bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral ulcers of COVID-19 patients: a scoping review protocol
Authors: Riad Abanoub , Issa Julien , Chuchmova Veronika , Slezakova Simona , Gomaa Esraa , Pokorna Andrea , Klugarova Jitka , Klugar Miloslav 
Published: January 2021

AbstractObjectiveThis scoping review aims to systematically identify the types, characteristics, and possible pathophysiologic etiologies of the oral ulcers that emerge in COVID-19 patients.IntroductionThe oral cavity is a vulnerable niche for the most diverse microbial ecosystem in the human body; therefore, it presents a wide array of mucocutaneous complications that could indicate various acute and chronic conditions. The COVID-19-related oral conditions, including oral ulcers, had been widely debated as direct manifestations or indirect complications of the SARS-CoV-2 infection. According to a preliminary search of PROSPERO, MEDLINE, the Cochrane Database of Systematic Reviews and theJBI Evidence Synthesis, there is no published nor registered scoping review concerned with the oral ulcers of COVID-19 patients.Inclusion criteriaThe review will include studies included COVID-19 patients whose infection had been confirmed by RT-PCR testing regardless of infection severity and clinical course. Only the studies that reported COVID-19 patients with oral ulcers.MethodsA three-phase search strategy will be carried out: an initial limited search, a full electronic search, and hand search using the reference lists of all included records. The main bibliographic databases of published literature will include MEDLINE® (Ovid), EMBASE (Elsevier), and Cochrane COVID-19 Study Register. All identified records will be managed using EndNote 9.2, and the titles and abstracts will be screened against the inclusion criteria before the full text of all potentially relevant studies will be examined. The data will be presented in tabular form, rating maps, and narrative summary.RegistrationThis protocol had been pre-registered in Open Science Framework (OSF) Registries.[1]
Adaptive design methods in dialysis clinical trials – a systematic review
Authors: Judge Conor , Murphy Robert , Reddin Catriona , Cormican Sarah , Smyth Andrew , O’Halloran Martin , O’Donnell Martin J 
Published: January 2021

AbstractBackgroundAdaptive design methods are intended to improve efficiency of clinical trials and are relevant to evaluating interventions in dialysis populations. We sought to quantify the use of adaptive designs in dialysis clinical trials.MethodsWe completed a full text systematic review and adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Our review utilised a machine learning classifier and a novel full text systematic review method. We searched MEDLINE (Pubmed) and performed a detailed data extraction of trial characteristics and a completed a narrative synthesis of the data.Results50 studies, available as 66 articles, were included after full text review. 31 studies were conducted in a dialysis population and 19 studies had renal replacement therapy as a primary or secondary outcome. While the absolute number of adaptive design methods is increasing over time, the relative use of adaptive design methods in dialysis trials is decreasing over time (6.1% in 2009 to 0.3% in 2019). Adaptive design methods impacted 52% of dialysis trials they were used in. Group sequential designs were the most common type of adaptive design method used. Acute Kidney Injury (AKI) was studied in 27 trails (54%), End Stage Kidney Disease (ESKD) was studied in 22 trials (44%) and Chronic Kidney Disease (CKD) was studied in 1 trial (2%). 26 studies (52%) were supported by public funding. 41 studies (82%) did not report their adaptive design method in the title or abstract and would not be detected by a standard systematic.ConclusionsAdaptive design methods are employed in dialysis trials, but there has been a decline in their relative use over time.Registration NumberPROSPERO: CRD42020163946Significance statementWhat was previously known about the specific topic of the manuscript?The use of adaptive designs methods in dialysis trials is unquantified.What were the most important findings? If studies are animals, this should be specifiedAlthough absolute numbers of adaptive design trials have increased over time, the proportion of dialysis trials using an adaptive design has reduced. Among trials that employed an adaptive design, 52% of dialysis trials were revised due to the adaptive criteria. Group sequential designs were the most common type of adaptive design method used in dialysis randomized clinical trials. Acute Kidney Injury (AKI) was studied in 54% of trials and End Stage Kidney Disease (ESKD) was studied in 44% of trials, which used an adaptive design.How does the new information advance a new understanding of the kidney and its diseases?Adaptive design methods are effective in dialysis trials, but their relative use has declined over time.
S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: a randomized, double-blind, placebo-controlled clinical trial
Authors: Brinck Elina C.V. , Virtanen Taru , Mäkelä Sanna , Soini Venla , Hynninen Ville-Veikko , Mulo Jukka , Savolainen Urmas , Rantakokko Juho , Maisniemi Kreu , Liukas Antti , Olkkola Klaus T. , Kontinen Vesa , Tarkkila Pekka , Peltoniemi Marko , Saari Teijo I. 
Published: January 2021

