Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibody pharmacokinetics in rat brain determined using microdialysis

ABSTRACT Here, we present the first case-study where microdialysis is used to investigate the pharmacokinetics of antibody in different regions of rat brain. Endogenous IgG was used to understand antibody disposition at steady-state and exogenously administered trastuzumab was used to understand the disposition in a dynamic setting. Microdialysis samples from the striatum (ST), lateral ventricle (LV), and cisterna magna (CM) were collected, along with plasma and brain homogenate, to comprehensively understand brain pharmacokinetics of antibodies. Antibody concentrations in cerebrospinal fluid (CSF) were found to vary based on the site-of-collection, where CM concentrations were several-fold higher than LV. In addition, antibody concentrations in CSF (CM/LV) were found to not accurately represent the concentrations of antibody inside brain parenchyma (e.g., ST). Elimination of CSF from CM was found to be slower than LV, and the entry and exit of antibody from ST was also slower. Pharmacokinetics of exogenously administered antibody revealed that the entry of antibody into LV via the blood-CSF barrier may represent an early pathway for antibody entry into the brain. Plasma concentrations of antibody were 247–667, 104–184, 165–435, and 377–909 fold higher than the antibody concentrations in LV, CM, ST, and brain homogenate. It was found that the measurement of antibody pharmacokinetics in different regions of the brain using microdialysis provides an unprecedented insight into brain disposition of antibody. This insight can help in designing better molecules, dosing regimens, and route of administration, which can in turn improve the efficacy of antibodies for central nervous system disorders.
CD4 T cells in protection from influenza virus: Viral antigen specificity and functional potential

CD4 T cells convey a number of discrete functions to protective immunity to influenza, a complexity that distinguishes this arm of adaptive immunity from B cells and CD8 T cells. Although the most well recognized function of CD4 T cells is provision of help for antibody production, CD4 T cells are important in many aspects of protective immunity. Our studies have revealed that viral antigen specificity is a key determinant of CD4 T cell function, as illustrated both by mouse models of infection and human vaccine responses, a factor whose importance is due at least in part to events in viral antigen handling. We discuss research that has provided insight into the diverse viral epitope specificity of CD4 T cells elicited after infection, how this primary response is modified as CD4 T cells home to the lung, establish memory, and after challenge with a secondary and distinct influenza virus strain. Our studies in human subjects point out the challenges facing vaccine efforts to facilitate responses to novel and avian strains of influenza, as well as strategies that enhance the ability of CD4 T cells to promote protective antibody responses to both seasonal and potentially pandemic strains of influenza.
Vitamin D and Inflammatory Bowel Disease: Mendelian Randomization Analyses in the Copenhagen Studies and UK Biobank

Context Vitamin D may be a modifiable risk factor for inflammatory bowel disease (IBD). Objectives We tested the hypothesis that plasma 25-hydroxyvitamin D levels are causally associated with risk of Crohn disease (CD) and ulcerative colitis (UC). Design, Setting, Patients, and Interventions We used a Mendelian randomization design to study 120,013 individuals from the Copenhagen City Heart Study, the Copenhagen General Population Study, and a Copenhagen-based cohort of patients with IBD. Of these, 35,558 individuals had plasma 25-hydroxyvitamin D measurements available, and 115,110 were genotyped for rs7944926 and rs11234027 in DHCR7 and rs10741657 and rs12794714 in CYP2R1, all variants associated with plasma 25-hydroxyvitamin D levels. We identified 653 cases of CD and 1265 cases of UC, of which 58 and 113, respectively, had 25-hydroxyvitamin D measurements available. We also included genetic data from 408,455 individuals from the UK Biobank, including 1707 CD cases and 3147 UC cases. Main Outcome Measure Hazard ratios for higher plasma 25-hydroxyvitamin D levels. Results The multivariable-adjusted hazard ratios for 10 nmol/L higher 25-hydroxyvitamin D level were 1.04 (95% CI: 0.93 to 1.16) for CD and 1.13 (95% CI: 1.06 to 1.21) for UC. A combined 25-hydroxyvitamin D allele score was associated with a 1.4-nmol/L increase in plasma 25-hydroxyvitamin D level and hazard ratios of 0.98 (95% CI: 0.94 to 1.03) for CD and 1.01 (95% CI: 0.97 to 1.05) for UC. Combining genetic data from the Copenhagen studies and the UK Biobank, genetically determined vitamin D did not appear to influence the risk of CD or UC. Conclusions Our results do not support a major role for vitamin D deficiency in the development of IBD.
Association between Altered Expression and Genetic Variations of Transforming Growth Factor β-Smad Pathway with Chronic Myeloid Leukemia

