bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic analysis of the domestication and post-Spanish conquest evolution of the llama and alpaca
Authors: Fan Ruiwen , Gu Zhongru , Guang Xuanmin , Marín Juan Carlos , Varas Valeria , González Benito A. , Wheeler Jane C. , Hu Yafei , Li Erli , Sun Xiaohui , Yang Xukui , Zhang Chi , Gao Wenjun , He Junping , Munch Kasper , Corbett-Detig Russel , Barbato Mario , Pan Shengkai , Zhan Xiangjiang , Bruford Michael W. , Dong Changsheng 
Published: July 2020

Abstract
Background
Despite their regional economic importance and being increasingly reared globally, the origins and evolution of the llama and alpaca remain poorly understood. Here we report reference genomes for the llama, and for the guanaco and vicuña (their putative wild progenitors), compare these with the published alpaca genome, and resequence seven individuals of all four species to better understand domestication and introgression between the llama and alpaca.

Results
Phylogenomic analysis confirms that the llama was domesticated from the guanaco and the alpaca from the vicuña. Introgression was much higher in the alpaca genome (36%) than the llama (5%) and could be dated close to the time of the Spanish conquest, approximately 500 years ago. Introgression patterns are at their most variable on the X-chromosome of the alpaca, featuring 53 genes known to have deleterious X-linked phenotypes in humans. Strong genome-wide introgression signatures include olfactory receptor complexes into both species, hypertension resistance into alpaca, and fleece/fiber traits into llama. Genomic signatures of domestication in the llama include male reproductive traits, while in alpaca feature fleece characteristics, olfaction-related and hypoxia adaptation traits. Expression analysis of the introgressed region that is syntenic to human HSA4q21, a gene cluster previously associated with hypertension in humans under hypoxic conditions, shows a previously undocumented role for PRDM8 downregulation as a potential transcriptional regulation mechanism, analogous to that previously reported at high altitude for hypoxia-inducible factor 1α.

Conclusions
The unprecedented introgression signatures within both domestic camelid genomes may reflect post-conquest changes in agriculture and the breakdown of traditional management practices.
Establishment of reference range of CD4 T-lymphocyte in healthy Nepalese adults
Authors: Mishra Shravan Kumar , Shrestha Lilee , Pandit Roshan , Khadka Sundar , Shrestha Bimal , Dhital Subhash , Sharma Saroj , Sharma Mukunda , Mahato Raj Kumar , Shakya Geeta , Das Manandhar Krishna 
Published: July 2020

Abstract
Objective
CD4 T lymphocytes are the most widely used cellular markers to assess the course of HIV infection, clinical staging and, monitoring the effect of antiretroviral therapy. The regional reference range for Eastern, Central and Western development region of Nepal had already been established whereas the same was still lacking in Mid-western and Far-western development region. The objective of this study was to establish reference range of CD4 T lymphocyte in the remaining two development regions and finally the national reference range using data from previous study.

Results
The average values (mean ± SD) of CD4 and CD3 T cell in present study was (819 ± 294) cells/μl and (1546 ± 532) cells/μl, respectively. The absolute CD4 T cell (914 ± 303) and CD3 T cell (1671 ± 560) count in female were significantly higher than those from male, CD4 (757 ± 270) and CD3 (1465 ± 499) (p value-0.000). National reference value of CD4 was determined to be (798 ± 335) cells/μl for healthy Nepalese adults.
Wandering along the epigenetic timeline
Authors: Topart Clémence , Werner Emilie , Arimondo Paola B. 
Published: July 2020

AbstractBackgroundIncreasing life expectancy but also healthspan seems inaccessible as of yet but it may become a reality in the foreseeable future. To extend lifespan, it is essential to unveil molecular mechanisms involved in ageing. As for healthspan, a better understanding of the mechanisms involved in age-related pathologies is crucial.Main bodyWe focus on the epigenetic side of ageing as ageing is traced by specific epigenetic patterns and can be measured by epigenetic clocks. We discuss to what extent exposure to environmental factor, such as alcohol use, unhealthy diet, tobacco and stress, promotes age-related conditions. We focused on inflammation, cancer and Alzheimer’s disease. Finally, we discuss strategies to reverse time based on epigenetic reprogramming.ConclusionsReversibility of the epigenetic marks makes them promising targets for rejuvenation. For this purpose, a better understanding of the epigenetic mechanisms underlying ageing is essential. Epigenetic clocks were successfully designed to monitor these mechanisms and the influence of environmental factors. Further studies on age-related diseases should be conducted to determine their epigenetic signature, but also to pinpoint the defect in the epigenetic machinery and thereby identify potential therapeutic targets. As for rejuvenation, epigenetic reprogramming is still at an early stage.Graphical abstract
Nonadherent culture method promotes MSC-mediated vascularization in myocardial infarction via miR-519d/VEGFA pathway
Authors: Deng Baoping , Zhang Xianlan , Liang Yi , Jiang Haiming , Huang Weizhao , Wu Yinmeng , Deng Weiping 
Published: July 2020

