of the impact of COVID-19 on last responders
Authors: Afifi Rima A. , Calderon Jorge Luis , Pham Hanh , Teahen Peter , Zarate-Sada Sydney , Sewell Daniel K. , Vander Weg Mark W.
Published: August 2023

Background

Last responders constitute an occupational category that includes all those that are involved in the postmortem care of deceased persons and their families. Last responders are exposed to several categories of work-related stressors that affect their health and well-being. COVID-19 exacerbated these stressors. Research to understand the consequences of COVID-19 on the health and wellbeing of last responders is nascent. This study aimed to assess COVID-19 related stress, coping and wellbeing among last responders in the United States.

Methods

We conducted a national cross-sectional survey of last responders in July through September of 2020. The survey measured wellbeing, stress, coping, and stigma; COVID-19 experiences, and socio-demographics. A ridge regression model was fit for the outcome variables.

Results

Analysis was conducted on 366 respondents from 43 states. Respondents were male (55.4%), age 50 + (57.4%), and White non-Hispanic (90.3%); 54% reported moderate-high stress and 41% endorsed mild-severe anxiety. Seventy-seven percent had experienced at least one form of stigma related to their occupation. Variables associated with higher perceived stress and anxiety included gender (female), shorter length of employment, perceiving a higher impact from COVID-19 on everyday life, and increased perceived stigma.

Conclusions

Last responders are a critical part of the health care system. Throughout this pandemic, last responders have been frequently ignored and not prioritized for protection and support. Interventions to support last responders cope with stress, and to decrease anxiety are urgently needed. There is also a critical need to challenge community stigma towards last responders.
Focus on the impact of social factors and lifestyle on the disease burden of low back pain: findings from the global burden of disease study 2019
Authors: Yang Yao , Lai Xigui , Li Conghui , Yang Yujie , Gu Shanshan , Hou Weiqian , Zhai Liwen , Zhu Yi
Published: August 2023

Background

Low back pain (LBP) is one of the leading causes of disability worldwide. Differences in social backgrounds and lifestyles in various regions and countries may contribute to the discrepancies in the disease burden of LBP.

Methods

Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of LBP disability-adjusted life years (DALYs). Temporal trends in ASR were also analyzed using estimated annual percentage change (EAPC). The Age-period-cohort (APC) model was used to estimate age, period and cohort trends in DALYs of LBP. An autoregressive integrated moving average (ARIMA) model was used to forecast DALYs of LBP trends from 2020 to 2035.

Results

The DALYs due to LBP increased from 1990 to 2019. The APC model showed that the risk of DALYs for global LBP increased with age and year and that the risk of DALYs was lower in the later-born cohort than in the earlier-born cohort. The main risk factors which GBD estimates were available for DALYs of LBP include smoking, occupational ergonomic factors and high BMI. It is expected that DALYs of LBP will continue to rise until 2035.

Conclusion

From 1990 to 2019, the global disease burden of LBP remained high. It is necessary to pay attention to the influence of social factors and lifestyle on LBP. Focusing on the impact of social factors as well as lifestyle on the prognosis of LBP and targeting interventions may further reduce the disease burden of LBP.
Harnessing cell reprogramming for cardiac biological pacing
Authors: Liu Chih-Min , Chen Yi-Chun , Hu Yu-Feng
Published: August 2023

Electrical impulses from cardiac pacemaker cardiomyocytes initiate cardiac contraction and blood pumping and maintain life. Abnormal electrical impulses bring patients with low heart rates to cardiac arrest. The current therapy is to implant electronic devices to generate backup electricity. However, complications inherent to electronic devices remain unbearable suffering. Therefore, cardiac biological pacing has been developed as a hardware-free alternative. The approaches to generating biological pacing have evolved recently using cell reprogramming technology to generate pacemaker cardiomyocytes in-vivo or in-vitro. Different from conventional methods by electrical re-engineering, reprogramming-based biological pacing recapitulates various phenotypes of de novo pacemaker cardiomyocytes and is more physiological, efficient, and easy for clinical implementation. This article reviews the present state of the art in reprogramming-based biological pacing. We begin with the rationale for this new approach and review its advances in creating a biological pacemaker to treat bradyarrhythmia.
CircRNAs in diagnosis, prognosis, and clinicopathological features of multiple myeloma; a systematic review and meta-analysis
Authors: Mirazimi Yasin , Aghayan Amir Hossein , Keshtkar Abbasali , Mottaghizadeh Jazi Mahsa , Davoudian Atefeh , Rafiee Mohammad
Published: August 2023

