bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory Compliance of Health Warnings on Tobacco Packs in Karnataka, India
Authors: Mullapudi Somya , Kulkarni Muralidhar M , Kamath Veena G , Britton John , Moodie Crawford , Kamath Asha 
Published: November 2020

AbstractIntroductionIn September 2014, the Government of India introduced legislation requiring all tobacco packaging to display a health warning covering 85% (60% pictorial, 25% text) of the principal display area of the pack, of at least 4 cm in height and 3.5 cm width, with legible text in a white font on a black background and in English and/or the same Indian language as the language used on the pack. We evaluated compliance with this legislation in the Udupi district of Karnataka, India.MethodsWe procured one example of every tobacco pack of cigarettes, beedis, chewing tobacco, and snuff sold by a convenience sample of retailers in one urban and two rural areas in each of the five administrative blocks of the Udupi district between June and August 2018. For each pack we measured the size of the health warning, calculated the proportion of the pack covered, and assessed the legibility.ResultsA total of 365 packs were collected from retailers, with 357 of these branded and eight, all packs of snuff, unbranded. Warnings on 320 (87.3%) packs did not reach the legally required proportional magnitude, warnings on 140 (38.4%) packs were not legible, and warnings on 117 packs (32.1%) did not meet the language requirement. Only 45 packs (12.3%) were fully compliant.ConclusionsCompliance with warning legislation in this district of India is low, highlighting the need for more effective enforcement.ImplicationsWarnings on tobacco packaging are an important and inexpensive means of communicating the harms associated with tobacco use. However, relatively few studies have explored regulatory compliance with warnings. We collected all unique tobacco packs from 66 retailers in a district in Karnataka in India and assessed whether each met the legislative requirements in terms of warning size and proportion of the pack covered, legibility, and the language used. Of the 365 packs collected, only one in eight was compliant with the legislative requirements. This study highlights the importance of assessing warning compliance and the need for enforcement in India.
Risk of depression, suicide and psychosis with hydroxychloroquine treatment for rheumatoid arthritis: a multinational network cohort study
Authors: Lane Jennifer C E , Weaver James , Kostka Kristin , Duarte-Salles Talita , Abrahao Maria Tereza F , Alghoul Heba , Alser Osaid , Alshammari Thamir M , Areia Carlos , Biedermann Patricia , Banda Juan M , Burn Edward , Casajust Paula , Fister Kristina , Hardin Jill , Hester Laura , Hripcsak George , Kaas-Hansen Benjamin Skov , Khosla Sajan , Kolovos Spyros , Lynch Kristine E , Makadia Rupa , Mehta Paras P , Morales Daniel R , Morgan-Stewart Henry , Mosseveld Mees , Newby Danielle , Nyberg Fredrik , Ostropolets Anna , Woong Park Rae , Prats-Uribe Albert , Rao Gowtham A , Reich Christian , Rijnbeek Peter , Sena Anthony G , Shoaibi Azza , Spotnitz Matthew , Subbian Vignesh , Suchard Marc A , Vizcaya David , Wen Haini , Wilde Marcel de , Xie Junqing , You Seng Chan , Zhang Lin , Lovestone Simon , Ryan Patrick , Prieto-Alhambra Daniel ,   for the OHDSI-COVID-19 consortium
Published: November 2020

Abstract

Objectives
Concern has been raised in the rheumatology community regarding recent regulatory warnings that HCQ used in the coronavirus disease 2019 pandemic could cause acute psychiatric events. We aimed to study whether there is risk of incident depression, suicidal ideation or psychosis associated with HCQ as used for RA.

Methods
We performed a new-user cohort study using claims and electronic medical records from 10 sources and 3 countries (Germany, UK and USA). RA patients ≥18 years of age and initiating HCQ were compared with those initiating SSZ (active comparator) and followed up in the short (30 days) and long term (on treatment). Study outcomes included depression, suicide/suicidal ideation and hospitalization for psychosis. Propensity score stratification and calibration using negative control outcomes were used to address confounding. Cox models were fitted to estimate database-specific calibrated hazard ratios (HRs), with estimates pooled where I2 &lt;40%.

