bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to and recovery from treatment in human liver-mimetic clinostat spheroids: a model for assessing repeated-dose drug toxicity
Authors: Fey Stephen J , Korzeniowska Barbara , Wrzesinski Krzysztof 
Published: May 2020

Abstract
Medicines are usually prescribed for repeated use over shorter or longer times. Unfortunately, repeated-dose animal toxicity studies do not correlate well with observations in man. As emphasized by the ‘3Rs’ and the desire to phase-out animal research, in vitro models are needed. One potential approach uses clinostat-cultured 3D HepG2–C3A liver-mimetic spheroids. They take 18 days to recover in vivo physiological functionality and reach a metabolic equilibrium, which is thereafter stable for a year. Acute and chronic repeated-dose studies of six drugs (amiodarone, diclofenac, metformin, phenformin, paracetamol and valproic acid) suggest that spheroids are more predictive of human in vivo toxicity than either 2D-cultured HepG2 cells or primary human hepatocytes. Repeated non-lethal treatment results in a clear response and return to equilibrium. Mitochondrial toxic compounds can be identified using a galactose-based medium. Some drugs induced a protective (or stress) response that intensifies after the second treatment. This 3D spheroid model is inexpensive, highly reproducible and well-suited for the determination of repeated-dose toxicity of compounds (naturally or chemically synthesized).
Low Splanchnic Oxygenation and Risk for Necrotizing Enterocolitis in Extremely Preterm Newborns
Authors: Palleri Elena , Wackernagel Dirk , Wester Tomas , Bartocci Marco 
Published: May 2020

ABSTRACTObjective:The aim of the study was to investigate whether splanchnic oxygenation (SrSO2), measured with near‐infrared spectroscopy (NIRS), during the first week of life is associated with the risk of developing necrotizing enterocolitis (NEC) in extremely preterm infants.Methods:This was a prospective observational cohort study including extremely preterm infants (<28 weeks of gestation) born at Karolinska University Hospital from September 2014 to December 2016. Using 1‐hour NIRS monitoring during enteral feeding, mainly continuous enteral feeding, in the first week of life we measured both cerebral and splanchnic oxygenation. Primary outcome was risk of developing NEC (Bell stage ≥ II). Secondary outcome was the association between low mean SrSO2 during the first week of life and postnatal age at full enteral nutrition.Results:We enrolled 52 extremely preterm newborns, but only 45 infants had complete NIRS data. One infant developed NEC within 1 day of NIRS monitoring and was excluded from the study. Median gestational age was 25.6 weeks (range 23.0–27.9) and median birth weight 698 g (range 485–1353). Eight infants developed NEC at the median postnatal age of 15 days (range 6–35). Median postnatal age at full enteral nutrition was 10 days (range 6–23). Infants with mean SrSO2 <30% had a higher risk for developing NEC compared with those with SrSO2 >30% (crude risk ratio 5.25; 95% CI [1.19–23.01]). Small for gestational age, gestational age, birth weight, postnatal age did not affect the results. We found no association between SrSO2 and age at full enteral nutrition.Conclusions:Low mean SrSO2 (<30%) during the first week of life is associated with an increased risk for developing NEC in extremely preterm infants on mainly continuous enteral nutrition.
Preconcentration with
Chlorella vulgaris
combined with energy dispersive X-ray fluorescence spectrometry for rapid determination of Cd in water
Authors: Gan Tingting , Zhao Nanjing , Yin Gaofang , Chen Min , Wang Xiang , Hua Hui 
Published: May 2020

