Miracle-dz/UniFAR-FTUs huggingface dataset:
Computed tomography derived fractional flow reserve testing in stable patients with typical angina pectoris: influence on downstream rate of invasive coronary angiography

Abstract Aims To assess the use of downstream coronary angiography (ICA) and short-term safety of frontline coronary CT angiography (CTA) with selective CT-derived fractional flow reserve (FFRCT) testing in stable patients with typical angina pectoris. Methods and results Between 1 January 2016 and 30 June 2016 all patients (N = 774) referred to non-emergent ICA or coronary CTA at Aarhus University Hospital on a suspicion of CAD had frontline CTA performed. Downstream testing and treatment within 3 months and adverse events ≥90 days were registered. Patients were divided into two groups according to the presence of typical angina pectoris, which according to local practice would have resulted in referral to ICA, (low-intermediate-risk, n = 593 [76%]; high-risk, n = 181 [24%]) with mean pre-test probability of CAD of 31 ± 16% and 67 ± 16%, respectively. Coronary CTA was performed in 745 (96%) patients in whom FFRCT was prescribed in 212 (28%) patients. In the high- vs. low-intermediate-risk group, ICA was cancelled in 75% vs. 91%. Coronary revascularization was performed more frequently in high-risk than in low-intermediate-risk patients, 76% vs. 52% (P = 0.03). Mean follow-up time was 157 ± 50 days. Serious clinical events occurred in four patients, but not in any patients with cancelled ICA by coronary CTA with selective FFRCT testing. Conclusion Frontline coronary CTA with selective FFRCT testing in stable patients with typical angina pectoris in real-world practice is associated with a high rate of safe cancellation of planned ICAs.
Job crafting among health care professionals: The role of work engagement

AIM The aim of this study was to examine the impact of job crafting on the quality of the work environment of health care professionals. BACKGROUND Job crafting refers to proactive behavior aimed at optimizing the fit between person and job. Using job demands-resources theory, we hypothesized that job crafting would be positively related to job resources and person-organisation fit, and negatively to hindrance demands. Furthermore, we hypothesized that these relationships would be qualified by work engagement. METHODS A total of 5,272 health care professionals from one of 35 different organisations filled out an electronic questionnaire (response is 55%). Regression analyses were used to test hypotheses. RESULTS Consistent with hypotheses, job crafting in the form of increasing job resources was positively related to opportunities for development, performance feedback and P-O fit; and negatively related to hindrance job demands - particularly when work engagement was high. CONCLUSIONS The combination of job crafting and work engagement is important for the realization of a resourceful work environment and fit between person and organisation. IMPLICATIONS FOR NURSING MANAGEMENT Interventions aimed at fostering job crafting should be tailored to the motivation of health care professionals.
A qualitative study of cognitive behavioural therapy in multiple sclerosis: experiences of psychotherapists

ABSTRACT Purpose: To investigate how psychotherapists experience using individual, face-to-face cognitive behavioural therapy (CBT) aimed at alleviating depressive symptoms in persons with multiple sclerosis (MS). Method: Semi-structured interviews with three psychotherapists were conducted after CBT with 12 participants with MS, and analysed using qualitative content analysis. Results: Two main themes emerged: Trusting their expertise as psychotherapists whilst lacking MS-specific knowledge, and The process of exploring the participants’ readiness for CBT with modifications of content and delivery. The psychotherapists perceived it difficult to know whether a symptom was attributable to depression or to MS, and for some participants the CBT needed to be adapted to a more concrete content. Conclusions: Psychotherapists may need more MS-specific knowledge and an insight into the individual’s functioning. The content of CBT in terms of concrete home assignments and behavioural activation needs to be individualised.
The response of soybean to nod factors and a bacteriocin