AbstractBackgroundMesenchymal stem cells (MSCs) can provide therapeutic benefits for myocardial infarction (MI) recovery; however, the molecular mechanism by which MSCs improve the heart function is unclear.MethodsMicroarray analysis was performed to examine the expression profiling of human MSCs (hMSCs) grown as adherent cultures (AC-hMSCs) or nonadherent cultures on ultra-low-adherent plates (nonAC-hMSCs). Real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, and enzyme-linked immunosorbent assays (ELISA) were used to assess VEGFA expression and secretion in the AC-hMSCs and nonAC-hMSCs. The paracrine effect of VEGFA-overexpressing AC-MSCs (AC-VEGFA-hMSCs) or VEGFA-knockdown nonAC-hMSCs (nonAC-shVEGFA-hMSCs) on the angiogenic ability of human umbilical vein endothelial cells (HUVECs) was evaluated using tube formation assay. AC-VEGFA-hMSCs or nonAC-shVEGFA-hMSCs were transplanted into myocardial infarction rats to investigate the therapeutic effect of AC-VEGFA-hMSCs or nonAC-shVEGFA-hMSCs. Luciferase reporter assay was used to confirm the association of VEGFA with miR-519d.ResultsMicroarray analysis revealed that VEGFA is downregulated in AC-hMSCs compared to nonAC-hMSCs. Functional assays revealed that high levels of VEGFA produced from AC-VEGFA-hMSCs increased the tube formation capacity of HUVECs in vitro, improved angiogenesis and cardiac performance, and reduced infarct size in a rat MI model. Low levels of VEGFA secretion from nonAC-shVEGFA-hMSCs had the opposite effects. Mechanistically, we found that miR-519d directly targets VEGFA. High levels of VEGFA secreted from VEGFA-overexpressing nonAC-hMSCs abolished the repressive effect of miR-519d on HUVEC angiogenesis.ConclusionOur findings indicate that nonadherent culture-induced secretion of VEGFA plays an important role in MSCs via the miR-519d/VEGFA pathway and may provide a novel therapeutic strategy for MI treatment.
Comparison of fuzzy Adomian decomposition method with fuzzy VIM for solving fuzzy heat-like and wave-like equations with variable coefficients
Authors: Osman Mawia , Gong Zengtai , Mustafa Altyeb Mohammed 
Published: July 2020

AbstractIn this work, we investigate the fuzzy Adomian decomposition method (ADM) and fuzzy variational iteration method (VIM) applied to solving fuzzy heat-like and wave-like equations with variable coefficients, in the sense of gH-differentiability. The methods clearly are very efficient and powerful techniques in finding the solutions to the proposed equations. We also illustrate them by some examples. The results reveal that the methods are very effective, convenient, and accurate mathematical tools for solving fuzzy heat-like and wave-like equations with variable coefficients.
Parameterized algorithms of fundamental NP-hard problems: a survey
Authors: Li Wenjun , Ding Yang , Yang Yongjie , Sherratt R. Simon , Park Jong Hyuk , Wang Jin 
Published: July 2020

Abstract
Parameterized computation theory has developed rapidly over the last two decades. In theoretical computer science, it has attracted considerable attention for its theoretical value and significant guidance in many practical applications. We give an overview on parameterized algorithms for some fundamental NP-hard problems, including MaxSAT, Maximum Internal Spanning Trees, Maximum Internal Out-Branching, Planar (Connected) Dominating Set, Feedback Vertex Set, Hyperplane Cover, Vertex Cover, Packing and Matching problems. All of these problems have been widely applied in various areas, such as Internet of Things, Wireless Sensor Networks, Artificial Intelligence, Bioinformatics, Big Data, and so on. In this paper, we are focused on the algorithms’ main idea and algorithmic techniques, and omit the details of them.
Tumor-associated collagen signatures: pushing tumor boundaries
Authors: Brett Elizabeth A. , Sauter Matthias A. , Machens Hans-Günther , Duscher Dominik 
Published: July 2020