Freshwater green algae
Chlorella vulgaris
was selected as an adsorbent, and a simple, rapid, economical and environmentally friendly method for the detection of heavy metal Cd in water samples based on preconcentration with
C. vulgaris
combined with energy dispersive X-ray fluorescence (EDXRF) spectrometry was proposed.
Chlorella vulgaris
could directly and rapidly adsorb Cd
2+
without any pretreatment, and the maximum adsorption efficiency could be obtained when the contact time was 1 min with an optimal pH of 10. The obtained Cd-enriched thin samples after preconcentration with
C. vulgaris
by suction filtration of reaction solution had very good uniformity, which could be directly measured by EDXRF spectrometry, and the net integral fluorescence intensity of Cd K
α
characteristic peak had a very good linear relationship with the initial concentration of Cd in the range of 0.703–74.957 µg ml
−1
with a correlation coefficient of 0.9979. When the Cd thin samples with a Cd-enriched region of 15.1 mm in diameter were formed by the developed preconcentration method with suction filtration of 10 ml reaction solution, the detection limit of this method was 0.0654 µg ml
−1
, which was lower than the maximum allowable discharge concentration of Cd in various industrial wastewaters. The proposed method was simple to operate, and could effectively remove the influence of matrix effect of water samples and effectively improve the sensitivity and stability of EDXRF spectrometry directly detecting heavy metals in water samples, which was successfully applied to detect Cd in real water samples with satisfactory results, and the recoveries ranged from 94.80% to 116.94%. Moreover, this method can be applied to the rapid detection and early warning of excessive Cd in discharged industrial wastewaters. This work will provide a methodological basis for the development of rapid and online monitoring technology and instrument of heavy metal pollutants in water.
Cancer Cell Intrinsic Expression of MHCII Regulates the Immune Microenvironment and Response to Anti-PD-1 Therapy in Lung Adenocarcinoma
Authors: Johnson Amber M. , Bullock Bonnie L. , Neuwelt Alexander J. , Poczobutt Joanna M. , Kaspar Rachael E. , Li Howard Y. , Kwak Jeff W. , Hopp Katharina , Weiser-Evans Mary C. M. , Heasley Lynn E. , Schenk Erin L. , Clambey Eric T. , Nemenoff Raphael A. 
Published: May 2020

AbstractMHC class II (MHCII) expression is usually restricted to antigen presenting cells, but can be expressed by cancer cells. We examined the effect ofcancer cell-intrinsicMHC class II (csMHCII) expression in lung adenocarcinoma on T cell recruitment to tumors and response to anti-PD-1 therapy. The functional significance of altering csMHCII expression was explored using two orthotopic immunocompetent murine models of non-small cell lung cancer: CMT167 (CMT) and Lewis Lung Carcinoma (LLC). We previously showed that CMT167 tumors are eradicated by anti-PD1 therapy, while LLC tumors are resistant. RNA-seq analysis of cancer cells recovered from tumors revealed that csMHCII correlated with response to anti-PD1 therapy, with immunotherapy-sensitive CMT167 cells being csMHCII positive, while resistant LLC cells were csMHCII negative. To test the functional effects of csMHCII, MHCII expression was altered on the cancer cells through loss- and gain-of-function of CIITA, a master regulator of the MHCII pathway. Loss of CIITA in CMT167 decreased csMHCII, and converted tumors from anti-PD-1-sensitive to anti-PD-1-resistant. This was associated with decreased T cell infiltration, lower levels of Th1 cytokines, increased B cell number and decreased macrophage recruitment. Conversely, overexpression of CIITA in LLC cells resulted in csMHCIIin vitroandin vivo. Enforced expression of CIITA increased T cell infiltration and sensitized tumors to anti-PD-1 therapy. csMHCII expression was also examined in a subset of surgically resected human lung adenocarcinomas by multispectral imaging, provided a survival benefit and positively correlated with T cell infiltration. These studies demonstrate a functional role for csMHCII in regulating T cell infiltration and sensitivity to anti-PD-1.
Treatment of COVID-19 Patients with Convalescent Plasma in Houston, Texas
Authors: Salazar Eric , Perez Katherine K. , Ashraf Madiha , Chen Jian , Castillo Brian , Christensen Paul A. , Eubank Taryn , Bernard David W. , Eagar Todd N. , Long S. Wesley , Subedi Sishir , Olsen Randall J. , Leveque Christopher , Schwartz Mary R. , Dey Monisha , Chavez-East Cheryl , Rogers John , Shehabeldin Ahmed , Joseph David , Williams Guy , Thomas Karen , Masud Faisal , Talley Christina , Dlouhy Katharine G. , Lopez Bevin Valdez , Hampton Curt , Lavinder Jason , Gollihar Jimmy D. , Maranhao Andre C. , Ippolito Gregory C. , Saavedra Matthew Ojeda , Cantu Concepcion C. , Yerramilli Prasanti , Pruitt Layne , Musser James M. 
Published: May 2020

ABSTRACTBackgroundCOVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years.MethodsPatients (n=25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28 – April 14, 2020. Patients were transfused with convalescent plasma obtained from donors with confirmed SARS-CoV-2 infection and had been symptom free for 14 days. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 post-transfusion. Clinical improvement was assessed based on a modified World Health Organization 6-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains.ResultsAt baseline, all patients were receiving supportive care, including anti-inflammatory and anti-viral treatments, and all patients were on oxygen support. At day 7 post-transfusion with convalescent plasma, nine patients had at least a 1-point improvement in clinical scale, and seven of those were discharged. By day 14 post-transfusion, 19 (76%) patients had at least a 1-point improvement in clinical status and 11 were discharged. No adverse events as a result of plasma transfusion were observed. The whole genome sequencing data did not identify a strain genotype-disease severity correlation.ConclusionsThe data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease. Randomized, controlled trials are needed to determine its efficacy.
The Epidemiology of COVID-19 and applying Non Pharmaceutical interventions by using the Susceptible, Infectious Recovered epidemiological Model in Pakistan
Authors: Wahid Abdul , Khan Amjad , Iqbal Qaiser , Khan Asad , Mohammad Nazar 
Published: May 2020

ABSTRACTIntroductionThe COVID-19 is caused by the virus known as sever acute respiratory syndrome corona virus 2 (SARS-CoV-2) having the common symptoms such as Flue, fever, dry cough and shortness of breath. The first case was reported in WUHAN city china in December 2019 and it spread to the whole world, WHO declared as world pandemic on 11thmarch 2020.SIR Epidemiological ModelThe first case in Pakistan was confirmed on 26thFeb 2020 as by the 8thApril 2020 the total no of confirmed cases 4187 with 58 deaths and 467 recoveries throughout the country. The upcoming situation of the COVID-19 in Pakistan is forecasted by using SIR epidemiological, which is one of the mathematical derivative models with great accuracy rate prediction used for infectious disease. This model was introduced in the early 20thcentury.ResultsPakistan is will be having a heavy burden of patients 80000 plus infected patients 45000 recoveries 10000 hospitalized 3000 ICU and 800 plus deaths in the next 20 days. A complete lock down, social distancing and imposing curfew to keep every person at home can save Pakistan from a very huge number 1000000 infected patients with huge number of causalities with next 2 months.
Serum protein profiling reveals a landscape of inflammation and immune signaling in early-stage COVID-19 infection
Authors: Hou Xin , Zhang Xiaomei , Wu Xian , Lu Minya , Wang Dan , Xu Meng , Wang Hongye , Liang Te , Dai Jiayu , Duan Hu , Xu Yingchun , Yu Xiaobo , Li Yongzhe 
Published: May 2020

SummaryCoronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=125) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.
The confounded crude case-fatality rates (CFR) for COVID-19 hide more than they reveal - a comparison of age-specific and age-adjusted CFRs between six countries
Authors: Green Manfred S , Peer Victoria , Swartz Naama , Nitzan Dorit 
Published: May 2020