AbstractBACKGROUNDSpinal fusion surgery causes severe pain. Strong opioids, commonly used as postoperative analgesics, may have unwanted side effects. S-ketamine may be an effective analgesic adjuvant in opioid patient-controlled analgesia (PCA). However, the optimal adjunct S-ketamine dose to reduce postoperative opioid consumption is still unknown.METHODSWe randomized 107 patients at two tertiary hospitals in a double-blinded, placebo-controlled clinical trial of adults undergoing major lumbar spinal fusion surgery. Patients were randomly allocated to four groups in order to compare the effects of three different doses of adjunct S-ketamine (0.25, 0.5, and 0.75 mg ml−1) or placebo on postoperative analgesia in oxycodone PCA. Study drugs were administered for 24 hours postoperative after which oxycodone-PCA was continued for further 48 hours. Our primary outcome was cumulative oxycodone consumption at 24 hours after surgery.RESULTSOf the 100 patients analyzed, patients receiving 0.75 mg ml−1 S-ketamine in oxycodone PCA needed 25% less oxycodone at 24 h postoperatively (61.2 mg) compared with patients receiving 0.5 mg ml−1 (74.7 mg) or 0.25 mg ml−1 (74.1 mg) S-ketamine in oxycodone or oxycodone alone (81.9 mg) (mean difference: −20.6 mg; 95% confidence interval [CI]: −41 to −0.20; P = 0.048). A beneficial effect in mean change of pain intensity at rest was seen in the group receiving 0.75 mg ml−1 S-ketamine in oxycodone PCA compared with patients receiving lower ketamine doses or oxycodone alone (standardized effect size: 0.17, 95% CI: 0.013–0.32, P = 0.033). The occurrence of adverse events was similar among the groups.CONCLUSIONSOxycodone PCA containing S-ketamine as an adjunct at a ratio of 1: 0.75 decreased cumulative oxycodone consumption at 24 h after major lumbar spinal fusion surgery without additional adverse effects.
Implant- and anesthesia-related factors affecting threshold intensities for vagus nerve stimulation
Authors: Ahmed Umair , Chang Yao-Chuan , Lopez Maria F. , Wong Jason , Datta-Chaudhuri Timir , Rieth Loren , Al-Abed Yousef , Zanos Stavros 
Published: January 2021

AbstractVagus nerve stimulation (VNS) is used as therapy in epilepsy and depression and is tested as a potential treatment for several chronic disorders. Typically, VNS is delivered at increasing stimulus intensity until a response is observed (threshold intensity). Factors that affect threshold intensities for engagement of different fiber types and concomitant physiological responses have not been studied. We determined neural and physiological responses to increasing stimulus intensities of VNS in anesthetized and awake animals, and examined the effect of implant- and anesthesia-related factors on threshold intensities in a rodent model of VNS. In acute and long-term cervical vagus nerve implants (53 and 14 rats, respectively) VNS was delivered under isoflurane, ketamine-xylazine, or awake at different intensities. Stimulus-evoked compound action potentials (eCAPs) were recorded, elicited physiological responses were registered, including changes heart rate (HR), breathing, and blood pressure (BP), and threshold intensities were determined. The intensity that elicits eCAPs (“neural threshold”) is significantly lower than what elicits a physiological response (“physiological threshold”, PT) (25 μA ±1.8 vs. 70 μA ±5.2, respectively; Mean ±SEM). Changes in BP occur at the lowest stimulus intensities (80 μA ±7), followed by changes in HR (105 μA ±8.4) and finally in breathing (310 μA ±32.5). PT is lower with than without electrode insulation (60 μA ±12, vs. 700 μA ±123). PT and electrode impedance are correlated in long-term (r=0.47;p<0.001) but not in acute implants (r=-0.34;pNS); both PT and impedance increase with implant age (Pearson correlationr=0.44;p<0.001 and r=0.64; p<0.001, respectively). PT is lowest when animals are awake (210 μA ±33; Mean ±SEM), followed by ketamine-xylazine (630 μA ±154), and isoflurane (1075 μA ±131). The sequence of physiological responses with increasing VNS intensity is similar in both anesthetized and awake states. Implant age, electrical impedance and the type of anesthesia affect VNS threshold and should be accounted for when determining stimulation dose.
Identifying the Link Between Chemical Exposures and Breast Cancer in African American Women via ToxCast High Throughput Screening Data
Authors: Polemi Katelyn , Nguyen Vy , Heidt Julien , Kahana Adam , Jolliet Olivier , Colacino Justin A. 
Published: January 2021

