bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vulvar myeloid sarcoma as the presenting symptom of acute myeloid leukemia: a case report and literature review of Chinese patients, 1999–2018
Authors: Zhang Xilin , Huang Peichen , Chen Zhuo , Bi Xinling , Wang Ying , Wu Jianhua 
Published: November 2019

AbstractBackgroundMyeloid sarcoma (MS), which represents a rare malignancy that comprises of myeloid blasts occurring at extra-medullary sites, closely correlates with the onset and relapse of acute myeloid leukemia (AML) and other hemopoietic neoplasm. Female genital system is an uncommon location of MS, with the vulvar MS being even rarer that only eight cases have been reported in English-written literature.Case presentationA 47-year-old woman presented with chronic ulceration on her vulva for one and a half month. Microscopic examination of incisional biopsy revealed dermal infiltration of myeloid precursor cells, which were positive for MPO, lysozyme, CD43, CD68, CD38 and CD117. Bone marrow flowcytometric analysis showed myeloblast count of 74%, which expressed CD13, CD33, CD117 and HLA-DR. A diagnosis of AML (M2 type) was made and vulvar MS was the earliest symptom. The patient achieved complete remission after chemotherapy with no evidence of recurrence in a 27-month follow-up. We reviewed the literature and identified 54 cases of Chinese patients with gynecological MS between 1999 and 2018, and discovered that in Chinese population, MS most frequently involved uterine cervix followed by the ovary and vulva, and ovarian MS onset much earlier than other sites. Remarkably, vulvar MS exhibited a high rate of concurrent AML and secondary myeloid leukemia within a short time of its occurrence. Despite its limited distribution, MS should be tackled aggressively with chemotherapy followed by allogeneic hematopoietic stem cell transplantation if the appropriate donor is available.ConclusionsFemale genital MS, especially vulvar MS, should be included in the differential diagnosis of gynecological neoplasm, which will facilitate its early diagnosis and prompt management.
Comparison of the outcomes of stereotactic body radiotherapy versus surgical treatment for elderly (≥70) patients with early-stage non-small cell lung cancer after propensity score matching
Authors: Dong Baiqiang , Wang Jin , Zhu Xuan , Chen Yuanyuan , Xu Yujin , Shao Kainan , Zheng Lei , Ying Hangjie , Chen Ming , Cao Jianping 
Published: November 2019

Abstract

Background
The optimal treatment for elderly patients with early-stage non-small cell lung cancer (NSCLC) remains inconclusive. Previous studies have shown that stereotactic body radiotherapy (SBRT) provides encouraging local control though higher incidence of toxicity in elderly than younger populations. The objective of this study was to compare the outcomes of SBRT and surgical treatment in elderly patients with clinical stage I-II NSCLC.

Methods
This retrospective analysis included 205 patients aged ≥70 years with clinical stage I NSCLC who underwent SBRT or surgery at Zhejiang Cancer Hospital (Hangzhou, China) from January 2012 to December 2017. A propensity score matching analysis was performed between the two groups. In addition, we compared outcomes and related toxicity in both study arms.

Results
Each group included 35 patients who met the inclusion criteria. Median follow-up was 50.1 (0.8–74.4) months for surgery and 35.5 (11.5–71.4) months for SBRT. The rate of cancer-specific survival was similar between the two treatment arms (p = 0.958). In patients who underwent surgery, the corresponding 3- and 5-year cancer-specific survival rates were 85.3 and 81.7%, respectively. In those who received radiotherapy, these rates were 91.3 and 74.9%, respectively. Moreover, the 3- and 5-year locoregional control in patients who underwent surgery were 90.0 and 80.0%, respectively. In those who received radiotherapy, these rates were 91.1 and 84.1%, respectively. Notably, the observed differences in progression-free survival were not statistically significant (p = 0.934). In the surgery group, grade 1–2 complications were observed in eleven patients (31%). One patient died due to perioperative infection within 30 days following surgery. There was no grade 3–5 toxicity observed in the SBRT group.

