bluuebunny/crossref_metadata_2025 huggingface dataset:
Chikusetsusaponin IVa Protects against H9N2 Avian Influenza Virus Infection by Inhibiting Inflammation and TLR4/NF-κB Signaling Pathways in vitro and in vivo
Authors: Dai Qi , Zheng Xin , Wu Song-Tao , You Peng-Tao , Huang Xiao , Liu Yan-Wen , Wu Yun , Zhang Xiu-Qiao
Published: January 2024

Background

The prevalence of Hemagglutinin 9 Neuraminidase 2 (H9N2) avian influenza virus (AIV) in poultry in Asia has raised serious concerns about its zoonotic transmission and the potential for a pandemic, underscoring the need for effective therapeutics. Chikusetsusaponin IVa (CHS), a bioactive triterpenoid saponin from Radix saposhnikoviae, has exhibited anti-inflammatory activity in preclinical studies. We hypothesized that CHS could mitigate immunopathology during tumor necrosis factor (TNF)-infection by suppressing excessive inflammation.

Objectives

CHS is a natural saponin with anti-inflammatory activity. This research aimed to explore the in vitro and in vivo protective effects and mechanisms of CHS against H9N2 AIV infection.

Materials and Methods

We employed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) analysis for the prediction of the underlying mechanisms, followed by a network analysis approach. In animal experiments, the toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) signaling pathways and associated proteins were assessed using immunohistochemistry and western blot analysis.

Results

In A549 cells, CHS treatment reduced H9N2 AIV-induced apoptosis in a dose-dependent manner. CHS was found to have a suppressive effect on the mRNA expression of various inflammatory cytokines (including TNF-α, interleukin (IL)-6, IL-1β, and IL-8) as well as mediators such as inducible nitric oxide synthase (iNOS) and prostaglandin-endoperoxide synthase 2 (PTGS2). It can be seen that CHS does have anti-inflammatory effects. Bioinformatics analysis indicated that CHS might exhibit anti-inflammatory effects by modulating cytokine–cytokine receptor interaction and the NF-κB signaling pathways. Building upon this, it was found that CHS blocked the activation of TLR4 and NF-κB signaling pathways in A549 cells infected with H9N2 AIV. In vivo, CHS prolonged the survival time and increased the survival rate of H9N2 AIV-infected mice. CHS was found to have a protective effect on the lungs of infected mice, resulting in reduced damage and lower levels of viral load and inflammation. CHS inhibited the production of proinflammatory cytokines (IL-1β, TNF-α, IL-6, and IL-8) and inhibited the activation of TLR4 and NF-κB signaling pathways in the pulmonary tissues of mice that were infected.

Conclusion

CHS exerts protective effects against H9N2 AIV infection in vitro and in vivo. The anti-inflammatory mechanisms may involve the inhibition of cytokine production and the blockade of TLR4 and NF-κB signaling pathways.
Assessment of Immunomodulatory Activity of AP-Bio® (KalmCold®), a Standardized Extract of Andrographis paniculata Using in vivo and ex vivo Models
Authors: Chalichem Nehru Sai Suresh , Nabhan Prathiksha , Bethapudi Bharathi , Agarwal Nikita , Murugan Sasi Kumar , Deepak Mundkinajeddu
Published: January 2024

Background

Andrographis paniculata (Burm. f.) Nees is a well-recognized medicinal plant known for its benefits against a multitude of ailments. The intent of the present study was to evaluate the effect of a standardized extract of A. paniculata on innate immunity.

Materials and Methods

Phagocytic activity was measured in terms of phagocytic index using carbon clearance methodology in mice. In another experiment, NK cells (effector cells) were isolated from the mouse spleen after the dosing period, and NK cells-mediated lysis of target cells (YAC-1 cells) were determined using an MTT assay.

Results

The phagocytic index and NK cell activity were found to be significantly ( p < 0.05) different in the treated group compared to the control group in the tested animal models at a dose of 41 mg/kg.

Conclusion

The results suggest the potential of A. paniculata to enhance innate immunity.
Role of Technology in Solid Waste Management: Social Enterprise in a Pandemic
Authors: Mitra Sumit , Deepak Aakriti
Published: January 2024

COVID-19 has changed the world. The pandemic was a public health crisis with profound implications for society. Accordingly, the quantum of waste generated also went up especially fast. The global nature of the pandemic demanding global communication and coordination, also required locally adopted responses for specific reasons like lack of opportunity to network and create bonding and bridging ties as lockdown conditions prohibited human interactions. This situation that needs the substitution of human interactions and communication with technology however did not encourage strong ties and only allowed for the sustenance of weak ties along with pressures of financial sustainability on the social enterprise in solid waste management (SWM). This research paper attempts to explore whether the SWM social enterprises could remain true to their mission in these uncertain times or would need to replace their true beneficiaries with technology. This would then test their aspects of ‘mission agility’ versus ‘mission drift’ as discussed in the article. The findings also lead us to conclude that a fine balance between objectives of value capture and value creation in determining the switch over to technology by SWM enterprises underscored the importance of social mission to them.