Background: Chronic myeloid leukemia (CML) is a hematological disorder caused by fusion of BCR and ABL genes. BCR-ABL dependent and independent pathways play equally important role in CML. TGFβ-Smad pathway, an important BCR -ABL independent pathway, has scarce data in CML. Present study investigate the association between TGFβ-Smad pathway and CML. Materials and Methods: Sixty-four CML patients and age matched healthy controls (n=63) were enrolled in this study. Patients were segregated into responder and resistant groups depending on their response to Imatinib mesylate (IM). TGFβ1 serum levels were evaluated by ELISA and transcript levels of TGFβ1 receptors, SMAD4 and SMAD7 were evaluated by Real-Time PCR. Sequencing of exons and exon-intron boundaries of study genes was performed using Next Generation Sequencing (NGS) in 20 CML patients. Statistical analysis was performed using SPSS version 16.0. Results: TGFβ1 serum levels were significantly elevated (p = 0.02) and TGFβR2 and SMAD4 were significantly down-regulated (p = 0.012 and p = 0.043 respectively) in the patients. c.69A>G in TGFβ1, c.1024+24G>A in TGFβR1 and g.46474746C>T in SMAD7 were the most important genetic variants observed with their presence in 10/20, 8/20 and 7/20 patients respectively. In addition, TGFβR1 transcript levels were reduced in CML patients with c.69A>G mutation. None of the genes differed significantly in terms of expression or genetic variants between responder and resistant patient groups. Conclusion: Our findings demonstrate the role of differential expression and genetic variants of TGFβ-Smad pathway in CML. Decreased TGFβR2 and SMAD4 levels observed in the present study may be responsible for reduced tumor suppressive effects of this pathway in CML.
Üniversite Öğrencilerinin Genel Erteleme, Karar Vermeyi Erteleme ve Akademik Erteleme Düzeylerinin Sürekli Kaygı Açısından İncelenmesi

Bu arastirmanin amaci, universite ogrencilerinin genel erteleme, karar vermeyi erteleme, akademik erteleme duzeylerinin surekli kaygi acisindan incelenmesi ve universite ogrencilerinin surekli kaygilarinin, genel erteleme, karar vermeyi erteleme, akademik ertelemelerin, cinsiyet, yas, ogrenim gordugu bolum, mezun oldugu lise turu, anne ve babanin egitim durumu, anne ve babanin meslegine gore anlamli duzeyde farklilasip farklilasmadigini saptamaktir. Arastirmanin calisma grubu 95’i erkek ve 193 kadin olmak uzere toplam 288 universite ogrencisinden olusmaktadir. Arastirma verileri surekli kaygi envanteri, genel erteleme, karar vermeyi erteleme, akademik erteleme olcegi ve kisisel bilgi formu kullanilarak toplanmistir. Arastirma sonucunda surekli kayginin genel erteleme, karar vermeyi erteleme ve akademik ertelemeyi anlamli duzeyde yordadigi gorulmektedir (p< 0,01). Ogrencilerin karar vermeyi erteleme duzeyleri, yas degiskeni acisindan anlamli duzeyde farklilasmaktadir. Genel erteleme ve akademik erteleme duzeylerinin sinif degiskeni acisindan anlamli duzeyde farklilastigi gorulmustur. Genel erteleme ve akademik erteleme duzeylerinin ogrencilerin ogrenim gormus olduklari bolum turune gore anlamli duzeyde farklilastigi saptanmistir. Karar vermeyi erteleme ve surekli kaygi puanlari ile aile geliri arasinda anlamli bir farklilik bulunmustur. Akademik, erteleme, genel erteleme, karar vermeyi erteleme ve surekli kaygi puan ortalamalarinin anne ve baba meslegi arasinda anlamli farklilasma bulunmamistir.
Syn2Real: A New Benchmark forSynthetic-to-Real Visual Domain Adaptation

