bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanical stretching of the pulmonary vein mediates pulmonary hypertension due to left heart disease by regulating SAC/MAPK pathway and the expression of IL-6 and TNF-α
Authors: Huang Wenhui , Liu Hongjin , Pan Yichao , Yang Hongwei , Lin Jing , Zhang Hui 
Published: May 2021

AbstractBackgroundThis study aimed to explore whether the mechanical stretching-induced expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in pulmonary veins occurred through the stretch-activated channel (SAC)/ mitogen-activated protein kinases (MAPKs) pathway.MethodsSixty male Sprague-Dawley rats were divided into three sham groups and seven model groups. A metal clip was placed on the ascending aorta in the model group to establish PH-LHD rat model. The sham group received a similar operation without ascending aorta clamped. On day 25, pulmonary vein was given mechanical stretching with 0 g, 2.0 g tension in two model groups and two sham groups. Another four model groups were given 2.0 g tension after MAPKs pathway inhibitors soaked. The last sham group and model group rats’ pulmonary veins, pulmonary artery and lung tissues were obtained on day 35. Pulmonary vein, pulmonary artery and lung tissue were evaluated by echocardiography, HE staining, immunohistochemistry and western blotting respectively.ResultsOn day 25, left heart weight, right ventricular pressure (35.339 cmH2O) and left atrial pressure (13.657 cmH2O) were increased in model group than those in sham group. Echocardiography showed left heart failure in the PH-LHD group (Interventrieular septum dimension 1.716 mm, left ventricular internal end diastolic dimension 4.888 mm, left ventricular posterior wall thickness in diastole 1.749 mm, ejection fraction 76.917%). But there was no difference in lung tissue between the sham group and PH-LHD group as showed by HE staining. Our results showed that the expression of IL-6 and TNF-α was highly expressed in PH-LHD rats’ serum and pulmonary vein, which were further increased after 2.0 g tension was given and were decreased after SAC/MAPKs inhibitors treatment. Meanwhile, on day 25, immunohistochemistry analysis showed the expression of IL-6 and TNF-α was higher in the PH-LHD rats’ pulmonary vein than that in pulmonary artery and lung tissue, and these expressions in pulmonary vein of PH-LHD group were also higher than that in sham group. However, on day 35, IL-6 and TNF-α were all increased in the pulmonary veins, arteries and lung tissues. Besides, our results uncovered that SAC/MAPKs pathway were upregulating in PH-LHD rats’ pulmonary vein.ConclusionIn conclusion, pulmonary vein mechanical stretching exacerbated PH-LHD possibly through the SAC/MAPKs pathway and upregulating expression of IL-6 and TNF-α.
Defining major trauma: a Delphi study
Authors: Thompson Lee , Hill Michael , Lecky Fiona , Shaw Gary 
Published: May 2021

AbstractIntroductionRetrospective trauma scores are often used to categorise trauma, however, they have little utility in the prehospital or hyper-acute setting and do not define major trauma to non-specialists. This study employed a Delphi process in order to gauge degrees of consensus/disagreement amongst expert panel members to define major trauma.MethodA two round modified Delphi technique was used to explore subject-expert consensus and identify variables to define major trauma through systematically collating questionnaire responses.After initial descriptive analysis of variables, Kruskal-Wallis tests were used to determine statistically significant differences (p < 0.05) in response to the Delphi statements between professional groups. A hierarchical cluster analysis was undertaken to identify patterns of similarity/difference of response.A grounded theory approach to qualitative analysis of data allowed for potentially multiple iterations of the Delphi process to be influenced by identified themes.ResultsOf 55 expert panel members invited to participate, round 1 had 43 participants (Doctorn = 20, Paramedicn = 20, Nursen = 5, othern = 2). No consistent patterns of opinion emerged with regards to professional group. Cluster analysis identified three patterns of similar responses and coded as trauma minimisers, the middle ground and the risk averse. Round 2 had 35 respondents with minimum change in opinion between rounds.Consensus of> 70% was achieved on many variables which included the identification of life/limb threatening injuries, deranged physiology, need for intensive care interventions and that extremes of age need special consideration. It was also acknowledged that retrospective injury severity scoring has a role to play but is not the only method of defining major trauma. Various factors had a majority of agreement/disagreement but did not meet the pre-set criteria of 70% agreement. These included the topics of burns, spinal immobilisation and whether a major trauma centre is the only place where major trauma can be managed.ConclusionBased upon the output of this Delphi study, major trauma may be defined as: “Significant injury or injuries that have potential to be life-threatening or life-changing sustained from either high energy mechanisms or low energy mechanisms in those rendered vulnerable by extremes of age”.
SpatialDWLS: accurate deconvolution of spatial transcriptomic data
Authors: Dong Rui , Yuan Guo-Cheng 
Published: May 2021

