Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of the WHO Framework Convention on Tobacco Control on global cigarette consumption: quasi-experimental evaluations using interrupted time series analysis and in-sample forecast event modelling

Abstract Objective To evaluate the impact of the WHO Framework Convention on Tobacco Control (FCTC) on global cigarette consumption. Design Two quasi-experimental impact evaluations, using interrupted time series analysis (ITS) and in-sample forecast event modelling. Setting and population 71 countries for which verified national estimates of cigarette consumption from 1970 to 2015 were available, representing over 95% of the world’s cigarette consumption and 85% of the world’s population. Main outcome measures The FCTC is an international treaty adopted in 2003 that aims to reduce harmful tobacco consumption and is legally binding on the 181 countries that have ratified it. Main outcomes were annual national estimates of cigarette consumption per adult from 71 countries since 1970, allowing global, regional, and country comparisons of consumption levels and trends before and after 2003, with counterfactual control groups modelled using pre-intervention linear time trends (for ITS) and in-sample forecasts (for event modelling). Results No significant change was found in the rate at which global cigarette consumption had been decreasing after the FCTC’s adoption in 2003, using either ITS or event modelling. Results were robust after realigning data to the year FCTC negotiations commenced (1999), or to the year when the FCTC first became legally binding in each country. By contrast to global consumption, high income and European countries showed a decrease in annual consumption by over 1000 cigarettes per adult after 2003, whereas low and middle income and Asian countries showed an increased annual consumption by over 500 cigarettes per adult when compared with a counterfactual event model. Conclusions This study finds no evidence to indicate that global progress in reducing cigarette consumption has been accelerated by the FCTC treaty mechanism. This null finding, combined with regional differences, should caution against complacency in the global tobacco control community, motivate greater implementation of proven tobacco control policies, encourage assertive responses to tobacco industry activities, and inform the design of more effective health treaties.
CNBP controls transcription by unfolding DNA G-quadruplex structures

Abstract Guanine-rich DNA strands can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4). Experimental evidences suggest that G4-DNA surrounding transcription start sites act as cis-regulatory elements by either stimulating or inhibiting gene transcription. Therefore, proteins able to target and regulate specific G4 formation/unfolding are crucial for G4-mediated transcriptional control. Here we present data revealing that CNBP acts in vitro as a G4-unfolding protein over a tetramolecular G4 formed by the TG4T oligonucleotide, as well as over the G4 folded in the promoters of several oncogenes. CNBP depletion in cellulo led to a reduction in the transcription of endogenous KRAS, suggesting a regulatory role of CNBP in relieving the transcriptional abrogation due to G4 formation. CNBP activity was also assayed over the evolutionary conserved G4 enhancing the transcription of NOGGIN (NOG) developmental gene. CNBP unfolded in vitro NOG G4 and experiments performed in cellulo and in vivo in developing zebrafish showed a repressive role of CNBP on the transcription of this gene by G4 unwinding. Our results shed light on the mechanisms underlying CNBP way of action, as well as reinforce the notion about the existence and function of G4s in whole living organisms.
One plus one does not always equal two, especially with regard to hypomethylating agents: the question of synergy of azacitidine and lenalidomide for treatment of relapsed acute myeloid leukemia and myelodysplastic syndromes post allogeneic hematopoietic stem cell transplant

ABSTRACT Key paper evaluation: Craddock C, et al. Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia. J Clin Oncol. 2019; 37: 580–8. Allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only potentially curative treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, most patients relapse after allo-HSCT and treatment options are limited. Craddock et al. reported recently in the Journal of Clinical Oncology results from a small phase Ib study combining azacitidine (AZA) and lenalidomide (LEN) for treatment of 29 patients (24 AML and 5 MDS patients) who relapsed after allo-HSCT. Overall response rate was 24%. Patients who received ≥3 cycles of treatment had a higher response rate and responders had a better survival compared to non-responders (27 months vs. 10 months; p = 0.004). Combination treatment was well tolerated with three cases of graft-versus-host disease. While this study suggests a potential synergistic effect of LEN + AZA combination therapy, many questions remain. Efficacy and safety should be confirmed in larger, ideally randomized, studies. Further research on mechanism of action of this combination, comparison with other treatment combinations (e.g. AZA + venetoclax) and use during other disease stages are needed.
Ledipasvir‐Sofosbuvir for 12 Weeks in Children 3 to <6 Years Old With Chronic Hepatitis C

