Miracle-dz/UniFAR-FTUs huggingface dataset:
Anticipated stigma and associated factors among chronic illness patients in Amhara Region Referral Hospitals, Ethiopia: A multicenter cross-sectional study

Background Anticipated stigma related to chronic illness patients undermines diagnosis, treatment, and successful health outcomes. The study aimed to assess the magnitude and factors associated with anticipated stigma among patients with chronic illness attending follow-up clinics in Amhara Region Referral Hospitals, Ethiopia. Methods A cross-sectional institution-based study was conducted in Amhara Region Referral Hospitals from 01 March to 15 April 2021. A simple random sampling technique was used to select the three Referral Hospitals in the region and study subjects. Data were collected using a pre-tested interview-based questionnaire. Data were entered and cleaned with Epi-Info version 6 and exported for analysis STATA version 14. Multiple linear regression was used to show the association between anticipated stigma and potential factors. Associations were measured using ß coefficients and were considered statistically significant if the p-value > 0.05. Results A total of 779 patients were included for analysis with a response rate of 97%. Their mean (Standard deviation) of anticipated stigma was estimated at 1.86 and 0.5, respectively. After running an assumption test for multiple linear regression; educational status, cigarette smoking, psychological distress, medication adherence, alcohol consumption, and social part of the quality of life were statically significantly associated with anticipated stigma. Conclusion and recommendation The result showed a high level of anticipated stigma reported among the participants. Emphasizing improving their social part of the quality of life, avoiding risky behaviors like alcohol consumption and cigarette smoking, access to health education for chronically ill patients, integrating mental health in all types of chronic disease, and developing strategies and protocols which will help to improve patient medication adherence to their prescribed medication will be crucial. This can provide a foundation for government andnon-governmental organizations, and researchers implementing evidence-based interventions and strategies on chronic care to address factors related to anticipated stigma.
Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells

Acute kidney injury (AKI) represents a common complication in critically ill patients that is associated with increased morbidity and mortality. In a murine AKI model induced by ischemia/reperfusion injury (IRI), we show that glutamine significantly decreases kidney damage and improves kidney function. We demonstrate that glutamine causes transcriptomic and proteomic reprogramming in murine renal tubular epithelial cells (TECs), resulting in decreased epithelial apoptosis, decreased neutrophil recruitment, and improved mitochondrial functionality and respiration provoked by an ameliorated oxidative phosphorylation. We identify the proteins glutamine gamma glutamyltransferase 2 (Tgm2) and apoptosis signal-regulating kinase (Ask1) as the major targets of glutamine in apoptotic signaling. Furthermore, the direct modulation of the Tgm2-HSP70 signalosome and reduced Ask1 activation resulted in decreased JNK activation, leading to diminished mitochondrial intrinsic apoptosis in TECs. Glutamine administration attenuated kidney damage in vivo during AKI and TEC viability in vitro under inflammatory or hypoxic conditions.
Cyclical depressurization degranulates platelets in an agonist-free mechanism of platelet activation

Activation of circulating platelets by receptor binding and subsequent coagulation events are defined by a well characterized physiological response. However, the growing prevalence of chronic kidney disease (CKD) and implication of platelet-released factors in worsening cardiovascular outcomes with hemodialysis warrant further investigation into the mechanobiology of platelet degranulation. The significant drops in pressure caused by high friction across the hemodialysis flow circuit present an overlooked platelet stimulant not involving immobilization as a driver for cytoskeletal rearrangement. In this study, platelets from healthy and dialysis (pre- and post-treatment) donors were cyclically depressurized in static suspension to measure changes in physiology by integrin αIIbβ3 activation and surface P-selectin expression. The progressive increase in CD62P with no changes in PAC1 over pressure-cycling duration regardless of uremia signifies that hydrostatic depressurization involves a novel agonist-free mechanism leading to platelet degranulation as a unique case in which CD62P and PAC1 do not interchangeably indicate platelet activation. Subsequent stimulation using ADP further suggests that sustained depressurization regimens desensitize integrin αIIbβ3 activation. Variability in platelet response caused by uremia and CKD are observed by elevated baseline PAC1 in pre-dialysis samples, PAC1 retention after ADP exposure, and maximum CD62P with ADP independent of pressure. Theory for hydrostatic pressure-induced degranulation circumventing integrin-initiated signal transduction is here presented based on the Starling Equation.
UDP-glucose dehydrogenase (UGDH) activity is suppressed by peroxide and promoted by PDGF in fibroblast-like synoviocytes: Evidence of a redox control mechanism