Results
A total of 918 144 and 290 383 users of HCQ and SSZ, respectively, were included. No consistent risk of psychiatric events was observed with short-term HCQ (compared with SSZ) use, with meta-analytic HRs of 0.96 (95% CI 0.79, 1.16) for depression, 0.94 (95% CI 0.49, 1.77) for suicide/suicidal ideation and 1.03 (95% CI 0.66, 1.60) for psychosis. No consistent long-term risk was seen, with meta-analytic HRs of 0.94 (95% CI 0.71, 1.26) for depression, 0.77 (95% CI 0.56, 1.07) for suicide/suicidal ideation and 0.99 (95% CI 0.72, 1.35) for psychosis.

Conclusion
HCQ as used to treat RA does not appear to increase the risk of depression, suicide/suicidal ideation or psychosis compared with SSZ. No effects were seen in the short or long term. Use at a higher dose or for different indications needs further investigation.

Trial registration
Registered with EU PAS (reference no. EUPAS34497; http://www.encepp.eu/encepp/viewResource.htm? id=34498). The full study protocol and analysis source code can be found at https://github.com/ohdsi-studies/Covid19EstimationHydroxychloroquine2.
Perturbations of the gut microbiome in anti-CCP positive individuals at risk of developing rheumatoid arthritis
Authors: Rooney Christopher M , Mankia Kulveer , Mitra Suparna , Moura Ines B , Emery Paul , Wilcox Mark H 
Published: November 2020

Abstract

Objective
Individuals with newly diagnosed RA have a distinct microbiome when compared with healthy controls. However, little is known as to when these microbiome perturbations begin. Using a prospective at-risk cohort of individuals positive for anti-citrullinated protein (anti-CCP) antibody with new onset musculoskeletal symptoms, but without clinical arthritis, we investigated for the presence of a gut dysbiosis before the onset of RA.

Methods
The gut microbiota of 25 anti-CCP positive individuals without clinical synovitis were sequenced targeting the V4 region of the 16S rRNA gene. Using a publicly available database, a control population of 44 individuals, approximately matched in age, gender, diet and ethnicity was selected for comparison, using the same sequencing methodology. Median interval between sample collection and progression to RA was 188 days. Taxonomic analysis was performed using QIIME and MEGAN, and statistical analysis using R software.

Results
There were significant differences (P =0.01) at family level in gut microbiomes of anti-CCP positive individuals vs controls. The anti-CCP positive population had an overabundance of Lachnospiraceae, Helicobacteraceae, Ruminococcaceae, Erysipelotrichaceae and Bifidobacteriaceae, among others. Five individuals progressed to RA between sample collection and analysis. Clustering of the progressor population was observed on a phylogenetic network created using a probabilistic similarity index (Goodall’s index).

Conclusions
Anti-CCP positive at-risk individuals without clinical synovitis appear to have a distinct gut microbiome compared with healthy controls. Phylogenetic clustering was observed in individuals who progressed to RA, suggesting that distinct taxa are associated with the development of RA many months before its onset.
Relationships between diuretic-related hyperuricemia and cardiovascular events: data from the URic acid Right for heArt Health study
Authors: Maloberti Alessandro , Bombelli Michele , Facchetti Rita , Barbagallo Carlo Maria , Bernardino Bruno , Rosei Enrico Agabiti , Casiglia Edoardo , Cicero Arrigo Francesco Giuseppe , Cirillo Massimo , Cirillo Pietro , Desideri Giovambattista , D’elia Lanfranco , Dell’Oro Raffaella , Ferri Claudio , Galletti Ferruccio , Giannattasio Cristina , Loreto Gesualdo , Iaccarino Guido , Lippa Luciano , Mallamaci Francesca , Masi Stefano , Mazza Alberto , Muiesan Maria Lorenza , Nazzaro Pietro , Parati Gianfranco , Palatini Paolo , Pauletto Paolo , Pontremoli Roberto , Quarti-Trevano Fosca , Rattazzi Marcello , Rivasi Giulia , Salvetti Massimo , Tikhonoff Valerie , Tocci Giuliano , Ungar Andrea , Verdecchia Paolo , Viazzi Francesca , Volpe Massimo , Virdis Agostino , Grassi Guido , Borghi Claudio 
Published: November 2020

Objective:
Although the relationship between hyperuricemia and cardiovascular events has been extensively examined, data on the role of diuretic-related hyperuricemia are still scanty. The present study was designed to collect information on the relationship between diuretic-related hyperuricemia and cardiovascular events.

