Miracle-dz/UniFAR-FTUs huggingface dataset:
Fenfluramine: New Treatment for Seizures in Dravet Syndrome

Investigators for the FAiRE DS Study Group assessed the efficacy and safety of Fenfluramine for treating seizures in patients less than 18 y.o. with Dravet Syndrome in an international double-blind, placebo-controlled clinical trial. A total of 119 patients (mean age 9.0 y, 54% male) were enrolled in the study.
Crosswalks Between Knee and Hip Arthroplasty Short Forms: HOOS/KOOS JR and Oxford.

BACKGROUND The Oxford Knee Score (OKS); Oxford Hip Score (OHS); Knee injury and Osteoarthritis Outcome Score, Joint Replacement (KOOS JR); and Hip disability and Osteoarthritis Outcome Score, Joint Replacement (HOOS JR) are well-validated and widely used short-form patient-reported outcome measures (PROMs) for assessing outcomes after total knee arthroplasty (TKA) and total hip arthroplasty (THA). We are not aware of the existence of any crosswalks to convert scores between these PROMs. We aimed to develop and validate crosswalks that will permit the comparison of scores between studies using different PROMs and the pooling of results for meta-analyses. METHODS We retrospectively analyzed scores from patients (486 in the knee cohort and 340 in the hip cohort) from the Syracuse Orthopedic Specialists Joint Registry who had completed the appropriate PROMs (OKS and KOOS JR in the knee cohort and OHS and HOOS JR in the hip cohort) as the standard of care before undergoing primary TKA or unicompartmental knee arthroplasty (UKA) between January 9, 2016, and June 19, 2017, or primary THA or hip resurfacing between November 29, 2010, and October 30, 2017, or when returning for postoperative care. Using the equipercentile equating method, we created 4 crosswalks: OKS to KOOS JR, KOOS JR to OKS, OHS to HOOS JR, and HOOS JR to OHS. To assess validity, Spearman coefficients were calculated using bootstrapping methods, and means for actual and crosswalk-derived scores were compared. RESULTS There were minimal differences between the means of the known and crosswalk-derived scores. As calculated with the use of bootstrapping methods, Spearman coefficients between the actual and derived scores were strong and positive for both knee arthroplasty crosswalks (0.888 to 0.889; 95% confidence interval [CI], 0.887 to 0.891) and hip arthroplasty crosswalks (0.916 to 0.918; 95% CI, 0.914 to 0.919). CONCLUSIONS We successfully created 4 crosswalks that allow conversion of Oxford scores to KOOS and HOOS JR scores and vice versa. These crosswalks will allow harmonization of PROMs assessment regardless of which of the short forms are used, which may facilitate multicenter collaboration or allow sites to switch PROMs without loss of historic comparison data. LEVEL OF EVIDENCE Level III. See Instructions for Authors for a complete description of levels of evidence.
Three-Dimensional Measurement of the Lateral Lip Element Sacrificed in Primary Repair of a Unilateral Cleft Lip.

BACKGROUND In most children with a unilateral cleft lip (UCL), because lateral lip tissue on the cleft side is congenitally short, the lateral lip element should be appropriately excised during primary cheiloplasty so that symmetric nasolabial features are obtained after surgery. The purpose of this study was to measure how much of the lateral lip element is removed during primary cheiloplasty and compare the amount of sacrifice between different incision designs. METHODS Preoperative 3-dimensional images of 50 infants with UCL were randomly selected. The incision designs of 3 representative techniques (Millard, Onizuka, and Fisher) were drawn on the images that were obtained before the primary repair. The lateral lip tissue excised by each technique was estimated as a percentage of the surface area of the sacrificed lateral lip to the entire lateral lip of the cleft side. RESULTS In the case of incomplete UCL, the median values (range) were 3.2% (1.1%-5.9%), 11.6% (8.3%-20.1%), and 27.2% (15.1%-42.3%) for the Millard, Onizuka, and Fisher repairs, respectively. In cases of complete UCL, no sacrifice was needed for the Millard repair, whereas the median values (range) were 10.6% (5.2%-28.9%) and 22.5% (11.5%-48.6%) for the Onizuka and Fisher repairs, respectively. In Millard repair, the median values (range) of the lateral lip element that was resected before skin closure according to the "cut-as-you-go" policy were 5.8% (2.2%-11.8%) in cases with an incomplete UCL and 4.9% (2.7%-9.1%) in cases with a complete UCL. CONCLUSIONS Our study demonstrated that sacrifice of the lateral lip element was minimal in the Millard repair, whereas it could exceed 20% in the Fisher repair. However, additional sacrifice of the advancement flap was needed in the Millard-type repair. The ratio of the lateral lip sacrifice varied between patients. Although UCL repair techniques should not be evaluated with the sacrifice ratio, excessive sacrifice of the lateral lip tissue can complicate the secondary lip correction. We recommend that surgeons estimate preoperatively how much lateral lip element will be sacrificed with each incision design using a 3-dimensional image for each child with a UCL.
A role for cell‐autocrine interleukin‐2 in regulatory T‐cell homeostasis

