bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and genetical features of probands and affected family members with familial exudative vitreoretinopathy in a large Chinese cohort
Authors: Wang Shiyuan , Zhang Xiang , Hu Yiqian , Fei Ping , Xu Yu , Peng Jie , Zhao Peiquan 
Published: April 2020

AimsTo explore the clinical and genetical features of families with strictly confirmed familial
exudative vitreoretinopathy (FEVR) in a large Chinese cohort.MethodsA retrospective chart review study was conducted on the FEVR families diagnosed by both angiography and targeted next-generation sequencing in six FEVR known genes (FZD4, LRP5, TSPAN12, NDP, KIF11, ZNF408) in the probands and at least one first-degree family member. Variation in expressivity and severity was evaluated in different gene groups.Results105 FEVR families (223 FEVR affected subjects with 434 eyes) met the inclusion criteria. There were 105 probands with mean age of 3.8 years old and 118 affected family members of 32.7 years old averagely. Mutations in FZD4 were most prevalent (33.33%), followed by LRP5 (29.52%), TSPAN12 (22.86%), NDP (5.71%), KIF11 (1.9%) and ZNF408 (0.95%). 81% of the probands were classified as stage 4 or worse which most prevalently contributed to FZD4 mutations. All of the three affected family members with stage 4 or worse carried FZD4 variants. More than half (51.43%) of the probands in FZD4 group showed asymmetry. Unilateral FEVR was detected in 11 (10.5%) families consisting of six probands and six affected relatives, and FZD4 mutations accounted for 63.64% of all the cases with variant (c.1282_1285del, p. D428fs) identified in three families.ConclusionsGenotype-phenotype correlation in FEVR was complex with family dependent. Mutations in FZD4 might initiate the most diverse and asymmetric phenotypes.
New clinical screening strategy to distinguishHNF1Avariant-induced diabetes from young early-onset type 2 diabetes in a Chinese population
Authors: Ma Yumin , Gong Siqian , Wang Xirui , Cai Xiaoling , Xiao Xinhua , Gu Weijun , Yang Jinkui , Zhong Liyong , Xiao Jianzhong , Li Meng , Liu Wei , Zhang Simin , Zhou Xianghai , Li Yufeng , Zhou Lingli , Zhu Yu , Luo Yingying , Ren Qian , Huang Xiuting , Gao Xueying , Zhang Xiuying , Zhang Rui , Chen Ling , Wang Fang , Wang Qiuping , Hu Mengdie , Han Xueyao , Ji Linong 
Published: April 2020

ObjectiveMaturity-onset diabetes of the young caused by hepatocyte nuclear factor-1 alpha (HNF1A) variants (HNF1A-MODY) is a common form of monogenetic diabetes. Although patients withHNF1A-MODY might specifically benefit from sulfonylurea treatment, available methods for screening this specific type of diabetes are not cost-effective. This study was designed to establish an optimized clinical strategy based on multiple biomarkers to distinguish patients withHNF1A-MODY from clinically diagnosed early-onset type 2 diabetes (EOD) for genetic testing in a Chinese population.Research design and methodsA case–control study including 125 non-related young patients with EOD and 15 probands withHNF1A-MODY (cohort 1) was conducted to evaluate reported biomarkers forHNF1A-MODY. A cut-off for the fasting insulin (Fins) level, the 97.5 percentile of 150 healthy subjects with normal components of metabolic syndrome (cohort 2), was used to filter out individuals with obvious insulin resistance (Fins <102 pmol/L). An optimized clinical screening strategy (HNF1A-CSS) was established, and its effectiveness was assessed in another group of 410 young patients with EOD (cohort 3).ResultsIn cohort 1, body mass index (BMI), serum high-density lipoprotein cholesterol (HDL-c) and high-sensitivity C reactive protein (hs-CRP) levels were confirmed to be useful for the differential diagnosis ofHNF1A-MODY. In cohort 3, eight probands withHNF1A-MODY were identified. In cohort 3 and young relatives withHNF1A-MODY, meeting three of four criteria (BMI <28 kg/m2, hs-CRP <0.75 mg/L, Fins <102 pmol/L and HDL-c >1.12 mmol/L), the sensitivity and specificity ofHNF1A-CSS were 100% and 69.3%, respectively. In the pooled analysis of all young patients,HNF1A-CSS displayed 90.5% sensitivity and 73.6% specificity for identifying patients withHNF1A-MODY among those with clinically diagnosed EOD.ConclusionOurHNF1A-CSS is useful for distinguishing patients withHNF1A-MODY from patients with EOD in a young Chinese population.
Prevalence, risk factors and consequences of newborns born small for gestational age: a multisite study in Nepal
Authors: Gautam Paudel Pragya , Sunny Avinash K , Gurung Rejina , Gurung Abhishek , Malla Honey , Budhathoki Shyam Sundar , Paudel Prajwal , KC Navraj , KC Ashish 
Published: April 2020