AbstractRecent development of spatial transcriptomic technologies has made it possible to characterize cellular heterogeneity with spatial information. However, the technology often does not have sufficient resolution to distinguish neighboring cell types. Here, we present spatialDWLS, to quantitatively estimate the cell-type composition at each spatial location. We benchmark the performance of spatialDWLS by comparing it with a number of existing deconvolution methods and find that spatialDWLS outperforms the other methods in terms of accuracy and speed. By applying spatialDWLS to a human developmental heart dataset, we observe striking spatial temporal changes of cell-type composition during development.
Efficacy and safety of Naoxintong capsule for treating chronic stable angina: study protocol for a randomized controlled trial
Authors: Huanjia Gao , Hairong Cai , Jieqin Zhuang , Xingzhen Dai , Xue Fu , Weizhang Zhang , Bojun Chen 
Published: May 2021

Abstract
Background
Cardiovascular disease is the leading cause of mortality and morbidity worldwide, Chronic stable angina (CSA) is the main symptom of myocardial ischemia, causes increased risk of major cardiovascular events such as sudden cardiac death and myocardial infarction. Naoxintong (NXT) capsule is a classical traditional Chinese medication used to treat CSA, however, few evidence to support the wide utility of NXT capsule for the treatment of CSA. We design this study to evaluate the efficacy and safety of NXT capsule versus placebo in patients with CSA.

Methods/design
This is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 260 eligible participants will be enrolled. The participants will be randomized assigned in an equal ratio to groups receiving either NXT or placebo for 12 weeks. After a 2-week run-in period, they will receive either NXT or placebo (3 pills, 3 times daily) for 12 weeks. The primary outcome is therapeutic efficacy. Secondary outcome measures include the quantitative score of TCM syndromes, severity grading of angina pectoris, the number of angina pectoris per week, nitroglycerin dosage, score of Seattle angina scale, serum homocysteine, and incidence of cardiovascular events. Safety outcomes and adverse events will be monitored throughout the trial.

Discussion
We designed this study in accordance with principles and regulations issued by the China Food and Drug Administration (CFDA). The results will provide clinical evidence of the efficacy and safety of NXT Capsule in the treatment of CSA.

Trial registration
Chinese Clinical Trial Registry ChiCTR2100044563. Registered on 24 March 2020.
A simple cognitive task intervention to prevent intrusive memories after trauma in patients in the Emergency Department: A randomized controlled trial terminated due to COVID-19
Authors: Kanstrup Marie , Singh Laura , Göransson Katarina E. , Gamble Beau , Taylor Rod S. , Iyadurai Lalitha , Moulds Michelle L. , Holmes Emily A. 
Published: May 2021

Abstract
Objective
This randomised controlled trial (RCT) aimed to investigate the effects of a simple cognitive task intervention on intrusive memories ("flashbacks") and associated symptoms following a traumatic event. Patients presenting to a Swedish emergency department (ED) soon after a traumatic event were randomly allocated (1:1) to the simple cognitive task intervention (memory cue + mental rotation instructions + computer game "Tetris" for at least 20 min) or control (podcast, similar time). We planned follow-ups at one-week, 1-month, and where possible, 3- and 6-months post-trauma. Anticipated enrolment was N = 148.

Results
The RCT was terminated prematurely after recruiting N = 16 participants. The COVID-19 pandemic prevented recruitment/testing in the ED because: (i) the study required face-to-face contact between participants, psychology researchers, ED staff, and patients, incurring risk of virus transmission; (ii) the host ED site received COVID-19 patients; and (iii) reduced flow of patients otherwise presenting to the ED in non-pandemic conditions (e.g. after trauma). We report on delivery of study procedures, recruitment, treatment adherence, outcome completion (primary outcome: number of intrusive memories during week 5), attrition, and limitations. The information presented and limitations may enable our group and others to learn from this terminated study.
Trial registration ClinicalTrials.gov: NCT04185155 (04-12-2019)
E-book of metacognitive learning strategies: design and implementation to activate student’s self-regulation
Authors: Susantini Endang , Puspitawati Rinie Pratiwi , Raharjo  , Suaidah Husfina Lailiyatus 
Published: May 2021