Activated T‐cells make both interleukin‐2 (IL2) and its high‐affinity receptor component CD25. Regulatory CD4 T‐cells (Treg cells) do not make IL2, and the IL2‐CD25 circuit is considered a paracrine circuit crucial in their generation and maintenance. Yet, all T‐cells are capable of making IL2 at some stage during differentiation, making a cell‐intrinsic autocrine circuit additionally possible. When we re‐visited experiments with mixed bone marrow chimeras using a wide range of ratios of wild‐type (WT) and IL2−/− genotype progenitors, we found that, as expected, thymic Treg cells were almost equivalent between WT and IL2−/− genotypes at ratios with WT prominence. However, at WT‐limiting ratios, the IL2−/− genotype showed lower thymic Treg frequencies, indicating a role for cell‐intrinsic autocrine IL2 in thymic Treg generation under IL2‐limiting conditions. Further, peripheral IL2−/− naive CD4 T‐cells showed poor conversion to inducible Tregs (pTregs) both in vivo and in vitro, again indicating a significant role for cell‐intrinsic autocrine IL2 in their generation. Peripherally, the IL2−/− genotype was less prominent at all WT:IL2−/− ratios among both thymic Tregs (tTregs) and pTregs, adoptively transferred IL2−/− Tregs showed poorer survival than WT Tregs did, and RNA‐seq analysis of WT and IL2−/− Tregs showed interesting differences in the T‐cell receptor and transforming growth factor‐beta‐bone morphogenetic protein‐JNK pathways between them, suggesting a non‐titrating role for cell‐intrinsic autocrine IL2 in Treg programming. These data indicate that cell‐intrinsic autocrine IL2 plays significant roles in Treg generation and maintenance.
Genetic Predictors of Circulating 25-Hydroxyvitamin D and Prognosis after Colorectal Cancer

Background: Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in patients with colorectal cancer have been consistently associated with higher mortality in observational studies. It is unclear whether low 25(OH)D levels directly influence colorectal cancer mortality. To minimize bias, we use genetic variants associated with vitamin D levels to evaluate the association with overall and colorectal cancer–specific survival. Methods: Six genetic variants have been robustly identified to be associated with 25(OH)D levels in genome-wide association studies. On the basis of data from the International Survival Analysis in Colorectal Cancer Consortium, the individual genetic variants and a weighted genetic risk score were tested for association with overall and colorectal cancer–specific survival using Cox proportional hazards models in 7,657 patients with stage I to IV colorectal cancer, of whom 2,438 died from any cause and 1,648 died from colorectal cancer. Results: The 25(OH)D decreasing allele of SNP rs2282679 (GC gene, encodes group-specific component/vitamin D–binding protein) was associated with poorer colorectal cancer–specific survival, although not significant after multiple-testing correction. None of the other five SNPs showed an association. The genetic risk score showed nonsignificant associations with increased overall [HR = 1.54; confidence interval (CI), 0.86–2.78] and colorectal cancer–specific mortality (HR = 1.76; 95% CI, 0.86–3.58). A significant increased risk of overall mortality was observed in women (HR = 3.26; 95% CI, 1.45–7.33; Pheterogeneity = 0.01) and normal-weight individuals (HR = 4.14; 95% CI, 1.50–11.43, Pheterogeneity = 0.02). Conclusions: Our results provided little evidence for an association of genetic predisposition of lower vitamin D levels with increased overall or colorectal cancer–specific survival, although power might have been an issue. Impact: Further studies are warranted to investigate the association in specific subgroups.
Dietary starch promotes hepatic lipogenesis in barramundi (Lates calcarifer)