ABSTRACT Microbe-to-plant signals can enhance the growth of a wide range of crops. The responses by soybean (Glycine max var. 91M01) to 2 signal molecules were investigated: Bradyrhizobium japonicum 532C lipo-chitooligosaccharide (Nod Bj V [C:18, MeFuc]) (LCO); and Bacillus thuringiensis strain NEB17 bacteriocin thuricin 17 (Th17). The objective was to assess and quantify the response by soybean, in terms of factors that contribute to yield, to the experimental signal molecules in germination experiments and field experiments. Soybean germination was stimulated by the experimental concentrations of Th17 under controlled 15°C and 22°C conditions, and 10−6 M LCO under 15°C. There were negative relationships between Th17 concentration and both the number of trifoliate leaves and the dry weight of nodules: lower concentrations resulted in plants with more leaves and nodules while higher concentrations resulted in plants with fewer leaves and nodules. The 10−8 M LCO treatment had a significant effect on the dry weight of nodules at the flowering stage of plant development (F4,21 = 6.06, p = 0.0019). Considering the harvest stage data from both field trials of 2011, the lower experimental concentrations of Th17 resulted in taller plants. The study of Th17 has the potential to expand our understanding of this relatively recent and unexpected finding; and to understand how best to apply this finding, to allow increased production of soybean. Collectively, these results indicate that Th17 has potential in this regard.
Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy

The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy.
Profiling of glycan alterations in regrowing limb tissues of Cynops orientalis

Glycans are known to play important roles in molecular recognition, cell–cell adhesion, molecular trafficking, receptor activation, and signal transduction during development and regeneration. Despite numerous investigations of regenerating salamander limbs, global analysis of the precise variation of glycans during the limb regeneration process has received little attention. Here, we have used lectin microarrays and lectin histochemistry to analyze the alterations and distribution of glycans during the early stages leading to blastema formation during Cynops orientalis limb regeneration in response to limb amputation. Compared with the control group, analysis at several time points (3, 7, and 14 days postamputation) using microarrays containing 37 lectins showed that limb tissues expressed significantly different complements of glycans recognized by 9 different lectins. Postamputation limb tissues showed higher expression of two glycan structures recognized by the lectins STL and LTL and lower expression of seven glycan structures recognized by PHA‐E, MAL‐I, SNA, UEA‐I, PHA‐E + L, VVA, and GNA. We also observed significant changes in glycans specifically at 7 days postamputation, including higher binding capacity by WFA, GSL‐I, and NPA and lower binding capacity by PNA, HHL, ConA, LCA, GSL‐II, and PWM. Next, we validated our lectin microarray data using lectin histochemistry in limb tissues. Glycans recognized by STL and GNA showed similar changes in signal intensity to those found in the lectin microarrays, with STL staining in the cytoplasm and GNA in the cytoplasm and nucleus. Our findings are the first report of significant postamputation changes in glycans in limb tissues and suggest that those glycans perform potentially important functions during the early stages of C. orientalis limb regeneration.
Readiness of Lung Cancer Screening Sites to Deliver Smoking Cessation Treatment: Current Practices, Organizational Priority, and Perceived Barriers.

INTRODUCTION Lung cancer screening represents an opportunity to deliver smoking cessation advice and assistance to current smokers. However, the current tobacco treatment practices of lung cancer screening sites are unknown. The purpose of this study was to describe organizational priority, current practice patterns, and barriers for delivery of evidence-based tobacco use treatment across lung cancer screening sites within the United States. METHODS Guided by prior work examining readiness of health care providers to deliver tobacco use treatment, we administered a brief online survey to a purposive national sample of site coordinators from 93 lung cancer screening sites. RESULTS Organizational priority for promoting smoking cessation among lung cancer screening enrollees was high. Most sites reported that, at the initial visit, patients are routinely asked about their current smoking status (98.9%) and current smokers are advised to quit (91.4%). Fewer (57%) sites provide cessation counseling or refer smokers to a quitline (60.2%) and even fewer (36.6%) routinely recommend cessation medications. During follow-up screening visits, respondents reported less attention to smoking cessation advice and treatment. Lack of patient motivation and resistance to cessation advice and treatment, lack of staff training, and lack of reimbursement were the most frequently cited barriers for delivering smoking cessation treatment. CONCLUSIONS Although encouraging that lung cancer screening sites endorsed the importance of smoking cessation interventions, greater attention to identifying and addressing barriers for tobacco treatment delivery is needed in order to maximize the potential benefit of integrating smoking cessation into lung cancer screening protocols. IMPLICATIONS This study is the first to describe practice patterns, organizational priority, and barriers for delivery of smoking cessation treatment in a national sample of lung cancer screening sites.
EGFR–TKI-Associated Interstitial Pneumonitis in Nivolumab-Treated Patients With Non–Small Cell Lung Cancer

