Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer in Adolescents and Young Adults: A Narrative Review of the Current Status and a View of the Future.

IMPORTANCE Although cancer remains the most common cause of disease-related death in adolescents and young adults (AYAs) in high-income countries, their overall survival rates continue to increase and now exceed 80% at 5 years in several high-income countries. This has been accomplished through progressive improvements in active treatment and supportive care, although accrual rates to therapeutic clinical trials remain disappointing. Recognition of the unique distribution of diseases in the AYA population with cancer and further understanding of the distinctive biology of cancers in AYAs will lead to continuing gains in clinical outcomes. OBSERVATIONS Many of the challenges faced by AYAs with a diagnosis of malignant disease are shared by others with chronic medical conditions and even their healthy peers, such as a sense of invulnerability that may contribute to delays in diagnosis. A particular need for psychological support has been identified for AYAs with cancer, even after active therapy has been completed and especially in the context of palliative care. Notable needs also include fertility preservation and navigation through the multiple transitions in the cancer journey. Additionally, there is a "cost of cure. " This is not only in the form of short-term, treatment-related morbidity and mortality but also in the burden of "late effects," including second cancers, that compromise quality of life and limit life expectancy. Establishing clinical programs devoted to AYAs with cancer, with complementary educational initiatives, will strengthen the advances made. It is anticipated that clinical trial accrual will increase substantially, providing further gains in survival. Likewise, addressing the challenges of survivorship, including secondary prevention of long-term morbidity and mortality, will lead to additional improvements in clinical outcomes. CONCLUSIONS AND RELEVANCE Transferring this knowledge to the care of an estimated 1 million incident cases of cancer in AYAs worldwide, most of whom do not live in high-income countries, remains a considerable challenge.
Peripheral blood clinical laboratory variables associated with outcomes following combination nivolumab and ipilimumab immunotherapy in melanoma

Both the combination of nivolumab + ipilimumab and single‐agent anti‐PD‐1 immunotherapy have demonstrated survival benefit for patients with advanced melanoma. As the combination has a high rate of serious side effects, further analyses in randomized trials of combination versus anti‐PD‐1 immunotherapy are needed to understand who benefits most from the combination. Clinical laboratory values that were routinely collected in randomized studies may provide information on the relative benefit of combination immunotherapy. To prioritize which clinical laboratory factors to ultimately explore in these randomized studies, we performed a single‐center, retrospective analysis of patients with advanced melanoma who received nivolumab + ipilimumab either as part of a clinical trial (n = 122) or commercial use (n = 87). Baseline routine laboratory values were correlated with overall survival (OS) and overall response rate (ORR). Kaplan–Meier estimation and Cox regression were performed. Median OS was 44.4 months, 95% CI (32.9, Not Reached). A total of 110 patients (53%) responded (CR/PR). Significant independent variables for favorable OS included the following: high relative eosinophils, high relative basophils, low absolute monocytes, low LDH, and a low neutrophil‐to‐lymphocyte ratio. These newly identified factors, along with those previously reported to be associated with anti‐PD‐1 monotherapy outcomes, should be studied in the randomized trials of nivolumab + ipilimumab versus anti‐PD‐1 monotherapies to determine whether they help define the patients who benefit most from the combination versus anti‐PD‐1 alone.
Onset patterns in autism: Variation across informants, methods, and timing

While previous studies suggested that regressive forms of onset were not common in autism spectrum disorder (ASD), more recent investigations suggest that the rates are quite high and may be under‐reported using certain methods. The current study undertook a systematic investigation of how rates of regression differed by measurement method. Infants with (n = 147) and without a family history of ASD (n = 83) were seen prospectively for up to 7 visits in the first three years of life. Reports of symptom onset were collected using four measures that systematically varied the informant (examiner vs. parent), the decision type (categorical [regression absent or present] vs. dimensional [frequency of social behaviors]), and the timing of the assessment (retrospective vs. prospective). Latent class growth models were used to classify individual trajectories to see whether regressive onset patterns were infrequent or widespread within the ASD group. A majority of the sample was classified as having a regressive onset using either examiner (88%) or parent (69%) prospective dimensional ratings. Rates of regression were much lower using retrospective or categorical measures (from 29 to 47%). Agreement among different measurement methods was low. Declining trajectories of development, consistent with a regressive onset pattern, are common in children with ASD and may be more the rule than the exception. The accuracy of widely used methods of measuring onset is questionable and the present findings argue against their widespread use. Autism Res 2018, 11: 788–797. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
ZCCHC17 is a master regulator of synaptic gene expression in Alzheimer's disease

