Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of Brain Microstructural Abnormalities in High Myopia Patients: A Preliminary Diffusion Kurtosis Imaging Study

Objective To evaluate microstructural damage in high myopia (HM) patients using 3T diffusion kurtosis imaging (DKI). Materials and Methods This prospective study included 30 HM patients and 33 age- and sex-matched healthy controls (HCs) with DKI. Kurtosis parameters including kurtosis fractional anisotropy (FA), mean kurtosis (MK), axial kurtosis (AK), and radial kurtosis (RK) as well as diffusion metrics including FA, mean diffusivity, axial diffusivity (AD), and radial diffusivity derived from DKI were obtained. Group differences in these metrics were compared using tract-based spatial statistics. Partial correlation analysis was used to evaluate correlations between microstructural changes and disease duration. Results Compared to HCs, HM patients showed significantly reduced AK, RK, MK, and FA and significantly increased AD, predominately in the bilateral corticospinal tract, right inferior longitudinal fasciculus, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, and left thalamus (all p < 0.05, threshold-free cluster enhancement corrected). In addition, DKI-derived kurtosis parameters (AK, RK, and MK) had negative correlations (r = −0.448 to −0.376, all p < 0.05) and diffusion parameter (AD) had positive correlations (r = 0.372 to 0.409, all p < 0.05) with disease duration. Conclusion HM patients showed microstructural alterations in the brain regions responsible for motor conduction and vision-related functions. DKI is useful for detecting white matter abnormalities in HM patients, which might be helpful for exploring and monitoring the pathogenesis of the disease.
Phase 1/2 Study of Lumasiran for Treatment of Primary Hyperoxaluria Type 1

Visual Abstract Background and objectives In the rare disease primary hyperoxaluria type 1, overproduction of oxalate by the liver causes kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an RNA interference therapeutic, suppresses glycolate oxidase, reducing hepatic oxalate production. The objective of this first-in-human, randomized, placebo-controlled trial was to evaluate the safety, pharmacokinetic, and pharmacodynamic profiles of lumasiran in healthy participants and patients with primary hyperoxaluria type 1. Design, setting, participants, & measurements This phase 1/2 study was conducted in two parts. In part A, healthy adults randomized 3:1 received a single subcutaneous dose of lumasiran or placebo in ascending dose groups (0.3–6 mg/kg). In part B, patients with primary hyperoxaluria type 1 randomized 3:1 received up to three doses of lumasiran or placebo in cohorts of 1 or 3 mg/kg monthly or 3 mg/kg quarterly. Patients initially assigned to placebo crossed over to lumasiran on day 85. The primary outcome was incidence of adverse events. Secondary outcomes included pharmacokinetic and pharmacodynamic parameters, including measures of oxalate in patients with primary hyperoxaluria type 1. Data were analyzed using descriptive statistics. Results Thirty-two healthy participants and 20 adult and pediatric patients with primary hyperoxaluria type 1 were enrolled. Lumasiran had an acceptable safety profile, with no serious adverse events or study discontinuations attributed to treatment. In part A, increases in mean plasma glycolate concentration, a measure of target engagement, were observed in healthy participants. In part B, patients with primary hyperoxaluria type 1 had a mean maximal reduction from baseline of 75% across dosing cohorts in 24-hour urinary oxalate excretion. All patients achieved urinary oxalate levels ≤1.5 times the upper limit of normal. Conclusions Lumasiran had an acceptable safety profile and reduced urinary oxalate excretion in all patients with primary hyperoxaluria type 1 to near-normal levels. Clinical Trial registry name and registration number: Study of Lumasiran in Healthy Adults and Patients with Primary Hyperoxaluria Type 1, NCT02706886
Detection of spatial and spatio‐temporal Salmonella Heidelberg and Salmonella Typhimurium human case clusters focused around licensed abattoirs in Ontario in 2015, and their potential relation to known outbreaks

