Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of famciclovir in cats with spontaneous acute upper respiratory tract disease

Objectives The aim of this study was to assess the effects of famciclovir administration in cats with spontaneously acquired acute upper respiratory tract disease. Methods Twenty-four kittens with clinical signs of acute upper respiratory tract disease were randomly allocated to receive doxycycline (5 mg/kg PO q12h) alone (group D; n = 12) or with famciclovir (90 mg/kg PO q12h; group DF; n = 12) for up to 3 weeks. Clinical disease severity was scored at study entry and daily thereafter. Oculo-oropharyngeal swabs collected at study entry and exit were assessed using quantitative PCR for nucleic acids of feline herpesvirus type 1 (FHV-1), feline calicivirus (FCV), Chlamydia felis, Bordetella bronchiseptica and Mycoplasma felis. Results The median (range) age of cats was 1.5 (1–6) months in group D vs 1.6 (1–5) months in group DF (P = 0.54). Pathogens detected in oculo-oropharyngeal swabs at study entry included FCV (n = 13/24; 54%), M felis (n = 8/24; 33%), FHV-1 (n = 7/24; 29%), C felis (n = 7/24; 29%) and B bronchiseptica (n = 3/24; 12%). Median (range) duration of clinical signs was 11.5 (3–21) days in group DF and 11 (3–21) days in group D (P = 0.75). Median (range) total disease score at the end of the study did not differ between groups (group D 1 [1–1] vs group DF 1 [1–3]; P = 0.08). Conclusions and relevance This study revealed no significant difference in response to therapy between cats treated with doxycycline alone or with famciclovir; cats improved rapidly in both groups. However, identification of FHV-1 DNA was relatively uncommon in this study and clinical trials focused on FHV-1-infected cats are warranted to better evaluate famciclovir efficacy.
Sensitivity analysis for the generalized shared-parameter model framework

ABSTRACT In this paper, we assess the effect of tuberculosis pericarditis treatment (prednisolone) on CD4 count changes over time and draw inferences in the presence of missing data. We accounted for the missing data and performed sensitivity analyses to assess robustness of inferences, from a model that assumes that the data are missing at random, to models that assume that the data are not missing at random. Our sensitivity approaches are within the shared-parameter model framework. We implemented the approach by Creemers and colleagues to the CD4 count data and performed simulation studies to evaluate the performance of this approach. We also assessed the influence of potentially influential subjects, on parameter estimates, via the global influence approach. Our results revealed that inferences from missing at random analysis model are robust to not missing at random models and influential subjects did not overturn the study conclusions about prednisolone effect and missing data mechanism. Prednisolone was found to have no significant effect on CD4 count changes over time and also did not interact with anti-retroviral therapy. The simulation studies produced unbiased estimates of prednisolone effect with lower mean square errors and coverage probabilities approximately equal the nominal coverage probability.
Drosophila melanogaster grooming possesses syntax with distinct rules at different temporal scales

Mathematical modeling of behavioral sequences yields insight into the rules and mechanisms underlying sequence generation. Grooming in Drosophila melanogaster is characterized by repeated execution of distinct, stereotyped actions in variable order. Experiments demonstrate that, following stimulation by an irritant, grooming progresses gradually from an early phase dominated by anterior cleaning to a later phase with increased walking and posterior cleaning. We also observe that, at an intermediate temporal scale, there is a strong relationship between the amount of time spent performing body-directed grooming actions and leg-directed actions. We then develop a series of data-driven Markov models that isolate and identify the behavioral features governing transitions between individual grooming bouts. We identify action order as the primary driver of probabilistic, but non-random, syntax structure, as has previously been identified. Subsequent models incorporate grooming bout duration, which also contributes significantly to sequence structure. Our results show that, surprisingly, the syntactic rules underlying probabilistic grooming transitions possess action duration-dependent structure, suggesting that sensory input-independent mechanisms guide grooming behavior at short time scales. Finally, the inclusion of a simple rule that modifies grooming transition probabilities over time yields a generative model that recapitulates the key features of observed grooming sequences at several time scales. These discoveries suggest that sensory input guides action selection by modulating internally generated dynamics. Additionally, the discovery of these principles governing grooming in D. melanogaster demonstrates the utility of incorporating temporal information when characterizing the syntax of behavioral sequences.
Thoracoscopic surgery for lung cancer is associated with improved survival and shortened admission length: a nationwide propensity-matched study.