ObjectiveTo identify the prevalence, risk factors and health impacts associated with small for gestational age (SGA) births in Nepal.MethodsA cross-sectional study was conducted in 12 public hospitals in Nepal from 1 July 2017 to 29 August 2018. A total of 60 695 babies delivered in these hospitals during the study period were eligible for inclusion. Clinical information of mothers and newborns was collected by data collectors using a data retrieval form. A semistructured interview was conducted at the time of discharge to gather sociodemographic information from women who provided the consent (n=50 392). Babies weighing less than the 10th percentile for their gestational age were classified as SGA. Demographic, obstetric and neonatal characteristics of study participants were analysed for associations with SGA. The association between SGA and likelihood of babies requiring resuscitation or resulting in stillbirth and neonatal death was also explored.ResultsThe prevalence of SGA births across the 12 hospitals observed in Nepal was 11.9%. After multiple variable adjustment, several factors were found to be associated with SGA births, including whether mothers were illiterate compared with those completing secondary and higher education (adjusted OR (AOR)=1.73; 95% CI 1.09 to 2.76), use of polluted fuel compared with use of clean fuel for cooking (AOR=1.51; 95% CI 1.16 to 1.97), first antenatal care (ANC) visit occurring during the third trimester compared with first trimester (AOR=1.82; 95% CI 1.27 to 2.61) and multiple deliveries compared with single delivery (AOR=3.07; 95% CI 1.46 to 6.46). SGA was significantly associated with stillbirth (AOR=7.30; 95% CI 6.26 to 8.52) and neonatal mortality (AOR=5.34; 95% CI 4.65 to 6.12).ConclusionsLow literacy status of mothers, use of polluted fuel for cooking, time of first ANC visit and multiple deliveries are associated with SGA births. Interventions encouraging pregnant women to attend ANC visits early can reduce the burden of SGA births.
Paediatric drugs trials in China
Authors: Hao Guo-Xiang , Yuan Xiao-Xiao , Guo Wei , Quan Xi-Yu , Qi Xue-Jie , Wang Tian-You , Zhao Wei 
Published: April 2020

ObjectiveClinical trials of children’s drugs are of great significance to rational drug use in children. However, paediatric drugs trials in China are facing complex challenges. At present, the investigation data on registration status of paediatric drug trials in China are still relatively lacking, and relevant research is urgently needed.MethodsThe advanced retrieval function is used to retrieve clinical trials data in the Clinical Trial.gov and Chinese Clinical Trial Registry databases in 22 April 2019. Fifteen key items were analysed to describe trial characteristics, including: registration number, study start date (year), mode of funding, type of disease, medicine type, research stage, research design, sample size, number of experimental groups, placebo group, blind method, implementation centre, child specific, newborn specific and participant age.ResultsA total of 1388 clinical trials of paediatric drugs conducted in China were registered. The number of paediatric drug trials grew steadily over time, from less than 20 per year before 2005 to more than 100 per year after 2012. Most clinical trials were postmarketing (n=800, 57.6%), single-centre (n=1045, 75.3%), intervention studies (n=1161, 83.6%) without blinded methods (1169, 84.2%) and funded by non-profit organisations (n=838, 60.4%). The number of clinical trials for antineoplastic agents (n=254, 18.3%), anti-infectives (n=156, 11.2%) and vaccines (n=154, 11.1%) is the largest.ConclusionPaediatric drug trials in China made a significant progress in recent years. Innovative method and trial design optimisation should be encouraged to accelerate paediatric clinical research. Pharmaceutical companies need to be further stimulated to carry out more high-quality paediatric clinical trials with support of paediatric drug legislation.
PRKDC: new biomarker and drug target for checkpoint blockade immunotherapy
Authors: Tan Kien Thiam , Yeh Chun-Nan , Chang Yu-Chan , Cheng Jen-Hao , Fang Wen-Liang , Yeh Yi-Chen , Wang Yu-Chao , Hsu Dennis Shin-Shian , Wu Chiao-En , Lai Jiun-I , Chang Peter Mu-Hsin , Chen Ming-Han , Lu Meng-Lun , Chen Shu-Jen , Chao Yee , Hsiao Michael , Chen Ming-Huang 
Published: April 2020