UDP-glucose dehydrogenase (UGDH) generates essential precursors of hyaluronic acid (HA) synthesis, however mechanisms regulating its activity are unclear. We used enzyme histostaining and quantitative image analysis to test whether cytokines that stimulate HA synthesis upregulate UGDH activity. Fibroblast-like synoviocytes (FLS, from N = 6 human donors with knee pain) were cultured, freeze-thawed, and incubated for 1 hour with UDP-glucose, NAD+ and nitroblue tetrazolium (NBT) which allows UGDH to generate NADH, and NADH to reduce NBT to a blue stain. Compared to serum-free medium, FLS treated with PDGF showed 3-fold higher UGDH activity and 6-fold higher HA release, but IL-1beta/TGF-beta1 induced 27-fold higher HA release without enhancing UGDH activity. In selected proliferating cells, UGDH activity was lost in the cytosol, but preserved in the nucleus. Cell-free assays led us to discover that diaphorase, a cytosolic enzyme, or glutathione reductase, a nuclear enzyme, was necessary and sufficient for NADH to reduce NBT to a blue formazan dye in a 1-hour timeframe. Primary synovial fibroblasts and transformed A549 fibroblasts showed constitutive diaphorase/GR staining activity that varied according to supplied NADH levels, with relatively stronger UGDH and diaphorase activity in A549 cells. Unilateral knee injury in New Zealand White rabbits (N = 3) stimulated a coordinated increase in synovial membrane UGDH and diaphorase activity, but higher synovial fluid HA in only 2 out of 3 injured joints. UGDH activity (but not diaphorase) was abolished by N-ethyl maleimide, and inhibited by peroxide or UDP-xylose. Our results do not support the hypothesis that UGDH is a rate-liming enzyme for HA synthesis under catabolic inflammatory conditions that can oxidize and inactivate the UGDH active site cysteine. Our novel data suggest a model where UGDH activity is controlled by a redox switch, where intracellular peroxide inactivates, and high glutathione and diaphorase promote UGDH activity by maintaining the active site cysteine in a reduced state, and by recycling NAD+ from NADH.
Impact of sociodemographic factors and screening, diagnosis, and treatment strategies on colorectal cancer mortality in Brazil: A 20-year ecological study

Colorectal cancer (CRC) caused 261,060 deaths in Brazil over a 20-year period, with a tendency to increase over time. This study aimed to verify the sociodemographic factors predicting higher mortality caused by CRC and survival rates. Moreover, we aimed to verify whether the performance of screening, diagnostic and treatment procedures had an impact on mortality. Ecological observational study of mortality due to CRC was conducted in Brazil from 2000–2019. The adjustment variable was age, which was used to calculate the age-standardized mortality rate (ASMR). The exposure variables were number of deaths and ASMR. Outcome variables were age-period-cohort, race classification, marital status, geographic region, and screening, diagnostic, and treatment procedures. Age-period-cohort analysis was performed. ANOVA and Kruskal-Wallis test with post hoc tests were used to assess differences in race classification, marital status, and geographic region. Multinomial logistic regression was used to test for interaction among sociodemographic factors. Survival analysis included Kaplan-Meier plot and Cox regression analysis were performed. Multivariate linear regression was used to test prediction using screening, diagnosis, and treatment procedures. In Brazil, mortality from CRC increased after age 45 years. The highest adjusted mortality rates were found among white individuals and in the South of the country (p < 0.05). Single, married, and widowed northern and northeastern persons had a higher risk of death than legally separated southern persons (p < 0.05). Lower survival rates were observed in brown and legally separated individuals and residents from the North (p < 0.05). An increase in first-line chemotherapy and a decrease in second-line chemotherapy were associated with high mortality in the north (p<0.05). In the south, second-line chemotherapy and abdominoperineal rectal resection were associated with high mortality (p < 0.05). Regional differences in sociodemographic factors and clinical procedures can serve as guidelines for adjusting public health policies.
T‐lymphocyte subtyping: an early warning and a potential prognostic indicator of active cytomegalovirus infection in patients with sepsis

