Miracle-dz/UniFAR-FTUs huggingface dataset:
Benefits and pitfalls of pegylated interferon-α2a therapy in patients with myeloproliferative neoplasm-associated myelofibrosis: a French Intergroup of Myeloproliferative neoplasms (FIM) study

We have previously described the safety and efficacy of pegylated interferon-α2a therapy in a cohort of 62 patients with myeloproliferative neoplasm-associated myelofibrosis followed in centers affiliated to the French Intergroup of Myeloproliferative neoplasms. In this study, we report their long-term outcomes and correlations with mutational patterns of driver and non-driver mutations analyzed by targeted next generation sequencing. The median age at diagnosis was 66 years old, the median follow-up since starting pegylated interferon was 58 months. At the time of analysis, 30 (48.4%) patients were alive including 16 still being treated with pegylated interferon. The median survival of patients with intermediate and high-risk prognostic Lille and dynamic International Prognostic Scoring System scores treated with pegylated interferon was increased in comparison to that of historical cohorts. In addition, overall survival was significantly correlated with the duration of pegylated interferon therapy (70 versus 30 months after 2 years of treatment, P<10−12). JAK2V617F allele burden was decreased by more than 50% in 58.8% of patients and two patients even achieved complete molecular response. Next-generation sequencing analyses performed in 49 patients showed that 28 (57.1%) of them carried non-driver mutations. The presence of at least one additional mutation was associated with a reduction of both overall and leukemia-free survival. These findings in a large series of patients with myelofibrosis suggest that pegylated interferon therapy may provide a survival benefit for patients with intermediate- or high-risk Lille and dynamic International Prognostic Scoring System scores. It also reduced the JAK2V617F allele burden in most patients. These results further support the use of pegylated interferon in selected patients with myelofibrosis.
Latent Classes of Polysubstance Use Among Adolescents in the United States: Intersections of Sexual Identity with Sex, Age, and Race/Ethnicity.

PURPOSE We aimed to estimate latent classes of concurrent polysubstance use and test for sexual orientation differences in latent class memberships with representative data from adolescents living in 19 U.S. states. We also tested whether sex, race/ethnicity, and age moderated the sexual identity differences in polysubstance use class memberships. METHODS We analyzed data from 119,437 adolescents from 19 states who participated in the 2015 Youth Risk Behavior Survey. Latent class analysis characterized polysubstance use patterns based on self-reported frequency of lifetime and past-month use of alcohol (including heavy episodic drinking), tobacco (cigarettes, cigars, and smokeless tobacco), and marijuana. Multinomial logistic regression models tested differences in latent class memberships by sexual identity. Interaction terms tested whether sex, race/ethnicity, and age moderated the sexual identity differences in polysubstance use class memberships. RESULTS A six-class model of polysubstance use fit the data best and included nonusers (61.5%), experimental users (12.2%), marijuana-alcohol users (14.8%), tobacco-alcohol users (3.8%), medium-frequency three-substance users (3.6%), and high-frequency three-substance users (4.1%). Gay/lesbian- and bisexual-identified adolescents had significantly higher odds than heterosexual-identified adolescents of being in all of the user classes compared with the nonuser class. These sexual identity differences in latent polysubstance use class memberships were generally larger for females than for males, varied occasionally by race/ethnicity, and were sometimes larger for younger ages. CONCLUSION Compared with their heterosexual peers, gay/lesbian and bisexual adolescents-especially females-are at heightened risk of engaging in multiple types of polysubstance use. Designing, implementing, and evaluating interventions will likely reduce these sexual orientation disparities.
Agmatine ameliorates acetic acid-induced colitis in rats: involvement of nitrergic system

