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Gender and cultural aspects of brucellosis transmission and management in Nakasongola cattle corridor in Uganda

Background Brucellosis is a zoonotic disease with significant public health and economic effects on societies. In Uganda, brucellosis is endemic and a primary contributor in livestock productivity losses. This is more worrisome for populations in the cattle corridor with high reliance on cattle and milk for nutritional value and symbol in social relations and identity. The community’s social construction may affect comprehension of brucellosis hence leading to exposure and increased vulnerability to transmission. Despite brucellosis’ high prevalence in the cattle corridor, little attention has been paid to its social construction. Hence, this study explored the interplay between gender dynamics, vulnerability and social construction of brucellosis transmission, in consideration of the unique socio-cultural context that characterizes cattle corridor populations. Methods Using an exploratory qualitative approach, the study was conducted in Nakasongola cattle corridor within three sub counties; Nabiswera, Nakitoma and Wabinyonyi using key informant interviews (KIIs) and focus group discussions (FGDs). Purposive sampling was used to identify participants for the four FGD [8–12] each from a subcounty though one was combined and 15 KIIs. Data were collected using face -to -face interviews with an interview guide that was structured using the Socio Ecological Model of Human Behaviour framework (SEMHB) constructs. Thematic analysis was conducted in NVivo 12 Pro incorporating both deductive (guided by the SEMHB) and inductive approaches (guided by the data). Findings The study identified important themes under each SEMHB influence level (Individual, Interpersonal, Community and Societal level). The study indicates that social composition and role distribution are driven by social and cultural expectations and significantly contribute to exposure and vulnerability to infection in the cattle corridor. For instance, it is paramount that women undergoing marriage preparations to be fed on raw milk for a certain period prior to their ceremony to enhance beauty. Also, important to note that use of personal protection to assist births is viewed by the community as opposing cultural norms, creating a perception of detachment from the highly valued cattle. Another noteworthy finding is the level of knowledge on brucellosis in terms of symptoms, transmission route, prevention and treatment at the interpersonal level. Furthermore, findings show practices such as the consumption of raw milk and assisted births, as being rooted in the social cultural norms, hence critical for transmission of brucellosis. At the community and organizational levels, the findings indicate an inadequate level of knowledge sharing and reluctance towards preventive measures as structural factors for the transmission of brucellosis and are ingrained in family and power relations. Conclusion The findings highlight that the social construction of brucellosis transmission is rooted in gender roles, social- cultural and power structures highlighting the influence of living process and spaces, at the different societal levels. Such complex dynamics play a critical role in determining individuals’ susceptibility to infection as well as transmission potential of the disease-causing agent in cattle keeping communities. The gendered induced vulnerabilities related to the socio-cultural norms and familial roles, also play an important role in the exposure and spill over at the individual, interpersonal and community levels. The insufficient knowledge-sharing and reluctance to adopt preventive measures emerge as structural contributors to the persistence of brucellosis and other emerging zoonoses. These factors, intertwined with family dynamics and power relations, call for targeted interventions that address both individual behaviors and broader socio-cultural and institutional barriers to effective disease management and prevention. Conversely, policies that align with the community’s social construction, gender and context are more likely to be feasible, adopted and sustained by the affected population.

Theoretical modeling of 2,4-dichlorophenoxyacetic acid on acid-treated peanut skin: microscopic analysis via statistical physics treatment

Muscle strengthening in individuals with Amyotrophic Lateral Sclerosis: a systematic review with meta-analyses