Salmonellosis is one of several zoonotic diseases for which individuals with occupational animal contact, including abattoir workers, are at an increased risk. If meat is contaminated during slaughter, this can increase the risk of enteric illness for consumers. In this study, we investigated whether reported cases of Salmonella Heidelberg and Typhimurium were clustered around abattoirs in Ontario in 2015 and whether there was any evidence (laboratory/exposure) to suggest an abattoir at the centre of a cluster might be the source of exposure. Data for each reported case of S. Heidelberg and S. Typhimurium in Ontario in 2015 were collected. Multi‐focused and non‐focused spatial and space‐time cluster detection tests were performed for each serotype, with and without cases linked to known outbreaks, using Poisson and space‐time permutation models. Focused tests included the location of abattoirs operational in all or part of 2015. Laboratory data and exposure information were used to explore the relatedness of cases within identified clusters. Focused spatial tests identified clusters of S. Heidelberg and S. Typhimurium around abattoirs. Focused space‐time permutation tests identified 2 significant space‐time clusters of S. Heidelberg; one cluster (n = 11 cases) included 8 of 9 cases associated with a known outbreak and the other cluster (n = 18 cases) was not part of a previously identified outbreak. Review of laboratory and risk factor information suggested that cases within each cluster shared a common exposure. Cases were not asked about goat or sheep meat consumption. The focused cluster test, particularly with the space‐time permutation model, could assist in identifying outbreaks associated with a particular physical location, such as an abattoir. Improvements to the current case investigation process, such as consistent collection and reporting of high‐risk occupation information and more detailed food consumption history, could assist in outbreak identification when coupled with this statistic.
Concomitant Coronary Artery Bypass in Patients with Acute Type A Aortic Dissection.

Coronary Artery Bypass Grafting (CABG) is sometimes necessary in acute Type A Aortic Dissection (AAAD) repair. The aim of this study is to analyze the incidence, indications and influence in-hospital outcomes of AAAD repair requiring concomitant CABG in a high-volume single-center experience. Retrospective study of all consecutive AAAD patients. Those who underwent concomitant CABG were identified. Preoperative, intraoperative, postoperative and follow-up data were collected and analyzed. Between January 1st 2010 and December 31st 2016, 382 patients underwent emergency surgery for AAAD. Forty-one (10.7%) underwent concomitant CABG. In this group, mean age was 64±14 years, 32 were male (78%). Indication for CABG was coronary dissection in 28 patients (68.3%), post-cardiopulmonary bypass (CPB) right heart failure in 7 (17.1%), post CPB left heart failure in (7.3%) and native coronary pathology in 3 (7.3%). In 33 (80.5%) one graft was needed, in 7 (17%) two were performed and in 1 patient (2.4%) 3 were necessary. The right coronary artery (RCA) was the only revascularized vessel in 26 cases (63.4%), the left coronary artery (LCA) alone in 11 (26.8%), and both coronary systems in 4 (9.8%). In-hospital mortality was 51.2% (N=21); eight (19.5%) patients had postoperative myocardial infarction (MI) and 11 (26.8%) had a major neurological event. Multivariable logistic regression identified concomitant CABG as a predictor of in-hospital mortality (Odds Ratio (OR) =3.8115, 95% CI= 0.514-2.138, p =0.001). In our study, concomitant CABG was performed in 10.7% of AAAD repair surgery and it was associated with high in-hospital mortality.
Maternal smoking and smokeless tobacco use during pregnancy and offspring development: sibling analysis in an intergenerational Swedish cohort

Abstract Background The association between maternal smoking in pregnancy and offspring intellectual disability (ID) is less well understood than that of smoking and fetal growth restriction. As fetal growth and cognitive development may share similar confounding structures, comparison of the two associations may improve understanding of the causal nature of the association with ID. Furthermore, comparisons of smoking with smokeless tobacco use may aid identification of mechanisms of action. Methods This was a cohort study of all Swedish births between 1999 and 2012 (n = 1 070 013), with prospectively recorded data. We assessed the association between maternal smoking during pregnancy and offspring outcomes ID and born small for gestational age (SGA). Analyses were repeated for snus use in pregnancy. Using a sibling design, we estimated within-family effects that control for shared sibling characteristics. Results Those exposed to maternal smoking in pregnancy had increased odds of ID [odds ratio (OR) = 1.24, 95% confidence interval (CI): 1.16-1.33] and SGA (OR = 2.19, 95% CI: 2.11-2.27) after confounder adjustment. Within-family effects were found for SGA (OR = 1.44, 95% CI: 1.27-1.63) but not ID (OR = 0.92, 95% CI: 0.74-1.14). For snus use, the results for ID were similar to smoking. We found increased odds of offspring SGA among mothers who used snus in pregnancy in sensitivity analyses but not in primary analyses. Conclusions Our findings are consistent with a causal effect of maternal smoking in pregnancy on risk of offspring born SGA but not on risk of ID. We found no evidence for a causal effect of snus use in pregnancy on ID and inconclusive evidence for SGA.
Effects of decision-making on indoor bouldering performances: A multi-experimental study approach

