Miracle-dz/UniFAR-FTUs huggingface dataset:
Biologic targets of prescription medications and risk of neurodegenerative disease in United States Medicare beneficiaries

Objective To identify prescription medications associated with a lower risk of three neurodegenerative diseases: Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. Methods We conducted a population-based, case-control study of U.S. Medicare beneficiaries in 2009 (42,885 incident neurodegenerative disease cases, 334,387 randomly selected controls). Using medication data from 2006–2007, we categorized all filled medications according to their biological targets and mechanisms of action on those targets. We used multinomial logistic regression models, while accounting for demographics, indicators of smoking, and health care utilization, to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for 141 target-action pairs and each neurodegenerative disease. For target-action pairs inversely associated with all three diseases, we attempted replication in a cohort study that included an active comparator group. We constructed the cohort by following controls forward for incident neurodegenerative disease from the beginning of 2010 until death or end of 2014, i.e., up to five years after the two-year exposure lag. We used Cox proportional hazards regression while accounting for the same covariates. Results The most consistent inverse association across both studies and all three neurodegenerative diseases was for xanthine dehydrogenase/oxidase blockers, represented by the gout medication, allopurinol. Allopurinol was associated with a 13–34% lower risk for each neurodegenerative disease group in multinomial regression, and a mean reduction of 23% overall, as compared to individuals who did not use allopurinol. In the replication cohort we observed a significant 23% reduction for neurodegenerative disease in the fifth year of follow-up, when comparing allopurinol users to non-users, and more marked associations with an active comparator group. We observed parallel associations for a related target-action pair unique to carvedilol. Discussion/Conclusion Xanthine dehydrogenase/oxidase blockade might reduce risk of neurodegenerative disease. However, further research will be necessary to confirm that the associations related to this pathway are causal or to examine whether this mechanism slows progression.
Association between Dysbiosis in the Gut Microbiota of Primary Osteoporosis Patients and Bone Loss

In recent decades, gut microbiome research has experienced significant growth, driven by technological advances that enable quantifying bacterial taxa with greater precision. Age, diet, and living environment have emerged as three key factors influencing gut microbes. Dysbiosis, resulting from alterations in these factors, may lead to changes in bacterial metabolites that regulate pro- and anti-inflammatory processes and consequently impact bone health. Restoration of a healthy microbiome signature could mitigate inflammation and potentially reduce bone loss associated with osteoporosis or experienced by astronauts during spaceflight. However, current research is hindered by contradictory findings, insufficient sample sizes, and inconsistency in experimental conditions and controls. Despite progress in sequencing technology, defining a healthy gut microbiome across global populations remains elusive. Challenges persist in identifying accurate gut bacterial metabolics, specific taxa, and their effects on host physiology. We suggest greater attention be directed towards this issue in Western countries as the cost of treating osteoporosis in the United States reaches billions of dollars annually, with expenses projected to continue rising.
Patient safety in prisons: a multi-method analysis of reported incidents in England

Objectives Prisoners use healthcare services three times more frequently than the general population with poorer health outcomes. Their distinct healthcare needs often pose challenges to safe healthcare provision. This study aimed to characterise patient safety incidents reported in prisons to guide practice improvement and identify health policy priorities. Design: We carried out an exploratory multi-method analysis of anonymised safety incidents from prisons. Setting Safety incidents had been reported to the National Reporting and Learning System by prisons in England between April 2018 and March 2019. Participants Reports were reviewed to identify any unintended or unexpected incident(s) which could have, or did, lead to harm for prisoners receiving healthcare. Main outcome measures Free-text descriptions were examined to identify the type and nature of safety incidents, their outcomes and harm severity. Analysis was contextualised with subject experts through structured workshops to explain relationships between the most common incidents and contributory factors. Results Of 4112 reports, the most frequently observed incidents were medication-related (n = 1167, 33%), specifically whilst administering medications (n = 626, 54%). Next, were access-related (n = 559,15%), inclusive of delays in patients accessing healthcare professionals (n = 236, 42%) and managing medical appointments (n = 171, 31%). The workshops contextualised incidents involving contributing factors (n = 1529, 28%) into three key themes, namely healthcare access, continuity of care and the balance between prison and healthcare priorities. Conclusions This study highlights the importance of improving medication safety and access to healthcare services for prisoners. We recommend staffing level reviews to ensure healthcare appointments are attended, and to review procedures for handling missed appointments, communication during patient transfers and medication prescribing.
Vegetable and Fruit Consumption and Its Relationship with Body Mass Index in Adults: A Cross-Sectional and Seasonal Research from Türkiye

