Miracle-dz/UniFAR-FTUs huggingface dataset:
Molt induced by gonadotropin-releasing hormone agonist as a model for studying endocrine mechanisms of molting in laying hens.

Molt induced by infusion of a gonadotropin-releasing hormone agonist (GnRH-A, ([D-Leu6,Pro9]-GnRH N-ethylamide]) has been used as a model for studying the endocrine mechanisms of molting. Molt induced by GnRH-A was also compared with that induced by feed withdrawal (FW). Thirty-three laying hens were divided into three groups: 1) sham infused (controls), 2) molted by GnRH-A infusion (GnRH-A), or 3) molted by FW. All groups had reduced day length. Birds were weighed and blood was sampled twice per week. Plasma was assayed for thyroxine (T4), triiodothyronine (T3), and progesterone (P4); egg production was recorded. A separate group of GnRH-A molted (n = 8) and control (n = 4) hens were killed during the molt and liver, ovary, and oviduct were weighed. Plasma T4 concentrations were elevated (P less than .01), whereas plasma T3 did not change and plasma P4 decreased (P less than .05) in the GnRH-A group compared with the control group. Plasma T4 was higher (P less than .05) in the GnRH-A group than in the FW group, whereas plasma T3 was higher (P less than .05) in the FW group than in the GnRH-A group. Plasma P4 concentrations declined to similar low levels in the GnRH-A and FW groups. The GnRH-A caused weight loss (P less than .05) from the ovary, oviduct, and liver. The GnRH-A-molted hens lost less BW (P less than .001) and were out of lay for 12 days less than FW-molted hens. Postmolt rates of lay were not significantly different for the two groups. (ABSTRACT TRUNCATED AT 250 WORDS)
A Randomized Controlled Trial of Cognitive Remediation and Work Therapy in the Early Phase of Substance Use Disorder Recovery for Older Veterans: Neurocognitive and Substance Use Outcomes

Objective: Cognitive remediation therapy (CRT) is reported to improve neurocognitive and substance use disorder (SUD) outcomes in residential treatments. This National Institute of Drug Abuse funded pilot study reports on CRT as an augmentation to outpatient treatment for SUD. Method: Recovering outpatient veterans were randomized into CRT + Work Therapy (n = 24) or work therapy (n = 24) with treatment-as-usual. Blind assessments of neurocognition and substance use were performed at baseline, 3 months (end of treatment), and 6-month follow-up. Results: Baseline assessments revealed high rates of cognitive impairment with 87.5% showing significant decline from premorbid IQ on at least 1 measure (median = 3/14 measures). Adherence to treatment was excellent. Follow-up rates were 95.7% at 3 months and 87.5% at 6 months. Mixed effects models of cognitive change over time revealed significant differences favoring CRT + Work Therapy on working memory (WM) and executive function indices. Global index of cognition showed a nonsignificant trend (effect size [ES] = .37) favoring CRT + Work Therapy. SUD outcomes were excellent for both conditions. CRT + Work Therapy had a mean of 97% days of abstinence at 3 months, 94% in the 30 days prior to 6-month follow-up, and 24/26 weeks of total abstinence; differences between conditions were not significant. Conclusions and Implications for Practice: CRT was well accepted by outpatient veterans with SUDs and led to significant improvements in WM and executive functions beyond that of normal cognitive recovery. No difference between conditions was found for SUD outcomes, perhaps because work therapy obscured the benefits of CRT.
Methionine sulfoxide reductase B3 requires resolving cysteine residues for full activity and can act as a stereospecific methionine oxidase