Motivation In an effort to better understand the molecular drivers of synaptic and neurophysiologic dysfunction in Alzheimer's disease (AD), we analyzed neuronal gene expression data from human AD brain tissue to identify master regulators of synaptic gene expression. Results Master regulator analysis identifies ZCCHC17 as normally supporting the expression of a network of synaptic genes, and predicts that ZCCHC17 dysfunction in AD leads to lower expression of these genes. We demonstrate that ZCCHC17 is normally expressed in neurons and is reduced early in the course of AD pathology. We show that ZCCHC17 loss in rat neurons leads to lower expression of the majority of the predicted synaptic targets and that ZCCHC17 drives the expression of a similar gene network in humans and rats. These findings support a conserved function for ZCCHC17 between species and identify ZCCHC17 loss as an important early driver of lower synaptic gene expression in AD. Availability and implementation Matlab and R scripts used in this paper are available at https://github.com/afteich/AD_ZCC
Alleviation of Heat Stress by a Polyherbal Formulation, Phytocee™: Impact on Zootechnical Parameters, Cloacal Temperature, and Stress Markers

Background: The range of thermoneutral zone of chickens is narrow, and they become easily susceptible to environmental stress, a common and major concern for poultry causing a production loss. Objective: The present study was designed to comparatively evaluate anti-stress activity of Phytocee™ and Vitamin C in chickens reared under heat stress. Materials and Methods: A total of 600-day-old chicks of Cobb 400 were randomly assigned to 4 groups with 6 replicates comprising 25 birds each (n = 150). G1 served as a normal control (NC) and supplemented with Vitamin C at 100 g/ton of feed. G2 served as a heat stress control (HSC), subjected to heat stress (34°C–36°C) without Vitamin C supplementation. G3 and G4 served as positive control and treatment group (TC), subjected to heat stress and supplemented with Vitamin C and Phytocee™ at 100 g/ton of feed, respectively. The impact on zootechnical parameters and cloacal temperature was assessed at regular intervals, and blood was collected at the end of the experiment for evaluation of stress parameters, namely heterophil lymphocyte ratio (H:L ratio) and serum corticosterone. Results: Exposure of chickens to heat stress caused a significant decrease in body weight, worsening of feed conversion ratio, higher mortality, and poor production efficiency. Moreover, serum corticosterone level, H:L ratio, and cloacal temperature were significantly increased in HSC as compared to NC. However, supplementation of Phytocee™ in feed significantly ameliorated the negative impact of heat stress in broiler birds. Conclusion: The supplementation of Phytocee™ demonstrated an anti-stress effect in chickens through restoration of serum corticosterone level, H:L ratio, and thermoregulatory mechanism.
Population Expansion and Genetic Structure in Carcharhinus brevipinna in the Southern Indo-Pacific

Background Quantifying genetic diversity and metapopulation structure provides insights into the evolutionary history of a species and helps develop appropriate management strategies. We provide the first assessment of genetic structure in spinner sharks (Carcharhinus brevipinna), a large cosmopolitan carcharhinid, sampled from eastern and northern Australia and South Africa. Methods and Findings Sequencing of the mitochondrial DNA NADH dehydrogenase subunit 4 gene for 430 individuals revealed 37 haplotypes and moderately high haplotype diversity (h = 0.6770 ±0.025). While two metrics of genetic divergence (ΦST and F ST) revealed somewhat different results, subdivision was detected between South Africa and all Australian locations (pairwise ΦST, range 0.02717–0.03508, p values ≤ 0.0013; pairwise F ST South Africa vs New South Wales = 0.04056, p = 0.0008). Evidence for fine-scale genetic structuring was also detected along Australia’s east coast (pairwise ΦST = 0.01328, p < 0.015), and between south-eastern and northern locations (pairwise ΦST = 0.00669, p < 0.04). Conclusions The Indian Ocean represents a robust barrier to contemporary gene flow in C. brevipinna between Australia and South Africa. Gene flow also appears restricted along a continuous continental margin in this species, with data tentatively suggesting the delineation of two management units within Australian waters. Further sampling, however, is required for a more robust evaluation of the latter finding. Evidence indicates that all sampled populations were shaped by a substantial demographic expansion event, with the resultant high genetic diversity being cause for optimism when considering conservation of this commercially-targeted species in the southern Indo-Pacific.
Cystic Fibrosis Pulmonary Exacerbations Attributable to Respiratory Syncytial Virus and Influenza: A Population-Based Study