For children under 12 years of age who have chronic hepatitis C virus (HCV) infection, there are currently no approved treatments with direct‐acting antiviral agents. We therefore evaluated the safety and efficacy of ledipasvir‐sofosbuvir in HCV‐infected children aged 3 to <6 years. In an open‐label study, patients 3 to <6 years old chronically infected with HCV genotype 1 (n = 33) or 4 (n = 1) received weight‐based doses of combined ledipasvir‐sofosbuvir as granules (33.75 mg/150 mg for weights <17 kg or 45 mg/200 mg for weights ≥17 kg) for 12 weeks. The primary endpoint was sustained virological response 12 weeks after treatment (SVR12). For the first 14 patients, intensive pharmacokinetic sampling was done on day 10 of treatment. All patients had been infected through perinatal transmission and were treatment naïve. No patients had known cirrhosis. Ten patients (29%) weighed <17 kg. SVR12 was achieved in 97% of patients (33 of 34); the patient who did not achieve SVR12 was 3 years old and discontinued treatment after 5 days because of an adverse event “abnormal drug taste. ” The most common adverse events were vomiting (24% of patients), cough (21%), and pyrexia (21%). No patients experienced a serious adverse event. Intensive pharmacokinetic analysis of 13 patients for whom data were evaluable confirmed that the doses selected were appropriate. Conclusion: Ledipasvir‐sofosbuvir was well tolerated and highly effective in children 3 to <6 years old with chronic HCV infection.
HIV diagnoses and testing patterns among young gay, bisexual and other men who have sex with men: an analysis of HIV surveillance data in British Columbia, 2008–2015

We examined changes in HIV testing indicators following a recent increase in diagnoses among young gay, bisexual and other men who have sex with men (GBMSM) in BC that accompanied implementation of a provincial HIV strategy. Surveillance and laboratory testing data were used to compare case counts and testing characteristics among GBMSM < 30 and ≥ 30 years diagnosed in 2008–2011 and 2012–2015. We tested differences in the proportion diagnosed on first testing episode, proportion diagnosed at late stage of infection and the median inter-test interval ((ITI) time in months between last negative test and first positive test) using χ2 and Wilcoxon rank-sum tests. In 2008–2011, 657 diagnoses were made among GBMSM: 24% among men < 30 years and 76% among men ≥ 30 years. In 2012–2015, 590 diagnoses were made: 28% among < 30 years and 28% among ≥ 30 years. Among men < 30 years, diagnoses made on first testing episode decreased (39.4% vs. 28.7% in 2012–2015; p = 0.042) and there were few late-stage diagnoses (5.1% in 2008–2011 vs. 9.1% in 2012–2015). The median ITI was 10 months in both periods. No changes were observed over time among men ≥ 30 years. However, in both periods, late-stage diagnosis was more common in men ≥ 30 years (2008–2011, 18.8%; 2012–2015, 18.6%; p < 0.01 for both). The ITI was also longer for men ≥ 30 years (2008–2011, 24.5 months; 2012–2015, 20 months; p < 0.001 for both). Testing indicators suggested better testing practices among GBMSM diagnosed at < 30 years compared to those diagnosed at older ages. However, there are clear needs for additional prevention measures in both age groups.
Predictors of incident hypertension in healthy non-diabetic postmenopausal women with normal renal function

Abstract Introduction: We aimed to investigate the incidence of hypertension and to identify potential risk factors in healthy, non-diabetic recently postmenopausal Greek women with normal renal function. Patients and methods: This retrospective cohort study evaluated 141 recently postmenopausal women at baseline and annually thereafter (follow-up time: 1 to 8 years). Blood samples were obtained, and ultrasound evaluations were performed at baseline. A detailed medical history, anthropometric parameters, blood pressure and cardiovascular risk factors were recorded for every woman at each visit. Incident hypertension was defined as the first occurrence of office systolic or diastolic blood pressure, measured at 2 different visits within 2 months or history of initiation of antihypertensive medication. Results: Incident hypertension was diagnosed in 30 out of 141 women (21.3%). The median time to incident hypertension was 3.5 years. Adiposity, elevated cholesterol and triglyceride levels, insulin resistance and parity were positively associated with incident hypertension. In multivariate analysis, however, obesity and insulin resistance were the only statistically significant variables associated with more than 3-fold and 2-fold respectively increased risk of incident hypertension (HOMA-IR, O.R = 1.988, p-value =.043; obesity, O.R = 3.746, p-value =.019). Conclusion: A significant proportion of women entering the menopause present incident hypertension and this is mostly associated with obesity and insulin resistance.
THETA-MARKING VIA AGREE