BackgroundImmunological checkpoint blockade is effective in treating various malignancies. Identifying predictive biomarkers to assist patient selection for immunotherapy has become a priority in both clinical and research settings.MethodsMutations in patients who responded to immunotherapy were identified through next-generation sequencing. Relationships among protein kinase, DNA-activated, catalytic polypeptide (PRKDC) mutations, mutation load and microsatellite instability (MSI) were analyzed using datasets from The Cancer Genome Atlas. These relationships were validated by conducting an in vitro study and by using tissue samples from 34 patients with gastric cancer. The CT26 animal model was used to evaluate the role of PRKDC as a predictive biomarker and the efficacy of the DNA-PK inhibitor.ResultsFrom the published literature, we found that among patients whose tumors harboredPRKDCmutations, 75%, 53.8%, and 50% of those with lung cancer, melanoma, and renal cell carcinoma, respectively, responded to immunotherapy. Most of these mutations were truncating and located in functional domains or in a destabilizing PRKDC protein structure. Additional analysis showed that aPRKDCmutation was significantly associated with a high mutation load in cervical cancer, colon adenocarcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, gastric adenocarcinoma and endometrial cancer. Patients with gastric cancer or colon cancer harboringPRKDCmutations were also highly associated with MSI-high status. Finally, we found that knockout PRKDC or DNA-PK inhibitor (PRKDCencodes the catalytic subunit of DNA-dependent protein kinase) enhanced the efficacy of the anti-programmed cell death protein one pathway monoclonal antibody in the CT26 animal model.ConclusionsPRKDC is not only a predictive biomarker but also a drug target for immune checkpoint inhibitors.
Wavevector-dependent optical properties from wavevector-independent proper conductivity tensor
Authors: Starke Ronald , Wirnata René , Schober Giulio A. H. , Bulut Nebahat , Kortus Jens 
Published: April 2020

AbstractWe discuss the calculation of the refractive index by means of the ab initioscalar dielectric functionand point out its inherent limitations. To overcome these, we start from the recently proposed fundamental, microscopic wave equation in materials in terms of the frequency-andwavevector-dependentdielectric tensor,and investigate under which conditions the standard treatment can be justified. Thereby, we address the question of neglecting the wavelength dependence of microscopic response functions. Furthermore, we analyze in how far the fundamental, microscopic wave equation is equivalent to the standard wave equation used intheoretical optics. In particular, we clarify the relation of the “effective” dielectric tensor used there to the microscopic dielectric tensor defined inab initio physics.Graphical abstract
FLRW cosmology with EDSFD parametrization
Authors: Singh J. K. , Nagpal Ritika 
Published: April 2020

