Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural products for the treatment and management of diabetes mellitus in Zimbabwe-a review

Use of medicinal plants and herbs in the treatment and management of diseases, including diabetes mellitus and its complications remains an integral part of African tradition. In Zimbabwe, nearly one million people are living with diabetes mellitus. The prevalence of diabetes mellitus in Zimbabwe is increasing every year due to lifestyle changes, and has accelerated the use of traditional medicines for its treatment and management in urban areas. In addition, the high cost of modern medicine has led many people in rural parts of Zimbabwe to rely on herbal plant medicine for the treatment of diabetes mellitus and its complications. This review highlights a number of studies carried out to evaluate the antidiabetic properties of indigenous plants found in Zimbabwe with the goal of treating diabetes mellitus. Further, we discuss the mechanism of action of various plant extracts in the treatment and management of diabetes mellitus. Together, this review article can open pathways leading to discovery of new plant derived medicines and regularization of use of crude plant remedies to treat diabetes mellitus by the Zimbabwean government and others across Africa.
Integrative analyses identify HIF-1α as a potential protective role with immune cell infiltration in adamantinomatous craniopharyngioma

Craniopharyngiomas (CPs) are histologically benign tumors located in the sellar–suprasellar region. Although the transcriptome development in recent years have deepened our knowledge to the tumorigenesis process of adamantinomatous craniopharyngioma (ACP), the peritumoral immune infiltration of tumor is still not well understood. In this study, weighted gene coexpression network analysis (WGCNA) was applied to identify different gene modules based on clinical characteristics and gene expression, and then, the protein–protein interaction (PPI) network with the Cytohubba plug-in were performed to screen pivotal genes. In addition, immune cell infiltration (ICI) analysis was used to evaluate the immune microenvironment of ACP patients. In total, 8,568 differential expression genes were identified based on our datasets and two microarray profiles from the public database. The functional enrichment analysis revealed that upregulated genes were mainly enriched in immune-related pathways while downregulated genes were shown in the hormone and transduction of signaling pathways. The WGCNA investigated the most relevant modules, and 1,858 hub genes was detected, from which the PPI network identified 14 pivotal genes, and the Hypoxia-inducible factor 1-alpha (HIF-1α) pathway including four critical genes may be involved in the development of ACP. Moreover, naïve CD4+ and CD8+ T cells were decreased while specific subtypes of T cells were significantly increased in ACP patients according to ICI analysis. Validation by immunofluorescence staining revealed a higher expression of HIF-1α in ACP (ACP vs. control) and adult-subtype (adult vs. children), suggesting a possible state of immune system activation. Notably, children with low HIF-1α scores were related to the hypothalamus involvement and hydrocephalus symptoms. In this study, we successfully identified HIF-1α as a key role in the tumorigenesis and development of ACP through comprehensive integrated analyses and systematically investigated the potential relationship with immune cells in ACP. The results may provide valuable resources for understanding the underlying mechanisms of ACP and strengthen HIF-1α as a potential immunotherapeutic target in clinical application.
Mesenchymal stromal cells isolated from chicken peripheral blood secrete bioactive factors with antimicrobial and regenerative properties

Mesenchymal stromal cells (MSCs) are adult multipotent progenitor cells that have been isolated from various tissue sources of many species, primarily mammals. Generally, these cells proliferate extensively in culture and have been shown to secrete bioactive factors that contribute to healing processes by regulating inflammation, modulating immune responses, inhibiting bacterial growth, and promoting tissue regeneration. The present study reports on the isolation and characterization of MSCs from the peripheral blood (PB) of chickens. Chicken PBMSCs were characterized based on their trilineage differentiation potential and gene and protein expression of MSC-specific cell surface markers. To determine functionality, conditioned medium (CM), which contains all bioactive factors secreted by MSCs, was collected from chicken PBMSCs, and used in in vitro antimicrobial, migration, and angiogenesis assays. Chicken PBMSC CM was found to (i) inhibit the growth of planktonic Staphylococcus aureus (S. aureus), and even more significantly the methicillin-resistant S. aureus (MRSA), (ii) decrease adhesion and promote migration of fibroblasts, and (iii) support endothelial cell tube formation. Collectively, these data indicate that chicken PBMSCs secrete bioactive factors with antimicrobial and regenerative properties, and as such, provide a novel source of cell-based therapies for the poultry industry.
Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload

Pulmonary arterial hypertension (PAH) is associated with substantial remodeling of the right ventricle (RV), which may at first be compensatory but at a later stage becomes detrimental to RV function and patient survival. Unlike the left ventricle (LV), the RV remains understudied, and with its thin-walled crescent shape, it is often modeled simply as an appendage of the LV. Furthermore, PAH diagnosis is challenging because it often leaves the LV and systemic circulation largely unaffected. Several treatment strategies such as atrial septostomy, right ventricular assist devices (RVADs) or RV resynchronization therapy have been shown to improve RV function and the quality of life in patients with PAH. However, evidence of their long-term efficacy is limited and lung transplantation is still the most effective and curative treatment option. As such, the clinical need for improved diagnosis and treatment of PAH drives a strong need for increased understanding of drivers and mechanisms of RV growth and remodeling (G&R), and more generally for targeted research into RV mechanics pathology. Computational models stand out as a valuable supplement to experimental research, offering detailed analysis of the drivers and consequences of G&R, as well as a virtual test bench for exploring and refining hypotheses of growth mechanisms. In this review we summarize the current efforts towards understanding RV G&R processes using computational approaches such as reduced-order models, three dimensional (3D) finite element (FE) models, and G&R models. In addition to an overview of the relevant literature of RV computational models, we discuss how the models have contributed to increased scientific understanding and to potential clinical treatment of PAH patients.
Immunomodulatory effects of the Bifidobacterium longum BL-10 on lipopolysaccharide-induced intestinal mucosal immune injury

The intestine is the largest digestive and immune organ in the human body, with an intact intestinal mucosal barrier. Bifidobacterium longum is the specific gut commensals colonized in the human gut for boosting intestinal immunity to defend against intestinal mucosal immune injury. In the LPS-induced intestinal injury model, the Bifidobacterium longum BL-10 was suggested to boost the intestinal immune. Detailly, compared with the LPS-induced mice, the BL10 group significantly reduced intestine (jejunum, ileum, and colon) tissue injury, pro-inflammatory cytokines (TNF-α, IFN-γ, IL-2, IL-6, IL-17, IL-22, and IL-12) levels and myeloperoxidase activities. Moreover, the B. longum BL-10 significantly increased the number of immunocytes (CD4+ T cells, IgA plasma cells) and the expression of tight junction protein (Claudin1 and Occludin). B. longum BL-10 regulated the body’s immune function by regulating the Th1/Th2 and Th17/Treg balance, which showed a greater impact on the Th1/Th2 balance. Moreover, the results also showed that B. longum BL-10 significantly down-regulated the intestinal protein expression of TLR4, p-IκB, and NF-κB p65. The B. longum BL-10 increased the relative abundance of the genera, including Lachnospiraceae_NK4A136_group and Clostridia_UCG-014, which were related to declining the levels of intestinal injury. Overall, these results indicated that the B. longum BL-10 had great functionality in reducing LPS-induced intestinal mucosal immune injury.
Craniomaxillofacial trauma in immature dogs–etiology, treatments, and outcomes

