bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma
Authors: Furuse Motomasa , Kuwabara Hiroko , Ikeda Naokado , Hattori Yasuhiko , Ichikawa Tomotsugu , Kagawa Naoki , Kikuta Kenichiro , Tamai Sho , Nakada Mitsutoshi , Wakabayashi Toshihiko , Wanibuchi Masahiko , Kuroiwa Toshihiko , Hirose Yoshinobu , Miyatake Shin-Ichi 
Published: November 2019

Abstract
Background: The prevalence of programmed death-ligand 1 (PD-L1) and PD-L2 expression on tumor cells and tumor-infiltrating immune cells in primary central nervous system lymphoma (PCNSL) remains unclear. In the present study, we analyzed needle biopsy and craniotomy specimens of patients with PCNSL to compare the PD-L1 and PD-L2 levels in the tumor and surrounding (peritumoral) tissue. We also assessed the correlation between biological factors and the prognostic significance of PD-L1 and PD-L2 expression.

Methods: We retrospectively analyzed the cases of 70 patients histologically diagnosed with PCNSL (diffuse large B-cell lymphoma). Immunohistochemistry for CD20, CD68, PD-L1, and PD-L2 was performed. In cases with specimens taken by craniotomy, the percentages of PD-L1- and PD-L2-positive macrophages were evaluated in both tumor and peritumoral tissue. The Kaplan-Meier method with log-rank test and Cox proportional hazard model were used for survival analysis.

Results: The tumor cells expressed little or no PD-L1 and PD-L2, but macrophages expressed PD-L1 and PD-L2 in most of the patients. The median percentage of PD-L2-positive cells was significantly higher among peritumoral macrophages (32.5%; 95%CI: 0–94.6) than intratumoral macrophages (27.5%; 95%CI: 0–81.1, p=0.0014). There was a significant correlation between the percentages of PD-L2-positive intratumoral macrophages and PD-L2-positive peritumoral macrophages (p=0.0429), with very low coefficient correlation (ρ=0.098535). PD-L1 expression on macrophages was significantly associated with biological factors (intratumoral macrophages: better KPS, p=0.0008; better MSKCC score, p=0.0103; peritumoral macrophages: low proportion of LDH elevation, p=0.0064) and longer OS (for intratumoral macrophages: high PD-L1=60 months, 95%CI=30–132.6; low PD-L1=24 months, 95%CI=11–48; p=0.032; for peritumoral macrophages: high PD-L1=60 months, 95%CI=30.7–NR; low PD-L1=14 months, 95%CI=3–26). PD-L1 expression on peritumoral macrophages was strongly predictive of a favorable outcome (HR=0.30, 95%CI=0.12–0.77, p=0.0129).

Conclusions: Macrophages in intratumoral and peritumoral tissue expressed PD-L1 and PD-L2 at a higher rate than tumor cells. PD-L1 expression, especially on peritumoral macrophages, seems to be an important prognostic factor in PCNSL. Future comprehensive analysis of checkpoint molecules in the tumor microenvironment, including the peritumoral tissue, is warranted.
Genomic measures of inbreeding coefficients and genome-wide scan for runs of homozygosity islands in Iranian river buffalo, Bubalus bubalis
Authors: Ghoreishifar Seyed Mohammad , Moradi-Shahrbabak Hossein , Fallahi Mohammad Hossein , Jalil-Sarghaleh Ali , Moradi-Shahrbabak Mohammad , Abdollahi-Arpanahi Rostam , Khansefid Majid 
Published: November 2019

