bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term outcomes in pulmonary arterial hypertension by functional class: a meta‐analysis of randomized controlled trials and observational registries
Authors: Kim Nick H. , Fisher Micah , Poch David , Zhao Carol , Shah Mehul , Bartolome Sonja 
Published: June 2020

Limited data about the long‐term prognosis and response to therapy in pulmonary arterial hypertension patients with World Health Organization functional class I/II symptoms are available. PubMed and Embase were searched for publications of observational registries and randomized, controlled trials in pulmonary arterial hypertension patients published between January 2001 and January 2018. Eligible registries enrolled pulmonary arterial hypertension patients ≥18 years, N > 30, and reported survival by functional class. Randomized, controlled trial inclusion criteria were pulmonary arterial hypertension patients ≥18 years, ≥6 months of treatment, and morbidity, mortality, or time to worsening as end points reported by functional class. The primary outcomes were survival for registries and clinical event rates for randomized, controlled trials. Separate random effects models were calculated for registries and randomized, controlled trials. Four randomized, controlled trials (n = 2482) and 10 registries (n = 6580) were included. Registries enrolled 9%–47% functional class I/II patients (the vast majority being functional class II) with various pulmonary arterial hypertension etiologies. Survival rates for functional class I/II patients at one, two, and three years were 93% (95% confidence interval (CI): 91%–95%), 86% (95% CI: 82%–89%), and 78% (95% CI: 73%–83%), respectively. The hazard ratio for the treatment effect in randomized, controlled trials overall was 0.61 (95% CI: 0.51–0.74) and 0.60 (95% CI: 0.44–0.82) for functional class I/II patients and 0.62 (95% CI: 0.49–0.78) for functional class III/IV. The calculated risk of death of 22% within three years for functional class I/II patients underlines the need for careful assessment and optimal treatment of patients with functional class I/II disease. The randomized, controlled trial analysis demonstrates that current medical therapies have a beneficial treatment effect in this population.
Concurrent Prophylactic Mastectomy, Immediate Reconstruction, and Salpingo-Oophorectomy in High-Risk Patients: A Case Series
Authors: D’Abbondanza Josephine A. , George Ralph , Kives Sari , Musgrave Melinda A. 
Published: June 2020

Purpose: There are limited data on coordinated breast and gynecological risk-reduction surgery for high-risk patients in Canada. Therefore, this study aims to evaluate the patient demographics, surgical details, and outcomes of prophylactic mastectomy (PM) with immediate reconstruction and bilateral salpingo-oophorectomy (BSO) in high-risk patients. Methods: We conducted a retrospective chart review at an academic center of patients who concurrently underwent PM with immediate reconstruction and laparoscopic BSO over a 7-year period (March 2010-February 2017) were identified. Results: A total of 16 patients underwent PM with immediate reconstruction and concurrent BSO. The mean age at the time of surgery was 46.2 ± 6.6 years. Thirteen (81%) patients were carriers of the BRCA1 or BRCA2 mutation. Two patients had prophylactic surgical therapy for BRCA1 mutation and 14 (87.5%) patients had prior oncological treatment. The most common type of procedures performed were skin-sparing, nipple-sparing mastectomy (56.2%) and reconstruction with acellular dermal matrix and implants (43.8%). All patients underwent laparoscopic BSO. The average combined case time was 282.5 ± 81.3 minutes with an average postoperative hospital stay of 1.3 ± 0.5 days. Six (37.5%) patients presented with 30-day postoperative complications, with higher rates in the alloplastic group. There were no gynecological complications. Conclusions: In conclusion, our results demonstrate that a combined multidisciplinary surgical approach did not increase length of stay or 30-day complication rates. Furthermore, concurrent risk-reducing strategies are an effective option for patients at high risk of breast or ovarian cancer.
Time to Laryngoscopy for Hoarseness in Canada: Are the American Academy of Otolaryngology Guidelines Feasible?
Authors: Howlett Joel , Singer Joel , Lee Terry , Hu Amanda 
Published: June 2020