The oxidation of methionine residues in proteins occurs during oxidative stress and can lead to an alteration in protein function. The enzyme methionine sulfoxide reductase (Msr) reverses this modification. Here, we characterise the mammalian enzyme Msr B3. There are two splice variants of this enzyme that differ only in their N-terminal signal sequence, which directs the protein to either the endoplasmic reticulum (ER) or mitochondria. We demonstrate here that the enzyme can complement a bacterial strain, which is dependent on methionine sulfoxide reduction for growth, that the purified recombinant protein is enzymatically active showing stereospecificity towards R-methionine sulfoxide, and identify the active site and two resolving cysteine residues. The enzyme is efficiently recycled by thioredoxin only in the presence of both resolving cysteine residues. These results show that for this isoform of Msrs, the reduction cycle most likely proceeds through a three-step process. This involves an initial sulfenylation of the active site thiol followed by the formation of an intrachain disulfide with a resolving thiol group and completed by the reduction of this disulfide by a thioredoxin-like protein to regenerate the active site thiol. Interestingly, the enzyme can also act as an oxidase catalysing the stereospecific formation of R-methionine sulfoxide. This result has important implications for the role of this enzyme in the reversible modification of ER and mitochondrial proteins.
Differential Effects of Bevacizumab, Ranibizumab, and Aflibercept on the Viability and Wound Healing of Corneal Epithelial Cells.

PURPOSE This study compared the effects of 3 antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) on corneal epithelial cell viability and wound healing using human corneal epithelial cells (HCECs). METHODS To determine the cytotoxic effects of anti-VEGF agents on HCECs, HCEC viability was determined at various concentrations of these agents. An in vitro migration assay was used to investigate the migration of HCECs treated with 3 anti-VEGF agents. The protein level of extracellular signal-regulated kinase was used to evaluate the effect of anti-VEGF treatment on cell proliferation. The protein levels of p38 mitogen-activated protein kinase (MAPK) were analyzed by Western blotting to investigate cell migration. RESULTS After 24 or 48 h of exposure, aflibercept treatment showed no apparent effect on cell viability; however, bevacizumab and ranibizumab treatment decreased cell viability at high concentrations (1 and 2 mg/mL). A migration assay showed that HCEC migration was different among the 3 anti-VEGF treatment groups. Bevacizumab significantly delayed HCEC migration. Western blotting showed that bevacizumab treatment decreased the expression levels of phosphorylated p38 MAPK. CONCLUSIONS Bevacizumab, the most widely used and investigated anti-VEGF agent, decreased epithelial cell migration and viability. Anti-VEGF agents other than bevacizumab might therefore be better for treating corneal neovascularization complicated with epithelial defects.
miFAST: A novel and rapid microRNA target capture method

MicroRNAs (miRNAs), small 22‐25 nucleotide non‐coding RNAs, play important roles in cellular and tumor biology. However, characterizing miRNA function remains challenging due to an abundance of predicted targets and an experimental bottleneck in identifying biologically relevant direct targets. Here, we developed a novel technique (miFAST) to identify direct miRNA target genes. Using miFAST, we confirmed several previously reported miR‐340 target genes and identified five additional novel direct miR‐340 targets in melanoma cells. This methodology can also be efficiently applied for the global characterization of miRNA targets. Utilizing miFAST to characterize direct miRNA targetomes will further our understanding of miRNA biology and function.
Age-dependent structural connectivity effects in fragile x premutation.

OBJECTIVE To examine the effects of premutation alleles on major brain fiber tracts in males. DESIGN Cross-sectional study performed in 2007-2009. SETTING Institutional practice. PATIENTS Fifteen younger (18-45 years old) carriers, 11 older (>45 years old) unaffected carriers, and 15 older carriers with fragile X-associated tremor/ataxia syndrome, together with 19 younger and 15 older controls matched by age and educational level. MAIN OUTCOME MEASURES Diffusion tensor imaging was performed on all study participants. Eleven fiber tracts important for motor, social, emotional, and cognitive functions were reconstructed and quantified. Complementary tract-based spatial statistical analyses were performed in core white matter. RESULTS In the younger carriers, premutation status was associated with a greater age-related connectivity decline in the extreme capsule. Among older carriers, unaffected individuals did not display structural alterations, whereas the affected carriers showed connectivity loss in 5 fiber tracts and exhibited greater age-related connectivity decline in all 11 tracts compared with the controls. In addition, 9 fiber tracts showed significantly higher variability relative to the controls, and symptom severity explained the variability in 6 measurements from the superior cerebellar peduncle, corpus callosum, and cingulum. CONCLUSIONS The findings revealed widespread alterations in structural connectivity associated with fragile X-associated tremor/ataxia syndrome and preserved or subtle changes in structural connectivity in unaffected carriers. Diffusion tensor imaging is sensitive to pathologic changes in the white matter associated with this neurodegenerative disorder. Wang et al examine the effects of premutation alleles on major brain fiber tracts in males, who are at risk of developing fragile X-associated tremor/ataxia syndrome and may manifest subtle cognitive, social, and emotional disturbances before clinical involvement.
Shedding Light on Important Waters for Drug Design: Simulations versus Grid-Based Methods

