Search

Background: Innate immune deficiencies can impair both cellular and humoral immune responses. In contrast, other immune functions may appear normal, leading to increased susceptibility to specific pathogens, such as severe viral infections or Mendelian Susceptibility to Mycobacterial Disease (MSMD). Studying these deficiencies is essential for understanding the pathophysiology of these infectious diseases. Main body: While primary immunodeficiencies (PIDs) generally cause vulnerability to multiple infections, innate immunodeficiencies increase susceptibility to specific pathogens, despite normal immune responses to others. Patients with these deficiencies show normal immunoglobulins and lymphocyte subpopulations, complicating diagnosis. This review highlights genetic susceptibility to mycobacteria, pneumococci, herpes simplex virus, and candidiasis, emphasizing recognizing this subset of PIDs. Conclusion: This review highlights the diverse spectrum of genetic mutations contributing to defects in innate and intrinsic immunity, including Mendelian susceptibility to mycobacterial disease (MSMD), chronic mucocutaneous candidiasis, and predispositions to invasive bacterial and viral infections. Identifying key mutations in pathprovideh such as TLR3, IFN signaling, and IL-17A/F immunity provides valuable insights into the pathogenesis of these conditions. Our findings underscore the need for early genetic diagnosis and targeted interventions, particularly in regions with high undiagnosed cases, to reduce the morbidity and mortality associated with defects in innate and intrinsic immunity. [ABSTRACT FROM AUTHOR]

Due to differences in their feeding behavior, sheep and goats are often assumed to respond differently to helminth infections. The present study compared Haemonchus contortus infection profile between sheep and goats under the same experimental setting. Experimental infection was conducted using a randomized block design in four groups of intact sheep (InfSH and ConSH) and goats (InfG, and ConG). Groups InfSH and InfG (N = 7 each) received 10,000L3 of H. contortus whereas the control groups ConSH and ConG (N = 7 each) remained uninfected. Faecal egg counts and PCV were measured from Day 0 to day 56 post infection (PI). On day 56 PI, animals were humanely slaughtered and abomasal contents were recovered to measure worm burden, worm length and in utero egg count. The findings show that: (1) Haemonchus infected animals showed an increase in FEC starting from day 21 PI, (2) progressive reduction in PCV was registered from day 7 PI and continued to the end of the experiment while this remained at pre-infection levels in control groups, (3) FEC was much higher (P < 0.001) and PCV was significantly lower (P < 0.05) in infected goats than in infected sheep, (4) at necropsy, total worm burden with worm establishment rates of 63% and 28.87% were registered respectively for infected goats and sheep with significant difference (P < 0.05), (5) Female worms were significantly longer (P < 0.05) in InfG (22.8(± 1.2) compared to InfSH (20.5 ± 0.67 mm) while (6) Mean worm fecundity was 974.8 ± 239.4 and 1162.5 ± 89.4 respectively for groups InfSH and InfG with no significant difference (P = 0.07), and (7) Parasite traits such as worm burden, FEC and female worm length were well correlated in sheep whereas few such patterns were observed in goats. In conclusion, under the same experimental infection, Arsi-Bale goats are more susceptible to H. contortus infection than Arsi-Bale sheep and hence deserve special attention when they are forced to live on grazing rather than browsing. [ABSTRACT FROM AUTHOR]

The Li-ferrite and graphene oxide (GO) nanocomposites, denoted as (Li 0.5-x/2 ZnₓFe 2.5-x/2 O 4 : x = 0.25), were produced through ultrasonication. The wet method generated Li-ferrite, while the Hummers' method synthesized the GO. X-ray diffraction (XRD) was used to validate the development of Li-ferrite and GO in the nanocomposites. The dimensions of the crystal were determined between 41 and 52 nm, and the porosity of the composites increased with the higher quantity of GO. The scanning electron micrographs (SEM) of ferrites illustrated the formation of uniform and well-defined grains with consistent shapes, exhibiting properties well-suited for effective microwave absorption. The electrical resistance of spinel ferrite was measured at approximately 3.34 × 1011 Ω-cm and significantly lowered as the fraction of GO increased at ambient temperature. As per Maxwell Wagner's model, the electrical permittivity exhibited interfacial polarization with distinct real and imaginary components. The AC conductivity exhibited a positive correlation with the GO content due to the conductive properties of GO and the improved charge hopping mechanism. The frequency exponent parameter's value falls from 0.36 to 0.95 b y the Jonscher's Power law. The magnetic susceptibility of all the samples exhibited a progressive decrease as the temperature increased. The choice of using lithium-based ferrite as filler is made to strengthen the ferrite/GO composites and improve their magnetic and electrical properties. This is undertaken to harness these composites for high-frequency applications, such as their use as microwave absorbers in microwave devices. [ABSTRACT FROM AUTHOR]

Background: Dengue is a serious public health problem worldwide, including Panama. During the last years, the number of dengue cases has increased. This may be due to the presence of mosquito populations resistant to insecticides. The aim of this study was to characterize the resistance status, its enzymatic mechanisms and Kdr mutations in wild populations of Aedes aegypti and Aedes albopictus. Methods: Standard WHO bioassays were performed using insecticide-treated filter papers to determine resistance in populations Ae. aegypti and Ae. albopictus to pyrethroids insecticides, organophosphates, to the carbamate propoxur and to the organochlorine DDT. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the Kdr mutations Val1016IIe and F1534C. Results: The strains Ae. aegypti El Coco showed confirmed resistance to deltamethrin (78.5% mortality) and lambda-cyhalothrin (81%), Aguadulce to deltamethrin (79.3%), David to deltamethrin (74.8%) and lambda-cyhalothrin (87.5%) and Puerto Armuelles to permethrin (83%). Aedes aegypti El Empalme showed confirmed resistance to pirimiphos-methyl (62.3% mortality), chlorpyrifos-methyl (55.5%) and propoxur (85.3%). All strains of Ae. albopictus showed possible resistance to PYs and five strains to DDT. Only Ae. albopictus Canto del Llano showed confirmed resistance to pirimiphos-methyl (70% mortality) and malathion (62%). Esterase activity was variable across sites with the most frequent expression of α-EST compared to β-EST in Ae. aegypti populations. In Ae. Albopictus, the expressed enzymes were β-EST and MFOs. Through ANOVA, significant differences were established in the levels of enzymatic activity of α- and β-EST, MFOs and GST, with p < 0.001 in the Ae. aegypti and Ae. albopictus. The Kdr Val1016IIe mutation was detected in Ae. aegypti Aguadulce, El Coco and David. The odds ratio for the Val1016Ile mutation ranged from 0.8 to 20.8 in resistant mosquitoes, indicating the association between pyrethroid phenotypic resistance and the kdr mutation. Conclusion: The presence of a varied and generalized resistance, enzymatic mechanisms and the Val1016IIe mutation may be associated with the intensive use and possibly misuse of the different insecticides applied to control Aedes populations. These results highlight the need to develop a program for resistance management. Also, alternative approaches to mosquito control that do not involve insecticides should be explored. [ABSTRACT FROM AUTHOR]

Each life is challenged to adapt to an ever-changing environment with integrity—simply put, to maintain identity. We hypothesize that this mission statement of adaptive homeostasis is particularly poignant in an adaptive response, like inflammation. A maladaptive response of unresolved inflammation can seed chronic disease over a lifetime. We propose the concept of a molecular thumbprint: a biological signature of loss of identity as a measure of incomplete return to homeostasis after an inflammatory response. Over time, personal molecular thumbprints can measure dynamic and precise trajectories to chronic inflammatory diseases and further loss of self to cancer. Why is this important? Because the phenotypes and molecular signatures of established complex inflammatory diseases are a far cry from the root of the complex problem, let alone the initial seed. Understanding the science behind key germinating seeds of disease helps to identify molecular factors of susceptibility, resilience, and early dietary or drug intervention. We pilot this hypothesis in a rat colitis model that is well-established for understanding molecular mechanisms of colonic health, disease, and transition of colitis to cancer. [ABSTRACT FROM AUTHOR]

