bluuebunny/crossref_metadata_2025_split huggingface dataset:
Profiling parvalbumin interneurons using iPSC: challenges and perspectives for Autism Spectrum Disorder (ASD)
Authors: Filice Federica , Schwaller Beat , Michel Tanja M. , Grünblatt Edna 
Published: January 2020

AbstractAutism spectrum disorders (ASD) are persistent conditions resulting from disrupted/altered neurodevelopment. ASD multifactorial etiology—and its numerous comorbid conditions—heightens the difficulty in identifying its underlying causes, thus obstructing the development of effective therapies. Increasing evidence from both animal and human studies suggests an altered functioning of the parvalbumin (PV)-expressing inhibitory interneurons as a common and possibly unifying pathway for some forms of ASD. PV-expressing interneurons (short: PVALB neurons) are critically implicated in the regulation of cortical networks’ activity. Their particular connectivity patterns, i.e., their preferential targeting of perisomatic regions and axon initial segments of pyramidal cells, as well as their reciprocal connections, enable PVALB neurons to exert a fine-tuned control of, e.g., spike timing, resulting in the generation and modulation of rhythms in the gamma range, which are important for sensory perception and attention.New methodologies such as induced pluripotent stem cells (iPSC) and genome-editing techniques (CRISPR/Cas9) have proven to be valuable tools to get mechanistic insight in neurodevelopmental and/or neurodegenerative and neuropsychiatric diseases. Such technological advances have enabled the generation of PVALB neurons from iPSC. Tagging of these neurons would allow following their fate during the development, from precursor cells to differentiated (and functional) PVALB neurons. Also, it would enable a better understanding of PVALB neuron function, using either iPSC from healthy donors or ASD patients with known mutations in ASD risk genes. In this concept paper, the strategies hopefully leading to a better understanding of PVALB neuron function(s) are briefly discussed. We envision that such an iPSC-based approach combined with emerging (genetic) technologies may offer the opportunity to investigate in detail the role of PVALB neurons and PV during “neurodevelopment ex vivo.”
Acute kidney injury and hepatitis associated with energy drink consumption: a case report
Authors: Al Yacoub Raed , Luczkiewicz Debra , Kerr Christopher 
Published: January 2020

Abstract
Introduction
In the USA, energy drinks are commonly consumed among adults. The side effects of these drinks are not well studied but consumers have reported multiple adverse events to the US Food and Drug Administration including acute kidney injury and acute hepatitis.

Case presentation
A 62-year-old white woman presented with progressive weakness, fatigue, confusion, and delirium secondary to acute kidney injury and acute hepatitis associated with excessive energy drink use. Clinical improvement occurred with supportive care and discontinuation of energy drinks, with resolution of acute kidney injury and progressive improvement of liver function. The defined mechanism of injury is unknown but thought due to energy drink ingredients.

Conclusion
Multiple cases of energy drink-induced acute kidney injury or acute hepatitis are reported in the literature but this case is the first to report them simultaneously. Ingredients and presumed doses to cause these events are outlined in this case report.
EphrinB2 overexpression enhances osteogenic differentiation of dental pulp stem cells partially through ephrinB2-mediated reverse signaling
Authors: Wang Wen , Yuan Changyong , Geng Tengyu , Liu Yi , Zhu Shaoyue , Zhang Chengfei , Liu Zongxiang , Wang Penglai 
Published: January 2020

Abstract
Background
Alveolar bone loss is a frequent occurrence. Dental pulp stem cells (DPSCs) which have invasive accessibility and high osteogenic potential is a promising source for cell-based bone regeneration. EphrinB2 is involved in bone homeostasis and osteogenesis. The aim of this study was to investigate the effect and mechanism of ephrinB2 overexpression on osteogenic differentiation of DPSCs and bone defect repair.

Methods
EphrinB2 expression was analyzed during osteogenic induction of human DPSCs (hDPSCs). Endogenous ephrinB2 expression in hDPSCs was then upregulated using EfnB2 lentiviral vectors. The effect of ephrinB2 overexpression on osteogenic differentiation capacity of hDPSCs was investigated in vitro, and activation of ephrinB2-EphB4 bidirectional signaling in ephrinB2-overexpressing hDPSCs was detected. In vivo, a canine alveolar bone defect model was established and canine DPSCs (cDPSCs) were cultured, characterized, EfnB2-tranfected, and combined with a PuraMatrix scaffold. Micro-CT analysis was performed to evaluate the therapeutic effect of ephrinB2-overexpressing cDPSCs on bone defect repair.

