bluuebunny/crossref_metadata_2025_split huggingface dataset:
First‐time offenders for recreational ketamine use under a new penalty system in Taiwan: incidence, recidivism and mortality in national cohorts from 2009 to 2017
Authors: Pan Wen‐Hsuan , Wu Kevin Chien‐Chang , Chen Chi‐Ya , Chu Yu‐Roo , Wu Shang‐Chi , Jou Susyan , Lu Tzu‐Pin , Tung Yu‐Chi , Hsu Jui , Chen Wei J. 
Published: November 2020

AbstractBackground and aimsKetamine has become a new recreational drug of choice among young people in parts of Asia. Using national databases in Taiwan, this study aimed to (1) examine the yearly trend in the ketamine offence rate over time; (2) estimate the 3‐year risk of drug‐related re‐offence and its correlates among the first‐time offenders; and (3) estimate the 3‐year standardized mortality ratio (SMR) among the first‐time offenders.Design, Setting and ParticipantsRetrospective cohort studies of offenders for recreational ketamine use in a penalty system initiated in 2009. Offenders for recreational ketamine use were identified from the Administrative Penalty System for Schedule III/IV Substances database from 2009 to 2017, and the re‐offence rate and mortality among first‐time offenders were assessed via record‐linkage within the database as well as with both the criminal drug offence database and the national mortality database. The cohort from 2009 to 2016 (n = 39 178) was used for the recidivism analysis and the cohort from 2009 to 2013 (n = 25 357) was used for the 3‐year SMR analysis.MeasurementsRecidivism was estimated using survival analysis of the event as re‐arrest for using ketamine, more serious illicit drugs (Schedules I/II), or any illicit drugs (ketamine or Schedules I/II). SMRs were estimated for overall and cause‐specific death within 3 years after the first offence for ketamine use.FindingsThe age‐standardized rates for both prevalent (1.38 per 1000) and first‐time offenders (0.65 per 1000) peaked in 2013 and then decreased steadily. The 3‐year risk of re‐offence was 33.85% [95% confidence interval (CI) = 33.23–34.47%) for ketamine use and 39.52% (95% CI = 39.00–40.04%) for any illicit drug use. These first‐time offenders had an SMR of 4.9 (95% CI = 4.3–5.4) for overall mortality, 2.1 (95% CI = 1.6–2.7) for natural deaths and 7.6 (95% CI = 6.7–8.6) for unnatural deaths.ConclusionsRecreational ketamine use in Taiwan appears to lead not only to high risk for drug‐related re‐offence but also to excess mortality.
Risk of neuropsychiatric and cardiovascular adverse events following treatment with varenicline and nicotine replacement therapy in the UK Clinical Practice Research Datalink: a case–cross‐over study
Authors: Thomas Kyla H. , Davies Neil M. , Taylor Amy E. , Taylor Gemma M. J. , Gunnell David , Martin Richard M. , Douglas Ian 
Published: November 2020

AbstractBackground and aimsVarenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care.DesignCase–cross‐over study.SettingUK‐based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality data sets.ParticipantsAdult smokers (n =282,429) observed during periods when exposed and not exposed to either varenicline or NRT.MeasurementsMain outcomes included suicide, self‐harm, myocardial infarction (MI), all‐cause death and cause‐specific death [MI, chronic obstructive pulmonary disease (COPD)]. In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure during the risk period (90 days prior to the event) with the chance of exposure during an earlier single reference period (91–180 days prior to the event) or multiple 90‐day reference periods to increase statistical power.FindingsIn the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, while NRT was associated with MI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.18–1.67]. Using multiple reference periods, varenicline was associated with an increased risk of self‐harm (OR = 1.32, 95% CI = 1.12–1.56) and suicide (OR = 3.56, 95% CI = 1.32–9.60) but a reduction in all‐cause death (OR = 0.75, 95% CI = 0.61–0.93). NRT was associated with MI (OR = 1.54, 95% CI = 1.36–1.74), self‐harm (OR = 1.30, 95% CI = 1.18–1.44) and deaths from MI (OR = 1.53, 95% CI = 1.11–2.10), COPD (OR = 1.33, 95% CI = 1.14–1.56) and all causes (OR = 1.28, 95% CI = 1.18–1.40) when using multiple reference periods.ConclusionsThere appear to be positive associations between (1) nicotine replacement therapy (NRT) and myocardial infarction, death and risk of self‐harm and (2) varenicline and increased risk of self‐harm and suicide, as well as a negative association between varenicline and all‐cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (nicotine replacement therapy is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self‐harm).
Why do doctors work in rural areas in high‐income countries? A qualitative systematic review of recruitment and retention
Authors: Holloway Patrick , Bain‐Donohue Suzanne , Moore Malcolm 
Published: November 2020

