Miracle-dz/UniFAR-FTUs huggingface dataset:
Timing and Impact of Psychiatric, Cognitive, and Motor Abnormalities in Huntington Disease

Objective To assess the prevalence, timing, and functional impact of psychiatric, cognitive, and motor abnormalities in Huntington disease (HD) gene carriers, we analyzed retrospective clinical data from individuals with manifest HD. Methods Clinical features of patients with HD were analyzed for 6,316 individuals in an observational study of the European Huntington's Disease Network (REGISTRY) from 161 sites across 17 countries. Data came from clinical history and the patient-completed Clinical Characteristics Questionnaire that assessed 8 symptoms: motor, cognitive, apathy, depression, perseverative/obsessive behavior, irritability, violent/aggressive behavior, and psychosis. Multiple logistic regression was used to analyze relationships between symptoms and functional outcomes. Results The initial manifestation of HD is increasingly likely to be motor and less likely to be psychiatric as age at presentation increases and is independent of pathogenic CAG repeat length. The Clinical Characteristics Questionnaire captures data on nonmotor symptom prevalence that correlate specifically with validated clinical measures. Psychiatric and cognitive symptoms are common in HD gene carriers, with earlier onsets associated with longer CAG repeats. Of patients with HD, 42.4% reported at least 1 psychiatric or cognitive symptom before motor symptoms, with depression most common. Each nonmotor symptom was associated with significantly reduced total functional capacity scores. Conclusions Psychiatric and cognitive symptoms are common and functionally debilitating in HD gene carriers. They require recognition and targeting with clinical outcome measures and treatments. However, because it is impossible to distinguish confidently between nonmotor symptoms arising from HD and primary psychiatric disorders, particularly in younger premanifest patients, nonmotor symptoms should not be used to make a clinical diagnosis of HD. Trial Registration Information ClinicalTrials.gov Identifier: NCT01590589
‘Living in parallel worlds’ – bereaved parents’ experience of family life when a parent with dependent children is at end of life from cancer: A qualitative study

Background: When a parent of dependent children (<18 years old) is at end of life from cancer, this has a profound impact on the family. Children less prepared for the death of a parent are more susceptive to poorer psychosocial adjustment in later life. There is a lack of understanding from the literature surrounding what support parents require, and how they navigate this end of life experience. Aim: To explore bereaved parents’ experience and needs for families when a parent is at end of life from cancer with dependent children. Design: In-depth, semi-structured qualitative interviews were conducted with 21 bereaved mothers and fathers, identified from the general public, a family support service and hospice. Data were analysed thematically. Results: Parents often live in ‘parallel worlds’ throughout the end of life period. In one world, ‘living in the moment’, cherishing the ordinariness of family life, remaining hopeful treatment will prolong life, whilst adapting as the illness unfolds. The other world presents as ‘intermitted glimpses that death is approaching’, shadowed with painful emotional concerns surrounding their children and the future. At the end, death rapidly approaches, characterised as suddenly ‘falling off the cliff’; placing significant demands on the well-parent. Conclusions: Amidst challenges, clinicians should provide parents with clear information surrounding a poor prognosis, so families can plan and prepare for parental death. There is a need for healthcare professionals to engage, encourage and equip parents, as they prepare their children throughout the end of life experience for the inevitable death of a parent.
Nitazoxanide versus rifaximin in preventing the recurrence of hepatic encephalopathy: A randomized double‐blind controlled trial

Hepatic encephalopathy (HE) is a neuropsychiatric complication of liver cirrhosis. HE is associated with poor survival and detrimental effects on quality of life (QOL). The drawbacks of the long‐term use of rifaximin in HE necessitates searching for alternative therapies. In this context, our study aimed at evaluating the safety and efficacy of nitazoxanide (NTZ) as compared to rifaximin (RFX) in preventing the recurrence of HE and assessing its impact on QOL.
Pressure Cooker Technique for Endovascular Treatment of Spinal Arteriovenous Fistulas: Experience in 15 Cases