Despite the observed benefits of properly prescribed exercises for people with Amyotrophic Lateral Sclerosis (ALS), the scarcity of studies and lack of consensus on the effects of muscle-strengthening exercises on this population has a negative impact on their rehabilitation. This study aimed to evaluate the effects of muscle-strengthening interventions in individuals with ALS. This systematic review of intervention studies included clinical trials that performed non-respiratory muscle strengthening in people with ALS compared to non-strengthening interventions, usual care, or placebo. Such studies were obtained from the MEDLINE, EMBASE, Cochrane Library, SPORTDiscus, and Physiotherapy Evidence Database databases, with no language or publication date restrictions. The outcomes considered were peripheral muscle strength, functionality, fatigue, and adverse events. The Physiotherapy Evidence Database scale was used to analyze the risk of bias, while the Grading of Recommendations Assessment, Development and Evaluation system was used to evaluate the quality of the evidence. Searches were conducted in October 2023 and eight studies were included, totaling 296 individuals. Seven of the eight studies showed superiority of the experimental intervention over the control, but this was not supported in the meta-analyses. Small sample size and high heterogeneity in the primary studies contributed significantly to the low quality of the evidence. There was no evidence of the superiority of interventions for muscle strengthening compared to interventions not aimed at strengthening, usual care, or placebo in terms of the outcomes analyzed immediately after the intervention. The quality of the evidence ranged from low to very low. Five of the studies evaluated adverse events, without reporting serious events. Interventions for muscle strengthening did not prove to be more effective when compared to the control group in the short term nor seem to produce serious adverse events. The low quality of the evidence indicates the need for studies with greater methodological rigor in this population, to more assertively assess the impacts of this intervention over the short, medium, and long term.

Gradient in grammatical structure of indigenous languages reflects pathway of human expansion in the Americas

Abstract The settlement of the Americas is one of the major episodes of prehistoric human dispersal, and involved multiple temporally and geographically uneven demographic events that continued into the Holocene. Here we suggest the possibility that these complex dynamics are reflected in the spatial structure of Indigenous linguistic diversity. On the basis of newly collated data, we find more pronounced spatial structure in linguistic diversity in North America than in South America after known genealogy and language contact are accounted for. Furthermore, we report a continent-wide gradient in aspects of sound systems and grammatical structure that mirrors early north–south dispersal paths, and that is not explained by local language contact and known phylogenetic relationships.

COVID-19 pandemic and risk factor measurement in individuals with cardio-renal-metabolic diseases: A retrospective study in the United Kingdom

Background Comprehensive research about changes in risk factor (RF) management of people with chronic conditions during the COVID-19 pandemic is sparse. We aimed to study the impact of the pandemic on RF assessment in people with type 2 diabetes (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD). Method Using UK Clinical Practice Research Datalink GOLD, we identified adults with T2DM, CVD and CKD who were alive and registered two years before (March 2018 – February 2019; March 2019 – February 2020) and one year during (March 2020 – February 2021) the pandemic. We estimated the proportion of people whose RFs (systolic (SBP) and diastolic (DBP) blood pressure, total cholesterol (TC), body mass index, smoking, and HbA1c) were assessed, mean values, and the proportion of controlled at each period for each cohort, overall and by age, sex, ethnicity, and deprivation. Multivariable logistic regression was used to estimate the association of patient characteristics (age, sex, ethnicity, deprivation, and comorbidity) with the outcome of having all RFs assessed during a given period. Results Within the T2DM cohort, 66.4% and 65.2% had assessments of HbA1c in 2018 and 2019, which reduced to 43.4% in 2020. In CVD cohort, 76.9% and 72.6% had their BP measurements (54.5% and 51.3% for TC) in 2018 and 2019 respectively, which declined to 40.6% (30.7% for TC) in 2020. In CKD cohort, BP assessments declined from 77.9% and 72.3% in 2018 and 2019 respectively to 45.0% in 2020. These findings were consistent across patient demographics. In those with T2DM, SBP and DBP increased (+1.65 mmHg and +1.02 mmHg) in 2020. Elderly people were less likely to have all their RFs assessed in 2020 in all three cohorts compared to previous years. Conclusions Among people with major cardiometabolic conditions, there have been substantial reductions in the assessment and control of several key RFs during the pandemic. These patients will need regular monitoring in future for the prevention of complications. Our findings also highlight the need for resilient healthcare systems to ensure continuity of care and mitigate disparities in high-risk populations.

