bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anticoagulation regimens during pregnancy in patients with mechanical heart valves: a protocol for a systematic review and network meta-analysis
Authors: He Shiwei , Zou Yue , Li Juan , Liu Jumei , Zhao Li , Yang Hua , Su Zhiying , Ye Huiming 
Published: February 2020

IntroductionPregnancy in patients with mechanical heart valves (MHVs) is associated with high maternal complications and fetal complications.Anticoagulation treatments serve to decrease their venous clotting risk. Although some anticoagulation regimens have been used for patients during pregnancy with MHVs, no one is definitively superior among different regimens in recent studies. For a better understanding of the clinical treatment which anticoagulation regimen is more effective and safer during the pregnancy in patients with MHVs, a Bayesian network meta-analysis is necessary.Methods and analysisThis protocol has been reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Related studies until April 2019 will be searched in the following databases: PubMed, Embase,SinoMed and the using the OVID interface to search for evidence-based medicine reviews. A clinical trial registry (www.ClinicalTrials.gov) was also searched for unpublished trials. Both experimental studies (randomised clinical trials) and observational studies (cohort studies, case–control studies and case series studies) will be included in this study. Quality assessment will be conducted using Cochrane Collaboration’s tool or Newcastle-Ottawa Scale based on their study designs. The primary outcomes of interest will be the frequencies of serious maternal and fetal events. The additional outcomes of interest will be adverse maternal events, mode of delivery and adverse fetal events. Pairwise and network meta-analysis will be conducted using R (V.3.4.4, R Foundation for Statistical Computing, Vienna, Austria) and Stata (V.14, StataCorp). The ranking probabilities will be estimated at each possible rank for each anticoagulation regimen using the surface under the cumulative ranking curve. Statistical inconsistency assessment, subgroup analysis, sensitivity analysis and publication bias assessment will be performed.Ethics and disseminationEither ethics approval or patient consent is not necessary, because this study will be based on literature. The results of this study will be published in a peer-reviewed journal.PROSPERO registration numberCRD42019130659
Lipid accumulation product and late-onset hypogonadism in middle-aged and elderly men: results from a cross-sectional study in China
Authors: Sun Kan , Wang Chengzhi , Lao Guojuan , Lin Diaozhu , Huang Chulin , Li Na , Li Lingling , Li Fangping , Xiao Huisheng , Yan Li 
Published: February 2020

ObjectivesHypogonadism in men is related to the deterioration of general health. However, the association between lipid overaccumulation and ageing-related hypogonadism remains an undetermined concept. We aimed to provide an insight into the possible links between the lipid accumulation product (LAP) and late-onset hypogonadism (LOH).SettingSun Yat-sen Memorial Hospital of Sun Yat-sen University.ParticipantsWe included a population sample of 997 subjects aged 40 years or older.Primary and secondary outcome measuresThe LAP was calculated by gender-specific equations using waist circumference (WC) and triglyceride (TG). LOH was defined by the presence of androgen deficiency symptoms and low serum total testosterone levels.ResultsThe prevalence of LOH was 9.4% in this population and gradually increased according to increasing LAP quartiles. Compared with subjects without LOH, ageing men with LOH had higher body mass index, WC, systolic blood pressure, percentage of subjects currently smoking, TG and follicle stimulating hormone and lower low-density lipoprotein cholesterol and sex hormone binding globulin. In multivariate logistic regression analysis, the adjusted ORs of LOH for increasing LAP quartiles 1–4 were 1.00 (reference), 1.10 (95% CI 0.45–2.69), 2.15 (95% CI 0.93–4.94) and 3.83 (95% CI 1.73–8.45), respectively.ConclusionBody lipid accumulation evaluated by the LAP is independently associated with the prevalence of LOH in middle-aged and elderly Chinese men.
Assessing full thickness oral mucosal grafting: complications and postoperative outcomes in a broad collective of patients
Authors: Pilger Daniel , von Sonnleithner Christoph , Bertelmann Eckart 
Published: February 2020

