bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intensive Insulin Therapy (Basal-Bolus)
Authors: Chico Ana , Corcoy Rosa 
Published: October 2020

Background:
Intensive insulin therapy (IIT) aims at achieving near-normal glycemic control and usually uses a basal-bolus (BB) schema to mimic physiologic insulin secretion.

Areas of Uncertainty:
The treatment burden of IIT should be outweighed by improved glycemic control and reduction of chronic complications, but reviews summarizing the effects of IIT in subjects with T1DM and T2DM in glycated hemoglobin, hypoglycemia, insulin doses, and weight are limited.

Data Sources:
We performed a PubMed search to identify relevant randomized control trials (RCTs) comparing IIT and conventional insulin treatment in T1DM and T2DM subjects and addressing glycated hemoglobin, hypoglycemia, insulin requirements, and weight.

Therapeutic Advances:
We have identified 11 RCTs in T1DM subjects, published years ago and very heterogenous in design. Throughout the studies there was a consistent superiority of IIT in glycated hemoglobin reduction, a higher rate of severe hypoglycemia and more weight gain in the IIT group without a clear effect on insulin doses. We have identified 2 RCTs in T2DM subjects, only one of them using a definite BB schema in the IIT group. IIT induced more hypoglycemia and better HbA1c, but not more weight gain.

Conclusions:
IIT is the best option for treatment of subjects with T1DM in HbA1c reduction with a cost in the rate of hypoglycemia and weight gain. In subjects with T2DM, IIT also yields improvement in HbA1c versus conventional treatment, also at the cost of more hypoglycemic episodes, but not of higher weight gain. RCT treatment arms did not only differ in the insulin schema, but also in treatment goals, therapeutic education, and frequency of clinical visits among other characteristics. However, most evidence was gained using a BB insulin schema in the intensive arm and it is likely that the insulin schema had a relevant contribution in the results.
Sedation With Midazolam After Cardiac Surgery in Children With and Without Down Syndrome: A Pharmacokinetic-Pharmacodynamic Study
Authors: Valkenburg Abraham J. , Goulooze Sebastiaan C. , Breatnach Cormac V. , Mathôt Ron A. A. , Tibboel Dick , van Dijk Monique , Knibbe Catherijne A. J. , Peeters Mariska Y. M. 
Published: October 2020

Objectives:
To compare the pharmacokinetics and pharmacodynamics of IV midazolam after cardiac surgery between children with and without Down syndrome.

Design:
Prospective, single-center observational trial.

Setting:
PICU in a university-affiliated pediatric teaching hospital.

Patients:
Twenty-one children with Down syndrome and 17 without, 3–36 months, scheduled for cardiac surgery with cardiopulmonary bypass.

Interventions:
Postoperatively, nurses regularly assessed the children’s pain and discomfort with the validated COMFORT-Behavioral scale and Numeric Rating Scale for pain. A loading dose of morphine (100 µg/kg) was administered after coming off bypass; thereafter, morphine infusion was commenced at 40 µg/kg/hr. Midazolam was started if COMFORT-Behavioral scale score of greater than 16 and Numeric Rating Scale score of less than 4 (suggestive of undersedation). Plasma midazolam and metabolite concentrations were measured for population pharmacokinetic- and pharmacodynamic analysis using nonlinear mixed effects modeling (NONMEM) (Version VI; GloboMax LLC, Hanover, MD) software.

Measurements and Main Results:
Twenty-six children (72%) required midazolam postoperatively (15 with Down syndrome and 11 without; p = 1.00). Neither the cumulative midazolam dose (p = 0.61) nor the time elapsed before additional sedation was initiated (p = 0.71), statistically significantly differed between children with and without Down syndrome. Population pharmacokinetic and pharmacodynamics analysis revealed no statistically significant differences between the children with and without Down syndrome. Bodyweight was a significant covariate for the clearance of 1-OH-midazolam to 1-OH-glucuronide (p = 0.003). Pharmacodynamic analysis revealed a marginal effect of the midazolam concentration on the COMFORT-Behavioral score.

