bluuebunny/crossref_metadata_2025_split huggingface dataset:
Latent Therapeutic Demand of Immunoglobulin therapies in neuropathies – chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain–Barré syndrome (GBS) and multifocal motor neuropathy (MMN) in the United States
Authors: Bansal Megha , Farrugia Albert 
Published: June 2020

AbstractChronic inflammatory demyelinating polyneuropathy (CIDP) is a neurological disorder characterized by progressive weakness and impaired sensory function in the legs and arms. Guillain-Barré syndrome is a disorder in which the body’s immune system attacks part of the peripheral nervous system. The first symptoms of this disorder include varying degrees of weakness or tingling sensations in the legs (NIH). Multifocal motor neuropathy is a progressive muscle disorder characterized by muscle weakness in the hands, with differences from one side of the body to the other in the specific muscles involved (NIH). We have modeled a latent therapeutic demand (LTD) of IVIg for CIDP and similar neuropathies in the US. We used the decision analysis methodology similar to the methods used by Stonebraker et al1for modeling LTD of IVIg. The model is based on the relationships of the epidemiological and clinical factors. Most of the usage patterns and dosage level of albumin are according to the epidemiological studies and clinical trials. The model is built in Microsoft Excel. The analysis is conducted based on oneway sensitivity analysis and probabilistic sensitivity analysis. The demand in terms of grams per 1,000 inhabitants is calculated depending on the treatment schedule and the prevalence of the disease. The model for CIDP has eight variables including prevalence of CIDP, patients using IVIg, dosage and treatment patterns. The annual demand of IVIg is based on initial treatment of 24 weeks followed by a maintenance period, with lower dosage and frequency of treatment for another 24 weeks2. The model for GBS has eight variables with a loading dose for 3-6 days followed by a second dose in case of relapse. The model for MMN has nine variables. It has a loading dose followed by maintenance dose every 1-6 weeks depending on the clinical factors of the patient. On an average, IVIg use was calculated as 100 gms, 5.6 gms and 35 gms per 1,000 inhabitants for CIDP, GBS and MMN, respectively, in the US annually.
Correlation of the global spread of coronavirus disease-19 with atmospheric air temperature
Authors: Bezabih Yihienew M. , Mequanint Alemitu , Alamneh Endalkachew , Bezabih Alemayehu , Sabiiti Wilber , Roujeinikova Anna , Bezabhe Woldesellassie M. 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus that may be sensitive to heat. We assessed whether the spread of coronavirus disease 2019 (COVID-19) correlates with air temperature. We also studied whether additional climate, geographical, and population variables were correlated. The total number of confirmed COVID-19 cases and mortality rates reported in each country between 1st Jan and 31st Mar 2020 were compared with the country’s three-month average atmospheric air temperature, precipitation and latitude. Spearman’s correlation coefficient (ρ) was used to identify significant correlations. Our analysis included a total of 748,555 confirmed COVID-19 cases worldwide. The total number of patients with COVID-19 decreased with increasing atmospheric air temperature (ρ = –0.54, 95%CI: [-0.64, –0.42]; P <0.001) and increased with an increasing latitude (ρ = 0.60, 95%CI: [0.48, 0.70]; P <0.001). Our findings justify further studies to examine the effect of air temperature on infectivity of SAR-CoV-2.
Toll-like Receptor 9 in breast carcinoma is a good prognostic marker in patients treated with neoadjuvant chemotherapy
Authors: Singh Aradhana , Bandyopadhyay Arghya , Mukherjee Narendranath , Basu Anupam 
Published: June 2020