Importance Nivolumab and epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are now the standard-of-care therapies in non–small cell lung cancer (NSCLC). Although EGFR-TKIs are well understood and have well-defined safety profiles, our experience with immune checkpoint inhibitors is still growing, particularly regarding the use of combinations of different classes of antitumor agents, including both the concomitant and sequential use of such agents. Objective To determine whether nivolumab increases EGFR–TKI-associated interstitial pneumonitis (IP). Design, Setting, and Participants A database study of 20 516 participants with NSCLC in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, performed between April 2015 and March 2017. Main Outcomes and Measures We compared the incidence of EGFR–TKI-associated IP in patients receiving and not receiving nivolumab treatment. Results The mean (SD) age of participants treated with EGFR-TKI, with and without nivolumab, was 64.4 (15.5) and 68.9 (11.8) years, respectively, and the proportion of men was 40.0% and 53.8%, respectively. Of the 20 516 participants with NSCLC, 985 cases (4.80%; 95% CI, 4.51-5.10) developed IP. Of 5777 patients treated with EGFR-TKI, 265 developed IP (4.59%; 95% CI, 4.06-5.16). Of 70 patients treated with both EGFR-TKI and nivolumab, 18 developed IP (25.7%; 95% CI, 16.0-37.6). The adjusted odds ratio for an interaction between EGFR-TKI and nivolumab was 4.31 (95% CI, 2.37-7.86; P < .001), suggesting the existence of an interaction. When we further stratified the patients by treatment with and without nivolumab, the odds ratio of EGFR–TKI-associated IP in cases with and without nivolumab treatment was 5.09 (95% CI, 2.87-9.03) and 1.22 (95% CI, 1.00-1.47), respectively. Conclusions and Relevance We found a higher proportion of reports of IP for nivolumab in combination with EGFR-TKI vs treatment with either drug alone. Owing to the limitations of this study, the results warrant further confirmation. However, careful consideration should be given to the possibility of an increased risk of IP when EGFR-TKI is administered in combination with nivolumab, including concomitant and sequential use, and careful monitoring for IP is recommended.
The Unique Cysteine Knot Regulates the Pleotropic Hormone Leptin

Leptin plays a key role in regulating energy intake/expenditure, metabolism and hypertension. It folds into a four-helix bundle that binds to the extracellular receptor to initiate signaling. Our work on leptin revealed a hidden complexity in the formation of a previously un-described, cysteine-knotted topology in leptin. We hypothesized that this unique topology could offer new mechanisms in regulating the protein activity. A combination of in silico simulation and in vitro experiments was used to probe the role of the knotted topology introduced by the disulphide-bridge on leptin folding and function. Our results surprisingly show that the free energy landscape is conserved between knotted and unknotted protein, however the additional complexity added by the knot formation is structurally important. Native state analyses led to the discovery that the disulphide-bond plays an important role in receptor binding and thus mediate biological activity by local motions on distal receptor-binding sites, far removed from the disulphide-bridge. Thus, the disulphide-bridge appears to function as a point of tension that allows dissipation of stress at a distance in leptin.
Validation of DPOAE screening conducted by village health workers in a rural community with real-time click evoked tele-auditory brainstem response