Conclusions
The outcomes of surgery and SBRT in elderly patients with early-stage NSCLC were similar.
The impact of mild renal dysfunction on isolated cardiopulmonary coronary artery bypass grafting: a retrospective propensity score matching analysis
Authors: Wang Xian , Zhu Yifan , Chen Wen , Li Liangpeng , Chen Xin , Wang Rui 
Published: November 2019

Abstract

Background
Mild preoperative renal dysfunction (RD) is not rare in patients receiving isolated cardiopulmonary coronary artery bypass grafting (CCABG). However, there are not too many studies about the impact of mild preoperative RD on in-hospital and follow-up outcomes after isolated CCABG. This single-centre, retrospective propensity score matching study designed to study the impact of mild preoperative RD on in-hospital and long-term outcomes after first isolated CCABG.

Methods
After propensity score matching, 1144 patients with preoperative estimated glomerular filtration rate (eGFR) of more than 60 ml/min/1.73 m2 receiving first isolated CCABG surgery from January 2012 to December 2015 entered the study, who were divided into 2 groups: A group (eGFR ≥90 ml/min/1.73 m2, n = 572) and B group (eGFR of 60–89 ml/min/1.73 m2, n = 572). The in-hospital and long-term outcomes were recorded and analyzed. The mean follow-up time was 54.4 ± 10.7 months. Acute kidney injury (AKI) was defined and classified according to the Acute Kidney Injury Network (AKIN) criteria.

Results
The 2 propensity score-matched groups had similar baseline and procedure except the baseline eGFR. There were 8 patients died in A group (mortality is 1.4%) and 14 died in B group (mortality is 2.5%) during the in hospital and 30-day postoperatively(χ2 = 1.159, p = 0.282). There were totally 38 patients lost to follow-up, 18 in group A and 20 in group B. 21 patients died in group A and 37 died in group B during the follow-up, and long-term survival in group A was higher than in group B (96.2% vs 93.1%, χ2 = 4.336, p = 0.037). Comparing with group A, group B was associated with an increased rates and severity of AKI postoperatively (total AKI: 62 vs 144. AKIN stageI: 54 vs 113; AKIN stageII: 6 vs 22; AKIN stageIII: 2 vs 9, p<0.0001). During follow-up, group B also had a higher rate of new onset of dialysis (0 vs 6, χ2 = 4.432, p = 0.039). Multivariable logistic regression showed that comparing with A group, the HR for long-term mortality and new onset of dialysis in B group was 1.67 and 1.52 respectively (95%CI 1.09–2.90, p = 0.035; 95%CI 1.14–2.49, p = 0.027).

Conclusions
Comparing with normal preoperative renal function, patients with mild preoperative RD had a similar in-hosptial mortality, but with an increased in-hosptial rates and severity of AKI, and with a decreased long-term survival and increased long-term new onset of dialysis.
Untypical autoimmune pancreatitis and pancreatic cancer: differential diagnosis experiences extracted from misdiagnose of two cases
Authors: Li Gaopeng , Liu Ting , Zheng Jian , Kang Wenqin , Xu Jun , Gao Zefeng , Ma Jinfeng 
Published: November 2019

Abstract

Background
Differentiation between pancreatic cancer (PC) and focal form of autoimmune pancreatitis (AIP) is very challenging, with similar clinical presentations, laboratory results and morphologic imagings of US, CT, EUS, MRI, ERCP, PET-CT. Even serum IgG4 and biopsy sometimes cannot give clear-cut differential accurate diagnostis. Considering the totally different management strategy of the two diseases, accurate diagnostic value is urgently needed to remind the clinicians of the rare diagnosis of untypical AIP among frequent PC-suspected patients.

Results
We present 2 laparotomy cases of AIP that had a high similar characteristic to PC and retrospectively extracted the warning signs that may help select untypical AIP in PC-suspected patients.

