bluuebunny/crossref_metadata_2025_split huggingface dataset:
Psychotropic drug use following venous thromboembolism versus diabetes mellitus in adolescence or young adulthood: a Danish nationwide cohort study
Authors: Højen Anette Arbjerg , Søgaard Mette , Melgaard Line , Lane Deirdre A. , Sørensen Erik Elgaard , Goldhaber Samuel Zachary , Larsen Torben Bjerregaard 
Published: May 2019

ObjectivesCritical and chronic illness in youth such as diabetes can lead to impaired mental health. Despite the potentially traumatic and life-threatening nature of venous thromboembolism (VTE), the long-term mental health of adolescents and young adults with VTE is unclear. We compared the long-term mental health of adolescents and young adults with VTE versus adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) using psychotropic drug purchase as proxy for mental health.DesignNationwide registry-based cohort study.SettingDenmark 1997–2015.ParticipantsAll patients aged 13–33 years with an incident diagnosis of VTE (n=5065) or IDDM (n=6609).ExposureFirst time primary hospital diagnosis of VTE or IDDM.Primary and secondary outcome measuresAdjusted absolute risk and risk difference at 1 and 5 years follow-up for first psychotropic drug purchase comparing patients with VTE and patients with IDDM.ResultsThe absolute 1 year risk of psychotropic drug use was 6.2% among VTE patients versus 3.6% among patients with IDDM, at 5 years this was 19.3%–14.7%, respectively. After adjusting for the effect of sex, age and risk factors for VTE this corresponded to a 1 year risk differences of 1.9% (95 % CI 0.1% to 3.3%). At 5 years follow-up the risk difference was 1.9% (95% CI 0.5% to 3.3%).ConclusionOne-fifth of adolescents and young adults with incident VTE had claimed a prescription for a psychotropic drug within 5 years, a risk comparable to that of young patients with IDDM.
How do potentially inappropriate medications and polypharmacy affect mortality in frail and non-frail cognitively impaired older adults? A cohort study
Authors: Porter Bryony , Arthur Antony , Savva George M 
Published: May 2019

ObjectivesTo test whether the use of potentially inappropriate central nervous system acting medications, proton pump inhibitors (PPIs) or polypharmacy are associated with mortality in cognitively impaired older adults and whether frailer people are at greater risk of harm.SettingA cohort study nested within the Cognitive Function and Ageing Study II, a population representative cohort study of the older population in Cambridgeshire, Nottingham and Newcastle, UK.ParticipantsA total of 1154 cognitively impaired participants, aged 65 years or older.ExposuresAny use of antipsychotics, antidepressants, other anticholinergic medication, benzodiazepines or PPIs, polypharmacy (5–9) and hyperpolypharmacy (≥10 reported medications) were ascertained at baseline. Frailty was assessed using the Fried criteria.Primary outcomeMortality up to 8 years follow-up. HRs associated with potentially inappropriate medication (PIM), frailty and their interaction were estimated adjusting for covariates.ResultsWithin the sample, 44% were taking one or more PIM. Apart from antipsychotics (adjusted HR=3.24, 95% CI 1.83 to 5.73), use of specific PIM was not associated with greater subsequent mortality. Polypharmacy (HR=1.17, 95% CI 0.95 to 1.45) and hyperpolypharmacy were associated with mortality (HR=1.60, 95% CI 1.16 to 2.22). Being frail (HR=1.90, 95% CI 1.32 to 2.72) or prefrail (HR=1.56, 95% CI 1.10 to 2.20) was associated with increased mortality. There was some evidence that the HR for polypharmacy on mortality was lower among frailer individuals, but the overall polypharmacy by frailty interaction was not statistically significant (p=0.102).ConclusionsFor those with cognitive impairment, greater concern should be afforded to the number of medications than the prescription of specific classes. Frailer individuals may have a lower relative risk of mortality associated with polypharmacy than less frail individuals.
Examining the effectiveness of a web-based intervention for symptoms of depression and anxiety in college students: study protocol of a randomised controlled trial
Authors: Karyotaki Eirini , Klein Anke M , Riper Heleen , Wit Leonore de , Krijnen Lisa , Bol Eline , Bolinski Felix , Burger Simone , Ebert David D , Auerbach Randy P , Kessler Ronald C , Bruffaerts Ronny , Batelaan Neeltje , van der Heijde Claudia M , Vonk Peter , Kleiboer Annet , Wiers Reinout W , Cuijpers Pim 
Published: May 2019