Abstract Aim: The aim of the present study is to investigate the anti-inflammatory effect of agmatine through the inhibition of iNOS enzyme in acetic acid-induced rat colitis. Methods: Acute colitis was induced by administration of 2 mL of diluted acetic acid (4%) solution rectally. Two hours after colitis induction, animals were treated with normal saline, dexamethasone (2 mg/kg), agmatine (2, 5, 10 mg/kg), L-NAME (30 mg/kg), Aminoguanidine (20 mg/kg), agmatine (2 mg/kg) with L-NAME (30 mg/kg) and agmatine (2 mg/kg) with aminoguanidine (20 mg/kg) intraperitoneally and continued for 3 consecutive days. Assessment of macroscopic and microscopic damage was performed. MPO activity was evaluated by biochemical method. Furthermore, the tissue level of TNF-α was determined by ELISA and the expression level of iNOS protein was detected by immunohistochemistry (IHC). Results: Dexamethasone (2 mg/kg) and agmatine (5, 10 mg/kg) and subeffective doses of agmatine (2 mg/kg) with aminoguanidine (20 mg/kg) improved macroscopic and microscopic damage compared to acetic acid group (p < .001). In addition, these drugs reduced the activity of MPO (p < .001) and the level of TNF-α (p < .001) in colon tissue compared to acetic acid group. Furthermore, they decreased acetic acid-induced expression of iNOS protein in colon tissue (p < .01, p < .001). Conclusion: It is suggested that the anti-inflammatory activity of agmatine on acetic acid-induced rat colitis may involve the inhibition of iNOS enzyme.
Development and Validation of a Patient Safety Culture Questionnaire in Acute Geriatric Units

Background: Older patients (≧65 years) are exposed to more harm resulting from adverse events in hospitals than younger patients. Theoretical considerations and empirical findings suggest that safety culture is the key to improving the quality of health care. Objective: To describe the development of a German-language instrument for assessing patient safety culture (PSC) and its reliability and validity; to verify criterion validity by means of a cross-sectional analysis of the impact of PSC on clinical quality that compares acute geriatric units with a sample from intensive care, surgery and trauma surgery departments, and to report variations in the PSC profile between these groups. Methodology: Using a review of existing safety culture surveys, multidimensional scaling procedures and expert interviews, we tested the content and convergent validity of a 158-item questionnaire completed by 508 physicians and nurses from 31 acute geriatric units and 7 comparison departments. Criterion validity was verified by various regression models with a self-reported measure of adverse events. Differences in PSC profiles were analyzed using a one-factorial ANOVA and regression models. Results: We identified 7 constructs of PSC and demonstrated substantial convergent and criterion validity. In the acute geriatric units, higher levels of ‘management commitment to patient safety’ and lower levels of ‘error fatalism’ were associated with a reduced incidence of medical errors. In the comparison group, only the variable ‘active learning from mistakes’ was relevant for safety performance. Our results also indicate that acute geriatric units display higher standards than the comparison group in all the aspects of patient safety examined. Conclusion: It is possible to measure salient features of PSC using a valid and reliable survey. Some aspects of PSC are more closely related to safety events than others. In acute geriatric units, patient safety appears to be influenced mainly by management’s determination of how things are done whereas improvement of the system itself in a more incremental manner is required in the other high-risk ward types.
Effects of gamma radiation (γ) on biochemical and antioxidant properties in black gram (Vigna mungo L. Hepper)

Abstract Purpose: The present study focused on the role of primary metabolites, antioxidant activities in black gram (Vigna mungo L. Hepper) variety Vamban-4 under the impact of gamma irradiation. Materials and methods: The black gram seeds were irradiated at a different dose of gamma rays viz., 200, 400, 600, 800, 1000 and 1200 Gray (Gy), and analyzed the changes of biochemical and antioxidant contents. Results: Biochemical contents increased with increasing doses up to 800 Gy and reduced at higher dose viz.,1000 and 1200 Gy of gamma-ray treatment, while malondialdehyde content increased at higher dose 1200 Gy compared to control, this indicates that the formation of more lipid peroxidation at higher radiation level. Gamma irradiation enhanced the activity of antioxidant enzymes such as catalase, peroxidase and superoxide dismutase with increasing doses rather than control plants. These studies depict that the effect of gamma irradiation on seeds increased the free radicals compared to control, which emphasize by the Electron spin resonance spectroscopy (ESR). Gamma irradiated seed samples contain more fractions of protein, lipids, amino acid and polysaccharides compared to control plants observed from the Fourier infrared transform spectroscopy (FTIR). Conclusion: The present result concludes that cellular metabolites and the antioxidant enzymes increased and these alterations of metabolism due to the effect of gamma rays which induced free radical production in seeds and plants grown under irradiation stress. These results confirm that the exposure of gamma irradiation produced free radicals as well as counteract by antioxidant enzymes and in addition to that accumulation and alteration of primary metabolites.
Distinguishing Characteristics of E-Cigarette Users Who Attempt and Fail to Quit: Dependence, Perceptions, and Affective Vulnerability.