Unlike improved treatment response in multiple myeloma (MM), the mortality rate in MM is still high. The study’s aim is to investigate the potential role of circRNAs as a new biomarker for diagnosis, prognosis, and clinicopathological features of MM. We identified studies through Web of Science, Scopus, PubMed and ProQuest databases, and Google Scholar to August 2022. The SEN, SPE, PLR, NLR, DOR, and AUC were combined to investigate the diagnostic performance of circRNAs in MM. Also, HR and RR were used for prognostic and clinicopathological indicators, respectively. 12 studies for prognosis, 9 studies about diagnosis, and 13 studies regarding clinicopathological features. The pooled SEN, SPE, DOR, and AUC were 0.82, 0.76, 14.70, and 0.86, respectively for the diagnostic performance of circRNAs. For the prognostic performance, oncogene circRNAs showed a poor prognosis for the patients (HR = 3.71) and tumor suppressor circRNAs indicated a good prognosis (HR = 0.31). Finally, we discovered that dysregulation of circRNAs is associated with poor clinical outcomes in beta-2-microglobulin (RR = 1.56), Durie-Salmon stage (RR = 1.36), and ISS stage (RR = 1.79). Furthermore, the presence of del(17p) and t(4;14) is associated with circRNA dysregulation (RR = 1.44 and 1.44, respectively). Our meta-analysis demonstrates that the expression analysis of circRNAs is valuable for MM’s diagnosis and prognosis determination. Also, dysregulation of circRNAs is associated with poor clinicopathological features and can be used as the applicable biomarkers for evaluating treatment effectiveness.
3,3′-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways
Authors: Reyes-Hernández Octavio Daniel , Figueroa-González Gabriela , Quintas-Granados Laura Itzel , Gutiérrez-Ruíz Stephany Celeste , Hernández-Parra Hector , Romero-Montero Alejandra , Del Prado-Audelo María Luisa , Bernal-Chavez Sergio Alberto , Cortés Hernán , Peña-Corona Sheila I. , Kiyekbayeva Lashyn , Ateşşahin Dilek Arslan , Goloshvili Tamar , Leyva-Gómez Gerardo , Sharifi-Rad Javad
Published: August 2023

