Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Xylo-Oligosaccharides Supplementation by Drinking Water on the Bone Properties and Related Calcium Transporters in Growing Mice

Xylo-oligosaccharides (XOS), non-digestible oligosaccharides, have the potential to regulate intestinal microorganisms, and thus, improve host health, but little evidence exists for the prebiotic effects on bone health. This study evaluates the dose-response effect of XOS supplementation on bone properties, the morphology of the intestine, cecum pH, and cecum wall weight, as well as the related calcium transporters. Ninety-six 28-day-old male mice were randomized into one of four groups, fed the same commercial diet, and given different types of deionized water containing 0, 1, 2, or 4% XOS by concentration for 30 days. Eight mice were randomly selected to accomplish particular tasks every 10 days. No significant differences in serum Ca and P levels and growth performance were observed among the four studied groups. XOS intervention significantly decreased cecum pH and increased cecum wall weight in a dose-dependent manner. At the late growth stage, compared with 0% XOS, the bone mineral density (BMD) and bone-breaking strength in 4% XOS were significantly higher. The bone crystallinity with 4% XOS, measured by Raman spectrum, was significantly enhanced compared to that with 0% XOS during later growth. The villus height and villus height to crypt depth (VH:CD) were enhanced with an increase of XOS concentration during the later stage of growth. The expression of transient receptor potential vanillin receptor 6 (TRPV6) and Na+/Ca2+ exchanger 1 (NCX1) in the duodenum were enhanced by XOS supplementation. XOS exerted a positive influence on bone properties by decreasing the cecum pH, increasing the cecum wall and villus structure, and upregulating the expression of related calcium transporters.
Evolution in Management Trends of Sporadic Vestibular Schwannoma in the United States Over the Last Half-century

Objective: Limited data currently characterize management trends of sporadic vestibular schwannoma (VS) in the United States over recent decades. Serving as the primary patient support organization in the United States, the Acoustic Neuroma Association (ANA) facilitates amalgamation of data from patients treated from 1970 through January 2019. The primary objective of the current study was to characterize the evolution in the management of sporadic VS among ANA survey respondents treated over the last half-century. Study Design/Intervention: Cross-sectional survey. Setting/Patients: ANA survey respondents diagnosed with sporadic VS. Main Outcome Measures: Trends in rates of microsurgery, radiosurgery, and observation from 1970 to 2019. Results: Among 953 patients with VS responding during the study period, 876 (92%) were included. Subjects reported the following management strategies: 220 observation (25%), 454 microsurgery (52%), and 193 radiosurgery (22%). The rate of microsurgery decreased from 86–88% from 1970 to 2000 to 44% in the last decade. The proportion of VS observed increased from 7% of all tumors in the 1990s, to 14% in the 2000s, to 33% in the 2010s. The rate of radiosurgery has increased to 28% in the last decades compared with 7% in the 1990s. The rate of subtotal resection in tumors > 2 cm increased from 34% in the 2000s to 60% in the 2010s (p = 0.0011). Conclusions: Overall, these data support a progression toward fewer patients treated with microsurgery in recent decades. Radiosurgery and observation became increasingly more common after the turn of the century, possibly due to better detection of small and asymptomatic tumors and a greater understanding of the natural history of disease.
Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020

Key Points Question What proportion of persons across 52 US jurisdictions had detectable antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from July to September 2020? Findings In this repeated, cross-sectional study of 177 919 residual clinical specimens, the estimated percentage of persons in a jurisdiction with detectable SARS-CoV-2 antibodies ranged from fewer than 1% to 23%. Over 4 sampling periods in 42 of 49 jurisdictions with calculated estimates, fewer than 10% of people had detectable SARS-CoV-2 antibodies. Meaning While SARS-CoV-2 antibody prevalence estimates varied widely across jurisdictions, most people in the US did not have evidence of previous SARS-CoV-2 infection.
Influence of MXene (Ti3C2) Phase Addition on the Microstructure and Mechanical Properties of Silicon Nitride Ceramics