AbstractICT-based learning provides opportunities for teachers and students to learn digitally, as well as letting the students become autonomous learners. One of the efforts to actualize such typical learning mode is to provide digitalized learning media, such as e-Books. An e-Book of metacognitive learning strategies aimed to train students’ metacognitive skills that emphasized self-regulated learning in order to make them become autonomous learners. This study was objected to describe the e-Book of metacognitive learning strategies in designing, implementing, and evaluating students’ metacognitive skills in a learning process. The e-Book was designed using ADDIE development model and used during the innovative learning I course for 84 biology students at Universitas Negeri Surabaya. The data were analyzed using descriptive-qualitative approach. The results showed that the e-Book’s validity was in a very good category. It also conveyed level 15 of readability according to the students and was responded very well with a positive response of 96%. Other findings depicted that the students’ metacognitive learning outcomes and students’ self-regulation were in a good category. Hence, the e-Books had the potential to be used in a digital learning mode as well as training students’ metacognitive skills and self-regulation.
Management of Soft Tissue Sarcomas in Extremities: Variation in Treatment Recommendations and Surveillance According to Specialty and Continent
Authors: Acem Ibtissam , Smit Merel M. , Verhoef Cornelis , van Houdt Winan J. , Haas Rick L. , van der Hage Jos A. , Grünhagen Dirk J. , van de Sande Michiel A. J. 
Published: May 2021

Abstract
Background
This study aimed to provide an insight into clinical decision-making and surveillance strategy of sarcoma specialists for patients with primary soft tissue sarcoma of the extremities (eSTS). The secondary aim was to quantify the role of patient- and tumor-specific factors in the perioperative management.

Methods
Members of sarcoma societies were sent a Web-based 21-item survey about eSTS management. The survey concerned only primary resectable high-grade eSTS in adults.

Results
The study enrolled 396 respondents. The majority of the surgical specialists thought the evidence for perioperative chemotherapy (CTX) for high-grade eSTS was insufficient. Radiotherapy (RTX) was less frequently offered in Asia than in North America and Europe. The specialties and continents also differed regarding the importance of patient and tumor characteristics influencing RTX and CTX recommendation. For surveillance after initial treatment outpatient visits, chest computed tomography (CT) scans, and magnetic resonance images of the extremity were the methods primarily used. The specialists in North America preferred chest CT scan over chest x-ray, whereas those in Asia and Europe had no clear preference.

Discussion
Specialty and continent are important factors contributing to the variation in clinical practice, treatment recommendations, and surveillance of patients with primary resectable high-grade eSTS.
Use of resorbable magnesium screws in children: Systematic review of the literature and short-term follow-up from our series
Authors: Baldini Marco , Coppa Valentino , Falcioni Danya , Senigagliesi Elisa , Marinelli Mario , Gigante Antonio Pompilio 
Published: May 2021

Purpose Biodegradable implants are of major interest in orthopaedics, especially in the skeletally immature population. Magnesium (Mg) implants are promising for selected surgical procedure in adults, but evidence is lacking. Thus, the aim of this study is to analyze the safety and efficacy of resorbable Mg screw in different orthopaedic procedures in skeletally immature patients. In addition, we present a systematic review of the current literature on the clinical use of Mg implants. Methods From 2018 until the writing of this manuscript, consecutive orthopaedic surgical procedures involving the use of Mg screws performed at our centre in patients < 15 years of age were retrospectively reviewed. In addition, a systematic review of the literature was performed in the main databases. We included clinical studies conducted on humans, using Mg-alloy implants for orthopaedic procedures. Results A total of 14 patients were included in this retrospective analysis. Mean age at surgery was 10.8 years (sd 2.4), mean follow-up was 13.8 months (sd 7.5). Healing was achieved in all the procedures, with no implant-related adverse reaction. No patients required any second surgical procedure. The systematic review evidenced 20 clinical studies, 19 of which conducted on an adult and one including paediatric patients. Conclusion Evidence on resorbable Mg implants is low but promising in adults and nearly absent in children. Our series included apophyseal avulsion, epiphyseal fractures, osteochondritis dissecans, displaced osteochondral fragment and tendon-to-bone fixation. Mg screws guaranteed stable fixation, without implant failure, with good clinical and radiological results and no adverse events. Level of evidence IV – Single cohort retrospective analysis with systematic review
Insecticide resistance status and mechanisms in Aedes aegypti populations from Senegal
Authors: Sene Ndeye Marie , Mavridis Konstantinos , Ndiaye El Hadji , Diagne Cheikh Tidiane , Gaye Alioune , Ngom El Hadji Malick , Ba Yamar , Diallo Diawo , Vontas John , Dia Ibrahima , Diallo Mawlouth 
Published: May 2021