AbstractObjectiveTo identify and assess the drivers and barriers to recruiting and retaining doctors in rural communities of high‐income countries.DesignA systematic review and thematic analysis.SettingPublications were sourced from medical and scientific databases online.ParticipantsQualitative, mixed‐methods and review studies from peer‐reviewed journals published since 2000 that discussed recruitment or retention of doctors to rural areas in high‐income countries.Main outcome measuresIdentification and assessment of themes in the literature pertaining to recruitment and retention of rural doctors. Recurrent themes were assessed for relevance and applicability to current rural shortages.ResultsA thematic analysis was completed on 41 papers assessed as in scope of the review. Papers were scrutinised for relevance to established rural recruitment and retention strategies. Key themes were rural background, education and training, personal and professional circumstances, and integration with the community.ConclusionWhile rural origin has long been promoted as the key factor for recruiting rural doctors, initiatives targeting only these individuals ignore a potentially larger cohort of future rural doctors. Rurally focused medical education and training need to encompass students and doctors from all backgrounds. The major barriers to rural recruitment are family‐unit considerations for partners and children, concerns over isolation and a poor perception of rural practice. Attracting doctors to practise rurally is only half the challenge however, and strategies to retain rural doctors need a greater focus on personal and professional support networks and community integration. Additional strategies are needed to retain international and bonded doctors restricted to rural areas.
Safety, pharmacokinetics and pharmacodynamics of SBT‐020 in patients with early stage Huntington's disease, a 2‐part study
Authors: van Diemen Marcus P.J. , Hart Ellen P. , Abbruscato Anthony , Mead Liz , van Beelen Ilse , Bergheanu Sandrin C. , Hameeteman Pieter W. , Coppen Emma , Winder Jessica Y. , Moerland Matthijs , Kan Hermien , van der Grond Jeroen , Webb Andrew , Roos Raymund A.C. , Groeneveld Geert Jan 
Published: November 2020

AimsHuntington's disease (HD) is a neurodegenerative disease with cognitive, motor and psychiatric symptoms. Toxic accumulation of misfolded mutant huntingtin protein induces mitochondrial dysfunction, leading to a bioenergetic insufficiency in neuronal and muscle cells. We evaluated the safety, pharmacokinetics and pharmacodynamics of SBT‐020, a novel compound to improve mitochondrial function, in a 2‐part study in early stage HD patients.MethodsPart 1 consisted of 7‐day multiple ascending dose study to select the highest tolerable dose for Part 2, a 28‐day multiple dose study. Mitochondrial function was measured in the visual cortex and calf muscle, using phosphorous magnetic resonance spectroscopy, and in circulating peripheral blood mononuclear cells.ResultsTreatment‐emergent adverse events were mild and more present in the SBT‐020 group. Injection site reactions occurred in 91% in Part 1 and 97% in Part 2. Mitochondrial function in calf muscle, peripheral blood mononuclear cells or visual cortex was not changed overall due to treatment with SBT‐020. In a posthoc analysis, patients with a higher degree of mitochondrial dysfunction (below the median [∆Ψm < 3412 and τPCr > 42.5 s]) showed more improvement than patients with a relatively lower level of mitochondrial dysfunction.ConclusionSBT‐020 was safe at all doses, but no significant differences in any of the pharmacodynamic measurements between the treatment groups and placebo group could be demonstrated. The data suggest that the better than expected mitochondrial function in our patient population at baseline might explain the lack of effect of SBT‐020.
Wnt8B, transcriptionally regulated by ZNF191, promotes cell proliferation of hepatocellular carcinoma via Wnt signaling
Authors: Liu Yufeng , Wu Di , Cheng Hanghang , Chen Lei , Zhang Weidi , Zou Liping , Gao Qiongmei , Zhao Zhonghua , Chen Qi , Zeng Wenjiao , Zhang Zhigang , Jiang Wei , Huang Cheng , Liu Guoyuan 
Published: November 2020

