bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and acceptability of metformin in preventing the onset of type 2 diabetes after gestational diabetes in postnatal women: a protocol for a randomised, placebo-controlled, double-blind feasibility trial — Optimising health outcomes with Metformin to prevent diAbetes After pregnancy (OMAhA)
Authors: Amaefule Chiamaka Esther , Bolou Angeliki , Drymoussi Zoe , Gonzalez Carreras Francisco Jose , Pardo Llorente Maria del Carmen , Lanz Doris , Dodds Julie , Sweeney Lorna , Pizzo Elena , D’Amico Maria , Thomas Amy , Heighway James , Daru Jahnavi , Sobhy Soha , Robson John , Sanghi Anita , Zamora Javier , Harden Angela , Hitman Graham , Khan Khalid , Pérez Teresa , Huda Mohammed SB , Thangaratinam Shakila 
Published: May 2020

IntroductionUp to half of all women diagnosed with gestational diabetes mellitus develop type 2 diabetes within 5 years after delivery. Metformin is effective in preventing type 2 diabetes in high-risk non-pregnant individuals, but its effect when commenced in the postnatal period is not known. We plan to assess the feasibility of evaluating metformin versus placebo in minimising the risk of dysglycaemia including type 2 diabetes after delivery in postnatal women with a history of gestational diabetes through a randomised trial.Methods and analysisOptimising health outcomes with Metformin to prevent diAbetes After pregnancy (OMAhA) is a multicentre placebo-controlled double-blind randomised feasibility trial, where we will randomly allocate 160 postnatal women with gestational diabetes treated with medication to either metformin (intervention) or placebo (control) tablets to be taken until 1 year after delivery. The primary outcomes are rates of recruitment, randomisation, adherence and attrition. The secondary outcomes are maternal dysglycaemia, cost and quality of life outcomes in both arms, and acceptability of the study and intervention, which will be evaluated through a nested qualitative study. Feasibility outcomes will be summarised using descriptive statistics, point estimates and 95% CIs.Ethics and disseminationThe OMAhA study received ethics approval from the London-Brent Research Ethics Committee (18/LO/0505). Trial findings will be published in a peer-reviewed journal, disseminated at conferences, through our Patient and Public Involvement advisory group (Katie’s Team) and through social media platforms.Trial registration numberISRCTN20930880
Efficacy of recombinant thrombomodulin for poor prognostic cases of acute exacerbation in idiopathic interstitial pneumonia: secondary analysis of the SETUP trial
Authors: Arai Toru , Kida Hiroshi , Ogata Yoshitaka , Marumo Satoshi , Matsuoka Hiroto , Gohma Iwao , Yamamoto Suguru , Mori Masahide , Sugimoto Chikatoshi , Tachibana Kazunobu , Akira Masanori , Inoue Yoshikazu 
Published: May 2020

BackgroundAcute exacerbation (AE) in idiopathic pulmonary fibrosis and other idiopathic interstitial pneumonias (IIPs) are poor prognostic events although they are usually treated with conventional therapy with corticosteroids and immunosuppressants. Previously, we demonstrated the safety and efficacy of recombinant human soluble thrombomodulin (rhTM) for AE-IIP in the SETUP trial. Here, we aimed to clarify the efficacy of rhTM for poor-prognosis cases of AE-IIP.MethodsIn this study, we included 85 patients, in whom fibrin degradation product (FDP)/d-dimer was evaluated at AE, from the 100 patients in the SETUP trial. The AE-IIP patients in the rhTM arm (n=39) were diagnosed using the Japanese criteria from 2014 to 2016 and treated with intravenous rhTM for 6 days in addition to the conventional therapy. The AE-IIP patients in the control arm (n=46) were treated with the conventional therapy without rhTM between 2011 and 2013. The subjects were classified into higher and lower FDP/d-dimer groups based on the Japanese Association for Acute Medicine Disseminated Intravascular Coagulation scoring system. A multivariate Cox proportional hazard regression analysis with stepwise selection was performed to reveal the prognostic factors of AE-IIP.ResultsWe developed a prognostic scoring system using two significant prognostic factors, higher FDP/d-dimer at AE and prednisolone therapy before AE, with 3 and 2 points assigned for each parameter, respectively. The prognostic scores ranged from 0 to 5. Survival of AE-IIP patients with a prognostic score=0 was significantly better than that of patients with score ≥2. Survival was improved with the rhTM therapy (p<0.05) in the poor prognostic cases (score ≥2), but not in the good prognostic cases (score=0).ConclusionsTreatment with rhTM might improve survival in AE-IIP cases with poor prognoses.Trial registration numberUMIN000014969, date: 28 August 2014.
Selecting esophageal cancer patients for lymphadenectomy after neoadjuvant chemoradiotherapy: a modeling study
Authors: Scholte Mirre , de Gouw Didi JJM , Klarenbeek Bastiaan R , Grutters Janneke PC , Rosman Camiel , Rovers Maroeska M 
Published: May 2020