Aedes aegypti is the main epidemic vector of arboviruses in Africa. In Senegal, control activities are mainly limited to mitigation of epidemics, with limited information available for Ae. aegypti populations. A better understanding of the current Ae. aegypti susceptibility status to various insecticides and relevant resistance mechanisms involved is needed for the implementation of effective vector control strategies. The present study focuses on the detection of insecticide resistance and reveals the related mechanisms in Ae. aegypti populations from Senegal.
Bioassays were performed on Ae. aegypti adults from nine Senegalese localities (Matam, Louga, Barkedji, Ziguinchor, Mbour, Fatick, Dakar, Kédougou and Touba). Mosquitoes were exposed to four classes of insecticides using the standard WHO protocols. Resistance mechanisms were investigated by genotyping for pyrethroid target site resistance mutations (V1016G, V1016I, F1534C and S989P) and measuring gene expression levels of key detoxification genes (CYP6BB2, CYP9J26, CYP9J28, CYP9J32, CYP9M6, CCEae3a and GSTD4).
All collected populations were resistant to DDT and carbamates except for the ones in Matam (Northern region). Resistance to permethrin was uniformly detected in mosquitoes from all areas. Except for Barkédji and Touba, all populations were characterized by a susceptibility to 0.75% Permethrin. Susceptibility to type II pyrethroids was detected only in the Southern regions (Kédougou and Ziguinchor). All mosquito populations were susceptible to 5% Malathion, but only Kédougou and Matam mosquitoes were susceptible to 0.8% Malathion. All populations were resistant to 0.05% Pirimiphos-methyl, whereas those from Louga, Mbour and Barkédji, also exhibited resistance to 1% Fenitrothion. None of the known target site pyrethroid resistance mutations was present in the mosquito samples included in the genotyping analysis (performed in > 1500 samples). In contrast, a remarkably high (20-70-fold) overexpression of major detoxification genes was observed, suggesting that insecticide resistance is mostly mediated through metabolic mechanisms. These data provide important evidence to support dengue vector control in Senegal.
Improving the continuum of care monitoring in Brazilian HIV healthcare services: An implementation science approach
Authors: Loch Ana Paula , Rocha Simone Queiroz , Fonsi Mylva , de Magalhães Caraciolo Joselita Maria , Kalichman Artur Olhovetchi , de Alencar Souza Rosa , Gianna Maria Clara , Gonçalves Alexandre , Short Duncan , Pimenta Shenia Liane , Bagnola Lea , Wonhnrath Menuzzo Carolina , da Rocha Meireles Zulmira , Natividade Diz Eunice , Zajdenverg Roberto , Prudente Isidoro , Battistella Nemes Maria Ines 
Published: May 2021

Objective
To evaluate the impact of an intervention improving the continuum of care monitoring (CCM) within HIV public healthcare services in São Paulo, Brazil, and implementing a clinical monitoring system. This system identified three patient groups prioritized for additional care engagement: (1) individuals diagnosed with HIV, but not receiving treatment (the treatment gap group); (2) individuals receiving treatment for >6 months with a detectable viral load (the virologic failure group); and (3) patients lost to follow-up (LTFU).

Methods
The implementation strategies included three training sessions, covering system logistics, case discussions, and development of maintenance goals. These strategies were conducted within 30 HIV public healthcare services (May 2019 to April 2020). After each training session, professionals shared their experiences with CCM at regional meetings. Before and after the intervention, providers were invited to answer 23 items from the normalization process theory questionnaire (online) to understand contextual factors. The mean item scores were compared using the Mann–Whitney U test. The RE-AIM implementation science framework (evaluating reach, effectiveness, adoption, implementation, and maintenance) was used to evaluate the integration of the CCM.