ObjectivesTo determine if a Canadian voice center is meeting the recommended time to laryngoscopy for hoarseness per the clinical practice guideline of the American Academy of Otolaryngology–Head and Neck Surgery.Study DesignRetrospective chart audit.SettingTertiary referral Canadian voice center.Participants and MethodsA total of 149 adult patients presenting with hoarseness over 6 months were included. Primary outcome measures were the time from onset of symptoms to laryngoscopy and the time from referral to laryngoscopy. Secondary outcome measures included patient‐ and disease‐modifying factors, diagnosis, and clinical management. Analysis was performed to determine what factors were associated with meeting the guideline.ResultsPatients were evaluated by the laryngologist after 21.9 ± 37.6 months (mean ± SD) of symptoms. One‐third (34.2%) of patients were seen within 3 months; 10.7% were seen within 4 weeks. Logistic regression showed that patients with neurologic symptoms (odds ratio, 4.04; 95% CI, 1.31‐12.43; P =. 015) and endotracheal intubation (odds ratio, 5.94; 95% CI, 2.21‐15.95; P <. 001) were associated with being seen within 3 months. Patients who had recent intubation (odds ratio, 6.04; 95% CI, 1.99‐18.34; P =. 002) were associated with being seen within 4 weeks.ConclusionIt is an ongoing challenge for our Canadian voice center to meet the American Academy of Otolaryngology–Head and Neck Surgery’s clinical practice guideline for recommended time to laryngoscopy. Patients with more severe pathologies were consistently triaged more urgently. It is debatable whether this 4‐week time recommendation is generalizable to a socialized health care system.
Origins and characterization of variants shared between databases of somatic and germline human mutations
Authors: Meyerson William , Leisman John , Navarro Fabio C. P. , Gerstein Mark 
Published: June 2020

Abstract
Background
Mutations arise in the human genome in two major settings: the germline and the soma. These settings involve different inheritance patterns, time scales, chromatin structures, and environmental exposures, all of which impact the resulting distribution of substitutions. Nonetheless, many of the same single nucleotide variants (SNVs) are shared between germline and somatic mutation databases, such as between the gnomAD database of 120,000 germline exomes and the TCGA database of 10,000 somatic exomes. Here, we sought to explain this overlap.

Results
After strict filtering to exclude common germline polymorphisms and sites with poor coverage or mappability, we found 336,987 variants shared between the somatic and germline databases. A uniform statistical model explains 34% of these shared variants; a model that incorporates the varying mutation rates of the basic mutation types explains another 50% of shared variants; and a model that includes extended nucleotide contexts (e.g. surrounding 3 bases on either side) explains an additional 4% of shared variants. Analysis of read depth finds mixed evidence that up to 4% of the shared variants may represent germline variants leaked into somatic call sets. 9% of the shared variants are not explained by any model. Sequencing errors and convergent evolution did not account for these. We surveyed other factors as well: Cancers driven by endogenous mutational processes share a greater fraction of variants with the germline, and recently derived germline variants were more likely to be somatically shared than were ancient germline ones.

Conclusions
Overall, we find that shared variants largely represent bona fide biological occurrences of the same variant in the germline and somatic setting and arise primarily because DNA has some of the same basic chemical vulnerabilities in either setting. Moreover, we find mixed evidence that somatic call-sets leak appreciable numbers of germline variants, which is relevant to genomic privacy regulations. In future studies, the similar chemical vulnerability of DNA between the somatic and germline settings might be used to help identify disease-related genes by guiding the development of background-mutation models that are informed by both somatic and germline patterns of variation.
Stress cardiomyopathy associated with the first manifestation of multiple sclerosis: a case report
Authors: Rapp Daniel , Keßler Mirjam , Pinkhardt Elmar , Otto Markus , Tumani Hayrettin , Senel Makbule 
Published: June 2020

Abstract
Background
We present a case with a close temporal association of the first diagnosis of multiple sclerosis and stress cardiomyopathy.