AbstractDysregulation of wingless‐type (Wnt) signaling is implicated in hepatocellular carcinoma (HCC). Wnt family member 8B (Wnt8B), one of the canonical Wnt ligands, is implicated in oncogenesis. However, the role of Wnt8B in human HCCs and its transcriptional regulation mechanism are presently unknown . Here, we report that Wnt8B expression was frequently increased in HCCs and was significantly associated with poorer patient prognosis. Wnt8B knockdown suppresses HCC cell growth both in vitro and in vivo via inhibiting the canonical Wnt signaling. Zinc finger transcription factor 191 (ZNF191) can positively regulate Wnt8B mRNA and protein expression, and promoter luciferase assay indicated that ZNF191 can increase the transcription activity of the 2‐Kbps WNT8B promoter. Chromatin immunoprecipitation‐qPCR and electrophoretic mobility shift assay showed that ZNF191 protein directly binds to the WNT8B promoter, and the binding sites are at nt‐1491(ATTAATT) and nt‐1178(ATTCATT). Moreover, Wnt8B contributes to the effect of ZNF191 on cell proliferation, and Wnt8B expression correlates positively with ZNF191 in human HCCs. Our findings suggested that Wnt8B, directly transcriptionally regulated by ZNF191, plays a pivotal role in HCC proliferation via the canonical Wnt pathway and may serve as a new prognostic biomarker and a potential therapeutic target for HCC patients.
Combining chemotherapy and autologous peptide‐pulsed dendritic cells provides survival benefit in stage IV melanoma patients
Authors: Eisendle Klaus , Weinlich Georg , Ebner Susanne , Forstner Markus , Reider Daniela , Zelle‐Rieser Claudia , Tripp Christoph H. , Fritsch Peter , Stoitzner Patrizia , Romani Nikolaus , Nguyen Van Anh 
Published: November 2020

SummaryBackground and ObjectivesWe examined retrospectively whether the combination of standard dacarbazine (DTIC) and/or fotemustine chemotherapy and autologous peptide‐loaded dendritic cell (DC) vaccination may improve survival of stage IV melanoma patients. Furthermore, a small cohort of long‐term survivors was studied in more detail.Patients and methodsBetween 1998 and 2008, 41 patients were vaccinated at least three times with DCs while receiving chemotherapy and compared to all other 168 patients in our database who only received chemotherapy (1993–2008).ResultsMedian life expectancy of patients receiving additional DC‐vaccination was 18 months, compared to eleven months for patients under standard chemotherapy alone. In contrast to patients with other haplotypes, the HLA‐A1/A1 subset of DC‐treated patients showed significantly lower median survival (12 vs. 25 months). Autoantibodies were frequently detected in serum of both vaccinated and non‐vaccinated patients, and there was no correlation between titers, loss or appearance of autoantibodies and survival. Additionally, phenotyping of DCs and PBMCs also did not reveal any conspicuous correlation with survival.ConclusionsCombining standard chemotherapy and DC vaccination appears superior to chemotherapy alone. The impact of HLA haplotypes on survival emphasizes the importance of a careful selection of patients with specific, well‐defined HLA haplotypes for future vaccination trials using peptide‐pulsed DCs, possibly combined with checkpoint inhibitors.
Selection and introgression facilitated the adaptation of Chinese native endangered cattle in extreme environments
Authors: Liu Xinfeng , Li Zhaohong , Yan Yubin , Li Ye , Wu Hui , Pei Jie , Yan Ping , Yang Ruolin , Guo Xian , Lan Xianyong 
Published: November 2020

