bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial Experience With Low-Dose 18F-Fluorodeoxyglucose Positron Emission Tomography/Magnetic Resonance Imaging With Deep Learning Enhancement
Authors: Park Christian J. , Chen Weijie , Pirasteh Ali , Kim David H. , Perlman Scott B. , Robbins Jessica B. , McMillan Alan B. 
Published: June 2021

Objective
To demonstrate the utility of deep learning enhancement (DLE) to achieve diagnostic quality low-dose positron emission tomography (PET)/magnetic resonance (MR) imaging.

Methods
Twenty subjects with known Crohn disease underwent simultaneous PET/MR imaging after intravenous administration of approximately 185 MBq of 18F-fluorodeoxyglucose (FDG). Five image sets were generated: (1) standard-of-care (reference), (2) low-dose (ie, using 20% of PET counts), (3) DLE-enhanced low-dose using PET data as input, (4) DLE-enhanced low-dose using PET and MR data as input, and (5) DLE-enhanced using no PET data input. Image sets were evaluated by both quantitative metrics and qualitatively by expert readers.

Results
Although low-dose images (series 2) and images with no PET data input (series 5) were nondiagnostic, DLE of the low-dose images (series 3 and 4) achieved diagnostic quality images that scored more favorably than reference (series 1), both qualitatively and quantitatively.

Conclusions
Deep learning enhancement has the potential to enable a 90% reduction of radiotracer while achieving diagnostic quality images.
CT Evaluation of Variations in the Middle Cranial Fossa Foramina: A Potential Guide for Skull Base Surgery
Authors: Orhan Soylemez Umut Percem , Atalay Basak 
Published: June 2021

Objectives
To evaluate and classify the variations of foramen ovale (FO), foramen spinosum (FS).

Methods
Six hundred fifty-eight computed tomographies (CTs) were evaluated by 2 observers. Foramen ovale was classified as oval, almond, round, and slit-like. Duplication, absence, and confluence for FS were noted. Bony outgrowths were categorized as tubercule, bony plate, and spine.

Results
Oval shaped FO was the most common subgroup. Most common FS variation was the confluence with FO. Of bony outgrowths, tubercule-shaped were the most common type and spine-shaped ones were the least. Substantial agreement for bony plate and tubercule, almost excellent agreement for all the other parameters were found between 2 observers.

Conclusions
Foramen ovale called lobulated and had not classified previously was described in this study. Computed tomography is a reliable tool for anatomical evaluation of FO and FS, which would effect the methods of middle cranial fossa surgery. Thus, radiologists should be a pathfinder about the variations of these structures.
Disease Activity and Rate and Severity of Flares During Peripartum Period in Thai Patients With Systemic Lupus Erythematosus
Authors: Louthrenoo Worawit , Trongkamolthum Thananant , Kasitanon Nuntana , Wongthanee Antika 
Published: June 2021

Background/Objective
The aim of this study was to compare disease activity and rate and severity of flares between pregnant and nonpregnant systemic lupus erythematosus (SLE) patients.

Methods
Medical records of pregnant SLE patients seen between January 1993 and June 2017 were reviewed. Nonpregnant SLE controls were matched by age at diagnosis and disease duration before pregnancy. Systemic lupus erythematosus disease activity and flares were determined by the cSLEDAI (clinical Systemic Lupus Erythematosus Disease Activity Index) and Safety of Estrogens in Lupus Erythematosus National Assessment–SLEDAI Flare Index, respectively. Disease activity was measured from 6 months before conception (−6 months) until the postpartum period. The repeated measures mixed model, Cox regression, and cumulative hazard plots were used for statistical analysis.

Results
Ninety pregnancies occurred in 77 patients. The cSLEDAI scores from −6 months to the postpartum period were comparable between the pregnancy and control group, but slightly yet significantly higher in the controls at conception (mean ± SEM, 3.57 ± 0.45 vs 1.90 ± 0.36; p = 0.019). When compared with the controls, during the pregnancy and postpartum period, the pregnancy group did not have significantly higher incidence of flare (41.11% vs 28.89%, p = 0.086 and 7.78% vs 11.11%, p = 0.445, respectively) or flare category (severe flare) (75.68% vs 53.85%, p = 0.070 and 85.71% vs 70.00%, p = 0.603, respectively). The flare incidence rate (95% confidence interval)/100 patient-months in the pregnancy and control group was 6.75 (4.89–9.32) and 4.34 (2.96–6.38), respectively, giving the adjusted hazards for flare (95% confidence interval) of 1.54 (0.91–2.61) (p = 0.110).