The data for this research was collected through qualitative and semi-structured interviews of Project Managers / Program Coordinators of various organisations working in the field of SWM.
Natromelansonite, Na3Zr[Si7AlO19]⋅4–5H2O, a new member of the rhodesite mero-plesiotype series from Mont Saint-Hilaire, Quebec, Canada
Authors: Lykova Inna , Rowe Ralph , Poirier Glenn , Friis Henrik , Barnes Stephanie
Published: January 2024

Natromelansonite, Na3Zr[Si7AlO19]⋅4–5H2O, was found at the Poudrette (Demix) quarry, Mont Saint-Hilaire, Quebec, Canada in a highly altered pegmatite together with a clay mineral, steacyite, polylithionite and rhodochrosite. It occurs as an outer zone of tabular crystals to 0.1 × 0.3 × 1 mm in size flattened on (001). The inner zone is made of melansonite. The mineral is grey with white powder colour and vitreous lustre. The cleavage is parallel to {010}, perfect. The Mohs hardness is 3.5. The mineral has green fluorescence under short-wave ultraviolet light. The Dcalc is 2.31 g/cm3. The infrared spectrum is reported. The composition (wt.%, average of 8 analyses) is Na2O 10.08, K2O 1.72, CaO 0.24, BaO 0.32, MnO 0.10, Al2O3 6.86, Y2O3 0.35, Yb2O3 0.55, SiO2 56.23, ZrO2 14.78, H2O 9.52, total 100.75. The empirical formula calculated on the basis of O = 23 apfu and H = 8 apfu is Na(□Na0.38Ca0.02Mn0.01)2(Na0.70K0.28Ba0.02)Σ1.00(Zr0.91Y0.02Yb0.02)Σ0.95(Si7.08Al1.02)Σ8.10O19⋅4H2O. The mineral is monoclinic, P21/m, a = 6.5156(3) Å, b = 24.061(1) Å, c = 6.9759(6) Å, β = 90.453(5)° and V = 1093.61(9) Å3 and Z = 2. The strongest reflections of the powder X-ray diffraction pattern [d,Å(I)(hkl)] are: 12.02(100)(020), 6.97(89)(001), 6.51(39)(100), 3.416(37)(160), 3.062(42)($\bar{1}$61, 102, 161 and $\bar{1}$12), 3.018(38)(230 and 042), 2.864(40)(240 and 132). The crystal structure, solved and refined from single-crystal X-ray diffraction data (R1 = 0.042), is based on a double sheet of tetrahedra (T) and a sheet of octahedra (O) that alternate along the [010] direction forming a TOT structure typical for members of the rhodesite mero-plesiotype series.
Different vulnerability of fast and slow cortical oscillations to suppressive effect of spreading depolarization: state-dependent features potentially relevant to pathogenesis of migraine aura
Authors: Medvedeva Tatiana M. , Smirnova Maria P. , Pavlova Irina V. , Vinogradova Lyudmila V.
Published: January 2024

Background

Spreading depolarization (SD), underlying mechanism of migraine aura and potential activator of pain pathways, is known to elicit transient local silencing cortical activity. Sweeping across the cortex, the electrocorticographic depression is supposed to underlie spreading negative symptoms of migraine aura. Main information about the suppressive effect of SD on cortical oscillations was obtained in anesthetized animals while ictal recordings in conscious patients failed to detect EEG depression during migraine aura. Here, we investigate the suppressive effect of SD on spontaneous cortical activity in awake animals and examine whether the anesthesia modifies the SD effect.

Methods

Spectral and spatiotemporal characteristics of spontaneous cortical activity following a single unilateral SD elicited by amygdala pinprick were analyzed in awake freely behaving rats and after induction of urethane anesthesia.

Results

In wakefulness, SD transiently suppressed cortical oscillations in all frequency bands except delta. Slow delta activity did not decline its power during SD and even increased it afterwards; high-frequency gamma oscillations showed the strongest and longest depression under awake conditions. Unexpectedly, gamma power reduced not only during SD invasion the recording cortical sites but also when SD occupied distant subcortical/cortical areas. Contralateral cortex not invaded by SD also showed transient depression of gamma activity in awake animals. Introduction of general anesthesia modified the pattern of SD-induced depression: SD evoked the strongest cessation of slow delta activity, milder suppression of fast oscillations and no distant changes in gamma activity.

Conclusion

Slow and fast cortical oscillations differ in their vulnerability to SD influence, especially in wakefulness. In the conscious brain, SD produces stronger and spatially broader depression of fast cortical oscillations than slow ones. The frequency-specific effects of SD on cortical activity of awake brain may underlie some previously unexplained clinical features of migraine aura.
Mechanosensitive receptors in migraine: a systematic review
Authors: Della Pietra Adriana , Gómez Dabó Laura , Mikulenka Petr , Espinoza-Vinces Christian , Vuralli Doga , Baytekin Isil , Martelletti Paolo , Giniatullin Rashid ,   On behalf of the School of Advanced Studies of the European Headache Federation (EHF-SAS)
Published: January 2024

Background

Migraine is a debilitating neurological disorder with pain profile, suggesting exaggerated mechanosensation. Mechanosensitive receptors of different families, which specifically respond to various mechanical stimuli, have gathered increasing attention due to their potential role in migraine related nociception. Understanding these mechanisms is of principal importance for improved therapeutic strategies. This systematic review comprehensively examines the involvement of mechanosensitive mechanisms in migraine pain pathways.