© 2009 by the English Linguistic Society of Japan * This is a radically revised and extended version of the paper presented at the 135th meeting of the Linguistic Society of Japan held at Shinshu University on November 24, 2007. I am deeply indebted to Brent de Chene, Sayaka Goto, Yumiko Ishikawa, Yoichi Miyamoto, Kenichi Namai, Masao Ochi, and two anonymous EL reviewers for their helpful suggestions and valuable comments. I am also grateful to Yasuhiro Iida, Wataru Kambayashi, Hiroshi Mito, Shinta Tamaki, and Yoko Yumoto for discussion. All remaining errors and inadequacies are, of course, mine.
Movement of model position just before vacuum forming to ensure mouthguard thickness: Part 2 Effect of model moving distance.

BACKGROUND/AIM Wearing a mouthguard during sports reduces the risk of dental injury via absorbing impact forces, and the effectiveness and safety of the mouthguard are closely linked to the mouthguard material and thickness. The aim of this study was to clarify the suppression effect of the thickness reduction of the mouthguard when changing the moving distance of the model forward in a stepwise manner. MATERIALS AND METHODS Ethylene-vinyl-acetate sheets of 4.0-mm-thick and a vacuum forming machine were used. The working model was placed at a position 40 mm from the front of the forming unit. The sheet was softened until it sagged 15 mm, and the sheet frame was lowered and covered the model. The model was then pushed from the back to move it forward, and the vacuum was switched on. The model was moved 10 (MP-10), 20 (MP-20), or 30 mm (MP-30). The control model was not moved. The thickness after formation was measured with a specialized caliper. Differences in the mouthguard thickness caused by the forming conditions were analyzed by one-way ANOVA and Bonferroni's multiple comparison tests. RESULTS Significant differences were observed between the control and each MP condition (P<0.01). Reduction rate of the thickness decreased as the moving distance of the model increased. In particular, the thickness difference depending on the forming conditions was greater at the labial site. The reduction rate of MP-30 was 33.8 ± 0.8% smaller than that of the control. CONCLUSION The thickness reduction in mouthguards was mitigated by moving the model forward just before vacuum forming. The reduction was smaller as the moving distance of the model increased. This study suggested that moving the model 20 mm or more forward just before vacuum forming could secure the labial thickness of 3 mm or more. This article is protected by copyright. All rights reserved.
Comparison of Radical Antegrade Modular Pancreatosplenectomy with Standard Retrograde Pancreatosplenectomy for Left-Sided Pancreatic Cancer: A Meta-Analysis and Experience of a Single Center

Background Radical antegrade modular pancreatosplenectomy (RAMPS) has been reported as a modified surgical technique used to achieve better margin resection and to retrieve more lymph nodes compared with standard retrograde pancreatosplenectomy (SRPS). Material/Methods A systematic literature review was performed to identify studies published in PubMed, EmBase, and Web of Science. Hazard ratio (HR), risk ratio (RR), weighted mean difference (WMD), and their 95% confidence intervals (95% CIs) were used as effect measures. In addition, the clinical data of 27 patients in our center were collected and retrospectively analyzed. Results Seven studies containing 474 patients were finally enrolled in this meta-analysis. The pooled results showed that the RAMPS group had a better overall survival (OS) compared with the SRPS group (HR=0.65, 95% CI: 0.43–0.99, P=0.046; I2=41.8%, P=0.143). Significantly more lymph nodes were harvested in the RAMPS group compared with in the SRPS group (WMD=4.74, 95% CI: 0.36–9.12, P=0.034). Recurrence rate (RR=0.8, 95% CI: 0.66–0.98, P=0.028) and blood loss (WMD=−153.19 ml, 95% CI: −303.95 to −2.42, P=0.046) were both significantly reduced in the RAMPS group. Retrospective analysis results showed that only significantly more harvested lymph nodes were noted in the RAMPS group compared with the SRPS group (7.55±0.91 vs. 2.81±0.73, P=0.001). Conclusions Our study suggests that RAMPS has better prognosis and surgical outcomes than SRPS for left-sided pancreatic cancer. Nevertheless, more high-quality clinical trials are required to validate the result.
Associations between Mental Workload and Sleep Quality in a Sample of Young Adults Recruited from a US College Town