The purpose of this study was to investigate whether novice, intermediate, and advanced bouldering athletes would differ in their decision-making abilities and to what extent distinct problem-solving tactics would affect the athletes’ bouldering performances. Seventy-seven male bouldering athletes participated in a multi-experimental study with the conceptual replication of three bouldering tasks. Participants were allocated according to their ability levels to the novice group (NOV with n = 18), the intermediate group (INT with n = 18), or the advanced group (ADV with n = 41). The data collected for movement analysis via video consisted of the pre-ascent decision-making times, the number of movement deviations from the best solution, the number of movement mistakes, the average gripping times, the bouldering times to the top, the number of successful ascents, and the number of attempts to complete the tasks. Results among all three experiments revealed shorter decision-making times, fewer movement mistakes, and shorter average gripping and bouldering times to the top in the ADV group than in the NOV group and the INT group. Furthermore, participants from the ADV group demonstrated fewer movement deviations than participants from the NOV group (in all three experiments) and the INT group (Experiment 1 and Experiment 2). Moreover, participants from the ADV group and the INT group were characterized, in all three experiments, by a higher number of successful ascents and a lower number of attempts to complete the tasks than participants from the NOV group. In total, these findings emphasize that accomplished decision-making abilities consist of a key determinant in successful indoor bouldering performances.
Mental-physical multimorbidity treatment adherence challenges in Brazilian primary care: A qualitative study with patients and their healthcare providers

Improved understanding of multimorbidity (MM) treatment adherence in primary health care (PHC) in Brazil is needed to achieve better healthcare and service outcomes. This study explored experiences of healthcare providers (HCP) and primary care patients (PCP) with mental-physical MM treatment adherence. Adults PCP with mental-physical MM and their primary care and community mental health care providers were recruited through maximum variation sampling from nine cities in São Paulo State, Southeast of Brazil. Experiences across quality domains of the Primary Care Assessment Tool-Brazil were explored through semi-structured in-depth interviews with 19 PCP and 62 HCP, conducted between April 2016 and April 2017. Through thematic conent analysis ten meta-themes concerning treatment adherence were developed: 1) variability and accessibility of treatment options available through PHC; 2) importance of coming to terms with a disease for treatment initation; 3) importance of person-centred communication for treatment initiation and maintenance; 4) information sources about received medication; 5) monitoring medication adherence; 6) taking medication unsafely; 7) perceived reasons for medication non-adherence; 8) most challenging health behavior change goals; 9) main motives for initiation or maintenance of treatment; 10) methods deployed to improve treatment adherence. Our analysis has advanced the understanding of complexity inherent to treatment adherence in mental-physical MM and revealed opportunities for improvement and specific solutions to effect adherence in Brazil. Our findings can inform research efforts to transform MM care through optimization.
Metabolic syndrome and its components in different phenotypes of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting reproductive‐age women. Important factors in its pathogenesis are hyperinsulinaemia and insulin resistance, which lead to higher risk of metabolic syndrome (MetS) and its complications. With the implementation of the Rotterdam diagnostic criteria in 2003, the group of PCOS patients became highly heterogeneous, with varying metabolic risk reported for different phenotypes of the syndrome. The aim of the present review is to assess the prevalence and severity of MetS and its components in patients with the four phenotypes of PCOS. A comprehensive search of Pubmed database was performed to identify studies comparing metabolic characteristics between PCOS patients with different phenotypes of the syndrome. The results of 60 studies published between 2004 and 2020 were retrieved and analysed. More adverse metabolic profile was observed in PCOS patients with hyperandrogenic phenotypes in comparison to normoandrogenic patients, as well as in classic phenotypes, defined by National Institutes of Health criteria, in comparison to newer phenotypes introduced by the Rotterdam criteria. In the majority of observations, normoandrogenic PCOS patients did not differ significantly from controls in terms of metabolic characteristics, although some East Asian studies reported more adverse metabolic profile in normoandrogenic phenotype in comparison to healthy women. In conclusion, metabolic abnormalities in PCOS seem to be associated with joint effects of hyperandrogenism, insulin resistance and visceral obesity. The differences observed between the four phenotypes of PCOS underline the need for individualised diagnostic and therapeutic approach.
A comprehensive pan-cancer analysis of CD274 gene amplification, tumor mutation burden, microsatellite instability, and PD-L1 expression in Chinese cancer patients