The transboundary Arun River Basin (ARB) spreads across Nepal and Tibet. Nearly 95% of the basin lies in Tibet through which the Pumqu River flows, forming the Arun River once it enters Nepal. The ARB has five large hydropower projects undergoing construction or planned for the future. Rainfall and earthquake‐induced landslides, landslide‐dammed lakes and landslide‐induced glacial lake outburst floods pose major risks to smooth operation of these projects. To safeguard upcoming hydropower projects, areas susceptible to landslides in the ARB must be identified. We used high‐resolution satellite imagery and open‐source tools to generate a multitemporal landslide inventory for the basin. The rigorously quality‐controlled inventory represents a yearly record of landslides from 2011 to 2020. A data‐driven approach was used to map areas susceptible to landslides within the ARB. The multitemporal landslide inventory combined with other readily available Earth observation‐based variables was used to create a landslide susceptibility map. The susceptibility analysis provides a valuable initial estimate of where landslides are likely to initiate. These landslide products could form the basis of more comprehensive local studies to inform hydropower project development. [ABSTRACT FROM AUTHOR]

RNA editing is increasingly recognized as a post-transcriptional modification that directly affects viral infection by regulating RNA stability and recoding proteins. the duck hepatitis A virus genotype 3 (DHAV-3) infection is seriously detrimental to the Asian duck industry. However, the landscape and roles of RNA editing in the susceptibility and resistance of Pekin ducks to DHAV-3 remain unclear. Here, we profiled dynamic RNA editing events in liver tissue and investigated their potential functions during DHAV-3 infection in Pekin ducks. We identified 11,067 informative RNA editing sites in liver tissue from DHAV-3-susceptible and -resistant ducklings at three time points during virus infection. Differential RNA editing sites (DRESs) between S and R ducks were dynamically changed during infection, which were enriched in genes associated with vesicle-mediated transport and immune-related pathways. Moreover, we predicted and experimentally verified that RNA editing events in 3′-UTR could result in loss or gain of miRNA–mRNA interactions, thereby changing the expression of target genes. We also found a few DRESs in coding sequences (CDSs) that altered the amino acid sequences of several proteins that were vital for viral infection. Taken together, these data suggest that dynamic RNA editing has significant potential to tune physiological processes in response to virus infection in Pekin ducks, thus contributing to host differential susceptibility to DHAV-3. [ABSTRACT FROM AUTHOR]

Impurity models describe localized impurities interacting with the spins of electrons. Strong correlations lead to non-trivial behaviours of the model. In this work we present 3 different impurity models: (1) the single-impurity Kondo model; (2) the two-impurity Kondo model; (3) the two-channel Kondo model. For each model we present a spin chain emulation and utilize the density matrix renormalization group (DMRG). We study the magnetization and zero-temperature susceptibility of the impurity when a local magnetic field is applied. We get the expected relations theoretically. [ABSTRACT FROM AUTHOR]

Pythium insidiosum is an important oomycete pathogen of mammals that causes pythiosis, an endemic disease in warm climates that stands out for its unfavorable prognosis, lethality in the affected species, and difficulties in treatment. This study evaluated in vitro anti-P. insidiosum potential of aqueous, hydroethanolic, and ethanolic extracts of indigenous wild mushrooms from southern Brazil. The extracts were prepared from Amanita gemmata, Amanita muscaria, Auricularia auricula, Gymnopilus junonius, Lactarius deliciosus, Laccaria laccata, Psilocybe cubensis, and Russula xerampelina. In vitro susceptibility assays employed the microdilution technique according to the M38-A2 protocol CLSI. The hydroethanolic and ethanolic extracts of R. xerampelina showed anti-P. insidiosum activity at minimum inhibitory concentrations ranging from 1.87--7.50 mg/mL. The other mushroom species extracts showed no inhibitory effects on growth of P. insidiosum. This is the first study to evaluate the antimicrobial activity of mushrooms on oomycetes, evidencing the antimicrobial potential of R. xerampelina on the pathogen P. insidiosum. So, the present study expands new perspectives, since the secondary metabolites produced by mushrooms can be potential targets for the development of new categories of medicines. However, considering the wide biodiversity of Brazilian mushrooms, we suggested that the search for other basidiomycetes species with anti-P. insidiosum action needs to be expanded. [ABSTRACT FROM AUTHOR]

Copyright of GeSec: Revista de Gestao e Secretariado is the property of Sindicato das Secretarias e Secretarios do Estado de Sao Paulo (SINSESP) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: SQ109 is a promising candidate drug for the treatment of patients with drug-resistant tuberculosis (DR-TB). The purpose of this study was to investigate the activity of SQ109 against clinical isolates of Mycobacterium tuberculosis (MTB) from patients with multidrug-resistant TB (MDR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB), and to explore new drug-resistant mechanisms of SQ109. Methods: We evaluated the in vitro activity of SQ109 against clinical isolates from patients with MDR-TB and pre-XDR-TB using minimal inhibitory concentration (MIC) assay. The drug-resistant gene, mmpL3 of SQ109-resistant strains was sequenced, and a quantitative real-time PCR assay was used to analyze 28 efflux pump genes in SQ109-resistant strains without mmpL3 mutations. The role of candidate efflux pumps mmpL5 and mmpL7 on the MIC of SQ109 was evaluated using recombinantly cloned MmpL5 and MmpL7 expressed in Mycobacterium smegmatis. Results: The MIC90, MIC95 and MIC99 values of SQ109 for 225 clinical isolates of MTB were 0.25 mg/L, 0.5 mg/L and 1.0 mg/L, respectively. Among the pre-XDR strains, six showed resistance to SQ109 despite the absence of gene mutations in mmpL3. In six resistant pre-XDR strains, the MIC of SQ109 decreased with the use of an efflux pump inhibitor, and there was significant upregulation of mmpL5 and mmpL7 in two strains after exposure to SQ109. The presence of MmpL7 in Mycobacterium smegmatis resulted in decreased susceptibility to SQ109, with the MIC increasing from 16 mg/L to 32 mg/L. Conclusions: Our data demonstrated that SQ109 exhibited excellent levels of in vitro activity against MTB. MmpL7 may be a potential gene for MTB resistance to SQ109, providing a useful target for detecting SQ109 resistance in MTB. [ABSTRACT FROM AUTHOR]

Background: Previous studies have investigated the association between the haptoglobin rs72294371 polymorphism and coronary artery disease (CAD) risk, but the results are controversial and uncertain. Therefore, this study aimed to systematically review the literature on haptoglobin polymorphism and susceptibility to CAD. Methods: PubMed, Embase, Web of Science, Cochrane Library, and Wanfang databases were used to identify relevant studies from their inception to April 2024. The pooled odds ratio (OR) with corresponding 95% confidence interval (CI) were used to assess the strength of the association. An OR value greater than one suggested an increased risk; otherwise, it suggested a protective risk. Results: A total of 15 studies comprising 8,632 individuals (2,988 cases and 5,644 controls) were included. In the current meta-analysis, a significant association between haptoglobin polymorphism and CAD was found under recessive model (OR:0.74, 95% CI:0.60-0.92), dominant model (OR: 0.82, 95% CI: 0.71-0.95), homozygote model (OR: 0.70, 95% CI: 0.53-0.92), and allelic genetic model (OR: 0.80, 95% CI: 0.69-0.94). In the analysis stratified by ethnicity, a statistically significant association was observed in Asians rather than Caucasian population. Conclusion: This meta-analysis indicates that haptoglobin polymorphism is associated with CAD susceptibility, especially in Asians. [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer, as the most prevalent malignancy among women globally, continues to exhibit rising incidence rates, particularly in China. The disease predominantly affects women aged 40 to 60 and is influenced by both genetic and environmental factors. This study focuses on the role of H19 gene polymorphisms, investigating their impact on breast cancer susceptibility, clinical outcomes, and response to treatment. Methods: We engaged 581 breast cancer patients and 558 healthy controls, using TaqMan assays and DNA sequencing to determine genotypes at specific loci (rs11042167, rs2071095, rs2251375). We employed in situ hybridization and immunohistochemistry to measure the expression levels of LincRNA H19, miR675, MRP3, HOXA1, and MMP16 in formalin-fixed, paraffin-embedded samples. Statistical analyses included chi-squared tests, logistic regression, and KaplanMeier survival curves to evaluate associations between genetic variations, gene expression, and clinical outcomes. Results: Genotypes AG at rs11042167, GT at rs2071095, and AC at rs2251375 were significantly associated with increased risk of breast cancer. Notably, the AA genotype at rs11042167 and TT genotype at rs2071095 were linked to favorable prognosis. High expression levels of LincRNA H19, miR-675, MRP3, HOXA1, and MMP16 in cancer tissues correlated with advanced disease stages and poorer survival rates. Spearman correlation analysis revealed significant positive correlations between the expression of LincRNA H19 and miR-675 and specific genotypes, highlighting their potential regulatory roles in tumor progression. Discussion: The study underscores the critical roles of LincRNA H19 and miR675 as prognostic biomarkers in breast cancer, with their overexpression associated with disease progression and adverse outcomes. The H19/LincRNA H19/miR-675/MRP3-HOXA1-MMP16 axis offers promising targets for new therapeutic strategies, reflecting the complex interplay between genetic markers and breast cancer pathology. Conclusion: The findings confirm that certain H19 SNPs are associated with heightened breast cancer risk and that the expression profiles of related genetic markers can significantly influence prognosis and treatment response. These biomarkers hold potential as targets for personalized therapy and early detection strategies in breast cancer, underscoring the importance of genetic research in understanding and managing this disease. [ABSTRACT FROM AUTHOR]