OBJECTIVES Population-based studies comparing long-term survival after minimally invasive and open surgery for lung cancer are lacking. The aim of this study was to compare long-term survival rates between minimally invasive [video-assisted thoracoscopic surgery (VATS)] and open surgery for lung cancer in an unselected nationwide setting. METHODS Patients undergoing minimally invasive (n = 710) or open (n = 2814) lung resection for lung cancer between 2004 and 2014 were identified from nationwide complete registries in Finland. Propensity score matching resulted in groups of 632 patients who had VATS and 632 who had a thoracotomy. The primary outcome was the 1-year survival rate. Secondary outcomes were 30-day, 90-day and 5-year survival rates and the length of surgical admission. Cox models were adjusted for sex, age, comorbidity, centre size, year of surgery, histological diagnosis, stage and adjuvant therapy. RESULTS In the propensity-matched cohort, the 1-year survival rate was 90.8% [confidence interval (CI) 88.3-92.8%] after VATS and 87.1% (CI 84.3-89.6%) after open surgery. The 5-year survival rate in the propensity-matched cohort was 59.6% (CI 54.9-63.9%) after VATS and 53.3% (CI 48.6-57.7%) after open surgery. The 30-day mortality rates showed no differences between approaches, but the 90-day mortality rate was better after VATS when adjusted for patient-, tumour- and operation-specific features (hazard ratio 0.56, 95% CI 0.30-0.92; P = 0.024). CONCLUSIONS According to this population-based nationwide study from Finland, minimally invasive surgery for lung cancer is associated with improved long- and short-term survival rates, supporting the use of VATS as a primary surgical method for treating lung cancer. Due to the complexity of confounding factors in this study, one should, however, interpret the results critically. Additional studies are needed.
Radiosensitization and a Less Aggressive Phenotype of Human Malignant Glioma Cells Expressing Isocitrate Dehydrogenase 1 (IDH1) Mutant Protein: Dissecting the Mechanisms

The presence of an isocitrate dehydrogenase 1 (IDH1) mutation is associated with a less aggressive phenotype, increased sensitivity to radiation, and increased overall survival in patients with diffuse glioma. Based on in vitro experimentations in malignant glioma cell lines, the consequences on cellular processes of IDH1R132H expression were analyzed. The results revealed that IDH1R132H expression enhanced the radiation induced accumulation of residual γH2AX foci and decreased the amount of glutathione (GSH) independent of the oxygen status. In addition, expression of the mutant IDH1 caused a significant increase of cell stiffness and induced an altered organization of the cytoskeleton, which has been shown to reinforce cell stiffness. Furthermore, IDH1R132H expression decreased the expression of vimentin, an important component of the cytoskeleton and regulator of the cell stiffness. The results emphasize the important role of mutant IDH1 in treatment of patients with diffuse gliomas especially in response to radiation. Hence, detection of the genetic status of IDH1 before therapy massively expands the utility of immunohistochemistry to accurately distinguish patients with a less aggressive and radiosensitive IDH1-mutant diffuse glioma suitable for radiotherapy from those with a more aggressive IDH1-wildtype diffuse glioma who might benefit from an individually intensified therapy comprising radiotherapy and alternative medical treatments.
First‐in‐Human Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of an Oral Formulation of DS‐1040, an Inhibitor of the Activated Form of Thrombin‐Activatable Fibrinolysis Inhibitor, in Healthy Subjects