Integrating bioinformatics and machine learning to discover sumoylation associated signatures in sepsis

Abstract Small Ubiquitin-like MOdifier-mediated modification (SUMOylation) is associated with sepsis; however, its molecular mechanism remains unclear. Herein, hub genes and regulatory mechanisms in sepsis was investigated. The GSE65682 and GSE95233 datasets were extracted from public databases. Differential analysis and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted in GSE65682 to identify differentially expressed genes (DEGs) and key module genes. Candidate genes were derived by intersecting with SUMOylation-related genes (SUMO-RGs). The Least Absolute Shrinkage and Selection Operator (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) were utilized to identify significant feature genes. The convergence of those genes was utilized for diagnostic assessment and expression validation. Hub genes were defined as those exhibiting an area under the curve (AUC) greater than 0.7, significant gene expression, and a consistent trend. Localization and functional analyses of hub genes were conducted to enhance the understanding of these genes. Immune analysis, regulatory network construction, and drug prediction were performed. Six hub genes were identified: RORA, L3MBTL2, PHC1, RPA1, CHD3, and RANGAP1. These genes possessed considerable diagnostic significance for sepsis and were also markedly downregulated in the condition. Hub genes were predominantly enriched in the ribosome pathway and exhibited a strong correlation with differential immune cells. Activated CD8 + T cells exhibited a positive correlation with RORA. Based on the predicted and established regulatory network, AC004687.1 was observed to modulate PHC1 expression via hsa-miR- 142 - 5p. A total of six hub genes (RORA, L3MBTL2, PHC1, RPA1, CHD3, and RANGAP1) associated with SUMOylation was identified in sepsis in the current study. The findings are likely to aid in the differentiation between control and disease states, offering substantiation for the diagnosis of sepsis.

Temporal changes in cecal luminal and mucosal microbiota of broiler chickens with clinical coccidiosis (Eimeria maxima)

Coccidiosis is a gastrointestinal disease caused by Eimeria parasites which leads to major economic losses in the poultry industry worldwide. Eimeria infection may alter the gut microbiota, which has been associated with chicken health and performance. This study aimed to determine the effects of Eimeria maxima infection on the luminal and mucosal microbiota of the cecum (CeL and CeM) at multiple time points post-infection (days 3, 5, 7, 10, and 14). Infection decreased Shannon diversity at d 3 (P = 0.03), increased observed features (ASVs) at d 5 (P < 0.01), and increased Shannon diversity at d 10 (P = 0.04) in the CeL microbiota compared to the control. In CeM microbiota, infection increased observed features at d 5 (P = 0.03), but later decreased observed features at d 14 (P = 0.01). Relative abundance of potential butyrate-producing bacteria such as [Ruminococcus] torques group in CeL and Butyricicoccus in CeM were decreased in infected birds, and some metabolic pathways related to butyrate production were predicted to be decreased. These findings show E. maxima may affect cecal microbiota alpha diversity in a time-dependent manner and reduce abundance of bacteria potentially important to gut health.

Mechanism and role of H. pylori CagA-induced NLRP3 inflammasome in gastric cancer immune cell infiltration

Genetic diversity and demographic history of the largest remaining migratory population of brindled wildebeest (Connochaetes taurinus taurinus) in southern Africa

The blue wildebeest (Connochaetes taurinus) is a keystone species in the savannahs of southern Africa, where it maintains shortgrass plains and serves as an important prey source for large carnivores. Despite being the second-largest migratory wildebeest population, the brindled wildebeest (C. t. taurinus) of the Greater Liuwa Ecosystem (GLE) of western Zambia have remained largely unstudied, until recently. While studies have increased understanding of recent demography, migration, and population limiting factors, the level of genetic diversity, patterns of gene flow, and long-term demographic history of brindled wildebeest in the GLE remains unknown. Most genetic studies of wildebeest have focused on small, heavily-managed populations, rather than large, migratory populations of high conservation significance. We used restriction-site associated DNA sequencing (RAD-seq) to assess genetic diversity, population structure, and demographic history of brindled wildebeest in the GLE. Using SNPs from 1,730 loci genotyped across 75 individuals, we found moderate levels of genetic diversity in GLE brindled wildebeest (He =  0.210), very low levels of inbreeding (FIS =  0.033), and an effective population size of about one tenth the estimated population size. No genetic population structure was evident within the GLE. Analyses of the site frequency spectrum found signatures of expansion during the Middle Pleistocene followed by population decline in the Late Pleistocene and early Holocene, a pattern previously observed in other African ungulates. These results will supplement field studies in developing effective conservation plans for wildebeest as they face continued and increasing threats of habitat loss, poaching, and other human impacts across their remaining range.