AbstractAlthough persistent efforts have identified and characterized a few candidate genes and related biological processes with potential functions in the adaptation of many species to extreme environments, few works have been conducted to determine the genomic basis of adaptation in endangered livestock breeds that have been living in extreme conditions for more than thousands of years. To fill this gap, we sequenced the whole genomes of nine individuals from three Chinese native endangered cattle breeds that are living in high‐altitude or arid environments. Phylogenetic and evolutionary history analyses of these three and other six breeds showed that the genetic structure of the cattle populations is primarily related to geographic location. Interestingly, we identified pervasive introgression from the yak to Zhangmu cattle (ZMC) that cover several genes (e.g., NOS2, EGLN1 and EPAS1) involved in the hypoxia response and previously identified as positive selection genes in other species, which suggested that the adaptive introgression from yak may have contributed to the adaptation of ZMC to high‐altitude environments. In addition, by contrasting the breeds in opposite living conditions, we revealed a set of candidate genes with various functions from hypoxia response, water metabolism, immune response and body shape change to embryo development and skeletal system development, etc., that may be related to high‐altitude or arid adaptation. Our research provides new insights into the recovery and adaptation of endangered native cattle and other species in extreme environments and valuable resources for future research on animal husbandry to cope with climate change.
Evolution of isoprene emission in Arecaceae (palms)
Authors: Li Mingai , Xu Jia , Lyu Fuling , Khomenko Iuliia , Biasioli Franco , Villani Mariacristina , Baldan Barbara , Varotto Claudio 
Published: November 2020

AbstractIsoprene synthase (IspS) is the sole enzyme in plants responsible for the yearly emission in the atmosphere of thousands of tonnes of the natural hydrocarbon isoprene worldwide. Species of the monocotyledonous family Arecaceae (palms) are among the highest plant emitters, but to date no IspS gene from this family has been identified. Here, we screened with PTR‐ToF‐MS 18 genera of the Arecaceae for isoprene emission and found that the majority of the sampled species emits isoprene. Putative IspS genes from six different genera were sequenced and three of them were functionally characterized by heterologous overexpression in Arabidopsis thaliana, demonstrating that they encode functional IspS genes. Site‐directed mutagenesis and expression in Arabidopsis demonstrated the functional relevance of a novel IspS diagnostic tetrad from Arecaceae, whose most variable amino acids could not preserve catalytic function when substituted by a putatively dicotyledonous‐specific tetrad. In particular, mutation of threonine 479 likely impairs the open–closed transition of the enzyme by altering the network of hydrogen bonds between helices H1α, H, and I. These results shed new light on the evolution of IspS in monocots, suggesting that isoprene emission is an ancestral trait within the Arecaceae family. The identification of IspS from Arecaceae provides promising novel enzymes for the production of isoprene in heterologous systems and allows the screening and selection of commercially relevant palm varieties with lower environmental impact.
Computational approach for content‐based image retrieval of K‐similar images from brain MR image database
Authors: Sampathila Niranjana , Pavithra  , Martis Roshan Joy 
Published: November 2020

AbstractContent‐based medical image retrieval (CBMIR) is a mechanism to handle a huge quantity of image data generated in various medical imaging modalities. In recent years, due to the evolution of computer vision and digital imaging modalities, a large number of medical images are generated. Consequently, the task of retrieving medical images from a large image database becomes more tedious due to variation in the size and shape of the images. Hence, it is necessary to design an appropriate system for medical image retrieval. In this paper a methodology for CBMIR using features of an image such as colour, shape, and texture is proposed to represent and retrieve the images from a large database that are relevant to a given query image. This methodology is evaluated for the application of retrieving the brain MRI images of different planes (coronal, sagittal, and transverse) from a dataset of normal and demented subjects. The features are determined in terms of Grey level co‐occurrence based Haralik's features and histogram based cumulative distribution function (CDF). The image retrieval mechanism is designed using the K‐Nearest Neighbour algorithm by finding the minimum distance between query and database images. The performance parameters such as precision and recall are calculated. The average accuracy of 95.5% are obtained. The results provided ensures the capability to use it as assistive framework for radiologists in radiology image retrieval and classification.
The relationship of sleep duration and quality to energy expenditure and physical activity in children
Authors: Jindal Ishita , Puyau Maurice , Adolph Anne , Butte Nancy , Musaad Salma , Bacha Fida 
Published: November 2020