Conclusions:
The majority of children with and without Down syndrome required additional sedation after cardiac surgery. This pharmacokinetic and pharmacodynamic analysis does not provide evidence for different dosing of midazolam in children with Down syndrome after cardiac surgery.
Gamma Probe–Guided Surgery in Postoperative Recurrent Osteoid Osteoma of Left Index Finger
Authors: Subramanyam Padma , Palaniswamy Shanmuga Sundaram 
Published: October 2020

Abstract
Osteoid osteomas are painful benign osteoblastic tumors that usually affect the metaphysis or diaphysis of long bones. Hands are rarely involved. Identification of recurrent lesion by anatomical imaging modalities is a challenge especially in postoperative setting. Diagnosis of osteoid osteoma is based on typical clinical signs, radiographs, bone scintigraphy, thin-slice computed tomography, or magnetic resonance imaging. Atypical locations, multicentricity of nidus, or incomplete excision of the nidus result in a high rate of recurrence. Here we present a case of recurrent osteoid osteoma at an unusual site in left index finger and was operated under gamma probe guidance.
99mTc-Mebrofenin SPECT/CT in Hepatic Infarction
Authors: Mattay Govind S. , O’Leary Cathal , Dubroff Jacob G. , R. Pantel Austin 
Published: October 2020

Abstract
A 68-year-old man with hereditary hypercoagulability was referred to nuclear medicine for elevated aminotransferases after a recent living-donor liver transplant. A hepatic infarction was suspected. A 99mTc-mebrofenin SPECT/CT was performed and showed decreased radiotracer uptake in a wedge-shaped distribution in the anterior liver suggestive of a hepatic infarction. Subsequently, an enhanced MRI corroborated the diagnosis. Oral anticoagulation therapy was then initiated, and aminotransferases soon normalized.
Gallbladder Perforation Into the Peritoneal Cavity
Authors: Wang Bing F. , Yi Steven , Keshavamurthy Jayanth , Williams Hadyn , Pucar Darko 
Published: October 2020

Abstract
Gallbladder perforation is an uncommon but morbid complication of acute cholecystitis with mural ischemia and necrosis. The most common site of perforation is the fundus because of limited blood supply in this region. The Niemeier classification proposed in 1934 remains the criterion standard in grading gallbladder perforation; type 1 is acute with free perforation into the peritoneal cavity, type 2 is subacute with pericholecystic abscess, and type 3 is chronic with cholecystoenteric fistula. We report a challenging case of type 1 gallbladder perforation due to acute acalculous cholecystitis.
Relapsing Mitral Involvement in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Briane Aurélie , Jamet Bastien , Mugniot Antoine , Néel Antoine , Agard Christian 
Published: October 2020

Abstract
Cardiac valvular involvement in antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is very rare. We report the case of a patient seen in 2019, followed for ANCA-associated vasculitis for 15 years, who had a first relapse with cardiac valvular involvement in 2012, and who underwent a second histologically proven vasculitis relapse involving mitral periprosthetic endocardium. PET/CT imaging showed an intense and focal FDG activity of paramitral bioprosthesis leak site. Mitral bioprosthesis was replaced, and the patient improved with steroids and rituximab. Through this exceptional case, we suggest that FDG PET/CT could be of interest in the follow-up of ANCA-associated vasculitis with cardiac valvular involvement.
Normothermic Ex Situ Liver Perfusion Enhances Mitochondrial Function of DCD Grafts as Evidenced by High-throughput Metabolomics
Authors: Bhat Mamatha , Linares-Cervantes Ivan , Pasini Elisa , Patel Preya , Goto Toru , Noguchi Yuki , Mazilescu Laura , Urbanellis Peter , Selzner Markus , Selzner Nazia 
Published: October 2020

Background.
Normothermic ex situ liver perfusion (NEsLP) reduces reperfusion injury of donation after circulatory death (DCD) grafts and optimizes graft function. The goal of our study was to elucidate how NEsLP impacts global metabolism in DCD grafts using high-throughput metabolomics.

Methods.
Pig livers were preserved by 2 different techniques: static cold storage and NEsLP. Grafts obtained from heart-beating donors were compared with donation after circulatory death (DCD) grafts with either 30 minutes (DCD30) or 60 minutes (DCD60) ischemia time. Liver tissues were collected at the end of preservation period (T0) with either cold storage or NEsLP (n = 5 per group). Grafts were transplanted into recipient pigs and a second liver biopsy was collected 2 hours following liver transplantation (T1). Snap-frozen tissue was processed and analyzed by Sciex 6600 Q-TOF high-resolution mass spectrometer. Data analysis was performed using MetaboAnalyst 4.0 software.

