Miracle-dz/UniFAR-FTUs huggingface dataset:
Compensating Circuit to Reduce the Impact of Wire Resistance in a Memristor Crossbar-Based Perceptron Neural Network

Wire resistance in metal wire is one of the factors that degrade the performance of memristor crossbar circuits. In this paper, an analysis of the impact of wire resistance in a memristor crossbar is performed and a compensating circuit is proposed to reduce the impact of wire resistance in a memristor crossbar-based perceptron neural network. The goal of the analysis is to figure out how wire resistance influences the output voltage of a memristor crossbar. It emerges that the wire resistance on horizontal lines causes the neuron’s output voltage to vary more than the wire resistance on vertical lines. More interesting, the voltage variation caused by wire resistance on horizontal lines increases proportionally to the length of metal wire. The first column has small voltage variation whereas the last column has large voltage variation. In addition, two adjacent columns have almost the same amount of voltage variation. Under these observations, a memristor crossbar-based perceptron neural network with compensating circuit is proposed. The neuron’s outputs of two columns are put into a subtractor circuit to eliminate the voltage variation caused by the wire resistance. The proposed memristor crossbar-based perceptron neural network is trained to recognize the 26 characters. The proposed memristor crossbar shows better recognition rate compared to the previous work when wire resistance is taken into account. The proposed memristor crossbar circuit can maintain the recognition rate as high as 100% when wire resistance is as high as 2.5 Ω. By contrast, the recognition rate of the memristor crossbar without the compensating circuit decreases by 1%, 5%, and 19% when wire resistance is set to be 1.5, 2.0, and 2.5 Ω, respectively.
An update on the pharmacokinetic considerations in the treatment of ADHD with long-acting methylphenidate and amphetamine formulations

ABSTRACT Introduction: Long-acting stimulant formulations are recommended as first-line pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Over the past 20 years, extended-release (ER) methylphenidate (MPH) and amphetamine (AMP) formulations have evolved to include varying drug delivery technologies, enantiomers/salts, and dosage forms. All formulations are characterized by a unique pharmacokinetic profile that is closely mirrored by pharmacodynamic response allowing clinicians to individualize therapy based on their patient’s clinical needs and dosing preferences. Areas covered: This review provides an update on the pharmacokinetic properties of approved and investigational ER MPH and AMP formulations and highlights pharmacokinetic features that clinicians should consider when selecting a long-acting stimulant. Expert opinion: Since there are no reliable biomarkers that can predict individualized response to long-acting stimulants, clinicians need to consider their distinctive pharmacokinetic properties, including the pharmacokinetic profile, rate and extent of absorption, variability, dose proportionality, bioequivalence, and potential for accumulation. Clinicians also need to understand that certain factors can contribute to increased variability in pharmacokinetics and potentially affect outcomes. Less invasive, high-throughput techniques and novel time-based scales are being developed to advance research on the pharmacokinetic-pharmacodynamic relationships of stimulants. Model-based pharmacokinetic-pharmacodynamic approaches can be applied to aid the development of novel formulations and individualize therapy with existing drugs.
Reconstructing the Dissemination Dynamics of the Major HIV-1 Subtype B Non-Pandemic Lineage Circulating in Brazil

Non-pandemic variants of the Human Immunodeficiency Virus Type 1 (HIV-1) subtype B accounts for a significant fraction of HIV infections in several Caribbean islands, Northeastern South American countries and the Northern Brazilian states of Roraima and Amazonas. In this paper, we used a comprehensive dataset of HIV-1 subtype B pol sequences sampled in Amazonas and Roraima between 2007 and 2017 to reconstruct the phylogeographic and demographic dynamics of the major HIV-1 subtype B non-pandemic Brazilian lineage, designated as BCAR-BR-I. Our analyses revealed that its origin could be traced to one of many viral introductions from French Guiana and Guyana into Northern Brazil, which probably occurred in the state of Amazonas around the late 1970s. The BCAR-BR-I clade was rapidly disseminated from Amazonas to Roraima, and the epidemic grew exponentially in these Northern Brazilian states during the 1980s and 1990s, coinciding with a period of economic and fast population growth in the region. The spreading rate of the BCAR-BR-I clade, however, seems to have slowed down since the early 2000s, despite the continued expansion of the HIV-1 epidemic in this region in the last decade.
Impact of stroke on affective well-being: findings from a large longitudinal nationally representative study