The pressure cooker technique is feasible, with either glue or ethylene-vinyl alcohol, for the embolization of spinal arteriovenous fistulas. BACKGROUND AND PURPOSE: Spinal arteriovenous fistulas are challenging to cure by endovascular means, with a risk of incomplete occlusion or delayed recurrence. The authors report herein their preliminary experience using the pressure cooker technique for the embolization of spinal arteriovenous fistulas. MATERIALS AND METHODS: Fifteen patients (8 men; mean age, 60.3 years) underwent an endovascular treatment of a spinal arteriovenous fistula (12 dural spinal arteriovenous fistulas and 3 epidural spinal arteriovenous fistulas) in 2 different institutions using the pressure cooker technique. Two microcatheters could be navigated in the segmental artery in all patients using 2 guiding catheters. A proximal plug was achieved with highly concentrated cyanoacrylate ± coils. The liquid embolic agent injected to cure the fistula was diluted cyanoacrylate (n = 11) or ethylene-vinyl alcohol (n = 4). Technical and clinical complications were systematically recorded. Clinical and angiographic outcomes were systematically evaluated at follow-up. RESULTS: One (6.7%) procedure-related complication was recorded, which consisted of a transient radicular deficit, related to nerve root ischemia. Clinical improvement was observed in 10/14 (71%) patients for whom clinical follow-up was available. Complete spinal arteriovenous fistula occlusion on a follow-up angiography was observed in 11/12 patients (91.7%) for whom angiographic follow-up was available. One patient (8.3%) presented with a delayed recurrence at 29 months. CONCLUSIONS: The pressure cooker technique is feasible, with either glue or ethylene-vinyl alcohol, for the embolization of spinal arteriovenous fistulas. Our results suggest the safety and effectiveness of this technique.
Speciation across the Tree of Life

Much of what we know about speciation comes from detailed studies of well‐known model systems. Although there have been several important syntheses on speciation, few (if any) have explicitly compared speciation among major groups across the Tree of Life. Here, we synthesize and compare what is known about key aspects of speciation across taxa, including bacteria, protists, fungi, plants, and major animal groups. We focus on three main questions. Is allopatric speciation predominant across groups? How common is ecological divergence of sister species (a requirement for ecological speciation), and on what niche axes do species diverge in each group? What are the reproductive isolating barriers in each group? Our review suggests the following patterns. (i) Based on our survey and projected species numbers, the most frequent speciation process across the Tree of Life may be co‐speciation between endosymbiotic bacteria and their insect hosts. (ii) Allopatric speciation appears to be present in all major groups, and may be the most common mode in both animals and plants, based on non‐overlapping ranges of sister species. (iii) Full sympatry of sister species is also widespread, and may be more common in fungi than allopatry. (iv) Full sympatry of sister species is more common in some marine animals than in terrestrial and freshwater ones. (v) Ecological divergence of sister species is widespread in all groups, including ~70% of surveyed species pairs of plants and insects. (vi) Major axes of ecological divergence involve species interactions (e.g. host‐switching) and habitat divergence. (vii) Prezygotic isolation appears to be generally more widespread and important than postzygotic isolation. (viii) Rates of diversification (and presumably speciation) are strikingly different across groups, with the fastest rates in plants, and successively slower rates in animals, fungi, and protists, with the slowest rates in prokaryotes. Overall, our study represents an initial step towards understanding general patterns in speciation across all organisms.
Sieve analysis to understand how SARS-CoV-2 diversity can impact vaccine protection

1 U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America, 2 Emerging Infectious Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America, 3 Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, United States of America, 4 Vaccine and Infectious Disease and Public Health Sciences Divisions, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America, 5 Department of Biostatistics, University of Washington, Seattle, Washington, United States of America
Entorhinal cortex and parahippocampus volume reductions impact olfactory decline in aged subjects