DS‐1040, a low‐molecular‐weight imidazole derivative, inhibits the enzymatic activity of thrombin‐activatable fibrinolysis inhibitor (TAFIa), enhancing endogenous tissue plasminogen activator–triggered fibrinolysis. This first‐in‐human, randomized, placebo‐controlled, phase 1 study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of an oral formulation of DS‐1040. Healthy adults (aged 20‐45 years; N = 56) were randomized 3:1 to receive DS‐1040 orally administered as single ascending doses (50, 100, 200, or 400 mg) or placebo, or DS‐1040 multiple ascending doses (100 mg once daily, 200 mg once daily, or 150 mg twice daily) or placebo for 14 days. Safety, PK, and PD parameters were assessed. All doses of DS‐1040 were well tolerated; no serious/severe adverse events (AEs) or discontinuations due to AEs occurred. DS‐1040 had no effect on coagulation parameters, and no treatment‐related trends in the bleeding time were observed. DS‐1040 exposure (peak concentration and area under the concentration‐time curve) increased in a dose‐proportional manner across the single‐dose range. With multiple doses, steady state was achieved by day 7 with minimal accumulation (mean accumulation ratio 1.15‐1.25), and the PK was time‐independent. After 72 hours, approximately 10% of the DS‐1040 400‐mg single dose was recovered in urine as intact parent drug. The mean terminal half‐life ranged from 17.2 to 24.9 hours, which was similar to previous intravenous administration data. Dose‐dependent inhibition of total TAFIa activity was observed following single and multiple doses of oral DS‐1040. The safety and PK/PD profiles of oral DS‐1040 in healthy subjects support further clinical development.
Ensuring a competent public health responder workforce: The CDC experience.

INTRODUCTION From 2009 to 2016, the Centers for Disease Control and Prevention (CDC) activated its Incident Management System for a public health emergency 91 percent of the time. The CDC must ensure its workforce is prepared for the evolving nature of emergencies. OBJECTIVES The purpose of this assessment was to identify perceived preparedness and response training needs for the CDC responder workforce. METHODS Between November 2012 and January 2013, focus groups and in-depth interviews were conducted with CDC responders, including senior leaders. The evaluation questions were: (1) How well does the current training system prepare CDC staff to respond to emergency events? (2) What gaps exist in the current training system? and (3) What trainings are essential and should be included in the training system? RESULTS Eight focus groups were conducted with 51 responders and 18 interviews with response leaders. Themes were identified for each main outcome measure and translated to training improvements. CONCLUSIONS The CDC workforce received foundational training. Recommendations are provided to better prepare responders during an emergency. Periodic assessments are necessary to expand training and remain responsive to the complexities of emerging threats.
Single-response appetitive Pavlovian to instrumental transfer is suppressed by aversive counter-conditioning

Environmental stimuli, when paired with reward, can influence behaviour in maladaptive ways, for example, by encouraging overeating or addiction. Such behaviour can be sensitive to reward value manipulations, under circumscribed conditions, but whether reward-seeking is also sensitive to stimulus value manipulations remains unclear. Thus, the current experiment investigated whether reducing the hedonic value of a reward-paired stimulus would reduce reward-seeking behaviour. In total, 36 participants successfully completed a single-response Pavlovian-instrumental transfer (PIT) task with a counter-conditioning procedure. The Pavlovian phase associated three conditioned stimuli (CSs) with money at 100%, 50%, or 0% contingency. Counter-conditioning then followed for the experimental group, who saw the 100% CS paired with unpleasant pictures, while the control group saw only neutral images. Instrumental training required participants to learn a button-pressing response to win money. The transfer phase contrasted instrumental responding during baseline and CS presentation. Both experimental and control groups liked the 100% CS more than the other CSs after Pavlovian training, but counter-conditioning reduced this 100% CS liking. In transfer, the experimental group showed an abolition of appetitive PIT, while the control group showed maintenance of appetitive PIT. However, this group difference was only evident in response vigour, not response initiation. In summary, CS hedonic value influences cue-potentiated instrumental responding. More specifically, hedonic value of a reward-paired cue influences the vigour of instrumental responses, but not the decision to initiate a response. These data may have relevance to smoking cessation policies, where the introduction of health warnings may be viewed as a real-world example of counter conditioning.
Unraveling Sugar Binding Modes to DC-SIGN by Employing Fluorinated Carbohydrates