ObjectivesTwo-thirds of patients do not harbor lymph node (LN) metastases after neoadjuvant chemoradiotherapy (nCRT). Our aim was to explore under which circumstances a selective lymph node dissection (LND) strategy, which selects patients for LND based on the restaging results after nCRT, has added value compared with standard LND in esophageal cancer.DesignA decision tree with state-transition model was developed. Input data on short-term and long-term consequences were derived from literature. Sensitivity analyses were conducted to assess promising scenarios and uncertainty.SettingDutch healthcare system.ParticipantsHypothetical cohort of esophageal cancer patients who have already received nCRT and are scheduled for esophagectomy.InterventionsA standard LND cohort was compared with a cohort of patients that received selective LND based on the restaging results after nCRT.Main outcome measuresQuality-adjusted life years (QALYs), residual LN metastases and LND-related complications.ResultsSelective LND could have short-term benefits, that is, a decrease in the number of performed LNDs and LND-related complications. However, this may not outweigh a slight increase in residual LN metastases which negatively impacts QALYs in the long-term. To accomplish equal QALYs as with standard LND, a new surgical strategy should have the same or higher treatment success rate as standard LND, that is, should show equal or less recurrences due to residual LN metastases.ConclusionsThe reduction in LND-related complications that is accomplished by selecting patients for LND based on restaging results after nCRT seems not to outweigh a QALY loss in the long-term due to residual LN metastases. Despite the short-term advantages of selective LND, this strategy can only match long-term QALYs of standard LND when its success rate equals the success rate of standard LND.
Telementoring for remote simulation instructor training and faculty
development using telesimulation
Authors: Gross Isabel Theresia , Whitfill Travis , Auzina Luize , Auerbach Marc , Balmaks Reinis 
Published: May 2020

Introduction
Simulation-based training is essential for high-quality medical care, but
it requires access to equipment and expertise. Technology can facilitate
connecting educators to training in simulation. We aimed to explore the use of
remote simulation faculty development in Latvia using telesimulation and
telementoring with an experienced debriefer located in the USA.

Methods
This was a prospective, simulation-based longitudinal study. Over the
course of 16 months, a remote simulation instructor (RI) from the USA and a
local instructor (LI) in Latvia cofacilitated with teleconferencing.
Responsibility gradually transitioned from the RI to the LI. At the end of each
session, students completed the Debriefing Assessment for Simulation in
Healthcare (DASH) student version form (DASH-SV) and a general feedback form,
and the LI completed the instructor version of the DASH form (DASH-IV). Outcome
measures were the changes in DASH scores over time.

Results
A total of eight simulation sessions were cofacilitated of 16 months. As
the role of the LI increased over time, the debrief quality measured with the
DASH-IV did not change significantly (from 89 to 87), although the DASH-SV
score decreased from a total median score of 89 (IQR 86–98) to 80 (IQR 78–85)
(p=0.005).

Conclusion
In this study, telementoring with telesimulations resulted in high-quality
debriefing. The quality—perceived by the students—was higher with the
involvement of the remote instructor and declined during the transition to the
LI. This concept requires further investigation and could potentially build
local simulation expertise promoting sustainability of high-quality
simulation.
Bystanders’ behaviours and associated factors in cyberbullying
Authors: Panumaporn Jidapa , Hongsanguansri Sirichai , Atsariyasing Wanlop , Kiatrungrit Komsan 
Published: May 2020