Objective: Apolipoprotein E (APOE) gene polymorphisms were associated with coronary atherosclerosis and hypertension. However, the relationship between APOE polymorphisms and coronary atherosclerosis susceptibility in hypertensive patients is unclear. The aim of this study was to assess the relationship. Methods: A total of 1713 patients with hypertension who were admitted to Meizhou People's Hospital from November 2019 to August 2023 were retrospectively analyzed, including 848 patients with coronary atherosclerosis and 865 patients without coronary atherosclerosis. The rs429358 and rs7412 polymorphisms of APOE were genotyped, and relationship between APOE polymorphisms and the risk of coronary atherosclerosis in hypertensive patients were analyzed. Results: There were 10 (0.6%), 193 (11.3%), 30 (1.8%), 1234 (72.0%), 233 (13.6%), and 13 (0.8%) individuals with APOE ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4 genotype, respectively. The frequency of APOE ɛ3/ɛ4 was higher (16.4% vs. 10.9%, p = 0.001) in the patients with coronary atherosclerosis than controls. Logistic analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (24.0 kg/m2 vs. 18.5–23.9 kg/m2, odds ratio (OR): 1.361, 95% confidence interval (CI): 1.112–1.666, p = 0.003), advanced age (≥ 65/<65, OR:1.303, 95% CI: 1.060–1.602, p = 0.012), history of smoking (OR: 1.830, 95% CI: 1.379–2.428, p < 0.001), diabetes mellitus (OR: 1.380, 95% CI: 1.119–1.702, p = 0.003), hyperlipidemia (OR: 1.773, 95% CI: 1.392–2.258, p < 0.001), and APOE ɛ3/ɛ4 genotype (ɛ3/ɛ4 vs. ɛ3/ɛ3, OR: 1.514, 95% CI: 1.133–2.024, p = 0.005) were associated with coronary atherosclerosis in hypertensive patients. Conclusions: Overweight (BMI ≥ 24.0 kg/m2), advanced age, history of smoking, diabetes mellitus, and APOE ɛ3/ɛ4 genotype were independent risk factors for coronary atherosclerosis in hypertensive patients. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aims to clarify the association between the TNF-α -308G > A and − 238G > A polymorphisms and lung cancer risk. Method: A comprehensive search was conducted for relevant articles across databases such as PubMed, Google Scholar, Web of Science, EMBASE, and CNKI, up to September 25, 2023. Lung cancer risk was assessed by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). The Z-test was used to determine the significance of combined ORs, with P < 0.05 considered statistically significant. All analyses were performed using Comprehensive Meta-Analysis (CMA) 2.0 software. Results: The analysis included 19 case-control studies with 3,838 cases and 5,306 controls for the TNF-α -308G > A polymorphism, along with 10 studies comprising 2,427 cases and 2,357 controls for the − 238G > A polymorphism. The − 308G > A polymorphism showed no significant overall relationships, though in the Asian subgroup, the A allele was significantly reduced compared to G (OR: 0.831, p = 0.028) and the AA genotype showed significant reductions versus GG (OR: 0.571, p = 0.021), with no significant correlation in Caucasians. In non-small cell lung cancer (NSCLC), the A allele was associated with increased risk compared to G (OR: 1.131, p = 0.049). For the − 238G > A polymorphism, the AA genotype significantly increased risk compared to GG (OR: 3.171, p = 0.014), while showing a protective effect in Caucasians (OR: 0.120, p = 0.024) and a heightened risk in Asians (OR: 7.990, p = 0.007). In small cell lung cancer (SCLC), the A allele conferred protective effects, whereas NSCLC showed increased risk for the AA genotype (OR: 11.375, p = 0.002). Conclusion: The − 308G > A polymorphism has no significant overall relationships but suggests a protective role of the A allele in the Asian subgroup. Conversely, the − 238G > A polymorphism presents a complex risk profile, increasing lung cancer likelihood in Asians while protecting Caucasians. Notably, the AA genotype significantly raises risk for NSCLC, indicating its potential as a risk factor. [ABSTRACT FROM AUTHOR]

Purpose: Susceptibility map weighted imaging (SMWI), based on quantitative susceptibility mapping (QSM), allows accurate nigrosome-1 (N1) evaluation and has been used to develop Parkinson’s disease (PD) deep learning (DL) classification algorithms. Neuromelanin-sensitive (NMS) MRI could improve automated quantitative N1 analysis by revealing neuromelanin content. This study aimed to compare classification performance of four approaches to PD diagnosis: (1) N1 quantitative “QSM-NMS” composite marker, (2) DL model for N1 morphological abnormality using SMWI (“Heuron IPD”), (3) DL model for N1 volume using SMWI (“Heuron NI”), and (4) N1 SMWI neuroradiological evaluation. Method: PD patients (n = 82; aged 65 ± 9 years; 68% male) and healthy-controls (n = 107; 66 ± 7 years; 48% male) underwent 3 T midbrain MRI with T2*-SWI multi-echo-GRE (for QSM and SMWI), and NMS-MRI. AUC was used to compare diagnostic performance. We tested for correlation of each imaging measure with clinical parameters (severity, duration and levodopa dosing) by Spearman-Rho or Kendall-Tao-Beta correlation. Results: Classification performance was excellent for the QSM-NMS composite marker (AUC = 0.94), N1 SMWI abnormality (AUC = 0.92), N1 SMWI volume (AUC = 0.90), and neuroradiologist (AUC = 0.98). Reasons for misclassification were right–left asymmetry, through-plane re-slicing, pulsation artefacts, and thin N1. In the two DL models, all 18/189 (9.5%) cases misclassified by Heuron IPD were controls with normal N1 volumes. We found significant correlation of the SN QSM-NMS composite measure with levodopa dosing (rho = −0.303, p = 0.006). Conclusion: Our data demonstrate excellent performance of a quantitative QSM-NMS marker and automated DL PD classification algorithms based on midbrain MRI, while suggesting potential further improvements. Clinical utility is supported but requires validation in earlier stage PD cohorts. [ABSTRACT FROM AUTHOR]

Diabetic Nephropathy (DN) stands as a primary cause of end-stage renal disease and its etiology remains unclear. Thus, this study aims to construct a genetic panel with potential biomarkers linked to the inflammatory pathway of DN associated with the pathology's susceptibility. Through a systematic review and meta-analysis, we selected observational studies in English, Portuguese, and Spanish, selected from the PubMed, SCOPUS, Virtual Health Library, Web of Science, and EMBASE databases. Additionally, a protein–protein interaction network was constructed to list hub genes, with differential expression analysis by microarray of kidneys with DN from the GSE30529 database to further refine results. Seventy-two articles were included, and 54 polymorphisms in 37 genes were associated with the inflammatory pathway of DN. Meta-analysis indicated a higher risk of complication associated with SNPs 59029 G/A, −511 C/T, VNTR 86 bp, −308 G/A, and −1031 T/C. Bioinformatics analyses identified differentially expressed hub genes, underscoring the scarcity of studies on CCL2 and VEGF-A genes in relation to DN. This study highlighted the intrinsic relationship between inflammatory activity in the etiology and progression of DN, enabling the effective application of precision medicine in diabetic patients for potential prognosis of the complications and contributing to cost reduction in the public health system. [ABSTRACT FROM AUTHOR]