Unsupervised transfer of object recognition models from synthetic to real data is an important problem with many potential applications. The challenge is how to "adapt" a model trained on simulated images so that it performs well on real-world data without any additional supervision. Unfortunately, current benchmarks for this problem are limited in size and task diversity. In this paper, we present a new large-scale benchmark called Syn2Real, which consists of a synthetic domain rendered from 3D object models and two real-image domains containing the same object categories. We define three related tasks on this benchmark: closed-set object classification, open-set object classification, and object detection. Our evaluation of multiple state-of-the-art methods reveals a large gap in adaptation performance between the easier closed-set classification task and the more difficult open-set and detection tasks. We conclude that developing adaptation methods that work well across all three tasks presents a significant future challenge for syn2real domain transfer.
Outcomes and Complications of Balloon and Conventional Functional Endoscopic Sinus Surgery

Background Since the Food and Drug Administration approval of balloon sinuplasty (BSP) in 2005, no nationally representative population-based studies have examined the outcomes and adverse events of BSP. Objective To assess the rates of complications and revision surgery in patients who received BSP, functional endoscopic sinus surgery (FESS), or a hybrid procedure. Methods Using one of the nation’s largest commercial insurance databases, we conducted a retrospective cohort study of pediatric and adult patients diagnosed with chronic rhinosinusitis between 2011 and 2014 who underwent BSP, conventional FESS, or a hybrid procedure. The primary outcomes were surgical complication and revision rates within 6 months of initial surgery. Results A total of 16,040 patients who underwent sinus surgery were included. Overall, 2,851 patients underwent BSP, 11,955 underwent conventional FESS, and 1 234 underwent a hybrid procedure. BSP surgery was more likely to have been performed in an office setting (86.53%) compared to FESS (0.74%). The complication rate was 5.26% for BSP and 7.35% for conventional FESS. Revision rates were 7.89% for BSP, 16.85% for FESS, and 15.15% for a hybrid procedure. Conclusion Despite the low overall risk, major complications occur with BSP including cerebrospinal fluid leak, pneumocephalus, orbital complications, and severe bleeding. Otolaryngologists should discuss these risks with their patients. Prospective studies are still needed to compare outcomes of BSP with those of FESS.
A scale-development study: Exploration of intensive-care nurses’ attitudes towards futile treatments

Abstract The study was conducted to determine the validity and reliability of the tool used to assess nurses’ attitudes towards futility, and to explore intensive-care nurses’ attitudes towards futility. Principal components analysis revealed that 18item scale was made up of four subdimensions that assess Identifying(beliefs), Decision-Making, Ethical Principles and Law, and Dilemma and Responsibilities related to futile treatments. The internal consistency of the scale was in the acceptable range, with a total Cronbach’s alpha value of 0.72. Overall the results of study suggest that scale can be used as a valid and reliable assessment tool to assess nurses’ attitudes towards futility.
Theoretical pneumococcal vaccine coverage: analysis of serotypes isolated from inpatients at a tertiary care hospital

ABSTRACT Objective: To evaluate Streptococcus pneumoniae serotypes isolated from an inpatient population at a tertiary care hospital, in order to determine the theoretical coverage of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23). Methods: This was a cross-sectional study involving 118 inpatients at the Hospital São Lucas, in the city of Porto Alegre, Brazil, whose cultures of blood, cerebrospinal fluid, or other sterile body fluid specimens, collected between January 2005 and December 2016, yielded pneumococcal isolates. The theoretical vaccine coverage was studied in relation to the serotypes identified in the sample and their relationship with those contained in the pneumococcal vaccines available in Brazil. Results: The majority of the population was male (n = 66; 55.9%), with a median age of 57 years (interquartile range: 33-72 years). The most common manifestation was pneumonia, and the pneumococcus was most commonly isolated from blood cultures. More than one fourth of the study population had some degree of immunosuppression (n = 34; 28.8%). Of the total sample, 39 patients (33.1%) died. There were no significant associations between mortality and comorbidity type, ICU admission, or need for mechanical ventilation. The theoretical vaccine coverage of PPV23 alone and PCV13 plus PPV23 was 31.4% and 50.8%, respectively. Conclusions: If the patients in this sample had been previously vaccinated with PCV13 plus PPV23, theoretically, 50.8% of the cases of invasive pneumococcal disease that required hospital admission could potentially have been prevented. Invasive pneumococcal disease should be prevented by vaccination not only of children and the elderly but also of adults in their economically productive years, so as to reduce the socioeconomic costs, morbidity, and mortality still associated with the disease, especially in underdeveloped countries.
Campylobacter control measures in indoor broiler chicken: critical re-assessment of cost-utility and putative barriers to implementation