Cytomegalovirus (CMV) infection is very common in patients suffering from sepsis and may cause poor prognosis. To explore the relationship between immune status of patients with sepsis and CMV infection, we assessed T lymphocyte subtyping and other commonly used clinical parameters in patients with sepsis upon admission to the intensive care unit (ICU) and evaluated their potential impact on diagnosis and outcomes of active CMV infection. In our study, 82 of 599 patients with sepsis were diagnosed with active CMV infection. The 28‐day mortality was higher in active CMV–infected than nonactive CMV–infected patients (20.7% versus 9.9%); 51of 82 active CMV–infected patients with sepsis were assessed to have CMV‐DNA–negative conversion, while 31 were persistently positive for CMV DNA. Higher CD8+CD28+ T‐cell counts at presentation were associated with CMV‐DNA–negative conversion and lower 28‐day mortality. The CMV‐DNA–negative conversion and 28‐day mortality of active CMV–infected patients with sepsis could be predicted using cutoff values of 151 (74.5% sensitivity and 87.1% specificity) and 64.5 (52.9% sensitivity and 92.3% specificity) CD8+CD28+ T cells mL−1 at ICU admission, respectively. Higher CD8+CD28+ T‐cell count was significantly associated with active CMV infection, higher CMV‐DNA–negative conversion and lower 28‐day mortality, which may be a potential marker for early warning of active CMV infection and outcome prediction.
Inhibition of Chk2 promotes neuroprotection, axon regeneration, and functional recovery after CNS injury

DNA double-strand breaks occur in many acute and long-term neurological conditions, including neurodegeneration, neurotrauma, and stroke. Nonrepaired breaks chronically activate the DNA damage response in neurons, leading to neural dysfunction and apoptosis. Here, we show that targeting of the central ATM-Chk2 pathway regulating the response to double-strand breaks slows neural decline in Drosophila models of chronic neurodegeneration. Inhibitors of ATM-Chk2, but not the parallel ATR-Chk1 pathway, also promote marked, functional recovery after acute central nervous system injury in rats, suggesting that inhibiting nonhomologous end-joining rather than homologous recombination is crucial for neuroprotection. We demonstrate that the Chk2 inhibitor, prexasertib, which has been evaluated in phase 2 clinical trials for cancer, has potent neuroprotective effects and represents a new treatment option to promote functional recovery after spinal cord or optic nerve injury.
An integrative cellular metabolomic study reveals downregulated tricarboxylic acid cycle and potential biomarkers induced by tetrabromobisphenol A in human lung A549 cells

Tetrabromobisphenol A (TBBPA) is extensively utilized as a brominated flame retardant in numerous chemical products. As an environmental contaminant, the potential human toxicity of TBBPA has been attracting increasing attention. Nonetheless, the exact underlying mechanisms of toxicological effects caused by TBBPA remain uncertain. In this study, we investigated the potential mechanisms of TBBPA toxicity in vitro in the A549 cell line, one of the widely used type II pulmonary epithelial cell models in toxicology research. Cell viability was determined after treatment with varying concentrations of TBBPA. Liquid chromatography–mass spectrometry (LC–MS) metabolomics and metabolic flux approaches were utilized to evaluate metabolite and tricarboxylic acid (TCA) cycle oxidative flux changes. Our findings demonstrated that TBBPA significantly reduced the viability of cells and attenuated mitochondrial respiration in A549 cells. Additionally, LC–MS data showed significant reductions in TCA cycle metabolites including citrate, malate, fumarate, and alpha‐ketoglutarate in 50 μM TBBPA‐treated A549 cells. Metabolic flux analysis indicated reduced oxidative capacity in mitochondrial metabolism following TBBPA exposure. Moreover, diverse metabolic pathways, particularly alanine, aspartate, and glutamate metabolism and the TCA cycle, were found to be dysregulated. In total, 12 metabolites were significantly changed (p < .05) in response to 50 μM TBBPA exposure. Our results provide potential biomarkers of TBBPA toxicity in A549 cells and help elucidate the molecular mechanisms of pulmonary toxicity induced by TBBPA exposure.
Interventions to increase racial and ethnic minority accrual into cancer clinical trials: A systematic review