Abstract Barramundi (Lates calcarifer) are a highly valued aquaculture species, and, as obligate carnivores, they have a demonstrated preference for dietary protein over lipid or starch to fuel energetic growth demands. In order to investigate how carnivorous fish regulate nutritional cues, we examined the metabolic effects of feeding two isoenergetic diets that contained different proportions of digestible protein or starch energy. Fish fed a high proportion of dietary starch energy had a higher proportion of liver SFA, but showed no change in plasma glucose levels, and few changes in the expression of genes regulating key hepatic metabolic pathways. Decreased activation of the mammalian target of rapamycin growth signalling cascade was consistent with decreased growth performance values. The fractional synthetic rate (lipogenesis), measured by TAG 2H-enrichment using 2H NMR, was significantly higher in barramundi fed with the starch diet compared with the protein diet (0·6 (se 0·1) v. 0·4 (se 0·1) % per d, respectively). Hepatic TAG-bound glycerol synthetic rates were much higher than other closely related fish such as sea bass, but were not significantly different (starch, 2·8 (se 0·3) v. protein, 3·4 (se 0·3) % per d), highlighting the role of glycerol as a metabolic intermediary and high TAG-FA cycling in barramundi. Overall, dietary starch significantly increased hepatic TAG through increased lipogenesis. Compared with other fish, barramundi possess a unique mechanism to metabolise dietary carbohydrates and this knowledge may define ways to improve performance of advanced formulated feeds.
Rapid Turnover of Hepatitis B Virus Covalently Closed Circular DNA Indicated by Monitoring Emergence and Reversion of Signature‐Mutation in Treated Chronic Hepatitis B Patients

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a pivotal role in the establishment and persistence of HBV infection. Understanding the turnover time of preexisting cccDNA pools would be helpful in designing strategies to clear HBV by fully blocking the de novo generation of cccDNA.
Trends in Reported Sexual Behavior and Y-Chromosomal DNA Detection Among Female Sex Workers in the Senegal Preexposure Prophylaxis Demonstration Project

A study among female sex workers in Senegal found no evidence of increased sexual risk behavior after preexposure prophylaxis initiation as measured by self-report or Y-chromosomal DNA detection. Supplemental digital content is available in the text. Background Preexposure prophylaxis (PrEP) can reduce HIV acquisition among female sex workers (FSWs). However, changes in condomless sex frequency after PrEP initiation could reduce PrEP effectiveness when PrEP adherence is suboptimal as well as increase the risk of acquiring other sexually transmitted infections. Objective measures of condomless sex may be more accurate for determining changes in sexual behavior than self-reported measures. Methods We longitudinally measured self-reported condom use, number of clients, and presence of Y-chromosomal DNA (Yc-DNA) in vaginal swabs among 267 FSWs accessing PrEP at 4 clinics in Senegal between 2015 and 2016. We assessed trends in sexual behavior over time since PrEP initiation using generalized estimating equations and evaluated predictors of Yc-DNA detection. Results We found no increase in self-reported condomless sex with clients (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.89–1.00), main partners (OR, 0.99; 95% CI, 0.96–1.02), or Yc-DNA detection (OR, 0.99; 95% CI, 0.90–1.08) over time since initiation. Y-chromosomal DNA was detected in 34 (22%) of 154 swabs tested and in 15 (26%) of 58 swabs from FSW reporting consistent condom use among both clients and main partners. Self-reported condom use with clients or main partners did not predict Yc-DNA detection. Conclusions In a FSW PrEP demonstration project in Senegal, we found no evidence of risk compensation among FSWs on PrEP as measured by self-reported behavior or through Yc-DNA detection. Y-chromosomal DNA detection was frequently detected among FSWs reporting consistent condom use, highlighting limitations of self-reported sexual behavioral measures.
Volatile organic compounds in 169 energy‐efficient dwellings in Switzerland