Background Immune checkpoint inhibitors blocking programmed cell death 1 (PD-1) or programmed cell death ligand 1 (PD-L1) have emerged as effective treatment options for cancer. However, immunotherapy is only effective in a subset of patients. Identifying effective biomarkers to predict the treatment response to PD-1/PD-L1 inhibitors remains an unmet clinical need. Methods This study retrospectively analyzed clinical information and genetic profiling results of 16,013 samples from Chinese patients with various cancer types in order to investigate the prevalence of CD274 (also known as PD-L1) amplification in various cancer types and its association with existing PD-1/PD-L1 biomarkers, including tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression. Results Amplification of CD274 was identified in 174 samples with an overall prevalence of 1.09% among all cancer types in the cohort. The prevalence of CD274 amplification in different cancer types and histological subtypes of lung cancer was varied, with cervical cancer having the highest prevalence. Distinct distributions of TMB, MSI, and PD-L1 expression between CD274-amplified and wild-type samples were observed in several cancer types as well as among different histological subtypes of lung cancer. Conclusions Although CD274 amplification was only observed in a small proportion of patients, it demonstrated an association with TMB, MSI, and PD-L1 expression in several common cancer types. The molecular features of CD274 in different cancer types are heterogeneous. The role of CD274 amplification as a novel biomarker of PD-1/PD-L1 inhibitors remains to be characterized in future prospective clinical studies.
Brain microstructural properties related to subjective well-being: diffusion tensor imaging analysis

Abstract Although it is known that health is not merely the absence of disease, the positive aspects of mental health have been less comprehensively researched compared with its negative aspects. Subjective well-being (SWB) is one of the indicators of positive psychology, and high SWB is considered to benefit individuals in multiple ways. However, the neural mechanisms underlying individual differences in SWB remain unclear, particularly in terms of brain microstructural properties as detected by diffusion tensor imaging. The present study aimed to investigate the relationship between measurements of diffusion tensor imaging [mean diffusivity (MD) and fractional anisotropy] and the degree of SWB as measured using a questionnaire. Voxel-based analysis was used to investigate the association between MD and SWB scores in healthy young adults (age, 20.7 ± 1.8 years; 695 males and 514 females). Higher levels of SWB were found to be associated with lower MD in areas surrounding the right putamen, insula, globus pallidus, thalamus and caudate. These results indicated that individual SWB is associated with variability in brain microstructural properties.
A real world investigation on prevalence, clinical features, and therapy of inflammatory bowel disease in the city of Messina, Italy

Background: The absence of a national register of inflammatory bowel diseases (IBD) hinders effective health care planning in Italy. Aims: to investigate prevalence of IBD in the city of Messina, Italy, based on General Practitioner (GP) records, and to establish current treatments prescribed by different health care providers. Methods: data were extracted from GP databases with the help of disease-specific healthcare cost exemption codes combined with ICD9 codes for ulcerative colitis (UC) and Crohn’s disease (CD), and prescription for mesalazine. Disease and treatment-related data were collected together with information on employment status and the current healthcare provider. Results: Eighty-six GPs participated covering a population of 100,834 people. IBD prevalence (419/105) was 80% higher than estimates of the Regional Health Authorities. Incidence showed a seven-fold increase over the past 30 years. Only 51% of CD and 26% of UC patients were followed by a dedicated IBD centre with more frequent prescriptions of immunomodulators and biologics (p<0.001) compared to GPs. Conclusions: Real world data show much higher figures on IBD prevalence than administrative estimates. Differences in therapeutic approaches between IBD-specialists and non-specialists may reflect poor confidence in managing immunosuppressive therapies by the latter, but may lead to inadequate therapy and cancer surveillance.
Utility of inflammatory biomarkers in patients with COVID-19 infections: Bahrain experience

