Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of De Novo Hepatocellular Carcinoma Following Use of Direct Acting Antiviral Medications for Treatment of Chronic Hepatitis C

Direct-acting antivirals (DAA) are now the mainstay of treatment for patients with chronic hepatitis C virus (HCV); however, there is some controversy over whether use of DAAs for HCV, as compared with IFN-based regimens, leads to an increased risk for hepatocellular carcinoma (HCC) development. We investigated the association between use of DAAs and subsequent development of HCC in longitudinal data from patients with HCV from diverse backgrounds (various ages, ethnicities, and geographic regions) across the United States. The design was a retrospective study performed using medical and pharmacy claims from OptumLabs. HCV treatment exposure was categorized as DAA-only, DAA + IFN, any-DAA, or IFN-only. To account for confounding by indication, inverse probability of treatment weighting was performed. Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). We identified 5,781 patients with HCV with no history of HCC at baseline. Compared with IFN-only regimen, no significant increase in HCC risk was found for use of DAA-only (HR, 1.53; 95% CI, 0.73–3.23), DAA + IFN (HR, 1.02; 95% CI, 0.51–2.06), or any-DAA (HR, 1.04; 95% CI, 0.65–1.65). When stratified by sustained virological response (SVR), we noted a higher HCC risk for DAA-only among patients who achieved SVR post-treatment (HR, 7.53; 95% CI, 1.48–38.34), but the CIs were wide, which might be due to the small sample size of the subgroups. Among those who did not achieve SVR, no association was found for use of DAA-only (HR, 0.59; 95% CI, 0.19–1.91). These findings do not provide compelling evidence for the conception that use of DAAs for HCV is associated with increased risk of HCC development.
Advanced age adversely affects chronic rhinosinusitis surgical outcomes

Patient‐specific and disease‐specific factors shape the course of chronic rhinosinusitis (CRS) and its response to treatment, with optimal management involving interventions tailored to these factors. Recent evidence suggests CRS inflammatory signatures depend on age. The objective of this study was to determine whether age also influences quality‐of‐life (QOL) and postoperative outcomes.
Therapy compliance in children with phenylketonuria younger than 5 years: A cohort study.

BACKGROUND Phenylketonuria (PKU) is a metabolic disease. It is manifested by a complete or partial inability to convert phenylalanine (Phe) to tyrosine and leads to increased concentrations of Phe in the blood and in other tissues, including the brain, causing irreversible neurological damage if left untreated. Low-phenylalanine diet is a key component of classical PKU therapy. OBJECTIVES The objective of this study was to assess the effectiveness of classical phenylketonuria therapy and compliance with doctors' recommendations in the first 5 years of life. MATERIAL AND METHODS Data was collected from all diagnosed and treated patients (n = 57) born 1999-2010. Phenylalanine blood levels, the number of visits to a specialist outpatients' center, the number of blood tests, as well as socioeconomic status (SES) and parents' education level have been analyzed, and potential relationships have been assessed. RESULTS In the 1st year of life patients visited their doctors (OR = 6.8267; 95% CI = 2.827-16.5163; p < 0.0001) and had their blood collected (OR = 2.7875; 95% CI = 1.0467-7.4234; p < 0.0402) significantly more frequently than in the 2nd year. This tendency persisted into subsequent years. Similarly, in infancy they had statistically significantly lower odds of exceeding more than 40% of their Phe levels over therapeutic range than 1 year later (OR = 3.6078; 95% CI = 1.4859-8.7599; p < 0.0046). No PKU child had more than 70% of Phe levels over the therapeutic range in the 1st year of life, whereas 4 years later there were 18 such children. Phe levels were correlated with the number of visits to a specialist (ρ = 0.39) and the number of Phe blood tests with index of dietary control (ρ = -0.33). The effectiveness of therapy and compliance with the doctor's recommendations seem to depend neither on the level of education of the patient's parents nor on their SES. CONCLUSIONS Therapy effectiveness and patients' compliance in PKU is very good in infancy. However, both deteriorate in subsequent years. Moreover, they do not seem to depend on the family background.
A Rare Consequence after Shoulder Dislocation in a Professional Cyclist: A Case Report