Abstract Exposure to elevated levels of certain volatile organic compounds (VOCs) in households has been linked to deleterious health effects. This study presents the first large‐scale investigation of VOC levels in 169 energy‐efficient dwellings in Switzerland. Through a combination of physical measurements and questionnaire surveys, we investigated the influence of diverse building characteristics on indoor VOCs. Among 74 detected compounds, carbonyls, alkanes, and alkenes were the most abundant. Median concentration levels of formaldehyde (14 μg/m3), TVOC (212 μg/m3), benzene (<0.1 μg/m3), and toluene (22 μg/m3) were below the upper exposure limits. Nonetheless, 90% and 50% of dwellings exceeded the chronic exposure limits for formaldehyde (9 μg/m3) and TVOC (200 μg/m3), respectively. There was a strong positive correlation among VOCs that likely originated from common sources. Dwellings built between 1950s and 1990s, and especially, those with attached garages had higher TVOC concentrations. Interior thermal retrofit of dwellings and absence of mechanical ventilation system were associated with elevated levels of formaldehyde, aromatics, and alkanes. Overall, energy‐renovated homes had higher levels of certain VOCs compared with newly built homes. The results suggest that energy efficiency measures in dwellings should be accompanied by actions to mitigate VOC exposures as to avoid adverse health outcomes.
Agency judgments in post-stroke patients with sensorimotor deficits

Sense of agency refers to the feeling of being in control of one’s actions. Previous research has demonstrated that sense of agency is produced through the sensorimotor system, which is involved in comparing internal predictions with sensory feedback in motor control. Therefore, sensorimotor deficits might impair agency through a sensorimotor system malfunction. The present study examined this hypothesis by investigating post-stroke patients who had suffered a subcortical stroke that damaged regions associated with sensorimotor function. To examine agency judgments with respect to motor control, we adopted a self-other attribution task and applied it to post-stroke patients. Participants traced a horizontal straight line and received visual feedback through a cursor on a monitor. The cursor movement reflected either the participants’ actual movement or the movement of an “other” that had been previously recorded. Participants judged whether the cursor movement reflected their own movement (self) or an other’s movement while they engaged in four cycles of the horizontal tracing movement. After each trial, participants reported their self-other judgment on a nine-point scale. Post-stroke patients completed the experiment with their paretic as well as their non-paralyzed upper limbs. Compared to healthy controls, patients made significantly more self-attributions of others’ movements. Interestingly, such misattributions were observed in the patients’ performance using both paretic and non-paralyzed upper limbs. These results suggest that post-stroke patients with sensorimotor deficits form misattributions that cannot be explained solely by the sensorimotor system’s role in motor control. We discuss these misattributions in post-stroke patients in terms of cue integration theory.
Dietary strategies to augment muscle mass in the elderly

Background: The world population is aging rapidly. This growth of the aging population is accompanied by an increased number of frail elderly people who are at risk of adverse health outcomes such as disability, co-morbidity and mortality. A dominant feature of frailty is the age related loss of muscle mass, strength and performance, also called sarcopenia. Resistance-type exercise training and dietary protein supplementation are considered promising strategies to reverse sarcopenia and subsequent frailty. However, strong evidence for the impact of protein supplementation with or without resistance exercise in frail elderly people is scarce. Well-designed intervention studies in frail elderly people are needed to define new leads for the development of nutritional and exercise interventions to effectively prevent or treat the progressive loss of muscle mass, strength and physical performance with aging. Therefore, the aims of this thesis are to study 1) the impact of protein supplementation and 2) the impact of protein supplementation during prolonged resistance-type exercise training on muscle mass, strength and physical performance in frail elderly people. Methods: First, we studied various characteristics of dietary protein intake, including the distribution of dietary protein intake throughout the day, and the use of protein-containing food sources in various elderly populations. With this knowledge, we designed two large intervention trials to study the impact of dietary protein supplementation with or without prolonged resistance-type exercise training on muscle mass, strength and physical performance in frail elderly people. In addition, we assessed the usefulness of handgrip strength as a measure of post exercise strength differences and studied the association of vitamin D status and vitamin D intake on muscle mass, strength and physical performance in a frail elderly population. Results: Dietary protein intake in frail and institutionalized elderly people were especially low at breakfast and lunch. Supplementing protein at breakfast and lunch did not increase muscle mass but improved physical performance in frail elderly people. Resistance-type exercise training improved muscle leg strength and physical performance, but not handgrip strength. Supplementing protein at breakfast and lunch was required to significantly increase muscle mass during prolonged resistance-type exercise training in frail elderly people. Furthermore, low vitamin D status and vitamin D intake were associated with impaired physical performance. Conclusions: Although dietary protein supplementation does not increase muscle mass, it represents a promising strategy to improve physical performance in frail elderly people. Prolonged resistance-type exercise training represents an effective strategy to improve strength and physical performance, but dietary protein supplementation is required to allow muscle mass gain during exercise training in frail elderly people.
Bayesian Inference of Ancestral Host–Parasite Interactions under a Phylogenetic Model of Host Repertoire Evolution