Case presentation
A 19-year-old man experienced severe dyspnoea. The cardiac biomarkers troponin T and NT-proBNP were elevated, and transthoracic echocardiography showed basal hypokinesia. The man was diagnosed with stress cardiomyopathy after main differential diagnoses such as acute coronary syndrome, myocarditis, and pheochromocytoma were excluded. Furthermore, the patient reported vertigo and paraesthesia. Brain and spinal MRI revealed T2-hyperintense lesions with a prominent acute lesion in the pontomedullary area. Cerebrospinal fluid findings revealed a lymphocytic pleocytosis and intrathecal IgG synthesis. Serum neurofilaments were elevated. The patient was diagnosed with MS, and treatment with intravenous Methylprednisolone was initiated. The brainstem lesion due to multiple sclerosis was assumed to be the cause of stress cardiomyopathy. The patient fully recovered.

Conclusion
Stress cardiomyopathy may be linked with the first manifestation of multiple sclerosis in the presented case since pontomedullary lesions could affect the sympathetic nervous system. This case highlights the importance of neurological history and examination in young patients with unexplained acute cardiac complaints.
Risk estimation of the SARS-CoV-2 acute respiratory disease outbreak outside China
Authors: Kim Soyoung , Choi Sunhwa , Ko Youngsuk , Ki Moran , Jung Eunok 
Published: June 2020

Abstract
Background
On December 31, 2019, the World Health Organization was alerted to the occurrence of cases of pneumonia in Wuhan, Hubei Province, China, that were caused by an unknown virus, which was later identified as a coronavirus and named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to estimate the reproductive number of SARS-CoV-2 in the Hubei Province and evaluate the risk of an acute respiratory coronavirus disease (COVID-19) outbreak outside China by using a mathematical model and stochastic simulations.

Results
We constructed a mathematical model of SARS-CoV-2 transmission dynamics, estimated the rate of transmission, and calculated the reproductive number in Hubei Province by using case-report data from January 11 to February 6, 2020. The possible number of secondary cases outside China was estimated by stochastic simulations in various scenarios of reductions in the duration to quarantine and rate of transmission. The rate of transmission was estimated as 0.8238 (95% confidence interval [CI] 0.8095–0.8382), and the basic reproductive number as 4.1192 (95% CI 4.0473–4.1912). Assuming the same rate of transmission as in Hubei Province, the possibility of no local transmission is 54.9% with a 24-h quarantine strategy, and the possibility of more than 20 local transmission cases is 7% outside of China.

Conclusion
The reproductive number for SARS-CoV-2 transmission dynamics is significantly higher compared to that of the previous SARS epidemic in China. This implies that human-to-human transmission is a significant factor for contagion in Hubei Province. Results of the stochastic simulation emphasize the role of quarantine implementation, which is critical to prevent and control the SARS-CoV-2 outbreak outside China.
Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas
Authors: Choi Euno , Chang Mee Soo , Byeon Sun-ju , Jin Heejin , Jung Kyeong Cheon , Kim Haeryoung , Lee Kook Lae , Kim Won , Park Jin Hyun , Kim Ki Hwan , Kim Jin-Soo , Choi In Sil , Han Dong-Seok , Ahn Hye Seong , Heo Seung Chul 
Published: June 2020

Abstract
Background
The prognostic potential of PD-L1 is currently unclear in gastric carcinomas, although the immune checkpoint PD-1/PD-L1 inhibitors have produced promising results in clinical trials.

Methods
We explored the prognostic implications of programmed death ligand 1 (PD-L1) in 514 consecutive surgically-resected gastric carcinomas. Overall survival and recurrence-free survival were evaluated. Immunohistochemistry for PD-L1, CD8, FOXP3, and PD-1, and molecular grouping by in situ hybridization for Epstein-Barr virus (EBV)-encoded small RNAs and multiplex PCR for microsatellite instability (MSI) markers were performed. Additionally, to explore the function inherent to PD-L1, PD-L1-specific siRNA transfection, cell proliferation, invasion, migration and apoptosis assays were conducted in five gastric carcinoma cell lines.