Conclusions
There was no overall significant increase in SLE disease activity, flare incidence, and flare severity in pregnant SLE patients when compared with their properly matched nonpregnant SLE controls.
Prevalence of Workforce Diversity Research Among Surgical Specialties in the United States
Authors: Reghunathan Meera , Blum Jessica , Gosman Amanda A. , Butler Paris D. , Chen Wendy 
Published: June 2021

BackgroundPlastic surgeons are not as diverse as expected in relation to the increasingly diverse patient and medical student population. The authors assess the state of diversity in 8 primary surgical specialties in the United States and evaluate trends in research interest in diversity over the past 30 years.MethodsArticles regarding diversity in surgery from 1990 to 2020 were systematically reviewed. The Association of American Medical Colleges Physician Specialty Data Reports and the Accreditation Council for Graduate Medical Education Data Resource Books provided resident/fellow and faculty data from 2011 to 2016. Trends were analyzed over time per specialty.ResultsFrom 1990 to 2020, a total of 199 publications related to diversity were identified among the various surgical specialties. Orthopedic surgery had significantly more publications per year compared with other specialties (P< 0.05). Every specialty demonstrated a significant increase in publications about diversity over time (P< 0.05). A majority of publications were related to sex rather than underrepresented in medicine topics. The proportion of female surgeons was significantly higher for plastic surgery than for orthopedic surgery and neurosurgery (P< 0.001). Plastic surgery exhibited the highest growth rate in female residents (+1.6% per year,P< 0.001). The proportion of underrepresented minorities composing surgical trainees has not significantly increased in any surgical specialty between 2011 and 2016 (P> 0.05).ConclusionsAlthough diversity representation in surgery has somewhat improved, the rate is too slow to match the growing diversity of the US population. Outcomes have been disparate between specialties and demonstrate greater increases in sex equality relative to ethnic/racial equality. Evidence-based interventions need to be developed and implemented.
Joint Salvage and Biological Repair of Massive-Cavity Bone Defects After Extensive Curettage of Campanacci Grade II or III Giant Cell Tumor Around the Knee With Vascularized Fibular Autograft and Cancellous Allograft
Authors: Yang Yun-Fa , Wang Jian-Wei , Gao Xiao-Sheng , Huang Jian-Wen , Xu Zhong-He 
Published: June 2021

Objective
The aim of the study was to report the clinical outcomes of repair of massive-cavity bone defects after extensive curettage of Campanacci grade II or III giant cell tumor (GCT) around knee with vascularized fibular autograft and cancellous allograft.

Methods
There were 12 consecutive patients with Campanacci grade II or III GCT around knee treated in our department between 2004 and 2016. All the patients underwent clinical evaluation, plain radiography, and/or magnetic resonance imaging of the knee right after admission. To preserve their knee function, we repaired the massive-cavity bone defects after extensive curettage of GCT by vascularized fibular autografts and cancellous allograft. All the patients were evaluated through clinical examinations, plain radiography of the knee and chest, and Musculoskeletal Tumor Society (MSTS) scores of the lower extremity in the follow-ups.

Results
The follow-up ranged from 1.5 to 12.0 years (mean, 4.2 years). There were no local recurrences or lung metastasis in any of the 12 patients at the last follow-up. Ten patients had no pain or experienced occasional pain, and 9 were able to resume their previous work. The mean range of motion of knee flexion was 117 degrees, and the extension was −6 degrees. The mean MSTS score was 24.7, and a total of 10 patients had excellent or good MSTS scores.