Racial and ethnic minorities (REMs) continue to be underrepresented in clinical trials despite the 1993 National Institutes of Health's Revitalization Act mandating the representation of women and underrepresented minority groups in clinical trials. Although Blacks represent 15% and Hispanics 13% of the cancer population, their clinical trial enrollment rates are disproportionately low at 4% to 6% and 3% to 6%, respectively. A systematic review exploring interventions aimed at improving cancer clinical trial (CCT) enrollment for REMs was conducted.
Community expectations of a village for people living with dementia

Abstract Small‐scale models of dementia care are a progressive approach to improve care for people living with dementia. These models intend to provide a home‐like environment with a small number of residents in each living unit, easy access to services and facilities, a dedicated team of staff and flexible routines. This study was undertaken during the construction phase of a new village and provided a unique opportunity to explore expectations of the village among the local community. Twelve community members participated in two sequential online focus groups over a 2‐month period. Focus group discussions were recorded, transcribed and analysed using a reflexive thematic analysis approach. Knowledge of the village varied and was informed by familiarity with other village developments and local marketing about the new village. The findings indicate that the community expect the village to provide residents with optimum dementia care, a safe and enabling physical environment and a vibrant daily life where they are engaged in ‘normal’ activities. While participants expected the village to be self‐contained, they also anticipated strong connections with the wider community. Participants acknowledged that the community need dementia education to ensure these interactions are positive. Community expectations of a new village development for people living with dementia are largely positive and often idealistic. Organisations need to consider these expectations when developing new small‐scale facilities and be mindful of how they market these developments to foster realistic expectations. While community enthusiasm about dementia care is encouraging, education is needed to ensure the success of the model.
Ranking Factors for Web Search: Case Study in the Netherlands

It is essential for search engines to constantly adjust ranking function to satisfy their users, at the same time SEO companies and SEO specialists are observed trying to keep track of the factors prioritized by these ranking functions. In this thesis, the problem of identifying highly influential ranking factors for better ranking on search engines is examined in detail, looking at two different approaches currently in use and their limitations. The first approach is, to calculate correlation coefficient (e.g. Spearman rank) between a factor and the rank of it’s corresponding webpages (ranked document in general) on a particular search engine. The second approach is, to train a ranking model using machine learning techniques, on datasets and select the features that contributed most for a better performing ranker. We present results that show whether or not combining the two approaches of feature selection can lead to a significantly better set of factors that improve the rank of webpages on search engines. We also provide results that show calculating correlation coefficients between values of ranking factors and a webpage’s rank gives stronger result if a dataset that contains a combination of top few and least few ranked pages is used. In addition list of ranking factors that have higher contribution to well-ranking webpages, for the Dutch web dataset(our case study) and LETOR dataset are provided.
Narrative review to capture patients’ perceptions and opinions about non-response and response to biological therapy for severe asthma