This paper discusses the influence of Ti3C2 (MXene) addition on silicon nitride and its impact on the microstructure and mechanical properties of the latter. Composites were prepared through powder processing and sintered using the spark plasma sintering (SPS) technic. Relative density, hardness and fracture toughness, were analyzed. The highest fracture toughness at 5.3 MPa·m1/2 and the highest hardness at HV5 2217 were achieved for 0.7 and 2 wt. % Ti3C2, respectively. Moreover, the formation of the Si2N2O phase was observed as a result of both the MXene addition and the preservation of the α-Si3N4→β-Si3N4 phase transformation during the sintering process.
Refractive surgery with simultaneous collagen cross-linking for borderline corneas - A review of different techniques, their protocols and clinical outcomes

Simultaneous corneal cross-linking (CXL) has been proposed as an adjunct therapy to corneal refractive procedures to prevent future ectasia, especially when performed in borderline corneas. This review analyses the currently available literature (minimum follow-up 6 months) on corneal refractive surgery and simultaneous CXL (PRK Xtra, LASIK Xtra, and SMILE Xtra) to evaluate the overall results including the safety, efficacy, and potential complications associated with these procedures. A comprehensive literature search of various electronic databases (PubMed, PubMed Central, Cochrane database, and MEDLINE) was performed up to 20th May 2020. Four relevant studies were found for PRK Xtra, 12 for LASIK Xtra, and 3 for SMILE Xtra. The total number of eyes included in this review was 1,512: 294 for PRK Xtra, 221 for PRK-only, 446 eyes for LASIK Xtra, 398 eyes for LASIK-only, 91 for SMILE Xtra and 62 for SMILE-only. Current literature suggests that refractive surgery and simultaneous CXL is generally safe and delivers comparable results in terms of visual and refractive outcomes than refractive surgery alone. However, there is no consensus on a standard cross-linking protocol, and complications such as diffuse lamellar keratitis, central toxic keratopathy, and corneal ectasia following Xtra procedures have been reported. It is therefore suggested that surgeons exercise caution in case-selection and counsel their patients regarding the potential risks and benefits with Xtra procedures. Also, further studies are required to standardize the UV-A irradiation protocols and to evaluate the long-term effect on safety, refractive predictability, and stability of these procedures.
A Comparison of Dizziness Handicap Inventory Scores by Categories of Vestibular Diagnoses

Objective: The Dizziness Handicap Inventory (DHI) is a 25-item self-report quantifying dizziness-related physical and emotional symptoms and restrictions in daily activities. DHI scores do not correlate with severity of structural vestibular deficits; thus, high DHI scores may reflect other causes of morbidity. This study investigated the relationship between total DHI scores and the presence of structural, functional, and psychiatric disorders in tertiary neurotology patients. Study Design: Retrospective. Setting: Tertiary center. Patients: Eighty-five patients who underwent multidisciplinary neurotologic evaluations. Intervention: Diagnostic. Main Outcome Measure(s): Active illnesses identified by a multidisciplinary neurotology team were abstracted from medical records, cataloged as structural, functional, or psychiatric disorders, and used to group patients into diagnostic categories: structural (structural disorders only), functional (functional disorders with/without structural disorders), and psychiatric (psychiatric disorders with/without other conditions). DHI scores were compared across diagnostic categories. Sensitivities and specificities of DHI scores for identifying structural versus functional or psychiatric disorders were calculated. Results: Mean DHI scores differed significantly by diagnostic category (structural 35 ± 18, functional 64 ± 15, and psychiatric 65 ± 19), before and after adjusting for age and sex (p < 0.001, Hedges’ g>1.62 for structural versus functional and psychiatric categories). DHI≤30 (mild handicap) had specificity = 0.98 for structural disorders alone, whereas DHI>60 (severe handicap) had specificity = 0.88 for functional or psychiatric disorders. Conclusions: In this tertiary cohort, categories of illnesses had large effects on total DHI scores. Patients with scores ≤30 were likely to have structural disorders alone, whereas those with scores >60 were likely to have functional or psychiatric disorders, with or without coexisting structural conditions.
Flipped Classrooms in Physician Assistant Education.