Most high-mountain regions worldwide are susceptible to snow avalanches during the winter or all year round. In this study, a Universal Snow Avalanche Modeling Index is developed, suitable for determining avalanche hazard in mountain regions. The first step in the research is the collection of data in the field and their processing in geographic information systems and remote sensing. In the period 2023–2024, avalanches were mapped in the field, and later, avalanches as points in geographic information systems (GIS) were overlapped with the dominant natural conditions in the study area. The second step involves determining the main criteria (snow cover, terrain slope, and land use) and evaluating the values to obtain the Snow Avalanche Formation Index (SAFI). Thresholds obtained through field research and the formation of avalanche inventory were used to develop the SAFI index. The index is applied with the aim of identifying locations susceptible to avalanche formation (source areas). The values used for the calculation include Normalized Difference Snow Index (NDSI > 0.6), terrain slope (20–60°) and land use (pastures, meadows). The third step presents the analysis of SAFI locations with meteorological conditions (winter precipitation and winter air temperature). The fourth step is the modeling of the propagation (simulation) of other parts of the snow avalanche in the Flow-R software 2.0. The results show that 282.9 km2 of the study area (Šar Mountains, Serbia) is susceptible to snow avalanches, with the thickness of the potentially triggered layer being 50 cm. With a 5 m thick snowpack, 299.9 km2 would be susceptible. The validation using the ROC-AUC method confirms a very high predictive power (0.94). The SAFI–Flow-R approach offers snow avalanche modeling for which no avalanche inventory is available, representing an advance for all mountain areas where historical data do not exist. The results of the study can be used for land use planning, zoning vulnerable areas, and adopting adequate environmental protection measures. [ABSTRACT FROM AUTHOR]

Copyright of Hydrogeology & Engineering Geology / Shuiwendizhi Gongchengdizhi is the property of Hydrogeology & Engineering Geology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Hydrogeology & Engineering Geology / Shuiwendizhi Gongchengdizhi is the property of Hydrogeology & Engineering Geology Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Uropathogens are microorganisms that cause urinary tract infections (UTIs). Owing to higher blood glucose levels and compromised immune functions, treatment of uropathogens in diabetic patients is a challenge. Aim: This study aims to assess the prevalence of uropathogens and their antibiotic susceptibility among diabetic patients at St. John of God Hospital at Duayaw Nkwanta (SJGHDN) in the Ahafo region of Ghana. Methods: The cross‐sectional study recruited 175 diabetic patients at SJGHDN between August and September 2023. Questionnaires were used to collect patients' background information. Fasting Blood Sugar (FBS) was assessed by using a glucometer. Urine samples were examined for the presence of uropathogens. A sterile inoculating loop with a calibrated volume of 2 µl was used for plating. Each colony equals 500 CFU/mL. Significant uropathogen was determined by multiplying the counted colonies by 500 to obtain CFU/mL. Positive uropathogen was defined as CFU ≥ 105/mL. Significant uropathogen was defined as ≥200 colonies per sample. The disc diffusion method was used to determine antibiotic susceptibility. Results: Out of the 175 patients, 19.4% expressed various uropathogens with Escherichia coli being the predominant. Suboptimal glucose level was the most significant risk factor (p = 0.038). Glucosuria (p = 0.036), hazy urine (p = 0.028), positive leukocyte esterase (p = 0.001), and pus cells in urine sediment (p = 0.020) were significant indicators of uropathogen occurrence. Klebsiella pneumonia and Proteus mirabilis were resistant to ≥4 antibiotics. Amikacin, nitrofurantoin, levofloxacin, ciprofloxacin, and ceftriaxone demonstrated efficacy against the isolates. Conclusion: This study underscores the notable prevalence of uropathogens in diabetic patients and the alarming levels of antibiotic resistance observed. The results highlight the critical need for vigilant monitoring and customized treatment approaches, particularly for diabetic patients exhibiting risk factors such as elevated urine glucose levels, cloudy urine, and presence of leukocyte esterase and pus cells in urine sediment. The significant resistance to frequently used antibiotics like co‐trimoxazole and tetracycline points to the necessity of routine susceptibility testing and the use of alternative antibiotics for effective treatment. These findings can assist healthcare providers in more effectively managing and preventing UTIs in diabetic populations. [ABSTRACT FROM AUTHOR]

The present study demonstrated the differences in the seed metabolome and mycobiome of two Aegilops tauschii Coss accessions with different resistance to brown rust and powdery mildew. We hypothesized that the seeds of resistant accession k-1958 Ae. tauschii ssp. strangulata can contain a larger number of metabolites with antifungal activity compared with the seeds of susceptible Ae. tauschii ssp meyeri k-340, which will determine differences in the seed fungal community. Our study emphasizes the differences in the seed metabolome of the studied Ae. tauschii accessions. The resistant accession k-1958 had a higher content of glucose and organic acids, including pyruvic, salicylic and azelaic acid, as well as pipecolic acids, galactinol, glycerol and sitosterol. The seeds of Ae. tauschii-resistant accession k-1958 were found to contain more active substances with antifungal activity. The genera Cladosporium and Alternaria were dominant in the seed mycobiome of the resistant accession. The genera Alternaria, Blumeria and Cladosporium dominated in seed mycobiome of susceptible accession k-340. In the seed mycobiome of the resistant k-1958, a higher occurrence of saprotrophic micromycetes was found, and many of the micromycetes were biocontrol agents. It was concluded that differences in the seed metabolome of Ae. tauschii contributed to the determination of the differences in mycobiomes. [ABSTRACT FROM AUTHOR]

It is increasingly important to rapidly receive information on the antimicrobial susceptibility of bacteria due to the rise in antimicrobial resistance worldwide. However, traditional phenotypic methods are time-consuming. Thus, the objective of this study was to develop a rapid assay that can detect antibiotic-resistant bacterial isolates phenotypically in less than 2 h. The microplate assay used in this study is based on absorbance measurements of pure bacterial isolates grown in liquid media with and without antibiotics. Absorbance was measured at the beginning of the assay and after 90 min of incubation at 37 °C. Susceptibility was calculated for bacterial isolates that, in the absence of antibiotics, exhibited more than a 50% growth increase by comparing the absorbance value of the culture in the presence of an antibiotic at 90 min with its initial value. Here, we show that it is possible to phenotypically screen the antibiotic susceptibility of Enterobacterales and Acinetobacter spp. isolates to three different antibiotics in 90 min. The test demonstrated an accuracy of 98.8%, sensitivity of 97.6%, and specificity of 99.6%. The false susceptibility rates were 0.2% and false resistance rates were 1.0%. This rapid and simple absorbance test has proven suitable for the screening of antibiotic susceptibility for a large number of strains with high accuracy and sensitivity. This method can be performed without specialized and costly materials and/or equipment, which makes it highly suitable for laboratories with limited resources. [ABSTRACT FROM AUTHOR]

Aim: MIR137 host gene (MIR137HG) variants were involved in a variety of diseases, but its role in high-altitude pulmonary edema (HAPE) has not been reported. The study aimed to study the association between MIR137HG single-nucleotide polymorphisms and HAPE risk in the Chinese population. Materials & methods: Based on the Plink software, odds ratio and 95% confidence interval were used for logistic regression analysis to evaluate the association between MIR137HG polymorphisms and the risk of HAPE. Results: We discovered that MIR137HG rs7554283 was associated with a reduced risk of HAPE. In both individuals older than 32 years and those younger than 32 years, we observed that rs7554283 was associated with a decreased risk of HAPE. Conclusion: In conclusion, MIR137HG rs7554283 may be related to a reduced susceptibility to HAPE in the Chinese population. These results provide a theoretical basis for the role of MIR137HG single-nucleotide polymorphisms in the occurrence of HAPE. Article highlights MIR137 host gene (MIR137HG) variants were involved in a variety of diseases, but its role in high-altitude pulmonary edema (HAPE) has not been reported. The overall analysis showed that MIR137HG rs7554283 was associated with a reduced risk of HAPE. In both individuals older than 32 years and those younger than 32 years, we observed that rs7554283 was associated with a decreased risk of HAPE. In conclusion, MIR137HG rs7554283 may be related to a reduced susceptibility to HAPE in the Chinese population. [ABSTRACT FROM AUTHOR]

The decline of oak canopies in Iberian woodlands is strongly influenced by abiotic and biotic stress factors, such as the oomycete Phytophthora cinnamomi which has the capacity to infect a wide range of plant species. Understory plant diversity plays an important role in the epidemiology of P. cinnamomi in these ecosystems. This study aimed to identify a set of woody and herbaceous plants that can impact oak decline. Twenty-two herbaceous plant species from three families, and nineteen woody plants (trees and shrubs) from seven families were assessed for their response to infection by P. cinnamomi. Most of the herbaceous species did not show evident susceptibility, only a few exhibited significant biomass root reduction and just seven were identified as hosts. Yellow lupin was the only herbaceous species showing high susceptibility. Among the woody plant species, only two shrub and two tree species exhibited disease symptoms. The other ones, mostly hosts, ranged between low susceptible and tolerant. These results highlight the possibility that many of these species can maintain the pathogen active in the soil or even increase its population. In this context, the findings of this study can contribute to effective management strategies to mitigate Phytophthora infection in woodland soils. [ABSTRACT FROM AUTHOR]