Results
EphrinB2 was upregulated after osteogenic induction of hDPSCs. EphrinB2 overexpression enhanced osteogenic differentiation capacity of hDPSCs in vitro. Moreover, p-ephrinB2 instead of p-EphB4 was upregulated by ephrinB2 overexpression, and activation of ephrinB2-mediated reverse signaling promoted osteogenic differentiation of hDPSCs. In a canine bone defect model, ephrinB2 overexpression in cDPSCs significantly improved trabecular bone volume per tissue volume (BV/TV) and trabecular thickness, as demonstrated by radiographic analysis.

Conclusions
EphrinB2 overexpression enhanced osteogenic potential of DPSCs partially via upregulation of ephrinB2-mediated reverse signaling and effectively promoted alveolar bone defect repair.
TGF-β/SMAD signaling regulation of mesenchymal stem cells in adipocyte commitment
Authors: Li Sheng-Nan , Wu Jia-Fa 
Published: January 2020

AbstractAdipocytes arising from mesenchymal stem cells (MSCs) requires MSC adipocyte commitment and differentiation of preadipocytes to mature adipocytes. Several signaling and some cytokines affect the adipogenesis of MSCs. This review focuses on the roles of TGF-β/SMAD signaling in adipocyte commitment of MSCs. BMP4 and BMP7 signaling are sufficient to induce adipocyte lineage determination of MSCs. The roles of BMP2, TGF-β, and myostatin signaling in this process are unclear. Other TGF-β/SMAD signaling such as BMP3 and BMP6 signaling have almost no effect on commitment because of limited research available, while GDF11 signaling inhibits adipocyte commitment in human MSCs. In this review, we summarize the available information on TGF-β/SMAD signaling regulation of MSCs in adipocyte commitment. Deeper study of this commitment mechanism will offer new approaches in treating obesity, diabetes mellitus, and obesity-related metabolism syndrome.
The use of micro-costing in economic analyses of surgical interventions: a systematic review
Authors: Potter Shelley , Davies Charlotte , Davies Gareth , Rice Caoimhe , Hollingworth William 
Published: January 2020

AbstractBackgroundCompared with conventional top down costing, micro-costing may provide a more accurate method of resource-use assessment in economic analyses of surgical interventions, but little is known about its current use. The aim of this study was to systematically-review the use of micro-costing in surgery.MethodsComprehensive searches identified complete papers, published in English reporting micro-costing of surgical interventions up to and including 22nd June 2018. Studies were critically appraised using a modified version of the Consensus on Health Economic Criteria (CHEC) Checklist. Study demographics and details of resources identified; methods for measuring and valuing identified resources and any cost-drivers identified in each study were summarised.ResultsA total of 85 papers were identified. Included studies were mainly observational comparative studies (n = 42, 49.4%) with few conducted in the context of a randomised trial (n = 5, 5.9%). The majority of studies were single-centre (n = 66, 77.6%) and almost half (n = 40, 47.1%) collected data retrospectively. Only half (n = 46, 54.1%) self-identified as being ‘micro-costing’ studies. Rationale for the use of micro-costing was most commonly to compare procedures/techniques/processes but over a third were conducted specifically to accurately assess costs and/or identify cost-drivers. The most commonly included resources were personnel costs (n = 76, 89.4%); materials/disposables (n = 76, 89.4%) and operating-room costs (n = 62,72.9%). No single resource was included in all studies. Most studies (n = 72, 84.7%) identified key cost-drivers for their interventions.ConclusionsThere is lack of consistency regarding the current use of micro-costing in surgery. Standardising terminology and focusing on identifying and accurately costing key cost-drivers may improve the quality and value of micro-costing in future studies.Trial registrationPROSPERO registrationCRD42018099604.
ATM, ATR and DNA-PKcs kinases—the lessons from the mouse models: inhibition ≠ deletion
Authors: Menolfi Demis , Zha Shan 
Published: January 2020