Dietary compounds in cancer prevention have gained significant consideration as a viable method. Indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM) are heterocyclic and bioactive chemicals found in cruciferous vegetables like broccoli, cauliflower, cabbage, and brussels sprouts. They are synthesized after glycolysis from the glucosinolate structure. Clinical and preclinical trials have evaluated the pharmacokinetic/pharmacodynamic, effectiveness, antioxidant, cancer-preventing (cervical dysplasia, prostate cancer, breast cancer), and anti-tumor activities of I3C and DIM involved with polyphenolic derivatives created in the digestion showing promising results. However, the exact mechanism by which they exert anti-cancer and apoptosis-inducing properties has yet to be entirely understood. Via this study, we update the existing knowledge of the state of anti-cancer investigation concerning I3C and DIM chemicals. We have also summarized; (i) the recent advancements in the use of I3C/DIM as therapeutic molecules since they represent potentially appealing anti-cancer agents, (ii) the available literature on the I3C and DIM characterization, and the challenges related to pharmacologic properties such as low solubility, and poor bioavailability, (iii) the synthesis and semi-synthetic derivatives, (iv) the mechanism of anti-tumor action in vitro/in vivo, (v) the action in cellular signaling pathways related to the regulation of apoptosis and anoikis as well as the cell cycle progression and cell proliferation such as peroxisome proliferator-activated receptor and PPARγ agonists; SR13668, Akt inhibitor, cyclins regulation, ER-dependent-independent pathways, and their current medical applications, to recognize research opportunities to potentially use these compounds instead chemotherapeutic synthetic drugs.
Assessing the susceptibility and efficacy of traditional neurotoxic (pyrethroid) and new-generation insecticides (chlorfenapyr, clothianidin, and pyriproxyfen), on wild pyrethroid-resistant populations of Anopheles gambiae from southern Benin
Authors: Zoungbédji David Mahouton , Padonou Germain Gil , Konkon Alphonse Keller , Hougbe Steve , Sagbohan Hermann , Kpanou Casimir , Salako Albert Sourou , Ossè Razaki , Aïkpon Rock , Afoukou Cyriaque , Sidick Aboubakar , Akinro Bruno , Chitou Saïd , Gnanguénon Virgile , Condo Patrick , Hassani Ahmed Saadani , Impoinvil Daniel , Akogbéto Martin
Published: August 2023

Background

The objective of this study was to determine the susceptibility of wild Anopheles gambiae sensu lato (s.l.) from southern Benin to the new insecticides (chlorfenapyr (CFP), pyriproxyfen (PPF), and clothianidin (CTD)) and assess the efficacy of insecticide-treated bed nets (ITNs) that contain these new products.

Methods

Wild An. gambiae from the Benin communes of Allada, Ifangni, Akpro-Missérété, and Porto-Novo were tested for their susceptibility to CFP and PPF using the WHO bottle tests, and pyrethroids (alpha-cypermethrin, deltamethrin, and permethrin) and CTD using WHO tube tests. WHO cone tests were used to evaluate the efficacy of Interceptor® (which contains alpha-cypermethrin (ACM) only), Interceptor® G2, (CFP + ACM), and Royal Guard® nets (PPF + ACM). The ovaries of blood-fed An. gambiae from Ifangni exposed to a new PPF net were dissected, and egg development status was examined using Christopher’s stages to determine the fertility status of the mosquitoes. Using a standardized protocol, the oviposition rate and oviposition inhibition rate were calculated from live blood-fed An. gambiae placed in oviposition chambers after exposure to PPF.

Results

In all four mosquito populations, pyrethroid mortality ranged from 5 to 80%, while chlorfenapyr and clothianidin mortality ranged from 98 to 100%. At Ifangni, all mosquitoes exposed to Royal Guard® nets were infertile (100%) while the majority (74.9%) of mosquitoes exposed to Interceptor® nets had fully developed their eggs to Christopher’s stage V. The oviposition inhibition rate after exposure of the mosquitoes to the PPF was 99% for the wild population of An. gambiae s.l. and the susceptible laboratory strain, An. gambiae sensu stricto (Kisumu).

Conclusions

The results of this study suggest that pyrethroid-resistant An. gambiae from the selected communes in southern Benin are susceptible to chlorfenapyr, clothianidin, and pyriproxyfen. In addition, based on bioassay results, new and unused Interceptor® G2 and Royal Guard® nets were effective on Ifangni’s mosquito populations. Despite the availability of new effective insecticides, continued vigilance is needed in Benin. Therefore, monitoring of resistance to these insecticides will continue to periodically update the Benin national insecticide resistance database and management plan.
Prompt treatment-seeking behaviour varies within communities among guardians of children with malaria-related fever in Malawi
Authors: Stanley Christopher C. , Chirombo James , Msuku Harrison , Phiri Vincent S. , Patson Noel , Kazembe Lawrence N. , Chinkhumba Jobiba , Kapito-Tembo Atupele , Mathanga Don P.
Published: August 2023

Background

In Malawi, malaria is responsible for 40% of hospital deaths. Prompt diagnosis and effective treatment within 24 h of fever onset is critical to prevent progression from uncomplicated to severe disease and to reduce transmission.

