bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classifying Microscopic Acute and Old Myocardial Infarction Using Convolutional Neural Networks
Authors: Garland Jack , Hu Mindy , Duffy Michael , Kesha Kilak , Glenn Charley , Morrow Paul , Stables Simon , Ondruschka Benjamin , Da Broi Ugo , Tse Rexson Datquen 
Published: April 2021

Abstract
Convolutional neural network (CNN) has advanced in recent years and translated from research into medical practice, most notably in clinical radiology and histopathology. Research on CNNs in forensic/postmortem pathology is almost exclusive to postmortem computed tomography despite the wealth of research into CNNs in surgical/anatomical histopathology. This study was carried out to investigate whether CNNs are able to identify and age myocardial infarction (a common example of forensic/postmortem histopathology) from histology slides. As a proof of concept, this study compared 4 CNNs commonly used in surgical/anatomical histopathology to identify normal myocardium from myocardial infarction. A total of 150 images of the myocardium (50 images each for normal myocardium, acute myocardial infarction, and old myocardial infarction) were used to train and test each CNN. One of the CNNs used (InceptionResNet v2) was able to show a greater than 95% accuracy in classifying normal myocardium from acute and old myocardial infarction. The result of this study is promising and demonstrates that CNN technology has potential applications as a screening and computer-assisted diagnostics tool in forensic/postmortem histopathology.
Fatal Coronary Artery Vasculitis With Mixed Features
Authors: Birsic George W. , Hentschel Brynn E. , Overton-Hennessy Zo C. , Ward Michael E. , Fiester Steven E. , Fulcher James W. 
Published: April 2021

Abstract
Atherosclerotic cardiovascular disease (ASCVD) is often investigated by medical examiners as a cause of sudden death. Because of the variation in presentation of atherosclerotic cardiovascular disease, the examiner must be cautious when assigning a final diagnosis. The presented case depended upon histologic examination of coronary artery lesions to reach an appropriate final diagnosis of vasculitis with mixed features. Autopsy findings showed hepatosplenic vasculitis with noncaseating granulomas, and multifocal diffuse coronary fibrosis with histologic findings consistent with late-stage polyarteritis nodosa (PAN). However, the patient lacked the hallmark renal involvement observed in PAN. Furthermore, the vasculitis within the liver showed a highly granulomatous appearance, more consistent with IgG4 disease. In these mixed-appearance cases with limited history, exact categorization of the disease may prove difficult to impossible. Herein, we review a differential diagnosis of classic vasculitides with a focus on those that commonly affect the coronary arteries in adults, namely, PAN.
Death Due to Adrenal Crisis
Authors: Gitto Lorenzo , Stoppacher Robert , Serinelli Serenella 
Published: April 2021

Abstract
Adrenal crisis is a life-threatening manifestation of acute adrenal insufficiency. One of the most important underlying causes is Addison disease (primary adrenal insufficiency).
A 42-year-old White woman with a medical history of Addison disease on chronic steroid therapy was admitted to the emergency department due to sustained episodes of cardiopulmonary arrest. Upon admission, she was hypotensive and hypoglycemic. Despite resuscitation attempts, she developed multiorgan failure and eventually died. At autopsy, no definitive adrenal gland tissue was grossly identified, but histology detected atrophy of adrenal glands with patchy chronic inflammation. Evidence of acute pneumonia was seen. The cause of death was determined to be complications of adrenal/Addisonian crisis.
A review of the literature showed only a few autopsy studies regarding deaths due to adrenal crisis. Forensic pathologists should include adrenal crisis in their differential diagnosis. Adequate medical history and pertinent autopsy findings can corroborate deaths due to adrenal crisis, but exhaustive biochemical analyses are mandatory to support the diagnosis further.
The Intra.Ox Near-Infrared Spectrometer Measures Variations in Flap Oxygenation That Correlate to Flap Necrosis in a Preclinical Rodent Model
Authors: Khavanin Nima , Darrach Halley , Kraenzlin Franca , Yesantharao Pooja S. , Sacks Justin M. 
Published: April 2021

Background:
Mastectomy flap necrosis affects 7 to 40 percent of patients undergoing immediate breast reconstruction, with many cases resulting in infection and/or explantation. The Intra.Ox near-infrared spectrometer is a novel device that assesses tissue perfusion by measuring the interactions of light with oxygenated and deoxygenated hemoglobin. This handheld device facilitates serial flap perfusion assessment and may objectively identify at-risk tissues and guide evidence-based treatment algorithms. In this preliminary study, we hypothesized that the Intra.Ox spectrometer detects differences in tissue oxygenation that correlate to tissue necrosis.