ABSTRACT This study examines the relationship between fruit and vegetable consumption and the BMI in Türkiye. In this cross-sectional study, which 6332 adults were included, fruit and vegetable consumption, and preferences were collected. The quantities of vegetables and fruits were classified based on the WHO and the national recommendations. Of the adults (33.39 ± 12.59 years), 52.9% of men and 39.7% of women had an above-normal BMI. Based on WHO recommendations, overweight and obese people consumed less vegetables and fruits compared to their counterparts (ORs for women, overweight: 1.2, obese: 1.3; ORs for men, overweight: 1.3, obese: 1.5; 95% CI). The regression analysis revealed that the quantities of vegetable and fruit intake were higher in young individuals, men, and married people. Although the majority consume more than 400 g/day of vegetables and fruits, the intake is inadequate in people with obesity.
The HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15–HISTONE DEACETYLASE9 complex associates with HYPONASTIC LEAVES 1 to modulate microRNA expression in response to abscisic acid signaling

After binding to nascent primary microRNA (miRNA) transcripts (pri-miRNAs), the miRNA biogenesis protein HYPONASTIC LEAVES 1 (HYL1) acts as a scaffold that recruits the HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15)–HISTONE DEACETYLASE9 (HDA9) complex to regulate the expression and processing of miRNAs in response to abscisic acid (ABA).
A comparison of the wake structure of a stationary and oscillating bluff body, using a conditional averaging technique

A conditional averaging technique to extract the underlying vortex pattern from a turbulent bluff body wake is described. Ensemble averages of wake velocities are developed on the basis of a reference phase position, determined from the outer flow irrotational fluctuations. The method is applied to the wakes of a stationary and oscillating D-shape cylinder, where, in the latter case, the vortex shedding is locked to the frequency of body movement. Direct comparisons of average circulation and vortex street spacings are obtained and these demonstrate the significant change in wake structure that accompanies and sustains vortex-induced vibrations. It is observed in both conditions that only 25% of the estimated shed vorticity is found in the fully developed wake. In addition the analysis produces profiles of vorticity and velocity in an ‘average vortex cycle’. A model, developed to help interpret these results, suggests that a good representation of an average wake situation is obtained by the addition of considerable mean shear to a street of finite area axisymmetric vortices.
The Stationary Wave Response to a Tropical SST Anomaly in an Idealized GCM

Abstract The upper tropospheric stationary wave response to a tropical sea surface temperature (SST) anomaly is examined with an idealized general circulation model (GCM) as well as steady linear and nonlinear models. The control climate of the GCM is zonally symmetric; this symmetric climate is then perturbed by a dipolar SST anomaly centered at the equator. Two experiments, with anomaly amplitudes differing by a fact of two, have been conducted. The response is very linear in the amplitude of the SST anomaly. A steady, baroclinic model linearized about a zonally symmetric basic state simulates the GCM's stationary wave reasonably well when it is forced by anomalous heating as well as anomalous transients. When decomposing the GCMs flow into parts forced separately by heating and transients, tropical transients are found to play a dissipative role to first approximation, reducing the amplitude of the response to heating by a factor of two. The effects of extratropical transients are relatively weak. A st.
Coronary microvascular dysfunction due to Chagas disease: where are we now?