Results
In the study, 47 (19.3%) of 243 patients with a treatment gap initiated treatment, 456 (49.1%) of 928 patients with virologic failure achieved suppression, and 700 of 1552 (45.1%) LTFU patients restarted treatment. Strategies for the search and reengagement of patients were developed and shared. Providers recognized the positive effects of CCM on their work and how it modified existing activities (3.7 vs. 4.4, p<0.0001, and 3.9 vs. 4.1, p<0.05); 27 (90%) centers developed plans to sustain routine CCM.

Conclusion
Implementing CCM helped identify patients requiring more intensive attention. This intervention led to changes in providers’ perceptions of CCM and care and management processes, which increased the number of patients engaged across the care continuum and improved outcomes.
The association between the expression of nuclear Yes-associated protein 1 (YAP1) and p53 protein expression profile in breast cancer patients
Authors: Cha Yoon Jin , Kim Dooreh , Bae Soong June , Ahn Sung Gwe , Jeong Joon , Cho Min Kyung , Paik Pill Sun , Yoo Tae-Kyung , Park Woo-Chan , Yoon Chang Ik 
Published: May 2021

BackgroundYes-associated protein 1 (YAP1) is a key effector molecule regulated by the Hippo pathway and described as a poor prognostic factor in breast cancer. Tumor protein 53 (TP53) mutation is well known as a biomarker related to poor survival outcomes. So far clinical characteristics and survival outcome according to YAP1 and TP53 mutation have been poorly identified in breast cancer.Patients and methodsRetrospectively, 533 breast tumor tissues were collected at the Seoul St Mary’s hospital and Gangnam Severance Hospital from 1992 to 2017. Immunohistochemistry with YAP1 and p53 specific antibodies were performed, and the clinical data were analyzed.ResultsMutant p53 pattern was associated with aggressive tumor features and advanced anatomical stage. Inferior overall survival (OS) and recurrence free survival (RFS) were related with mutant p53 pattern cases with low nuclear YAP1 expression (P= 0.0009 andP= 0.0011, respectively). Multivariate analysis showed that mutant p53 pattern was an independent prognostic marker for OS [hazard ratios (HR): 2.938, 95% confidence intervals (CIs): 1.028–8.395, P = 0.044] and RFS (HR: 1.842, 95% CIs: 1.026–3.304). However, in cases with high nuclear YAP1 expression, there were no significantly difference in OS and RFS according to p53 staining pattern.ConclusionWe found that mutant p53 pattern is a poor prognostic biomarker in breast tumor with low nuclear YAP1 expression. Our findings suggest that interaction between nuclear YAP1 and p53 expression pattern impact survival outcomes.
A EMPRESA DE BENEFÍCIOS EM FACE DO DIREITO EMPRESARIAL AMBIENTAL BRASILEIRO
Authors: Fiorillo Celso Antonio Pacheco , Ferreira Renata Marques 
Published: May 2021

Saudada pela mídia italiana, com anúncios entusiásticos, como uma ferramenta que quer reescrever a economia e tendo como principal objetivo permitir a difusão no ordenamento jurídico itálico de empresas que no exercício da sua atividade económica têm também como objetivo a melhoria do ambiente natural e social em que operam, as denominadas empresas de benefícios, ainda que possam representar a primeira disposição da União Europeia para regulamentar este tipo de sociedade e tornar a Itália o país líder na divulgação de sociedades de benefício comum, não revelam, salvo melhor juízo, qualquer contribuição significativa para o direito empresarial ambiental brasileiro. Assim, embora guardando em certa medida compatibilidade com os principais vetores ambientais constitucionais que estruturam todas as empresas no Brasil, conforme demonstrado no presente trabalho, e mesmo representando um interessante avanço em proveito do desenvolvimento sustentável em face do balizamento normativo que sempre condicionou uma empresa tradicional geralmente definida para maximizar tão somente o lucro para os acionistas, as denominadas empresas de benefícios revelam objetivamente tímida contribuição normativa em face de nosso bem elaborado balizamento que condiciona todas as atividades econômicas no plano constitucional.
Global well-posedness of the full compressible Hall-MHD equations
Authors: Tao Qiang , Zhu Canze 
Published: May 2021

Abstract
This paper deals with a Cauchy problem of the full compressible Hall-magnetohydrodynamic flows. We establish the existence and uniqueness of global solution, provided that the initial energy is suitably small but the initial temperature allows large oscillations. In addition, the large time behavior of the global solution is obtained.