BackgroundConjunctival defects can be repaired with several mucosal tissues. The simplicity of harvesting oral mucosa and its wide availability makes it the preferred graft tissue for all indications requiring mucosal grafting. Through analysing the postsurgical outcomes and rate of revisions, this study explores the suitability of oral mucosa grafts, depending on the initial diagnosis.MethodsWe reviewed all the files of patients with a history of oral mucosal graft surgery, performed at our clinic between 2012 and 2018, focusing on complications and revision rates.ResultsIn total, we analysed 173 oral mucosa grafts in 131 patients. The most common initial diagnosis was tumour resection, followed by surgical complications, postenucleation socket syndrome, trauma and ocular surface disorders. Complication and revision rates depended highly on the initial diagnosis. Revision rates were highest if the initial diagnosis included ocular surface disorders or chemical trauma.ConclusionsOral mucosa grafting (OMG) is the most effective treatment for a wide range of ocular conditions involving conjunctival defects. Conjunctival defects that result from trauma or cicatricial surface diseases seem less suitable for OMG and may benefit from alternative graft tissue or treatment options.
Doing our work better, together: a relationship-based approach to defining the quality improvement agenda in trauma care
Authors: Purdy Eve Isabelle , McLean Darren , Alexander Charlotte , Scott Matthew , Donohue Andrew , Campbell Don , Wullschleger Martin , Berkowitz Gary , Winearls James , Henry Doug , Brazil Victoria 
Published: February 2020

BackgroundTrauma care represents a complex patient journey, requiring multidisciplinary coordinated care. Team members are human, and as such, how they feel about their colleagues and their work affects performance. The challenge for health service leaders is enabling culture that supports high levels of collaboration, co-operation and coordination across diverse groups. We aimed to define and improve relational aspects of trauma care at Gold Coast University Hospital.MethodsWe conducted a mixed-methods collaborative ethnography using the relational coordination survey—an established tool to analyse the relational dimensions of multidisciplinary teamwork—participant observation, interviews and narrative surveys. Findings were presented to clinicians in working groups for further interpretation and to facilitate co-creation of targeted interventions designed to improve team relationships and performance.FindingsWe engaged a complex multidisciplinary network of ~500 care providers dispersed across seven core interdependent clinical disciplines. Initial findings highlighted the importance of relationships in trauma care and opportunities to improve. Narrative survey and ethnographic findings further highlighted the centrality of a translational simulation programme in contributing positively to team culture and relational ties. A range of 16 interventions—focusing on structural, process and relational dimensions—were co-created with participants and are now being implemented and evaluated by various trauma care providers.ConclusionsThrough engagement of clinicians spanning organisational boundaries, relational aspects of care can be measured and directly targeted in a collaborative quality improvement process. We encourage healthcare leaders to consider relationship-based quality improvement strategies, including translational simulation and relational coordination processes, in their efforts to improve care for patients with complex, interdependent journeys.
‘Hospice inpatient deep vein thrombosis detection (HIDDen) in advanced non-malignant diseases’: a longitudinal pilot study
Authors: White Clare , Noble Simon , Swan Flavia , Watson Max , Allgar Victoria , Napier Eoin , Nelson Annmarie , Johnson Miriam J 
Published: February 2020

ObjectivesTo gain preliminary data regarding the prevalence of proximal deep vein thrombosis (DVT) in those with non-malignant conditions admitted to specialist palliative care units (SPCUs).MethodsData were collected as part of a prospective longitudinal observational study in five SPCUs in England, Wales and Northern Ireland (Registration:ISRCTN97567719) to estimate the prevalence of proximal femoral vein DVT in people admitted to SPCUs. The primary outcome for this exploratory substudy was the prevalence of DVT in patients with non-malignant palliative conditions. Consecutive consenting adults underwent bilateral femoral vein ultrasonography within 48 hours of admission. Data were collected on symptoms associated with venous thromboembolism. Patients were ineligible if the estimated prognosis was <5 days. Cross-sectional descriptive analysis was conducted on baseline data and prevalence estimates presented with 95% CIs.Results1390 patients were screened, 28 patients had non-malignant disease and all were recruited. The mean age 68·8 (SD 12·0), range 43–86 years; men 61%; survival mean 86 (SD 108.5) range 1–345 days. No patient had a history of venous thromboembolism. Four (14%) were receiving thromboprophylaxis. Of 22 evaluable scans, 8 (36%, 95% CI: 17% to 59%) showed femoral vein DVT. The level of reported relevant symptoms (leg oedema, leg pain, chest pain and breathlessness) was high irrespective of the presence of DVT.ConclusionsOur exploratory data indicate one in three people admitted to an SPCU with non-malignant disease had a femoral vein DVT. Although definitive conclusions cannot be drawn, these data justify a larger prospective survey.
Placebo response in trials of drug treatments for cancer-related fatigue: a systematic review, meta-analysis and meta-regression
Authors: Roji Rocio , Stone Patrick , Ricciardi Federico , Candy Bridget 
Published: February 2020