AbstractAmong women, breast cancer is the most prevalent form of cancer worldwide and has the second highest mortality rate of any cancer in the United States. The breast cancer related death rate is 40% higher in African American women compared to European American women. The incidence of triple negative breast cancer (TNBC), an aggressive subtype of breast cancer for which there is no targeted therapy, is approximately three times higher in non-Hispanic Black women (NHBW) compared to non-Hispanic White women (NHWW). The drivers of these differences in breast cancer incidence and mortality are still poorly understood, and likely lie in an interaction between genetic and environmental factors. Here, we aimed to identify chemical exposures which may play a role in breast cancer disparities. Using chemical biomonitoring data from the National Health and Nutrition Examination Survey (NHANES) and biological activity data from the EPA’s ToxCast program, we assessed the toxicological profiles of chemicals with higher biomarker concentrations in US NHBW. We conducted a literature search to identify a gene set of breast cancer targets included in ToxCast to analyze the response of prioritized chemicals in these assays. Forty-three chemical biomarkers are significantly higher in NHBW. Investigation of these chemicals in ToxCast resulted in a total of 32,683 assays for analysis, 5,172 of which contained nonzero values for the concentration at which the dose-response fitted model reaches the cutoff considered “active” and the scaled top value of dose response curve. Of these chemicals BPA, PFOS, and thiram are most comprehensively assayed. 2,5-dichlorophenol, 1,4-dichlorobenzene, and methyl and propyl parabens had higher biomarker concentrations in NHBW and moderate testing and activity in ToxCast. The distribution of active concentrations for these chemicals in ToxCast assays are comparable to biomarker concentrations in NHBW. Through this integrated analysis, we have identified that multiple chemicals, including thiram, propylparaben, and p,p’ DDE, with disproportionate exposures in NHBW, have breast cancer associated biological activity at human exposure relevant doses.
CONTROLLING COCKROACH POPULATIONS IN HUMAN AND ANIMAL HABITATIONS BY REDUCING FOOD AVAILABILITY
Authors: Hayward William A. , Haseler Luke J. , Muruganandam Maheswari , Gibb James I. , Sibbitt John H. , Sibbitt Wilmer L. 
Published: January 2021