Methods

A systematic search across the Cochrane Library, Scopus, Web of Science, and Medline was conducted on 8th August 2023 for the period from 2000 to 2023, according to PRISMA guidelines. The review was constructed following a meticulous evaluation by two authors who independently applied rigorous inclusion criteria and quality assessments to the selected studies, upon which all authors collectively wrote the review.

Results

We identified 36 relevant studies with our analysis. Additionally, 3 more studies were selected by literature search. The 39 papers included in this systematic review cover the role of the putative mechanosensitive Piezo and K2P, as well as ASICs, NMDA, and TRP family of channels in the migraine pain cascade. The outcome of the available knowledge, including mainly preclinical animal models of migraine and few clinical studies, underscores the intricate relationship between mechanosensitive receptors and migraine pain symptoms. The review presents the mechanisms of activation of mechanosensitive receptors that may be involved in the generation of nociceptive signals and migraine associated clinical symptoms. The gender differences of targeting these receptors as potential therapeutic interventions are also acknowledged as well as the challenges related to respective drug development.

Conclusions

Overall, this analysis identified key molecular players and uncovered significant gaps in our understanding of mechanotransduction in migraine. This review offers a foundation for filling these gaps and suggests novel therapeutic options for migraine treatments based on achievements in the emerging field of mechano-neurobiology.
A multimodal graph neural network framework for cancer molecular subtype classification
Authors: Li Bingjun , Nabavi Sheida
Published: January 2024

Background

The recent development of high-throughput sequencing has created a large collection of multi-omics data, which enables researchers to better investigate cancer molecular profiles and cancer taxonomy based on molecular subtypes. Integrating multi-omics data has been proven to be effective for building more precise classification models. Most current multi-omics integrative models use either an early fusion in the form of concatenation or late fusion with a separate feature extractor for each omic, which are mainly based on deep neural networks. Due to the nature of biological systems, graphs are a better structural representation of bio-medical data. Although few graph neural network (GNN) based multi-omics integrative methods have been proposed, they suffer from three common disadvantages. One is most of them use only one type of connection, either inter-omics or intra-omic connection; second, they only consider one kind of GNN layer, either graph convolution network (GCN) or graph attention network (GAT); and third, most of these methods have not been tested on a more complex classification task, such as cancer molecular subtypes.

Results

In this study, we propose a novel end-to-end multi-omics GNN framework for accurate and robust cancer subtype classification. The proposed model utilizes multi-omics data in the form of heterogeneous multi-layer graphs, which combine both inter-omics and intra-omic connections from established biological knowledge. The proposed model incorporates learned graph features and global genome features for accurate classification. We tested the proposed model on the Cancer Genome Atlas (TCGA) Pan-cancer dataset and TCGA breast invasive carcinoma (BRCA) dataset for molecular subtype and cancer subtype classification, respectively. The proposed model shows superior performance compared to four current state-of-the-art baseline models in terms of accuracy, F1 score, precision, and recall. The comparative analysis of GAT-based models and GCN-based models reveals that GAT-based models are preferred for smaller graphs with less information and GCN-based models are preferred for larger graphs with extra information.
Methodology for biomarker discovery with reproducibility in microbiome data using machine learning
Authors: Rojas-Velazquez David , Kidwai Sarah , Kraneveld Aletta D. , Tonda Alberto , Oberski Daniel , Garssen Johan , Lopez-Rincon Alejandro
Published: January 2024

Background

In recent years, human microbiome studies have received increasing attention as this field is considered a potential source for clinical applications. With the advancements in omics technologies and AI, research focused on the discovery for potential biomarkers in the human microbiome using machine learning tools has produced positive outcomes. Despite the promising results, several issues can still be found in these studies such as datasets with small number of samples, inconsistent results, lack of uniform processing and methodologies, and other additional factors lead to lack of reproducibility in biomedical research. In this work, we propose a methodology that combines the DADA2 pipeline for 16s rRNA sequences processing and the Recursive Ensemble Feature Selection (REFS) in multiple datasets to increase reproducibility and obtain robust and reliable results in biomedical research.

Results

Three experiments were performed analyzing microbiome data from patients/cases in Inflammatory Bowel Disease (IBD), Autism Spectrum Disorder (ASD), and Type 2 Diabetes (T2D). In each experiment, we found a biomarker signature in one dataset and applied to 2 other as further validation. The effectiveness of the proposed methodology was compared with other feature selection methods such as K-Best with F-score and random selection as a base line. The Area Under the Curve (AUC) was employed as a measure of diagnostic accuracy and used as a metric for comparing the results of the proposed methodology with other feature selection methods. Additionally, we use the Matthews Correlation Coefficient (MCC) as a metric to evaluate the performance of the methodology as well as for comparison with other feature selection methods.