BackgroundCyberbullying is presently an alarming problem worldwide due to its impact on the emotions, behaviour and psychological well-being of not only the victims, but the bullies themselves and also bystanders.AimThis study aims to investigate bystanders’ behaviours in cyberbullying and associated factors.MethodsThis research is a cross-sectional study of 578 secondary school students in Bangkok, Thailand. Simple random sampling was used to select four secondary schools. Data were collected through online questionnaires which included four sections: (1) demographic data, (2) bystanders’ behaviour in cyberbullying (cyberbullying experience and attitude towards cyberbullying were included in this section), (3) parental attachment (Inventory of Parent Attachment-Revised), and (4) self-esteem (Rosenberg Self-Esteem Scale-Revised).ResultsIt was found that most occurrences of bystanders’ behaviour were: (a) willing to intervene or help victims (34.6%), (b) ignoring the cyberbullying (28%) or (c) partaking in cyberbullying (26.3%). Participants who either were victims of cyberbullying or knew of cyberbullying happening to friends or relatives and had high parental attachment would intervene more than those who never had such experiences. Participants who knew of cyberbullying happening to the general public had tendencies towards ignoring the cyberbullying. Participants who indicated they were bullies and had positive attitude towards joining in tended to partake in the cyberbullying more than those who were not.ConclusionFactors relating to the behaviours of bystanders in cyberbullying should be further explored to provide support in the discouragement of ignoring and averting participation in cyberbullying. Secure parental attachment is one important factor that should be instilled during childhood years.
Targeting dual signalling pathways in concert with immune checkpoints for the treatment of pancreatic cancer
Authors: Knudsen Erik S , Kumarasamy Vishnu , Chung Sejin , Ruiz Amanda , Vail Paris , Tzetzo Stephanie , Wu Jin , Nambiar Ram , Sivinski Jared , Chauhan Shailender S , Seshadri Mukund , Abrams Scott I , Wang Jianmin , Witkiewicz Agnieszka K 
Published: May 2020

ObjectiveThis study exploits the intersection between molecular-targeted therapies and immune-checkpoint inhibition to define new means to treat pancreatic cancer.DesignPatient-derived cell lines and xenograft models were used to define the response to CDK4/6 and MEK inhibition in the tumour compartment. Impacts relative to immunotherapy were performed using subcutaneous and orthotopic syngeneic models. Single-cell RNA sequencing and multispectral imaging were employed to delineate effects on the immunological milieu in the tumour microenvironment.ResultsWe found that combination treatment with MEK and CDK4/6 inhibitors was effective across a broad range of PDX models in delaying tumour progression. These effects were associated with stable cell-cycle arrest, as well as the induction of multiple genes associated with interferon response and antigen presentation in an RB-dependent fashion. Using single-cell sequencing and complementary approaches, we found that the combination of CDK4/6 and MEK inhibition had a significant impact on increasing T-cell infiltration and altering myeloid populations, while potently cooperating with immune checkpoint inhibitors.ConclusionsTogether, these data indicate that there are canonical and non-canonical features of CDK4/6 and MEK inhibition that impact on the tumour and immune microenvironment. This combination-targeted treatment can promote robust tumour control in combination with immune checkpoint inhibitor therapy.
Global epidemiology of
Neisseria gonorrhoeae
in infertile populations: systematic review, meta-analysis and metaregression
Authors: Chemaitelly Hiam , Majed Alzahraa , Abu-Hijleh Farah , Blondeel Karel , Matsaseng Thabo Christopher , Kiarie James , Toskin Igor , Abu-Raddad Laith J 
Published: May 2020

Objective
To provide an in-depth systematic assessment of the global epidemiology of gonorrhoea infection in infertile populations.

Methods
A systematic literature review was conducted up to 29 April 2019 on international databases and WHO regional databases, and reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All prevalence measures of gonorrhoea infection among infertile populations, based on primary data, qualified for inclusion. Infertile populations were broadly defined to encompass women/men undergoing infertility evaluation or treatment (infertility clinic attendees and partners). Pooled mean prevalence by relevant strata was estimated using random-effects meta-analysis. Associations with prevalence and sources of heterogeneity were explored using metaregression. Risk of bias was assessed using four quality domains.

Findings
A total of 147 gonorrhoea prevalence studies were identified from 56 countries. The pooled mean prevalence of current gonorrhoea infection was estimated globally at 2.2% (95% CI 1.3% to 3.2%), with the highest prevalence in Africa at 5.0% (95% CI 1.9% to 9.3%). The mean prevalence was higher for populations with tubal factor infertility (3.6%, 95% CI 0.9%–7.7%) and mixed cause and unexplained infertility (3.6%, 95% CI 0.0% to 11.6%) compared with other diagnoses, such as ovarian and non-tubal infertility (0.1%, 95% CI 0.0% to 0.8%), and for secondary (2.5%, 95% CI 0.2% to 6.5%) compared with primary (0.5%, 95% CI 0.0% to 1.7%) infertility. Metaregression identified evidence of variations in prevalence by region and by infertility diagnosis, higher prevalence in women than men and a small-study effect. There was a trend of declining prevalence by about 3% per year over the last four decades (OR=0.97, 95% CI 0.95 to 0.99).