Leveraging TME features and multi-omics data with an advanced deep learning framework for improved Cancer survival prediction

Study protocol for a randomized single-center cross-over study: Dapagliflozin treatment in recurring kidney stone patients

Introduction Urolithiasis is one of the most common diseases worldwide, characterized by high morbidity and significant treatment-related costs, with a rising prevalence of up to 20%. The relapse rate within the first 10 years after initial treatment is estimated to be about 60%. Given the increasing prevalence, healthcare-related costs associated with urinary tract stones in the USA are expected to reach up to US $1.24 billion annually by 2030. Current prophylactic therapy for urolithiasis recurrence includes lifestyle modifications, citrate supplementation, and pharmaceuticals. However, a high number of cases remain unresponsive to available pharmacological therapies. Though initially developed for the treatment of Diabetes mellitus, SGLT-2 inhibitors have shown promise in decreasing cardiac and renal endpoints across multiple indications. Recent registry studies have indicated that patients receiving SGLT-2 inhibitors exhibit lower rates of urolithiasis incidence, suggesting a potential reduction in recurrence rates and associated mortality. Objectives We hypothesize that SGLT-2 inhibitors (Dapagliflozin), owing to their multiple pleiotropic effects, may offer a viable treatment option for the prophylaxis of high-risk calcium oxalate kidney stones and reduce urinary calcium oxalate output. Methods This study will proceed in two phases: an exploratory phase and a randomized controlled phase. In the exploratory phase, 22 participants with indications for dapagliflozin treatment will be evaluated before and after treatment initiation to ascertain the concrete effect size regarding oxalate and calcium-sparing effects. This data will inform the calculation of the study sample size (ranging from 17 to 104 participants) to include high-risk calcium oxalate kidney stone formers in a randomized controlled crossover study design. Treatment phases—one with dapagliflozin and one with placebo—will alternate with wash-out phases involving placebo. The primary outcome is the reduction of oxalate excretion in 24-hour urine samples compared to baseline values after 8 weeks of therapy. Secondary objectives include analysing effects on kidney function, the frequency of urolithiasis, and treatment tolerance. Additionally, in-depth metabolomics analyses will explore pathophysiological pathways during treatment. Investigators, patients, and research staff will be blinded to the randomization list. This study was initially registered under EudraCT (Nr:2022-000994-13) and has been transitioned to CTIS (Nr: 2024-519371-25-00) to comply with EU Regulation 536/2014, ensuring streamlined management and transparency. Discussion Dapagliflozin’s pleiotropic effects may provide a novel prophylactic treatment option for urolithiasis. This study aims to evaluate potential treatment effects in a prospective RCT and elucidate potential pathophysiological pathways through in-depth metabolomics analyses. SGLT-2 inhibitors have the potential to transform the landscape of urolithiasis treatment, reduce the healthcare burden on individuals and the system, and significantly improve patient quality of life.