Abstract
Background: Consecutive homozygous fragments of the genome inherited from a common ancestor to offspring are known as runs of homozygosity (ROH). ROH can be used to calculate genomic inbreeding and to identifying genomic regions that are potentially under historical selection pressure. The dataset of our study consisted of 254 Azeri (AZ) and 115 Khuzestani (KHZ) river buffalo genotyped for ~65000 SNPs for the following two purposes: 1) to estimate and compare inbreeding calculated using ROH (FROH), excess of homozygosity (FHOM), correlation between uniting gametes (FUNI), and diagonal elements of the genomic relationship matrix (FGRM); 2) to identify frequently occurring ROH (i.e. ROH islands) for our selection signature and gene enrichment studies. Results: In this study, 9102 ROH were identified, with an average number of 21.2±13.1 and 33.2±15.9 segments per animal in AZ and KHZ breeds, respectively. On average in AZ, 4.35% (108.8±120.3 Mb), and in KHZ, 5.96% (149.1±107.7 Mb) of the genome was autozygous. The estimated inbreeding values based on FHOM, FUNI and FGRM were higher in AZ than they were in KHZ, which was in contrast to the FROH estimates. We identified 11 ROH islands (four in AZ and seven in KHZ). In the KHZ breed, the genes located in ROH islands were enriched for multiple Gene Ontology (GO) terms (P<0.05). The genes located in ROH islands were associated with diverse biological functions and traits such as body size and muscle development (BMP2), immune response (CYP27B1), milk production and components (MARS, ADRA1A, and KCTD16), coat colour and pigmentation (PMEL and MYO1A), reproductive traits (INHBC, INHBE, STAT6 and PCNA), and bone development (SUOX). Conclusion: The calculated FROH was in line with expected higher inbreeding in KHZ than in AZ because of the smaller effective population size of KHZ. Thus, we find that FROH can be used as a robust estimate of genomic inbreeding. Further, the majority of ROH peaks were overlapped with or in close proximity to the previously reported genomic regions with signatures of selection. This tells us that it is likely that the genes in the ROH islands have been subject to artificial and/or natural selection.
Towards accurate exclusion of neonatal bacterial meningitis: a feasibility study of a novel 16S rDNA PCR assay.
Authors: Abelian Arthur , Mund Thomas , Curran Martin , Savill Stuart , Mitra Nipa , Charan Carol , Ogilvy-Stuart Amanda , Pelham Hugh , Dear Paul 
Published: November 2019

Abstract
Background: PCRctic is an innovative assay based on 16S rDNA PCR technology that has been designed to detect a single intact bacterium in a specimen of cerebro-spinal fluid (CSF). The assay’s potential for accurate, fast and inexpensive discrimination of bacteria-free CSF makes it an ideal adjunct for confident exclusion of bacterial meningitis in newborn babies where the negative predictive value of bacterial culture is poor. This study aimed to stress-test and optimize PCRctic in the “field conditions” to attain a clinically useful level of specificity. Methods: The specificity of PCRctic was evaluated in CSF obtained from newborn babies investigated for meningitis on a tertiary neonatal unit. Following an interim analysis, the method of skin antisepsis was changed to increase bactericidal effect, and snap-top tubes (EppendorfTM) replaced standard universal containers for collection of CSF to reduce environmental contamination. Results: The assay’s specificity was 90.5% in CSF collected into the snap-top tubes – up from 60% in CSF in the universal containers. The method of skin antisepsis had no effect on the specificity. All CSF cultures were negative and no clinical cases of neonatal bacterial meningitis occurred during the study.Conclusions: a simple and inexpensive optimization of CSF collection resulted in a high specificity output. The low prevalence of neonatal bacterial meningitis means that a large multi-centre study will be required to validate the assay’s sensitivity and its negative predictive value.
The effect of information on prostate cancer screening decision process: A discrete choice experiment
Authors: Charvin Maud , Launoy Guy , Berchi Célia 
Published: November 2019

Abstract
Background: Prostate cancer screening is controversial because of uncertainty about its benefits and risks. The aim of this survey was to reveal preferences of men concerning prostate cancer screening and to test the effect of an informative video on these preferences. Methods: A stated preferences questionnaire was sent by e-mail to men aged 50-75 with no history of prostate cancer. Half of them were randomly assigned to view an informative video. A discrete choice model was established to reveal men’s preferences for six prostate cancer screening characteristics: mortality by prostate cancer, number of false positive and false negative results, number of overdiagnosis, out-of-pocket costs and recommended frequency. Results: 1024 men representative of the French general population filled in the entire questionnaire. Each attribute gave the expected sign except for overdiagnosis. The video seemed to increase the intention to abstain from prostate cancer screening. Conclusions: The participants attached greater importance to a decrease in the number of false negatives and a reduction in prostate cancer mortality than to other risks such as the number of false positives and overdiagnosis. Further research is needed to help men make an informed choice regarding screening.
Genomic analysis of demographic history and ecological niche modeling in the endangered Chinese Grouse Tetrastes sewerzowi
Authors: Song Kai , Gao Bin , Halvarsson Peter , Fang Yun , Jiang Ying-Xin , Sun Yue-Hua , Höglund Jacob 
Published: November 2019