Coastal erosion has posed significant challenges to sustainability and socio-economic stability along Senegal's coastline, leading to substantial infrastructure losses. Using GIS multi-criteria decision analysis (MCDA), two sub-indices were derived for Senegal's coastal departments: the physical susceptibility (PSI) and the social-economic vulnerability (SVI) to coastal erosion. The integrated coastal erosion vulnerability (ICER) model was derived by their aggregation. A total of 26 criteria were used, 18 for PSI and 8 for SVI. The criteria weighting coefficients of the sub-indices were determined using the analytic hierarchy process (AHP). Validation of the model accuracy was performed using receiver operating characteristic (ROC) curves that were calculated based on a created coastal erosion cadaster and true positive (TP) sites and manually acquired true negative (TN) sites. The accuracy assessment confirmed the consistency of the physical susceptibility model (PSI) and proved that existing coastal erosion sites are within (5) very high susceptibility areas. Through the generated ICER, the coastal departments were divided into areas of (1) very low, (2) low, (3) medium, (4) high and (5) very high vulnerability to coastal erosion. Very high (5) and high (4) classes cover around 31% of the coastal departments, mostly encompassing a narrow coastal strip and low river valleys and mouths. The presented coastal susceptibility and vulnerability maps, with a spatial resolution of 30 m, identified problematic areas in Senegal's coastal departments and can help decision-makers in the construction of effective coastal zone management and sustainable development. [ABSTRACT FROM AUTHOR]

Abstract Background Innate immune deficiencies can impair both cellular and humoral immune responses. In contrast, other immune functions may appear normal, leading to increased susceptibility to specific pathogens, such as severe viral infections or Mendelian Susceptibility to Mycobacterial Disease (MSMD). Studying these deficiencies is essential for understanding the pathophysiology of these infectious diseases. Main body While primary immunodeficiencies (PIDs) generally cause vulnerability to multiple infections, innate immunodeficiencies increase susceptibility to specific pathogens, despite normal immune responses to others. Patients with these deficiencies show normal immunoglobulins and lymphocyte subpopulations, complicating diagnosis. This review highlights genetic susceptibility to mycobacteria, pneumococci, herpes simplex virus, and candidiasis, emphasizing recognizing this subset of PIDs. Conclusion This review highlights the diverse spectrum of genetic mutations contributing to defects in innate and intrinsic immunity, including Mendelian susceptibility to mycobacterial disease (MSMD), chronic mucocutaneous candidiasis, and predispositions to invasive bacterial and viral infections. Identifying key mutations in pathprovideh such as TLR3, IFN signaling, and IL-17A/F immunity provides valuable insights into the pathogenesis of these conditions. Our findings underscore the need for early genetic diagnosis and targeted interventions, particularly in regions with high undiagnosed cases, to reduce the morbidity and mortality associated with defects in innate and intrinsic immunity.

Bladder cancer is one of the most common malignant tumors in the urinary system. There are a large number of bladder cancer patients globally, concentrated in the middle-aged and old-aged population, and some of them are first diagnosed with muscle invasive bladder cancer or metastatic bladder cancer, with a poor prognosis. In China, bladder cancer has become one of the most important tumors of the urinary system, with its incidence and mortality increasing year by year. The susceptibility of bladder cancer is affected by a combination of environmental and genetic factors, similar to the global trend. Smoking is considered to be one of the most important environmental risk factors for bladder cancer, which is closely related to the pathogenesis of bladder cancer and is one of the major public health problems in China. In terms of genetics, previous studies have shown that polymorphisms in cell cycle regulatory genes, tumor angiogenesis regulatory genes, DNA damage repair genes, and carcinogen metabolism enzyme regulatory genes can significantly affect the risk of bladder cancer in individuals. In recent years, with the development of environmental genomics research, the joint effect of smoking and gene variants on the susceptibility to bladder cancer has also received widespread attention. Exploring the joint effects will help to identify potential susceptibility biomarkers of bladder cancer and provide an important theoretical basis for its prevention and control. In this review, the joint effects of smoking and gene variants on bladder cancer susceptibility were elaborated.

Abstract Due to differences in their feeding behavior, sheep and goats are often assumed to respond differently to helminth infections. The present study compared Haemonchus contortus infection profile between sheep and goats under the same experimental setting. Experimental infection was conducted using a randomized block design in four groups of intact sheep (InfSH and ConSH) and goats (InfG, and ConG). Groups InfSH and InfG (N = 7 each) received 10,000L3 of H. contortus whereas the control groups ConSH and ConG (N = 7 each) remained uninfected. Faecal egg counts and PCV were measured from Day 0 to day 56 post infection (PI). On day 56 PI, animals were humanely slaughtered and abomasal contents were recovered to measure worm burden, worm length and in utero egg count. The findings show that: (1) Haemonchus infected animals showed an increase in FEC starting from day 21 PI, (2) progressive reduction in PCV was registered from day 7 PI and continued to the end of the experiment while this remained at pre-infection levels in control groups, (3) FEC was much higher (P

Abstract Objectives South Africa was the worst affected country in Africa by the COVID-19 pandemic and it is important to interrogate the attitude of the populace towards the pandemic for future interventions. Therefore, this study examined effects of mass media messages, susceptibility to COVID-19 and self-rated health on the attitudes of South Africans towards the COVID-19 pandemic. Methods Data was from the National Income Dynamics Study – Coronavirus Rapid Mobile Survey (NIDS-CRAM) of 2021 which is a nationally representative panel survey of about 7,000 South African individuals in all the nine provinces. Analyses of data were through descriptive statistics, chi square test and logistic regression models. Results The results showed that 61.28% of the resondents did not take COVID-19 test while 91.09% of them engaged in behavioral changes such as social distancing and wearing of face masks. In addition, 74.27% of the respondents had access to mass media information, 70.44% believed they have good physical health while 32.43% felt they were not susceptible to COVID-19. The chi-square results of attitude towards COVID-19 showed significant differences in access to mass media messages on COVID-19, race, and province of residence. Furthermore, respondents who had access to mass media information on COVID-19 (OR = 1.469; p = 0.001) and respondents who believed that they were susceptible to COVID-19 infection (OR = 1.443; p = 0.001) were significantly associated with increased likelihood of engagement in behavioral changes to avoid the COVID-19. Conclusion These findings therefore emphasize the need for increased awareness and sensitization of the people about the susceptibility and adverse effects of diseases to ensure that they adopt the appropriate attitudes that will safeguard them from such diseases outbreak.

Abstract The transboundary Arun River Basin (ARB) spreads across Nepal and Tibet. Nearly 95% of the basin lies in Tibet through which the Pumqu River flows, forming the Arun River once it enters Nepal. The ARB has five large hydropower projects undergoing construction or planned for the future. Rainfall and earthquake‐induced landslides, landslide‐dammed lakes and landslide‐induced glacial lake outburst floods pose major risks to smooth operation of these projects. To safeguard upcoming hydropower projects, areas susceptible to landslides in the ARB must be identified. We used high‐resolution satellite imagery and open‐source tools to generate a multitemporal landslide inventory for the basin. The rigorously quality‐controlled inventory represents a yearly record of landslides from 2011 to 2020. A data‐driven approach was used to map areas susceptible to landslides within the ARB. The multitemporal landslide inventory combined with other readily available Earth observation‐based variables was used to create a landslide susceptibility map. The susceptibility analysis provides a valuable initial estimate of where landslides are likely to initiate. These landslide products could form the basis of more comprehensive local studies to inform hydropower project development.