AbstractIn this paper, we study a cosmological model in the background of Friedmann–Lemaitre–Robertson–Walker (FLRW) space time by assuming an appropriate parametrization in the form of a differential equation in terms of energy density of scalar field $$\rho _{\phi } $$ρϕ, which is defined as Energy Density Scalar Field Differential equation (EDSFD) parametrization. The EDSFD parametrization leads to a required phase transition from early deceleration to present cosmic acceleration. This parametrization is used to reconstruct the equation of state parameter $$ \omega _{\phi }$$ωϕ in terms of redshift z i.e. $$ \omega _{\phi }(z) $$ωϕ(z) to examine the evolutionary history of the universe in a flat FLRW space time. Here, we constrain the model parameter using the various observational datasets of Hubble parameter H(z) , latest Union 2.1 compilation dataset SNeIa, BAO, joint dataset $$H(z)+SNeIa $$H(z)+SNeIa and $$ H(z)+SNeIa+BAO $$H(z)+SNeIa+BAO for detail analysis of the behavior of physical parameters and we find its best fit present value. Also, we discuss the dynamics of reheating phase after inflation, analyse the behaviors of the physical features using some diagnostic tools, and examine the viability of our parametric model.
CSF1R Is Required for Differentiation and Migration of Langerhans Cells and Langerhans Cell Histiocytosis
Authors: Lonardi Silvia , Scutera Sara , Licini Sara , Lorenzi Luisa , Cesinaro Anna Maria , Gatta Luisa Benerini , Castagnoli Carlotta , Bollero Daniele , Sparti Rosaria , Tomaselli Michela , Medicina Daniela , Calzetti Federica , Cassatella Marco Antonio , Facchetti Fabio , Musso Tiziana , Vermi William 
Published: April 2020

AbstractLangerhans cell histiocytosis (LCH) is a rare disorder characterized by tissue accumulation of CD1a+CD207+ LCH cells. In LCH, somatic mutations of the BRAFV600E gene have been detected in tissue LCH cells, bone marrow CD34+ hematopoietic stem cells, circulating CD14+ monocytes, and BDCA1+ myeloid dendritic cells (DC). Targeting BRAFV600E in clonal Langerhans cells (LC) and their precursors is a potential treatment option for patients whose tumors have the mutation. The development of mouse macrophages and LCs is regulated by the CSF1 receptor (CSF1R). In patients with diffuse-type tenosynovial giant cell tumors, CSF1R inhibition depletes tumor-associated macrophages (TAM) with therapeutic efficacy; however, CSF1R signaling in LCs and LCH has not been investigated. We found through IHC and flow cytometry that CSF1R is normally expressed on human CD1a+CD207+ LCs in the epidermis and stratified epithelia. LCs that were differentiated from CD14+ monocytes, BDCA1+ DCs, and CD34+ cord blood progenitors expressed CSF1R that was downregulated upon maturation. Immature LCs migrated toward CSF1, but not IL34. Administration of the c-FMS/CSF1R kinase inhibitors GW2580 and BLZ945 significantly reduced human LC migration. In LCH clinical samples, LCH cells (including BRAFV600E cells) and TAMs retained high expression of CSF1R. We also detected the presence of transcripts for its ligand, CSF1, but not IL34, in all tested LCH cases. CSF1R and CSF1 expression in LCH, and their role in LC migration and differentiation, suggests CSF1R signaling blockade as a candidate rational approach for treatment of LCH, including the BRAFV600E and wild-type forms of the disease.
Immune Escape during Breast Tumor Progression
Authors: Gil Del Alcazar Carlos R. , Alečković Maša , Polyak Kornelia 
Published: April 2020

Abstract

Immunotherapy using checkpoint inhibitors is one of the most promising current cancer treatment strategies. However, in breast cancer, its success has been limited to a subset of patients with triple-negative disease, whose durability of observed responses remain unclear. The lack of detailed understanding of breast tumor immune evasion mechanisms and the treatment of patients with highly heterogeneous metastatic disease contribute to these disappointing results. Here we discuss the current knowledge about immune-related changes during breast tumor progression, with special emphasis on the in situ-to-invasive breast carcinoma transition that may represent a key step of immunoediting in breast cancer. Comprehensive characterization of early-stage disease and better understanding of immunologic drivers of disease progression will likely expand the tools available for immunotherapy and improve patient stratification.
Mythopoesis, Mysticism, Messianism, and Modernity in Aaron Zeitlin’s Metatron
Authors: Wolski Nathan 
Published: April 2020

Abstract
This article presents an analysis of Aaron Zeitlin’s Metatron: Apokaliptishe poeme, published in Warsaw in 1922. Written at the height of the Yiddish avant-garde, the book-length poem represents the highpoint of Zeitlin’s “neo-kabbalistic” phase. Focusing on the mythopoesis and mystical messianism in the composition, I situate Zeitlin’s thought in the context of Uri Tsvi Greenberg’s Mefisto as well as Hillel Zeitlin’s messianism and ruminations on duality and evil. Paul Tillich’s writings about the divine-demonic provide another lens. Uncovering Zeitlin’s kabbalistic sources reveals the depth of his mythopoetic imagination, which I locate amidst divergent attitudes to myth in Yiddish literature in the early 1920s.
وَهْم اجتماع الحركات وتبعاتُه النحويّة
Authors: الزين عبد الفتّاح 
Published: April 2020