Abstract
Background: The Quaternary is characterized by marked climatic oscillations between glacial and interglacial periods that had worldwide consequences in forming the contemporary diversity of many populations, species and communities. The origin and evolution of biodiversity in mountainous areas are highly dependent on historical orogenesis and associated climatic changes. The Chinese grouse Tetrastes sewerzowi is a forest-dwelling species endemic to the mountains to the east of the Qinghai–Tibet Plateau, which has been listed as Near Threatened with a decreasing trend by the IUCN because of ongoing deforestation and fragmentation of coniferous forests. Understanding demographic history is important in placing current population status into a broader ecological and evolutionary context. Results: Analysis of the Chinese Grouse genome reveals fluctuation in effective population size throughout the Pleistocene. Populations decreased during early to middle Pleistocene but showed an expansion during late Pleistocene then followed a sharp decline during the last glacial maximum (LGM). Ecological niche modeling indicated that suitable habitat shift between high altitude regions to low altitude regions were due to a changing climate. The result parallels patterns of population size change in Chinese Grouse estimated from PSMC modelling, which suggested an expansion in population size from the last interglacial period and then a peak and a bottleneck occurring at the LGM. Furthermore, the present-day distribution of Chinese Grouse is greatly reduced and will become highly fragmented if boreal forest cover restricts the ecological niche. Conclusions: The Chinese Grouse have experienced substantial population size changes from the beginning to the LIG and reached a peak before the LGM. A sharp decrease and bottleneck happened during the LGM, when the conifer forests were subjected to extensive loss. The results inferred from the whole genome sequencing and species distribution models both support the historical population fluctuation. The distribution of the Chinese Grouse was strongly dependent on the boreal forest cover. To protect the fragmented boreal forest is an essential action to protect the Chinese Grouse.
Exploring characteristics of COPD patients with clinical improvement after integrated disease management or usual care: post-hoc analysis of the RECODE study
Authors: Meijer Eline , Eeden Annelies E. van , Kruis Annemarije L. , Boland Melinde R.S. , Assendelft W. J.J. (Pim) , Tsiachristas Apostolos , Mölken Maureen P.M.H. Rutten-van , Kasteleyn Marise J. , Chavannes Niels H. 
Published: November 2019

Abstract
Background: The cluster randomized controlled trial on (cost-)effectiveness of integrated chronic obstructive pulmonary disease (COPD) management in primary care (RECODE) showed that integrated disease management (IDM) in primary care had no effect on quality of life (QOL) in COPD patients compared with usual care. It is possible that only a subset of COPD patients in primary care benefit from IDM. We therefore examined which patients benefit from IDM, and whether patient characteristics predict clinical improvement over time. Method: Post-hoc analyses of the RECODE trial among 1086 COPD patients. Logistic regression analyses were performed with baseline characteristics as predictors to examine determinants of improvement in QOL, defined as a minimal decline in Clinical COPD Questionnaire (CCQ) of 0.4 points after 12 and 24 months of IDM. We also performed moderation analyses to examine whether predictors of clinical improvement differed between IDM and usual care. Results: Regardless of treatment type, more severe dyspnea (MRC) was the most important predictor of clinically improved QOL at 12 and 24 months, suggesting that these patients have most room for improvement. Although the interaction effect between gender and treatment condition was nonsignificant, it appeared that male patients were worse off with IDM than usual care. Conclusions: More severe dyspnea is a key predictor of improved QOL in COPD patients over time. Future IDM programs, provided that they are effective, may benefit from tailoring to gender such that the programs meet the individual needs of both female and male COPD patients. Trial registration: Netherlands Trial Register, NTR2268. Registered 31 March 2010, https://www.trialregister.nl/trial/2144 .
Software Engineering for Machine Learning in Health Informatics
Authors: Moreb Mohammed , Ata Oguz 
Published: November 2019