Abstract Background Dengue is a serious public health problem worldwide, including Panama. During the last years, the number of dengue cases has increased. This may be due to the presence of mosquito populations resistant to insecticides. The aim of this study was to characterize the resistance status, its enzymatic mechanisms and Kdr mutations in wild populations of Aedes aegypti and Aedes albopictus. Methods Standard WHO bioassays were performed using insecticide-treated filter papers to determine resistance in populations Ae. aegypti and Ae. albopictus to pyrethroids insecticides, organophosphates, to the carbamate propoxur and to the organochlorine DDT. Biochemical assays were conducted to detect metabolic resistance mechanisms and real-time PCR was performed to determine the frequencies of the Kdr mutations Val1016IIe and F1534C. Results The strains Ae. aegypti El Coco showed confirmed resistance to deltamethrin (78.5% mortality) and lambda-cyhalothrin (81%), Aguadulce to deltamethrin (79.3%), David to deltamethrin (74.8%) and lambda-cyhalothrin (87.5%) and Puerto Armuelles to permethrin (83%). Aedes aegypti El Empalme showed confirmed resistance to pirimiphos-methyl (62.3% mortality), chlorpyrifos-methyl (55.5%) and propoxur (85.3%). All strains of Ae. albopictus showed possible resistance to PYs and five strains to DDT. Only Ae. albopictus Canto del Llano showed confirmed resistance to pirimiphos-methyl (70% mortality) and malathion (62%). Esterase activity was variable across sites with the most frequent expression of α-EST compared to β-EST in Ae. aegypti populations. In Ae. Albopictus, the expressed enzymes were β-EST and MFOs. Through ANOVA, significant differences were established in the levels of enzymatic activity of α- and β-EST, MFOs and GST, with p

Abstract Background Malaria is a serious public health concern. Artemisinin and its derivatives are first-line drugs for the treatment of Plasmodium falciparum malaria. In mammals, artemisinin exhibits potent anti-inflammatory and immunoregulatory properties. However, it is unclear whether artemisinin plays a regulatory role in the innate immunity of mosquitoes, thereby affecting the development of Plasmodium in Anopheles when artemisinin and its metabolites enter mosquitoes. This study aims to determine the effect of dihydroartemisinin (DHA), a first-generation semisynthetic derivative of artemisinin, on innate immunity and malaria vector competence of Anopheles stephensi. Methods Anopheles stephensi was fed Plasmodium-infected mice treated with DHA via gavage, Plasmodium-infected blood containing DHA in vitro, or DHA-containing sugar, followed by Plasmodium yoelii infection. The engorged female mosquitoes were separated and dissected 8 and 17 days after infection. Plasmodium oocysts and sporozoites were counted and compared between the control and DHA-treated groups. Additionally, total RNA and proteins were extracted from engorged mosquitoes 24 and 72 h post infection (hpi). Real-time polymerase chain reaction (PCR) and western blotting were performed to detect the transcriptional levels and protein expression of immune molecules in mosquitoes. Finally, the Toll signaling pathway was inhibited via RNA interference and the infection density was analyzed to confirm the role of the Toll signaling pathway in the effect of DHA on the vector competence of mosquitoes. Results DHA treatment via different approaches significantly reduced the number of Plasmodium oocysts and sporozoites in mosquitoes. The transcriptional levels of anti-Plasmodium immune genes (including TEP1, LRIM1, and APL1C), Toll pathway genes (including Tube, MyD88, and Rel1), and the effector defensin 1 were upregulated by DHA treatment at 24 and 72 hpi. TEP1 and Rel1 protein expression was significantly induced under DHA treatment. However, Rel1 knockdown in DHA-treated mosquitoes abrogated DHA-mediated refractoriness to Plasmodium infection. Conclusions DHA treatment effectively inhibited the development of P. yoelii in A. stephensi by upregulating mosquitoes’ Toll signaling pathway, thereby influencing the susceptibility of Anopheles to Plasmodium. Graphical Abstract

Background & objectives: Anopheles stephensi is responsible for the transmission of malaria in urban areas. Vector competence of An. stephensi from a non-malarious (Coimbatore) and highly malarious (Chennai) urban area were investigated to find out the reason for the non-transmission of malaria in Coimbatore. Methods: Vector competence (Susceptibility/refractoriness) of An. stephensi mosquitoes from Chennai (Malarious) and Coimbatore (Non-malarious), Tamil Nadu, India to Plasmodium vivax (Chennai) were investigated. Bioassays were carried out concurrently in both these strains by artificial membrane feeding technique using the same malaria infected blood. An. stephensi were dissected to observe infection in the midgut and salivary glands. The parasite infection, oocyst and sporozoite positivity rate, the oocyst load, correlation between male-female gametocyte ratio and infection, and Survival Analysis of parasitic stages during sporogony were analyzed and compared. Results: The overall infection rate was 45.8 and 41.2 per cent in Chennai and Coimbatore. Oocyst count ranged from 1-80 and 1-208 respectively and not statistically significant. Oocyst positivity was high from Day 8-21in both strains. The Mean Survival Day (MSD) for oocyst was Day 14 in both strains. Sporozoite was observed in four experiments in each of the strains and the MSD for sporozoites was Day 20 and Day 17 in Chennai and Coimbatore. Interpretation & conclusion: An. stephensi of Chennai and Coimbatore are equally susceptible to P. vivax infection and the non-transmission of malaria in Coimbatore can be attributed to external factors such as the presence of preferential breeding habitat, vector density, vector survival, and weather. The only difference observed was the comparatively shortened oocyst maturation time in the Coimbatore strain which requires further investigation.

Abstract Background SQ109 is a promising candidate drug for the treatment of patients with drug-resistant tuberculosis (DR-TB). The purpose of this study was to investigate the activity of SQ109 against clinical isolates of Mycobacterium tuberculosis (MTB) from patients with multidrug-resistant TB (MDR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB), and to explore new drug-resistant mechanisms of SQ109. Methods We evaluated the in vitro activity of SQ109 against clinical isolates from patients with MDR-TB and pre-XDR-TB using minimal inhibitory concentration (MIC) assay. The drug-resistant gene, mmpL3 of SQ109-resistant strains was sequenced, and a quantitative real-time PCR assay was used to analyze 28 efflux pump genes in SQ109-resistant strains without mmpL3 mutations. The role of candidate efflux pumps mmpL5 and mmpL7 on the MIC of SQ109 was evaluated using recombinantly cloned MmpL5 and MmpL7 expressed in Mycobacterium smegmatis. Results The MIC90, MIC95 and MIC99 values of SQ109 for 225 clinical isolates of MTB were 0.25 mg/L, 0.5 mg/L and 1.0 mg/L, respectively. Among the pre-XDR strains, six showed resistance to SQ109 despite the absence of gene mutations in mmpL3. In six resistant pre-XDR strains, the MIC of SQ109 decreased with the use of an efflux pump inhibitor, and there was significant upregulation of mmpL5 and mmpL7 in two strains after exposure to SQ109. The presence of MmpL7 in Mycobacterium smegmatis resulted in decreased susceptibility to SQ109, with the MIC increasing from 16 mg/L to 32 mg/L. Conclusions Our data demonstrated that SQ109 exhibited excellent levels of in vitro activity against MTB. MmpL7 may be a potential gene for MTB resistance to SQ109, providing a useful target for detecting SQ109 resistance in MTB.

Type I diabetes susceptibility is caused by both environmental and genetic factors, the latter comprising approximately half of the total risk as evidenced by the fact that identical twins have approximately 50% concordance, suggesting 50% of the disease risk is environmental. The human leukocyte antigen (HLA) genes account for approximately half of the genetic risk, as demonstrated by the concordance between HLA identical siblings. Because environmental and genetic differences vary between racial groups, the incidence of type 1 diabetes (TID) differs across the world, being highest in Caucasians. Recent GWAS (genome-wide association studies) studies have suggested there may be up to 50 genomic regions contributing to the non-major histocompatibility complex (MHC) genetic risk contribution. This review presents and discusses the latest research on the MHC and non-MHC genes. Only the non-MHC regions, which have been confirmed in multiple studies and which are considered definite regions of genetic susceptibility, are included in the review.

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate gene expression and play critical roles in tumorigenesis. Genetic variants in miRNA processing genes, DROSHA and DICER, have been implicated in cancer susceptibility and progression in various populations. However, their role in Egyptian patients with breast cancer (BC) remains unexplored. This study aims to investigate the association of DROSHA rs10719 and DICER rs3742330 polymorphisms with BC risk and clinical outcomes. This case–control study included 209 BC patients and 106 healthy controls. Genotyping was performed using TaqMan assays in blood, tumor tissue, and adjacent non-cancerous tissue samples. Associations were analyzed using logistic regression and Fisher’s exact test. The DROSHA rs10719 AA genotype was associated with a 3.2-fold increased risk (95%CI = 1.23–9.36, p < 0.001), and the DICER rs3742330 GG genotype was associated with a 3.51-fold increased risk (95%CI = 1.5–8.25, p = 0.001) of BC. Minor allele frequencies were 0.42 for rs10719 A and 0.37 for rs3742330 G alleles. The risk alleles were significantly more prevalent in tumor tissue than adjacent normal tissue (rs10719 A: 40.8% vs. 0%; rs3742330 G: 42.7% vs. 0%; p < 0.001). However, no significant associations were observed with clinicopathological features or survival outcomes over a median follow-up of 17 months. In conclusion, DROSHA rs10719 and DICER rs3742330 polymorphisms are associated with increased BC risk and more prevalent in tumor tissue among our cohort, suggesting a potential role in miRNA dysregulation during breast tumorigenesis. These findings highlight the importance of miRNA processing gene variants in BC susceptibility and warrant further validation in larger cohorts and different ethnic populations.