Conclusions
We find that mild fluctuating jaundice with abdominal pain, young age, tumor marker of TPS, TPA and diverse results between variable radiological tests can help to differentiate AIP mass from PC, through retrospectively analyzing work-up process of AIP in two patients who underwent laparotomy for suspected PC.
NOTCH2 negatively regulates metastasis and epithelial-Mesenchymal transition via TRAF6/AKT in nasopharyngeal carcinoma
Authors: Zou You , Yang Rui , Huang Mao-Ling , Kong Yong-Gang , Sheng Jian-Fei , Tao Ze-Zhang , Gao Ling , Chen Shi-Ming 
Published: November 2019

AbstractBackgroundClinically, distant metastasis after primary treatment remains a key problem in nasopharyngeal carcinoma (NPC). Thus, identification of the underlying mechanisms and development of novel therapeutic strategies are urgently needed. NOTCH has been shown to function as a tumor promotor that enhances angiogenesis, cancer invasion and metastasis in NPC. However, the precise roles of the four individual NOTCH receptors and their mechanisms of action are unclear.MethodsWe used Western blot analysis, immunofluorescence, immunohistochemical analysis, phalloidin staining, mouse tumor metastatic dissemination models, gene set enrichment analysis, immunoprecipitation assays and a series of functional assays to determine the potential role of NOTCH2 in regulating NPC metastasis.ResultsNOTCH2 expression in the NPC tissues of patients with cervical lymph node metastasis was lower than that of patients without cervical lymph node metastasis. Correspondingly, NOTCH2 expression was low in metastatic and poorly differentiated NPC cells. NOTCH2 expression correlated negatively with survival time in patients with NPC. Suppression of NOTCH2 expression promoted NPC cell metastasis, whereas NOTCH2 overexpression inhibited this process. Furthermore, NOTCH2 attenuated the TRAF6–AKT signaling axis via an interaction between the NOTCH2 intracellular domain (N2ICD) and TRAF6, which inhibited epithelial–mesenchymal transition (EMT) and eventually suppressed NPC metastasis.ConclusionsThese findings reveal that loss of NOTCH2 activates the TRAF6/AKT axis and promotes metastasis in NPC, suggesting that NOTCH2 may represent a therapeutic target for the treatment of NPC.
Causes of brain dysfunction in acute coma: a cohort study of 1027 patients in the emergency department
Authors: Schmidt Wolf Ulrich , Ploner Christoph J. , Lutz Maximilian , Möckel Martin , Lindner Tobias , Braun Mischa 
Published: November 2019

Abstract

Background
Coma of unknown etiology (CUE) is a major challenge in emergency medicine. CUE is caused by a wide variety of pathologies that require immediate and targeted treatment. However, there is little empirical data guiding rational and efficient management of CUE. We present a detailed investigation on the causes of CUE in patients presenting to the ED of a university hospital.

Methods
One thousand twenty-seven consecutive ED patients with CUE were enrolled. Applying a retrospective observational study design, we analyzed all clinical, laboratory and imaging findings resulting from a standardized emergency work-up of each patient. Following a predefined protocol, we identified main and accessory coma-explaining pathologies and related these with (i.a.) GCS and in-hospital mortality.

Results
On admission, 854 of the 1027 patients presented with persistent CUE. Their main diagnoses were classified into acute primary brain lesions (39%), primary brain pathologies without acute lesions (25%) and pathologies that affected the brain secondarily (36%). In-hospital mortality associated with persistent CUE amounted to 25%. 33% of patients with persistent CUE presented with more than one coma-explaining pathology. In 173 of the 1027 patients, CUE had already resolved on admission. However, these patients showed a spectrum of main diagnoses similar to persistent CUE and a significant in-hospital mortality of 5%.

Conclusion
The data from our cohort show that the spectrum of conditions underlying CUE is broad and may include a surprisingly high number of coincidences of multiple coma-explaining pathologies. This finding has not been reported so far. Thus, significant pathologies may be masked by initial findings and only appear at the end of the diagnostic work-up. Furthermore, even transient CUE showed a significant mortality, thus rendering GCS cutoffs for selection of high- and low-risk patients questionable. Taken together, our data advocate for a standardized diagnostic work-up that should be triggered by the emergency symptom CUE and not by any suspected diagnosis. This standardized routine should always be completed - even when initial coma-explaining diagnoses may seem evident.
RNA sequencing of identical twins discordant for autism reveals blood-based signatures implicating immune and transcriptional dysregulation
Authors: Saffari Ayden , Arno Matt , Nasser Eric , Ronald Angelica , Wong Chloe C. Y. , Schalkwyk Leonard C. , Mill Jonathan , Dudbridge Frank , Meaburn Emma L. 
Published: November 2019

Abstract

Background
A gap exists in our mechanistic understanding of how genetic and environmental risk factors converge at the molecular level to result in the emergence of autism symptoms. We compared blood-based gene expression signatures in identical twins concordant and discordant for autism spectrum condition (ASC) to differentiate genetic and environmentally driven transcription differences, and establish convergent evidence for biological mechanisms involved in ASC.