Pathological abnormalities first appear in the medial temporal regions including entorhinal cortex and parahippocampus in patients with Alzheimer's disease. Previous studies showed that olfactory decline in elderly subjects was associated with volume reductions in the left hippocampus and left parahippocampus without cognitive impairment. The aim of this study is to investigate the link between olfaction and volume reductions in the medial temporal regions including the parahippocampus, entorhinal cortex, and hippocampal subfields.
Adolescent Dating Violence: Results of a Mixed Study in Quito, Ecuador

Dating violence is a public health problem affecting people worldwide. This study evaluated the occurrence of different types of adolescent dating violence using a mixed analysis of each data source. The present study addresses the following research questions: does the occurrence of the types of violence analyzed in the quantitative phase match with the narratives obtained in the qualitative phase? and does the additional information obtained in the qualitative phase improve the understanding of the analyzed phenomenon? In the quantitative phase, 410 participants (aged 13 to 19 years) answered a questionnaire based on the Modified Conflict Tactics Scale, while in the qualitative phase, 26 participated in two focus groups. Data were collected from May to June 2019. Written informed consent was obtained from the parents or legal guardians of those who had agreed to participate. The present research was approved by the Human Research Ethics Committee of the Pontifical Catholic University of Ecuador. The results were divided on: prevalence of dating violence based on age groups and gender, management and resolution of dating conflicts, victimization and perpetration of intimate partner violence, factors favoring intimate partner violence and acceptance of abuse. The results were analyzed via triangulation and indicated that adolescents were involved in the perpetration and victimization of psychological as well as mild and severe physical violence. An analysis of the contributing factors revealed a strong tendency toward the acceptance of the traditional gender model. Challenging these models is crucial to deconstruct hierarchical models, develop conflict resolution skills, and promptly identify abusive behaviors that affect emotional development. The combination of different methodological approaches improved the understanding of the phenomenon studied.
Association between myocardial work and functional capacity in patients with arterial hypertension: an echocardiographic study

Abstract Purpose The aim of this study was to examine myocardial performance using pressure-strain loops in hypertensive patients with different level of blood pressure control. Material and methods This cross-sectional study included 204 subjects (45 controls, 70 patients with well-controlled hypertension, 58 patients with uncontrolled hypertension and 31 patients with resistant hypertension) who underwent complete two-dimensional echocardiographic examination including two-dimensional speckle-tracking echocardiography. Pressure-strain curve was used to determine global myocardial work, constructive work, wasted work and work efficiency in all study participants. Results Left ventricular (LV) longitudinal strain gradually reduced from controls throughout well-controlled hypertensive patients, to patients with uncontrolled and resistant hypertension. Global myocardial work was higher in patients with uncontrolled and resistant hypertension than in controls and well-controlled hypertension. Constructive work was also higher in all hypertensive patients than in controls. Global wasted work and work efficiency were similar between different groups. Global myocardial work index was associated with peak oxygen consumption independently of sex, age, body mass index (BMI), LV structural and functional parameters in all hypertensive participants. Conclusions Myocardial work was significantly deteriorated in patients with uncontrolled and resistant arterial hypertension compared to controls and well-controlled hypertensive patients. Global myocardial work was associated with functional capacity independent of clinical and echocardiographic parameters.
Ultrasound performed shortly after birth can predict the respiratory support needs of late preterm and term infants: A diagnostic accuracy study

Late preterm and term infants may develop respiratory issues with severe outcomes. Early identification of these diseases shortly after infants' birth can improve their management. Lung ultrasound (LUS) has been used to diagnose neonatal respiratory diseases. However, few LUS methods have been reported to predict the need for respiratory support, the basis of infant respiratory diseases management.
Copper-Catalyzed Synthesis of Tetrasubstituted Alkenes via Regio- and anti-Selective Addition of Silylboronates to Internal Alkynes.