Methods:
The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, observational cohort study involving data on individuals recruited from all the Italy territory under the patronage of the Italian Society of Hypertension with an average follow-up period of 122.3 ± 66.9 months. Patients were classified into four groups according to the diuretic use (yes vs. no) and serum uric acid (SUA) levels (higher vs. lower than the median value of 4.8 mg/dl). All-cause death, cardiovascular deaths and first cardiovascular event were considered as outcomes.

Results:
Seventeen thousand, seven hundred and forty-seven individuals were included in the analysis. Mean age was 57.1 ± 15.2 years, men were 45.3% and SBP and DBP amounted to 144.1 ± 24.6 and 85.2 ± 13.2 mmHg. 17.2% of individuals take diuretics of whom 58% had SUA higher than median value. Patients with hyperuricemia without diuretic use served as reference group. In multivariate adjusted analysis (sex, age, SBP, BMI, glucose, total cholesterol, and glomerular filtration rate) individuals with hyperuricemia and diuretic use exhibit a similar risk for the three outcomes as compared with the reference group.

Conclusion:
Our study showed that diuretic-related hyperuricemia carry a similar risk of cardiovascular events and all-cause mortality when compared with individuals that present hyperuricemia in absence of diuretic therapy.
The HIPARCO-2 study: long-term effect of continuous positive airway pressure on blood pressure in patients with resistant hypertension: a multicenter prospective study
Authors: Navarro-Soriano Cristina , Torres Gerard , Barbé Ferrán , Sánchez-de-la-Torre Manuel , Mañas Pedro , Lloberes Patricia , Cambriles Trinidad Díaz , Somoza María , Masa Juan F. , González Mónica , Mañas Eva , de la Peña Mónica , García-Río Francisco , Montserrat Josep María , Muriel Alfonso , Oscullo Grace , García-Ortega Alberto , Posadas Tomás , Campos-Rodríguez Francisco , Martínez-García Miguel-Ángel 
Published: November 2020

Introduction:
Short-term treatment with continuous positive airway pressure (CPAP) produces a clinically significant reduction in blood pressure (BP) in patients with obstructive sleep apnea (OSA) and resistant hypertension. However, it is unknown whether this effect continues over the long-term. Our objective was to assess the effect of long-term CPAP on BP in patients with OSA and resistant hypertension.

Methods:
The study included 161 patients diagnosed with both OSA [apnea--hypopnea index (AHI) ≥15] and resistant hypertension diagnosed via 24-hour ambulatory BP measurement (24-h ABPM), in whom a second analysis via 24-h ABPM was performed at the end of the follow-up.

Results:
Patients were followed up within 59 months [interquartile range (IQR): 44–70]. CPAP treatment was prescribed to 82% of the patients (70% with good adherence to CPAP defined as use of CPAP at least 4 h/night). A comparison between the adherent group and nonadherent group (including those with CPAP not prescribed) showed that CPAP adherents had a significant drop in the 24-h BP, both systolic [−3.9 mmHg; 95% confidence interval (CI): −8.1 to 0.3] and diastolic pressure (−3.5 mmHg [95% [CI]: −6.4–0.5]), with a higher magnitude during the night (−5.5 and −4.9 mmHg, respectively). The CPAP adherent group needed a mean of 1.1 less antihypertensive drugs (particularly spironolactone). Finally, there was a positive correlation between the drop in 24-h SBP and the hours of CPAP use (r = 0.24; P = 0.01).

Conclusion:
Good adherence to long-term CPAP treatment largely succeeded in significantly reducing BP in those patients with OSA and resistant hypertension, despite the use of a lower number of antihypertensive drugs.
Prevalence, awareness, treatment and control of hypertension in Greece: EMENO national epidemiological study
Authors: Stergiou George S. , Menti Ariadni , Kalpourtzi Natasa , Gavana Magda , Vantarakis Apostolos , Chlouverakis Grigoris , Hajichristodoulou Christos , Trypsianis Grigoris , Voulgari Paraskevi V. , Alamanos Yannis , Karakosta Argiro , Touloumi Giota 
Published: November 2020

Objective:
The evidence on the epidemiology of hypertension in Greece is limited. The prevalence and control of hypertension was assessed in randomly selected adults of the general population in Greece within the nationwide epidemiological study EMENO.

Method:
On the basis of 2011 census, EMENO applied a multistage stratified random sampling method involving 577 areas throughout Greece (2013–2016). Participants were assessed at home visits with standardized questionnaires, blood tests and triplicate seated blood pressure (BP) measurements (validated upper-arm automated oscillometric device Microlife BPA100 Plus). Hypertension was defined as BP at least 140/90 mmHg (average of second--third measurement) and/or use of antihypertensive drugs. Sampling weights were applied for study design and post-stratification weights to match the age/sex distribution to the general population in Greece. Nonresponse was adjusted by inverse probability weighting.