Results.
Prolonged ischemia resulted in 38 out of 81 metabolites being differentially abundant over time. Mitochondrial metabolism was significantly affected, with disruption in oxidative phosphorylation capacity i.e the Warburg effect (P = 3.62E-03) and urea cycle (P = 7.95E-0.4). NEsLP resulted in improved mitochondrial metabolism and glycolysis (4.20E-02) oxidation of branched chain fatty acids (P = 4.07E-02).

Conclusions.
This unbiased, high-throughput metabolomics study reveals that mitochondrial function is globally rescued with NEsLP, associated with improvement in DCD graft function. NEsLP is able to rescue DCD grafts, improving their metabolic function to that of livers not exposed to DCD procurement.
FOXP3 mRNA Profile Prognostic of Acute T Cell–mediated Rejection and Human Kidney Allograft Survival
Authors: Luan Danny , Dadhania Darshana M. , Ding Ruchuang , Muthukumar Thangamani , Lubetzky Michelle , Lee John R. , Sharma Vijay K. , August Phyllis , Mueller Franco B. , Schwartz Joseph E. , Suthanthiran Manikkam 
Published: October 2020

Background.
T cell–mediated rejection (TCMR) is the most frequent type of acute rejection and is associated with kidney allograft failure. Almost 40% of TCMR episodes are nonresponsive to therapy, and molecular mechanisms for the nonresponsiveness are unknown. Our single-center study identified that urinary cell FOXP3 mRNA abundance predicts TCMR reversibility and allograft survival.

Methods.
We developed PCR assays and measured absolute copy numbers of transcripts for FOXP3, CD25, CD3E, perforin, and 18S rRNA in 3559 urines from 480 kidney allograft recipients prospectively enrolled in the multicenter Clinical Trials in Organ Transplantation-04. In this replication study, we investigated the association between mRNA profile and TCMR diagnosis, TCMR reversibility, and allograft survival.

Results.
18S rRNA normalized levels of mRNA for FOXP3 (P = 0.01, Kruskal-Wallis test), CD25 (P = 0.01), CD3E (P < 0.0001), and perforin (P < 0.0001) were diagnostic of TCMR, but only FOXP3 mRNA level predicted TCMR reversibility (ROC AUC = 0.764; 95% confidence interval, 0.611-0.917; P = 0.008). Multivariable logistic regression analyses showed that urinary cell FOXP3 mRNA level predicted reversal, independent of clinical variables. A composite model of clinical variables and FOXP3 mRNA (AUC = 0.889; 95% CI, 0.781-0.997; P < 0.001) outperformed FOXP3 mRNA or clinical variables in predicting TCMR reversibility (P = 0.01, likelihood ratio test). Multivariable Cox proportional hazards regression analyses showed that FOXP3 mRNA level predicts kidney allograft survival (P = 0.047) but not after controlling for TCMR reversal (P = 0.477).

Conclusions.
Urinary cell level of FOXP3 mRNA is diagnostic of TCMR, predicts TCMR reversibility, and is prognostic of kidney allograft survival via a mechanism involving TCMR reversal.
Nutritional status and its associated factors among HIV positive adolescents on Atazanavir-based regimen attending an urban clinic in Uganda
Authors: Darshit Dave , Provia Ainembabazi , Nakiddu Nana , Sodawasser Erin , Harper Katrina , Ssenkusu John M. , Bakeera-Kitaka Sabrina , Nicol Melanie , Musaazi Joseph , Sekaggya-Wiltshire Christine 
Published: October 2020

AbstractBackgroundAdolescents between the ages of 10-19 represent a growing portion of people living with HIV worldwide. A large proportion of adolescents living with HIV suffer from severe malnutrition because of the chronic ill health and this has been associated with increased morbidity and mortality particularly in Sub-Saharan Africa. Little is known about the nutrition status of adolescents living with HIV who are on second line treatment particularly Atazanavir. Therefore, we assessed the nutrition status and associated factors among HIV positive adolescents on Atazanavir-based regimen attending an urban clinic in Uganda.MethodThis was a cross-sectional study carried out between December 2017 and July 2018. Using convenience sampling, adolescents aged 10-19 years attending an urban clinic in Kampala on Atazanavir-based regimen were enrolled into the study. Nutritional status was assessed using BMI-for-Age and Height-for-age as measures of thinness and stunting respectively. Standard deviation scores (Z scores) were applied to determine the nutritional status. WHO and CDC Z-score cut offs were used to categorize the nutrition status. Data was entered into an electronic database using REDCap. Statistical analysis was done using STATA version 15.1 (Texas, USA).ResultsData from 132 adolescents were included. We found that 28% were malnourished (composite outcome of stunting and thinness). The prevalence malnutrition of thinness was 7.6% with 2.3% being severely thin. The prevalence of stunting was 23.7% with 1.5% being severely stunted. Adolescents with no parent were more likely to be malnourished than adolescents who had either one or both parents (Adjusted Odds Ratio [AOR]: 3.70 95% Confidence Interval [CI]: 1.20-11.37, p=0.023). In addition, adolescents who had attained at least secondary education were less likely to be malnourished (AOR: 0.40, CI:0.17-0.95, P-value=0.037).ConclusionThere is a high proportion of adolescents with HIV who are malnourished. Low level of education (No education and elementary) and having no parent are important risk factors to malnutrition in this population. There is need for optimizing nutrition care for adolescents on HIV treatment.
MultiPhATE2: Code for Functional Annotation and Comparison of Bacteriophage Genomes
Authors: Ecale Zhou Carol L. , Kimbrel Jeffrey , Edwards Robert , McNair Katlyn , Souza Brian A. , Malfatti Stephanie 
Published: October 2020