Abstract Objectives To examine whether the incidence of stroke influences affective well-being (positive affect and negative affect), and whether such a relationship is moderated by general self-efficacy. Method Longitudinal data from 2008, 2011 and 2014 were used from a population-based sample of community-residing individuals ≥ 40 years in Germany (n = 9,659 in regression analysis). Affective well-being was quantified using the established Positive and Negative Affect Schedule (PANAS). A well-established scale by Schwarzer and Jerusalem was used to assess general self-efficacy. General practitioner diagnosed stroke was reported. Results Fixed effects regressions showed that the incidence of stroke was associated with a decrease in positive affect in the total sample (β = –.17, p < .001) and in both sexes (men: β = –.16, p < .05; women: β = –.19, p < .01). In contrast to these findings, the incidence of stroke was not associated with changes in negative affect (total sample; stratified by sex). Moreover, general self-efficacy moderated the relation between stroke and positive affect. Conclusion Panel regression models showed that the incidence of stroke was associated with a decline in positive affect in the total sample and in both sexes. As the general self-efficacy moderated this association, it may be beneficial to enhance self-efficacy and prioritize coping strategies among stroke survivals.
The reliability, validity, interpretability, and responsiveness of the Norwegian version of the Anterior Knee Pain Scale in patellofemoral pain

Abstract Purpose To determine the reliability, validity, responsiveness, and interpretability of the Norwegian Anterior Knee Pain Scale (AKPS) in patients with patellofemoral pain (PFP). Methods The AKPS was translated into Norwegian. One hundred and twelve patients with PFP participated in a randomized controlled trial. Fifty stable patients completed the AKPS at a one-week interval for test–retest reliability. Smallest detectable change (SDC) and floor/ceiling effects were evaluated. Validity and responsiveness were assessed using hypothesis testing for correlations with other scores and known-group validity. Minimal important change (MIC) and responsiveness were evaluated at three months. Results Intraclass correlation coefficient (ICCagreement) for sum score was 0.83. Smallest detectable change was 13. No floor/ceiling effects were found for total score, but ceiling effects were found on eight of 13 individual items. Hypothesis testing for construct validity and responsiveness was largely confirmed but correlations were moderate to low. The MIC was 11. Area under receiver operating characteristic curve was 0.66 (95% CI 0.56–0.77) indicating moderate responsiveness. Conclusions The Norwegian AKPS had comparable measurement properties to other versions, with acceptable reliability and construct validity. We found moderate responsiveness which may be related to ceiling effects on several items. Implications for rehabilitation The Anterior Knee Pain Scale (AKPS) is a commonly used outcome measure in patellofemoral pain, having acceptable reliability and moderate responsiveness. A change in AKPS total score of 11 points would be considered important by the patient, although changes up to 13 points may be due to measurement error. The AKPS has limitations including ceiling effects on most individual items in this patient population, and low correlation between pain and AKPS that questions the validity of the score. A revision of the score should be considered.
Osteoporosis from an Endocrine Perspective: The Role of Hormonal Changes in the Elderly