AbstractIn 2006, a new model of invasive breast tumor emerged and, since 2011, is gaining recognition and research momentum. “Tumor-associated collagen signatures” describe 3 distinct layers of collagen which radiate outward in shells from the main body of the tumor. The outermost layer (TACS3) features branches of collagen radiating away from the tumor, 90° perpendicular to the tumor surface. TACS3 increases tumor span and correlates directly with metastasis, though presently difficult to detect in breast tissue. TACS is an emerging model but has been validated by multiple labs in vitro and in vivo, specifically for breast cancer prognostics. Newly recognized and accepted tumor borders will impact both R0 resections and downstream surgical reconstruction. This review aims to comprehensively introduce and connect the ranging literature on linearized collagen of invasive tumor borders. Using PubMed keyword searches containing “aligned,” “linear,” “oriented,” and “organized,” we have gathered the studies on TACS, integrated the concept into the clinic, and projected future platforms.
Quantitative patterns of motor cortex proteinopathy across ALS genotypes
Authors: Nolan Matthew , Scott Connor , Gamarallage Menuka Pallebage , Lunn Daniel , Carpenter Kilda , McDonough Elizabeth , Meyer Dan , Kaanumalle Sireesha , Santamaria-Pang Alberto , Turner Martin R. , Talbot Kevin , Ansorge Olaf 
Published: July 2020

AbstractDegeneration of the primary motor cortex is a defining feature of amyotrophic lateral sclerosis (ALS), which is associated with the accumulation of microscopic protein aggregates in neurons and glia. However, little is known about the quantitative burden and pattern of motor cortex proteinopathies across ALS genotypes. We combined quantitative digital image analysis with multi-level generalized linear modelling in an independent cohort of 82 ALS cases to explore the relationship between genotype, total proteinopathy load and cellular vulnerability to aggregate formation. Primary motor cortex phosphorylated (p)TDP-43 burden and microglial activation were more severe in sporadic ALS-TDP disease than C9-ALS. Oligodendroglial pTDP-43 pathology was a defining feature of ALS-TDP in sporadic ALS, C9-ALS and ALS with OPTN, HNRNPA1 or TARDBP mutations. ALS-FUS and ALS-SOD1 showed less cortical proteinopathy in relation to spinal cord pathology than ALS-TDP, where pathology was more evenly spread across the motor cortex-spinal cord axis. Neuronal pTDP-43 aggregates were rare in GAD67+ and Parvalbumin+ inhibitory interneurons, consistent with predominant accumulation in excitatory neurons. Finally, we show that cortical microglia, but not astrocytes, contain pTDP-43. Our findings suggest divergent quantitative, genotype-specific vulnerability of the ALS primary motor cortex to proteinopathies, which may have implications for our understanding of disease pathogenesis and the development of genotype-specific therapies.
Performance estimate of some prototypes of inertial platform and strapdown marine gravimeters
Authors: Yuan Yuan , Gao Jinyao , Wu Zhaocai , Shen Zhongyan , Wu Guochao 
Published: July 2020

AbstractMarine gravimeter has been proved to be the primary technique to efficiently obtain middle-to-short wavelength signals of the earth’s gravity field in geodesy, geodynamics and marine sciences research. In recent years, some prototypes of inertial platform and strapdown marine gravimeters have been developed, where the inertial platform gravimeter systems include CHZ-II and ZL11, and strapdown gravimeter systems include SAG-2M and SGA-WZ. In order to validate the performance of these marine gravimeter prototypes, a synchronous test with the widely used gravimeters GT-2M and LCR arranged on the same vessel was carried out in the north of South China Sea. All the data are processed according to the survey standard flow, and the performance is estimated by analyzing the errors of the repeat lines and the crossover points under the same environment. The compared results show that all the six gravimeters can meet the precision requirement of marine gravity survey. Meanwhile, the precision results of the improved gravimeters can get close to the precision of gravimeter GT-2M, higher than the precision gravimeter LCR.
Allometric models for estimating aboveground biomass in the tropical woodlands of Ghana, West Africa
Authors: Aabeyir Raymond , Adu-Bredu Stephen , Agyare Wilson Agyei , Weir Michael J. C. 
Published: July 2020