AbstractBackgroundThe reported crude case-fatality rates (CFRs) vary widely between countries. The serious limitations of using crude COVID-19 CFRs for comparisons between countries have been addressed in the literature but are often overlooked or misunderstood, both in the scientific literature and in the media. In this paper we examined the extent to which age distribution of the cases is responsible for the differences in CFRs between countries.MethodsData on COVID-19 were extracted from the reports of individual countries. Overall and age-specific CFRs were available for six countries. The CFRs by country were adjusted for age using the direct method, using the combined age-specific number of cases of all six countries as the standard population.FindingsThe age distribution of the cases varied widely between countries. The crude CFRs varied between 1.6% and 11%. The differences in the age-specific CFRs were much smaller and the age-adjusted rates were much closer than the crude rates. The ratio of the crude CFR for the country with the highest CFR to that with the lowest, was reduced substantially for the age-adjusted rates, from 7.4 to 2.3ConclusionsThe age structure of the cases dramatically impacts on the differences in the crude CFRs between countries. Adjusting for age substantially reduces this variation. Other factors such as the differences in the definition of the denominators, the definition of a case and the standard of healthcare are likely to account for much of the residual variation. It is misleading to compare the crude COVID-19 CFRs between countries and should be avoided. At the very least, comparisons should be based on age-specific and age-adjusted rates.
Lower State COVID-19 Deaths and Cases with Earlier School Closure in the U.S.
Authors: Rauscher Emily 
Published: May 2020

AbstractThis study quantifies the relationship between school closure timing and COVID-19 deaths and cases in the general population in all U.S. states. COVID-19 has higher symptomatic infection rates among the elderly, suggesting school closures could be unrelated to transmission. However, predicting daily cumulative COVID-19 deaths by state, earlier school closure is related to fewer deaths per capita and slower growth in deaths per capita. Results are similar for COVID-19 cases per capita.
Effects of long-termin vivomicro-CT imaging on hallmarks of osteopenia and frailty in aging mice
Authors: Scheuren Ariane C. , Kuhn Gisela A. , Müller Ralph 
Published: May 2020

AbstractIn vivomicro-CT has already been used to monitor microstructural changes of bone in mice of different ages and in models of age-related diseases such as osteoporosis. However, as aging is accompanied by frailty and subsequent increased sensitivity to external stimuli such as handling and anesthesia, the extent to which longitudinal imaging can be applied in aging studies remains unclear. Consequently, the potential of monitoring individual mice during the entire aging process – from healthy to frail status – has not yet been exploited. In this study, we assessed the effects of long-termin vivomicro-CT imaging - consisting of 11 imaging sessions over 20 weeks - on hallmarks of aging both on a local (i.e., static and dynamic bone morphometry) and systemic (i.e., frailty index (FI) and body weight) level at various stages of the aging process. Furthermore, using a premature aging model (PolgA(D257A/D257A)), we assessed whether these effects differ between genotypes.The 6thcaudal vertebrae of 4 groups of mice (PolgA(D257A/D257A)and PolgA(+/+)) were monitored byin vivomicro-CT every 2 weeks. One group was subjected to 11 scans between weeks 20 and 40 of age, whereas the other groups were subjected to 5 scans between weeks 26-34, 32-40 and 40-46, respectively. The long-term monitoring approach showed small but significant changes in the static bone morphometric parameters compared to the other groups. However, no interaction effect between groups and genotype was found, suggesting that PolgA mutation does not render bone more or less susceptible to long-term micro-CT imaging. The differences between groups observed in the static morphometric parameters were less pronounced in the dynamic morphometric parameters. Moreover, the body weight and FI were not affected by more frequent imaging sessions. Finally, we observed that longitudinal designs including baseline measurements at young adult age are more powerful at detecting effects ofin vivomicro-CT imaging on hallmarks of aging than cross-sectional comparisons between multiple groups of aged mice subjected to fewer imaging sessions.
Walking pattern analysis using deep learning for energy harvesting smart shoes with IoT
Authors: Shah Neel , Kamdar Laxit , Gokalgandhi Drashti , Mehendale Ninad 
Published: May 2020