AbstractPurposeTLR9 is the sensor of fragmented nucleic acid signature as a part of innate immune surveillance. TLR9 can recognize the DNA fragments released from the chemotherapy-treated cancer cells in tumour tissue and induce an inflammatory response.The aim of this was toinvestigate the prognostic importance and survivability benefit of TLR9 expression in breast cancer patients treated with neoadjuvant chemotherapy.MethodsExpression of TLR9 in breast carcinoma samples was studied in two patient cohorts, with neoadjuvant chemotherapy (NACT), and without NACT, by immunohistochemistry. Expression of TLR9 was analysed in relation to prognosis, overall survivability as well as risk factor analysis for neoadjuvant chemotherapy treatment using web-tools like SurvExpress and K-M Plotter.ResultsTLR9 was expressed in malignant epithelial cancer cells as well as in adjacent stromal cells. TLR9 in malignant epithelial cells was significantly high in patients treated with neoadjuvant chemotherapy compared to the patients without neoadjuvant chemotherapy. The prognostic and survival analysis by SurvExpress and Kaplan-Meier plotter demonstrated that high TLR9 expression is related to better overall survival in patients treated with NACT.ConclusionsThus, we are showing for the first time that TLR9 is good prognostic marker in breast cancer treated with neoadjuvant chemotherapy and can be used for the selection of the neo-adjuvant regime.
A Simple, SIR-like but Individual-Based l-i AIR Model: Application in Comparison of COVID-19 in New York City and Wuhan
Authors: Liu Xiaoping 
Published: June 2020

AbstractCOVID-19 has spread around the world with nearly 360,000 deaths from the virus as of today (5/28/2020). Mathematical models have played an important role in many key policy discussions about COVID-19. SIR or SIR-derived models are a common modeling technique. However, the application of these models needs to solve complicated differential equations, enabling use of these models only by professional researchers. In this study, a simple, SIR-like but individual-based model, the l-i AIR model, is presented. The parameters l and i represent the length of the latent period and the infectious period, respectively. The variable A stands for the number of the infected people in the active infectious period, I for the number of cumulative infected people, and R for the number of the people in recovery or death. The nth terms of the three variables are derived, which can be easily calculated in Microsoft Excel, making the program easy to be used in most offices. A transmission coefficient k and a transient incidence rate a of the infected people are induced in the model to examine the effect of social distancing and the testing capacity of coronavirus on the epidemic curves. The simulated daily new cases from this l-i AIR model can fit very well with the reported daily new cases of COVID-19 in Wuhan, China and in New York City, USA, providing important information about latent period, infectious period and lockdown efficiency, and calculating the number of actual infected people who are positive in antibodies.
Direct diagnostic testing of SARS-CoV-2 without the need for prior RNA extraction
Authors: Wei Shan , Kohl Esther , Djandji Alexandre , Morgan Stephanie , Whittier Susan , Mansukhani Mahesh , Hod Eldad , D’Alton Mary , Suh Yousin , Williams Zev 
Published: June 2020

AbstractThe COVID-19 pandemic has resulted in an urgent global need for rapid, point-of-care diagnostic testing. Existing methods for nucleic acid amplification testing (NAAT) require an RNA extraction step prior to amplification of the viral RNA. This step necessitates the use of a centralized laboratory or complex and costly proprietary cartridges and equipment, and thereby prevents low-cost, scalable, point-of-care testing. We report the development of a highly sensitive and robust, easy-to-implement, SARS-CoV-2 test that utilizes isothermal amplification and can be run directly on viral transport media following a nasopharyngeal swab without the need for prior RNA extraction. Our assay provides visual results in 30 min with 85% sensitivity, 100% specificity, and a limit of detection (LoD) of 2.5 copies/μl, and can be run using a simple heat block.
Induction of pancreatic neoplasia in theKRAS/TP53Oncopig
Authors: Mondal Pinaki , Patel Neesha S. , Bailey Katie , Aravind Shruthishree , Hollingsworth Michael A. , Lazenby Audrey J. , Carlson Mark A. 
Published: June 2020