Conclusions
Gonorrhoea prevalence in infertile populations is several folds higher than that in the general population, with even higher prevalence in women with tubal factor infertility and in individuals with secondary infertility. These findings support the potential role of gonorrhoea in infertility and suggest that some infertility is possibly preventable by controlling gonorrhoea transmission.

PROSPERO registration number
CRD42018102934.
ГЕНДЕРНІ АСПЕКТИ КАРДІОПРОТЕКТОРНОЇ ЕФЕКТИВНОСТІ МЕЛАТОНІНУ ПРИ РОЗВИТКУ АДРЕНАЛІНІНДУКОВАНОГО НЕКРОЗУ МІОКАРДА НА ТЛІ ПЕРМАНЕНТНОГО ОСВІТЛЕННЯ
Authors: Bezkorovaina H. O. , Klishch I. M. , Khara M. R. 
Published: May 2020

Вступ. Світловий десинхроноз є важливим фактором ризику розвитку ішемічної хвороби серця, яка частіше виникає в чоловіків. Ушкодження міокарда за умов стресу, викликаного порушенням режиму освітлення (його надлишком), призводить до значного дефіциту ендогенного мелатоніну, який має антиоксидантні властивості. Це дозволяє прогнозувати зменшення негативного впливу стресу або катехоламінів на серце за умов перманентного освітлення при застосуванні екзогенного мелатоніну. На сьогодні недостатньо вивчено питання гендерної відмінності кардіопротекторних ефектів мелатоніну при порушенні активності пінеальної залози.
Мета дослідження – вивчити кардіопротекторну ефективність екзогенного мелатоніну при розвитку некрозу міокарда на тлі перманентного освітлення залежно від статі.
Методи дослідження. У міокарді шлуночків самців і самиць щурів визначали відсоток некротизованих кардіоміоцитів, активність пероксидного окиснення ліпідів та антиоксидантної системи при ушкодженні адреналіном. Некроз міокарда викликали шляхом введення адреналіну (0,5 мг/кг, внутрішньом’язово) на тлі перманентного освітлення (10 днів освітлення 500 люкс, 24 год/добу). Групу контролю становили тварини, які перебували в умовах зміни циклів день/ніч (12 год освітлення 500 люкс/12 год освітлення 0,5–1,0 люкс). Мелатонін (5 мг/кг, інтраперитонеально) з метою корекції вводили за 1 год до ін’єкції адреналіну.
Результати й обговорення. При застосуванні мелатоніну розвиток некрозу міокарда характеризувався меншим відсотком некротизованих кардіоміоцитів, нижчою, ніж без корекції, активацією пероксидного окиснення ліпідів, більшою активністю супероксиддисмутази і глутатіонпероксидази. Про кращу збалансованість прооксидантно-антиоксидантних процесів свідчило вище, ніж без корекції, значення антиоксидантно-прооксидантного індексу, особливо в самиць. Ця закономірність демонструвала позитивний вплив екзогенного мелатоніну та непрямо підтверджувала його дефіцит за умов перманентного освітлення.
Висновок. Застосування екзогенного мелатоніну для корекції його дефіциту при перманентному освітленні має позитивний вплив на розвиток адреналініндукованого некрозу міокарда, що підтверджується нижчою, ніж без такої корекції, активацією пероксидного окиснення ліпідів, менш вираженою депресією системи антиоксидантів, меншим відсотком некротизованих кардіоміоцитів. Самиці щурів більш чутливі до позитивного впливу екзогенного мелатоніну порівняно із самцями.
ВИЗНАЧЕННЯ АРБУТИНУ В ГРУШІ ЗВИЧАЙНОЇ ЛИСТІ СОРТІВ ЛИМОНКА, ЛІСОВА КРАСУНЯ ТА НОЯБРСЬКА
Authors: Novosel О. М. , Kyslychenko V. S. , Fedosov А. І. , Andriukova L. М. , Voloshyna А. А. 
Published: May 2020