Methods
Genome-wide gene expression data were generated using RNA-seq on whole blood samples taken from 16 pairs of monozygotic (MZ) twins and seven twin pair members (39 individuals in total), who had been assessed for ASC and autism traits at age 12. Differential expression (DE) analyses were performed between (a) affected and unaffected subjects (N = 36) and (b) within discordant ASC MZ twin pairs (total N = 11) to identify environmental-driven DE. Gene set enrichment and pathway testing was performed on DE gene lists. Finally, an integrative analysis using DNA methylation data aimed to identify genes with consistent evidence for altered regulation in cis.

Results
In the discordant twin analysis, three genes showed evidence for DE at FDR < 10%: IGHG4, EVI2A and SNORD15B. In the case-control analysis, four DE genes were identified at FDR < 10% including IGHG4, PRR13P5, DEPDC1B, and ZNF501. We find enrichment for DE of genes curated in the SFARI human gene database. Pathways showing evidence of enrichment included those related to immune cell signalling and immune response, transcriptional control and cell cycle/proliferation. Integrative methylomic and transcriptomic analysis identified a number of genes showing suggestive evidence for cis dysregulation.

Limitations
Identical twins stably discordant for ASC are rare, and as such the sample size was limited and constrained to the use of peripheral blood tissue for transcriptomic and methylomic profiling. Given these primary limitations, we focused on transcript-level analysis.

Conclusions
Using a cohort of ASC discordant and concordant MZ twins, we add to the growing body of transcriptomic-based evidence for an immune-based component in the molecular aetiology of ASC. Whilst the sample size was limited, the study demonstrates the utility of the discordant MZ twin design combined with multi-omics integration for maximising the potential to identify disease-associated molecular signals.
A multiple classifier system identifies novel cannabinoid CB2 receptor ligands
Authors: Ruano-Ordás David , Burggraaff Lindsey , Liu Rongfang , van der Horst Cas , Heitman Laura H. , Emmerich Michael T. M. , Mendez Jose R. , Yevseyeva Iryna , van Westen Gerard J. P. 
Published: November 2019

Abstract
Drugs have become an essential part of our lives due to their ability to improve people’s health and quality of life. However, for many diseases, approved drugs are not yet available or existing drugs have undesirable side effects, making the pharmaceutical industry strive to discover new drugs and active compounds. The development of drugs is an expensive process, which typically starts with the detection of candidate molecules (screening) after a protein target has been identified. To this end, the use of high-performance screening techniques has become a critical issue in order to palliate the high costs. Therefore, the popularity of computer-based screening (often called virtual screening or in silico screening) has rapidly increased during the last decade. A wide variety of Machine Learning (ML) techniques has been used in conjunction with chemical structure and physicochemical properties for screening purposes including (i) simple classifiers, (ii) ensemble methods, and more recently (iii) Multiple Classifier Systems (MCS). Here, we apply an MCS for virtual screening (D2-MCS) using circular fingerprints. We applied our technique to a dataset of cannabinoid CB2 ligands obtained from the ChEMBL database. The HTS collection of Enamine (1,834,362 compounds), was virtually screened to identify 48,232 potential active molecules using D2-MCS. Identified molecules were ranked to select 21 promising novel compounds for in vitro evaluation. Experimental validation confirmed six highly active hits (> 50% displacement at 10 µM and subsequent Ki determination) and an additional five medium active hits (> 25% displacement at 10 µM). Hence, D2-MCS provided a hit rate of 29% for highly active compounds and an overall hit rate of 52%.
Health shock and preference instability: assessing health-state dependency of willingness-to-pay for corrective eyeglasses
Authors: Islam Muhammed Nazmul , Rabbani Atonu , Sarker Malabika 
Published: November 2019