Conclusions

We developed a methodology for reproducible biomarker discovery for 16s rRNA microbiome sequence analysis, addressing the issues related with data dimensionality, inconsistent results and validation across independent datasets. The findings from the three experiments, across 9 different datasets, show that the proposed methodology achieved higher accuracy compared to other feature selection methods. This methodology is a first approach to increase reproducibility, to provide robust and reliable results.
Evaluation of biocontrol efficacy of rhizosphere dwelling bacteria for management of Fusarium wilt and Botrytis gray mold of chickpea
Authors: Bhargavi Gurreddi , Arya Meenakshi , Jambhulkar Prashant Prakash , Singh Anshuman , Rout Ajaya Kumar , Behera Bijay Kumar , Chaturvedi Sushil Kumar , Singh Ashok Kumar
Published: January 2024

Background

Chickpea (Cicer arietinum L.) production is affected by many biotic factors, among them Fusarium wilt caused by Fusarium oxysporum f. sp. ciceri and Botrytis gray mold caused by Botrytis cinerea led to severe losses. As fungicide application is not advisable, biological management is the best alternative for plant protection. The rhizosphere-dwelling antagonistic bacteria are one of the important successful alternative strategy to manage these diseases of chickpea. Rhizosphere dwelling bacteria serve as biocontrol agents by different mechanisms like producing antibiotics, different enzymes, siderophores against pathogens and thereby reducing the growth of pathogens.

Results

The present study aimed to isolate rhizospheric bacteria from the soils of different chickpea fields to evaluate biocontrol efficacy of the isolated bacteria to manage Fusarium wilt and Botrytis gray mold in chickpea. A total of 67 bacteria were isolated from chickpea rhizosphere from Bundelkhand region of India. Study revealed the isolated bacteria could reduce the Fusarium oxysporum f. sp. ciceris and Botrytis cinerea infection in chickpea between 17.29 and 75.29%. After screening of all the bacteria for their biocontrol efficacy, 13 most promising bacterial isolates were considered for further study out of which, three bacterial isolates (15d, 9c and 14a) have shown the maximum in vitro antagonistic effects against Fusarium oxysporum f. sp. ciceri and Botrytis cinerea comparable to in vivo effects. However, Isolate (15d) showed highest 87.5% and 82.69% reduction in disease against Fusarium wilt and Botrytis gray mold respectively, under pot condition. Three most potential isolates were characterized at molecular level using 16S rRNA gene and found to be Priestia megaterium (9c and 14a) and Serratia marcescens (15d).

Conclusion

This study identified two native biocontrol agents Priestia megaterium and Serratia marcescens from the rhizospheric soils of Bundelkhand region of India for control of Fusarium wilt, Botrytis gray mold. In future, efforts should be made to further validate the biocontrol agents in conjugation with nanomaterials for enhancing the synergistic effects in managing the fungal diseases in chickpea. This study will definitely enhance our understanding of these bioagents, and to increase their performance by developing effective formulations, application methods, and integrated strategies.
Characteristics of gut microbiota in patients with asthenozoospermia: a Chinese pilot study
Authors: Pan Yang , Wang Shangren , Liu Li , Liu Xiaoqiang
Published: January 2024

Background

Identification of intestinal flora composition is significant for exploring the cause and pathogenic mechanisms of the gut-testis axis and clarifying the relationship between microbiota and infertility. Our study aimed to examine the alternation in gut microbiota composition and identify potential microbes associated with development of Asthenozoospermia (AS).

Method

A total of 580 males were recruited in the outpatient department of Tianjin Medical University General Hospital between September 2021 and March 2023. Sperm parameters were analyzed according to the WHO laboratory manual. The 16 S rRNA gene high-throughput sequencing was performed to detect the gut microbiota composition in fecal samples. LEfSe analysis was used to screen key microbiota. PICRUSt2 software was utilized to predict relevant pathways.

Results

After rigorous screening, 60 isolated AS patients (AS group) and 48 healthy men (NC group) were enrolled. No significant differences were observed in demographic characteristics (p > 0.05), semen volume (p = 0.718), sperm concentration (p = 0.109), or total sperm count (p = 0.200). Sperm total motility and progressive motility were significantly decreased in the AS group (p < 0.001). AS patients had significantly lower alpha diversity indices (Chao1, observed OTUs, and PD Whole-tree; p < 0.05). The beta-diversity of gut microbiota in AS patients significantly differed from NC men (PCoA analysis, p = 0.001). Firmicutes, Bacteroidota, Proteobacteria, and Actinobacteria were the primary phyla, with the dominant genera including Bacteroides, Prevotella, and Blautia. Eleven key genera such as Escherichia_Shigella and Prevotellaceae_UCG_001 were identified by LEfSe analysis. Most of these genera were negatively correlated with sperm mobility. Eighty-eight KEGG pathways, including steroid biosynthesis and meiosis, were significantly enriched between the two groups.

Conclusions

It appears that gut microbiota composition in AS patients significantly differed from that in healthy men, and the development of AS might be associated with intestinal flora dysbiosis.
Enhancing productivity, modifying biochemical parameters, and regulating the phenylpropanoid pathway in 'Le-Conte' pears through optimal protocatechuic acid treatments
Authors: Khedr Emad Hamdy , Khedr Nagwa
Published: January 2024

Background

This study aimed to investigate the impact of protocatechuic acid (PRC) treatments on the productivity and fruit quality of 'Le-Conte' pears, with a specific focus on productivity, stone cells content, and antioxidant activity. The research spanned over three consecutive cultivating seasons, with the first season serving as a preliminary study to determine the optimal PRC concentrations and the most effective number of spray applications. During the initial season, response surface methodology (RSM) was employed to optimize PRC concentration and application frequency. PRC was evaluated at concentrations ranging from 50 to 400 ppm, with treatment frequencies of either once or twice. Considering the optimal conditions obtained from RSM results, PRC treatments at 200 ppm and 300 ppm were applied twice, and their respective effects were studied in comparison to the control in the following seasons.