Background: Cycling is a popular source of recreation and physical activity for children and adults. With regard to the total number of sports injuries, cycling has the highest absolute number of injuries per year in the United States population. Cycling injuries can be classified into bicycle contact, traumatic, or overuse injuries. Aim of this study: The aims of this case report are to report a rare clinical complication of glenohumeral joint anterior dislocation that resulted in a patient experiencing continuous GHJ dislocations secondary to involuntary violent muscular spasms and emphasize the role of the physical therapist’s differential diagnosis and clinical decision-making process in a patient following direct access referral. Case presentation: A professional 23-year-old cyclist presented to a physical therapist with spontaneous multidirectional dislocations to the right shoulder after the recurrence of trauma occurred during a recent cycling race. The dislocations do not occur at night, but occur during the day, randomly, and mostly associated with changes in the patient’s psychological conditions. Directly from the clinical history, the physical therapist identified a neuro-physiological orange flag as well as an orthopedic red flag and, therefore, decided it was appropriate to refer the patient to a neurologist. It was determined by the physical therapist to be a priority to focus on the patient’s neurologic status and then to evaluate the orthopedic problem. The neurological examination revealed a condition of spontaneous multidirectional dislocation associated with recurrent antero-posterior pain spasms of the shoulder joint. The neurologist prescribed medication. Following the second cycle of medication assumption, the patient was able to continue physiotherapy treatment and was referred to the orthopedic specialist to proceed with shoulder stabilization surgery. Discussion and conclusion: Currently, the diagnosis of this unusual clinical condition is still unclear. It is a shared opinion of the authors that the trauma during the past bicycle race awakened an underlying psychological problem of the patient that resulted in a clinical condition of weakness of all the structures of the shoulder, such that these spasms could result in multiple multidirectional dislocations.
The treatment of adolescents and young adults with acute lymphoblastic leukemia

Abstract Adolescents and young adults (AYAs) with ALL represent a unique population in terms of their biology and treatment. Studies have demonstrated an improved outcome when these patients are treated with pediatric-inspired regimens. Novel antibody based therapies have demonstrated impressive results in relapsed/refractory B-ALL and are starting to be evaluated in the upfront setting. Immunotherapy with CAR T cells had great success in ALL and clinical trials are ongoing and further studies are being done to expand access to this therapy and decrease toxicities. Although our outcomes with this disease have improved significantly, transplant still plays a role for high risk patients in CR1 (based on MRD status) and for patients with relapsed/refractory ALL.
Design of Plasmonic-Waveguiding Structures for Sensor Applications

Surface plasmon resonance has become a widely accepted optical technique for studying biological and chemical interactions. Among others, detecting small changes in analyte concentration in complex solutions remains challenging, e.g., because of the need of distinguishing the interaction of interest from other effects. In our model study, the resolution ability of plasmonic sensing element was enhanced by two ways. Besides an implementation of metal-insulator-metal (MIM) plasmonic nanostructure, we suggest concatenation with waveguiding substructure to achieve mutual coupling of surface plasmon polariton (SPP) with an optical waveguiding mode. The dependence of coupling conditions on the multilayer parameters was analyzed to obtain optimal field intensity enhancement.
GABAergic Inhibition Gates Perceptual Awareness During Binocular Rivalry