AbstractBackgroundDifferences in contingent valuation (CV) estimates for identical healthcare goods can cast considerable doubt on the true economic measures of consumer preferences. Hypothetical nature of CV methods can potentially depend on the salience, context and perceived relevance of the good or service under consideration. Thus, the high demand elasticity for healthcare goods warrants careful selection of study population as the contexts of valuation significantly changes after experiencing health shock.MethodsIn this study, using triple-bounded dichotomous choice (TBDC) experiments, we test how negative health shock (namely, being diagnosed with refractive errors), can alter preference over a common health good (namely, corrective eyeglasses). We compared elicited WTP of diagnosed patients with a synthetically constructed comparable cohort without the same health shock, controlling for the possible self-selection using a number of matching techniques based on the observable socio-demographic characteristics.ResultsThe consumers diagnosed with vision problems exhibit a rightward shift in their demand curve compared to observationally identical consumers without such problems resulting in about 17% higher consumer surplus. The consumers without the health shock are willing to pay about BDT 762.4 [95% CI: BDT 709.9 - BDT 814.9] for corrective eyeglasses, which gets 15–30% higher for the matched with-health-shock consumers. Multivariable analyses suggest more educated and wealthier individuals are willing to pay respectively BDT 208 and BDT 119 more for corrective eyeglasses. We have tested the models for different matching protocols. Our results are fairly robust to alternate specifications and various matching techniques.ConclusionThe preferences for healthcare goods, such as eyeglasses, can significantly depend upon the respondent being diagnosed with refractive errors. Our findings have implications for general cost-benefit analyses often relying on WTP, which can vary depending on the contexts. There are also increasing interests in cost recovery models, which require understanding the demand for healthcare goods and services. We find eliciting the demand needs to consider the health status of the population from which the respondents are sampled.
Systematic review of the use of process evaluations in knowledge translation research
Authors: Scott Shannon D. , Rotter Thomas , Flynn Rachel , Brooks Hannah M. , Plesuk Tabatha , Bannar-Martin Katherine H. , Chambers Thane , Hartling Lisa 
Published: November 2019

Abstract

Background
Experimental designs for evaluating knowledge translation (KT) interventions can provide strong estimates of effectiveness but offer limited insight into how the intervention worked. Consequently, process evaluations have been used to explore the causal mechanisms at work; however, there are limited standards to guide this work. This study synthesizes current evidence of KT process evaluations to provide future methodological recommendations.

Methods
Peer-reviewed search strategies were developed by a health research librarian. Studies had to be in English, published since 1996, and were not excluded based on design. Studies had to (1) be a process evaluation of a KT intervention study in primary health, (2) be a primary research study, and (3) include a licensed healthcare professional delivering or receiving the intervention. A two-step, two-person hybrid screening approach was used for study inclusion with inter-rater reliability ranging from 94 to 95%. Data on study design, data collection, theoretical influences, and approaches used to evaluate the KT intervention, analysis, and outcomes were extracted by two reviewers. Methodological quality was assessed with the Mixed Methods Appraisal Tool (MMAT).

Results
Of the 20,968 articles screened, 226 studies fit our inclusion criteria. The majority of process evaluations used qualitative forms of data collection (43.4%) and individual interviews as the predominant data collection method. 72.1% of studies evaluated barriers and/or facilitators to implementation. 59.7% of process evaluations were stand-alone evaluations. The timing of data collection varied widely with post-intervention data collection being the most frequent (46.0%). Only 38.1% of the studies were informed by theory. Furthermore, 38.9% of studies had MMAT scores of 50 or less indicating poor methodological quality.

Conclusions
There is widespread acceptance that the generalizability of quantitative trials of KT interventions would be significantly enhanced through complementary process evaluations. However, this systematic review found that process evaluations are of mixed quality and lack theoretical guidance. Most process evaluation data collection occurred post-intervention undermining the ability to evaluate the process of implementation. Strong science and methodological guidance is needed to underpin and guide the design and execution of process evaluations in KT science.

Registration
This study is not registered with PROSPERO.