Introduction: Osteoporosis is increasingly prevalent in the elderly, with fractures mostly occurring in women and men who are older than 55 and 65 years of age, respectively. The aim of this review was to examine the evidence regarding the influence of hormones on bone metabolism, followed by clinical data of hormonal changes in the elderly, in the attempt to provide possible poorly explored diagnostic and therapeutic candidate targets for the management of primary osteoporosis in the aging population. Material and methods: An extensive Medline search using PubMed, Embase, and Cochrane Library was performed. Results: While the rise in Thyroid-stimulating hormone (TSH) levels has a protective role on bone mass, the decline of estrogen, testosterone, Insulin-like growth factor 1 (IGF1), and vitamin D and the rise of cortisol, parathyroid hormone, and follicle-stimulating hormone (FSH) favor bone loss in the elderly. Particularly, the AA rs6166 FSH receptor (FSHR) genotype, encoding for a more sensitive FSHR than that encoded by the GG one, is associated with low total body mass density (BMD), independently of circulating estrogen. A polyclonal antibody with a FSHR-binding sequence against the β-subunit of murine FSH seems to be effective in ameliorating bone loss in ovariectomized mice. Conclusions: A complete hormonal assessment should be completed for both women and men during bone loss evaluation. Novel possible diagnostic and therapeutic tools might be developed for the management of male and female osteoporosis.
Optimized Treatment for Infantile Spasms: Vigabatrin versus Prednisolone versus Combination Therapy

Hormone therapies and vigabatrin are first-line agents in infantile spasms, but more than one-third of patients fail to respond to these treatments. This was a retrospective study of patients with infantile spasms who were treated between January 2005 and December 2017. We analyzed the response rates of initial treatment and second-line treatment. Responders were defined as those in whom cessation of spasms was observed for a period of at least one month, within 2 weeks of treatment initiation. Regarding the response rate to initial treatment, combination therapy of vigabatrin with prednisolone showed a significantly better response than that of vigabatrin monotherapy (55.3% vs. 39.1%, p = 0.037). Many drugs, such as clobazam, topiramate, and levetiracetam, were used as second-line agents after the failure of vigabatrin. Among these, no antiepileptic drug showed as good a response as prednisolone. For patients who used prednisolone, the proportion of responders was significantly higher in the higher-dose group (≥40 mg/day) than in the lower-dose group (66.7% vs. 12.5%, p = 0.028). Further studies of combination therapy to assess dosage protocols and long-term outcomes are needed.
PhaSepDB: a database of liquid–liquid phase separation related proteins

Abstract It's widely appreciated that liquid–liquid phase separation (LLPS) underlies the formation of membraneless organelles, which function to concentrate proteins and nucleic acids. In the past few decades, major efforts have been devoted to identify the phase separation associated proteins and elucidate their functions. To better utilize the knowledge dispersed in published literature, we developed PhaSepDB (http://db.phasep.pro/), a manually curated database of phase separation associated proteins. Currently, PhaSepDB includes 2914 non-redundant proteins localized in different organelles curated from published literature and database. PhaSepDB provides protein summary, publication reference and sequence features of phase separation associated proteins. The sequence features which reflect the LLPS behavior are also available for other human protein candidates. The online database provides a convenient interface for the research community to easily browse, search and download phase separation associated proteins. As a centralized resource, we believe PhaSepDB will facilitate the future study of phase separation.
Agaricus blazei-Based Mushroom Extract Supplementation to Birch Allergic Blood Donors: A Randomized Clinical Trial

Since Agaricus blazei Murill (AbM) extract reduced specific IgE and ameliorated a skewed Th1/Th2 balance in a mouse allergy model, it was tested in blood donors with self-reported, IgE-positive, birch pollen allergy and/or asthma. Sixty recruited donors were randomized in a placebo-controlled, double-blinded study with pre-seasonal, 7-week, oral supplementation with the AbM-based extract AndosanTM. Before and after the pollen season, questionnaires were answered for allergic rhino-conjunctivitis, asthma, and medication; serum IgE was measured, and Bet v 1-induced basophil activation was determined by CD63 expression. The reported general allergy and asthma symptoms and medication were significantly reduced in the AbM compared to the placebo group during pollen season. During the season, there was significant reduction in specific IgE anti-Bet v 1 and anti-t3 (birch pollen extract) levels in the AbM compared with the placebo group. While the maximal allergen concentrations needed for eliciting basophil activation before the season, changed significantly in the placebo group to lower concentrations (i.e., enhanced sensitization) after the season, these concentrations remained similar in the AndosanTM AbM extract group. Hence, the prophylactic effect of oral supplementation before the season with the AbM-based AndosanTM extract on aeroallergen-induced allergy was associated with reduced specific IgE levels during the season and basophils becoming less sensitive to allergen activation.
Using the Immunophenotype to Predict Response to Biologic Drugs in Rheumatoid Arthritis