Treatment of craniomaxillofacial (CMF) trauma in dogs often requires a multidisciplinary approach and a thorough understanding of the CMF anatomical structures involved. This retrospective study aimed to utilize computed tomography (CT) studies of immature dogs evaluated for CMF trauma and to describe common fracture locations, treatment modalities, and complications, as well as the fracture healing outcomes. The medical records and CT studies of 94 dogs under 1 year of age over a 13-year period were evaluated. The skeletal location of CMF fractures, as well as the severity of displacement and fragmentation of each fracture, was recorded. Case demographic data and trauma etiology were also recorded. Animal bites accounted for the majority of trauma (71.0%). The most likely bone or region to be fractured was the maxillary bones, followed by the molar region of the mandibles. Up to 37 bones or specific regions were fractured in any given patient, with an average of 8.8 ± 3.1 fractured bones or regions per dog. Rostral mandibular trauma was associated with intra-articular fractures of the temporomandibular joint (p = 0.016). Patients sustained concomitant injuries in 32% of the cases. Muzzle therapy was the main treatment performed for most dogs (53.2%), followed by soft tissue closure (47.9%) and selective dental extractions (27.6%). Healing complications were recorded in 71.6% of the dogs, with malocclusion being the most reported complication (55.2%), and associated with dentate mandibular jaw fractures (p = 0.05). The average number of complications per dog was 2.4. No statistically significant association was found between treatment modality and healing outcome. There was a positive correlation between the severity of fracture fragmentation and displacement and a negative healing outcome (all rho >0.7). Further treatment was required in 55.6% of the dogs. Additional dental extractions were performed in 77.7% of patients. Healing complications were common in the immature CMF trauma case. Thus, the need for a comprehensive assessment of the entire CMF region during the initial visit, as well as follow-up, preferably using CT or cone beam CT, is underscored.
Efficacy and safety of sacubitril/valsartan vs. valsartan in patients with acute myocardial infarction: A meta-analysis

Background The angiotensin-receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to the angiotensin receptor blocker (ARB) valsartan in terms of reversing heart failure classification (NYHA classification), reducing N-terminal pro-brain natriuretic peptide (NT-proBNP) level and cardiovascular mortality in many studies. Yet, the efficacy of ARNI did not come from patients with acute myocardial infarction (AMI). Methods We searched databases for research published from inception to July 29, 2022, that reported cardiac reverse remodeling (CRR) or security indices. Two reviewers independently screened literature, extracted data, and assessed the risk of bias. Nine studies enrolling 1,369 patients were included to perform a meta-analysis. There were 716 patients in the ARNI group and 653 in the ARB group. Results ARNI outperformed ARBs in terms of CRR indices, with striking changes in left ventricular ejection fraction (EF) (MD: 4.12%, 95%CI: 2.36, 5.88, P < 0.0001), diameter (MD: –3.40 mm, 95%CI: –4.30, –2.94, P < 0.00001, I2 = 0%) and left atrial diameter (MD: –2.41 mm, 95%CI: –3.85, –0.97, P = 0.001, I2 = 0%), other indices there showed no significant improvements. The incidences of major adverse cardiac events (RR: 0.47, 95%CI: 0.34–0.65, P < 0.00001, I2 = 0%), the heart failure (RR: 0.37, 95%CI: 0.23–0.61, P < 0.0001, I2 = 0%), readmission (RR: 0.54, 95%CI: 0.36–0.80, P = 0.003, I2 = 29%) in the sacubitril/valsartan group were lower than the ARB group, while the incidences of cardiac death (RR: 0.56, 95%CI: 0.28, 1.09, P = 0.09), the myocardial infarction (RR: 0.83, 95% CI: 0.39, 1.77, P = 0.63), adverse side effects (RR: 1.67, 95% CI: 0.89, 3.13, P = 0.11) showed no difference. Conclusion This research indicated that early initiation of sacubitril/valsartan in patients after AMI was superior to ARBs in reducing the risks of major adverse cardiac events, heart failure, readmission, and enhancing left ventricular EF, decreasing diameter, left atrial diameter. As for the other outcomes (the incidences of cardiac death, myocardial infarction, and adverse side effects), sacubitril/valsartan demonstrated no obvious advantage over ARBs. Systematic review registration https://www.crd. york.ac. uk/prospero/, identifier [CRD42022307237].
Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis

Mycobacterium tuberculosis remains a leading cause of infectious disease morbidity and mortality for which new drug combination therapies are needed. Mycobacterial bioenergetics has emerged as a promising space for the development of novel therapeutics. Further to this, unique combinations of respiratory inhibitors have been shown to have synergistic or synthetic lethal interactions, suggesting that combinations of bioenergetic inhibitors could drastically shorten treatment times. Realizing the full potential of this unique target space requires an understanding of which combinations of respiratory complexes, when inhibited, have the strongest interactions and potential in a clinical setting. In this review, we discuss (i) chemical-interaction, (ii) genetic-interaction and (iii) chemical-genetic interaction studies to explore the consequences of inhibiting multiple mycobacterial respiratory components. We provide potential mechanisms to describe the basis for the strongest interactions. Finally, whilst we place an emphasis on interactions that occur with existing bioenergetic inhibitors, by highlighting interactions that occur with alternative respiratory components we envision that this information will provide a rational to further explore alternative proteins as potential drug targets and as part of unique drug combinations.
Childhood maltreatment, depression and their link to adult economic burdens

Background Adult depression is a common consequence of adverse childhood experiences. There is also a higher likelihood of being affected by economic burdens after having experienced a traumatic event in childhood. As depression has been associated with economic burden, these long-term sequelae of childhood adversity are likely to interact. Goals We investigated depression and economic consequences, such as unemployment, lower level of education, lower income as long-term sequelae of adverse childhood experiences in adulthood and their interaction. Methods Childhood Maltreatment was measured by the German version of the Adverse Childhood Experience (ACE) questionnaire. Depression was measured by the Patient Health Questionnaire (PHQ-2). Logistic regressions were applied to investigate the risks of suffering economic burdens, with depression as a moderator. Results Depressive symptoms increased with the number of ACEs and were highest in those reporting four or more ACEs, especially amongst those who experienced sexual and emotional abuse, as well as neglect. Moderation analysis showed a significant effect of depression increasing almost all economic burdens. Migration background additionally increased the risk of unemployment and working in a blue-collar job. Female gender decreased the risk of unemployment and working in a blue-collar job, but increased the risk of low income and part-time employment. Conclusion The moderation effect of depression increased the negative impact of exposure to multiple ACEs on economic life in adulthood. Prevention of ACEs and early intervention are needed to prevent the mental health and economic consequences.
Parents’ Working Conditions in the Early COVID-19 Pandemic and Children’s Health-Related Quality of Life: The Ciao Corona Study

Objective: To assess the associations between parents’ working conditions during the lockdown period (March-May 2020) and children’s health-related quality of life (HRQOL) over the first year of the COVID-19 pandemic in Zurich, Switzerland. Methods: We included 2211 children (6–16 years) and their parents from the prospective study Ciao Corona. Parents reported their employment status and working conditions during the lockdown. Children’s HRQOL was assessed in June-July 2020, January and March 2021 using the parents-report of the KINDL®. We used mixed models to assess the associations between parents’ working conditions and children’s HRQOL at the three time points. Results: Children from families in which at least one parent changed their working conditions during the lockdown showed lower HRQOL in June-July 2020, than children from families in which neither parent experienced changes. Children from families in which at least one parent had to work remotely continued to show lower HRQOL in January and March 2021. Conclusion: Changes in parents’ working conditions during lockdown were negatively associated with children’s HRQOL. Public health policies aiming to support families susceptible to adverse changes are needed.
Modest association between health literacy and risk for peripheral vascular disease in patients with type 2 diabetes