OBJECTIVE Electronic cigarettes (e-cigarettes) are a prevalent form of substance use among adults. Because of the novelty of e-cigarettes, users may not fully understand the consequences of long-term use and the potential difficulties involved with quitting e-cigarettes. Given the projected rise in the use of e-cigarettes, it is important to understand possible contributing factors that may influence e-cigarette quit difficulty. METHOD In the current study, we evaluated whether those with a previous e-cigarette quit attempt differed from those who made no such attempt on specific and broad-based use factors among 560 current adult e-cigarette users (51.5% female; mean age = 35.27 years, SD = 10.22). RESULTS Results demonstrated that e-cigarette users with previous quit attempts had significantly higher rates of e-cigarette dependence, had perceived barriers to quitting, and held both positive and negative expectancies regarding e-cigarette use. Those with previous e-cigarette quit attempts also endorsed higher levels of affective vulnerability across most studied constructs. CONCLUSIONS Findings suggest that a substantial portion of current e-cigarette users struggle to remain abstinent from e-cigarette use and highlight potential factors that may portend relapse. Longitudinal work is needed to provide a more thorough understanding of e-cigarette use patterns, perceptions, and quit behavior.
Mutation in afsR Leads to A-Factor Deficiency in Streptomyces griseus B2682

Background/Aims: A-factor, a γ-butyrolactone autoregulator, in Streptomyces griseus is involved in the regulation of differentiation and antibiotic production. Here we studied the S. griseus B2682-AFN (A-factor negative) bald mutant that harbors a nonsense mutation in the afsR gene encoding a pleiotropic regulator. Our aim was to prove that this mutation is the cause of the A-factor deficiency in AFN. We also studied whether AfsR regulates A-factor production by AfsA, which is supposed to be the only specific key enzyme in A-factor biosynthesis. Methods: Wild afsR was cloned to the pHJL401 shuttle vector and was transformed to the S. griseus AFN and B2682 strains. During phenotypic characterization, sporulation, antibiotic, protease, A-factor, and AfsA protein production were studied. Results: Transformation of AFN by a wild afsR restored its phenotype including sporulation, antibiotic, extracellular protease, and A-factor production. Introduction of afsR to the B2682 wild-type strain resulted in antibiotic and extracellular protease overproduction that was accompanied with an elevated A-factor level. AfsA was detected both in AFN and B2682. Conclusions: AfsR has an effect on the regulation of A-factor production in S. griseus. The presence of AfsA is not sufficient for normal A-factor production. AfsR regulates A-factor biosynthesis independently of AfsA.
Large-scale, quantitative protein assays on a high-throughput DNA sequencing chip

High-throughput DNA sequencing techniques have enabled diverse approaches for linking DNA sequence to biochemical function. In contrast, assays of protein function have substantial limitations in terms of throughput, automation, and widespread availability. We have adapted an Illumina high-throughput sequencing chip to display an immense diversity of ribosomally-translated proteins and peptides, and then carried out fluorescence-based functional assays directly on this flow cell, demonstrating that a single, widely-available high-throughput platform can perform both sequencing-by-synthesis and protein assays. We quantified the binding of the M2 anti-FLAG antibody to a library of 1.3×104 variant FLAG peptides, exploring non-additive effects of combinations of mutations and discovering a “superFLAG” epitope variant. We also measured the enzymatic activity of 1.56×105 molecular variants of full-length of human O6-alkylguanine-DNA alkyltransferase (SNAP-tag). This comprehensive corpus of catalytic rates linked to amino acid sequence perturbations revealed amino acid interaction networks and cooperativity, linked positive cooperativity to structural proximity, and revealed ubiquitous positively-cooperative interactions with histidine residues.
Mouth self-examination as a screening tool for oral potentially malignant disorders among a high-risk Indigenous population.