PURPOSE This study assessed the impact of flipped classrooms on physician assistant (PA) students' performance and opinions. METHODS Students completed quizzes and an opinion survey in Genetics, Human Pathophysiology (HPP), Clinical Medicine (CM) (n = 105) and Physical Exam (PE) (n = 98) courses. RESULTS In Genetics and PE, the quiz scores were significantly higher for flipped classrooms (Genetics 95.00 ± 6.56; PE 83.09 ± 11.47) compared to the traditional lectures (Genetics 90.00 ± 10.53; PE 55.43 ± 16.66). In HPP, students performed better with traditional lectures (86.54 ± 8.82) compared to the flipped classrooms (75.12 ± 8.54). In CM, students' gain score was significantly higher for flipped classrooms (37.85 ± 16.73) than for traditional lectures (20.97 ± 15.55). The opinion surveys showed that the students surveyed preferred traditional lectures over flipped classrooms in Genetics (4.58 ± 0.46 vs. 2.29 ± 0.71) and HPP (4.14 ± 0.35 vs. 2.09 ± 0.53). CONCLUSION Flipped classrooms improved the quality of learning in courses that deliver a hands-on skill or use case-based scenarios. They may not be an ideal choice for courses that require explanation of intricate scientific concepts.
Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma.

BACKGROUND Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials. METHODS We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided. RESULTS In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group. CONCLUSIONS Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.
Predicting conformational ensembles of the intrinsically disordered protein α-Synuclein via molecular simulation

Intrinsically disordered proteins (IDPs) represent 30% of the human genome. They are frequently involved in a variety of diseases including neurodegenerative disorders, cancer and cardiovascular diseases. Interfering with the function of disease-associated IDPs offers a highly attractive objective for drug development. Unfortunately, the highly dynamic nature of IDPs, the presence of continuous local and global conformational rearrangements, the transient secondary and long-range tertiary structure pose serious limits to experimental approaches aimed at designing rationally new drugs. Computational methods may be of great help to characterize IDPs and their binding to drugs, yet they also faces critical challenges in sampling the wide IDPs’ conformational space, with force field and analysis tools tailored for structured proteins. My thesis addresses IDPs computational issues by adopting apt computational protocols, combined with new analysis tools developed here. I focus on human α-synuclein (AS), a presynaptic protein of poorly defined function, whose aggregations constitute the main component of Parkinson disease-associated Lewy bodies. The first aim of this thesis is to characterize the structural determinants of the binding between AS and an anti-aggregation ligand, dopamine (DOP), which has been shown to prevent aggregation. We developed a new conformational analysis tool based on directional statistics. The tool not only is able to detect and quantitatively analyze protein residues’ flexibility and backbone conformational transitions, it is also able to quantitative detect the effects of the ligand on the dynamical spectra of the protein, avoiding problems associated with usual computational analysis tools based on Cartesian coordinates, which are biased by the problematic alignment of extremely flexible structures, besides being affected by the movements of neighboring residues. This tool provided a rationale for experimentally observed changes in chemical shifts on passing from free AS to AS DOP adducts, distinguishing variations arising from conformational rearrangements of residues with respect to the ones due to direct contacts with the drug. The second aim of the thesis is to adapt an enhanced sampling method to investigate the changes of conformational ensemble upon a physiologically relevant chemical modification, the N-term acetylation, recently revealed in human cells. The degree of sampling of our simulations and the quality of our models, in the first and second project, has been carefully validated against experimental data. Structural experimental quantities have been successfully reproduced. The methods proposed in my thesis provide a solid computational framework, which could be of great help for the characterization of the structural determinants of IDPs of pharmacological relevance also in the presence of drugs. Computational and semiquantitative characterizations methods, like the ones adopted here, may provide crucial insights for future therapeutic strategies in drug design.
The effect of gamma irradiation on platelet redox state during storage

As a method with insignificant adverse effects on in vitro quality of platelet concentrates (PCs), gamma irradiation is applied to abrogate the risk of transfusion‐associated graft‐vs‐host disease in vulnerable recipients. However, there is some evidence of lower posttransfusion responses and proteomic alterations in gamma‐irradiated platelets (PLTs), which raises some questions about their quality, safety, and efficacy. Since reactive oxygen species (ROS) are considered as markers of PLT storage lesion (PSL), the study presented here investigated oxidant state in gamma‐irradiated PCs.
Distribution of serum uric acid levels and prevalence of hyper- and hypouricemia in a Korean general population of 172,970

Background/Aims We investigated the distribution of serum uric acid (SUA) levels and estimated the prevalence of hyperuricemia and hypouricemia in the Korean population. Methods This cross-sectional study used data from the Korean Genome and Epidemiology Study and included 172,970 participants (58,981 men and 113,989 women) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. Results The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall prevalence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prevalence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. Conclusions The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.
Review of current status of refractive lens exchange and role of dysfunctional lens index as its new indication