Abstract
Background
Modelling aboveground biomass (AGB) in forest and woodland ecosystems is critical for accurate estimation of carbon stocks. However, scarcity of allometric models for predicting AGB remains an issue that has not been adequately addressed in Africa. In particular, locally developed models for estimating AGB in the tropical woodlands of Ghana have received little attention. In the absence of locally developed allometric models, Ghana will continue to use Tier 1 biomass data through the application of pantropic models. Without local allometric models it is not certain how Ghana would achieve Tier 2 and 3 levels under the United Nations programme for reducing emissions from deforestation and forest degradation. The objective of this study is to develop a mixed-species allometric model for use in estimating AGB for the tropical woodlands in Ghana. Destructive sampling was carried out on 745 trees (as part of charcoal production) for the development of allometric equations. Diameter at breast height (dbh, i.e. 1.3 m above ground level), total tree height (H) and wood density (ρ) were used as predictors for the models. Seven models were compared and the best model selected based on model efficiency, bias (%) and corrected Akaike Information Criterion. The best model was validated by comparing its results with those of the pantropic model developed by Chave et al. (Glob Chang Biol 20:3177–3190, 2014) using equivalence test and conventional paired t-test.

Results
The results revealed that the best model for estimating AGB in the tropical woodlands is AGB = 0.0580ρ((dbh)2H)0.999. The equivalence test showed that this model and the pantropic model developed by Chave et al. (Glob Chang Biol 20:3177–3190, 2014) were equivalent within ±10% of their mean predictions (p-values < 0.0001 for one-tailed t-tests for both lower and upper bounds at 5% significant level), while the paired t-test revealed that the mean (181.44 ± 18.25 kg) of the model predictions of the best model of this study was significantly (n = 745, mean diff. = 16.50 ± 2.45 kg; S.E. = 1.25 kg; p < 0.001) greater than that (164.94 ± 15.82 kg) of the pantropic model of Chave et al. (Glob Chang Biol 20:3177–3190, 2014).

Conclusion
The model developed in this study fills a critical gap in estimating AGB in tropical woodlands in Ghana and other West African countries with similar ecological conditions. Despite the equivalence with the pantropic model it remains superior to the model of Chave et al. (Glob Chang Biol 20:3177–3190, 2014) for the estimation of AGB in local tropical woodlands. It is a relevant tool for the attainment of Tier 2 and 3 levels for REDD+. The model is recommended for use in the tropical woodlands in Ghana and other West African countries in place of the use of pantropic models.
Guidance on authorship with and acknowledgement of patient partners in patient-oriented research
Authors: Richards Dawn P. , Birnie Kathryn A. , Eubanks Kathleen , Lane Therese , Linkiewich Delane , Singer Lesley , Stinson Jennifer N. , Begley Kimberly N. 
Published: July 2020

AbstractThe Strategy for Patient-Oriented Research Chronic Pain Network was founded in 2016 and is a patient-oriented research network funded by the Canadian Institutes of Health Research. The Network incorporates patient partners throughout its governance and operations meaning that patient partners may contribute to research projects in ways that warrant scientific authorship as defined by the International Committee of Medical Journal Editors. The Network did a brief informal review of guidance on patient authorship in 2019, but could not find any practical documentation to guide its members on this topic. Note the term patient partner here refers to a patient (or caregiver or other person with lived experience) who is a partner or collaborator on a research team. This guidance does not address patients as participants in a research study.This guidance has been co-written by a group of researchers and patient partners of the Chronic Pain Network in an effort to address this gap. It is intended for both researchers and patient partner audiences. This guidance is meant to facilitate conversations between researchers and patient partners about authorship and/or acknowledgement regarding research projects on which they collaborate. While the overall principles of academic authorship and acknowledgement remain unchanged, nuances for interpreting these principles through the lens of patient engagement or patient-oriented research is provided.Teams that carry out patient-oriented research projects will require different preparation to empower all team members (researchers and patient partners) to discuss authorship and acknowledgement. To facilitate these conversations, we have included an overview of the scientific publishing process, explanation of some common terms, and sets of considerations are provided for both patient partners and researchers in determining the range of team member contribution from acknowledgement to authorship. Conversations about authorship can be difficult, even for established research teams. This guidance, and the resources discussed within it, are provided with the intention of making these conversations easier and more thoughtful.
When self-harm is about preventing harm: emergency management of obsessive–compulsive disorder and associated self-harm
Authors: Palombini Erika , Richardson Joel , McAllister Emma , Veale David , Thomson Alex B. 
Published: July 2020