Results:
A total of 6006 individuals were recruited and 4699 with valid data were analysed [mean (SD) age 49.2 (18.6) years, men 48.6%, BMI 28.2 (5.7) kg/m2]. The prevalence of hypertension was 39.6% and was higher in men than women (42.7 vs. 36.5%, P < 0.001). Among patients with hypertension, 31.8% were unaware (men/women 39.2/23.6%, P < 0.001), 2.7% aware but untreated (men/women 2.9/2.5%, P = NS), 35.1% treated uncontrolled (32.1/38.3%, P < 0.01) and 30.5% treated controlled (25.8/35.6%, P < 0.001).

Conclusion:
The prevalence of hypertension in Greece seems to be rising and affects 40% of the adults. One-third of them are undiagnosed and only 30% are controlled with treatment. Nationwide programmes are needed to prevent hypertension and improve its awareness and control aiming at reducing the rate cardiovascular diseases.
Predicting pain: differential pain thresholds during self-induced, externally induced, and imagined self-induced pressure pain
Authors: Lalouni Maria , Fust Jens , Vadenmark-Lundqvist Viktor , Ehrsson H. Henrik , Kilteni Konstantina , Birgitta Jensen Karin 
Published: November 2020

Abstract
During self-induced pain, a copy of the motor information from the body's own movement may help predict the painful sensation and cause downregulation of pain. This phenomenon, called sensory attenuation, enables the distinction between self-produced stimuli vs stimuli produced by others. Sensory attenuation has been shown to occur also during imagined self-produced movements, but this has not been investigated for painful sensations. In the current study, the pressure pain thresholds of 40 healthy participants aged 18 to 35 years were assessed when pain was induced by the experimenter (other), by themselves (self), or by the experimenter while imagining the pressure to be self-induced (imagery). The pressure pain was induced on the participants left lower thigh (quadriceps femoris) using a handheld algometer. Significant differences were found between all conditions: other and self (P < 0.001), other and imagery (P < 0.001), and self and imagery (P = 0.004). The mean pressure pain threshold for other was 521.49 kPa (SE = 38.48), for self 729.57 kPa (SE = 32.32), and for imagery 618.88 kPa (SE = 26.67). Thus, sensory attenuation did occur both in the self condition and the imagery condition. The results of this study may have clinical relevance for understanding the mechanisms involved in the elevated pain thresholds seen in patients with self-injury behavior and the low pain thresholds seen in patients with chronic pain conditions. Imagery of sensory attenuation might also be used to alleviate the pain experience for patients undergoing procedural pain.
Brain imaging signature of neuropathic pain phenotypes in small-fiber neuropathy: altered thalamic connectome and its associations with skin nerve degeneration
Authors: Chao Chi-Chao , Tseng Ming-Tsung , Lin Yea-Huey , Hsieh Paul-Chen , Lin Chien-Ho (Janice) , Huang Shin-Leh , Hsieh Sung-Tsang , Chiang Ming-Chang 
Published: November 2020

Abstract
Small-fiber neuropathy (SFN) has been traditionally considered as a pure disorder of the peripheral nervous system, characterized by neuropathic pain and degeneration of small-diameter nerve fibers in the skin. Previous functional magnetic resonance imaging studies revealed abnormal activations of pain networks, but the structural basis underlying such maladaptive functional alterations remains elusive. We applied diffusion tensor imaging to explore the influences of SFN on brain microstructures. Forty-one patients with pathology-proven SFN with reduced skin innervation were recruited. White matter connectivity with the thalamus as the seed was assessed using probabilistic tractography of diffusion tensor imaging. Patients with SFN had reduced thalamic connectivity with the insular cortex and the sensorimotor areas, including the postcentral and precentral gyri. Furthermore, the degree of skin nerve degeneration, measured by intraepidermal nerve fiber density, was associated with the reduction of connectivity between the thalamus and pain-related areas according to different neuropathic pain phenotypes, specifically, the frontal, cingulate, motor, and limbic areas for burning, electrical shocks, tingling, mechanical allodynia, and numbness. Despite altered white matter connectivity, there was no change in white matter integrity assessed with fractional anisotropy. Our findings indicate that alterations in structural connectivity may serve as a biomarker of maladaptive brain plasticity that contributes to neuropathic pain after peripheral nerve degeneration.
Mig6 decreases hepatic EGFR activation and survival during saturated fatty acid-induced endoplasmic reticulum stress
Authors: Lutkewitte Andrew J. , Chen Yi-Chun , Hansen Jeffrey L. , Fueger Patrick T. 
Published: November 2020