ABSTRACT Objective To evaluate associations between perceived mental workload (number of hours spent studying and perceived mental intensity) and sleep quality among young adults. Participants 656 participants [62% male, median age (IQR) = 20 (19, 21) years] recruited from a US college town Methods As part of an online screener, participants answered questions about perceived workload and sleep quality (Pittsburgh Sleep Quality Index (PSQI)). Number of hours/day of mentally engaging work/study, and mental intensity score were the exposures, categorized into quartiles. Linear regression models were used for continuous sleep quality score, and modified Poisson models were used for poor quality sleep (>5 PSQI score) and individual sleep components, adjusting for sex, age, race, physical activity, and caffeine intake. Results Higher mental work-hours were associated with lower-quality sleep; those in the highest quartile of mental work-hours had a 28% higher likelihood of poor sleep quality (95% CI 2% to 62%). Higher mental intensity scores were also related to lower quality sleep; comparing the highest to the lowest quartiles, there was a 45% higher probability of being a poor sleeper (95% CI 15% to 83%). Associations with PSQI components were partly sex-specific: while both sexes had associations between mental intensity and short sleep, males had positive associations with poor sleep quality and sleep medication use. Conversely, females with higher mental intensity reported higher-quality sleep overall and lower sleep medication use but lower sleep efficiency. Conclusions Higher mental workload is associated with lower overall sleep quality in young adults. Associations with individual sleep quality components differed by sex.
Should We Assess Vitamin D Status in Pediatric Patients with Celiac Disease?

OBJECTIVES Screening for vitamin D status in celiac disease (CD) has been recommended but the literature provides varying support. We sought to assess the vitamin D status in newly-diagnosed children with CD and in a non-CD control population and relate them to vitamin D intake. METHODS In a cross-sectional study serum 25-hydroxyvitamin D (25-OHD) levels were drawn in children with newly-diagnosed CD and compared to pediatric outpatients with functional abdominal complaints. Anthropometric data as well as vitamin D intake based on milk and multivitamin ingestion were collected. RESULTS 38 newly-diagnosed CD patients (10.4 ± 3.0 years old; 50% F) and 82 controls (11.2 ± 4.2 years old; 58.5% F) were studied. Both groups were similar except for average daily D intake and Body Mass Index (BMI). There was no statistical difference in mean 25-OHD levels between CD (26.4 ± 8.0 ng/ml) and controls (23.5 ± 8.2 ng/ml) [p ≤ 0.07]. Both groups had high percentages of suboptimal D status (65.8% CD and 79.3% controls). 25-OHD levels significantly correlated with age (r = -0.262; p < 0.0038) and estimated vitamin D intake (r = 0.361; p < 0.0001). CONCLUSIONS No significant difference in 25-OHD levels was noted between newly diagnosed CD and controls, but inadequate 25-OHD levels were common in both. 25-OHD levels were highly associated with vitamin D intake demonstrating similar vitamin D absorption between patients and controls. Since CD is associated with bone disease and D status is frequently low, efforts at optimizing D such as screening levels at diagnosis need to be conducted.
Main Barriers to Optimal Breastfeeding Practices in Armenia: A Qualitative Study