SummaryMental health staff may have limited exposure to emergencies associated with obsessive–compulsive disorder (OCD) during postgraduate training. The first time they encounter a person in the midst of severe obsessions, or one who has compulsively self-harmed in response to such obsessions, might be when working on call covering the emergency department. This educational article presents the lived experience of one of the authors as a clinical scenario. The scenario is then used to illustrate the severity of disability and the rates of self-harm and suicide-related mortality caused by OCD. The recognition and assessment of OCD is described, along with what helps in emergency situations. Written informed consent was obtained for the publication of clinical details.
Pyrotinib in HER2-Mutant Advanced Lung Adenocarcinoma After Platinum-Based Chemotherapy: A Multicenter, Open-Label, Single-Arm, Phase II Study
Authors: Zhou Caicun , Li Xingya , Wang Qiming , Gao Guanghui , Zhang Yiping , Chen Jianhua , Shu Yongqian , Hu Yanping , Fan Yun , Fang Jian , Chen Gongyan , Zhao Jun , He Jianxing , Wu Fengying , Zou Jianjun , Zhu Xiaoyu , Lin Xiang 
Published: July 2020

PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of pyrotinib in patients with HER2-mutant advanced NSCLC in a prospective, multicenter, open-label, single-arm, phase II study. PATIENTS AND METHODS Patients with stage IIIB or IV HER2-mutant lung adenocarcinoma who were previously treated with platinum-based chemotherapy were enrolled to receive pyrotinib at a dose of 400 mg/d for 21-day cycles. The primary end point was objective response rate per independent review committee (IRC). RESULTS Between October 20, 2016, and December 10, 2018, 60 patients received pyrotinib monotherapy. At baseline, 58 (96.7%) were stage IV, and 25 (41.7%) received at least 2 lines of prior chemotherapy. As of data cutoff on June 20, 2019, IRC-assessed objective response rate was 30.0% (95% CI, 18.8% to 43.2%). All subgroups of patients with different HER2 mutation types showed a favorable objective response rate. The objective response rates were similar between patients with and without brain metastases (25.0% v 31.3%). The median duration of response was 6.9 months (95% CI, 4.9 to 11.1 months). The median progression-free survival was 6.9 months (95% CI, 5.5 to 8.3 months) per IRC. The median overall survival was 14.4 months (95% CI, 12.3 to 21.3 months). Treatment-related adverse events of grade 3 or 4 occurred in 28.3% of patients, with the most common being diarrhea (20.0%; all grade 3). No treatment-related deaths were reported. CONCLUSION Pyrotinib showed promising antitumor activity and an acceptable safety profile in chemotherapy-treated patients with HER2-mutant NSCLC.
Landscape of Oncology Clinical Trials in Africa
Authors: Odedina Folakemi T. , Shamley Delva , Okoye Ifeoma , Ezeani Adaora , Ndlovu Ntokozo , Dei-Adomakoh Yvonne , Meza Kimberly , Agaba Ruth , Fathi Parisa , Askins Nissa 
Published: July 2020

PURPOSE The burden of cancer in Africa is of significant concern for several reasons, including that incidence of cancer in Africa continues to rise while Africa is also dealing with communicable diseases. To combat cancer in Africa, oncology clinical trials are needed to develop innovative interventions for cancer prevention, screening, diagnosis, treatment, and survivorship. Unfortunately, there is a paucity of clinical trials in Africa and it is difficult for African clinicians to get information on open oncology clinical trials and impossible for African patients with cancer to access this information. The primary objective of this study was to identify open oncology clinical trials in Africa. METHODS This project was part of a large-scale study to develop an African Virtual Platform for Oncology Clinical Trials Registry. The study was a quantitative, web-based, retrospective review of clinical trials registries. RESULTS A total of 109 open oncology clinical trials were identified. Most of the trials were in Egypt, South Africa, Algeria, and Kenya. The top cancer types for oncology clinical trials in Africa were breast, cervical, and lung cancers. The top sponsor of oncology clinical trials in Africa was academic institutions, especially institutions in the United States. CONCLUSION The paucity of clinical trials in Africa will continue to magnify the global disparities of cancer in the African population. Clinical trials are needed to ensure therapeutic interventions are safe and effective in the African population. In the era of personalized and precision health, it no longer suffices to assume that drugs developed in North America, Europe, or Asia will be effective in the African population.