OBJECTIVES To evaluate the efficacy of mouth self-examination (MSE) as a self-screening tool for detection of oral mucosal lesions among an Indigenous population in Malaysia at high risk for oral premalignant and malignant disorders. METHODS Two villages were selected as the sampling frame based on prevalence of tobacco and betel quid chewing habit. Respondents were asked to check their mouth for presence of lesion or abnormalities. Education on oral cancer, including MSE, was provided. Subsequently, respondents were asked to perform MSE. Finally, a clinical oral examination (COE) was done by a specialist and the presence of oral mucosal lesions was recorded. RESULTS Almost 64.5 percent of respondents exhibited high levels of difficulty and low mucosal visualization and retracting ability, whereas 3.0 percent demonstrated high attention level when performing MSE. Prevalence of oral mucosal lesions was 59.0 percent, whereas the prevalence of oral potentially malignant disorders (OPMDs) was 9.0 percent. Detection of oral lesions by respondents using MSE was lower than detection by the gold standard. Sensitivity and specificity of MSE for detection of all types of lesions were 8.6 and 95.0 percent respectively. When analyzing each lesion type separately, MSE was found to be most sensitive in detection of swellings (10.0 percent), and most specific in identifying white lesions (97.8 percent). For detection of OPMDs, although specificity was high (98.9 percent), sensitivity (0 percent), and +LR (0) was poor. CONCLUSION MSE is not an effective self-screening tool for early detection of potentially malignant lesions for this population.
The Prevalence of Marginally Significant Results in Psychology Over Time

We examined the percentage of p values (.05 < p ≤ .10) reported as marginally significant in 44,200 articles, across nine psychology disciplines, published in 70 journals belonging to the American Psychological Association between 1985 and 2016. Using regular expressions, we extracted 42,504 p values between . 05 and . 10. Almost 40% of p values in this range were reported as marginally significant, although there were considerable differences between disciplines. The practice is most common in organizational psychology (45.4%) and least common in clinical psychology (30.1%). Contrary to what was reported by previous researchers, our results showed no evidence of an increasing trend in any discipline; in all disciplines, the percentage of p values reported as marginally significant was decreasing or constant over time. We recommend against reporting these results as marginally significant because of the low evidential value of p values between . 05 and . 10.
Cyclase‐associated protein 1 is a key negative regulator of milk synthesis and proliferation of bovine mammary epithelial cells

Adenylyl cyclase‐associated protein (CAP) is a highly conserved protein. Previous reports have suggested that CAP1 may be a negative regulator of cellular proliferation, migration, and adhesion and the development of cell carcinomas. The molecular mechanism of CAP1 regulation of downstream pathways, as well as how CAP1 is regulated by environmental stimuli and upstream signalling, is not well understood. In this present study, we assessed the role of CAP1 in milk synthesis and proliferation of bovine mammary epithelial cells. Using gene overexpression and silencing methods, CAP1 was found to negatively regulate milk synthesis and proliferation of cells via the PI3K‐mTOR/SREBP‐1c/Cyclin D1 signalling pathway. Hormones, such as prolactin and oestrogen, and amino acids, such as methionine and leucine, stimulate MMP9 expression and trigger CAP1 degradation, and thus, abrogate its inhibition of synthesis of milk protein, fat, and lactose by and proliferation of bovine mammary epithelial cells. The results of our study help deepen our understanding of the regulatory mechanisms underlying milk synthesis and aid in characterizing the molecular mechanisms of CAP1.
Extracellular Fluid Volume Expansion Uncovers a Natriuretic Action of GLP-1: A Functional GLP-1-Renal Axis in Man.