The efficacy of the theory of planned behaviour and value-belief-norm theory for predicting young Chinese intention to choose green hotels

Abstract Although hotels have begun to pay more attention to green practices in providing products and services to satisfy guests’ green needs, the percentage of guests visiting green hotels is still low. Researchers undervalue the connection between consumers’ values, attitudes, norms, and intentions to stay at green hotels. Recently, scholars suggested that the attitude-intention gap can be closed by combining the theory of planned behaviour and the value-belief-norm theory. Therefore, this study examined the interrelationships among various constructs based on both theories. A total of 406 university students from Xuzhou City, China were employed quantitatively, utilising a purposive sample technique to test hypotheses using the Statistical Package for the Social Sciences and structural equation modelling. The results demonstrated that altruistic value, biospheric value, and collectivistic value positively influenced ecocentric attitude respectively. Implicit attitude was positively influenced by biospheric value, collectivistic value, and ecocentric attitude. Meanwhile, ecocentric attitude positively influenced awareness of consequence, subsequently ascription of responsibility, then the personal norm, and finally intention. Furthermore, implicit attitude, subjective norm, and perceived behavioural control positively influenced intention separately while subjective norm favourably influenced implicit attitude, perceived behavioural control, and personal norm respectively. The findings of this study would significantly contribute to a deeper understanding of consumers’ green hotel visits based on a combined theoretical framework from a developing country with a highly collectivistic value orientation, which benefits the growth of the green hotel industry and other key stakeholders.

A sharp volatile-rich cap to the Yellowstone magmatic system

FGF18 induces chondrogenesis and anti-osteoarthritic effects in a mouse model for TMJ degeneration

Objective Temporomandibular Joint Osteoarthritis (TMJ-OA) is a degenerative disease characterized by progressive loss of cartilage and subchondral bone sclerosis. Currently there are no effective treatments for TMJ-OA. FGF18 is a member of the fibroblast growth factor family with essential roles for chondrogenesis, selectively binding to FGFR3 receptor. Studies have reported FGF18 attenuates cartilage degradation. Whereas the anti-osteoarthritic effects of FGF18 in the articular cartilage are known, the effects of FGF18 in a TMJ fibrocartilage degeneration mouse model remain to be determined. The goal of this project was to determine the effects of intra-articular injections of FGF18 in a mouse model for TMJ degeneration. Method Prosthesis tubes were bonded at the left lower incisor of 6-week-old triple collagen transgenic mice (Col1a1XCol2a1XCol10a1), creating unilateral crossbite and degeneration of the TMJ fibrocartilage. Six weeks after placement of prosthesis tubes, experimental and control mice received intra-articular injections of rmFGF18 (5µg/week) or saline, respectively, for 3 weeks. Results Mice receiving saline intra-articular injections presented with a thinner cartilage layer with decreased proteoglycan distribution and Edu positive cells (chondrocyte proliferation marker), while mice injected with rmFGF18 presented with significant increased fibrocartilage thickness, remarkable proteoglycan distribution and chondrocyte proliferation, suggesting healing of the induced degeneration. Furthermore, reversal of the TMJ degeneration achieved by rmFGF18 injection was accompanied by a substantial reduction in Noggin (antagonist of BMP signaling), increase in TIMP1 (inhibitor of metalloproteinases such as MMP13) and decrease in MMP13 expression. Conclusion Our results postulate FGF18 as a powerful growth factor for the healing of TMJ fibrocartilage.

Retraction Note: A Tunguska sized airburst destroyed Tall el-Hammam a Middle Bronze Age city in the Jordan Valley near the Dead Sea

The impact of Connexin 43 deficiency on the cell shape and cytoskeleton of murine Sertoli cells: A house with ramshackle walls?

Genetically induced loss of the gap-junction protein Connexin 43 (Cx43) in murine Sertoli cells leads to an arrest of spermatogenesis at the level of spermatogonia, highly vacuolated tubules, and intratubular cell clusters. Transmission electron microscopy as well as 3D-reconstruction of Sertoli cells based on serial block-face scanning electron microscopy imaging revealed severe cell shape changes in Cx43 deficient Sertoli cells. Since the cytoskeleton is important for the transport of germ cells within the seminiferous epithelium and for keeping the cell shape, the study at hand aimed to reveal correlations of Cx43 loss and changes of cytoskeletal components and their spatial organization in the seminiferous epithelium. Immunohistochemistry, immunofluorescence, conventional transmission electron microcopy and immunogold labeling indicated alterations in microtubule and actin filament distribution patterns in Cx43 deficient Sertoli cells compared to wildtype mice. Firstly, microtubules seemed to be misoriented in mutant Sertoli cells. Secondly, the actin filament based basal ectoplasmic specializations were increased in spatial extension, but the apical ectoplasmic specialization was missing. Lastly, Sertoli cells of both genotypes immunostained positive for vimentin, the prevalent intermediate filament of Sertoli cells, but not for keratins, markers for Sertoli cell immaturity or dedifferentiation. In conclusion, Cx43 deficiency in Sertoli cells correlates not only with severe cell shape alterations but also with changes in microtubule and actin filament distribution patterns, while intermediate filament expression seems to be only negligibly influenced.