In August, 2022, forest fires occurred in Jiangjin District, Banan District, and Beibei District in Chongqing, respectively, with a total burned area of approximately 35 km2. After the wildfire, an ash layer with a thickness of 1～5 cm was deposited on the slope, and the vegetation and soil structure of the burned area were devastated. Affected by concentrated rainfall, it will pose a serious threat to the infrastructure of nearby villages and towns and residents’ lives and properties once the post-fire debris flow occurs. Based on the remote sensing, field investigation, and in-situ tests, the distribution characteristics of burned areas after the fire were identified. The measured data including the thickness of the ash layer, and the saturated hydraulic conductivity of the soil were derived. The severe, moderate, and low burned areas accounted for 9.6%, 34.0%, and 56.4% of the entire area, respectively, with the corresponding average thickness of ash and soil disturbance layer of 15.10 cm, 3.28 cm, and 1.15 cm. According to the prediction model based on expert experience, a total of 95 potential debris flow gullies in burned areas were evaluated for the susceptibility of post-fire debris flow, of which 1 was of high susceptibility, 43 were of medium susceptibility, 44 were of low susceptibility, and 7 were not prone to occur, contributing to 1.05%, 45.26%, 46.32%, and 7.37% of the total, respectively. Considering that a large number of loose solid sources besides ash and sediment still exist in the moderate and severe burned areas within watersheds under the current conditions, with strong water repellency of burned soil, once the medium and high susceptibility gullies are affected by concentrated rainfall in the rainy season, there is a relatively high probability for the post-fire debris flow occurrence. This study provides basic information for the prevention and risk management of post-fire debris flows.

Yanyuan County is located on the southeastern edge of the Qinghai-Tibet Plateau, with strong regional tectonic activities. Under the internal and external dynamics actions, landslide disasters are extremely developed in the country, which has caused huge casualties and economic losses. It is necessary to carry out landslide susceptibility assessment and then control the regional landslide disasters scientifically. Based on the 1∶50000 geological disaster survey in Yanyuan County, this study selected 13 landslide susceptibility evaluation factors, including elevation, slope, slope direction, terrain curvature, distance from fault, stratigraphic lithology, distance from water body, average annual rainfall, topographic wetness index, stream power index, normalized difference vegetation index, distance from road, and land use type. Based on 27596 grid points of landslide disaster data, combining the traditional Frequency Ratio (FR) model with the advantages of quantitative analysis and data quantification and the emerging Deep Neural Network (DNN) model with the powerful nonlinear learning and fitting ability, The FR-DNN coupling model was constructed to evaluate landslide susceptibility. The study area is divided into five levels: extremely high susceptibility area, high susceptibility area, medium susceptibility area, low susceptibility area, and extremely low susceptibility area, with an area percentage of 11.90%, 18.38%, 18.34%, 9.13%, and 42.25%, respectively. The accuracy was verified by the AUC value of the ROC curve. The AUC values of the FR model and the FR-DNN coupling model are 0.754 and 0.859, respectively. The prediction accuracy of the FR-DNN coupling model is improved by 10.5% compared with that of the FR model, indicating that the FR-DNN coupling model has better prediction ability and is more suitable for landslide susceptibility evaluation in the study area.

Abstract Objective Apolipoprotein E (APOE) gene polymorphisms were associated with coronary atherosclerosis and hypertension. However, the relationship between APOE polymorphisms and coronary atherosclerosis susceptibility in hypertensive patients is unclear. The aim of this study was to assess the relationship. Methods A total of 1713 patients with hypertension who were admitted to Meizhou People’s Hospital from November 2019 to August 2023 were retrospectively analyzed, including 848 patients with coronary atherosclerosis and 865 patients without coronary atherosclerosis. The rs429358 and rs7412 polymorphisms of APOE were genotyped, and relationship between APOE polymorphisms and the risk of coronary atherosclerosis in hypertensive patients were analyzed. Results There were 10 (0.6%), 193 (11.3%), 30 (1.8%), 1234 (72.0%), 233 (13.6%), and 13 (0.8%) individuals with APOE ɛ2/ɛ2, ɛ2/ɛ3, ɛ2/ɛ4, ɛ3/ɛ3, ɛ3/ɛ4, and ɛ4/ɛ4 genotype, respectively. The frequency of APOE ɛ3/ɛ4 was higher (16.4% vs. 10.9%, p = 0.001) in the patients with coronary atherosclerosis than controls. Logistic analysis showed that body mass index (BMI) ≥ 24.0 kg/m2 (24.0 kg/m2 vs. 18.5–23.9 kg/m2, odds ratio (OR): 1.361, 95% confidence interval (CI): 1.112–1.666, p = 0.003), advanced age (≥ 65/

Landslides and slope processes constitute one of the most frequent natural hazards in valleys near major rivers and mountainous regions. The surface layer, characterized by its relatively loose composition, is prone to sliding due to a combination of distinct natural and human-related factors. Specific sections along the right bank of the Danube River in Smederevo city exhibit significant susceptibility to landslide activation, often leading to substantial material losses and posing a risk to the local population. The initial step in the provided research involves analyzing existing literature and mapping landslides within the study area. The initial analysis covers both natural conditions and anthropogenic activities. The second step includes establishing a geospatial database in the Geographic Information System and generating eight thematic maps. In the third step, different weight coefficients were assigned to the criteria, which facilitated the creation of the Landslide Susceptibility Index using the Best–Worst Method. Subsequently, in the fourth step, a composite map illustrating landslide susceptibility was produced. According to this research, about 4% of the territory of Smederevo, or 19.3 km2, is highly or very highly susceptible to landslides. These localities are located on the right bank of the Danube River and around the Ralja River. Receiver operating characteristic-area under the curve value indicates very high predictive power (approximately 1), thus suggesting the reliability of the used methodology. This visualization of areas highly prone to such occurrences empowers policymakers to implement more effective environmental protection measures and institute sustainable management practices for agricultural parcels in this region. Also, the provided research represents the inaugural integration of advanced remote sensing techniques and interdisciplinary investigations, offering deeper insights into landslide activity in the study area and yielding more comprehensive results.

Abstract Objective This meta-analysis aims to clarify the association between the TNF-α -308G > A and − 238G > A polymorphisms and lung cancer risk. Method A comprehensive search was conducted for relevant articles across databases such as PubMed, Google Scholar, Web of Science, EMBASE, and CNKI, up to September 25, 2023. Lung cancer risk was assessed by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). The Z-test was used to determine the significance of combined ORs, with P A polymorphism, along with 10 studies comprising 2,427 cases and 2,357 controls for the − 238G > A polymorphism. The − 308G > A polymorphism showed no significant overall relationships, though in the Asian subgroup, the A allele was significantly reduced compared to G (OR: 0.831, p = 0.028) and the AA genotype showed significant reductions versus GG (OR: 0.571, p = 0.021), with no significant correlation in Caucasians. In non-small cell lung cancer (NSCLC), the A allele was associated with increased risk compared to G (OR: 1.131, p = 0.049). For the − 238G > A polymorphism, the AA genotype significantly increased risk compared to GG (OR: 3.171, p = 0.014), while showing a protective effect in Caucasians (OR: 0.120, p = 0.024) and a heightened risk in Asians (OR: 7.990, p = 0.007). In small cell lung cancer (SCLC), the A allele conferred protective effects, whereas NSCLC showed increased risk for the AA genotype (OR: 11.375, p = 0.002). Conclusion The − 308G > A polymorphism has no significant overall relationships but suggests a protective role of the A allele in the Asian subgroup. Conversely, the − 238G > A polymorphism presents a complex risk profile, increasing lung cancer likelihood in Asians while protecting Caucasians. Notably, the AA genotype significantly raises risk for NSCLC, indicating its potential as a risk factor.