Water molecules play an important role in the association of drugs with their pharmaceutical targets. For this reason, calculating the energetic contribution of water is essential to make accurate predictions of compounds' affinity and selectivity. Water molecules can also modify the binding mode of compounds by forming water bridges, or clusters, that stabilize a particular orientation of the ligand. Several computational methods have been developed for solvent mapping, but few studies have attempted to compare them in a drug design context. In this paper, four commercially available solvent mapping tools (SZMAP, WaterFLAP, 3D-RISM, and WaterMap) are evaluated on three different protein targets. The methods were compared by looking at their ability to predict the structure-activity relations of lead compounds. All methods were found to be useful to some degree and to improve the predictions from docking alone. However, the only simulation-based approach tested, WaterMap, was found in some cases to be more accurate than grid-based methods.
Physiological-based Dynamic Difficulty Adaptation in a Theragame for Children with Cerebral Palsy

The purpose of this research is to provide a physiological-based Dynamic Difficulty Adaptation (DDA) for rehabilitation of children with Cerebral Palsy (CP). In this paper, we present all the steps of the DDA development by going through (1) the acquisition of physiological signals, (2) the extraction of the physiological signalsâ features, (3) the training of a learning classifier of physiological signals' features, and (4) the implementation of the DDA in a game-based rehabilitation system. As a result, we successfully implement a physiological-based DDA based on the user affective state (anxiety and boredom).
Super-resolution method and its application to medical image processing

In medical imaging, X-ray photographic images are commonly used, but these have low resolution and a significant amount of noise because radiation levels are minimized for patient safety. In this paper, we propose a novel measurement algorithm for X-ray images generated by our proposed super-resolution method. To validate the measurement accuracy of our proposed algorithm, we construct a model for the measurement algorithm for joint space distance using a 3D printer, and obtain X-ray images of it. Experimental results show that the distances are measured with high accuracy.
Role of topical oxytocin in improving vaginal atrophy in postmenopausal women: a randomized, controlled trial

Abstract Objective and design: Prospective randomized controlled trial to test the effectiveness of topical oxytocin gel to improve vaginal atrophy in postmenopausal women. Patients and methods: A total of 140 postmenopausal women presenting with vaginal atrophy and who satisfied the inclusion and exclusion criteria were randomized into two groups each of 70 patients; they received intravaginal oxytocin gel or placebo gel for 30 days. Serum estrogen level, visual, colposcopic and histological vaginal examination were performed before and after treatment. Results: Forty-seven out of 70 women in the oxytocin gel group improved after treatment and none in the placebo group (p = 0.001). Forty-five participants in the oxytocin group and seven in the placebo group reported relief of dyspareunia (p = 0.001). Thirty-four participants in the oxytocin group and seven in the placebo group reported relief of soreness (p = 0.001). There was no significant difference between the circulating levels of estradiol in both groups before and after treatment (p = 0.4 and 0.6 for the oxytocin group and the placebo group, respectively). Conclusion: Oxytocin gel is useful in the restoration of the vaginal epithelium in cases of postmenopausal atrophic vaginitis. Further studies with a longer follow-up period are required to test the long-term effects of oxytocin as a treatment for vaginal atrophy.
Multikernel Data Partitioning With Channel on OpenCL-Based FPGAs