Publisher Correction: Green HPLC technique development for the simultaneous determination of the potential combination of Mirabegron and Tamsulosin

Association between pre-existing Pulmonary Hypertension and COVID-19 related outcomes in inpatient and ambulatory care settings

Background Afflicting up to 1% of population, pulmonary hypertension (PH) is commonly associated with cardiopulmonary and metabolic diseases, but the effect of COVID-19 in patients with pre-existing PH remains unclear. Methods We conducted a retrospective cohort study in patients who had undergone right-heart-catheterization within the VA Healthcare system and had a subsequent hospital admission with COVID-19 (inpatient cohort, n=1204) or had COVID-19 positivity but not admitted (outpatient cohort, n=6576). Inpatient findings were confirmed in a non-VA validation cohort (n=656) who had undergone echocardiography with subsequent admission. PH was defined invasively as mean pulmonary artery pressure (mPAP) >20 mmHg and non-invasively as estimated right ventricular systolic pressure (RVSP) >30 mmHg. In-hospital outcomes (inpatient cohort) and 1-year mortality (outpatient cohort) were assessed using multivariable logistic or Cox regression adjusting for confounders. Results Pre-existing PH was independently associated with greater in-hospital mortality (PH using mPAP: adjusted odds ratio [aOR] 1.60, 95%CI: 1.04–2.46; PH using RVSP: aOR 2.12, 95% CI 1.18–3.82). Among outpatients, those with COVID-19 had >8-fold higher 90-day and 2.8 fold higher 91–365 day adjusted hazard of mortality irrespective of PH status. Hazards of 90-day hospitalization were similarly driven by COVID-19. The findings were comparable for patient subgroup with normal pulmonary capillary wedge pressures. Conclusion Pre-existing PH is independently associated with higher in-hospital COVID-19 mortality. In outpatients, COVID-19 positivity was associated with increased mortality over 1 year irrespective of PH status, with highest risk within the first 90 days.

Fracture propagation characteristics and failure mechanisms of parallel-fractured sandstone

R&D and pricing strategies in the intelligent vehicle supply chain under cross-organizational cooperative models

With the development of automotive intelligence, vehicle manufacturers and technology companies have engaged in cross-industry cooperative research and development (R&D), leading to new cooperative R&D models. In this context, this paper develops game-theoretic models for four distinct cooperative frameworks: the technology-dominant model, the supplier-cooperation model, the manufacturer-dominant model, and the joint decision-making model. This paper aims to explore the conditions under which different cooperative R&D models are applicable and examines the strategic choices associated with each model. The results indicate that if a company is a core industry player, the core component supplier should select the technology-dominant model, while the vehicle manufacturer should choose the manufacturer-dominant model. If it is not a core player, the joint decision-making model is the next best choice. If the goal of R&D cooperation is achieving a high level of intelligence rather than short-term profits, the manufacturer-dominant model is more suitable. Though price wars may emerge, under the technology-dominant model, the supply chain adopts a quality strategy. Across the other three models, quality strategies remain consistent. As the consumer price sensitivity coefficient increases, the supply chain is more likely to adopt both quality and low-price strategies simultaneously. These findings offer valuable insights for making R&D and pricing strategy decisions under cross-organizational cooperative models in the intelligent vehicle supply chain.