Abstract As campylobacteriosis is one of the most important foodborne infections, a European Union (EU)-27 level cost-effectiveness model has been developed on the socio-economic costs and benefits of applying certain control measures for the reduction of Campylobacter in broiler meat. This is expected to be a gold standard for food safety policymakers in the EU; hence, the validity of its modelling assumptions is essential. The authors of the present paper conducted an independent review of model input parameters on health and economic burden and found that the model most probably overestimated the burden of human campylobacteriosis. A discounted, quality-adjusted life year (QALY)-based European estimate has been developed for human campylobacteriosis and resulted in 15.23 QALY loss per 1000 human gastroenteritis cases. Country-specific cost of illness estimates have been developed for various countries in the EU-27. Based on these model adaptations, a selected Campylobacter control strategy was re-assessed and its high cost-effectiveness was confirmed at the EU level, and also in all but three Member States. Bacteriocin treatment or vaccination of the animals, two alternative control measures were also re-evaluated, and these strategies seemed to be far less cost-effective than the investigated strategy. Putative barriers to the rapid implementation of the investigated Campylobacter control strategy are discussed, and potential solutions are proposed. Further research is required on stakeholder perspectives pertaining to the realistic barriers and implementation opportunities.
Optimal Beamforming and Time Allocation for Partially Wireless Powered Sensor Networks With Downlink SWIPT

Wireless powered sensor networks (WPSNs) have emerged as a key development toward the future self-sustainable Internet of Things networks. To achieve a good balance between self-sustainability and reliability, partially WPSNs with a mixed power solution are desirable for practical applications. Specifically, most of the sensor nodes are wireless powered but the key sensor node adopts traditional wire/battery power for reliability. As a result, this paper mainly investigates optimal resource allocation for the partially WPSNs in which simultaneous wireless information and power transfer (SWIPT) is adopted in the downlink. Two scenarios with space division multiple access (SDMA) and time division multiple access (TDMA) in the uplink are considered. For both SDMA-enabled and TDMA-enabled partially WPSNs, joint design of downlink beamforming, uplink beamforming, and time allocation is investigated to maximize the uplink sum rate while guaranteeing the quality-of-service (i.e., satisfying the downlink rate constraint) at the key sensor node. After analyzing the feasibility of uplink sum rate maximization problems and the influence of the downlink rate constraint, semiclosed-form optimal solutions for both SDMA-enabled and TDMA-enabled WPSNs are proposed with guaranteed global optimality and low complexity. Extension to partially WPSNs with multiple traditionally wire/battery powered sensor nodes is also discussed for generality. The effectiveness and optimality of the proposed optimal solutions are finally demonstrated by simulations.
Serotonergic antidepressant use and morbidity and mortality among older adults with COPD

We evaluated the relationship between new selective serotonin reuptake inhibitor (SSRI) or serotonin–noradrenaline reuptake inhibitor (SNRI) drug use and respiratory-related morbidity and mortality among older adults with chronic obstructive pulmonary disease (COPD). This was a retrospective population-based cohort study using heath administrative data from Ontario, Canada. Individuals aged ≥66 years, with validated, physician-diagnosed COPD (n=131 718) were included. New SSRI/SNRI users were propensity score matched 1:1 to controls on 40 relevant covariates to minimise potential confounding. Among propensity score matched community-dwelling individuals, new SSRI/SNRI users compared to non-users had significantly higher rates of hospitalisation for COPD or pneumonia (hazard ratio (HR) 1.15, 95% CI 1.05–1.25), emergency room visits for COPD or pneumonia (HR 1.13, 95% CI 1.03–1.24), COPD or pneumonia-related mortality (HR 1.26, 95% CI 1.03–1.55) and all-cause mortality (HR 1.20, 95% CI 1.11–1.29). In addition, respiratory-specific and all-cause mortality rates were higher among long-term care home residents newly starting SSRI/SNRI drugs versus controls. New use of serotonergic antidepressants was associated with small, but significant, increases in rates of respiratory-related morbidity and mortality among older adults with COPD. Further research is needed to clarify if the observed associations are causal or instead reflect unresolved confounding. Serotonergic antidepressants are associated with increased adverse respiratory outcomes in older adults with COPD http://ow.ly/E5ex30khSLq
Evaluation of clinical decision support systems for diabetes care: An overview of current evidence