BackgroundCancer-related fatigue (CRF) is one of the most distressing symptoms experienced by patients. There is no gold standard treatment, although multiple drugs have been tested with little evidence of efficacy. Randomised controlled trials (RCTs) of these drugs have commented on the existence or size of the placebo response (PR). The objective of this systematic review was to establish the magnitude of the PR in RCTs of drugs to relieve CRF and to identify contributing factors.MethodRCTs were included in which the objective was to treat CRF. A meta-analysis was conducted using the standardised mean change (SMC) between baseline and final measurement in the placebo group. To explore factors that may be associated with the PR (eg, population or drug), a meta-regression was undertaken. Risk of bias was assessed using the revised Cochrane tool.ResultsFrom 3916 citations, 30 relevant RCTs were identified. All had limitations that increased their risk of bias. The pooled SMC in reduction in fatigue status in placebo groups was −0.23 (95% confidence intervals −0.42 to −0.04). None of the variables analysed in the meta-regression were statistically significant related to PR.ConclusionThere is some evidence, based on trials with small samples, that the PR in trials testing drugs for CRF is non-trivial in size and statistically significant. We recommend that researchers planning drug studies in CRF should consider implementing alternative trial designs to better account for PR and decrease impact on the study results.
Evaluation of a temporal causal model for predicting the mood of clients in an online therapy
Authors: Becker Dennis , Bremer Vincent , Funk Burkhardt , Hoogendoorn Mark , Rocha Artur , Riper Heleen 
Published: February 2020

BackgroundSelf-reported client assessments during online treatments enable the development of statistical models for the prediction of client improvement and symptom development. Evaluation of these models is mandatory to ensure their validity.MethodsFor this purpose, we suggest besides a model evaluation based on study data the use of a simulation analysis. The simulation analysis provides insight into the model performance and enables to analyse reasons for a low predictive accuracy. In this study, we evaluate a temporal causal model (TCM) and show that it does not provide reliable predictions of clients’ future mood levels.ResultsBased on the simulation analysis we investigate the potential reasons for the low predictive performance, for example, noisy measurements and sampling frequency. We conclude that the analysed TCM in its current form is not sufficient to describe the underlying psychological processes.ConclusionsThe results demonstrate the importance of model evaluation and the benefit of a simulation analysis. The current manuscript provides practical guidance for conducting model evaluation including simulation analysis.
A cadaveric study of the erector spinae plane block in a neonatal sample
Authors: Govender Sabashnee , Mohr Dwayne , Bosenberg Adrian , Van Schoor Albert Neels 
Published: February 2020

BackgroundThe aim of this article was to provide a detailed description of the neonatal anatomy related to the erector spinae plane block and to report the spread of the dye within the fascial planes and potential dermatomal coverage.MethodsUsing ultrasound guidance, the bony landmarks and anatomy of the erector spinae fascial plane space were identified. The erector spinae plane block was then replicated unilaterally in two fresh unembalmed neonatal cadavers. Using methylene blue dye, the block was performed at vertebral levels T5—using 0.5 mL in cadaver 1—and T8—using 0.2 mL in cadaver 2. The craniocaudal spread of dye was tracked within the space on the ultrasound screen and further confirmed on dissection.ResultsCraniocaudal spread was noted from vertebral levels T3 to T6 when the dye was introduced at vertebral level T5 and from vertebral levels T7 to T11 when the dye was introduced at vertebral level T8. Furthermore, the methylene blue spread was found anteriorly in the paravertebral and epidural spaces, staining both the dorsal and ventral rami of the spinal nerves T2 to T12. Small amounts of dye were also found in the intercostal spaces.ConclusionIn two neonatal fresh cadavers, the dye was found to spread to multiple levels and key anatomic locations.
Skipping Nonsense to Maintain Function: The Paradigm of BRCA2 Exon 12
Authors: Meulemans Laëtitia , Mesman Romy L.S. , Caputo Sandrine M. , Krieger Sophie , Guillaud-Bataille Marine , Caux-Moncoutier Virginie , Léone Mélanie , Boutry-Kryza Nadia , Sokolowska Johanna , Révillion Françoise , Delnatte Capucine , Tubeuf Hélène , Soukarieh Omar , Bonnet-Dorion Françoise , Guibert Virginie , Bronner Myriam , Bourdon Violaine , Lizard Sarab , Vilquin Paul , Privat Maud , Drouet Aurélie , Grout Charlotte , Calléja Fabienne M.G.R. , Golmard Lisa , Vrieling Harry , Stoppa-Lyonnet Dominique , Houdayer Claude , Frebourg Thierry , Vreeswijk Maaike P.G. , Martins Alexandra , Gaildrat Pascaline 
Published: February 2020