Background There are now many biological therapies to treat severe asthma. To assess which work best for which patient, we need to develop definitions of response. This narrative review aims to capture severe asthma patients’ perceptions about non-response and response to biological therapy. Methods Four bibliographic databases were searched from inception to September 2021. Grey literature was searched with the involvement of patient representatives. A thematic approach was used for synthesis. No qualitative studies specifically explore patients’ perspectives on response to biological therapy for severe asthma. Three papers and one published asthma patient interview were included. Relevant grey literature was included from online discussion forums, blogs and social media websites. Results Adult patients framed positive response to biological therapy in terms of reduced burden of disease and treatment. Both were multifaceted. Some patients experienced reduced benefit from biological therapy over time. There was a group of patients who described a limited response or non-response to biological therapy. This was framed within the context of continuing hospitalisation and oral corticosteroid treatment. The speed of onset of benefit was felt to be important by some. Conclusions Definitions of non-response and response need to be patient-centred, yet there is a complete lack of qualitative research focused on this topic. By combining relevant published and grey literature we have provided a description of adult patients’ perceptions of response to biological therapy in severe asthma. We now need to understand the views of children and adolescents with severe asthma and their carers, and diverse patient experiences in real-world settings. When considering response and non-response to biological therapy, people with severe asthma value participation in everyday activities, reduced exacerbations and reduced exposure to oral corticosteroids https://bit.ly/3Cix28n
Patterns of relapse and long-term outcome in patients treated with a curative intent for advanced Hodgkin lymphoma

Abstract Background Consolidation radiotherapy for advanced Hodgkin lymphoma (AHL) is controversial. Precise knowledge of the most likely relapse location is crucial for radiotherapy planning. We performed detailed patterns of relapse analyses and evaluated if initial bulky disease, initial 18F-fluoro-deoxy-glucose (FDG)-avidity and/or a residual mass on computed tomography (CT)-scan after chemotherapy are sites with a high risk of relapse. This information could provide guidance for optimal use of radiotherapy in AHL. Material and methods We included 133 patients treated with curatively intended chemotherapy for AHL. 23 patients received consolidation radiotherapy. For relapsed patients, imaging from diagnosis, response evaluation, relapse, and any radiotherapy planning, were retrieved and co-registered to determine the exact site(s) of relapse relative to initial site(s), residual mass(es) and to any irradiated volumes. Size and FDG-avidity of initial sites with later relapse, and residual CT-abnormalities after chemotherapy in these sites were registered. Survival analyses were done using the Kaplan–Meier method. Results Nine (6.8%) patients relapsed, eight in initially involved sites. One relapse was in an initially irradiated site (as well as other sites). Initial bulky disease, high initial FDG-uptake, and/or residual masses on CT-scan after chemotherapy did not predict sites with a high risk of relapse. Overall survival was 79.6% (95% CI, 72.7–86.5%) and 70.6% (95% CI, 62.4–78.8%) at 5 and 10 years, respectively. Time to progression analysis showed 91.8% (95% CI, 86.9–96.7%) and 90.7% (95% CI, 85.4–96.0%) without progression at 5 and 10 years, respectively. Conclusion Current treatment strategies for AHL provide excellent disease control. Neither initial bulk, high initial FDG-uptake, nor a residual CT-abnormality post-chemotherapy seem to indicate sites with a high risk of relapse.
Where do you go when your periods go?: A case-study examining secondary amenorrhea in a professional internationally-capped female soccer player through the lens of the sport nutritionist

ABSTRACT This case study follows a professional internationally capped female soccer player’s two-year journey from eumenorrhea, through injury, to amenorrhea, and the challenges faced by the player and nutritionist. The two years are split into three sections: (Areta et al. 2013) longitudinal profiling of the player, (Baker et al. 2020) nutrition to support her return from injury, and (Beato et al. 2018) investigation into the observed secondary amenorrhea. The cause of amenorrhea was investigated through the assessment of energy availability via doubly labelled water, remote food photography, blood biomarkers and resting metabolic rate. Despite having secondary amenorrhea and anovulatory cycles, the player did not have low energy availability. This study shows the importance for practitioner’s, particularly nutritionists, to not assume that all menstrual irregularities are caused by low energy availability and could be caused by a combination of factors (e.g., clinical, physiological, and psychological), which requires a multi-disciplinary investigation and intervention team. This study also showed that education needs to be provided about menstrual health to elite female soccer players as the player (i) believed that not having a period was beneficial for performance and unsure of possible health implications; (ii) was convinced that a one-day bleed indicated a regular menstrual cycle; and (iii) was reluctant to waste the practitioners time discussing menstrual issues and was nervous of finding out if she had an actual health issue. It is therefore crucial that players feel comfortable in discussing their menstrual status with practitioners to support their performance and long-term health.