Вступ. Цистит – одна з доволі частих нозологічних форм інфекційно-запальних захворювань сечовивідних шляхів. Розповсюдженість гострого циститу в Україні становить 314 на 100 тис. населення, хронічного циститу – 135 на 100 тис. населення. Для лікування даного захворювання успішно використовують лікарську рослинну сировину, що містить арбутин і гідрохінон, зокрема сировину груші звичайної.
Мета дослідження – виявити і визначити кількісний вміст арбутину в груші звичайної листі сортів Лимонка, Лісова красуня та Ноябрська.
Методи дослідження. Об’єктом дослідження було груші звичайної листя сортів Лимонка, Лісова красуня та Ноябрська. Виявлення арбутину проводили за допомогою хімічних реакцій і хроматографії в тонкому шарі сорбенту. Його кількісний вміст визначали спектрофотометричним методом при довжині хвилі 455 нм за методикою Державної Фармакопеї України.
Результати й обговорення. У результаті проведення хімічних реакцій і хроматографічного аналізу в груші звичайної листі сортів, які вивчали, встановлено наявність арбутину. Вміст арбутину, який було визначено спектрофотометричним методом, у груші звичайної листі сортів Лимонка, Лісова красуня та Ноябрська становив 1,07, 3,32 і 3,01 % відповідно.
Висновки. У груші звичайної листі сортів Лимонка, Лісова красуня та Ноябрська встановлено наявність і визначено вміст арбутину, який становив 1,07, 3,32 та 3,01 % відповідно. Одержані експериментальні дані буде використано при стандартизації груші звичайної листя, розробці методів контролю якості на досліджувану сировину, а також одержанні фармакологічно активних субстанцій на її основі.
Implicações do tempo em filas na capacidade de carga e na satisfação dos visitantes de parques temáticos
Authors: Machado Ana Carolina Padua , Lobo Heros Augusto Santos 
Published: May 2020

Os parques temáticos são estruturas de lazer criadas a partir do uso da tecnologia e baseada em temas específicos, desenvolvidas para atrair grandes contingentes de pessoas em um espaço relativamente restrito. São compostos por serviços aos visitantes como estacionamento e bilheteria, além de sua finalidade maior, que são suas atrações. A lógica de funcionamento destes parques leva à formação de filas em diversos momentos da visitação. Neste contexto, a presente pesquisa teve por objetivo desenvolver um panorama sobre a percepção dos visitantes dos parques temáticos acerca do tempo de espera nas filas dos principais serviços oferecidos nestes estabelecimentos. Para tanto, foram aplicados questionários pré-estruturados para preenchimento online, com pessoas que já frequentaram parques temáticos. Os dados coletados foram descritos com apoio estatístico – regressão linear e matriz de correlação de similaridade – bem como analisados e relacionados com conceitos de satisfação na visitação, capacidade de carga social e qualidade da experiência. Os resultados demonstraram que os tempos de espera nas filas não afetaram de forma significativa a percepção dos respondentes, uma vez que as avaliações no questionário foram em sua maioria positivas. Assim, concluise que o tempo de espera em filas não afeta negativamente a percepção de lotação e a capacidade de carga social dos parques temáticos na percepção dos visitantes brasileiros.
Palavras-chave: Capacidade de carga social; Percepção de lotação; Turismo de experiência.
Relação entre a dignidade da pessoa com deficiência e o valor de embriões humanos
Authors: Sanches Mário Antônio , Silva Daiane Priscila Simão , Oliveira Houda Izabela de 
Published: May 2020

Nas últimas décadas, foi notória a ampliação da oferta de testes genéticos de diagnóstico pré-natal, inclusive para fins de interrupção de gravidez ou descarte de embriões na reprodução assistida. Paralelamente, surgiram muitos movimentos e organizações no sentido de afirmar a dignidade das pessoas com deficiência e seu direito a uma vida plenamente incluída na sociedade. Este artigo pretende analisar esses dois movimentos e destacar suas contradições. Questionamos se é possível dissociar as práticas de eliminação de embriões e fetos anômalos dos pressupostos eugênicos do início do século XX, bem como a coerência dessas práticas. A reflexão é conduzida considerando que, claramente, estamos assistindo a movimentos que apontam para posições opostas e que a discussão precisa ser ampliada de forma coerente. Os movimentos em prol das pessoas com deficiência já alcançaram muitos avanços legislativos e políticos nas últimas décadas, contudo ainda têm muito a enfrentar em relação ao modelo médico ou determinista de deficiência, construído e reforçado socialmente apontando a deficiência como um problema a ser eliminado. O ápice desse discurso se dá na legitimidade conferida aos testes genéticos como forma de superação do problema das deficiências através da eliminação do próprio “deficiente”.