Abstract
Background We propose a novel framework for health Informatics: framework and methodology of Software Engineering for machine learning in Health Informatics (SEMLHI). This framework shed light on its features, that allow users to study and analyze the requirements, determine the function of objects related to the system and determine the machine learning algorithms that will be used for the dataset.Methods Based on original data that collected from the hospital in Palestine government in the past three years, first the data validated and all outlier removed, analyzed using develop framework in order to compare ML provide patients with real-time. Our proposed module comparison with three Systems Engineering Methods Vee, agile and SEMLHI. The result used by implement prototype system, which require machine learning algorithm, after development phase, questionnaire deliver to developer to indicate the result using three methodology. SEMLHI framework, is composed into four components: software, machine learning model, machine learning algorithms, and health informatics data, Machine learning Algorithm component used five algorithms use to evaluate the accuracy for machine learning models on component.Results we compare our approach with the previously published systems in terms of performance to evaluate the accuracy for machine learning models, the results of accuracy with different algorithms applied for 750 case, linear SVG have about 0.57 value compared with KNeighbors classifier, logistic regression, multinomial NB, random forest classifier. This research investigates the interaction between SE, and ML within the context of health informatics, our proposed framework define the methodology for developers to analyzing and developing software for the health informatic model, and create a space, in which software engineering, and ML experts could work on the ML model lifecycle, on the disease level and the subtype level.Conclusions This article is an ongoing effort towards defining and translating an existing research pipeline into four integrated modules, as framework system using the dataset from healthcare to reduce cost estimation by using a new suggested methodology. The framework is available as open source software, licensed under GNU General Public License Version 3 to encourage others to contribute to the future development of the SEMLHI framework.
3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: One disease- many faces
Authors: Grünert Sarah Catharina , Sass Jörn Oliver 
Published: November 2019

Abstract
Background 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL .Method We performed a systematic literature search to identify all published cases. 211 patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided.Results More than 95% of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4% already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6% of patients showing normal development.Conclusion This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.
Why is misdiagnosis more likely among some people with rare diseases than others? Insights from a population-based cross-sectional study in China
Authors: Dong Dong , Chung Roger Yat-Nork , Chan Rufina , Gong Shiwei , Xu Huan 
Published: November 2019

Abstract
Background For patients with rare diseases (RD), misdiagnosis has been regarded as one of the key issues that hinder RD patients’ accessibility to timely treatment. Yet, less is known about the main factors associated with RD patients’ misdiagnosis. The objective of this study is to use the data from a national survey among 2,040 RD patients from China to explore the association between misdiagnosis and other factors, including patients’ demographics, socio-economic characteristics, medical history, and their accessibility to RD information.Results Three binary logistic regression analyses were performed to estimate the relationships between misdiagnosis and level of rarity of the RDs (mild, moderate and severe), demographics, health insurance levels and accessibility to disease-related information by using the total sample, and the adult and minor sub-samples.It is found that accessibility to RD information is the most critical factor influencing the patients’ chances of being misdiagnosed. In other words, the greater the difficulty in accessing information on RD management, the higher the possibility of experiencing misdiagnosis.Such influences from information accessibility to misdiagnosis were repeatedly discovered when exploring the adult and the minor sub-samples. The association between perceived economic status and misdiagnosis only occurs in the total sample. The only other factor significantly associated misdiagnosis was disease complication: participants who reported no complications are less likely to experience misdiagnosis.Conclusions Our study indicated that patients with RDs who have difficulty in accessing disease-related information have nearly two to five times higher chances of being misdiagnosed. Even after considering the patients’ age, gender, economic levels and education levels, the impact of information accessibility still stands out. Our finding highlights the fact that accessibility to information is the key to reducing misdiagnosis among RD patients.
The Azoles in Pharmacochemistry: Perspectives on the Synthesis of New Compounds and Chemoinformatic Contributions
Authors: de Oliveira Viana Jéssika , Monteiro Alex France Messias , Filho José Maria Barbosa , Scotti Luciana , Scotti Marcus Tullius 
Published: November 2019