ABSTRACT Introduction Myocardial ischemia is common in patients with chronic Chagas cardiomyopathy (CCC), but only recently clinical and experimental studies highlighted the involvement of this abnormality as contributing to the progression of myocardial damage. Areas covered Despite the absence of obstructive epicardial coronary artery disease at angiography, and limited evidence of abnormal flow regulation at the macrovascular level, remarkable functional and structural microvascular abnormalities are consistently reported by independent investigations of CCC. These derangements occur early and contribute to myocardial dysfunction. Recent research focused on reversing microvascular dysfunction as a target to positively impact the course of CCC. We conducted an extensive review of the scientific literature, aiming to summarize the role of coronary dysfunction causing myocardial ischemia in CCC, with a focus on implications for clinical management of individuals affected by this disease. Expert Opinion Preclinical studies showed a clear correlation between perfusion defects and inflammation in viable but impaired dysfunctional myocardium. These findings provided further insight into the CCC complex pathophysiology and support the role of very few recent therapeutic interventions aiming to relieve myocardial ischemia. Further research is warranted to assess the efficacy of new interventions addressing reversal of microvascular ischemia and inflammation modulation and halting ventricular dysfunction progression in CCC.
Alterations in the Gut Microbiome and Metabolisms in Pregnancies with Fetal Growth Restriction

Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications. ABSTRACT Fetuses diagnosed with fetal growth restriction (FGR) are at an elevated risk of stillbirth and adulthood morbidity. Gut dysbiosis has emerged as one of the impacts of placental insufficiency, which is the main cause of FGR. This study aimed to characterize the relationships among the intestinal microbiome, metabolites, and FGR. Characterization was conducted on the gut microbiome, fecal metabolome, and human phenotypes in a cohort of 35 patients with FGR and 35 normal pregnancies (NP). The serum metabolome was analyzed in 19 patients with FGR and 31 normal pregnant women. Multidimensional data was integrated to reveal the links between data sets. A fecal microbiota transplantation mouse model was used to determine the effects of the intestinal microbiome on fetal growth and placental phenotypes. The diversity and composition of the gut microbiota were altered in patients with FGR. A group of microbial species altered in FGR closely correlated with fetal measurements and maternal clinical variables. Fecal and serum metabolism profiles were distinct in FGR patients compared to those in the NP group. Altered metabolites were identified and associated with clinical phenotypes. Integrated multi-omics analysis revealed the interactions among gut microbiota, metabolites, and clinical measurements. Microbiota from FGR gravida transplanted to mice progestationally induced FGR and placental dysfunction, including impaired spiral artery remodeling and insufficient trophoblast cell invasion. Taken together, the integration of microbiome and metabolite profiles from the human cohort indicates that patients with FGR endure gut dysbiosis and metabolic disorders, which contribute to disease pathogenesis. IMPORTANCE Downstream of the primary cause of fetal growth restriction are placental insufficiency and fetal malnutrition. Gut microbiota and metabolites appear to play an important role in the progression of gestation, while dysbiosis induces maternal and fetal complications. Our study elaborates the significant differences in microbiota profiles and metabolome characteristics between women with FGR and normal pregnancies. This is the first attempt so far that reveals the mechanistic links in multi-omics in FGR, providing a novel insight into host-microbe interaction in placenta-derived diseases.
Evaluation of Strabocheck® as an objective measurement method of comitant horizontal strabismus in children undergoing surgery