Recently, field-programmable gate array (FPGA) vendors (such as Altera) have started to address the programmability issues of FPGAs via OpenCL SDKs. In this paper, we analyze the performance of relational database applications on FPGAs using OpenCL. In particular, we study how to improve the performance of data partitioning, which is a very important building block in relational database. Since the data partitioning causes random memory accesses, it is time-consuming, and then, it has been the major bottleneck for database operators, such as partitioned hash join. In particular, we import the state-of-the-art OpenCL implementation of data partitioning from OmniDB, which was originally designed and optimized for CPUs/GPUs, and we find that this implementation suffers from both lock overhead and memory bandwidth overhead. Accordingly, we present a multikernel approach to address the lock overhead by leveraging two emerging features (task kernel and channel) from Altera OpenCL software development kit. In order to reduce the memory bandwidth overhead, on-chip buckets are used to reduce the number of random global memory transactions. We further develop an FPGA-specific cost model to guide the parameter configuration. We evaluate the proposed design on a recent OpenCL-based FPGA. We have applied our optimized partitioning method to a number of data processing tasks, including hash join, histogram, and hash search. Our experimental results demonstrate that our cost model can accurately guide the user to determine the optimal parameter combination for data partitioning and the optimal parameter combination can achieve $16.6\times$ speedup over the default multithreaded implementation.
A Team-Based Online Game Improves Blood Glucose Control in Veterans With Type 2 Diabetes: A Randomized Controlled Trial

OBJECTIVE Rigorous evidence is lacking whether online games can improve patients’ longer-term health outcomes. We investigated whether an online team-based game delivering diabetes self-management education (DSME) to patients via e-mail or mobile application (app) can generate longer-term improvements in hemoglobin A1c (HbA1c). RESEARCH DESIGN AND METHODS Patients (n = 456) on oral diabetes medications with HbA1c ≥58 mmol/mol were randomly assigned between a DSME game (with a civics booklet) and a civics game (with a DSME booklet). The 6-month games sent two questions twice weekly via e-mail or mobile app. Participants accrued points based on performance, with scores posted on leaderboards. Winning teams and individuals received modest financial rewards. Our primary outcome measure was HbA1c change over 12 months. RESULTS DSME game patients had significantly greater HbA1c reductions over 12 months than civics game patients (−8 mmol/mol [95% CI −10 to −7] and −5 mmol/mol [95% CI −7 to −3], respectively; P = 0.048). HbA1c reductions were greater among patients with baseline HbA1c >75 mmol/mol: −16 mmol/mol [95% CI −21 to −12] and −9 mmol/mol [95% CI −14 to −5] for DSME and civics game patients, respectively; P = 0.031. CONCLUSIONS Patients with diabetes who were randomized to an online game delivering DSME demonstrated sustained and meaningful HbA1c improvements. Among patients with poorly controlled diabetes, the DSME game reduced HbA1c by a magnitude comparable to starting a new diabetes medication. Online games may be a scalable approach to improve outcomes among geographically dispersed patients with diabetes and other chronic diseases.
Influence Of Nitrogen Flow Rate In Reducing Tin Microdroplets On Biomedical TI-13ZR-13NB Alloy

Cathodic arc physical vapor deposition (CAPVD) is one of the promising techniques that have a potential to coat titanium nitride (TiN) on biomedical implants due to its good adhesion and high evaporation rate. However, this method emits microdroplets which have the possible detrimental effect on the coating performance. Past studies indicated that micro droplets can be controlled through proper deposition parameters. In the present work, an attempt was made to study the effect of nitrogen gas flow rates (100 to 300 sccm) on TiN coating of the Ti-13Zr-13Nb biomedical alloy. Scanning electron microscopy (SEM) was used to evaluate surface morphology and coating thickness while crystal phase of the coated substrates was determined using X-Ray Diffraction (XRD). Image analysis software was employed to quantify microdroplets counts. Results show that higher nitrogen gas flow rate able to decrease a significant amount of microdroplets and concurrently increase the thickness of TiN coating. A mixed crystal planes of (111) and (220) are obtained on the coated substrates at this setting which exhibits denser structure with higher adhesion strength as compared to substrates coated at the lower N2 gas flow rate.
Economic burden of schizophrenia in Italy: a probabilistic cost of illness analysis