Methods:
Dorsal, random-pattern flaps measuring 10 × 3 cm were raised in eight male Sprague-Dawley rats. Intraoperative tissue oxygen saturation was measured using Intra.Ox in 10 standardized locations. On postoperative day 7, the skin flaps were evaluated for full-thickness necrosis. Data were analyzed using the chi-square test and one-way analysis of variance. A receiver operating characteristic curve assessed the accuracy of intraoperative tissue oxygenation in predicting the risk of flap necrosis.

Results:
Tissue oxygen saturation exhibited a strong negative correlation to distance from the flap pedicle (r = −0.798). Oxygen saturation in tissue that developed necrosis averaged 32 percent, compared to 59 percent in tissues that did not (p < 0.001). The area under the receiver operating characteristic curve was 0.969. Post hoc oxygen saturation cutoffs with 100 percent specificity and sensitivity in predicting necrosis were identified at 46 percent and 54 percent, respectively.

Conclusions:
Intra.Ox detects significant differences in tissue oxygenation saturation that are associated with the risk for flap necrosis. This technology can be used to identify at-risk tissues and represents an avenue for research aimed at preventing flap necrosis.
Altered subcutaneous adipose tissue parameters after switching ART-controlled HIV+ patients to raltegravir/maraviroc
Authors: Bastard Jean-Philippe , Pelloux Véronique , Alili Rohia , Fellahi Soraya , Aron-Wisnewsky Judith , Capel Emilie , Fève Bruno , Assoumou Lambert , Prifti Edi , Katlama Christine , Clément Karine , Capeau Jacqueline 
Published: April 2021

Objective:
To evaluate the effect on anthropometric, metabolic and adipose tissue parameters of switching ART-controlled persons living with HIV (PLWH) from a protease inhibitor regimen to raltegravir/maraviroc.

Design:
Sub-study of the ANRS157 ROCnRAL study with the investigation of subcutaneous abdominal adipose tissue (SCAT) biopsy at inclusion and study end.

Methods:
We performed lipoaspiration of paired SCAT samples, histology on fresh/fixed samples and examined the transcriptomic profile analyzed using Illumina microarrays after RNA extraction. Statistical analyses used the Wilcoxon-paired test.

Results:
The patients (n = 8) were mainly male (7/8), aged (mean ± standard error of the mean) 54.9 ± 1.2 years, BMI 26.1 ± 1.2 kg/m2, CD4+ 699 ± 56 cells/mm3, all viral load (VL) <50 copies/ml. After a follow-up of 6 ± 0.5 months, all PLWH remained with VL <50 copies/ml. BMI, trunk and limb fat amounts were unchanged yet systemic insulin resistance increased. Adipose tissue histology was unchanged except for borderline increased adipocyte diameter (P = 0.1). Among the 16 094 RNA transcripts, 458 genes were up-regulated and 244 were down-regulated. Analyses of the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases, evaluating modifications in the main functional pathways, revealed that genes related to immune recognition/function were less expressed as were genes encoding T-cell receptor and receptor signaling pathways. The gene expression profiles indicated decreased inflammation but genes involved in adipogenesis and insulin resistance were overexpressed.

Conclusion:
After 6 months of raltegravir/maraviroc, adipogenesis-related gene profile was enhanced in SCAT, in agreement with a tendency for increased adipocyte size. Enhanced SCAT insulin resistance-related profile was concordant with higher systemic insulin resistance. However, the immune activation/inflammation profile was globally lowered. We propose that raltegravir/maraviroc might favor SCAT gain but reduce inflammation/immune activation.
Etravirine in treatment-experienced HIV-1-infected children 1 year to less than 6 years of age
Authors: MacBrayne Christine E. , Rutstein Richard M. , Wiznia Andrew A. , Graham Bobbie , Alvero Carmelita G. , Fairlie Lee , Lypen Kathryn , George Kathleen H. , Townley Ellen , Moye Jack , Costello Diane G. , Reding Christina A. , Barroso Hofer Cristina , Crauwels Herta M. , Woot de Trixhe Xavier , Tambuyzer Lotke , Vanveggel Simon , Opsomer Magda , Kiser Jennifer J. 
Published: April 2021

Objective:
To describe the pharmacokinetics, safety, and efficacy of etravirine (ETR) in HIV-infected children 1 to less than 6 years of age.