Aim: COVID-19 pandemic continues and dearth of information remains considering the utility of various inflammatory biomarkers. We carried out the present study to delineate the roles of these biomarkers in various strata of patients with coronavirus infection. Materials & methods: A retrospective study was carried out after obtaining approval from the relevant Ethics Committee. Patients established with COVID-19 infection as shown by positive real-time quantitative PCR test were included. Details on their demographics, diagnosis, whether they received tocilizumab, and the values of the following biomarkers were obtained: IL-6, C-reactive protein (CRP), serum ferritin, D-dimer, procalcitonin, fibrinogen, lactate dehydrogenase and creatinine kinase. Receiver operating characteristic curves were plotted and correlation of biomarkers with IL-6 were estimated. Results: One-hundred and three patients were recruited. We observed that serum ferritin followed by D-dimer had better predictive accuracy in identifying patients with pneumonia compared with asymptomatic; and CRP in addition to the earlier markers had better accuracy for predicting severe illness compared with mild–moderate. Serum IL-6 levels were significantly higher in patients with severe illness admitted in intensive care unit. Significantly, higher levels of IL-6 and serum ferritin were observed in patients receiving tocilizumab. A trend of increased IL-6 levels was observed immediately following the initiation of tocilizumab therapy followed by a drop thereafter. Conclusion: We observed serum ferritin, D-dimer and CRP to accurately predict patients developing severe COVID-19 infections as well as those at risk of developing COVID pneumonia. A trend in IL-6 levels was observed in patients on tocilizumab therapy.
Dermoscopy of papulopustular rosacea and comparison of dermoscopic features in patients with or without concomitant Demodex folliculorum

The dermoscopic findings of papulopustular rosacea include tiny papules and pustules, follicular plugs and follicular dilatation. Demodex tails and Demodex follicular openings are dermoscopic indicators that are mainly found in primary demodicosis and, less frequently, in rosacea.
Epidemiology of human West Nile virus infections in the European Union and European Union enlargement countries, 2010 to 2018

Background West Nile virus (WNV) circulates in an enzootic cycle involving mosquitoes and birds; humans are accidental hosts. Aim We analysed human WNV infections reported between 2010 and 2018 to the European Centre for Disease Prevention and Control to better understand WNV epidemiology. Methods We describe probable and confirmed autochthonous human cases of WNV infection reported by European Union (EU) and EU enlargement countries. Cases with unknown clinical manifestation or with unknown place of infection at NUTS 3 or GAUL 1 level were excluded from analysis. Results From southern, eastern and western Europe, 3,849 WNV human infections and 379 deaths were reported. Most cases occurred between June and October. Two large outbreaks occurred, in 2010 (n = 391) and in 2018 (n = 1,993). The outbreak in 2018 was larger than in all previous years and the first cases were reported unusually early. The number of newly affected areas (n = 45) was higher in 2018 than in previous years suggesting wider spread of WNV. Conclusion Real-time surveillance of WNV infections is key to ensuring that clinicians and public health authorities receive early warning about the occurrence of cases and potential unusual seasonal patterns. Human cases may appear shortly after first detection of animal cases. Therefore, public health authorities should develop preparedness plans before the occurrence of human or animal WNV infections.
(Chemo)Radiotherapy–Immunotherapy Combinations: Time to Get Tailored?

Chemoradiotherapy is considered an immunogenic anticancer treatment. Data obtained during the course of chemoradiotherapy treatment of patients with cervical cancer show heterogeneous changes in the tumor immune landscape, highlighting the need for patient selection to rationally design successful combined immunotherapies. Blood-based biomarkers could be valuable to perform such stratification. See related article by Chen et al., p. 3990