ABSTRACTIntroductionFive year survival of pancreatic cancer (PC) remains low. Current murine models may not adequately mimic human PC and can be too small for medical device development. A large animal PC model could address these issues. We induced and characterized pancreatic tumors in Oncopigs (transgenic swine with a somatic floxed cassette containingKRASG12DandTP53R167H).MethodsOncopigs underwent injection of adenovirus expressing Cre recombinase (AdCre) +/– interleukin 8 (IL-8) into one of the main pancreatic ducts (induction procedure). Subjects were necropsied after ≤10 week, followed by histological analysis, cytokine expression analysis, exome sequencing and transcriptome analysis of resultant tumors.ResultsFourteen Oncopigs underwent the induction procedure; ten (71%) had gross tumor within three weeks, one of these subjects expired suddenly and the other 9 required premature euthanasia secondary to lack of oral intake. At necropsy all of ten of these subjects had gastric outlet obstruction secondary to pancreatic tumor and phlegmon. Two Oncopigs underwent a control injection (no AdCre) and four WT littermates of the Oncopigs underwent AdCre injection without notable effect. Exome and transcriptome analysis of the porcine pancreatic tumors revealed similarity with the molecular signatures and pathways of human PC.ConclusionOncopigs with ductal injection of AdCre developed pancreatic tumor in a short period of time with molecular characteristics similar to human PC. While further optimization and validation of this porcine PC model would be beneficial, it is anticipated that this model will be useful for focused research and development of diagnostic and therapeutic technologies for PC.
A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors
Authors: Crowley Laura , Cambuli Francesco , Aparicio Luis , Shibata Maho , Robinson Brian D. , Xuan Shouhong , Li Weiping , Hibshoosh Hanina , Loda Massimo , Rabadan Raul , Shen Michael M. 
Published: June 2020

SummaryUnderstanding the cellular constituents of the prostate is essential for identifying the cell of origin for benign prostatic hyperplasia and prostate adenocarcinoma. Here we describe a comprehensive single-cell atlas of the adult mouse prostate epithelium, which demonstrates extensive heterogeneity. We observe distinct lobe-specific luminal epithelial populations (LumA, LumD, LumL, and LumV) in the distal region of the four prostate lobes, a proximally-enriched luminal population (LumP) that is not lobe-specific, as well as a periurethral population (PrU) that shares both basal and luminal features. Functional analyses suggest that LumP and PrU cells have multipotent progenitor activity in organoid formation and tissue reconstitution assays. Furthermore, we show that mouse distal and proximal luminal cells are most similar to human acinar and ductal populations, that a PrU-like population is conserved between species, and that the mouse lateral prostate is most similar to the human peripheral zone. Our findings elucidate new prostate epithelial progenitors, and help resolve long-standing questions about the anatomical relationships between the mouse and human prostate.
A Time-Dependent SEIRD Model for Forecasting the COVID-19 Transmission Dynamics
Authors: Rapolu Taarak , Nutakki Brahmani , Rani T. Sobha , Bhavani S. Durga 
Published: June 2020

AbstractThe spread of a disease caused by a virus can happen through human to human contact or could be from the environment. A mathematical model could be used to capture the dynamics of the disease spread to estimate the infections, recoveries, and fatalities that may result from the disease. An estimation is crucial to make policy decisions and for the alerts for the medical emergencies that may arise. Many epidemiological models are being used to make such an estimation. One major factor that is important in the forecasts using the models is the dynamic nature of the disease spread. Unless we can come up with a way of estimating the parameters that guide this dynamic spread, the models may not give accurate forecasts. The main principle is to keep the model generic while making minimal assumptions. In this work, we have derived a data-driven model from SEIRD, where we attempt to forecast Infected, Recovered and Deceased rates of COVID-19 up to a week. A method of estimating the parameters of the model is also discussed thoroughly in this work. The model is tested for India at a district level along with the most affected foreign cities like Lombardia from Italy and Moscow from Russia.The forecasts can help the governments in planning for emergencies such as ICU requirements, PPEs, hospitalizations, and so on as the infection is going to be prevalent for some time until a vaccine or cure is invented.
Dose-response effect of dietary nitrate on muscle contractility and blood pressure in older subjects
Authors: Gallardo Edgar J. , Gray Derrick A. , Hoffman Richard L. , Yates Brandon A. , Moorthi Ranjani N. , Coggan Andrew R. 
Published: June 2020