Tumour necrosis factor (TNF)-α is a key mediator of inflammation in rheumatoid arthritis, and its discovery led to the development of highly successful anti-TNF therapy. Subsequently, other biologic drugs targeting immune pathways, namely interleukin-6 blockade, B cell depletion, and T cell co-stimulation blockade, have been developed. Not all patients respond to a biologic drug, leading to a knowledge gap between biologic therapies available and the confident prediction of response. So far, genetic studies have failed to uncover clinically informative biomarkers to predict response. Given that the targets of biologics are immune pathways, immunological study has become all the more pertinent. Furthermore, advances in single-cell technology have enabled the characterization of many leucocyte subsets. Studying the blood immunophenotype may therefore, define biomarker profiles relevant to each individual patient’s disease and treatment outcome. This review summarises our current understanding of how immune biomarkers might be able to predict treatment response to biologic drugs.
Nonparametric Analysis of Thermal Proteome Profiles Reveals Novel Drug-binding Proteins

A method for nonparametric analysis of response curves from thermal proteome profiling (TPP) experiments is proposed. The approach achieves high proteome coverage and sensitivity while controlling the false discovery-rate. Free open source software for NPARC is provided. Graphical Abstract Highlights Method for the analysis of response curves from thermal proteome profiling (TPP). NPARC uses nonparametric statistics and provides false discovery-rate (FDR) control. Increased proteome coverage and sensitivity to identify drug-binding proteins. Detecting the targets of drugs and other molecules in intact cellular contexts is a major objective in drug discovery and in biology more broadly. Thermal proteome profiling (TPP) pursues this aim at proteome-wide scale by inferring target engagement from its effects on temperature-dependent protein denaturation. However, a key challenge of TPP is the statistical analysis of the measured melting curves with controlled false discovery rates at high proteome coverage and detection power. We present nonparametric analysis of response curves (NPARC), a statistical method for TPP based on functional data analysis and nonlinear regression. We evaluate NPARC on five independent TPP data sets and observe that it is able to detect subtle changes in any region of the melting curves, reliably detects the known targets, and outperforms a melting point-centric, single-parameter fitting approach in terms of specificity and sensitivity. NPARC can be combined with established analysis of variance (ANOVA) statistics and enables flexible, factorial experimental designs and replication levels. An open source software implementation of NPARC is provided.
Low fitness at low latitudes: Wintering in the tropics increases migratory delays and mortality rates in an Arctic breeding shorebird

Abstract Evolutionary theories of seasonal migration generally assume that the costs of longer migrations are balanced by benefits at the non‐breeding destinations. We tested, and rejected, the null hypothesis of equal survival and timing of spring migration for High Arctic breeding sanderling Calidris alba using six and eight winter destinations between 55°N and 25°S, respectively. Annual apparent survival was considerably lower for adult birds wintering in tropical West Africa (Mauritania: 0.74 and Ghana: 0.75) than in three European sites (0.84, 0.84 and 0.87) and in subtropical Namibia (0.85). Moreover, compared with adults, second calendar‐year sanderlings in the tropics, but not in Europe, often refrained from migrating north during the first possible breeding season. During northward migration, tropical‐wintering sanderlings occurred at their final staging site in Iceland 5–15 days later than birds wintering further north or south. Namibia‐wintering sanderlings tracked with solar geolocators only staged in West Africa during southward migration. The low annual survival, the later age of first northward migration and the later passage through Iceland during northward migration of tropical‐wintering sanderlings, in addition to the skipping of this area during northward but not southward migration by Namibia‐wintering sanderlings, all suggest they face issues during the late non‐breeding season in West Africa. Migrating sanderlings defy long distances but may end up in winter areas with poor fitness prospects. We suggest that ecological conditions in tropical West Africa make the fuelling prior to northward departure problematic.
Breeding performance of Indonesian beef cattle as recipients for embryo transfer