Methods

As part of the large evaluation of the malaria vaccine implementation programme (MVIP), this study analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics.

Results

From 4563 households included in the survey, 4856 children aged 5–48 months were enrolled. Out of 4732 children with documented gender, 52.2% were female and 47.8% male. Among the 4856 children, 33.8% reported fever in the two weeks prior to the survey. Fever prevalence was high in communities with low socio-economic status (SES) (38.3% [95% CI: 33.7–43.5%]) and low in areas with high SES (29.8% [95% CI: 25.6–34.2%]). Among children with fever, 648 (39.5%) sought treatment promptly i.e., within 24 h from onset of fever symptoms. Children were more likely to be taken for prompt treatment among guardians with secondary education compared to those without formal education (aOR:1.37, 95% CI: 1.11–3.03); in communities with high compared to low SES [aOR: 2.78, 95% CI: 1.27–6.07]. Children were less likely to be taken for prompt treatment if were in communities far beyond 5 km to health facility than within 5 km [aOR: 0.44, 95% CI: 0.21–0.92].

Conclusion

The high heterogeneity in prevalence of fever and levels of prompt treatment-seeking behaviour underscore the need to promote community-level malaria control interventions (such as use of long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent preventive therapy (IPT), presumptive treatment and education). Programmes aimed at improving treatment-seeking behaviour should consider targeting communities with low SES and those far from health facility.
Focused ultrasound-mediated blood-brain barrier opening combined with magnetic targeting cytomembrane based biomimetic microbubbles for glioblastoma therapy
Authors: He Chuanshi , Wu Zhisheng , Zhuang Min , Li Xiangyu , Xue Shunxu , Xu Songjie , Xu Jinshun , Wu Zhe , Lu Man
Published: August 2023

Glioblastoma is the most common type of brain tumor. Due to the presence of the blood-brain barrier, the effects of chemotherapy have been unsatisfactory. The combination of focused ultrasound and microbubbles to reversibly open the blood-brain barrier is now considered a key factor in improving treatment outcomes of glioblastoma. In this study, we developed bionic drug delivery microbubbles, which in combination with focused ultrasound had an obvious inhibitory effect on glioblastoma. We extracted the brain microvascular cell membranes, combined them with lipid components, and loaded them with superparamagnetic iron oxide and doxorubicin to prepare biomimetic drug delivery microbubbles (FeDOX@cellMBs). We demonstrated that FeDOX@cellMBs retained the intrinsic properties of loading, such as magnetic properties and drug toxicity, both in vitro and in vivo. FeDOX@cellMBs exhibited good tumor targeting and uptake under the combined action of magnetic and focused ultrasound. Importantly, the FeDOX@cellMBs demonstrated excellent internal stability and effectively inhibited tumor growth in orthotopic glioblastoma mice. Finally, organ H&E staining confirmed that FeDOX@cellMBs were safe for use. In conclusion, FeDOX@cellMBs successfully penetrated the blood-brain barrier and effectively inhibited glioblastoma growth under the combined effects of focused ultrasound and magnetic stimulation. These results provide a new approach for the treatment of glioblastoma, with implications for future clinical translation.
Exploring the perception of key stakeholders toward khat policy approaches in Ethiopia: a qualitative study
Authors: Habtamu Kassahun , Teferra Solomon , Mihretu Awoke
Published: August 2023

Background

Khat is an amphetamine-like plant, produced and commonly chewed in Ethiopia by a large group of the population. Although significant multidimensional harms of khat use have been reported, currently, there are no policies or organized activities against khat use in Ethiopia. Therefore, the current study aimed to explore the perception of key stakeholders toward khat policy approaches for Ethiopia.