AbstractPurposeWe have recently demonstrated that dietary nitrate, a source of nitric oxide via the enterosalivary pathway, can improve muscle contractile function in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown.MethodsA randomized, double-blind, placebo-controlled crossover study was performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice (BRJ) containing 0, 200, or 400 µmol/kg of nitrate in nine healthy older subjects (one man, eight women; mean age 70±1 y). Maximal knee extensor power (Pmax) and speed (Vmax) were measured 2 h after BRJ ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study.ResultsPmax (in W/kg) was higher (P< 0.05) after the low dose (3.9±0.4) compared to the placebo (3.7±0.4) or high dose (3.7±0.4). Vmax (in rad/s) also tended higher (P = 0.08) in the low (11.9±0.7) compared to the placebo (10.8±0.8) or high dose (11.2±0.8) trials. Eight out of nine subjects achieved a higher Pmax and Vmax after the lower vs. the higher dose. These dose-related changes in muscle contractility paralleled changes in nitric oxide (NO) bioavailability, as reflected by changes in breath NO and plasma 3-nitrotyrosine levels. No significant changes were found in systolic, diastolic, or mean arterial pressure.ConclusionsVarying doses of dietary nitrate have differential effects on muscle function and blood pressure in older individuals. A moderate dose of nitrate increases muscle speed and power, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.
Antibody profiling of COVID-19 patients in an urban low-incidence region in Northern Germany
Authors: Solbach Werner , Schiffner Julia , Backhaus Insa , Burger David , Staiger Ralf , Tiemer Bettina , Bobrowski Andreas , Hutchings Timothy , Mischnik Alexander 
Published: June 2020

AbstractThis explorative monocentric study shows IgA and IgG antibody profiles from 110 patients with self-reported mild to moderate, or no COVID-19 related symptoms after laboratory-confirmed infection with SARS-CoV-2. The study region is in an urban and well-defined environment in a low-incidence region in Northern Germany. We found that approx. 70 % of the patients developed sustainable antibodies 3 weeks or later after the infection. In about 30 % of the patients with mild to moderate symptoms, no significant antibodies could be detected in two consecutive analyses. Conversely, out of ten patients without symptoms, four were repeatedly positive. Expectedly, six had no specific antibodies. The data indicate that antibody-positivity is a useful indicator of a previous SARS-CoV-2 infection. Negative antibodies do not rule out SARS-CoV-2 infection. Future studies need to determine the functionality of the antibodies in terms of personal protection and ability to transmit the virus.
A Scalable Topical Vectored Vaccine Candidate Against SARS-CoV-2
Authors: Rohaim Mohammed A , Munir Muhammad 
Published: June 2020

AbstractThe severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of SARS-CoV-2 vaccine which would be safe, efficacious and scalable. Owing to unavailability of the vaccine, we propose ade novosynthesised avian orthoavulavirus 1 (AOaV-1)-based topical respiratory vaccine candidate against CoVID-19. Avirulent strain of Newcastle disease virus, proto-type virus of AOaV-1, was engineered to express full length spike (S) glycoprotein which is highly neutralizing and major protective antigen of the SARS-CoV-2. Broad-scalein vitrocharacterization of recombinant vaccine candidate demonstrated efficient co-expression of the hemagglutinin-neuraminidase (HN) of AOaV-1 and S protein of SARS-CoV-2, and comparable replication kinetics were observed in cell culture model. The recombinant vaccine candidate virus actively replicated and spread within cells independently of exogenous trypsin. Interestingly, incorporation of S protein of SARS-CoV-2 into the recombinant AOaV-1 particles attributed the sensitivity to anti-SARS-CoV-2 antiserum and more prominently to anti-AOaV-1 antiserum. Finally, our results demonstrated that the recombinant vaccine vector stably expressed S protein after multiple propagation in chicken embryonated eggs, and this expression did not significantly impact thein vitrogrowth characteristics of the recombinant. Taken together, the presented respiratory vaccine candidate is highly attenuated in primatesper se, safe and lacking pre-existing immunity in human, and carries the potential for accelerated vaccine development against CoVID-19 for clinical studies.
Performance evaluation of Xpert HBV viral load (VL) assay: Point-of-care molecular test to strengthen and decentralize management of chronic hepatitis B (CHB) infection
Authors: Arvind Khodare , Ekta Gupta , Rani Nitiksha , Gaurav Singh , Kavita Aggarwal , Manoj Sharma , Sarin SK 
Published: June 2020