A fluorine nuclear magnetic resonance (19F-NMR)-based method is employed to assess the binding preferences and interaction details of a library of synthetic fluorinated monosaccharides towards dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN), a lectin of biomedical interest, which is involved in different viral infections, including HIV and Ebola, and is able to recognize a variety of self- and non-self-glycans. The strategy employed allows not only screening of a mixture of compounds, but also obtaining valuable information on the specific sugar–protein interactions. The analysis of the data demonstrates that monosaccharides Fuc, Man, Glc, and Gal are able to bind DC-SIGN, although with decreasing affinity. Moreover, a new binding mode between Man moieties and DC-SIGN, which might have biological implications, is also detected for the first time. The combination of the 19F with standard proton saturation transfer difference (1H-STD-NMR) data, assisted by molecular dynamics (MD) simulations, permits us to successfully define this new binding epitope, where Man coordinates a Ca2+ ion of the lectin carbohydrate recognition domain (CRD) through the axial OH-2 and equatorial OH-3 groups, thus mimicking the Fuc/DC-SIGN binding architecture.
Cloud Computing of E-Government

Over the past years, many businesses, government and individuals have been started to adopt the internet and web-based technologies in their works to take benefits of costs reduction and better utilization of existing resources. The cloud computing is a new way of computing which aims to provide better communication style and storage resources in a safe environment via the internet platform. The E-governments around the world are facing the continued budget challenges and increasing in the size of their computational data so that they need to find ways to deliver their services to citizens as economically as possible without compromising the achievement of desired outcomes. Considering E-government is one of the sectors that is trying to provide services via the internet so the cloud computing can be a suitable model for implementing E-government architecture to improve E-government efficiency and user satisfaction. In this paper, the adoption of cloud computing strategy in implementing E-government services has been studied by focusing on the relationship between E-government and cloud computing by listing the benefits of creation E-government based on cloud computing. Finally in this paper, the challenges faced the implementation of cloud computing for E-government are discussed in details. As a result from understanding the importance of cloud computing as new, green and cheap technology is contributed to fixing and minimizing the existing problems and challenges in E-government so that the developed and developing countries need to achieve E-government based on cloud computing.
Comparison of physical and social risk-reducing factors for the development of disability in older adults: a population-based cohort study

Background Considerations of modifiable risk factors for the development of disability in older age have traditionally focused on physical activity. However, there is increasing evidence that psychological, social, and cognitive factors also help to maintain functional independence. This study compared the protective associations between physical and social activities and disability onset. Methods We analysed data from 5434 adults aged 50+ years tracked biennially from 2004/2005 to 2016/2017, measuring self-reported difficulty in carrying out any basic activities of daily living (ADLs) or instrumental ADLs. Exposures included mild, moderate and vigorous physical activity, frequency of socialising with friends/family, cultural engagement (eg, going to the theatre/museums/concerts), and participation in community groups. Results Over the 12-year follow-up, 1945 adults developed disability. Using Cox proportional hazards regression models adjusted for all identified demographic and health-related variables, vigorous exercise or activity once a month or more (HR 0.82, 95% CI 0.71 to 0.96), moderate exercise or activity more than once a week (HR 0.81, 95% CI 0.67 to 0.97) or cultural engagement once or twice a year or more (HR 0.84, 95% CI 0.73 to 0.97) were associated with a lower hazard of developing disability. Other exposures did not show independent protective associations. Results were robust to sensitivity analyses considering reverse causality and exploring the potential confounding role of time-invariant factors, such as socioeconomic status. Conclusion These results suggest the importance of either developing multimodal interventions to protect against disability and promote healthy ageing or promoting greater physical and social engagement with existing community activities among older adults.
Editorial: How youth mental healthcare is being transformed in diverse settings across Canada: Reflections on the experience of the ACCESS Open Minds network