Background In 2015, the median duration of exclusive breastfeeding was 2.2 months in Armenia, and only 15% of 4–5-month-old children were exclusively breastfed, indicating an issue with breastfeeding knowledge and practices. Research aim To identify the main barriers to optimal breastfeeding practices in Armenia. Methods We used qualitative research methods via focus group discussions and in-depth interviews with four groups of providers from different levels of care, and mothers of young children, from Yerevan city and two provinces, Lori and Shirak. Overall, eight in-depth interviews and 13 focus group discussions were conducted with a total of 99 participants. Qualitative content analysis was applied, with elements of both inductive and deductive approaches. Results We identified two main categories of barriers to optimal breastfeeding—systemic barriers and knowledge deficiencies. The main themes within systemic barriers were lack of skilled breastfeeding support services and low motivation of providers—mainly related to inadequate recognition of their role in breastfeeding counseling and low remuneration. The main knowledge-related barriers were insufficient counseling of mothers, lack of reliable information sources about infant feeding, and misconceptions among both mothers and providers. Conclusion Optimal breastfeeding is crucial for the best start to an infant’s life; however, there were a number of barriers to optimal breastfeeding practices in Armenia. Our findings and recommendations could help policymakers apply effective strategies for improving breastfeeding rates in Armenia. Considering the similar historical backgrounds of the post-Soviet countries, our findings could also be applicable to other Commonwealth of Independent States countries.
Depressive Symptoms Assessed Near the End of Pregnancy Predict Differential Response to Postpartum Smoking Relapse Prevention Intervention.

BACKGROUND Depressive symptoms are prevalent during pregnancy and the postpartum period and affect risk for smoking relapse. Whether and how depression affects response to postpartum interventions designed to sustain smoking abstinence is unknown. PURPOSE We examined end-of-pregnancy depressive symptoms as a moderator of response to two postpartum-adapted smoking relapse prevention interventions. METHODS Women (N = 300) who quit smoking during pregnancy were randomized to receive either a postpartum intervention focused on psychosocial factors linked to postpartum smoking (Strategies to Avoid Returning to Smoking [STARTS]) or an attention-controlled comparison intervention (SUPPORT). Women completed the Edinburgh Postnatal Depression Scale at the end of pregnancy. Smoking status was biochemically assessed at the end of pregnancy and at 12, 24, and 52 weeks postpartum. RESULTS End-of-pregnancy depressive symptoms moderated response to postpartum smoking relapse prevention interventions (χ2 = 10.18, p = .001). After controlling for variables previously linked to postpartum smoking relapse, women with clinically significant end-of-pregnancy depressive symptoms (20%) were more likely to sustain abstinence through 52 weeks postpartum if they received STARTS. In contrast, women with few end-of-pregnancy depressive symptoms were more likely to sustain abstinence through 52 weeks postpartum if they received SUPPORT. Changes in the psychosocial factors addressed in the STARTS intervention did not mediate this moderation effect. CONCLUSION Assessment of end-of-pregnancy depressive symptoms may help determine success following postpartum smoking relapse prevention interventions. Women with elevated end-of-pregnancy depressive symptoms benefited from postpartum relapse prevention intervention tailored to their psychosocial needs, while those with few symptoms were more successful in postpartum intervention that used standard behavioral components. CLINICAL TRIAL REGISTRATION NCT00757068.
p73 regulates epidermal wound healing and induced keratinocyte programming

p63 is a transcriptional regulator of ectodermal development that is required for basal cell proliferation and stem cell maintenance. p73 is a closely related p53 family member that is expressed in select p63-positive basal cells and can heterodimerize with p63. p73-/- mice lack multiciliated cells and have reduced numbers of basal epithelial cells in select tissues; however, the role of p73 in basal epithelial cells is unknown. Herein, we show that p73-deficient mice exhibit delayed wound healing despite morphologically normal-appearing skin. The delay in wound healing is accompanied by decreased proliferation and increased levels of biomarkers of the DNA damage response in basal keratinocytes at the epidermal wound edge. In wild-type mice, this same cell population exhibited increased p73 expression after wounding. Analyzing single-cell transcriptomic data, we found that p73 was expressed by epidermal and hair follicle stem cells, cell types required for wound healing. Moreover, we discovered that p73 isoforms expressed in the skin (ΔNp73) enhance p63-mediated expression of keratinocyte genes during cellular reprogramming from a mesenchymal to basal keratinocyte-like cell. We identified a set of 44 genes directly or indirectly regulated by ΔNp73 that are involved in skin development, cell junctions, cornification, proliferation, and wound healing. Our results establish a role for p73 in cutaneous wound healing through regulation of basal keratinocyte function.