The purpose of this paper is to consider the grammatical implications that result from the traditional philological misconception of the succession of short and long vowels. Most grammarians accepted the analysis of morphologists, thus wrongly assuming that short vowels that are represented in writing after long ones are separate entities. In fact, it is impossible for our vocal apparatus to utter consecutive “sister” vowels (i.e. short and long ones) in one single place, even though we can represent them separately in writing.
But the misconceptions of the ancient grammarians regarding certain issues should not deter us from rejecting them and proposing alternative suggestions. This research will present some of the methods of parsing (iʿrāb) that grammarians have enacted and which can still be found in books of grammar up to the present day. It will also adduce arguments in favor of the suggested alternatives.
Africa Rising: a Pathway of Three Frontiers – Internet of Things, Population Growth and Free Trade Area
Authors: Mutuku Richard Kyalo 
Published: April 2020

Abstract
Africa rising is a raging discourse among policy wonks and African scholars. Some have questioned the veracity of this proposition, while others agree that indeed Africa’s prospects are incontrovertible. In this article, the author developed an exegesis to theorize that Africa’s future growth, at least for the next one century, shall depend on three praxes: internet of things, population growth and the eventual implementation of AfCFTA. Internet of things accentuated by increased internet connectivity is going to create prodigious solutions to African problems, especially in increasing financial inclusion, solving election malpractices through blockchain technology, raising income earnings for rural communities via the sharing economy and improving agribusiness productivity through smart farming. These solutions will mostly target small-holder business players and poor households in hinterland Africa, aiming to lift them from poverty and narrowing the inequality gap. Besides, Africa’s population growth is estimated to reach 2.4 billion by 2050 and theorized to create a market revolution punctuated by a demographic dividend of 15–64-year-olds. The youthful population shall be necessary for providing workforce and technological innovations for driving the wheels of growth in the continent. Moreover, AfCFTA shall be the largest Free Trade Area since the formation of WTO, providing a 1.2 billion people mass market (Signe, 2018: 3). In retrospect, the author intends to demonstrate that the three pathways – the internet of things, population growth and AfCFTA – shall be quintessential building blocks for actualizing the Africa Rising narrative.
Managing uncertainty and references to time in prognostic conversations with family members at the end of life: A conversation analytic study
Authors: Anderson Rebecca J , Stone Patrick C , Low Joseph T S , Bloch Steven 
Published: April 2020

Background: When patients are likely to die in the coming hours or days, families often want prognostic information. Prognostic uncertainty and a lack of end-of-life communication training make these conversations challenging. Aim: The objective of this study is to understand how clinicians and the relatives/friends of patients at the very end of life manage uncertainty and reference time in prognostic conversations. Design: Conversation analysis of audio-recorded conversations between clinicians and the relatives/friends of hospice inpatients. Setting/participants: Experienced palliative care clinicians and relatives/friends of imminently dying hospice inpatients. Twenty-three recorded conversations involved prognostic talk and were included in the analysis. Results: Requests for prognostic information were initiated by families in the majority of conversations. Clinicians responded using categorical time references such as ‘days’, allowing the provision of prognostic estimates without giving a precise time. Explicit terms such as ‘dying’ were rare during prognostic discussions. Instead, references to time were understood as relating to prognosis. Relatives displayed their awareness of prognostic uncertainty when requesting prognostic information, providing clinicians with ‘permission’ to be uncertain. In response, clinicians often stated their uncertainty explicitly, but presented evidence for their prognostic estimates, based on changes to the patient’s function previously discussed with the family. Conclusion: Prognostic uncertainty was managed collaboratively by clinicians and families. Clinicians were able to provide prognostic estimates while being honest about the related uncertainty, in part because relatives displayed their awareness of uncertainty within their requests. The conversation analytic method identified contributions of both clinicians and families, and identified strategies based on real interactions, which could inform communication training.