AbstractTo address the need for improved tools for annotation and comparative genomics of bacteriophage genomes, we developed multiPhATE2. As an extension of the multiPhATE code, multiPhATE2 performs gene finding and functional sequence annotation of predicted gene and protein sequences, and additional search algorithms and databases extend the search space of the original functional annotation subsystem. MultiPhATE2 includes comparative genomics codes for gene matching among sets of input bacteriophage genomes, and scales well to large input data sets with the incorporation of multiprocessing in the functional annotation and comparative genomics subsystems. MultiPhATE2 was implemented in Python 3.7 and runs as a command-line code under Linux or MAC-OS. MultiPhATE2 is freely available under an open-source GPL-3 license at https://github.com/carolzhou/multiPhATE2. Instructions for acquiring the databases and third party codes used by multiPhATE2 are found in the README file included with the distribution. Users may report bugs by submitting issues to the project GitHub repository webpage. Contact: zhou4@llnl.gov or multiphate@gmail.com. Supplementary materials, which demonstrate the outputs of multiPhATE2, are available in a GitHub repository, at https://github.com/carolzhou/multiPhATE2_supplementaryData/.
Higher Order AMMI (HO-AMMI) analysis: A novel stability model to study genotype-location interactions
Authors: Ajay BC , Abdul Fiyaz R , Bera SK , kumar Narendra , Gangadhar K , kona Praveen , Rani Kirti , Radhakrishnan T 
Published: October 2020

AbstractAdditive main effects and multiplicative interaction (AMMI) model is most widely used to analyse genotype*environment interactions (GEI) wherein interaction effects of location is masked by year effect. Hence, presently available models are not able to estimate interaction effects of genotype*location (GLI) and genotype*year (GYI) separately. Moreover, genotype ranking differs as number of years of evaluation vary making selection of genotype for target location difficult. In the present study we propose a novel stability model i.e Higher-order-AMMI (HO-AMMI) analysis which is capable of calculating GLI without the confounding effect of GYI and GLYI. GEI of AMMI model and all 2-way interactions of HO-AMMI model follow χ2distribution, whereas 3-way interaction (GLYI) of HO-AMMI follow noncentral χ2distribution. With increase in number of years of evaluation contribution of GLI towards total variation increased whereas in AMMI model contribution of GEI towards total variation decreased. Variation explained by multiplicative components is higher in HO-AMMI compared to AMMI model. Genotypes were ranked using GL, GY and GL+GY+GLY interactions of HO-AMMI and GEI of AMMI for stability and yield and compared their ranks with field ranking. Correlation and linear regression analysis have indicated high association of GLI (HO-AMMI) with field ranking with high R2values. Further, HO-AMMI model was able to remove the confounding effect of GYI and GLYI on GLI for accurate identification of genotype for target location irrespective of number of years of evaluation. Hence, HO-AMMI model can be used under multi-environment trials (MET) for selecting genotypes efficiently.Availability and InformationSource code implemented in R is available from corresponding author.
BayesSMILES: Bayesian Segmentation Modeling for Longitudinal Epidemiological Studies
Authors: Jiang Shuang , Zhou Quan , Zhan Xiaowei , Li Qiwei 
Published: October 2020