Design:
Phase I/II, open-label, multicenter, dose-finding study.

Methods:
Antiretroviral therapy (ART)-experienced children in two age cohorts (I: 2 to <6 years; II: 1 to less than 2 years) received weight-based ETR, swallowed whole or dispersed in liquid, with optimized ART including a ritonavir-boosted protease inhibitor. Intensive pharmacokinetics occurred 7–18 days after starting ETR. Participants with ETR AUC12h less than 2350 ng h/ml had a dose increase and repeat pharmacokinetics.

Results:
Twenty-six children enrolled and 21 (15 in cohort I and 6 in cohort II) had evaluable intensive pharmacokinetics sampling at the final weight-based dose. On the final dose, the geometric mean ETR AUC12h was 3823 ng h/ml for cohort I and 3328 ng h/ml for cohort II. Seven children (33.3%) on the final dose, all taking ETR dispersed, had an AUC12
h less than 2350 ng h/ml and underwent a dose increase. ETR AUC12
h was 3.8-fold higher when ETR was swallowed whole vs. dispersed, P less than 0.0001. On the final dose, 75 and 33.3% in cohorts I and II, respectively, had HIV-1 RNA 400 copies/ml or less or at least 2 log reductions from baseline at week 48. Three children (11.5%) experienced a grade at least 3 adverse event related to ETR but only 1 discontinued.

Conclusion:
ETR was well tolerated. Predefined pharmacokinetics targets were met but overall exposures were low vs. historical data in adults, particularly in young children taking dispersed tablets. A high rate of viral efficacy was observed among those aged 2 to more than 6 years but not in those less than 2 years.
Performance of Repeat BinaxNOW SARS-CoV-2 Antigen Testing in a Community Setting, Wisconsin, November-December 2020
Authors: Shah Melisa M. , Salvatore Phillip P. , Ford Laura , Kamitani Emiko , Whaley Melissa J. , Mitchell Kaitlin , Currie Dustin W. , Morgan Clint N. , Segaloff Hannah E. , Lecher Shirley , Somers Tarah , Van Dyke Miriam E. , Bigouette John Paul , Delaney Augustina , DaSilva Juliana , O’Hegarty Michelle , Boyle-Estheimer Lauren , Abdirizak Fatima , Karpathy Sandor E. , Meece Jennifer , Ivanic Lynn , Goffard Kimberly , Gieryn Doug , Sterkel Alana , Bateman Allen , Kahrs Juliana , Langolf Kimberly , Zochert Tara , Knight Nancy W. , Hsu Christopher H. , Kirking Hannah L. , Tate Jacqueline E. 
Published: April 2021

AbstractRepeating the BinaxNOW antigen test for SARS-CoV-2 by two groups of readers within 30 minutes resulted in high concordance (98.9%) in 2,110 encounters. BinaxNOW test sensitivity was 77.2% (258/334) compared to real-time reverse transcription-polymerase chain reaction. Repeating antigen testing on the same day did not significantly improve test sensitivity while specificity remained high.
Infant RSV immunoprophylaxis changes nasal epithelial DNA methylation at six years of age
Authors: Xu Cheng-Jian , Scheltema Nienke M. , Qi Cancan , Vedder Rolf , Klein Laura B.C. , Nibbelke Elisabeth E. , van der Ent Cornelis K , Bont Louis J. , Koppelman Gerard H. 
Published: April 2021