Abstract Intimate ecological interactions, such as those between parasites and their hosts, may persist over long time spans, coupling the evolutionary histories of the lineages involved. Most methods that reconstruct the coevolutionary history of such interactions make the simplifying assumption that parasites have a single host. Many methods also focus on congruence between host and parasite phylogenies, using cospeciation as the null model. However, there is an increasing body of evidence suggesting that the host ranges of parasites are more complex: that host ranges often include more than one host and evolve via gains and losses of hosts rather than through cospeciation alone. Here, we develop a Bayesian approach for inferring coevolutionary history based on a model accommodating these complexities. Specifically, a parasite is assumed to have a host repertoire, which includes both potential hosts and one or more actual hosts. Over time, potential hosts can be added or lost, and potential hosts can develop into actual hosts or vice versa. Thus, host colonization is modeled as a two-step process that may potentially be influenced by host relatedness. We first explore the statistical behavior of our model by simulating evolution of host–parasite interactions under a range of parameter values. We then use our approach, implemented in the program RevBayes, to infer the coevolutionary history between 34 Nymphalini butterfly species and 25 angiosperm families. Our analysis suggests that host relatedness among angiosperm families influences how easily Nymphalini lineages gain new hosts. [Ancestral hosts; coevolution; herbivorous insects; probabilistic modeling. ]
FcRn augments induction of tissue factor activity by IgG-containing immune complexes.

Thromboembolism complicates disorders caused by IgG-containing immune complexes (ICs), but the underlying mechanisms are incompletely understood. Prior evidence indicates that induction of tissue factor (TF) on monocytes, a pivotal step in the initiation, localization and propagation of coagulation by ICs, is mediated through Fc gamma receptor IIa (FcγRIIa), yet the involvement of other receptors has not been investigated in detail. The neonatal Fc receptor (FcRn) that mediates IgG and albumin recycling also participates in cellular responses to IgG-containing ICs. Here we asked whether FcRn is also involved in the induction of TF-dependent factor Xa activity by IgG-ICs by THP-1 monocytic cells and human monocytes. Induction of factor Xa activity by ICs containing IgG antibodies to platelet factor 4 (PF4) involved in heparin-induced thrombocytopenia (HIT), b-2-glycoprotein-1 implicated in the antiphospholipid syndrome (APS), or red blood cells coated with anti-(α)-Rh(D) antibodies that mediate hemolysis in vivo were inhibited by a humanized monoclonal antibody (MoAb) that blocks IgG binding to human FcRn. IgG ICs that bind to FcγR and FcRn induced Factor Xa activity, whereas IgG-ICs with an Fc engineered to be unable to engage FcRn did not. Infusion of an α-FcRn MoAb prevented fibrin deposition following microvascular injury in a murine model of HIT in which human FcgRIIa is expressed as a transgene. These data implicate FcRn in TF-dependent FXa activity induced by soluble and cell-associated IgG-containing ICs. Antibodies to FcRn, now in clinical trials in warm autoimmune hemolytic anemic to lower IgG antibodies and IgG containing ICs may also reduce the risk of venous thromboembolism.
IJPTFI Available

Recent advances in relational algorithms and metamorphic epistemologies provide a feasible alternative to DNS. In our studies, we disconﬁrm the research of internet offerings, which embodies the theoretical ideas of hardware and structure. even though this could seem counterintuitive, it continuously conﬂicts with the need to provide multicast frameworks to analysts. on this paper, we inspect how multiprocessors may be applied to the simulation of courseware