Abstract

Germline nonsense and canonical splice site variants identified in disease-causing genes are generally considered as loss-of-function (LoF) alleles and classified as pathogenic. However, a fraction of such variants could maintain function through their impact on RNA splicing. To test this hypothesis, we used the alternatively spliced BRCA2 exon 12 (E12) as a model system because its in-frame skipping leads to a potentially functional protein. All E12 variants corresponding to putative LoF variants or predicted to alter splicing (n = 40) were selected from human variation databases and characterized for their impact on splicing in minigene assays and, when available, in patient lymphoblastoid cell lines. Moreover, a selection of variants was analyzed in a mouse embryonic stem cell–based functional assay. Using these complementary approaches, we demonstrate that a subset of variants, including nonsense variants, induced in-frame E12 skipping through the modification of splice sites or regulatory elements and, consequently, led to an internally deleted but partially functional protein. These data provide evidence, for the first time in a cancer-predisposition gene, that certain presumed null variants can retain function due to their impact on splicing. Further studies are required to estimate cancer risk associated with these hypomorphic variants. More generally, our findings highlight the need to exercise caution in the interpretation of putative LoF variants susceptible to induce in-frame splicing modifications.

Significance:
This study presents evidence that certain presumed loss-of-function variants in a cancer predisposition gene can retain function due to their direct impact on RNA splicing.
Pathologic Complete Response after Neoadjuvant Chemotherapy and Impact on Breast Cancer Recurrence and Survival: A Comprehensive Meta-analysis
Authors: Spring Laura M. , Fell Geoffrey , Arfe Andrea , Sharma Chandni , Greenup Rachel , Reynolds Kerry L. , Smith Barbara L. , Alexander Brian , Moy Beverly , Isakoff Steven J. , Parmigiani Giovanni , Trippa Lorenzo , Bardia Aditya 
Published: February 2020

AbstractPurpose:While various studies have highlighted the prognostic significance of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAT), the impact of additional adjuvant therapy after pCR is not known.Experimental Design:PubMed was searched for studies with NAT for breast cancer and individual patient-level data was extracted for analysis using plot digitizer software. HRs, with 95% probability intervals (PI), measuring the association between pCR and overall survival (OS) or event-free survival (EFS), were estimated using Bayesian piece-wise exponential proportional hazards hierarchical models including pCR as predictor.Results:Overall, 52 of 3,209 publications met inclusion criteria, totaling 27,895 patients. Patients with a pCR after NAT had significantly better EFS (HR = 0.31; 95% PI, 0.24–0.39), particularly for triple-negative (HR = 0.18; 95% PI, 0.10–0.31) and HER2+ (HR = 0.32; 95% PI, 0.21–0.47) disease. Similarly, pCR after NAT was also associated with improved survival (HR = 0.22; 95% PI, 0.15–0.30). The association of pCR with improved EFS was similar among patients who received subsequent adjuvant chemotherapy (HR = 0.36; 95% PI, 0.19–0.67) and those without adjuvant chemotherapy (HR = 0.36; 95% PI, 0.27–0.54), with no significant difference between the two groups (P = 0.60).Conclusions:Achieving pCR following NAT is associated with significantly better EFS and OS, particularly for triple-negative and HER2+ breast cancer. The similar outcomes with or without adjuvant chemotherapy in patients who attain pCR likely reflects tumor biology and systemic clearance of micrometastatic disease, highlighting the potential of escalation/deescalation strategies in the adjuvant setting based on neoadjuvant response.See related commentary by Esserman, p. 2771
Oncogenic KRAS-Driven Metabolic Reprogramming in Pancreatic Cancer Cells Utilizes Cytokines from the Tumor Microenvironment
Authors: Dey Prasenjit , Li Jun , Zhang Jianhua , Chaurasiya Surendra , Strom Anders , Wang Huamin , Liao Wen-Ting , Cavallaro Frederick , Denz Parker , Bernard Vincent , Yen Er-Yen , Genovese Giannicola , Gulhati Pat , Liu Jielin , Chakravarti Deepavali , Deng Pingna , Zhang Tingxin , Carbone Federica , Chang Qing , Ying Haoqiang , Shang Xiaoying , Spring Denise J. , Ghosh Bidyut , Putluri Nagireddy , Maitra Anirban , Wang Y. Alan , DePinho Ronald A. 
Published: February 2020