Binocular rivalry is a classic experimental tool to probe the neural machinery of perceptual awareness. During rivalry, perception alternates between the two eyes, and the ebb and flow of perception is modeled to rely on the strength of inhibitory interactions between competitive neuronal populations in visual cortex. As a result, rivalry has been suggested as a noninvasive perceptual marker of inhibitory signaling in visual cortex, and its putative disturbance in psychiatric conditions, including autism. Yet, direct evidence causally implicating inhibitory signaling in the dynamics of binocular rivalry is currently lacking. We previously found that people with higher GABA levels in visual cortex, measured using magnetic resonance spectroscopy, have stronger perceptual suppression during rivalry. Here, we present direct causal tests of the impact of GABAergic inhibition on rivalry dynamics, and the contribution of specific GABA receptors to these dynamics. In a crossover pharmacological design with male and female adult participants, we found that drugs that modulate the two dominant GABA receptor types in the brain, GABAA (clobazam) and GABAB (arbaclofen), increase perceptual suppression during rivalry relative to a placebo. Crucially, these results could not be explained by changes in reaction times or response criteria, as determined through rivalry simulation trials, suggesting a direct and specific influence of GABA on perceptual suppression. A full replication study of the GABAB modulator reinforces these findings. These results provide causal evidence for a link between the strength of inhibition in the brain and perceptual suppression during rivalry and have implications for psychiatric conditions including autism. SIGNIFICANCE STATEMENT How does the brain accomplish perceptual gating? Here we use a direct and causal pharmacological manipulation to present insight into the neural machinery of a classic illusion of perceptual awareness: binocular rivalry. We show that drugs that increase GABAergic inhibition in the brain, clobazam (GABAA modulator) and arbaclofen (GABAB modulator), increase perceptual suppression during rivalry relative to a placebo. These results present the first causal link between GABAergic inhibition and binocular rivalry in humans, complementing classic models of binocular rivalry, and have implications for our understanding of psychiatric conditions, such as autism, where binocular rivalry is posited as a behavioral marker of disruptions in inhibitory signaling in the brain.
Reduction of Tetrachloroaurate(III) Ions With Bioligands: Role of the Thiol and Amine Functional Groups on the Structure and Optical Features of Gold Nanohybrid Systems

In this review, the presentation of the synthetic routes of plasmonic gold nanoparticles (Au NPs), fluorescent gold nanoclusters (Au NCs), as well as self-assembled Au-containing thiolated coordination polymers (Au CPs) was highlighted. We exclusively emphasize the gold products that are synthesized by the spontaneous interaction of tetrachloroaurate(III) ions (AuCl4¯) with bioligands using amine and thiolate derivatives, including mainly amino acids. The dominant role of the nature of the applied reducing molecules as well as the experimental conditions (concentration of the precursor metal ion, molar ratio of the AuCl4¯ ions and biomolecules; pH, temperature, etc.) of the syntheses on the size and structure-dependent optical properties of these gold nanohybrid materials have been summarized. While using the same reducing and stabilizing biomolecules, the main differences on the preparation conditions of Au NPs, Au NCs, and Au CPs have been interpreted and the reducing capabilities of various amino acids and thiolates have been compared. Moreover, various fabrication routes of thiol-stabilized plasmonic Au NPs, as well as fluorescent Au NCs and self-assembled Au CPs have been presented via the formation of –(Au(I)-SR)n– periodic structures as intermediates.
Dexamethasone therapy in symptomatic chronic subdural hematoma: A retrospective evaluation of initial corticosteroid therapy versus primary surgery (DECSA - R).

Worldwide different strategies are being applied for symptomatic chronic subdural hematoma (CSDH). Aim of this study was to evaluate the efficacy of two treatment strategies for symptomatic CSDH: initial dexamethasone (DXM) therapy versus primary surgery by burr hole craniostomy (BHC). We retrospectively collected data of 120 symptomatic CSDH patients in two neurotrauma centers between 2014 and 2016, each with their own treatment protocol. Sixty patients received primary BHC (center A), and another 60 initial DXM therapy (center B). Primary outcome was evaluated by dichotomized modified Rankin Scale (mRS) score (0-3 and 4-6) and MGS score at three months. Secondary outcomes were additional interventions, CSDH recurrence, mortality, complications and duration of hospital stay. Baseline characteristics were similar in both groups. At three months a favorable mRS score (0-3) was observed in 70% and 76% in cohort A and B respectively (OR 0.77, 95% CI 0.30-1.98, p=0.59). A favorable MGS score (0-1) was observed in 96% in both groups (OR 0.98, 95% CI 0.45-2.15, p=0.95). CSDH recurrence was 12% in cohort A and 22% in cohort B (p=0.15). Mortality was 10% in both cohorts. In cohort B additional surgery was performed in 83% at a median of six days and significantly more patients had complications (55% vs 35%, p=0.02), a prolonged hospitalization (10 vs. 5 days; p=0.02) and one or more follow-up cranial CT's (85% vs. 48%; p<0.001). To achieve a favorable clinical outcome, initial DXM therapy was associated with a high rate of cross-over to surgery, significantly longer overall hospital stay and more complications compared to primary surgery. Chronic subdural hematoma, CSDH, corticosteroid therapy, dexamethasone, burr hole craniostomy.
Art‐omics: multi‐omics meet archaeology and art conservation