Results

RSM results indicated that PRC at 200 and 300 ppm, applied twice, once during full bloom and again three weeks later, yielded the most significant effects. Subsequent studies revealed that PRC treatments had a substantial impact on various aspects of fruit production and quality. Applying 300 ppm PRC once during full bloom and again three weeks later resulted in higher fruit set percentages, lower fruit abscission, and enhanced fruit yield compared to untreated trees. Additionally, the 200 ppm PRC treatment maintained physicochemical characteristics such as fruit color, increased total soluble solids (TSS), and total sugar, and maintained higher ascorbic acid content and antioxidant capacity in the fruits while reducing stone cells content and lignin. Notably, enzyme activities related to phenylpropanoid metabolism and stone cells, including phenylalanine ammonia-lyase (PAL), cinnamate-4-hydroxylase (C4H), 4-Coumarate-CoA Ligase (4CL), cinnamyl alcohol dehydrogenase (CAD), and cinnamoyl-CoA reductase (CCR), as well as peroxidase, polyphenol oxidase, and laccase, were significantly regulated by PRC treatments.

Conclusion

Overall, this study suggests that PRC treatments are suitable for enhancing pear yield and quality, with PRC at 200 ppm being the more recommended option over 300 ppm. This approach serves as an effective strategy for achieving a balance between enhancing the productivity and fruit quality of 'Le-Conte' pears.
Rare complications of infective endocarditis in marfan-like morphotype: diagnosis of multiple mitral valve aneurysms and aortic root abscess using three-dimensional transesophageal echocardiography
Authors: Boumaaz Meriem , Lahjouji Mohamed Reda , Faraj Raid , Mouine Najat , Asfalou Iliyasse , Benyass Aatif
Published: January 2024

Mitral valve aneurysm (MVA) is characterized by a saccular outpouching of the mitral leaflet, and it represents a rare condition typically associated with aortic valve endocarditis. Three-Dimensional Transesophageal Echocardiography (3D-TEE) serves as an effective tool for detecting the presence of MVA and its potential complications. In this report, we present a case involving a young man with striking images of bicuspid aortic valve endocarditis complicated by an aortic root abscess and multiple perforated mitral valve aneurysms, diagnosed using 3D TEE. This case suggests the uncommon coexistence of Marfan like morphotype, bicuspid aortic valve, and infective endocarditis as a triple mechanism in the occurrence of MVA. It underscores the significance of early and accurate imaging diagnosis for facilitating prompt surgical intervention.
Diabetes mellitus and associated factors among HIV-positive patients at primary health care facilities in Harare, Zimbabwe: a descriptive cross-sectional study
Authors: Chireshe Rumbidzai , Manyangadze Tawanda , Naidoo Keshena
Published: January 2024

Background

Highly active antiretroviral therapy (HAART) has improved the life expectancy of people living with HIV (PLWH) and has increased the risk of chronic non-communicable diseases. Comorbid HIV and diabetes mellitus (DM) significantly increase cardiovascular disease and mortality risk. This study aimed to determine the prevalence of type 2 diabetes mellitus among HIV-positive patients receiving HAART in Zimbabwe and its associated risk factors.

Methods

This cross-sectional study was conducted at eight primary healthcare facilities in Harare, Zimbabwe, between January 2022 and March 2023. Non-probability convenience sampling was used to recruit adult HIV-positive patients undergoing HAART attending the facilities. Data were captured on clinical history and socio-demographic and behavioral characteristics, and analyzed using descriptive statistics to determine DM prevalence rates. Additionally, bivariate and multivariate logistic regression models were employed to examine factors associated with HIV and DM comorbidities.

Results

A total of 450 participants were included in this study, of which 57.6% (n = 259) were female. The majority were married (73.8%) and older than 35 years (80.2%). Most participants had completed high school (87.6%) and 68.9% were employed either formally or self-employed. The prevalence of diabetes mellitus (DM) was 14.9%. HIV/DM comorbidity was more prevalent in patients who were female, self-employed, and smoked (p < 0.05). Multivariate logistic regression analysis revealed that the factors associated with DM-HIV comorbidity were gender, age, education, marital status, employment status, smoking, physical activities, duration of HAART, and diet. Age, level of education, marital status, and occupation were not associated with HIV-DM comorbidity. Obesity (body mass index > 30 kg/m2), smoking, and alcohol consumption were associated with an increased risk of DM. Regular physical activity is associated with a reduced risk of DM.

Conclusion

A substantial burden of DM was found in PLWH. The intersectoral integration approach is advocated, and active screening for DM is recommended. Gender-specific interventions are necessary to target diseases and health behaviors that differ between men and women. These interventions should be customized to the specific diseases and behaviors of each group.
A volunteer-supported walking programme to improve physical function in older people with restricted mobility (the POWER Study): a randomised controlled trial
Authors: Grede Nina , Trampisch Ulrike , Weissbach Sabine , Heinzel-Gutenbrunner Monika , Freiberger Ellen , Sönnichsen Andreas , Donner-Banzhoff Norbert
Published: January 2024

Background

Regular physical activity has multiple health benefits, especially in older people. Therefore, the World Health Organization recommends at least 2.5 h of moderate physical activity per week. The aim of the POWER Study was to investigate whether volunteer-assisted walking improves the physical performance and health of older people.