BACKGROUND Systematic reviews (SRs) have shown that clinical decision support systems (CDSSs) have the potential to improve diabetes care. However, methods of measuring and presenting outcomes are varied, and conclusions have been inconsistent. In addition, the reporting and methodological quality in this field is unknown, which could affect the integrity and accuracy of research. Therefore, it is difficult to confirm whether CDSSs are effective in improving diabetes care. OBJECTIVE To comprehensively evaluate the effects of CDSS on diabetes care and to examine the methodological and reporting qualities. METHODS We searched PubMed, EMBASE, and Cochrane Library from their inception to February 2017. Systematic reviews investigating the effects of CDSS on diabetes care were included. Outcomes were determined in advance and assessed separately for process of care and patient outcomes. Methodological and reporting qualities were assessed by AMSTAR and PRISMA, respectively. RESULTS Seventeen SRs, consisting of 222 unique randomized controlled trials and 102 nonrandomized controlled trials, were included. Evidence that CDDS significantly impacted patient outcomes was found in 32 of 102 unique studies of the 15 SRs that examined this effect (31%). A significant impact of CDSS on process of care was found in 117 out of 143 unique studies of the 11 SRs that examined this effect (82%). Ratings for overall scores of AMSTAR resulted in a mean score of 6.5 with a range of scores from 3.5 to 10.0. Reporting quality related to methodological domains was particularly incomplete. CONCLUSIONS Clinical decision support systems improved the quality of diabetes care by inconsistently improving process of care or patient outcomes. There is evidence that CDSS for providing alerts, reminders, or feedback to participants were most likely to impact diabetes care. Poor reporting of methodological domains, together with qualitative or narrative methods to combine findings, may limit the confidence in research evidence.
Pre-Treatment with Curcumin Ameliorates Cisplatin-Induced Kidney Damage by Suppressing Kidney Inflammation and Apoptosis in Rats

Abstract Objective In addition to oxidative stress, inflammation and apoptosis have an important role in the pathogenesis of cisplatin-induced kidney damage. This study aimed to investigate the molecular mechanisms of protective effects of curcumin against cisplatin-induced kidney inflammation and apoptosis in rats. Materials and Methods Eighteen rats were equally divided into three groups; normal (0.5% CMC-Na), cisplatin (CDPP) (7 mg/kg i.p.), and cisplatin+curcumin (CMN100) groups. Curcumin was given at a dose of 100 mg/kg orally for nine days, starts one week before giving a single dose of cisplatin. Kidney and plasma were taken for analysis. Results Cisplatin challenged rats demonstrated kidney injury as shown by reduced creatinine clearance, increased of plasma BUN, plasma creatinine, and kidney MDA, decreased of kidney GSH levels, and kidney histopathology alterations. Also, cisplatin increased ERK1/2 phosphorylation and NF-κB expression, which subsequently increased mRNA expression of TNF-α, IL-6, KIM-1, NGAL, and Bax/Bcl-2 ratio as well as decreased mRNA expression of IL-10 in kidney tissues. Pre-treatment with curcumin significantly ameliorated inflammation and apoptosis induced by cisplatin. In addition, curcumin downregulated Ctr1 and OCT2 drug transporters as compared to cisplatin group. Histopathological examination furthers confirmed the kidney damage protection effect of curcumin. Conclusions These data indicate that curcumin has nephroprotective properties against cisplatin-induced kidney damage in rats and this effect is associated with its anti-inflammatory and anti-apoptosis profiles, in addition to its antioxidant. Hence, curcumin may be useful for preventing kidney damage against cisplatin administration.