Abstract Objective: This study assessed the validity of DPOAE screening conducted by village health workers (VHWs) in a rural community. Real-time click evoked tele-auditory brainstem response (tele-ABR) was used as the gold standard to establish validity. Design: A cross-sectional design was utilised to compare the results of screening by VHWs to those obtained via tele-ABR. Study samples: One hundred and nineteen subjects (0 to 5 years) were selected randomly from a sample of 2880 infants and young children who received DPOAE screening by VHWs. Method: Real time tele-ABR was conducted by using satellite or broadband internet connectivity at the village. An audiologist located at the tertiary care hospital conducted tele-ABR testing through a remote computing paradigm. Tele-ABR was recorded using standard recording parameters recommended for infants and young children. Wave morphology, repeatability and peak latency data were used for ABR analysis. Results: Tele-ABR and DPOAE findings were compared for 197 ears. The sensitivity of DPOAE screening conducted by the VHW was 75%, and specificity was 91%. The negative and positive predictive values were 98.8% and 27.2%, respectively. Conclusions: The validity of DPOAE screening conducted by trained VHW was acceptable. This study supports the engagement of grass-root workers in community-based hearing health care provision.
Activation of Nrf2 Pathways Correlates with Resistance of NSCLC Cell Lines to CBP501 In Vitro

CBP501 is an anticancer drug candidate that was investigated in two randomized phase II clinical trials for patients with nonsquamous non–small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM). CBP501 has been shown to have two mechanisms of action, namely calmodulin modulation and G2 checkpoint abrogation. Here, we searched for a biomarker to predict sensitivity to CBP501. Twenty-eight NSCLC cell lines were classified into two subgroups, CBP501-sensitive and -insensitive, by quantitatively analyzing the cis-diamminedichloro-platinum (II) (CDDP)–enhancing activity of CBP501 through treatments with short-term (1 hour) coexposure to CDDP and CBP501 or to either alone. Microarray analysis was performed on these cell lines to identify gene expression patterns that correlated with CBP501 sensitivity. We found that multiple nuclear factor erythroid-2–related factor 2 (Nrf2) target genes showed high expression in CBP501-insensitive cell lines. Western blot and immunocytochemical analysis for Nrf2 in NSCLC cell lines also indicated higher protein level in CBP501-insensitive cell lines. Moreover, CBP501 sensitivity is modulated by silencing or sulforaphane-induced overexpression of Nrf2. These results indicate that Nrf2 transcription factor is a potential candidate as a biomarker for resistance to CBP501. This study might help to identify those subpopulations of patients who would respond well to the CBP501 and CDDP combination treatment of NSCLC. Mol Cancer Ther; 13(9); 2215–25. ©2014 AACR.
Utilizing Clinical Pharmacy Specialists to Address Access to Care Barriers in the Veteran Population for the Management of Diabetes

Objective: To show that clinical pharmacy specialists (CPSs) can be utilized in remote facilities to provide appropriate diabetes outcomes along with potential cost savings. Methods: A retrospective cohort chart review conducted at the Veterans Affairs North Texas Healthcare System (VANTHCS) evaluated outcomes in patients with type 2 diabetes mellitus referred to CPSs at Fort Worth Outpatient Clinic (FWOPC) or the endocrinologist-managed specialty clinic at the Dallas VA Medical Center (DVAMC). The primary outcome was percentage of patients reaching hemoglobin A1c (HbA1c) goal of <8%. Secondary outcomes were percentage of patients reaching HbA1c <7%, time to reach HbA1c goals of <8% and <7%, and cost savings. Results: There was no statistically significant difference in the number of patients reaching HbA1c goal <8% in the FWOPC (65.3%) compared to the DVAMC (55.8%). Secondary end points comparing FWOPC and DVAMC found no difference in patients reaching HbA1c <7% (20.8% vs 19.2%) and time to reach HbA1c goal of <8% (4.5 vs 6 months) and <7% (8.5 vs 7.5 months). Cost-saving analysis demonstrated a composite of US$350 292 could be saved by the VANTHCS facility if patients continued to be referred to CPS. Conclusion: CPSs can be utilized in diabetes management to provide similar health outcomes as the endocrinologist-managed clinic and to potentially allow for facility cost savings.
Are fetal growth impairment and preterm birth causally related to child attention problems and ADHD? Evidence from a comparison between high-income and middle-income cohorts