As a new and complementary method for the synthesis of structurally defined tetrasubstituted alkenes, a copper-catalyzed regio- and anti-selective addition of silylboronates to unsymmetric internal alkynes has been developed. A variety of unactivated alkynes can be employed with high selectivity under simple and mild conditions and the resulting products have been further functionalized by utilizing silyl and boryl groups on the alkene.
Genetic Engineering in Combination with Semi‐Synthesis Leads to a New Route for Gram‐Scale Production of the Immunosuppressive Natural Product Brasilicardin A

Abstract Brasilicardin A (1) consists of an unusual anti/syn/anti‐perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre‐clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low‐yielding fermentation process using a pathogenic organism and an elaborate, multi‐step total synthesis. Our semi‐synthetic approach included a) the heterologous expression of the brasilicardin A gene cluster in different non‐pathogenic bacterial strains producing brasilicardin A aglycone (5) in excellent yield and b) the chemical transformation of the aglycone 5 into the trifluoroacetic acid salt of brasilicardin A (1 a) via a short and straightforward five‐steps synthetic route. Additionally, we report the first preclinical data for brasilicardin A.
Training the social brain: Clinical and neural effects of an 8-week real-time functional magnetic resonance imaging neurofeedback Phase IIa Clinical Trial in Autism

Autism spectrum disorder is characterized by abnormal function in core social brain regions. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback. Following up the demonstration of neuromodulation in healthy participants, in this repeated-measure design clinical trial, 15 autism spectrum disorder patients were enrolled in a 5-session training program of real-time functional magnetic resonance imaging neurofeedback targeting facial emotion expressions processing, using the posterior superior temporal sulcus as region-of-interest. Participants were able to modulate brain activity in this region-of-interest, over multiple sessions. Moreover, we identified the relevant clinical and neural effects, as documented by whole-brain neuroimaging results and neuropsychological measures, including emotion recognition of fear, immediately after the intervention and persisting after 6 months. Neuromodulation profiles demonstrated subject-specificity for happy, sad, and neutral facial expressions, an unsurprising variable pattern in autism spectrum disorder. Modulation occurred in negative or positive directions, even for neutral faces, in line with their often-perceived ambiguity in autism spectrum disorder. Striatal regions (associated with success/failure of neuromodulation), saliency (insula/anterior cingulate cortex), and emotional control (medial prefrontal cortex) networks were recruited during neuromodulation. Recruitment of the operant learning network is consistent with participants’ engagement. Compliance, immediate intervention benefits, and their persistence after 6 months pave the way for a future Phase IIb/III, randomized controlled clinical trial, with a larger sample that will allow to conclude on clinical benefits from neurofeedback training in autism spectrum disorder (NCT02440451). Lay abstract Neurofeedback is an emerging therapeutic approach in neuropsychiatric disorders. Its potential application in autism spectrum disorder remains to be tested. Here, we demonstrate the feasibility of real-time functional magnetic resonance imaging volitional neurofeedback in targeting social brain regions in autism spectrum disorder. In this clinical trial, autism spectrum disorder patients were enrolled in a program with five training sessions of neurofeedback. Participants were able to control their own brain activity in this social brain region, with positive clinical and neural effects. Larger, controlled, and blinded clinical studies will be required to confirm the benefits.
Industrial Synthesis of the Key Precursor in the Synthesis of the Anti-Influenza Drug Oseltamivir Phosphate (Ro 64-0796/002, GS-4104-02): Ethyl (3R,4S,5S)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate

Starting from (−)-quinic acid, the title compound was synthesized in seven chemical steps and an overall yield of 35−38%. The route of the improved Gilead synthesis was not changed. However, significant improvements in each step led to a doubled overall yield, a 30% reduction in the number of unit operations, and an excellent quality (≥99%) of the resulting epoxide. A highly regioselective method for the dehydration of a quinic acid to a shikimic acid derivative and for the reduction of a cyclic ketal was found. Alternatively, the title compound was synthesized in six chemical steps and 63−65% yield from commercially available (−)-shikimic acid. Compared to the optimized quinic acid route, the production time was reduced by about 50%. The quality of epoxide produced from either natural product was equivalent. Therefore (−)-shikimic acid is the preferred raw material. The absolute configuration of the epoxide was determined by X-ray single crystal structure analysis and it was demonstrated that the epoxide.
Nonmedical Use of Prescription Stimulants as a “Red Flag” for Other Substance Use