AbstractBackgroundRespiratory syncytial virus (RSV) infection has been associated with childhood wheeze and asthma, and potential mechanisms include persistent epigenetic effects.MethodsIn the randomized, placebo-controlled MAKI trial, 429 preterm infants randomly received RSV immunoprophylaxis with palivizumab or placebo during their first RSV season. Children were followed until age 6 for asthma evaluation. DNA methylation in cells obtained by nasal brushes at age 6 was measured by Illumina MethylationEPIC array.ResultsRSV immunoprophylaxis in infancy had significant impact on global methylation patterns in nasal cells at age 6. The first principal component related to the immunoprophylaxis intervention was enriched for the pathway “positive regulation of defense response to virus by host” and “antigen processing and presentation” and driven by methylation changes in NOD2, DGKG, MSH3, and ITPR2. Three CpGsites, cg18040241, cg08243963, cg19555973 were differentially methylated at genome-wide significance, but were not associated with asthma. Differential methylation region analysis identified regions near genes that were previously implicated in the development of asthma and allergy such as HLA-DPA1, HLA-DPB1, FASLG, and CHI3L1.ConclusionsThe study provides the first proof of concept that RSV immunoprophylaxis during infancy has long-term effects on nasal epigenetic signatures at age 6, relating to host antiviral defense pathways.
Metabolome-wide association study on ABCA7 demonstrates a role for ceramide metabolism in impaired cognitive performance and Alzheimer’s disease
Authors: Dehghan Abbas , Pinto Rui , Karaman Ibrahim , Huang Jian , Durainayagam Brenan R , Liggi Sonia , Whiley Luke , Mustafa Rima , Kivipelto Miia , Solomon Alina , Ngandu Tiia , Kanekiyo Takahisa , Aikawa Tomonori , Chekmeneva Elena , Camuzeaux Stephane , Lewis Matthew R. , Kaluarachchi Manuja R , Ghanbari Mohsen , Ikram M Arfan , Holmes Elaine , Tzoulaki Ioanna , Matthews Paul M. , Griffin Julian L. , Elliott Paul 
Published: April 2021

AbstractGenome-wide association studies (GWAS) have identified genetic loci associated with risk of Alzheimer’s disease (AD), but underlying mechanisms are largely unknown. We conducted a metabolome-wide association study (MWAS) of AD-associated loci from GWAS using untargeted metabolic profiling (metabolomics) by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). We identified an association of lactosylceramides (LacCer) with AD-related single nucleotide polymorphisms (SNPs) in ABCA7 (P = 5.0x 10−5 to 1.3 x 10−44). We show that plasma LacCer concentrations are associated with cognitive performance in humans and concentrations of sphingomyelins, ceramides, and hexose-ceramides were altered in brain tissue from ABCA7 knock out mice, compared to wild type (WT) (P =0.049 to 1.4 x10−5). We then used Mendelian randomisation to show that the association of LacCer with AD risk is potentially causal. Our work suggests that risk for AD arising from functional variations in ABCA7 are mediated at least in part through ceramides. Modulation of their metabolism or downstream signalling may offer new therapeutic opportunities for AD.
Performance Comparison of a Flow Cytometry-based and Two Commercial Chemiluminescent Immunoassays for Detection and Quantification of Antibodies Binding to SARS-CoV-2 Spike Protein
Authors: Valdivia Arantxa , Tarín Fabián , Alcaraz María Jesús , Piñero Paula , Torres Ignacio , Marco Francisco , Albert Eliseo , Navarro David 
Published: April 2021

ABSTRACTThe performance of a laboratory-developed quantitative IgG/IgA flow cytometry-based immunoassay (FCI) using Jurkat T cells stably expressing full-length native S protein was compared against Elecsys® electrochemiluminiscent (ECLIA) Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), and LIAISON®SARS-CoV-2 TrimericS IgG chemiluminiscent assay (CLIA) (Diasorin S.p.a, Saluggia, IT) for detection and quantitation of SARS-CoV-2-specific antibodies. A total of 225 serum/plasma specimens from 120 acute or convalescent COVID-19 individuals were included. Overall, IgG/IgA-FCI yielded the highest number of positives (n=179), followed by IgA-FCI (n=177), Roche ECLIA (n=175), IgG-FCI (n=172) and Diasorin CLIA (n=154). Positive percent agreement between FCI and compared immunoassays was highest for Roche ECLIA, ranging from 96.1% (IgG/IgA-FCI) to 97.7% (IgG-FCI), whereas negative percent agreement was higher between FCI and Diasosin CLIA, regardless of antibody isotype. A strong correlation (Rho:0.6-0.8) was found between IgG-FCI or IgA-FCI levels and antibodies quantified by Roche ECLIA and Diasorin CLIA. The trajectory of antibody levels delineated by the different immunoassays in 22 of patients with sequential specimens (≥3) was frequently discordant, with the exception of IgG and IgA determined by FCI assay and to a lesser extent antibodies quantified by Roche ECLIA and Diasorin CLIA. The data suggest that FCI may outperform Roche ECLIA and Diasorin CLIA in terms of clinical sensitivity for serological diagnosis of SARS-CoV-2 infection.
Decoding Neural Activity in Sulcal and White Matter Areas of the Brain to Accurately Predict Individual Finger Movement and Tactile Stimuli of the Human Hand
Authors: Bouton Chad , Bhagat Nikunj , Chandrasekaran Santosh , Herrero Jose , Markowitz Noah , Espinal Elizabeth , Kim Joo-won , Ramdeo Richard , Xu Junqian , Glasser Matthew F. , Bickel Stephan , Mehta Ashesh 
Published: April 2021