SummaryBackgroundShorter sleep duration has been linked to the risk for obesity in children. The pathways linking sleep duration and quality to the risk of obesity are unclear, particularly the effect of sleep on energetics.ObjectiveWe investigated the relationship between sleep duration, quality and timing in children, to the basal metabolic rate (BMR), total energy expenditure (TEE) and physical activity (PA).MethodsFifty nine children in two age‐groups (5‐11 and 12‐18 years) underwent evaluation of body composition (DXA), BMR in a room calorimeter, free‐living TEE by doubly labelled water method, sleep and PA (7‐day Actiheart monitor) during school break.ResultsSleep duration contributed to the variance in BMR (β = 0.11, P = .009) after adjusting for age‐group, sex, lean and fat mass, but not to the variance in TEE. Late sleep timing was related to lower PA. In the younger age‐group, children who met recommended sleep duration on ≥50% of the 7 days had higher light PA (P = .03) and lower sedentary time (P = .009).ConclusionSuboptimal sleep is associated with lower BMR, lower PA, and higher sedentary behaviours in young children. Prospective studies are needed to confirm if insufficient sleep duration or late sleep timing contribute to obesity risk by increasing sedentary behaviours and decreasing BMR.
Predictors of bleeding in patients receiving direct oral anticoagulants
Authors: Chua Geoh Soon , Pham Jonathan , Anpalahan Mahesan 
Published: November 2020

AbstractBackgroundThe predictors of clinically significant bleeding events (CSBE) associated with direct oral anticoagulants (DOAC) are poorly characterised in the literature.AimTo determine the incidence and predictors of CSBE in patients receiving DOAC.MethodsPatients who received DOAC during admission to a general medical unit over a 2‐year period were retrospectively studied. Following the index admission, patients were followed for 12 months or for the duration of treatment (if the latter was less than 12 months). The relevant data were obtained by review of medical records.ResultsA total of 203 patients was studied over a mean follow‐up period of 293 (±81) days. The incidence of CSBE was 13.7 (95% confidence interval (CI): 9.5–21.1) per 100 person‐years. Age ≥ 75 years (P = 0.01), concurrent use of antiplatelet medications (P = 0.02) and lower estimated creatinine clearance (CrCl) (P = 0.03) had a significant univariate association with CSBE. However, in the multivariate logistic regression, only concurrent use of antiplatelet medications remained significantly associated with CSBE (adjusted odds ratio (OR) 3.6; 95% CI: 1.4–9.6; P = 0.01). Concurrent use of antiplatelet medications was also independently associated with major bleeding events (MBE) (adjusted OR 4.9; 95% CI: 1.1–21.4; P = 0.04). Although 39 (19.2%) patients received antiplatelet medications, the indications for concurrent antiplatelet use complied with current guidelines in only 3 (7.7%) patients.ConclusionCaution should be exercised when prescribing antiplatelet medications with DOAC as this combination is a potential risk factor for both major and non‐major clinically significant bleeding events. In most patients, the concurrent use of antiplatelet medications was discordant with the current consensus guidelines.
Lay theories and ageist attitudes at work: Essentialist beliefs about cognitive aging, fixed mindsets, and cyclical perception of time are linked to ageist attitudes toward older workers
Authors: Hiu Shaun Kuan Wei , Rabinovich Anna 
Published: November 2020

AbstractTo resolve the problem of ageist attitudes in organizational contexts, the psychological processes that contribute to their endorsement must be investigated. We suggest that lay theories of aging (essentialist beliefs about cognitive aging, EBCA), fixed versus growth mindsets, and lay theories of time (LTT, perceptions of time as change versus. repetition) represent a set of beliefs linked to ageist attitudes toward older workers. We also propose that relationships between these beliefs and ageism are mediated by stereotypical perceptions of older workers. In a pilot study, we constructed a measure of ageist attitudes toward older workers (AATOW). In the main study, we surveyed 166 younger workers (18–30 years old, employed full‐time), measuring EBCA, mindsets, LTT, age‐related stereotypes, and AATOW. The results demonstrated that there were significant relationships between EBCA, fixed mindset, LTT, and ageist attitudes. The relationships between EBCA and ageism, and mindsets and ageism were mediated by perceptions of older workers as not adaptable, while the relationship between LTT and ageism was not mediated by age‐related stereotypes. Implications for organizational efforts to nurture an age‐inclusive intergenerational workforce are discussed.