Objectives Schizophrenia is a chronic, debilitating psychiatric disease with highly variable treatment pathways and consequent economic impacts on resource utilisation. The aim of the study was to estimate the economic burden of schizophrenia in Italy for both the societal and Italian National Healthcare perspective. Methods A probabilistic cost of illness model was applied. A systematic literature review was carried out to identify epidemiological and economic data. Direct costs were calculated in terms of drugs, hospitalisations, specialist services, residential and semiresidential facilities. Indirect costs were calculated on the basis of patients’ and caregivers’ loss of productivity. In addition, the impact of disability compensation was taken into account using a database from the Italian National Social Security Institute —Italy (INPS). Results Overall, 303 913 prevalent patients with schizophrenia were estimated. Of these, 212 739 (70%) were diagnosed and 175 382 (82%) were treated with antipsychotics. The total economic burden was estimated at €2.7 billion (95% CI €1771.93 to €3988.65), 50.5% due to indirect costs and 49.5% to direct costs. Drugs corresponded to 10% of direct costs and hospitalisations (including residential and semiresidential facilities) accounted for 81%. Conclusions This study highlighted that indirect costs and hospitalisations (including residential and semiresidential facilities) play a major role within the expenses associated with schizophrenia in Italy, and this may be considered as a tool for public decision-makers.
Large-Scale Distributed Graph Computing Systems: An Experimental Evaluation

With the prevalence of graph data in real-world applications (e.g., social networks, mobile phone networks, web graphs, etc.) and their ever-increasing size, many distributed graph computing systems have been developed in recent years to process and analyze massive graphs. Most of these systems adopt Pregel's vertex-centric computing model, while various techniques have been proposed to address the limitations in the Pregel framework. However, there is a lack of comprehensive comparative analysis to evaluate the performance of various systems and their techniques, making it difficult for users to choose the best system for their applications. We conduct extensive experiments to evaluate the performance of existing systems on graphs with different characteristics and on algorithms with different design logic. We also study the effectiveness of various techniques adopted in existing systems, and the scalability of the systems. The results of our study reveal the strengths and limitations of existing systems, and provide valuable insights for users, researchers and system developers.
Continuous-Domain Solutions of Linear Inverse Problems With Tikhonov Versus Generalized TV Regularization

We consider one-dimensional (1-D) linear inverse problems that are formulated in the continuous domain. The object of recovery is a function that is assumed to minimize a convex objective functional. The solutions are constrained by imposing a continuous-domain regularization. We derive the parametric form of the solution (representer theorems) for Tikhonov (quadratic) and generalized total-variation (gTV) regularizations. We show that, in both cases, the solutions are splines that are intimately related to the regularization operator. In the Tikhonov case, the solution is smooth and constrained to live in a fixed subspace that depends on the measurement operator. By contrast, the gTV regularization results in a sparse solution composed of only a few dictionary elements that are upper-bounded by the number of measurements and independent of the measurement operator. Our findings for the gTV regularization resonates with the minimization of the $\ell _1$ norm, which is its discrete counterpart and also produces sparse solutions. Finally, we find the experimental solutions for some measurement models in one dimension. We discuss the special case when the gTV regularization results in multiple solutions and devise an algorithm to find an extreme point of the solution set which is guaranteed to be sparse.
Slit-Dependent Endocytic Trafficking of the Robo Receptor Is Required for Son of Sevenless Recruitment and Midline Axon Repulsion

Understanding how axon guidance receptors are activated by their extracellular ligands to regulate growth cone motility is critical to learning how proper wiring is established during development. Roundabout (Robo) is one such guidance receptor that mediates repulsion from its ligand Slit in both invertebrates and vertebrates. Here we show that endocytic trafficking of the Robo receptor in response to Slit-binding is necessary for its repulsive signaling output. Dose-dependent genetic interactions and in vitro Robo activation assays support a role for Clathrin-dependent endocytosis, and entry into both the early and late endosomes as positive regulators of Slit-Robo signaling. We identify two conserved motifs in Robo’s cytoplasmic domain that are required for its Clathrin-dependent endocytosis and activation in vitro; gain of function and genetic rescue experiments provide strong evidence that these trafficking events are required for Robo repulsive guidance activity in vivo. Our data support a model in which Robo’s ligand-dependent internalization from the cell surface to the late endosome is essential for receptor activation and proper repulsive guidance at the midline by allowing recruitment of the downstream effector Son of Sevenless in a spatially constrained endocytic trafficking compartment.