Abstract Background Nonmedical use of prescription stimulants (NMPS) has increased on college campuses during the past two decades. NMPS is primarily driven by academic enhancement motives, and normative misperceptions exist as well. However, large, nationwide studies have not yet been conducted to generalize findings more broadly and gain a deeper understanding of the relationship between NMPS and other substance use (e.g. alcohol use, marijuana, etc.). The present study was conducted to lay the foundation for prevention efforts related to NMPS by establishing NMPS prevalence, practices surrounding NMPS, and other substance use. Methods N = 2,989 students from seven universities around the U.S. completed a web-based survey assessing NMPS practices and related behaviors. Prevalence and factors associated with NMPS were explored. Results Analyses revealed a 17% past-year prevalence of NMPS with associated widespread misperceptions of peer use. NMPS was significantly related to alcohol use, binge drinking, and marijuana use, as well as skipped classes and affiliation with Greek life. Conclusions Although most college students do not report NMPS, those who do also are more likely to report alcohol use, binge drinking, and marijuana use, and NMPS could be a “red flag” for other risk behaviors worth exploring. Implications for prevention and intervention are discussed.
Development of a prediction model of treatment response in patients with cutaneous arteritis: Insights from a cohort of 33 patients

Cutaneous arteritis (CA) is necrotizing vasculitis invading the small‐ to medium‐sized arteries of the skin. The majority of patients can be favorably managed by low‐ to medium‐dose systemic corticosteroids (prednisolone, <0.5 mg/kg/day) or other oral medications such as non‐steroidal anti‐inflammatory drugs, dapsone, and azathioprine. Meanwhile, some patients require more intensive therapy including high‐dose systemic corticosteroids (prednisolone, ≥0.5 mg/kg/day), i.v. immunoglobulin, and i.v. cyclophosphamide therapy. Although predicting such treatment response among CA patients is critical in clinical decision‐making, prediction rules have not yet been established. Herein, we retrospectively reviewed 33 patients regularly visiting our clinic to reveal predictive factors of their treatment response. Clinical data were collected from electronic medical records. Association between each factor and treatment response was examined by logistic regression analysis. Progression‐free time was calculated by Kaplan–Meier’s method and analyzed by log–rank test and Cox progression hazard model. Potential predictive factors were selected, given 1 point for each, and integrated into a classification model. Discrimination of the model was examined by the receiver operating characteristic (ROC) curve analysis. In total, 33 CA patients were enrolled in our study. Of these, 11 patients required intensive therapy, classified as treatment non‐responders. Logistic analyses revealed that treatment response was significantly associated with male sex, presence of skin ulcers, and elevated serum levels of C‐reactive protein at the initial work‐up. Kaplan–Meier analyses also demonstrated that those factors are predictive of progression‐free time. The area under the ROC curve of our classification model was 0.92 (95% confidence interval, 0.83–1.00), which classified non‐responders from the others with a sensitivity of 90.9% and specificity of 81.8% at the cut‐off point of 2 or more. Collectively, treatment response of CA could be predictable by a combination of sex, presence of skin ulcers, and serum levels of C‐reactive protein.
RAD21 is a driver of chromosome 8 gain in Ewing sarcoma to mitigate replication stress

In this study, Su et al. investigate why ∼50% of Ewing sarcomas, driven by the EWS-FLI1 fusion oncogene, harbor chromosome 8 gains. Using an evolution approach, they show that trisomy 8 mitigates EWS-FLI1-induced replication stress through gain of a copy of RAD21, and deleting one copy of RAD21 in trisomy 8 cells largely neutralizes the fitness benefit of chromosome 8 gain and reduces tumorgenicity of a Ewing sarcoma cancer cell line in soft agar assays.