IntroductionThe college years are a peak period for the onset of common mental disorders. Poor mental health is associated with low academic attainment, physical, interpersonal and cognitive impairments. Universities can use online approaches to screen students for mental disorders and treat those in need. The present study aims to assess the effectiveness of a guided web-based transdiagnostic individually tailored intervention to treat students with symptoms of depression and/or anxiety.Methodsand analysisThe present study is a randomised controlled trial. Participants are Dutch college students (≥18 years) with mild to moderate depression and/or anxiety symptoms. The intervention is a guided web-based transdiagnostic individually tailored intervention that targets symptoms of depression and/or anxiety. The intervention consists of seven online sessions with a duration ranging from 4 to 7 weeks depending on individual progress. A booster session is administered 4 weeks after the completion of the seventh session. Primary outcome measures are the Patient Health Questionnaire for depression and the Generalised Anxiety Disorder 7-item scale for anxiety. These scales are administered at screening, post-treatment and follow-up assessments (6 and 12 months post-randomisation).Ethics and disseminationThe Medical Ethics Committee of the Vrije Universiteit Medical Centre has approved the protocol (registration number 2016.583, A2017.362andA2018.421). Results of the trial will be published in a peer-reviewed journal.Trial registration numberNTR6797; Pre-results.
Doctors’ perceptions of how resource limitations relate to futility in end-of-life decision making: a qualitative analysis
Authors: Close Eliana , White Ben P , Willmott Lindy , Gallois Cindy , Parker Malcolm , Graves Nicholas , Winch Sarah 
Published: May 2019

ObjectiveTo increase knowledge of how doctors perceive futile treatments and scarcity of resources at the end of life. In particular, their perceptions about whether and how resource limitations influence end-of-life decision making. This study builds on previous work that found some doctors include resource limitations in their understanding of the concept of futility.SettingThree tertiary hospitals in metropolitan Brisbane, Australia.DesignQualitative study using in-depth, semistructured, face-to-face interviews. Ninety-six doctors were interviewed in 11 medical specialties. Transcripts of the interviews were analysed using thematic analysis.ResultsDoctors’ perceptions of whether resource limitations were relevant to their practice varied, and doctors were more comfortable with explicit rather than implicit rationing. Several doctors incorporated resource limitations into their definition of futility. For some, availability of resources was one factor of many in assessing futility, secondary to patient considerations, but a few doctors indicated that the concept of futility concealed rationing. Doctors experienced moral distress due to the resource implications of providing futile treatment and the lack of administrative supports for bedside rationing.ConclusionsDoctors’ ability to distinguish between futility and rationing would be enhanced through regulatory support for explicit rationing and strategies to support doctors’ role in rationing at the bedside. Medical policies should address the distinction between resource limitations and futility to promote legitimacy in end-of-life decision making.
Genital and analChlamydia trachomatisbacterial load in concurrently infected women: a cross-sectional study
Authors: Dirks J A M C , van Liere Genevieve A F S , Hoebe Christian J P A , Wolffs Petra , Dukers-Muijrers Nicole H T M 
Published: May 2019