Results
PD-L1(+) tumor and immune cells were observed in 101 (20%) and 244 patients (47%), respectively. “Tumoral PD-L1(+)/immune cell PD-L1(-)/CD8+/low tumor-infiltrating lymphocytes (TILs),” and more advanced-stage tumors were associated with unfavorable clinical outcomes in the entire cohort through multivariate analysis. Furthermore, tumoral PD-L1(+)/FOXP3+/low TILs were associated with worse clinical outcomes in EBV-positive and MSI-high carcinomas. Tumoral PD-L1(+) alone was an adverse prognostic factor in EBV-positive carcinomas, but not in MSI-high carcinomas, whereas PD-L1(+) immune cells or FOXP3+/high TILs alone were correlated with a favorable prognosis. PD-L1 knockdown in gastric carcinoma cells suppressed cell proliferation, invasion and migration, and increased apoptosis, which were all statistically significant in two EBV(+) cell lines, but not all in three EBV(−) cell lines.

Conclusions
The prognostic impact of PD-L1 may depend on the tumor microenvironment, and statuses of EBV and MSI, although PD-L1 innately promotes cancer cell survival in cell-based assays. The combination of “tumoral PD-L1/immune cell PD-L1/CD8+ TILs” may serve as an independent prognostic factor. Tumoral PD-L1(+)/immune cell PD-L1(−)/CD8+/low TILs showing a worse prognosis may be beneficial for combinatorial therapies of anti-PD-L1/PD-1 and anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA4) that would promote effector T cells, thus attack the tumor.
Are our babies off to a healthy start? The state of implementation of the Global strategy for infant and young child feeding in Europe
Authors: Zakarija-Grković Irena , Cattaneo Adriano , Bettinelli Maria Enrica , Pilato Claudia , Vassallo Charlene , Borg Buontempo Mariella , Gray Helen , Meynell Clare , Wise Patricia , Harutyunyan Susanna , Rosin Stefanie , Hemmelmayr Andrea , Šniukaitė-Adner Daiva , Arendt Maryse , Gupta Arun 
Published: June 2020

Abstract
Background
To protect children’s right to optimal nutrition, WHO/UNICEF developed a Global Strategy for Infant and Young Child Feeding, endorsed by all 53 WHO/EURO Member States. The World Breastfeeding Trends Initiative (WBTi) is a tool for monitoring implementation of the Global Strategy. It comprises 15 indicators, ten referring to policies and programmes, and five to feeding practices. Each is scored on a scale of 10, giving a total score of 150 for Global Strategy implementation. To date, 18 WHO/EURO Member States – Armenia, Austria, Belgium, Bosnia and Herzegovina, Croatia, France, Georgia, Germany, Italy, Lithuania, North Macedonia, Malta, Moldova, Portugal, Spain, Turkey, Ukraine and United Kingdom – have conducted a WBTi assessment and produced a report.

Methods
Between June 2018 and May 2019, all 18 WBTi European reports were carefully read and analysed by a group of national WBTi coordinators. Descriptive data analysis, including inter-country comparisons, was conducted using frequencies and percentages. This paper summarises the findings. The full 88-page report will be published on the WBTi website.

Results
Three-quarters of 18 European countries have adequate maternity protection, and two-thirds have breastfeeding initiation rates of 50% or higher. However, ‘Preparedness and planning for appropriate and safe Infant and Young Child Feeding (IYCF) in emergencies’ is seriously neglected. Breastfeeding duration is far below WHO recommendations, with an average of 8.7 months. Only three European countries have a budget allocated for implementing IYCF policies and plans, and a third currently have no Baby-friendly designated maternity facilities. Bottle feeding is prevalent, despite its inherent risks, monitoring of IYCF practices is inadequate, with most countries not routinely collecting data, and violations of the International Code of Marketing of Breast-milk Substitutes are commonplace.