Background. Characterization of the role of respiratory viral pathogens on cystic fibrosis (CF) pulmonary disease is needed. We aimed to determine the association of influenza and respiratory syncytial virus (RSV) activity with risk of pulmonary exacerbation (PEx) in persons with CF in the United States. Methods. We conducted a cohort study from January 2003 to March 2009 using the CF Foundation Patient Registry merged with Centers for Disease Control and Prevention respiratory virus surveillance data. The primary goal was to determine the association between regional influenza or RSV detections with risk of PEx requiring intravenous antibiotics or hospitalization. We analyzed outcomes by geographic region and week of event using multivariable regression models adjusted for demographic and clinical predictors of PEx stratified for children (<18 years) and adults (≥18 years) to calculate relative risks (RRs) of PEx. Results. There were 21022 individuals (52% male) in the CF patient cohort in 2003 comprised of 12702 children and 8320 adults. The overall incidence rate of PEx was 521.9 per 10000 person-months. In children, a 10% increase in the proportion of surveillance tests positive for influenza or RSV was significantly associated with increased PEx risk (RR, 1.02; 95% confidence interval [CI], 1.01-1.03) and (RR, 1.05; 95% CI, 1.02-1.07), respectively. In adults, surveillance tests positive for influenza (RR, 1.02; 95% CI, 1.01-1.02), but not RSV (RR, 0.99; 95% CI, .98-1.01), had a significant association with PEx risk. Conclusions. Our large CF population-based cohort demonstrated a significant association between PEx risk and influenza activity in children and adults and with RSV activity in children.
Online product reviews and the description-experience gap

People can access information about choices in at least two ways: via summary descriptions that provide an overview of potential outcomes and their likelihood of occurrence or via sequential presentation of outcomes. Provided with the former, people make decisions from description; with the latter, they make decisions from experience. Recent investigations involving risky choices have demonstrated a robust and systematic description–experience gap. Specifically, when people make decisions from experience, rare events tend to have less impact than what they deserve according to their objective probability. Here, we show that this description–experience gap generalizes from choices involving monetary gambles to choices based on (hypothetical) online product ratings. We further show that causes that have been identified in the context of risky choice also contribute to the description–experience gap in choice based on online product ratings: reliance on relatively small samples of information and overweighting of recently sampled information (recency). We conclude with a discussion of the practical implications of our results and identify promising directions for cross-disciplinary investigations. Copyright © 2014 John Wiley & Sons, Ltd.
Comparison of the Relative Potential for Epigenetic and Genetic Variation To Contribute to Trait Stability

The theoretical ability of epigenetic variation to influence the heritable variation of complex traits is gaining traction in the study of adaptation. This theory posits that epigenetic marks can control adaptive phenotypes but the relative potential of epigenetic variation in comparison to genetic variation in these traits is not presently understood. To compare the potential of epigenetic and genetic variation in adaptive traits, we analyzed the influence of DNA methylation variation on the accumulation of chemical defense compounds glucosinolates from the order Brassicales. Several decades of work on glucosinolates has generated extensive knowledge about their synthesis, regulation, genetic variation and contribution to fitness establishing this pathway as a model pathway for complex adaptive traits. Using high-throughput phenotyping with a randomized block design of ddm1 derived Arabidopsis thaliana epigenetic Recombinant Inbred Lines, we measured the correlation between DNA methylation variation and mean glucosinolate variation and within line stochastic variation. Using this information, we identified epigenetic Quantitative Trait Loci that contained specific Differentially Methylated Regions associated with glucosinolate traits. This showed that variation in DNA methylation correlates both with levels and variance of glucosinolates and flowering time with trait-specific loci. By conducting a meta-analysis comparing the results to different genetically variable populations, we conclude that the influence of DNA methylation variation on these adaptive traits is much lower than the corresponding impact of standing genetic variation. As such, selective pressure on these traits should mainly affect standing genetic variation to lead to adaptation.
The role of extracellular Tau in the spreading of neurofibrillary pathology