Methods

A qualitative study was conducted using focus group discussion (FGD) and in-depth interview (IDI). Ten stakeholders participated in the IDIs, and another 15 individuals participated in the FGDs. Key stakeholders were appropriately mapped and purposively selected based on their experience related to khat use and khat harm reduction. Interviews and FGDs were led by the study authors and were audio-recorded. The audio-recorded data were transcribed verbatim and then translated into English language. The data were analyzed using thematic analysis approach.

Results

Participants preferred prevention and law regulation measures for khat policy approaches for Ethiopia. Proposed prevention and law regulation measures included regulating the transportation of khat, limiting the minimum age to buy and sell khat, prohibiting khat use at some public places, banning khat advertising and promotion, and imposing excise tax. Individual level khat harm reduction strategies were also proposed to be useful. However, the participants asserted that total khat ban in Ethiopia is not likely to be feasible and acceptable.

Conclusion

Prevention, treatment or care for individuals with problematic khat use, law regulation, and harm reduction were preferred approaches by stakeholders for khat policy in Ethiopia instead of total banning.
Health-related quality of life in Chinese individuals with type 2 diabetes mellitus: a multicenter cross-sectional study
Authors: Zeng Zihuan , Wang Xingli , Chen Yanhan , Zhou Hengyu , Zhu Wenfen , Xiong Xiu , Tang Jiao , Zhao Qinghua
Published: August 2023

Background

Type 2 diabetes mellitus (T2DM) is a chronic and life-threatening disease. Health-related quality of life (HRQoL) is vital for individuals with T2DM. However, little is known about the impact of psychological stability factors on HRQoL among individuals with T2DM in mainland China.

Methods

This multicenter cross-sectional study was conducted in five tertiary grade-A hospitals in Chongqing, China, from January to December 2019. A total of 385 individuals with T2DM were included by the convenient sample method. Fear of Progression (FOP) Questionnaire-short Form, Hypoglycemia Fear Survey II, diabetes-management self-efficacy scale, and EuroQol-5 Dimensions were used for data collection.

Results

The mean age of the 385 individuals was 57.65 (SD = 15.15) years, three-quarters of whom had a high school or above education level. The participants in our study had moderate HRQoL and were more likely to have poor scores in the pain/discomfort dimension. The FOP level was moderate on average, and 23.1% of individuals suffered from psychological dysfunction. The participants had higher levels of fear of hypoglycemia (FOH) and self-efficacy (SE). Multiple steppage-regression analysis predicted that higher levels of FOP and FOH, reduced SE, older age, longer duration since diagnosis, lower educational attainment, higher levels of HbA1c, and living with comorbid conditions were related to lower HRQoL.

Conclusion

This study showed that the HRQoL among Chinese T2DM patients may be impaired by increased FOP and FOH, decreased SE, and poor glycemic control. In addition, as the patient’s age and duration since diagnosis increase, their HRQoL further declines. We recommend improving HRQoL by encouraging individuals to attain more health education and resilience skills to enhance SE and reduce negative emotions among individuals with T2DM.
Separating lymph node stations by the surgeon from the gastric cancer specimen improves the quality of nodal status evaluation
Authors: Fernström Aleksi , Kokkola Arto , Korpela Akseli , Puolakkainen Pauli , Louhimo Johanna
Published: August 2023

Background

In gastric cancer (GC), the pN-stage is an important prognostic factor influencing treatment. Along with the depth of invasion of the tumor, the presence of nodal metastases is one of the most important prognostic factors guiding treatment strategies in gastric cancer. Examining a small number of lymph nodes may lead to understaging of the disease; hence, it is essential for the nodal status to be precisely assessed. In this study, we explored whether dissecting lymph node stations into separate samples by the surgeon from the gastric cancer surgical specimen affects the quality of nodal status evaluation and patient outcome.

Methods

The clinical data of 130 GC patients treated at the Helsinki University Hospital between 2016 and 2019 was reviewed. The performed operations included 59 total and 71 subtotal gastrectomies. The processing of the surgical specimen before the pathological examination was assessed from the operation records and pathology reports.