Multi‐omics can informally be described as the combined use of high‐throughput techniques allowing the characterization of complete microbial communities by the sequencing/identification of total pools of biomolecules including DNA, proteins or metabolites. These techniques have allowed an unprecedented level of knowledge on complex microbial ecosystems, which is having key implications in land and marine ecology, industrial biotechnology or biomedicine. Multi‐omics have recently been applied to artistic or archaeological objects, with the goal of either contributing to shedding light on the original context of the pieces and/or to inform conservation approaches. In this minireview, we discuss the application of ‐omic techniques to the study of prehistoric artworks and ancient man‐made objects in three main technical blocks: metagenomics, proteomics and metabolomics. In particular, we will focus on how proteomics and metabolomics can provide paradigm‐breaking results by unambiguously identifying peptides associated with a given, palaeo‐cultural context; and we will discuss how metagenomics can be central for the identification of the microbial keyplayers on artworks surfaces, whose conservation can then be approached by a range of techniques, including using selected microorganisms as ‘probiotics’ because of their direct or indirect effect in the stabilization and preservation of valuable art objects.
Cellular and Synaptic Dysfunctions in Parkinson’s Disease: Stepping Out of the Striatum

The basal ganglia (BG) are a collection of interconnected subcortical nuclei that participate in a great variety of functions, ranging from motor programming and execution to procedural learning, cognition, and emotions. This network is also the region primarily affected by the degeneration of midbrain dopaminergic neurons localized in the substantia nigra pars compacta (SNc). This degeneration causes cellular and synaptic dysfunctions in the BG network, which are responsible for the appearance of the motor symptoms of Parkinson’s disease. Dopamine (DA) modulation and the consequences of its loss on the striatal microcircuit have been extensively studied, and because of the discrete nature of DA innervation of other BG nuclei, its action outside the striatum has been considered negligible. However, there is a growing body of evidence supporting functional extrastriatal DA modulation of both cellular excitability and synaptic transmission. In this review, the functional relevance of DA modulation outside the striatum in both normal and pathological conditions will be discussed.
Large-scale identification and functional analysis of NLR genes in blast resistance in the Tetep rice genome sequence

Significance Rice resistance against blast, a devastating fungal disease, is typically mediated by nucleotide-binding site leucine-rich repeat (NLR) proteins. Most previous studies focused on individual NLR genes, but single R genes typically confer no durable resistance owing to their narrow resistance spectrum. In this study, we sequenced the genome of Tetep, a widely used resistance donor, to decipher the molecular basis of its broad-spectrum and durable blast resistance. Large-scale cloning and functional analysis of annotated NLRs uncovered a large number of functional NLR genes and interactive NLR networks in the genome. Moreover, pedigree tracing of elite cultivars indicated the more NLRs inherited from Tetep the better resistance of the cultivar. Various datasets were provided for facilitating breeding for new resistant cultivars. Tetep is a rice cultivar known for broad-spectrum resistance to blast, a devastating fungal disease. The molecular basis for its broad-spectrum resistance is still poorly understood. Is it because Tetep has many more NLR genes than other cultivars? Or does Tetep possess multiple major NLR genes that can individually confer broad-spectrum resistance to blast? Moreover, are there many interacting NLR pairs in the Tetep genome? We sequenced its genome, obtained a high-quality assembly, and annotated 455 nucleotide-binding site leucine-rich repeat (NLR) genes. We cloned and tested 219 NLR genes as transgenes in 2 susceptible cultivars using 5 to 12 diversified pathogen strains; in many cases, fewer than 12 strains were successfully cultured for testing. Ninety cloned NLRs showed resistance to 1 or more pathogen strains and each strain was recognized by multiple NLRs. However, few NLRs showed resistance to >6 strains, so multiple NLRs are apparently required for Tetep’s broad-spectrum resistance to blast. This was further supported by the pedigree analyses, which suggested a correlation between resistance and the number of Tetep-derived NLRs. In developing a method to identify NLR pairs each of which functions as a unit, we found that >20% of the NLRs in the Tetep and 3 other rice genomes are paired. Finally, we designed an extensive set of molecular markers for rapidly introducing clustered and paired NLRs in the Tetep genome for breeding new resistant cultivars. This study increased our understanding of the genetic basis of broad-spectrum blast resistance in rice.
Cyanine-Gemcitabine Conjugates as Targeted Theranostic Agents for Glioblastoma Tumor Cells.