ObjectivesMost international STI guidelines recommendChlamydia trachomatisanorectal testing in women after self-reported sexual exposure or symptoms in women. However, it has been shown that the prevalence of anorectalC. trachomatisis as high (7%–17 %) in women who do not report anorectal intercourse (AI) as in women who do. This study assessed the correlation between the genital and anorectalC. trachomatisload in concurrently infected women for increased microbiological insight.MethodsA convenience sample of 105 women with a concurrent (genital and anorectal)C. trachomatisinfection was included from the STI clinic in South Limburg, the Netherlands. Women provided self-collected vaginal and anorectal swabs. TheC. trachomatisload was quantified with qPCR and the human cell load was assessed to ensure sample adequacy. Genital and anorectalC. trachomatisloads were divided into tertiles for comparison. The χ2test and linear regression were used to compare genital and anorectalC. trachomatisloads and identify determinants associated with load.ResultsThe overall medianC. trachomatisload was higher in genital (median 5.3 log10C. trachomatis/ml) than anorectal samples (median 3.4, p ≤ 0.001), but both loads were within the same range. The genital and anal load categories were not related within one woman (p = 0.99), both in women with and without AI. The anorectalC. trachomatisload was in the same or higher load category than the genital load in 56% of women without AI, and 79% of women with AI.ConclusionsAlthough no cut-off for clinical relevance is known, an anorectalC. trachomatisload in the same or higher load category than the genitalC. trachomatisload is likely to be clinically relevant. Other measurements should also be taken into account, such as leucocytes or bacterial viability to distinguish infection from contamination or exposure.
A Novel Fault Classification Technique in Series Compensated Transmission Line using Ensemble Method
Authors: Raval Pranav D. , Pandya A. S. 
Published: May 2019

The paper presents a novel approach for classification of faults in Extra High Voltage (EHV) transmission line with series compensation. The proposed algorithm utilizes single end currents extracted from three phases of a transmission line given to a fault detection and classification system. A detailed model is constructed to analyze fault patterns occurring on a dual feed system with multiple series compensation provided on EHV transmission line. The algorithm uses a full cycle of post-fault currents. A Multiresolution Analysis Wavelet-based decomposition technique is used to provide a joint time frequency analysis. Extensive study is done by designing different fault classifiers using Support Vector Machine (SVM) with different feature vector groups. The SVMs with different parameters are compared to show performance of SVMs in given feature space of faults. A new algorithm is proposed with Ensemble method having group of different classifiers, namely, Artificial Neural Network (ANN), K-Nearest Neighborhood (KNN) and SVM. A combination of feature selection with Ensemble Classifiers is trained and tested on a wide range of fault patterns. A significant improvement in performance is obtained with different combination of features in Ensemble Classifier using subspace partition method.The proposed Ensemble Classifier provides an accuracy of 99.5%.
1D network simulations for evaluating regional flow and pressure distributions in healthy and asthmatic human lungs
Authors: Choi Sanghun , Yoon Sujin , Jeon Jichan , Zou Chunrui , Choi Jiwoong , Tawhai Merryn H. , Hoffman Eric A. , Delvadia Renishkumar , Babiskin Andrew , Walenga Ross , Lin Ching-Long 
Published: May 2019

This study aimed to introduce a one-dimensional (1D) computational fluid dynamics (CFD) model for airway resistance and lung compliance to examine the relationship between airway resistance, pressure, and regional flow distribution. We employed five healthy and five asthmatic subjects who had dynamic computed tomography (CT) scans (4D CT) along with two static scans at total lung capacity and functional residual capacity. Fractional air-volume change ([Formula: see text]) from 4D CT was used for a validation of the 1D CFD model. We extracted the diameter ratio from existing data sets of 61 healthy subjects for computing mean and standard deviation (SD) of airway constriction/dilation in CT-resolved airways. The lobar mean (SD) of airway constriction/dilation was used to determine diameters of CT-unresolved airways. A 1D isothermal energy balance equation was solved, and pressure boundary conditions were imposed at the acinar region ( model A) or at the pleural region ( model B). A static compliance model was only applied for model B to link acinar and pleural regions. The values of 1D CFD-derived [Formula: see text] for model B demonstrated better correlation with 4D CT-derived [Formula: see text] than model A. In both inspiration and expiration, asthmatic subjects with airway constriction show much greater pressure drop than healthy subjects without airway constriction. This increased transpulmonary pressures in the asthmatic subjects, leading to an increased workload (hysteresis). The 1D CFD model was found to be useful in investigating flow structure, lung hysteresis, and pressure distribution for healthy and asthmatic subjects. The derived flow distribution could be used for imposing boundary conditions of 3D CFD. NEW & NOTEWORTHY A one-dimensional (1D) computational fluid dynamics (CFD) model for airway resistance and lung compliance was introduced to examine the relationship between airway resistance, pressure, and regional flow distribution. The 1D CFD model investigated differences of flow structure, lung hysteresis, and pressure distribution for healthy and asthmatic subjects. The derived flow distribution could be used for imposing boundary conditions of three-dimensional CFD.
Eccentric training enhances the αB-crystallin binding to the myofibrils and prevents skeletal muscle weakness in adjuvant-induced arthritis rat
Authors: Himori Koichi , Tatebayashi Daisuke , Ashida Yuki , Yamada Takashi 
Published: May 2019