Having been part of the ACCESS Open Minds (ACCESS OM) project since before its inception, we take pleasure in reflecting on the conception and implementation of the project in its diverse contextual realities. In 2013, partnering with the Graham Boeckh Foundation, the Canadian Institutes of Health Research, launched a call for grant applications under their new Strategy for Patient-Oriented Research. The 18-month application process brought together various stakeholders from across Canada—youth, families, community organisations, clinicians, researchers, and decision-/policy-makers—around the common recognition that extant systems were not meeting the mental health needs of youth. The resultant ACCESS OM network faced a task that represented both an immense opportunity and a substantial challenge. We were to create a model for youth mental health services transformation that had to be evidence-informed yet anchored in all pertinent stakeholders' perspectives. Our model's core strategies had to have inbuilt flexibility to leverage the strengths and accommodate the realities of diverse sites. Some of the flexibility was necessitated by the nature of Canada's public healthcare system, which is federally mandated but provincially administered (with varying combinations of federal, provincial, and local governance in Indigenous jurisdictions). This has proven to be a strength that makes our model likelier to enjoy local buy-in and ownership and broad applicability in and beyond Canada. ACCESS OM is being implemented in 14 diverse settings across Canada (Malla et al., 2018). The articles in this supplement describe how the project's core service objectives are being addressed at seven sites that represent distinct contexts. The transformation of youth mental healthcare on such a large scale has been coordinated by a central office in Montreal through common structures and processes that standardise, support, and accelerate implementation.
Prognostic Impact of Extended Lymph Node Dissection versus Limited Lymph Node Dissection on pN0 Proximal Advanced Gastric Cancer: a Propensity Score Matching Analysis

Purpose Splenic hilar lymph node dissection (LND) during total gastrectomy is regarded as the standard treatment for proximal advanced gastric cancer (AGC). This study aimed to investigate whether splenic hilar LND or D2 LND is essential for proximal AGC of pT2-4aN0M0 stage. Materials and Methods Data of curative total gastrectomies (n=370) performed from 2000 to 2010 for proximal AGC of pT2-4aN0 stage were retrospectively reviewed. Clinicopathological characteristics and long-term outcomes were compared using propensity score matching between patients who underwent splenectomy (n=43) and those who did not (n=327) and between patients who underwent D2 LND (n=122) and those who underwent D1+ LND (n=248). Results Tumors of larger size and a more advanced T stage and significantly lower overall and relapse-free survival (P<0.001) were observed in the splenectomy group than in the 2 spleen-preserving groups. Before propensity score matching, worse overall and relapse-free survival (P<0.001) was observed in the splenectomy group than in the non-splenectomy group. After matching, although the overall survival became similar (P=0.123), relapse-free survival was worse in the splenectomy group (P=0.021). Compared with D1+ LND, D2 LND had no positive impact on the overall (P=0.619) and relapse-free survival (P=0.112) after propensity score matching. Conclusions Splenic hilar LND with or without splenectomy may not have an oncological benefit for patients with pathological AGC with no LN metastasis.
Lift-Off Assisted Patterning of Few Layers Graphene

Graphene and 2D materials have been exploited in a growing number of applications and the quality of the deposited layer has been found to be a critical issue for the functionality of the developed devices. Particularly, Chemical Vapor Deposition (CVD) of high quality graphene should be preserved without defects also in the subsequent processes of transferring and patterning. In this work, a lift-off assisted patterning process of Few Layer Graphene (FLG) has been developed to obtain a significant simplification of the whole transferring method and a conformal growth on micrometre size features. The process is based on the lift-off of the catalyst seed layer prior to the FLG deposition. Starting from a SiO2 finished Silicon substrate, a photolithographic step has been carried out to define the micro patterns, then an evaporation of Pt thin film on Al2O3 adhesion layer has been performed. Subsequently, the Pt/Al2O3 lift-off step has been attained using a dimethyl sulfoxide (DMSO) bath. The FLG was grown directly on the patterned Pt seed layer by Chemical Vapor Deposition (CVD). Raman spectroscopy was applied on the patterned area in order to investigate the quality of the obtained graphene. Following the novel lift-off assisted patterning technique a minimization of the de-wetting phenomenon for temperatures up to 1000 °C was achieved and micropatterns, down to 10 µm, were easily covered with a high quality FLG.