ABSTRACTWearable Health Devices (WHDs) benefit people to monitor their health status and have become a necessity in today’s world. The smart shoe is the type of WHD, that provides comfort, convenience, and fitness tracking. Hence smart shoes can be considered as one of the most useful innovations in the field of wearable devices. In this paper, we propose a unique system, in which the smart shoes are capable of energy harvesting when the user is walking, running, dancing, or carrying out any other similar activities. This generated power can be used to charge portable devices (like mobile) and to light up the LED torch. It also has Wi-Fi-that allows it to get connected to smartphones or any device on a cloud. The recorded data was used to determine the walking pattern of the user (gait analysis) using deep learning. The overall classification accuracy obtained with proposed smart shoes could reach up to 96.2 %. This gait analysis can be further used for detecting any injury or disorder that the shoe user is suffering from. One more unique feature of the proposed smart shoe is its capability of adjusting the size by using inflatable technology as per the user’s comfort.
Pan-cancer identification of clinically relevant genomic subtypes using outcome-weighted integrative clustering
Authors: Arora Arshi , Olshen Adam B. , Seshan Venkatraman E. , Shen Ronglai 
Published: May 2020

ABSTRACTMolecular phenotypes of cancer are complex and influenced by a multitude of factors. Conventional unsupervised clustering of heterogeneous cancer patient populations is inevitably driven by the dominant variation from major factors such as cell-of-origin or histology. Drawing from ideas in supervised text classification, we developed survClust, an outcome-weighted clustering algorithm for integrative patient stratification. We show survClust outperforms unsupervised clustering in identifying cancer patient subpopulations characterized by specific genomic phenotypes with more aggressive clinical behavior. The algorithm and tools we developed have direct utility toward clinically relevant patient stratification based on tumor genomics to inform clinical decision-making.
Inhibition of 2-Hydroxyglutrate Elicits Metabolic-reprograming and Mutant IDH1 Glioma Immunity
Authors: Kadiyala Padma , Carney Stephen V. , Gauss Jessica C. , Garcia-Fabiani Maria B. , Núñez Felipe J. , Nunez Fernando M. , Alghamri Mahmoud S. , Liu Yayuan , Yu Minzhi , Li Dan , Edwards Marta B. , Moon James J. , Schwendeman Anna , Lowenstein Pedro R. , Castro Maria G. 
Published: May 2020

AbstractMutant isocitrate-dehydrogenase-1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas. Lower grade mIDH1 gliomas are classified into two molecular subgroups: (i) 1p/19q co-deletion/TERT-promoter mutations or (ii) inactivating mutations in α-thalassemia/mental retardation syndrome X-linked (ATRX) andTP53.This work, relates to the gliomas’ subtype harboring mIDH1,TP53andATRXinactivation. IDH1-R132H is a gain-of-function mutation that converts α-ketoglutarate into 2-hydroxyglutarate (D-2HG). The role of D-2HG within the tumor microenvironment of mIDH1/mATRX/mTP53 gliomas remains unexplored. Inhibition of 2HG, when used as monotherapy or in combination with radiation and temozolomide (IR/TMZ), led to increased median survival (MS) of mIDH1 glioma bearing mice. Also, 2HG inhibition elicited anti-mIDH1 glioma immunological memory. In response to 2HG inhibition, PD-L1 expression levels on mIDH1-glioma cells increased to similar levels as observed in wild-type-IDH1 gliomas. Thus, we combined 2HG inhibition/IR/TMZ with anti-PDL1 immune checkpoint-blockade and observed complete tumor regression in 60% of mIDH1 glioma bearing mice. This combination strategy reduced T-cell exhaustion and favored the generation of memory CD8+T-cells. Our findings demonstrate that metabolic reprogramming elicits anti-mIDH1 glioma immunity, leading to increased MS and immunological memory. Our preclinical data supports the testing of IDH-R132H inhibitors in combination with IR/TMZ and anti-PDL1 as targeted therapy for mIDH1/mATRX/mTP53 glioma patients.Brief SummaryInhibition of 2-Hydroxyglutrate in mutant-IDH1 glioma in the genetic context of ATRX and TP53 inactivation elicits metabolic-reprograming and anti-glioma immunity.