ABSTRACTHyperlipidemia associated with obesity and type 2 diabetes (T2D) promotes excess hepatic lipid storage (steatosis) and endoplasmic reticulum (ER) stress, thereby reducing hepatic cell proliferation and survival. An important receptor tyrosine kinase controlling liver proliferation and survival is the epidermal growth factor receptor (EGFR). EGFR expression and activation are decreased during steatosis in humans and several animal models of obesity. Therefore, restoring EGFR activation in obesity-induced ER stress and diabetes could restore the liver’s capacity for survival and regeneration. As an inducible feedback inhibitor of EGFR activity, mitogen-inducible gene 6 (Mig6) is a novel target for enhancing EGFR signaling during diet-induced obesity (DIO) and T2D. Thus, we hypothesized hepatic ER stress induces Mig6 expression and decreases EGFR activation during DIO and diabetes. We identified that Mig6 expression was increased during obesity-induced insulin resistance in C57Bl/6J mice fed a high fat diet. We also discovered that both pharmacological- and fatty acid-driven ER stress increased Mig6 expression and decreased EGF-mediated EGFR activation in primary rat hepatocytes and cell lines. Furthermore, siRNA-mediated Mig6 knockdown restored EGFR signaling and reduced caspase 3/7 activation during ER stress. Therefore, we conclude Mig6 is increased during ER stress in DIO, thereby reducing EGFR activation and enhancing cell death. The implications are the induction of Mig6 during DIO and diabetes may decrease hepatocyte survival, thus hindering cellular repair and regenerative mechanisms.
Population history and the differential consequences of inbreeding and outcrossing in a plant metapoplation
Authors: Fields Peter D. , Arnold Gretchen , Kniskern Joel M. , Taylor Douglas R. 
Published: November 2020

ABSTRACTThe phenotypic consequences of inbreeding typically result in a fitness decline proportional to the increase in the inbreeding coefficient,F. This basic assumption of a predictable, inverse relationship between fitness andFhas been questioned by a number of empirical studies. We explored the relationship between population history and inbreeding in a metapopulation of the plantSilene latifolia, for which long-term data are available for the historical size and spatial distribution of hundreds of local demes. We used a population genetic analysis to estimate gene flow and bi-parental inbreeding (FIS) in demes with different histories of spatial isolation. A controlled crossing experiment examined whether the effect of inbreeding and outcrossing on fitness-related traits varied with different histories of population size and isolation. Historically isolated demes experienced less gene flow and an increase inFIS, as well as significant inbreeding advantage and outbreeding depression for traits expressed early in life. The causes of variation in theF-fitness relationship among populations will include variance in the distribution of deleterious recessive alleles driven by aspects of population history, including population size, founder effects, gene flow, bi-parental inbreeding, and opportunities for the purging of genetic load. Our findings show that isolation and historical variation in population size likely contribute substantial variation in past inbreeding and the consequences of future inbreeding across the metapopulation.
distinct: a novel approach to differential distribution analyses
Authors: Tiberi Simone , Crowell Helena L , Samartsidis Pantelis , Weber Lukas M , Robinson Mark D 
Published: November 2020

AbstractWe presentdistinct, a general method for differential analysis of full distributions that is well suited to applications on single-cell data, such as single-cell RNA sequencing and high-dimensional flow or mass cytometry data. High-throughput single-cell data reveal an unprecedented view of cell identity and allow complex variations between conditions to be discovered; nonetheless, most methods for differential expression target differences in the mean and struggle to identify changes where the mean is only marginally affected.distinctis based on a hierarchical non-parametric permutation approach and, by comparing empirical cumulative distribution functions, identifies both differential patterns involving changes in the mean, as well as more subtle variations that do not involve the mean. We performed extensive bench-marks across both simulated and experimental datasets from single-cell RNA sequencing and mass cytometry data, wheredistinctshows favourable performance, identifies more differential patterns than competitors, and displays good control of false positive and false discovery rates.distinctis available as a Bioconductor R package.