Methods

We approached people aged 65 years and older with restricted mobility due to physical limitations and asked them to participate in this multicentre randomised controlled trial. The recruitment took place in nursing homes and the community setting. Participants randomly assigned to the intervention group were accompanied by volunteer companions for a 30–50 min walk up to three times a week for 6 months. Participants in the control group received two lectures that included health-related topics. The primary endpoint was physical function as measured with the Short Physical Performance Battery (SPPB) at baseline and 6 and 12 months. The secondary and safety endpoints were quality of life (EQ-5D-5L), fear of falling (Falls Efficacy Scale), cognitive executive function (the Clock Drawing Test), falls, hospitalisations and death.

Results

The sample comprised 224 participants (79% female). We failed to show superiority of the intervention with regard to physical function (SPPB) or other health outcomes in the intention-to-treat analyses. However, additional exploratory analyses suggest benefits in those who undertook regular walks. The intervention appears to be safe regarding falls.

Conclusions

Regular physical activity is essential to preserve function and to improve health and quality of life. Against the background of a smaller-than-planned sample size, resulting in low power, and the interference of the COVID-19 pandemic, we suggest that community based low-threshold interventions deserve further exploration.

Trial registration

The trial was registered with the German Clinical Trials Register (www.germanctr.de), with number DRKS00015188 on 31/08/2018.
First global report about the prevalence of multi-drug resistant Haemophilus influenzae: a systematic review and meta-analysis
Authors: Abavisani Mohammad , Keikha Masoud , Karbalaei Mohsen
Published: January 2024

Background

In recent decades, the prevalence of antibiotic resistance is increasing in Haemophilus influenzae (Haemophilus influenzae), which poses important challenges to global health. This research offers a comprehensive meta-analysis of the global epidemiology of multi-drug resistant (MDR) H. influenzae.

Methods

In this study, we conducted a meta-analysis based on PRISMA checklist. Electronic databases including PubMed, ISI Web of Science, Scopus, EMBASE, and Google Scholar were reviewed using keywords related to H. influenzae and antibiotic resistance. Eligible studies were selected based on stringent inclusion and exclusion criteria. Then, data from these studies were analyzed using the Comprehensive Meta-Analysis (CMA) software.

Results

Of 375 retrieved articles, 16 met the inclusion criteria. These studies were conducted from 2003 to 2023 and analyzed data from 19,787 clinical isolates of H. influenzae. The results showed different levels of resistance of H. influenzae to different antibiotics: ampicillin (36%), azithromycin (15.3%), ceftriaxone (1.4%), etc. The global prevalence for beta-lactamases producing H. influenzae and MDR H. influenzae was measured 34.9% and 23.1%, respectively. The prevalence rate of MDR H. influenzae was higher in Asian countries (24.6%) compared to Western regions (15.7%). MDR H. influenzae had the highest prevalence in meningitis cases (46.9%) and the lowest prevalence in acute otitis media (0.5%).

Conclusions

The prevalence of MDR H. influenzae has been increasing worldwide, especially in Asian regions. This highlights the urgent need for monitoring and implementation of effective antibiotic stewardship programs globally.
Poor nutritional status is associated with the severity of omicron infection in the older adults
Authors: Gu Xiaohan , Guo Yongchao , Shi Yongmei , Lu Yaxiong , Yang Shihan , Jiang Yongmei , Jin Qianwen , Li Qing Yun
Published: January 2024

Background

The Omicron wave of Coronavirus disease 2019 (COVID-19) remains the dominant strain worldwide. The studies of nutritional status in geriatric people with COVID-19 Omicron variant are limited. Thus, the aim of this study was to investigate the incidence of poor nutritional status among Omicron infected older patients, and to explore the correlation between the nutritional status and the severity of Omicron infection in older patients.

Methods

This is a retrospective cross-sectional study. According to the clinical symptoms, patients were divided into two groups: mild and moderate to severe. Mini Nutritional Assessment short-form (MNA-SF) was conducted when patients were admitted and poor nutritional status was defined as MNA-SF score of 0–11. The inflammatory markers including neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR) and systemic inflammatory index (SII) were calculated and compared between two groups.

Results

Total of 324 patients were enrolled, with median [interquartile range (IQR)] age of 73 (17) years. Overall, 241 cases were mild, 83 cases were moderate to severe at the time of diagnosis and that 54.3% of patients had poor nutritional status. Patients with poor nutritional status were found to be older (P < 0.001) and less vaccinated (P < 0.001), with a longer virus shedding duration (P = 0.022), more comorbidities (≥ 2) (P = 0.004) and higher value of NLR (P < 0.001), PLR (P < 0.001) and SII (P = 0.012). Vaccination, cycle threshold value in ORF1ab gene (OR CT value) and female, higher MNA-SF score was negatively connected with probability of moderate to severe infection. For every 1 score increase in MNA-SF, the odds ratio of moderate to severe infection decreased by 14.8% [adjusted odds ratio (aOR), 0.852; 95% confidence interval (CI): 0.734–0.988; P = 0.034].