A small sub-set of heptamethine dyes (cyanine-7 or Cy7) share an intriguing characteristic: preferential tumor accumulation and retention. These dyes absorb in the near infrared (NIR) region (above 750 nm), and perform active targeting to deliver therapeutic and toxic cargoes to various tumor models in vivo, offering theranostic effect. In this work, four heptamethines 1 were synthesized, which have gemcitabine fragment attached to the meso-position of the Cy7 core. Compound 1a, a theranostic agent was discovered, that localized in glioblastoma tumor cells, has absorption maxima in NIR region and showed similar therapeutic effect to gemcitabine, but at one-third the molar dose.
Prediction of short‐ and long‐term mortality in takotsubo syndrome: the InterTAK Prognostic Score

Recent evidence suggests comparable inhospital and long-term outcomes between takotsubo syndrome (TTS) and acute coronary syndrome.1,2 Medical scoring systems are practical tools for decision making and prognostic assessment. However, TTSspecific scoring systems for risk stratification have not yet been established. Recently, classification based on triggering conditions proved useful in predicting adverse outcomes in TTS (InterTAK Classification). 1 Since clinical parameters other than triggering conditions can be associated with adverse outcomes in TTS, such as systolic blood pressure and heart rate,3 the present study aimed to establish a scoring system combining triggering factors with other important but easilyobtainable clinical parameters of daily clinical practice. Takotsubo syndrome patients were enrolled from the International Takotsubo (InterTAK) Registry, which is an all-comers TTS registry in collaboration with 26 centres worldwide.2 Univariate Cox regression analyses for all-cause mortality were performed with variables of interest based on updated knowledge and recent literature1–6: age (cut-off = 70 years), triggering factors (InterTAK Classification), sex, hypertension, diabetes mellitus, typical or atypical TTS type,
Age Differences in the Effects of Speaking Rate on Auditory, Visual, and Auditory-Visual Speech Perception

Objectives: This study was designed to examine how speaking rate affects auditory-only, visual-only, and auditory-visual speech perception across the adult lifespan. In addition, the study examined the extent to which unimodal (auditory-only and visual-only) performance predicts auditory-visual performance across a range of speaking rates. The authors hypothesized significant Age × Rate interactions in all three modalities and that unimodal performance would account for a majority of the variance in auditory-visual speech perception for speaking rates that are both slower and faster than normal. Design: Participants (N = 145), ranging in age from 22 to 92, were tested in conditions with auditory-only, visual-only, and auditory-visual presentations using a closed-set speech perception test. Five different speaking rates were presented in each modality: an unmodified (normal rate), two rates that were slower than normal, and two rates that were faster than normal. Signal to noise ratios were set individually to produce approximately 30% correct identification in the auditory-only condition and this signal to noise ratio was used in the auditory-only and auditory-visual conditions. Results: Age × Rate interactions were observed for the fastest speaking rates in both the visual-only and auditory-visual conditions. Unimodal performance accounted for at least 60% of the variance in auditory-visual performance for all five speaking rates. Conclusions: The findings demonstrate that the disproportionate difficulty that older adults have with rapid speech for auditory-only presentations can also be observed with visual-only and auditory-visual presentations. Taken together, the present analyses of age and individual differences indicate a generalized age-related decline in the ability to understand speech produced at fast speaking rates. The finding that auditory-visual speech performance was almost entirely predicted by unimodal performance across all five speaking rates has important clinical implications for auditory-visual speech perception and the ability of older adults to use visual speech information to compensate for age-related hearing loss.