ABSTRACT The gold standard of angle measurement is the prism alternating cover test (PCT). This method requires cooperation from the child, experience, and presents a significant inter-observer variability. Strabocheck®(SK) is a new simple tool for objective and semi-automated angle measurement. Our purpose is to evaluate Strabocheck® in children undergoing surgery for comitant horizontal strabismus. The study population was divided into 3 groups: infantile esotropia, partially accommodative esotropia and intermittent exotropia. The primary endpoint was the agreement between Strabocheck®and the PCT. A total of 44 children were included prospectively. The correlation between the angle measured by the PCT and the angle measured by SK was strong (R = 0.87). The mean absolute difference in the angle measured by the two methods was Δ = 11.9+/- 9.8 diopters. The Bland-Altman plot shows a 95% interval limit between −30.0 [−34.4; −25.6] and 31.0 [26.7; 35.4] diopters. SK is an interesting tool to evaluate the angle of strabismus in children. However, the residual discordance between PCT and SK leads us to question the real value of the angle, which can only be approximated. A better clinical experience of this new tool in relation to the clinical condition and the PCT will allow to have a more accurate idea on the true angle and will probably help the surgeon to adapt this procedure.
Comparison of two point-of-care respiratory panels for the detection of influenza A/B virus

Abstract Background Rapid and accurate diagnostics of patients with suspected seasonal influenza or pathogens of the upper respiratory tract is crucial. Fast detection is important especially for influenza A/B virus, so that isolation measures should be taken to prevent the spread of the virus. Methods We compared the performance of two syndromic testing methodologies (QIAstat-Dx RP, BioFire RP2plus) against the Alere™ i as the comparator method. Totally, 97 swab samples were included from patients with symptoms of acute respiratory infection admitted in the hospitals of the wider region of Crete, Greece. Results The Positive Percent Agreement (PPA) of the BioFire RP2plus was 100% (95% CI 87.66%-100%), while the Negative Percent Agreement (NPA) was estimated at 91.3% (95% CI 82.03%–96.74%). This method produced no invalid results. For QIAstat-Dx RP the PPA was 89.29% (95% CI 71.77%-97.73%), while the NPA was 91.3% (95% CI 82.03%-96.74%, 63/69). The BioFire RP2plus managed to determine the subtype in more samples than the QIAstat-Dx RP. Conclusions Both panels can be valuable tools for clinicians, since they both display high sensitivity and specificity. We report a slightly better performance for BioFire RP2plus, since it produced no invalid results.
Identification of Type 4B Secretion System Substrates That Are Conserved among Coxiella burnetii Genomes and Promote Intracellular Growth

Coxiella burnetii secretes effector proteins via a T4BSS that are required for successful infection. Over 150 C. burnetii proteins are reported to be T4BSS substrates and often by default considered putative effectors, but few have assigned functions. ABSTRACT Coxiella burnetii is a Gram-negative pathogen that infects a variety of mammalian hosts. Infection of domesticated ewes can cause fetal abortion, whereas acute human infection normally manifests as the flu-like illness Q fever. Successful host infection requires replication of the pathogen within the lysosomal Coxiella-containing vacuole (CCV). The bacterium encodes a type 4B secretion system (T4BSS) that delivers effector proteins into the host cell. Disruption of C. burnetii T4BSS effector export abrogates CCV biogenesis and bacterial replication. Over 150 C. burnetii T4BSS substrates have been designated often based on heterologous protein translocation by the Legionella pneumophila T4BSS. Cross-genome comparisons predict that many of these T4BSS substrates are truncated or absent in the acute-disease reference strain C. burnetii Nine Mile. This study investigated the function of 32 proteins conserved among diverse C. burnetii genomes that are reported to be T4BSS substrates. Despite being previously designated T4BSS substrates, many of the proteins were not translocated by C. burnetii when expressed fused to the CyaA or BlaM reporter tags. CRISPR interference (CRISPRi) indicated that of the validated C. burnetii T4BSS substrates, CBU0122, CBU1752, CBU1825, and CBU2007 promote C. burnetii replication in THP-1 cells and CCV biogenesis in Vero cells. When expressed in HeLa cells tagged at its C or N terminus with mCherry, CBU0122 localized to the CCV membrane and the mitochondria, respectively. Collectively, these data further define the repertoire of bona fide C. burnetii T4BSS substrates. IMPORTANCE Coxiella burnetii secretes effector proteins via a T4BSS that are required for successful infection. Over 150 C. burnetii proteins are reported to be T4BSS substrates and often by default considered putative effectors, but few have assigned functions. Many C. burnetii proteins were designated T4BSS substrates using heterologous secretion assays in L. pneumophila and/or have coding sequences that are absent or pseudogenized in clinically relevant C. burnetii strains. This study examined 32 previously reported T4BSS substrates that are conserved among C. burnetii genomes. Of the proteins tested that were previously designated T4BSS substrates using L. pneumophila, most were not exported by C. burnetii. Several T4BSS substrates that were validated in C. burnetii also promoted pathogen intracellular replication and one trafficked to late endosomes and the mitochondria in a manner suggestive of effector activity. This study identified several bona fide C. burnetii T4BSS substrates and further refined the methodological criteria for their designation.
Noncommutative $\overline{M}_{0,n+1}$