Conclusions

Older patients with poor nutritional status are more likely to develop moderate to severe Omicron infection.
Early to mid-pregnancy HbA1c levels and its association with adverse pregnancy outcomes in three low middle-income countries in Asia and Sub-Saharan Africa
Authors: Nisar Muhammad Imran , das Sayan , Khanam Rasheda , Khalid Javairia , Chetia Swagata , Hasan Tarik , Shahid Shahira , Marijani Msafiri Ladislaus , Ahmed Salahuddin , Khalid Farah , Ali Said Mohammed , Chowdhury Nabidul Haque , Mehmood Usma , Dutta Arup , Rahman Sayedur , Qazi Muhammad Farrukh , Deb Saikat , Mitra Dipak Kumar , Usmani Asra Abeer , Dhingra Usha , Raqib Rubhana , Manu Alexander , Yoshida Sachiyo , Minckas Nicole , Bahl Rajiv , Baqui Abdullah H. , Sazawal Sunil , Jehan Fyezah
Published: January 2024

Background

Hyperglycemia during pregnancy leads to adverse maternal and fetal outcomes. Thus, strict monitoring of blood glucose levels is warranted. This study aims to determine the association of early to mid-pregnancy HbA1c levels with the development of pregnancy complications in women from three countries in South Asia and Sub-Saharan Africa.

Methods

We performed a secondary analysis of the AMANHI (Alliance for Maternal and Newborn Health Improvement) cohort, which enrolled 10,001 pregnant women between May 2014 and June 2018 across Sylhet-Bangladesh, Karachi-Pakistan, and Pemba Island-Tanzania. HbA1c assays were performed at enrollment (8 to < 20 gestational weeks), and epidemiological data were collected during 2–3 monthly household visits. The women were followed-up till the postpartum period to determine the pregnancy outcomes. Multivariable logistic regression models assessed the association between elevated HbA1c levels and adverse events while controlling for potential confounders.

Results

A total of 9,510 pregnant women were included in the analysis. The mean HbA1c level at enrollment was found to be the highest in Bangladesh (5.31 ± 0.37), followed by Tanzania (5.22 ± 0.49) and then Pakistan (5.07 ± 0.58). We report 339 stillbirths and 9,039 live births. Among the live births were 892 preterm births, 892 deliveries via cesarean section, and 532 LGA babies. In the multivariate pooled analysis, maternal HbA1c levels of ≥ 6.5 were associated with increased risks of stillbirths (aRR = 6.3, 95% CI = 3.4,11.6); preterm births (aRR = 3.5, 95% CI = 1.8–6.7); and Large for Gestational Age (aRR = 5.5, 95% CI = 2.9–10.6).

Conclusion

Maternal HbA1c level is an independent risk factor for predicting adverse pregnancy outcomes such as stillbirth, preterm birth, and LGA among women in South Asia and Sub-Saharan Africa. These groups may benefit from early interventional strategies.
Maternal plasma cortisol’s effect on offspring birth weight: a Mendelian Randomisation study
Authors: Thompson WD , Reynolds RM , Beaumont RN , Warrington NM , Tyrrell J , Wood AR , Evans DM , McDonald TJ , Hattersley AH , Freathy RM , Lawlor DA , Borges MC
Published: January 2024

Background

Observational studies and randomized controlled trials have found evidence that higher maternal circulating cortisol levels in pregnancy are associated with lower offspring birth weight. However, it is possible that the observational associations are due to residual confounding.

Methods

We performed two-sample Mendelian Randomisation (MR) using a single genetic variant (rs9989237) associated with morning plasma cortisol (GWAS; sample 1; N = 25,314). The association between this maternal genetic variant and offspring birth weight, adjusted for fetal genotype, was obtained from the published EGG Consortium and UK Biobank meta-analysis (GWAS; sample 2; N = up to 406,063) and a Wald ratio was used to estimate the causal effect. We also performed an alternative analysis using all GWAS reported cortisol variants that takes account of linkage disequilibrium. We also tested the genetic variant’s effect on pregnancy cortisol and performed PheWas to search for potential pleiotropic effects.

Results

The estimated effect of maternal circulating cortisol on birth weight was a 50 gram (95% CI, -109 to 10) lower birth weight per 1 SD higher log-transformed maternal circulating cortisol levels, using a single variant. The alternative analysis gave similar results (-33 grams (95% CI, -77 to 11)). The effect of the cortisol variant on pregnancy cortisol was 2-fold weaker than in the original GWAS, and evidence was found of pleiotropy.