Patients with rheumatoid arthritis (RA) frequently suffer from muscle weakness. We examined whether eccentric training prevents skeletal muscle weakness in adjuvant-induced arthritis (AIA) rat, a widely used animal model for RA. AIA was induced in the knees of Wistar rats by injection of complete Freund’s adjuvant. To induce eccentric contractions (ECCs), neuromuscular electrical stimulation (45 V) was applied to the plantar flexor muscles simultaneously with forced dorsiflexion of the ankle joint (0–40°) and was given every 6 s. ECC exercise was applied every other day for a total of 11 sessions and consisted of 4 sets of 5 contractions. There was a significant reduction in in vitro maximum Ca2+-activated force in skinned fibers in gastrocnemius muscle from AIA rats. These changes were associated with reduced expression levels of contractile proteins (i.e., myosin and actin), increased levels of inflammation redox stress-related biomarkers (i.e., TNF-α, malondialdehyde-protein adducts, NADPH oxidase 2, and neuronal nitric oxide synthase), and autolyzed active calpain-1 in AIA muscles. ECC training markedly enhanced the steady-state levels of αB-crystallin, a small heat shock protein, and its binding to the myofibrils and prevented the AIA-induced myofibrillar dysfunction, reduction in contractile proteins, and inflammation-oxidative stress insults. Our findings demonstrate that ECC training preserves myofibrillar function without muscle damage in AIA rats, which is at least partially attributable to the protective effect of αB-crystallin on the myofibrils against oxidative stress-mediated protein degeneration. Thus ECC training can be a safe and effective intervention, counteracting the loss of muscle strength in RA patients. NEW & NOTEWORTHY Eccentric contractions (ECCs) are regarded as an effective way to increase muscle strength. No studies, however, assess safety and effectiveness of ECC training on muscle weakness associated with rheumatoid arthritis. Here, we used adjuvant-induced arthritis (AIA) rats to demonstrate that ECC training prevents intrinsic contractile dysfunction without muscle damage in AIA rats, which may be attributed to the protective effect of αB-crystallin on the myofibrils against inflammation-oxidative stress insults.
TAS4464, A Highly Potent and Selective Inhibitor of NEDD8-Activating Enzyme, Suppresses Neddylation and Shows Antitumor Activity in Diverse Cancer Models
Authors: Yoshimura Chihoko , Muraoka Hiromi , Ochiiwa Hiroaki , Tsuji Shingo , Hashimoto Akihiro , Kazuno Hiromi , Nakagawa Fumio , Komiya Yu , Suzuki Satoshi , Takenaka Toru , Kumazaki Masafumi , Fujita Naoya , Mizutani Takashi , Ohkubo Shuichi 
Published: May 2019

Abstract
NEDD8-activating enzyme (NAE) is an essential E1 enzyme of the NEDD8 conjugation (neddylation) pathway, which controls cancer cell growth and survival through activation of cullin-RING ubiquitin ligase complexes (CRL). In this study, we describe the preclinical profile of a novel, highly potent, and selective NAE inhibitor, TAS4464. TAS4464 selectively inhibited NAE relative to the other E1s UAE and SAE. TAS4464 treatment inhibited cullin neddylation and subsequently induced the accumulation of CRL substrates such as CDT1, p27, and phosphorylated IκBα in human cancer cell lines. TAS4464 showed greater inhibitory effects than those of the known NAE inhibitor MLN4924 both in enzyme assay and in cells. Cytotoxicity profiling revealed that TAS4464 is highly potent with widespread antiproliferative activity not only for cancer cell lines, but also patient-derived tumor cells. TAS4464 showed prolonged target inhibition in human tumor xenograft mouse models; weekly or twice a week TAS4464 administration led to prominent antitumor activity in multiple human tumor xenograft mouse models including both hematologic and solid tumors without marked weight loss. As a conclusion, TAS4464 is the most potent and highly selective NAE inhibitor reported to date, showing superior antitumor activity with prolonged target inhibition. It is, therefore, a promising agent for the treatment of a variety of tumors including both hematologic and solid tumors. These results support the clinical evaluation of TAS4464 in hematologic and solid tumors.
A Short SOX9 Peptide Mimics SOX9 Tumor Suppressor Activity and Is Sufficient to Inhibit Colon Cancer Cell Growth
Authors: Blache Philippe , Canterel-Thouennon Lucile , Busson Muriel , Verdié Pascal , Subra Gilles , Ychou Marc , Prévostel Corinne 
Published: May 2019