AbstractDNA damage, especially DNA double strand breaks (DSBs) and replication stress, activates a complex post-translational network termed DNA damage response (DDR). Our review focuses on three PI3-kinase related protein kinases—ATM, ATR and DNA-PKcs, which situate at the apex of the mammalian DDR. They are recruited to and activated at the DNA damage sites by their respective sensor protein complexes—MRE11/RAD50/NBS1 for ATM, RPA/ATRIP for ATR and KU70–KU80/86 (XRCC6/XRCC5) for DNA-PKcs. Upon activation, ATM, ATR and DNA-PKcs phosphorylate a large number of partially overlapping substrates to promote efficient and accurate DNA repair and to coordinate DNA repair with other DNA metabolic events (e.g., transcription, replication and mitosis). At the organism level, robust DDR is critical for normal development, aging, stem cell maintenance and regeneration, and physiological genomic rearrangements in lymphocytes and germ cells. In addition to endogenous damage, oncogene-induced replication stresses and genotoxic chemotherapies also activate DDR. On one hand, DDR factors suppress genomic instability to prevent malignant transformation. On the other hand, targeting DDR enhances the therapeutic effects of anti-cancer chemotherapy, which led to the development of specific kinase inhibitors for ATM, ATR and DNA-PKcs. Using mouse models expressing kinase dead ATM, ATR and DNA-PKcs, an unexpected structural function of these kinases was revealed, where the expression of catalytically inactive kinases causes more genomic instability than the loss of the proteins themselves. The spectrum of genomic instabilities and physiological consequences are unique for each kinase and depends on their activating complexes, suggesting a model in which the catalysis is coupled with DNA/chromatin release and catalytic inhibition leads to the persistence of the kinases at the DNA lesion, which in turn affects repair pathway choice and outcomes. Here we discuss the experimental evidences supporting this mode of action and their implications in the design and use of specific kinase inhibitors for ATM, ATR and DNA-PKcs for cancer therapy.
Design and implementation of intelligent accounting data analysis platform based on industrial cloud computing
Authors: Ting Wang , Liu Yang 
Published: January 2020

AbstractIn order to improve the ability of accounting data analysis and statistics, a method of constructing modern accounting data analysis platform based on industrial cloud computing is proposed. The time series model of modern accounting data analysis is constructed by using block bit sequence analysis method, and the association rule characteristic quantity of accounting data is extracted. Combined with cloud computing technology, the modern accounting data analysis platform is constructed, and the fuzzy C-means clustering algorithm is used to realize the clustering of modern accounting data, which can improve the ability of parallel computing and statistical analysis of accounting data. The simulation results show that the intelligent data analysis platform designed makes the statistical analysis ability of accounting data better and the parallel computing efficiency higher.
Whole‐transcriptome sequencing uncovers core regulatory modules and gene signatures of human fetal growth restriction
Authors: Wang Guiying , Yu Jun , Yang Yiwei , Liu Xiaoqin , Zhao Xiaobo , Guo Xudong , Duan Tao , Lu Chenqi , Kang Jiuhong 
Published: January 2020

AbstractBackgroundFetal growth restriction (FGR) contributes the primary cause of perinatal mortality and morbidity with impacts on the long‐term health. To determine the core gene expression network and gene signatures, which in combination with ultrasound confirmation will more effectively differentiate constitutionally normal small for gestational age and pathological FGR groups, we performed RNA sequencing for protein‐coding genes, lncRNAs, and small RNAs in a case–control study of umbilical cord blood.ResultsFive pairs of FGR case and control umbilical cord blood samples were used for RNA sequencing and weighted gene co‐expression network analysis (WGCNA). Results showed that 339 mRNAs, 295 lncRNAs, and 13 miRNAs were significantly differentially expressed between FGR cases and controls. Bioinformatics analysis indicated that these differentially expressed molecules were mainly involved in metabolism, neural, cardiac, and immune systems, and identified 18 WGCNA modules for FGR. Further quantitative verification was performed using umbilical cord blood and maternal peripheral blood from 12 pairs of FGR cases and controls. The logistic regression and receiver operating characteristic curve indicated that RP11_552M6.1, LINC01291, and Asgr1 in umbilical cord blood, while Sfrp2, miR‐432‐5p, and miR‐1306‐3p in maternal peripheral blood had potential significance for FGR.ConclusionsWe comprehensively profiled the whole‐transcriptome landscape of human umbilical cord blood with FGR, constructed the core WGCNA modules, and delineated the critical gene signatures of FGR. These findings provide key insight into intrauterine perturbations and candidate signatures for FGR.
Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series
Authors: Carmen Matthew , Safer Debra Lynn , Saslow Laura R. , Kalayjian Tro , Mason Ashley E. , Westman Eric C. , Sethi Shebani 
Published: January 2020