AbstractBackgroundCockroaches, carriers of pathogenic organisms that cause human and animal disease, typically have access to human or pet food in bowls, allowing cockroaches to expand their colonies and infestations.HypothesisWe hypothesized that existing anti-ant technology could be converted to anti-cockroach technology by simple design changes.MethodsA base of various heights was affixed to the bottom of an anti-ant bowl to increase the distance of the anti-ant shield from the native height“x”to the hypothesized cockroach-resistant height“z”. The effects of z =0, 12.7, 15.9, 19.1, 25.4, 44.5, and 57.2 mm were studied. 118.3 cc (4 oz) of dry cat food was used as cockroach bait. The modified anti-ant bowls were placed in a high-intensity cockroach environment during summer nights where the temperatures varied between 23.9-29.4 degrees Celsius for 3 hours and then cockroach counts were performed. Ten runs at each height z were performed.ResultsMean numbers of infesting cockroaches ± SD at each height z were 21.3±2.9 at 0 mm, 22.0±2.9 at 12.7 mm, 11.2±2.6 at 15.9 mm, 0.9±0.8 at 19.1mm, 0.4±0.5 at 25.4 mm, 0±0 at 44.5 mm, and 0±0 at 57.2 mm (p<0.001 withz≥15.9 mm for all). Cockroach numbers began declining whenz= 15.9 mm and declined to only large cockroaches atz= 25.4 mm. The cockroaches that were able to overcome thez=25.4 mm were the larger American cockroaches that can exceed 76.2 mm (3 inch) in length. However, atz= 44.5 mm and 57.2 mm no cockroaches penetrated the modified bowl.ConclusionsTo defeat the majority of species of cockroaches the anti-insect shield should be at a height of at least 25.4 mm and to defeat the larger American cockroaches preferably greater than 25.4 mm with 44.5 mm and 57.2 mm defeating all tested cockroaches
Evaluation of Drug/Ligand Binding Constants for Human Serum Albumin Using Differential Scanning Calorimetry
Authors: Eskew Matthew W. , Benight Albert S. 
Published: January 2021

ABSTRACTThis paper reports utilization of differential scanning calorimetry measurements to evaluate binding constants for Human Serum Albumin of 28 different drug ligands. Protein/ligand mixtures were prepared at various ligand concentrations and subjected to thermal denaturation analysis by calorimetry. From the measurements, the melting temperature,Tm, and free-energyΔGcal(37°C) for melting ligand-bound Albumin were evaluated as a function of ligand concentration. Concentration dependent behaviors ofΔGcal(37°C) andTmderived from protein/ligand mixtures were used to construct dose-response curves. Model fits of dose-response curves yielded quantitative evaluation of the ligand binding constant,KD, and semi-quantitative estimates of the binding stoichiometry, n. Many of the ligands had known binding affinity for Albumin with binding constants reported in the literature. Evaluated Albumin binding parameters for the ligands impressively agreed with reported literature values determined using other standard experimental methods. These results demonstrated utility of our calorimetry-based process for applications in pre-clinical drug screening.
Evaluation of deep convolutional neural networks for in situ hybridization gene expression image representation
Authors: Abed-Esfahani Pegah , Darwin Benjamin C , Howard Derek , Wang Nick , Kim Ethan , Lerch Jason , French Leon 
Published: January 2021

AbstractHigh resolutionin situhybridization (ISH) images of the brain capture spatial gene expression at cellular resolution. These spatial profiles are key to understanding brain organization at the molecular level. Previously, manual qualitative scoring and informatics pipelines have been applied to ISH images to determine expression intensity and pattern. To better capture the complex patterns of gene expression in the human cerebral cortex, we applied a machine learning approach. We propose gene re-identification as a contrastive learning task to compute representations of ISH images. We train our model on a ISH dataset of ~1,000 genes obtained from postmortem samples from 42 individuals. This model reaches a gene re-identification rate of 38.3%, a 13x improvement over random chance. We find that the learned embeddings predict expression intensity and pattern. To test generalization, we generated embeddings in a second dataset that assayed the expression of 78 genes in 53 individuals. In this set of images, 60.2% of genes are re-identified, suggesting the model is robust. Importantly, this dataset assayed expression in individuals diagnosed with schizophrenia. Gene and donor-specific embeddings from the model predict schizophrenia diagnosis at levels similar to that reached with demographic information. Mutations in the most discriminative gene,SCN4B, may help understand cardiovascular associations with schizophrenia and its treatment. We have publicly released our source code, embeddings, and models to spur further application to spatial transcriptomics. In summary, we propose and evaluate gene re-identification as a machine learning task to represent ISH gene expression images.
The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study
Authors: Sepulcri Chiara , Dentone Chiara , Mikulska Malgorzata , Bruzzone Bianca , Lai Alessia , Fenoglio Daniela , Bozzano Federica , Bergna Annalisa , Parodi Alessia , Altosole Tiziana , Delfino Emanuele , Bartalucci Giulia , Orsi Andrea , Di Biagio Antonio , Zehender Gianguglielmo , Ballerini Filippo , Bonora Stefano , De Palma Raffaele , Silvestri Guido , De Maria Andrea , Bassetti Matteo 
Published: January 2021

AbstractBackgroundImmunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a lymphoma patient.MethodsNasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients’ adaptive and innate immunity to characterize T and NK cell subsets.FindingsSARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive with cycle threshold mean values of 22 ± 1·3 for over 8 months. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course.InterpretationIn our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia.FundingNone.
Assessment of the knowledge, preferences and concern regarding the prospective COVID- 19 vaccine among adults residing in New Delhi, India-A cross sectional study
Authors: Islam Farzana , Agarwalla Rashmi , Panda Meely , Alvi Yasir , Singh Vishal , Debroy Arup , Ray Arindam , Vadnerkar Amruta , Uttekar Shraddha 
Published: January 2021

AbstractBackgroundUnderstanding the perception and concerns of people about COVID-19 vaccine in developing and populous country like India will help in understanding demand for the vaccine and further tailoring out public health information and education activities before the launch of the vaccine. The study was carried out to assess the present state of knowledge people have about the probable vaccine for COVID-19, to know the preferences of respondents about this vaccine and to learn the expectations and apprehensions of people about features of this prospective COVID-19 vaccine residing in the capital city of India.MethodsThis cross-sectional study was conducted amongst the residents of Delhi, India from July-October 2020. Both offline and online interview method was used to collect date from 513 participants representing various occupational strata. Data was collected on socio demographic variable, vaccine acceptance and concerns regarding COVID-19 vaccine.ResultsAmong the study population 79.5% said they will take the vaccine while 8.8% said they were not going to take the vaccine and remaining 11.7% had not yet decided about it. Most of them(78.8%),believed that vaccine would be available to public next year but at the same time half(50.1%) of them believe that it may not be in sufficient amount for everyone to get. More than 50% were willing to pay for the vaccine and 72% felt vaccine should first be given to health workers and high risk group.ConclusionThe following study has helped to understand the percentage of people who are hesitant to take the vaccine and also the concerns regarding the vaccine. Also since half of the population is willing to pay for the vaccine, a strategical approach considering the various economical classes of people could be applied in a developing country like India.
Super-Spreaders Out, Super-Spreading In: The Effects of Infectiousness Heterogeneity and Lockdowns on Herd Immunity
Authors: Tavori Jhonatan , Levy Hanoch 
Published: January 2021

AbstractRecently, [8] has proposed that heterogeneity of infectiousness (and susceptibility) across individuals in infectious diseases, plays a major role in affecting the Herd Immunity Thresh-old (HIT). Such heterogeneity has been observed in COVID-19 and is recognized asoverdis-persion(or “super-spreading”). The model of [8] suggests that super-spreaders contribute significantly to the effective reproduction factor,R, and that they are likely to get infected and immune early in the process. Consequently, underR0≈ 3 (attributed to COVID-19), the Herd Immunity Threshold (HIT) is as low as 5%, in contrast to 67% according to the traditional models [1, 2, 4, 10].This work follows up on [8] and proposes that heterogeneity of infectiousness (susceptibility) has two “faces” whose mix affects dramatically the HIT: (1)Personal-Trait-, and (2)Event-Based-Infectiousness (Susceptibility). The former is a personal trait of specific individuals (super-spreaders) and is nullified once those individuals are immune (as in [8]). The latter is event-based (e.g culturalsuper-spreadingevents) and remains effective throughout the process, even after the super-spreaders immune. We extend [8]’s model to account for these two factors, analyze it and conclude that the HIT is very sensitive to the mix between (1) and (2), and underR0≈ 3 it can vary between 5% and 67%. Preliminary data from COVID-19 suggests that herd immunity is not reached at 5%.We address operational aspects and analyze the effects of lockdown strategies on the spread of a disease. We find that herd immunity (and HIT) is very sensitive to the lock-down type. While some lockdowns affect positively the disease blocking and increase herd immunity, others haveadverseeffects andreducethe herd immunity.