Conclusions
European governments are not doing enough to protect, promote and support sound infant and young child feeding practices. Political commitment at the highest level and adequate funding are required to ensure optimal IYCF for Europe’s babies. This report highlights worrying gaps, thereby providing governments, international organisations and other concerned parties with an opportunity to invest in priority areas and, by doing so, hopefully create a better future for our babies.
Digital tools for the recruitment and retention of participants in randomised controlled trials: a systematic map
Authors: Frampton Geoff K. , Shepherd Jonathan , Pickett Karen , Griffiths Gareth , Wyatt Jeremy C. 
Published: June 2020

Abstract
Background
Recruiting and retaining participants in randomised controlled trials (RCTs) is challenging. Digital tools, such as social media, data mining, email or text-messaging, could improve recruitment or retention, but an overview of this research area is lacking. We aimed to systematically map the characteristics of digital recruitment and retention tools for RCTs, and the features of the comparative studies that have evaluated the effectiveness of these tools during the past 10 years.

Methods
We searched Medline, Embase, other databases, the Internet, and relevant web sites in July 2018 to identify comparative studies of digital tools for recruiting and/or retaining participants in health RCTs. Two reviewers independently screened references against protocol-specified eligibility criteria. Included studies were coded by one reviewer with 20% checked by a second reviewer, using pre-defined keywords to describe characteristics of the studies, populations and digital tools evaluated.

Results
We identified 9163 potentially relevant references, of which 104 articles reporting 105 comparative studies were included in the systematic map. The number of published studies on digital tools has doubled in the past decade, but most studies evaluated digital tools for recruitment rather than retention. The key health areas investigated were health promotion, cancers, circulatory system diseases and mental health. Few studies focussed on minority or under-served populations, and most studies were observational. The most frequently-studied digital tools were social media, Internet sites, email and tv/radio for recruitment; and email and text-messaging for retention. One quarter of the studies measured efficiency (cost per recruited or retained participant) but few studies have evaluated people’s attitudes towards the use of digital tools.

Conclusions
This systematic map highlights a number of evidence gaps and may help stakeholders to identify and prioritise further research needs. In particular, there is a need for rigorous research on the efficiency of the digital tools and their impact on RCT participants and investigators, perhaps as studies-within-a-trial (SWAT) research. There is also a need for research into how digital tools may improve participant retention in RCTs which is currently underrepresented relative to recruitment research.

Registration
Not registered; based on a pre-specified protocol, peer-reviewed by the project’s Advisory Board.
Nodular pulmonary deposition disease in a patient with the acquired immunodeficiency syndrome: a case report
Authors: Mezzanotte Jessica N. , Gibbons-Fideler I-Sanna , Shilo Konstantin , Lustberg Mark , Devarakonda Srinivas 
Published: June 2020

Abstract
Background
Pulmonary nodules are a common cause for concern in patients with human immunodeficiency virus and acquired immunodeficiency syndrome. Most commonly, they are the result of an infection, given the patients’ immunocompromised state; however, in some cases, pulmonary nodules in patients with human immunodeficiency virus and patients with acquired immunodeficiency syndrome can result from cellular or protein deposits. We report a rare case of nodular pulmonary light chain deposition disease in a patient with acquired immunodeficiency syndrome and monoclonal gammopathy of undetermined significance.

Case presentation
A 53-year-old African American woman with acquired immunodeficiency syndrome had pulmonary nodules detected incidentally by imaging of her lungs. Pulmonary tuberculosis was high on the differential diagnosis, but she had a negative test result for pulmonary tuberculosis. Imaging also revealed multiple lucent bone lesions, and earlier in the year, serum protein electrophoresis had shown an immunoglobulin G-kappa monoclonal protein (M spike). She was mildly anemic, so there was concern for progression to myeloma; however, the result of her bone marrow biopsy was unremarkable. Lung biopsy revealed finely granular eosinophilic material with negative Congo red staining, consistent with light chain deposition disease.

Conclusions
The extent of this patient’s light chain deposition disease was thought to be caused by a combination of acquired immunodeficiency syndrome and monoclonal gammopathy of undetermined significance, and the interval decrease in lung nodule size after restarting antiretroviral therapy confirms this hypothesis and also highlights a potentially unique contribution of the hypergammaglobulinemia to this disease process in patients with human immunodeficiency virus and patients with acquired immunodeficiency syndrome .