Conclusions

Our findings provide some evidence that higher maternal morning plasma cortisol causes lower birth weight. Identification of more independent genetic instruments for morning plasma cortisol are necessary to explore the potential bias identified.
Prophylactic pectoralis major flap to compensate for increased risk of pharyngocutaneous fistula in laryngectomy patients with low skeletal muscle mass (PECTORALIS): study protocol for a randomized controlled trial
Authors: van Beers Maartje A. , Speksnijder Caroline M. , van Gils Carla H. , Frederix Geert W.J. , Dankbaar Jan Willem , de Bree Remco
Published: January 2024

Background

Total laryngectomy (TL) is a surgical procedure commonly performed on patients with advanced laryngeal or hypopharyngeal carcinoma. One of the most common postoperative complications following TL is the development of a pharyngocutaneous fistula (PCF), characterized by a communication between the neopharynx and the skin. PCF can lead to extended hospital stays, delayed oral feeding, and compromised quality of life. The use of a myofascial pectoralis major flap (PMMF) as an onlay technique during pharyngeal closure has shown potential in reducing PCF rates in high risk patients for development of PCF such as patients undergoing TL after chemoradiation and low skeletal muscle mass (SMM). Its impact on various functional outcomes, such as shoulder and neck function, swallowing function, and voice quality, remains less explored. This study aims to investigate the effectiveness of PMMF in reducing PCF rates in patients with low SMM and its potential consequences on patient well-being.

Methods

This multicenter study adopts a randomized clinical trial (RCT) design and is funded by the Dutch Cancer Society. Eligible patients for TL, aged ≥ 18 years, mentally competent, and proficient in Dutch, will be enrolled. One hundred and twenty eight patients with low SMM will be centrally randomized to receive TL with or without PMMF, while those without low SMM will undergo standard TL. Primary outcome measurement involves assessing PCF rates within 30 days post-TL. Secondary objectives include evaluating quality of life, shoulder and neck function, swallowing function, and voice quality using standardized questionnaires and functional tests. Data will be collected through electronic patient records.

Discussion

This study’s significance lies in its exploration of the potential benefits of using PMMF as an onlay technique during pharyngeal closure to reduce PCF rates in TL patients with low SMM. By assessing various functional outcomes, the study aims to provide a comprehensive understanding of the impact of PMMF deployment. The anticipated results will contribute valuable insights into optimizing surgical techniques to enhance patient outcomes and inform future treatment strategies for TL patients.

Trial registration

NL8605, registered on 11-05-2020; International Clinical Trials Registry Platform (ICTRP).
A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol
Authors: Mastall Maximilian , Roth Patrick , Bink Andrea , Fischer Maranta Angela , Läubli Heinz , Hottinger Andreas Felix , Hundsberger Thomas , Migliorini Denis , Ochsenbein Adrian , Seystahl Katharina , Imbach Lukas , Hortobagyi Tibor , Held Leonhard , Weller Michael , Wirsching Hans-Georg
Published: January 2024

Background

Glioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma.

Methods/design

GLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland.

Trial registration

NCT05664464. Registered 23 December 2022.
Lnc-PSMA8-1 activated by GEFT promotes rhabdomyosarcoma progression via upregulation of mTOR expression by sponging miR-144-3p
Authors: Meng Lian , Shang Hao , Liu Qianqian , Li Zhenzhen , Wang Xiaomeng , Li Qianru , Li Feng , Zhao Zhenguo , Liu Chunxia
Published: January 2024

Background

GEFT is a key regulator of tumorigenesis in rhabdomyosarcoma (RMS), and overexpression of GEFT is significantly correlated with distant metastasis, lymph node metastasis, and a poor prognosis, yet the underlying molecular mechanism is still poorly understood. This study aimed to investigate and validate the molecular mechanism of GEFT-activated lncRNAs in regulating mTOR expression to promote the progression of RMS.

Methods

GEFT-regulated lncRNAs were identified through microarray analysis. The effects of GEFT-regulated lncRNAs on the proliferation, apoptosis, invasion, and migration of RMS cells were confirmed through cell functional experiments. The target miRNAs of GEFT-activated lncRNAs in the regulation of mTOR expression were predicted by bioinformatics analysis combined with quantitative real-time polymerase chain reaction (qRT–PCR) analysis. The expression of lnc-PSMA8-1, miR-144-3p, and mTOR was measured by qRT–PCR in RMS tissue samples and cell lines. The regulatory mechanisms of the lnc-PSMA8-1-miR-144-3p-mTOR signaling axis were verified by RNA-binding protein immunoprecipitation (RIP), a luciferase reporter assay, qRT–PCR analysis, Western blot analysis, and cell functional experiments.

Results

The microarray-based analysis identified 31 differentially expressed lncRNAs (fold change > 2.0, P < 0.05). Silencing the 4 upregulated lncRNAs (lnc-CEACAM19-1, lnc-VWCE-2, lnc-GPX7-1, and lnc-PSMA8-1) and overexpressing the downregulated lnc-FAM59A-1 inhibited the proliferation, invasion, and migration and induced the apoptosis of RMS cells. Among the factors analyzed, the expression of lnc-PSMA8-1, miR-144-3p, and mTOR in RMS tissue samples and cells was consistent with the correlations among their expression indicated by the lncRNA–miRNA–mRNA regulatory network based on the ceRNA hypothesis. lnc-PSMA8-1 promoted RMS progression by competitively binding to miR-144-3p to regulate mTOR expression.

Conclusion

Our research demonstrated that lnc-PSMA8-1 was activated by GEFT and that the former positively regulated mTOR expression by sponging miR-144-3p to promote the progression of RMS. Therefore, targeting this network may constitute a potential therapeutic approach for the management of RMS.