Objective Health literacy plays a crucial role in managing chronic health conditions. Previous studies have revealed the positive relationship between health literacy and diabetes knowledge but few studies have focused on peripheral vascular disease (PVD) in diabetes in relation to health literacy in diabetes management. This study investigated the relationship between the risk for PVD and health literacy level with other determining factors among patients with type 2 diabetes. Method We conducted a survey on health literacy using the Mandarin Multidimensional Health Literacy Questionnaire in the department of metabolism and endocrine systems at a regional hospital in northern Taiwan from December 2021 to May 2022 and obtained data from the hospital's health information system (HIS) from 2013 to 2020 to identify occurrences of PVD (n = 429). We performed logistic regression analysis to identify the relationship between PVD events and health literacy levels (overall and in five separate subdimensions) adjusted with other variables. Results A longer duration of diabetes increased the risk for PVD events (P = 0.044 and 0.028). In terms of health literacy, the overall level was not significant; however, the dimension of higher levels of health literacy in acquiring health information increased the risk for PVD events (P = 0.034). Other variables were not significantly associated with the risk for PVD events. Conclusion This study examined the risk for PVD events in terms of the duration of diabetes and provided evidence across the range of dimensions of health literacy concerning the ability to control diabetes. Those with a higher level of health literacy may be more aware of their disease situation, seek and cooperate with their healthcare providers earlier, and have more opportunities to be made aware of their health status from regular checkups than those with inadequate health literacy. These results may help providers make available more self-management tools that are adequate and sustainable for diabetes patients with poor health literacy.
Recent progress in simulating two types of ENSO – from CMIP5 to CMIP6

The new emerging type of El Niño brings challenges to the state-of-the-art coupled models to simulated features of El Niño - Southern Oscillation (ENSO) diversity. The Coupled Model Intercomparison Project (CMIP), containing the advanced worldwide coupled models, has recently released the model outputs in phase 6. In this paper, the characteristics of two types of ENSO in 19 models from CMIP phase 5 and their counterparts in phase 6 are assessed regarding the spatial and temporal features and the seasonal cycle features. The weaker amplitude of Eastern Pacific (EP) and Central Pacific (CP) ENSO in CMIP5 is increased and the spatial structure of CP ENSO is better depicted in CMIP6. However, no significant improvement in the ENSO periodicity and the ENSO phase-locking behavior compared to CMIP5. A synthetic ENSO score, containing eight metrics, is defined and employed to evaluate the performance of each CMIP model. The average ENSO score for CMIP6 is 2.375, indicating modest improvement compared to the average score of 2.441 for CMIP5. Furthermore, the slight improvement in the ENSO score is partly related to the reduced climatology bias of sea surface temperature in the Niño4 region. The overall evaluation provides necessary information for future investigation about the mechanism exploration of the ENSO diversity based on the models with better performance.
Performance of presepsin and procalcitonin predicting culture-proven bacterial infection and 28-day mortality: A cross sectional study

Presepsin is a highly specific biomarker for diagnosing bacterial infections, but its clinical usefulness is not well validated. A retrospective cross-sectional study was conducted. Among the patients suspected bacterial infection or fulfilled the criteria of systemic inflammatory response syndrome (SIRS) and patients who underwent blood culture, presepsin, procalcitonin (PCT), and C-reactive protein (CRP) at the same time were included. Receiver operating characteristic (ROC) curve analysis and logistic regression were used to compare performance of three biomarkers. A total of 757 patients were enrolled, including 256 patients (33.8%) with culture-proven bacterial infection and 109 patients (14.4%) with bacteremia. The 28-day mortality rate was 8.6%. ROC curve analysis revealed that the area under the curve (AUC) of PCT was higher than that of presepsin for both culture-proven bacterial infection (0.665 and 0.596, respectively; p = 0.003) and bacteremia (0.791 and 0.685; p < 0.001). In contrast, AUC of PCT for 28-day mortality was slower than presepsin (0.593 and 0.720; p = 0.002). In multivariable logistic regression analysis, PCT showed the highest ORs for culture-proven bacterial infection (OR 2.23, 95% CI 1.55–3.19; p < 0.001) and for bacteremia (OR 5.18, 95% CI 3.13–8.56; p < 0.001), while presepsin showed the highest OR for 28-day mortality (OR 3.31, 95% CI 1.67–6.54; p < 0.001). CRP did not show better performance than PCT or presepsin in any of the analyses. PCT showed the best performance predicting culture-proven bacterial infection and bacteremia, while presepsin would rather be useful as a prognostic marker.