Objectives: Acinetobacter baumannii is classified by the centre for Disease Control and Prevention (CDC) as an ''urgent threat'' due to its ability to acquire and develop resistance to multiple classes of antibiotics. As a result, it is one of the most concerning pathogens in healthcare settings, with increasing incidence of infections due to carbapenem-resistant Acinetobacter baumannii (CRAB) associated with high morbidity and mortality rates. Therefore, there are ongoing efforts to find novel treatment options, one of which is cefiderocol. We aim to review available evidence on cefiderocol use for severe nosocomial pneumonia due to carbapenem-resistant Acinetobacter baumannii. Methods: A comprehensive review was conducted from 2017 to 2023, covering articles from databases such as Pubmed, Scopus, and Embase, along with conference proceedings from ECCMID 2023. The primary focus was on severe nosocomial pneumonia due A. baumannii and cefiderocol. Discussion: Cefiderocol, targeting periplasmic space Penicillin-Binding Proteins (PBPs) via siderophore transport pathways, exhibits promise against multi-drug resistant Gram-negative bacilli. Its effectiveness in treating CRAB pneumonia remains debated. The CREDIBLE trial reported higher mortality with cefiderocol compared to the best available treatment, while other cohort studies showed contrasting outcomes. Patient variations and pharmacokinetic factors may underlie these discrepancies. The recommended cefiderocol dosage regimen may fall short of desired pharmacokinetic targets, especially in critically ill patients and lung infections. Pulmonary factors hindering cefiderocol's entry into bacteria through iron transporters are overlooked in clinical breakpoints. Optimized dosing or combination regimens may enhance infection site exposure and outcomes. Conclusions: Further research is needed to determine the optimal cefiderocol dosage and administration (mono vs. dual therapy, continuous vs. intermittent infusion), in severe Acinetobacter baumannii nosocomial pneumonia.

BACKGROUND: Autism Spectrum Disorder (ASD) risk is highly heritable, with potential additional non-genetic factors, such as prenatal exposure to ambient particulate matter with aerodynamic diameter

Land and soil resources are scarce in the Tibetan Plateau, and the region is facing ecological pressure from climate warming and increasing human activities. As a major ecological problem, gully erosion is destroying land and soil resources on the Tibetan Plateau, but related research is limited, and susceptibility areas and influencing factors are unclear. Machine learning methods are often applied to study gully initiation susceptibility, but they require a programming foundation. Therefore, the Redui watershed on the southern Tibetan Plateau with severe gully erosion was selected to evaluate the susceptibility and influencing factors of gully initiation through 12 influencing factors including topography, human activity, and underlying surface conditions, and all 2310 gully headcut sites. Two non-code nonlinear modeling methods, the categorical Regression (CATREG) and geographical detector (Geodetector) methods, were first used in the spatial modeling of gully initiation susceptibility. The results showed that the gully initiation susceptibility of the hillslope around the alluvial fan was highest. The very high susceptibility areas of the CATREG model and Geodetector model account for 18.2% and 16% of the total, respectively. The main influencing factors of gully initiation were elevation, relief, and soil type recognized by CATREG, and elevation, human footprint, and soil type recognized by Geodetector. Elevation is the primary factor controlling downstream susceptibility in both models. The primary factors in the upper and middle reaches are soil type and relief identified by CATREG. Human footprint, soil type, and distance to road are primary factors in the upper and middle reaches identified by Geodetector. The explanatory power of elevation, elevation-relief interaction, Geodetector model and CATREG model were 39%, 54%, 46.4% and 73.8%, respectively, at extremely significant levels (P

The Velachery Municipality is highly vulnerable to natural disasters such as Storms, and floods due to its geo-environmental settings. It is evident that the Nivar cyclone has severely hit and caused flooding in the Velachery region during the fourth week of November 2020. Along with the increasing urbanization, it is also expected to experience severe impacts of climate change soon. Urbanization exerts additional environmental stress and amplifies the impact of natural disasters. The study area has been divided into 3 clusters based on the geographical location. The survey has been carried out in 180 households and data was statically analyzed. Indicators such as exposure, sensitivity, and adaptive capacity were grouped and aligned with available data. Data were aggregated using a composite index and Urban Flood Vulnerability was compared to Cluster wise. The results reveal an extreme variability in terms of flood magnitude and frequency in Velachery. The vulnerability spider diagram suggests that Cluster 2 is more vulnerable in terms of less capacity to cope, and Cluster 3 is more vulnerable in terms of Exposure, Health, Economic susceptibility, physical susceptibility, less capacity to anticipate, cope and recover. Overall Cluster 3 has higher flood vulnerability compared to other clusters. The identification of flood-vulnerable zones has been done in the study and recommended flood resilience measures for Velachery Municipality, Chennai.

The numerical and analytical results of a study on the paramagnetism of a two-dimensional electron gas depending on concentration and temperature are presented. The dependence of spin susceptibility on the width of the quantum well, temperature, concentration, and chemical potential at the resonance points and away from it was analyzed. The susceptibility was analyzed in the model of an ideal gas with a parabolic spectrum and a quantum well of infinite depth. The numerical results of the susceptibility calculation will be presented in graphs for different temperatures, quantum well widths, and concentrations. [ABSTRACT FROM AUTHOR]

Vector-borne pathogens induce hemoparasitism in cattle causing substantial economic losses in tropical and subtropical areas. Infectious cattle actively contribute to maintaining the transmission cycle, and the presence of these animals must be associated with husbandry management and environmental changes. In the present study, we conducted a cross-sectional study sampling 1,000 bovines to identify infectious cattle diagnosed by a direct technique and employed a dichotomic questionnaire for association analyses, hierarchical clustering, and Principal Component Analysis (PCA). Overall prevalence with infectious cattle was 34.99%, where 97% of the farms had at least one infectious animal per genera, and the prevalence in properties ranged between 16.39 and 53.85%. Of these animals, 26.20% tested positive for Anaplasma sp., 8.40% for Babesia spp., and 1.30% for Trypanosome spp. The main co-infection showed 5% Anaplasma sp. – Trypanosome spp., followed by 4% Babesia spp. – Trypanosome spp. These bovines showed association with the use of the Jersey breed (OR = 2.016 C.I:1.188–3.419), selling animals for replacement (OR = 1.417 CI:1.022–1.965), participation in livestock exhibitions (OR = 2.009 CI:1.262–3.199), premises with burials (OR = 2,064 CR: 1.414–3.011), use of palm kernel (OR = 1.935 C.I:1.198–3.124), and the use of ivermectin (OR = 1.548 CI: 1.085–2.210) as a susceptibility. The hierarchical clustering revealed clusters among properties with different hemoparasite prevalence, with notable co-infections observed. The subsequent PCA identified that significant risk factors contributed to hemoparasitism positivity. We conclude that infectious cattle in the endemic area showed an association with husbandry management that permits the success of vector and maintenance of the enzootic or epizootic cycle in the herds. [ABSTRACT FROM AUTHOR]

Ischia island represents the westernmost portion of the Phlegraean Volcanic District (Campania Region, Italy) and is characterized by the presence of Mt. Epomeo, a giant centrally located resurgent volcanic horst. This horst is controlled by fault systems and magmatic dynamics able to generate recurrent seismicity. Such seismicity, associated with the presence of volcanic terrains with different degrees of erodibility, makes Ischia highly subjected to several ground instability phenomena such as landslides. This multidisciplinary study aimed to map the seismically induced landslide susceptibility of the island, taking into account the Md 4.0 earthquake that occurred on August 21, 2017, as a reference seismic event. Eight parameters were isolated as relevant predisposing factors for landslide occurrence and combined, through GIS elaborations, to compute a numerical index (SNAP index) that quantified the seismically induced landslide susceptibility for each 5 × 5 m area. The resulting map, through five classes of susceptibility, highlights that the highest exposed areas are mainly localized along the N–NW flanks of Mt. Epomeo, involving mainly the municipality of Casamicciola Terme. Moreover, the map is discussed considering the spatial distribution of historical and recent seismically induced ground effects, an ERT field survey carried out on significant test sites, and the displacement map obtained by 2015–2022 InSAR data.

The decline of oak canopies in Iberian woodlands is strongly influenced by abiotic and biotic stress factors, such as the oomycete Phytophthora cinnamomi which has the capacity to infect a wide range of plant species. Understory plant diversity plays an important role in the epidemiology of P. cinnamomi in these ecosystems. This study aimed to identify a set of woody and herbaceous plants that can impact oak decline. Twenty-two herbaceous plant species from three families, and nineteen woody plants (trees and shrubs) from seven families were assessed for their response to infection by P. cinnamomi. Most of the herbaceous species did not show evident susceptibility, only a few exhibited significant biomass root reduction and just seven were identified as hosts. Yellow lupin was the only herbaceous species showing high susceptibility. Among the woody plant species, only two shrub and two tree species exhibited disease symptoms. The other ones, mostly hosts, ranged between low susceptible and tolerant. These results highlight the possibility that many of these species can maintain the pathogen active in the soil or even increase its population. In this context, the findings of this study can contribute to effective management strategies to mitigate Phytophthora infection in woodland soils.