Advances in phacodynamics and intraocular lenses (IOLs) has given second life to clear lens extraction (CLE) or refractive lens exchange (RLE) in recent years for the treatment of patients with high degrees of myopia, hyperopia, and astigmatism who are unsuitable for laser surgery. Furthermore, presbyopia treatment with RLE supplemented with multifocal or accommodating IOLs gives the dual benefit of correcting refractive errors with eliminating the need for cataract surgery. RLE should be consistent and effective for a good refractive outcome along with safety during the surgical procedure and in the postoperative period. Therefore, proper patient selection and accurate preoperative protocols for IOL power calculations and selection are important along with an appropriate choice of surgical procedure. Dysfunctional lens index is a new objective tool that helps surgeon to aid in diagnosing, counseling, and educating patients with dysfunctional clear lens. In this article, we give a brief overview about the application of RLE for individuals with presbyopia and refractive errors like myopia, hyperopia, and astigmatism who are not suitable for laser correction.
Genetic testing in patients with possible foetal alcohol spectrum disorder

Objective To assess the diagnostic yield of genetic conditions in patients referred to a regional genetics service to consider a diagnosis of foetal alcohol spectrum disorder. Design Retrospective case series. Setting A regional genetics centre in Yorkshire. Patients All referrals to the Yorkshire Regional Genetics Service coded with mentions of maternal alcoholism or foetal alcohol were considered for inclusion. Exclusion criteria were follow-up patients, patients with missing case notes and patients failing to attend their appointment. Methods Medical records were reviewed and the following information was extracted: referring specialty, reason for referral, gender, age at assessment by clinical genetics, accompanying individual, history of alcohol exposure in pregnancy, clinical examination details, neurodevelopmental deficits, genetic testing prior to referral, genetic testing organised by the genetics department and diagnosis made by clinical genetics. Results and conclusion 110 patients were included. 130 tests were carried out, including 86 array comparative genomic hybridisation tests. The overall diagnostic rate for a contributing genetic disorder was 3.6%, all being chromosomal disorders and chromosome copy number variants.
Development and External Validation of a Machine Learning Tool to Rule Out COVID-19 Among Adults in the Emergency Department Using Routine Blood Tests: A Large, Multicenter, Real-World Study

Background Conventional diagnosis of COVID-19 with reverse transcription polymerase chain reaction (RT-PCR) testing (hereafter, PCR) is associated with prolonged time to diagnosis and significant costs to run the test. The SARS-CoV-2 virus might lead to characteristic patterns in the results of widely available, routine blood tests that could be identified with machine learning methodologies. Machine learning modalities integrating findings from these common laboratory test results might accelerate ruling out COVID-19 in emergency department patients. Objective We sought to develop (ie, train and internally validate with cross-validation techniques) and externally validate a machine learning model to rule out COVID 19 using only routine blood tests among adults in emergency departments. Methods Using clinical data from emergency departments (EDs) from 66 US hospitals before the pandemic (before the end of December 2019) or during the pandemic (March-July 2020), we included patients aged ≥20 years in the study time frame. We excluded those with missing laboratory results. Model training used 2183 PCR-confirmed cases from 43 hospitals during the pandemic; negative controls were 10,000 prepandemic patients from the same hospitals. External validation used 23 hospitals with 1020 PCR-confirmed cases and 171,734 prepandemic negative controls. The main outcome was COVID 19 status predicted using same-day routine laboratory results. Model performance was assessed with area under the receiver operating characteristic (AUROC) curve as well as sensitivity, specificity, and negative predictive value (NPV). Results Of 192,779 patients included in the training, external validation, and sensitivity data sets (median age decile 50 [IQR 30-60] years, 40.5% male [78,249/192,779]), AUROC for training and external validation was 0.91 (95% CI 0.90-0.92). Using a risk score cutoff of 1.0 (out of 100) in the external validation data set, the model achieved sensitivity of 95.9% and specificity of 41.7%; with a cutoff of 2.0, sensitivity was 92.6% and specificity was 59.9%. At the cutoff of 2.0, the NPVs at a prevalence of 1%, 10%, and 20% were 99.9%, 98.6%, and 97%, respectively. Conclusions A machine learning model developed with multicenter clinical data integrating commonly collected ED laboratory data demonstrated high rule-out accuracy for COVID-19 status, and might inform selective use of PCR-based testing.