Background Cross-cohort comparison is an established method for improving causal inference. This study compared 2 cohorts, 1 from a high-income country and another from a middle-income country, to (1) establish whether birth exposures may play a causal role in the development of childhood attention problems; and (2) identify whether confounding structures play a different role in parent-reported attention difficulties compared with attention deficit hyperactivity disorder (ADHD) diagnoses. Methods Birth exposures included low birth weight (LBW), small-for-gestational age (SGA), small head circumference (HC) and preterm birth (PTB)). Outcomes of interest were attention difficulties (Strengths and Difficulties Questionnaire, SDQ) and ADHD (Development and Well-Being Assessment, DAWBA). Associations between exposures and outcomes were compared between 7-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK (N=6849) and the 2004 Pelotas cohort in Brazil (N=3509). Results For attention difficulties (SDQ), the pattern of association with birth exposures was similar between cohorts: following adjustment, attention difficulties were associated with SGA (OR=1.59, 95% CI 1.20 to 2.19) and small HC (OR=1.64, 95% CI 1.11 to 2.41) in ALSPAC and SGA (OR=1.35, 95% CI 1.04 to 1.75) in Pelotas. For ADHD, however, the pattern of association following adjustment differed markedly between cohorts. In ALSPAC, ADHD was associated with LBW (OR=2.29, 95% CI 1.09 to 4.80) and PTB (OR=2.33, 95% CI 1.23 to 4.42). In the Pelotas cohort, however, ADHD was associated with SGA (OR=1.69, 95% CI 1.02 to 2.82). Conclusions The findings suggest that fetal growth impairment may play a causal role in the development of attention difficulties in childhood, as similar associations were identified across both cohorts. Confounding structures, however, appear to play a greater role in determining whether a child meets the full diagnostic criteria for ADHD.
Correlation between body mass index (BMI) and the Gleason score of prostate biopsies in Chinese population

We assessed the correlation between BMI and Gleason score in prostate biopsies in Chinese Population. In this retrospective study, we collected the Gleason score, PSA, BMI, age, race, and other related clinical data on 290 patients who had undergone prostatic biopsy. We then compared the prostate cancer detection rates and Gleason scores between the high BMI group (BMI ≥ 25; 143 cases) and low BMI group (< 25; 147 cases). Among the 137 patients in whom prostate cancer detected, 70 had high BMIs and 67 had normal BMIs, making the detection rates 48.95% and 45.58% respectively. Seventeen prostate cancer patients had low Gleason scores (Gleason score < 7), while 120 had high Gleason scores (≥ 7). Within the high BMI group, 44.76% had high Gleason scores, which was significantly greater than the 38.10% in the low BMI group (P = 0.027). These results indicate that while there was no effect of BMI on the rate of positive prostate cancer biopsies, the rate of high Gleason scores was greater in the high BMI group than the normal BMI group.
Silencing steroid receptor coactivator-1 in the nucleus of the solitary tract reduces estrogenic effects on feeding and apolipoprotein A-IV expression

We previously found that 17β-estradiol (E2) stimulates apolipoprotein A-IV (apoA-IV) gene expression in the nucleus of the solitary tract (NTS) of lean ovariectomized (OVX) rodents. Here we report that in the NTS of high-fat diet-induced obese (DIO) rats, the apoA-IV mRNA level is significantly reduced and that the estrogenic effects on apoA-IV gene expression and food intake are impaired. E2 regulates apoA-IV gene expression through its nuclear receptor α (ERα), which requires co-activators, such as steroid receptor coactivator-1 (SRC-1), to facilitate the transcription of targeted genes. Interestingly, SRC-1 gene expression is significantly reduced in DIO OVX rats. SRC-1 is colocalized with apoA-IV in the cells of the NTS and E2 treatment enhances the recruitment of ERα and SRC-1 to the estrogen response element at the apoA-V promoter, implying the participation of SRC-1 in E2's stimulatory effect on apoA-IV gene expression. Using small hairpin RNA (shRNA), which was validated in cultured neuronal cells, we found that SRC-1 gene knockdown specifically in the NTS significantly diminished E2's anorectic action, leading to increased food intake and body weight. More importantly, the stimulatory effect of E2 on apoA-IV gene expression in the NTS was significantly attenuated in SRC-1 knockdown rats. These results collectively demonstrate the critical roles of NTS SRC-1 in mediating E2's actions on food intake and apoA-IV gene expression and suggest that reduced levels of endogenous SRC-1 and apoA-IV expression are responsible for the impaired E2's anorectic action in obese females.