AbstractThe coronavirus disease of 2019 (COVID-19) is a pandemic. To characterize its disease transmissibility, we propose a Bayesian change point detection model using daily actively infectious cases. Our model builds on a Bayesian Poisson segmented regression model that can 1) capture the epidemiological dynamics under the changing conditions caused by external or internal factors; 2) provide uncertainty estimates of both the number and locations of change points; and 3) adjust any explanatory time-varying covariates. Our model can be used to evaluate public health interventions, identify latent events associated with spreading rates, and yield better short-term forecasts.
Nudging the N170 forward with prior stimulation – Bridging the gap between N170 and recognition potential
Authors: Luo Canhuang , Chen Wei , VanRullen Rufin , Gaspar Carl Michael , Zhang Ye 
Published: October 2020

AbstractSome neural responses are classified by the stimulus conditions leading up to that response while other neural responses are also classified by the morphology of the responses themselves. However, morphology-based classification may not be appropriate if one can nudge a neural response into looking like another neural response. Morphology-based classification occurs with the N170 and RP (Recognition Potential), ERP components that are studied in separate literatures and yet share much in common in terms of functionality. In this study, we demonstrate a gradual transformation in the morphology of the N170 to the RP using a simple parametric manipulation of forward masks that is unlikely to cause a change in the underlying processing. Both the N170 and RP are N1 components, meaning that they are the first negative deflection of the evoked response. However, the RP is often measured with a forward mask that ends at stimulus onset whereas the N170 is often measured with no masking at all. This study investigates how ISI may delay and distort the N170 into an RP by manipulating the temporal gap (ISI) between forward mask and target. The results revealed reverse relationships between the ISI on the one hand, and the N170 latency, single-trial N1 jitter (an approximation of N1 width) and reaction time on the other hand. Importantly, we find that scalp topographies have a unique signature at the N1 peak across all conditions, from the longest gap (N170) to the shortest (RP). These findings prove that the mask-delayed N1 is still the same N170, even under conditions that are normally associated with a different component like the RP. In general, our results suggest that greater caution should be taken to interpret the time course of a measured effect when forward masks are employed.
Genetic and metabolite biomarkers reveal actinobacteria-mediated estrogen biodegradation in urban estuarine sediment
Authors: Hsiao Tsun-Hsien , Chen Yi-Lung , Meng Menghsiao , Chuang Meng-Rong , Horinouchi Masae , Hayashi Toshiaki , Wang Po-Hsiang , Chiang Yin-Ru 
Published: October 2020

AbstractSteroidal estrogens are often accumulated in urban estuarine sediments worldwide at microgram per gram levels. These aromatic steroids have been classified as endocrine disruptors with an EC50 at sub-nanomolar concentrations and classified as Group 1 carcinogens by the World Health Organization. Microbial degradation is a naturally occurring mechanism that mineralizes estrogens in the biosphere; however, the corresponding genes in estrogen-degrading actinobacteria remain unidentified. In this study, we identified a gene cluster encoding several putative estrogen-degrading genes in actinobacteriumRhodococcussp. strain B50. Among them, theoecBandoecCgenes involved in estrogenic A-ring cleavage were identified through gene-disruption experiments. We also detected the accumulation of two extracellular estrogenic metabolites, including pyridinestrone acid (PEA) and 3aα-H-4α(3’-propanoate)-7aβ-methylhexahydro-1,5-indanedione (HIP), in the estrone-fed strain B50 cultures. Since actinobacterialoecCand proteobacterialoecCshared less than 40% sequence identity,oecCcould serve as a specific biomarker to differentiate the contribution of actinobacteria and proteobacteria in environmental estrogen degradation. Therefore,oecCand the extracellular metabolites PEA and HIP were used as biomarkers to investigate estrogen biodegradation in an urban estuarine sediment. Interestingly, our data suggested that actinobacteria, rather than alpha-proteobacteria function in sewage treatment plants, are actively degrading estrogens in the urban estuarine sediment.Graphical AbstractHighlightsIsolation of an estrogen-degrading actinobacteriumRhodococcussp. strain B50 and establishment of a strain B50 genetic manipulation system.Strain B50 exhibits a two-fold estrogen degradation rate of that of estrogen-degrading alpha-proteobacteria under the same cultivation conditions.Functional characterization of two oxygenase genes,oecBandoecC, involved in estrogenic A-ring cleavage in actinobacteria.Identification of two extracellular estrogenic metabolites, PEA and HIP, in the estrone-fed strain B50 cultures.Detection of actinobacterialoecCsequences as well as PEA and HIP in the estrone-spiked urban estuarine sediments.