The association of the number of examined lymph nodes with other variables was assessed, and multivariate survival analysis was performed to explore the independent prognostic factors in disease-specific survival.

Results

Dissecting lymph node stations into separate specimens before pathological evaluation yielded a significantly greater number of examined lymph nodes compared with a specimen without intervention (median 34.5 vs 21.0, p < 0.001). The pT-stage, the pN-stage, and the extent of lymphadenectomy were identified as independent prognostic factors, whereas dissecting the specimen’s lymph node stations did not associate with survival.

Conclusions

Dissecting lymph node stations into separate specimens results in a greater number of examined lymph nodes, which has the potential to lead to a more reliable pN-stage assessment.
Glutathione Peroxidase 3 induced mitochondria-mediated apoptosis via AMPK /ERK1/2 pathway and resisted autophagy-related ferroptosis via AMPK/mTOR pathway in hyperplastic prostate
Authors: Li Yan , Zhou Yongying , Liu Daoquan , Wang Zhen , Qiu Jizhang , Zhang Junchao , Chen Ping , Zeng Guang , Guo Yuming , Wang Xinghuan , DiSanto Michael E. , Zhang Xinhua
Published: August 2023

Background

Benign prostatic hyperplasia (BPH) is a common disease in elderly men, mainly resulted from an imbalance between cell proliferation and death. Glutathione peroxidase 3 (GPX3) was one of the differentially expressed genes in BPH identified by transcriptome sequencing of 5 hyperplastic and 3 normal prostate specimens, which had not been elucidated in the prostate. This study aimed to ascertain the mechanism of GPX3 involved in cell proliferation, apoptosis, autophagy and ferroptosis in BPH.

Methods

Human prostate tissues, GPX3 silencing and overexpression prostate cell (BPH-1 and WPMY-1) models and testosterone-induced rat BPH (T-BPH) model were utilized. The qRT-PCR, CCK8 assay, flow cytometry, Western blotting, immunofluorescence, hematoxylin and eosin, masson’s trichrome, immunohistochemical staining and transmission electron microscopy analysis were performed during in vivo and in vitro experiments.

Results

Our study indicated that GPX3 was localized both in the stroma and epithelium of prostate, and down-regulated in BPH samples. Overexpression of GPX3 inhibited AMPK and activated ERK1/2 pathway, thereby inducing mitochondria-dependent apoptosis and G0/G1 phase arrest, which could be significantly reversed by MEK1/2 inhibitor U0126 preconditioning. Moreover, overexpression of GPX3 further exerted anti-autophagy by inhibiting AMPK/m-TOR and up-regulated nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4, mitochondrial GPX4 and cytoplasmic GPX4) to antagonize autophagy-related ferroptosis. Consistently, GPX3 deficiency generated opposite changes in both cell lines. Finally, T-BPH rat model was treated with GPX3 indirect agonist troglitazone (TRO) or GPX4 inhibitor RAS-selective lethal 3 (RSL3) or TRO plus RSL3. These treatments produced significant atrophy of the prostate and related molecular changes were similar to our in vitro observations.

Conclusions

Our novel data manifested that GPX3, which was capable of inducing apoptosis via AMPK/ERK1/2 pathway and antagonizing autophagy-related ferroptosis through AMPK/m-TOR signalling, was a promising therapeutic target for BPH in the future.
DARS2 overexpression is associated with PET/CT metabolic parameters and affects glycolytic activity in lung adenocarcinoma
Authors: Liu Xu-Sheng , Yuan Ling-Ling , Gao Yan , Ming Xing , Zhang Yao-Hua , Zhang Yu , Liu Zi-Yue , Yang Yi , Pei Zhi-Jun
Published: August 2023

Background

This study investigated the correlation between the expression of DARS2 and metabolic parameters of 18F-FDG PET/CT, and explored the potential mechanisms of DARS2 affecting the proliferation and glycolysis of lung adenocarcinoma (LUAD) cells.