AbstractBackgroundMany patients with obesity and comorbid binge eating symptoms present with the desire to lose weight. Although some studies suggest that dietary restriction can exacerbate binge eating, others show dietary restriction is associated with significant reductions in binge eating. The effect of a particular type of dieting on binge eating, the ketogenic diet (a high fat, moderate protein, very low carbohydrate diet), is not known.Case presentationsWe report on the feasibility of a low-carbohydrate ketogenic diet initiated by three patients (age 54, 34, and 63) with obesity (average BMI 43.5 kg/m2) with comorbid binge eating and food addiction symptoms. All patients tolerated following the ketogenic diet (macronutrient proportion 10% carbohydrate, 30% protein, and 60% fat; at least 5040 kJ) for the prescribed period (e.g., 6–7 months) and none reported any major adverse effects. Patients reported significant reductions in binge eating episodes and food addiction symptoms including cravings and lack of control as measured by the Binge-Eating Scale, Yale Food Addiction Scale, or Yale-Brown Obsessive-Compulsive Scale modified for Binge Eating, depending on the case. Additionally, the patients lost a range of 10–24% of their body weight. Participants reported maintenance of treatment gains (with respect to weight, binge eating, and food addiction symptoms) to date of up to 9–17 months after initiation and continued adherence to diet.ConclusionsAlthough the absence of control cases precludes conclusions regarding the specific role of ketogenic diets versus other forms of dietary restriction, this is the first report to demonstrate the feasibility of prescribing a ketogenic diet for patients with obesity who report binge eating and food addiction symptoms. Further research should seek to reproduce the observed effects in controlled trials as well as to explore potential etiologies.
PSCA is a target of chimeric antigen receptor T cells in gastric cancer
Authors: Wu Di , Lv Jiang , Zhao Ruocong , Wu Zhiping , Zheng Diwei , Shi Jingxuan , Lin Simiao , Wang Suna , Wu Qiting , Long Youguo , Li Peng , Yao Yao 
Published: January 2020

Abstract
Background
Gastric cancer is a deadly malignancy and is a prognostically unfavorable entity with restricted therapeutic strategies available. Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein widely expressed in bladder, prostate, and pancreatic cancers. Existing studies have thoroughly recognized the availability of utilizing anti-PSCA CAR-T cells in the treatment of metastatic prostate cancer and non-small-cell lung cancer. However, no previous study has investigated the feasibility of using anti-PSCA CAR-T cells to treat gastric cancer, irrespective of the proven expression of PSCA on the gastric cancer cell surface.

Methods
We determined the expression of PSCA in several primary tumor tissues and constructed third-generation anti-PSCA CAR-T cells. We then incubated anti-PSCA CAR-T cells and GFP-T cells with target tumor cell lines at E:T ratios of 2:1, 1:1, 1:2, and 1:4 to evaluate the therapeutic efficacy of anti-PSCA CAR-T cells in vitro. We also assayed canonical T cell activation markers after coculturing anti-PSCA CAR-T cells with target cell lines by flow cytometry. The detection of a functional cytokine profile was carried out via enzyme-linked immunosorbent assays. We then evaluated the antitumor activity of anti-PSCA CAR-T cells in vivo by establishing two different xenograft GC mouse models.

Results
Anti-PSCA CAR-T cells exhibited upregulated activation markers and increased cytokine production profiles related to T cell cytotoxicity in an antigen-dependent manner. Moreover, anti-PSCA CAR-T cells exhibited robust anti-tumor cytotoxicity in vitro. Importantly, we demonstrated that anti-PSCA CAR-T cells delivered by peritumoral injection successfully stunted tumor progression in vivo. However, intravenous administration of anti-PSCA CAR-T cells failed to reveal any therapeutic improvements.

Conclusions
Our findings corroborated the feasibility of anti-PSCA CAR-T cells and their efficacy against gastric cancer, implicating the potential of applying anti-PSCA CAR-T cells to treat GC patients in the clinic.
Effect of concentration, aging, and annealing on sol gel ZnO and Al-doped ZnO thin films
Authors: Speaks D. T. 
Published: January 2020