We introduce and study noncommutative analogues of the Deligne-Mumford compactifications of moduli spaces of genus zero curves with marked points which exhibit all the remarkable algebraic and geometric features that the Deligne-Mumford compactifications possess. These analogues admit three different interpretations: as the brick manifolds recently defined by Escobar, as the toric varieties of Loday's realisations of the associahedra, or, equivalently, as the projective wonderful models of De Concini and Procesi for certain subspace arrangements.
Achilles tendon structure is associated with regular running volume and biomechanics

ABSTRACT Achilles tendinopathy was reported to have the highest incidence proportion of all running-related injuries. The purpose of this study was to analyse the association between the Achilles tendon structure and running activity status. 350 healthy participants (runners and inactive controls, 30-50 years) participated in this research. Each participant completed questionnaires: socioeconomic, psychological, physical activity habits, running status and history and VISA-A. Magnetic resonance imaging, anthropological, running biomechanics and 14 days of physical activity monitoring assessments were performed. There was a higher odd of being in the upper quartile of the Achilles tendon T2* relaxation time with higher maximal knee extension moment independent of age and sex. Compared with runners who ran 21–40 km per week, non-runners and those who ran more than 40 km per week had increased odds of having longest the Achilles tendon T2* relaxation time. Regular running of 21 to 40 km per week is related to the Achilles tendon T2* relaxation time indicating possibly better water content and collagen orientation in these runners with compare to inactive non-runners or highly active individuals. In addition, Achilles tendon T2* relaxation time as indirect indicator of the Achilles tendon structure was positively related to the maximal knee extension moment during running.
Impact of COVID-19 on health care and quality of life in women with breast cancer

Abstract Background The aims of this study were to explore the impact of COVID-19 on health-care services and quality of life (QoL) in women diagnosed with breast cancer (BC) in Ireland and whether the impact varied by social determinants of health (SDH). Methods Women diagnosed with BC completed a questionnaire measuring the impact of COVID-19, disruption to BC services, QoL, SDH, and clinical covariates during COVID-19 restrictions. The association between COVID-19 impact and disruption to BC services and QoL was assessed using multivariable regression with adjustment for SDH and clinical covariates. An interaction between COVID-19 impact and health insurance status was assessed within the regression models. Results A total of 30.5% (n = 109) of women reported high COVID-19 impact, and these women experienced more disruption in BC services (odds ratio = 4.95, 95% confidence interval = 2.28 to 10.7, P < .001) and lower QoL (β = −12.01, SE = 3.37, P < .001) compared with women who reported low COVID-19 impact. Health insurance status moderated the effect of COVID-19 on disruption to BC services and QoL. Women who reported high COVID-19 impact experienced more disruption to BC services and lower QoL compared with women with low COVID-19 impact; however, the magnitude of these unfavorable effects differed by insurance status (Pinteraction < .05). Conclusions There was a large disruption to BC services and decrease in QoL for women with BC in Ireland during the pandemic. However, the impact was not the same for all women. It is important that women with BC are reintegrated into proper care and QoL is addressed through multidisciplinary support services.