AbstractIntroductionEstimation of hepatitis B (HBV) viral load (VL) is critical in hepatitis-B cascade-of-care and currently there is no point of care (POC) molecular assay available for that. This study evaluated the performance of a new near point of care molecular assay Xpert HBV-VL assay against FDA approved Real time PCR assays.Materials & methodsIn this retrospective study 119 archived plasma samples from HBV infected patients, and 53 hepatitis B surface antigen (HBsAg) patients were simultaneously tested for HBV DNA quantification on 2 real time PCR conventional assays and Xpert assay. The routine method for reporting to patient was Abbott Real Time PCR.ResultsThe range of HBV DNA load in samples was 1 to 8.76 log10IU/ml with a median load of 4.46 (IQR: 1-8.76) log10IU/ml as detected by routine assay (Abbott Real-Time HBV VL assay). Genotyping could be done in 95 (79.8%) samples and genotype D (83; 87.37%) was found commonest. The Xpert assay demonstrated good correlation with Abbott (R2= 0.944) and Roche (R2= 0.963). On comparison the mean difference (95% Confidence Interval) in average viral load was −0.018 log10 IU/ml and −0.043 log10 IU/ml when Xpert was compared with the Abbott and Roche assay, respectively. The overall sensitivity, specificity, negative predictive value and positive predictive value of the Xpert assay was found 97.5%, 100%, 94.65 & 100% respectively.ConclusionXpert HBV-VL assay which has a potential for near point of care molecular testing has shown excellent performance and found to be a reliable method for HBV DNA quantification.
An open resource for T cell phenotype changes in COVID-19 identifies IL-10-producing regulatory T cells as characteristic of severe cases
Authors: Neumann Julika , Prezzemolo Teresa , Vanderbeke Lore , Roca Carlos P. , Gerbaux Margaux , Janssens Silke , Willemsen Mathijs , Burton Oliver , Van Mol Pierre , Van Herck Yannick ,   CONTAGIOUS co-authors, Wauters Joost , Wauters Els , Liston Adrian , Humblet-Baron Stephanie 
Published: June 2020

AbstractThe pandemic spread of the novel coronavirus SARS-CoV-2 is due, in part, to the immunological properties of the host-viral interaction. The clinical presentation varies greatly from individual to individual, with asymptomatic carriers, mild to moderate-presenting patients and severely affected patients. Variation in immune response to SARS-CoV-2 may underlie this clinical variation. Using a high dimensional systems immunology platform, we have analyzed the peripheral blood compartment of 6 healthy individuals, 23 mild-to-moderate COVID-19 patients and 20 severe COVID-19 patients. We identify distinct immunological signatures in the peripheral blood of the mild-to-moderate and severe COVID-19 patients, including T cell lymphopenia, more consistent with peripheral hypo-than hyper-immune activation. Unique to the severe COVID-19 cases was a large increase in the proportion of IL-10-secreting regulatory T cells, a lineage known to possess anti-inflammatory properties in the lung. Annotated data is openly available (https://flowrepository.ors/experiments/2713) with clinical correlates, as a systems immunology resource for the COVID-19 research community.