:
Due to their versatile biological activity, Azoles are widely studied in pharmacochemistry. It is possible
to use them in many applications and in studies aimed at discovering antiparasitic, antineoplastic, antiviral,
antimicrobial compounds; and in the production of materials for treatment of varied pathologies. Based on their
biological activity, our review presents several studies that involve this class of organic compounds. A bibliographic
survey of this type can effectively contribute to pharmaceutical sciences, stimulating the discovery of new
compounds, and structural improvements to biological profiles of interest. In this review, articles are discussed
involving the synthesis of new compounds and chemoinformatic contributions. Current applications of azoles in
both the pharmaceutical and agri-business sectors are well known, yet as this research highlights, azole compounds
can also bring important contributions to the fight against many diseases. Among the heterocyclics, azoles
are increasingly studied by research groups around the world for application against tuberculosis, HIV, fungal and
bacterial infections; and against parasites such as leishmaniasis and trypanosomiasis. Our hope is that this work
will help arouse the interest of research groups planning to develop new bioactives to fight against these and
other diseases.
Progress in the Mechanism and Clinical Application of Cilostazol
Authors: Zheng Huilei , Yang Hua , Gong Danping , Mai Lanxian , Qiu Xiaoling , Chen Lidai , Su Xiaozhou , Wei Ruoqi , Zeng Zhiyu 
Published: November 2019

:Cilostazol is a unique platelet inhibitor that has been used clinically for more than 20 years. As a phosphodiesterase type III inhibitor, cilostazol is capable of reversible inhibition of platelet aggregation and vasodilation, has antiproliferative effects, and is widely used in the treatment of peripheral arterial disease, cerebrovascular disease, percutaneous coronary intervention, etc. This article briefly reviews the pharmacological mechanisms and clinical application of cilostazol.
Design of Arylsulfonylhydrazones as Potential FabH Inhibitors: Synthesis, Antimicrobial Evaluation and Molecular Docking
Authors: Fernandes Thais Batista , Segretti Natanael Dante , Lourenço Felipe Rebello , Cândido Thalita Marcílio , Baby André Rolim , Barbosa Euzébio Guimarães , Parise-Filho Roberto 
Published: November 2019

Background:
Antimicrobial resistance is a persistent problem regarding infection
treatment and calls for developing new antimicrobial agents. Inhibition of bacterial β-ketoacyl acyl
carrier protein synthase III (FabH), which catalyzes the condensation reaction between a CoAattached
acetyl group and an ACP-attached malonyl group in bacteria is an interesting strategy to
find new antibacterial agents.

Objective:
The aim of this work was to design and synthesize arylsulfonylhydrazones potentially
FabH inhibitors and evaluate their antimicrobial activity.

Methods:
MIC50 values of sulfonylhydrazones against E. coli and S. aureus were determined. Antioxidant
activity was evaluated by DPPH (1-1’-diphenyl-2-picrylhydrazyl) assay and cytotoxicity
against LL24 lung fibroblast cells was verified by MTT method. Principal component analysis
(PCA) was performed in order to suggest a structure-activity relationship. Molecular docking allowed
to propose sulfonylhydrazones interactions with FabH.

Results:
The most active compound showed activity against S. aureus and E. coli, with MIC50 =
0.21 and 0.44 μM, respectively. PCA studies correlated better activity to lipophilicity and molecular
docking indicated that sulfonylhydrazone moiety is important to hydrogen-bond with FabH
while methylcatechol ring performs π-π stacking interaction. The DPPH assay revealed that some
sulfonylhydrazones derived from the methylcatechol series had antioxidant activity. None of the
evaluated compounds was cytotoxic to human lung fibroblast cells, suggesting that the compounds
might be considered safe at the tested concentration.

Conclusion:
Arylsufonylhydrazones is a promising scaffold to be explored for the design of new
antimicrobial agents.