Abstract

A hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant stroma comprised of diverse cell types that enable or suppress tumor progression. Here, we explored the role of oncogenic KRAS in protumorigenic signaling interactions between cancer cells and host cells. We show that KRAS mutation (KRAS*) drives cell-autonomous expression of type I cytokine receptor complexes (IL2rγ–IL4rα and IL2rγ–IL13rα1) in cancer cells that in turn are capable of receiving cytokine growth signals (IL4 or IL13) provided by invading Th2 cells in the microenvironment. Early neoplastic lesions show close proximity of cancer cells harboring KRAS* and Th2 cells producing IL4 and IL13. Activated IL2rγ–IL4rα and IL2rγ–IL13rα1 receptors signal primarily via JAK1–STAT6. Integrated transcriptomic, chromatin occupancy, and metabolomic studies identified MYC as a direct target of activated STAT6 and that MYC drives glycolysis. Thus, paracrine signaling in the tumor microenvironment plays a key role in the KRAS*-driven metabolic reprogramming of PDAC.

Significance:
Type II cytokines, secreted by Th2 cells in the tumor microenvironment, can stimulate cancer cell–intrinsic MYC transcriptional upregulation to drive glycolysis. This KRAS*-driven heterotypic signaling circuit in the early and advanced tumor microenvironment enables cooperative protumorigenic interactions, providing candidate therapeutic targets in the KRAS* pathway for this intractable disease.
ЕКСПРЕСІЯ ГЕНУ NFATC1 У ДІТЕЙ З ДВОСТУЛКОВИМ АОРТАЛЬНИМ КЛАПАНОМ СЕРЦЯ ЗАЛЕЖНО ВІД НАЯВНОСТІ КЛАПАННОГО ФІБРОЗУ
Authors: Каmеnshchyk A. V. 
Published: February 2020

РЕЗЮМЕ. Двостулковий аортальний клапан (ДАК) є частою вродженою вадою серця, що призводить до розвитку серйозних серцевих ускладнень. Є відомості про протективну роль клітин імунної системи при розвитку фібротичних процесів у міокарді. Гени сімейства нуклеарного фактора активованих Т-клітин (NFATC), регулюючи транскрипційні реакції шляхом активації Ca-залежного шляху кальциневрину, беруть участь як у вальвулогенезі, так і в імунній відповіді.
Мета – визначення величини відносної нормалізованої експресії NFATC1, параметрів клітинного імунітету, рівнів сироваткового кальцію при фіброзі стулок аортального клапана у дітей з ДАК та виявлення взаємозв’язків між зазначеними показниками.
Матеріал і методи. У 40 дітей з ДАК, у 18 з яких мав місце фіброз стулок клапана аорти, визначені параметри кровотоку на клапані, діаметр кореня аорти (Ао) і товщина задньої стінки лівого шлуночка (ЗСЛШ) й міжшлуночкової перегородки (МШП), рівень експресії NFATC1 (expNFATC1) методом екстракції РНК, абсолютний та відносний вміст CD95+ апоптоз регулюючої і CD25+ – активованих інтерлейкін-2 рецепторнесучої субпопуляції лімфоцитів методом моноклональних антитіл, а також сироваткового кальцію (Ca).
Результати. У дітей з ДАК при наявності фіброзу стулок клапана встановлено достовірне підвищення expNFATC1, збільшення Ао, Ca, абсолютного вмісту CD25+, зменшення абсолютного і відносного вмісту CD95+ субпопопуляцій лімфоцитів. Встановлено прямі кореляції між expNFATC1 і Ca, абсолютними значеннями CD25+ і CD95+ Т-клітин, що свідчило про важливу діагностичну роль expNFATC1 при розвитку фіброзу клапана у цієї категорії пацієнтів.