Methods

This study used genomics and proteomics to analyze the difference in DARS2 expression between LUAD samples and control samples. An analysis of 62 patients with LUAD who underwent 18F-FDG PET/CT examinations before surgery was conducted retrospectively. The correlation between DARS2 expression and PET/CT metabolic parameters, including SUVmax, SUVmean, MTV, and TLG, was examined by Spearman correlation analysis. In addition, the molecular mechanism of interfering with DARS2 expression in inhibiting LUAD cell proliferation and glycolysis was analyzed through in vitro cell experiments.

Results

DARS2 expression was significantly higher in LUAD samples than in control samples (p < 0.001). DARS2 has high specificity (98.4%) and sensitivity (95.2%) in the diagnosis of LUAD. DARS2 expression was positively correlated with SUVmax, SUVmean, and TLG (p < 0.001). At the same time, the sensitivity and specificity of SUVmax in predicting DARS2 overexpression in LUAD were 88.9% and 65.9%, respectively. In vitro cell experiments have shown that interfering with DARS2 expression can inhibit the proliferation and migration of LUAD cells, promote cell apoptosis, and inhibit the glycolytic activity of tumor cells by inhibiting the expression of glycolytic related genes SLC2A1, GPI, ALDOA, and PGAM1.

Conclusions

Overexpression of DARS2 is associated with metabolic parameters on 18F-FDG PET/CT, which can improve LUAD diagnosis accuracy. DARS2 may be a useful biomarker to diagnose, prognosis, and target treatment of LUAD patients.
Significant pain decrease in children with non-systemic Juvenile Idiopathic Arthritis treated to target: results over 24 months of follow up
Authors: Spekking Katinka , Anink Janneke , de Boer Piroska , Bergstra Sytske Anne , van den Berg J. Merlijn , Schonenberg-Meinema Dieneke , van Suijlekom-Smit Lisette W. A. , van Rossum Marion A. J. , Koopman-Keemink Yvonne , Cate Rebecca ten , Allaart Cornelia F. , Brinkman Daniëlle M. C. , Muller Petra C. E. Hissink
Published: August 2023

Background

The aim of this study was to compare pain-scores in three targeted treatment-strategies in JIA-patients and to identify characteristics predicting persistent pain.

Methods

In the BeSt-for-Kids-study 92 DMARD-naïve JIA-patients were randomized in 3 treatment-strategies: 1) initial sequential DMARD-monotherapy 2) initial methotrexate (MTX)/prednisolone-bridging or 3) initial MTX/etanercept. Potential differences in VAS pain scores (0-100 mm) over time between treatment-strategies were compared using linear mixed models with visits clustered within patients. A multivariable model was used to assess the ability of baseline characteristics to predict the chance of high pain-scores during follow-up.

Results

Pain-scores over time reduced from mean 55.3 (SD 21.7) to 19.5 (SD 25.3) mm after 24 months. On average, pain-scores decreased significantly with β -1.37 mm (95% CI -1.726; -1.022) per month. No significant difference was found between treatment-strategies (interaction term treatment arm*time (months) β (95% CI) arm 1: 0.13 (-0.36; 0.62) and arm 2: 0.37 (-0.12; 0.86) compared to arm 3). Correction for sex and symptom duration yielded similar results. Several baseline characteristics were predictive for pain over time. Higher VAS pain [β 0.44 (95% CI 0.25; 0.65)] and higher active joint count [0.77 (0.19; 1.34)] were predictive of higher pain over time, whereas, low VAS physician [ -0.34 (-0.55; -0.06)], CHQ Physical [ -0.42 (-0.72; -0.11)] and Psychosocial summary Score [ -0.42 (-0.77; -0.06)] were predictive of lower pain.

Conclusions

Treatment-to-target seems effective in pain-reduction in non-systemic JIA-patients irrespective of initial treatment-strategy. Several baseline-predictors for pain over time were found, which could help to identify patients with a high risk for development of chronic pain.

Trial registration

Dutch Trial Registry number 1574.