The objective of this study was to evaluate the breeding performance of Indonesian beef cattle (Ongole cross) as recipients for embryo transfer using Limousin embryos. As a result, the pregnancy rate was 35% (7 out of 20 cows). There was a significant difference (P<0.01) in the serum progesterone concentration between the nonpregnant and pregnant cows at the time of the embryo transfer (day 7 after the estrus). The pregnancy rate in the Indonesian beef cows was low, which may be due to their insufficient genetic quality and/or low physical conditions caused by the poor management, like a low-nutrition diet. The low progesterone concentration in the nonpregnant cows on day 7 may be associated with the failure of embryo implantation.
The p75NTR Influences Cerebellar Circuit Development and Adult Behavior via Regulation of Cell Cycle Duration of Granule Cell Progenitors

Development of brain circuitry requires precise regulation and timing of proliferation and differentiation of neural progenitor cells. The p75 neurotrophin receptor (p75NTR) is highly expressed in the proliferating granule cell precursors (GCPs) during development of the cerebellum. In a previous paper, we showed that proNT3 promoted GCP cell cycle exit via p75NTR. Here we used genetically modified rats and mice of both sexes to show that p75NTR regulates the duration of the GCP cell cycle, requiring activation of RhoA. Rats and mice lacking p75NTR have dysregulated GCP proliferation, with deleterious effects on cerebellar circuit development and behavioral consequences persisting into adulthood. In the absence of p75NTR, the GCP cell cycle is accelerated, leading to delayed cell cycle exit, prolonged GCP proliferation, increased glutamatergic input to Purkinje cells, and a deficit in delay eyeblink conditioning, a cerebellum-dependent form of learning. These results demonstrate the necessity of appropriate developmental timing of the cell cycle for establishment of proper connectivity and associated behavior. SIGNIFICANCE STATEMENT The cerebellum has been shown to be involved in numerous behaviors in addition to its classic association with motor function. Cerebellar function is disrupted in a variety of psychiatric disorders, including those on the autism spectrum. Here we show that the p75 neurotrophin receptor, which is abundantly expressed in the proliferating cerebellar granule cell progenitors, regulates the cell cycle of these progenitors. In the absence of this receptor, the cell cycle is dysregulated, leading to excessive progenitor proliferation, which alters the balance of inputs to Purkinje cells, disrupting the circuitry and leading to functional deficits that persist into adulthood.
A systematic literature review on the use of platelet transfusions in patients with thrombocytopenia

ABSTRACT Objective: Investigate globally, current treatment patterns, benefit-risk assessments, humanistic, societal and economic burden of platelet transfusion (PT). Methods: Publications from 1998 to June 27, 2018 were identified, based on databases searches including MEDLINE®; Embase and Cochrane Database of Systematic Reviews. Data from studies meeting pre-specified criteria were extracted and validated by independent reviewers. Data were obtained for efficacy and safety from randomized controlled trials (RCTs); data for epidemiology, treatment patterns, effectiveness, safety, humanistic and societal burden from real-world evidence (RWE) studies; and economic data from both. Results: A total of 3425 abstracts, 194 publications (190 studies) were included. PT use varied widely, from 0%–100% of TCP patients; 1.7%–24.5% in large studies (>1000 patients). Most were used prophylactically rather than therapeutically. 5 of 43 RCTs compared prophylactic PT with no intervention, with mixed results. In RWE studies PT generally increased platelet count (PC). This increase varied by patient characteristics and hence did not always translate into a clinically significant reduction in bleeding risk. Safety concerns included infection risk, alloimmunization and refractoriness with associated cost burden. Discussion: In RCTs and RWE studies there was significant heterogeneity in study design and outcome measures. In RWE studies, patients receiving PT may have been at higher risk than those not receiving PT creating potential bias. There were limited data on humanistic and societal burden. Conclusion: Although PTs are used widely for increasing PC in TCP, it is important to understand the limitations of PTs, and to explore the use of alternative treatment options where available.