PURPOSE We have previously demonstrated that glucagon-like peptide-1 (GLP-1) does not affect renal hemodynamics or function under baseline conditions in healthy participants and in patients with type 2 diabetes mellitus. However, it is possible that GLP-1 promotes natriuresis under conditions with addition of salt and water to the extracellular fluid. The current study was designed to investigate a possible GLP-1-renal axis, inducing natriuresis in healthy, volume-loaded participants. METHODS Under fixed sodium intake, eight healthy men were examined twice in random order during a 3-hour infusion of either GLP-1 (1.5 pmol/kg/min) or vehicle together with an intravenous infusion of 0.9% NaCl. Timed urine collections were conducted throughout the experiments. Renal plasma flow (RPF), glomerular filtration rate (GFR), and uptake and release of hormones and ions were measured via Fick's principle. RESULTS During GLP-1 infusion, urinary sodium and osmolar excretions increased significantly compared with vehicle. Plasma renin levels decreased similarly on both days, whereas angiotensin II (ANG II) levels decreased significantly only during GLP-1 infusion. RPF and GFR remained unchanged on both days. CONCLUSIONS In volume-loaded participants, GLP-1 induces natriuresis, probably brought about via a tubular mechanism secondary to suppression of ANG II, independent of renal hemodynamics, supporting the existence of a GLP-1-renal axis.
Major lower limb amputations in Far North Queensland

Major lower limb amputation is a devastating operation most commonly performed for complications of peripheral artery disease or diabetes mellitus. Data suggest that there is a widespread variation in major amputation rates within and between countries. This study aimed to identify key characteristics of patients undergoing this procedure in our region, and to compare our population to the rest of Australia. Secondary analysis was performed to assess differences seen in the Indigenous population.
Single Nucleotide Polymorphisms in β-Carotene Oxygenase 1 are Associated with Plasma Lycopene Responses to a Tomato-Soy Juice Intervention in Men with Prostate Cancer.

BACKGROUND Human plasma and tissue lycopene concentrations are heterogeneous even when consuming controlled amounts of tomato or lycopene. OBJECTIVES Our objective is to determine whether single nucleotide polymorphisms (SNPs) in or near known or putative carotenoid metabolism genes [β-carotene 15,15' monooxygenase 1 (BCO1), scavenger receptor class B type 1 (SCARB1), ATP-binding cassette transporter subfamily A member 1 (ABCA1), microsomal triglyceride transfer protein (MTTP), apolipoprotein B-48, elongation of very long chain fatty acids protein 2 (ELOVL2), and ATP-binding cassette subfamily B member 1 (ABCB1), and an intergenic superoxide dismutase 2, mitochondrial-associated SNP] are predictive of plasma lycopene responses to steady state tomato juice consumption. METHODS Secondary linear regression analyses of data from a dose-escalation study of prostate cancer patients [n = 47; mean ± SEM age: 60 ± 1 y; BMI (in kg/m2): 32 ± 1] consuming 0, 1, or 2 cans of tomato-soy juice/d (163 mL/can; 20.6 mg lycopene 1.2 mg β-carotene/can) for 24 ± 0.7 d before prostatectomy were conducted to explore 11 SNP genotype effects on the change in plasma lycopene and plasma and prostate tissue concentrations of lycopene, β-carotene, phytoene, and phytofluene. RESULTS Two BCO1 SNP genotypes were significant predictors of the change in plasma lycopene, with SNP effects differing in magnitude and direction, depending on the level of juice intake (rs12934922 × diet group P = 0.02; rs6564851 × diet group P = 0.046). Further analyses suggested that plasma β-carotene changes were predicted by BCO1 rs12934922 (P < 0.01), prostate lycopene by trending interaction and main effects of BCO1 SNPs (rs12934922 × diet group P = 0.09; rs12934922 P = 0.02; rs6564851 P = 0.053), and prostate β-carotene by BCO1 SNP interaction and main effects (rs12934922 × diet group P = 0.01; rs12934922 P < 0.01; rs7501331 P = 0.02). CONCLUSIONS In conclusion, SNPs in BCO1 and other genes may modulate human plasma and prostate tissue responses to dietary lycopene intake and warrant validation in larger, human controlled feeding intervention and cohort studies. Genetic variants related to carotenoid metabolism may partially explain heterogeneous human blood and tissue responses and may be critical covariates for population studies and clinical trials. This trial was registered at clinicaltrials.gov as NCT01009736.