AbstractPresented are experimental results on the effect of concentration, aging, and annealing time on the optical and structural properties of sol gel zinc oxide (ZnO) and Al-doped ZnO thin films. ZnO and ZnO:Al thin films were fabricated on glass substrates using spin coating followed by annealing. XRD confirmed that the films are polycrystalline wurtzite. For low concentration films (0.2 and 0.4 M), grain size increased with aging time up to 72 hours. For high concentration samples (0.6 and 0.8 M), grain size increased only up to 48 hours. Additional aging resulted in a decrease in the grain size. The largest grain sizes were found for 0.4 M at 72 hours and 0.6 M at 48 hours. The band gap tended to decrease with increasing aging time for all concentrations. The smallest band gap for each aging time (24, 48, and 72 hours) was observed for 0.6 M films. These results suggest that higher concentration sol gel near 0.6 M may yield better properties with shorter aging times than 0.2 and 0.4 M films. Annealing data suggests that 350oC is the minimum annealing at 1 hour to achieve high-quality films and higher concentration ZnO films have stronger diffraction peaks. ZnO:Al also exhibits stronger diffraction peaks and a larger blue shift of the band edge with increasing sol gel concentration.
Three-dimensional finite element analysis of extra short implants focusing on implant designs and materials
Authors: Araki Haruka , Nakano Tamaki , Ono Shinji , Yatani Hirofumi 
Published: January 2020

Abstract
Aim
When using short implants, fracture of the implant body and bone resorption are a concern because stress concentrates on and around a short implant. The purpose of this research is to investigate the differences in stress distribution between tissue level (TL) and bone level (BL) implant body designs, and between commercially pure titanium (cpTi) and the newer titanium–zirconium (TiZr) alloy in using short implants.

Materials and methods
Models of TL and BL implants were prepared for three-dimensional finite element analysis. The implants were produced in 10 mm, 8 mm, and 6 mm lengths, and the TL was also produced in a 4-mm length. A static load of 100 N inclined at 30° to the long axis was applied to the buccal side of the model. The largest maximum principal stress value in the cortical bone and the largest von Mises stress value in the implant body were evaluated.

Results
Stress concentration was observed at the connection part of the implant, especially above the bone in TL and within the bone in BL. In the TL design, tensile stress occurred on the buccal side and compressive stress on the lingual side of the cortical bone. Conversely, in the BL design, tensile stress occurred on the lingual side of the cortical bone. CpTi and TiZr showed a similar stress distribution pattern. The maximum stress values were lower in the TL design than the BL design, and they were lower with TiZr than cpTi for both the cortical bone and implant body. The maximum value tended to increase as the length of the implant body decreased. In addition, the implant body design was more influential than its length, with the TL design showing a stress value similar to the longer BL design.

Conclusion
Using TiZr and a TL design may be more useful mechanically than cpTi and a BL design when the length of the implant body must be shorter because of insufficient vertical bone mass in the mandible.
Molecular epidemiology of malaria parasite amongst patients in a displaced people’s camp in Sudan
Authors: Eshag Hamza Adam , Elnzer Elfadel , Nahied Elkhatieb , Talib Mustafa , Mussa Ali , Muhajir Abd Elhafiz M. A. , Ibrahim Ibrahim Khider , Sabo Abdulwali , Elzaki Salah-Eldin Gumma , Mohamed Zeehaida , Hajissa Khalid 
Published: January 2020

AbstractBackgroundDespite the importance of epidemiological studies in the development of effective control strategies and provision of basic health services for refugees and internally displaced persons (IDPs), data on the prevalence of malaria are limited. Thus, this study was conducted to estimate the molecular prevalence of malaria amongst the displaced population in Ardamata IDP camp in Al-Geneina City, Sudan.MethodsA cross-sectional study was conducted from July 2018 to December 2018 to estimate malaria prevalence amongst the displaced population in Ardamata IDP camp in Al-Geneina City, Sudan. A total of 380 patients with suspected malaria were recruited. Nested polymerase chain reaction (nPCR) assays were performed to detect thePlasmodiumgenus and species.ResultsOf 380 patients, 232 (61.1%) were positive for malaria.Plasmodium falciparumwas the only prevalent species detected amongst the study population. nPCR analysis revealed that none of the samples hadPlasmodium vivax,Plasmodium ovaleorPlasmodium malariae. The malaria prevalence rate was higher amongst males (67.1%) than in females (56.8%), and gender was the only risk factor that was significantly associated with malaria infection (p = .042).ConclusionsDespite control programmes, malaria remains a significant cause of illness amongst a displaced population. The high prevalence of malaria infection in this study indicates that additional health facilities and control strategies should be implemented in displaced camps and the surrounding areas.