AbstractDifferently from cytotoxic chemotherapies, targeted therapies do not necessarily drive cancer cells toward death, but reduce cell proliferation, angiogenesis, and/or prevent metastasis without affecting healthy cells. Oncogenic proteins that are hyperactivated and/or overexpressed in cancer cells are prime targets for such therapies. On the other hand, the activity of tumor suppressor proteins is more difficult to harness. Here, we identified a short SOX9 sequence (S9pep) located at the hinge between the HMG DNA-binding domain and the SOX-E central conserved domain that mimics SOX9 tumor-suppressive properties. Doxycycline-induced S9pep expression in DLD-1 colorectal cancer cells inhibited the growth potential of these cells, including colorectal cancer stem cells, restored cell–cell contact inhibition, and inhibited the activity of the oncogenic Wnt/β-catenin signaling pathway. It also significantly decreased tumor growth in BALB/cAnNCrl mice grafted with mouse doxycycline-inducible CT26 colorectal cancer cells in which S9pep was induced by treating them with doxycycline. As the Wnt/β-catenin signaling pathway is constitutively activated in 80% of colorectal cancer and SOX9-inactivating mutations are present in up to 11% of colorectal cancer, S9pep could be a promising starting point for the development of a peptide-based therapeutic approach to restore a SOX9-like tumor suppressor function in colorectal cancer.
АНТИОКСИДАНТНА ТЕРАПІЯ У ЖІНОК З БЕЗПЛІДДЯМ НА ФОНІ ЕНДОМЕТРІОЗУ
Authors: Khmil S. V. , Kulyk I. I. , Mykula R. P. 
Published: May 2019

Мета. Підвищити результативність протоколів допоміжних репродуктивних технологій з використанням комплексної прегравідарної терапії, у жінок з безпліддям на фоні генітального ендометріозу.
Матеріали і методи. Рандомізоване клініко-лабораторне дослідження було проведено серед 104 пацієнток репродуктивного віку з безпліддям та гістологічно підтвердженим діагнозом генітального ендометріозу. Лікування безпліддя всім пацієнткам було проведено із застосуванням допоміжних репродуктивних технологій – екстракорпоральне запліднення ЕКЗ/ICSI.
Результати. Після включення в програму допоміжних репродуктивних технологій, усіх жінок було обстежено та розділено на 2 групи, залежно від лікувальної схеми: І група – (контрольна) включала 51 пацієнтку з ендометріоз-асоційованим безпліддям, яким проводилась КОС за допомогою стандартного «довгого» протоколу; ІІ група – (дослідна) 53 жінки з ендометріоз-асоційованим безпліддям, яким проводилась модифікована схема КОС. Оцінку ефективності лікування із застосуванням прегравідарної терапії використовували наступні показники: сумарна доза р-ФСГ, тривалість стимуляції, кількість фолікулів діаметром більше 17 мм на момент введення тригера фінального дозрівання фолікулів, сумарний коефіцієнт ефективності отриманих ооцит-кумулюсних комплексів при трансвагінальній пункції, ступінь зрілості ооцитів, частоту дегенеративних змін в яйцеклітинах, відсоток запліднення, дроблення ембріонів, вихід бластоцист.
Висновки. Прегравідарна терапія комбінацією препаратів інозитолу та вітаміну D, підвищує чутливість яйників до стимуляції та покращує результати допоміжних репродуктивних технологій. Проведення оперативних втручань у пацієнток із генітальним ендометріозом І та ІІ ступеня важкості рекомендовано після стимуляції суперовуляції у програмах ДРТ.