AbstractMillions of people worldwide suffer motor or sensory impairment due to stroke, spinal cord injury, multiple sclerosis, traumatic brain injury, diabetes, and motor neuron diseases such as ALS (amyotrophic lateral sclerosis). A brain-computer interface (BCI), which links the brain directly to a computer, offers a new way to study the brain and potentially restore these losses in patients living with debilitating conditions. One of the challenges currently facing BCI technology, however, is how to minimize surgical risk. Minimally invasive techniques, such as stereoelectroencephalography (SEEG) have become more widely used in clinical applications since they can lead to fewer complications. SEEG electrodes also give access to sulcal and white matter areas of the brain but have not been widely studied in brain-computer interfaces. We therefore investigated the viability of using SEEG electrodes in a BCI for recording and decoding neural signals related to movement and the sense of touch and compared its performance to electrocorticography electrodes (ECoG) placed on gyri. Initial poor decoding performance and the observation that most neural modulation patterns were highly variable trial-to-trial and transient (significantly shorter than the sustained finger movements studied), led to the development of a feature selection method based on a repeatability metric using temporal correlation. An algorithm based on temporal correlation was developed to isolate features that consistently repeated (required for accurate decoding) and possessed information content related to movement or touch-related stimuli. We subsequently used these features, along with deep learning methods, to automatically classify various motor and sensory events for individual fingers with high accuracy. Repeating features were found in sulcal, gyral, and white matter areas and were predominantly phasic or phasic-tonic across a wide frequency range for both HD (high density) ECoG and SEEG recordings. These findings motivated the use of long short-term memory (LSTM) recurrent neural networks (RNNs) which are well-suited to handling both transient and sustained input features. Combining temporal correlation-based feature selection with LSTM yielded decoding accuracies of up to 92.04 +/-1.51% for hand movements, up to 91.69 +/-0.49% for individual finger movements, and up to 80.64 +/-1.64% for focal tactile stimuli to the finger pads and palm while using a relatively small number of SEEG electrodes. These findings may lead to a new class of minimally invasive brain-computer interface systems in the future, increasing its applicability to a wider variety of conditions.
Short-range exposure to airborne virus transmission and current guidelines
Authors: Wang Jietuo , Alipour Mobin , Soligo Giovanni , Roccon Alessio , Paoli Marco De , Picano Francesco , Soldati Alfredo 
Published: April 2021

After the Spanish flu pandemic, it was apparent that airborne transmission was crucial to spreading virus contagion, and research responded by producing several fundamental works like the experiments of Duguid [J. Hyg. 44:6, 1946] and the model of Wells [Am. J. Hyg., 20:611–18,1934]. These seminal works have been pillars to past and current guidelines published by health organizations. However, in about one century, understanding of turbulent aerosol transport by jets and plumes has enormously progressed and it is now time to use this body of developed knowledge. In this work, we use detailed experiments and accurate computationally-intensive numerical simulations of droplet-laden turbulent puffs emitted during sneezes in a wide range of environmental conditions. We consider the same emission – number of drops, drop size distribution and initial velocity – and we change environmental parameters as temperature and humidity, and we observe strong variation in droplets evaporation or condensation in accordance with their local temperature and humidity microenvironment. We assume that 3% of the initial droplet volume is made of non-volatile matter. Our systematic analysis confirms that droplets lifetime is always about one order of magnitude larger compared to previous predictions, in some cases up to 200 times. Finally, we have been able to produce original virus exposure maps, which can be a useful instrument for health scientists and practitioners to calibrate new guidelines to prevent short-range airborne disease transmission.Significance StatementViolent expiratory events represent an important route for the spread of respiratory viruses, as the SARS-CoV-2 virus. We use finely-resolved experiments and simulations to quantify how the turbulent cloud of moist air exhaled during a sneeze largely increases the airborne time and the lifespan of virus-loaded droplets. By providing visualizations of the spatial distribution of the virus copies, we highlight the high infection risk associated with droplets that remain airborne in the near proximity of an infected individual. The present study aims at raising awareness among public health authorities about this infection risk, which is grossly underestimated by current guidelines.