The microtubule-associated protein (MAP) tau plays a critical role in the pathogenesis of Alzheimer’s disease (AD) and several related disorders collectively known as tauopathies. Development of tau pathology is associated with progressive neuronal loss and cognitive decline. In the brains of AD patients, tau pathology spreads following an anatomically defined pattern. Mounting evidence strongly suggests that accumulation of abnormal tau is mediated through spreading of seeds of the protein from cell to cell and point at the involvement of extracellular tau species as the main agent in the interneuronal propagation of neurofibrillary lesions and spreading of tau toxicity throughout different brain regions in these disorders. That would support the concept that pathology initiates in a very small part of the brain many years before becoming symptomatic, spreading progressively to the whole brain within 10–20 years. Understanding the precise molecular mechanism underlying tau propagation is crucial for the development of therapeutics for this devastating disorder. In this work, we will discuss recent research on the role of extracellular tau in the spreading of tau pathology, through synaptic and non-synaptic mechanisms.
A Systematic Review of Outcome Measurements and Quality of Studies Evaluating Fixed Tooth-Supported Restorations

Purpose The purpose of this systematic review was to review clinical studies of fixed tooth-supported prostheses, and to assess the quality of evidence with an emphasis on the assessment of the reporting of outcome measurements. Multiple hypotheses were generated to compare the effect of study type on different outcome modifiers and to compare the quality of publications before and after January 2005. Materials and Methods An electronic search was conducted using specific databases (MEDLINE via Ovid, EMBASE via Ovid, Cochrane Library) through July 2012. This was complemented by hand searching the past 10 years of issues of the Journal of Oral Rehabilitation, Journal of Prosthetic Dentistry, Journal of Prosthodontics, and the International Journal of Prosthodontics. All experimental and observational clinical studies evaluating survival, success, failure, and complications of tooth-supported extracoronal fixed partial dentures, crowns, and onlays were included. No restrictions on age or follow-up time were placed. Results The electronic search generated 14,869 papers, of which 206 papers were included for full-text review. Hand-searching added 23 papers. Inclusion criteria were met by 182 papers and were included for the review. The majority were retrospective studies. Only 8 (4.4%) were randomized controlled trials. The majority of the studies measured survival and failure, and few studies recorded data on success; however, more than 60% of the studies failed to define survival, success, and failure. Many studies did not use any standardized criteria for assessment of the quality of the restorations and, when standardized criteria were used, they were modified, thereby not allowing for comparisons with other studies. There was an increase of 21.8% in the number of studies evaluating outcome measurements of all-ceramic restorations in past 8 years. Conclusions Prosthodontic literature presents with a reduced percentage of RCTs compared to other disciplines in dentistry. The overall quality of recording prosthodontic outcome measurements has not improved greatly in the past 8 years.
Preventing Clinical Leakage of Colonic Anastomoses with A Fibrin-Coated Collagen Patch Sealing - An Experimental Study

Background: Anastomotic leakage remains a major complication following colorectal surgery, with a largely unknown pathophysiology and limited treatment options. Previous clinical studies have revealed that many leakages on colo-rectal anastomoses remain subclinical. Prior attempts at prophylactic mechanical sealing of gastrointestinal anastomoses, i.e., the application of various forms of mesh and fibrin components, have been disappointing. We therefore decided to determine whether a collagen patch coated with fibrin glue components (TachoSil®) is able to seal leaking colonic anastomoses and thereby prevent clinical leakage and peritonitis. Material and methods: Prospective study on 20 pigs operated with experimentally induced defects in colonic anastomoses randomized to sealing vs. no sealing with a collagen patch coated with fibrin glue components. The primary study endpoints were visible leakage at the anastomotic site, death or illness causing sacrifice and fecal peritonitis (local or diffuse). Results: A significant reduction in macroscopic anastomotic leakage in the group of pigs with sealed anastomoses was found (2/10 vs. 9/10, p=0.0055). Furthermore, macroscopic examination of the abdominal cavity (n=20) showed a significant decrease in peritonitis in the sealed vs. non-sealed groups (2 vs. 9, p=0.0055). Additionally, a reduction, although non-significant, in dead and sacrificed animals before the end of the observation period (1 vs. 4) was found in the sealed group. Conclusion: A collagen patch coated with fibrin glue components efficiently seals leaking gastrointestinal anastomoses in pigs. Whether these results may be applied to humans in order to prevent clinical anastomotic dehiscence must be investigated in future randomized clinical studies.
Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions

After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females.