Conclusions
It is reliable to achieve knee joint salvage and repair massive-cavity bone defects after extensive curettage with vascularized fibular autograft and cancellous allograft in patients with Campanacci grade II or III GCT around the knee.
Recent advances in biomedical, biosensor and clinical measurement devices for use in humans and the potential application of these technologies for the study of physiology and disease in wild animals
Authors: Macdonald Alexander , Hawkes Lucy A. , Corrigan Damion K. 
Published: June 2021

The goal of achieving enhanced diagnosis and continuous monitoring of human health has led to a vibrant, dynamic and well-funded field of research in medical sensing and biosensor technologies. The field has many sub-disciplines which focus on different aspects of sensor science; engaging engineers, chemists, biochemists and clinicians, often in interdisciplinary teams. The trends which dominate include the efforts to develop effective point of care tests and implantable/wearable technologies for early diagnosis and continuous monitoring. This review will outline the current state of the art in a number of relevant fields, including device engineering, chemistry, nanoscience and biomolecular detection, and suggest how these advances might be employed to develop effective systems for measuring physiology, detecting infection and monitoring biomarker status in wild animals. Special consideration is also given to the emerging threat of antimicrobial resistance and in the light of the current SARS-CoV-2 outbreak, zoonotic infections. Both of these areas involve significant crossover between animal and human health and are therefore well placed to seed technological developments with applicability to both human and animal health and, more generally, the reviewed technologies have significant potential to find use in the measurement of physiology in wild animals.This article is part of the theme issue ‘Measuring physiology in free-living animals (Part II)’.
DNA methylation changes in glial cells of the normal-appearing white matter in Multiple Sclerosis patients
Authors: Kular Lara , Ewing Ewoud , Needhamsen Maria , Kakhki Majid Pahlevan , Covacu Ruxandra , Gomez-Cabrero David , Brundin Lou , Jagodic Maja 
Published: June 2021

AbstractBackgroundMultiple Sclerosis (MS), the leading cause of non-traumatic neurological disability in young adults, is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Due to the poor accessibility to the target organ, CNS-confined processes underpinning the later progressive form of MS remain elusive thereby limiting treatment options. We aim to examine DNA methylation, a stable epigenetic mark of genome activity, in glial cells to capture relevant molecular changes underlying MS neuropathology.MethodsWe profiled DNA methylation in nuclei of glial cells, isolated from 38 post-mortem normal-appearing white matter (NAWM) specimens of MS patients (n=8) in comparison to white matter of control individuals (n=14), using Infinium MethylationEPIC BeadChip.FindingsWe identified 1,226 significant (genome-wide adjusted P-value < 0.05) differentially methylated positions (DMPs) between MS patients and controls. Functional annotation of the altered DMP-genes uncovered alterations of processes related to cellular motility, cytoskeleton dynamics, metabolic processes, synaptic support, neuroinflammation and signaling, such as Wnt and TGF-β pathways. A fraction of the affected genes displayed transcriptional differences in the brain of MS patients, as reported by publically available transcriptomic data. Cell type-restricted annotation of DMP-genes attributed alteration of cytoskeleton rearrangement and extracellular matrix remodelling to all glial cell types, while some processes, including ion transport, Wnt/TGF-β signaling and immune processes were more specifically linked to oligodendrocytes, astrocytes and microglial cells, respectively.ConclusionOur findings strongly suggest that NAWM glial cells are highly altered, even in the absence of lesional insult, collectively exhibiting a multicellular reaction in response to diffuse inflammation.
Development and validation of blood-based prognostic biomarkers for severity of COVID disease outcome using EpiSwitch 3D genomic regulatory immuno-genetic profiling
Authors: Hunter Ewan , Koutsothanasi Christina , Wilson Adam , Santos Francisco C. , Salter Matthew , Westra Jurjen W. , Powell Ryan , Dring Ann , Brajer Paulina , Egan Benedict , Parnall Matthew , Williams Catriona , Katzinski Aemilia , Lavin Thomas , Ramadass Aroul , Messer William , Brunton Amanda , Lyski Zoe , Vancheeswaran Rama , Barlow Andrew , Pchejetski Dmitri , Robbins Peter A. , Mellor Jane , Akoulitchev Alexandre 
Published: June 2021

AbstractThe COVID-19 pandemic has raised several global public health challenges to which the international medical community have responded. Diagnostic testing and the development of vaccines against the SARS-CoV-2 virus have made remarkable progress to date. As the population is now faced with the complex lifestyle and medical decisions that come with living in a pandemic, a forward-looking understanding of how a COVID-19 diagnosis may affect the health of an individual represents a pressing need. Previously we used whole genome microarray to identify 200 3D genomic marker leads that could predict mild or severe COVID-19 disease outcomes from blood samples in a multinational cohort of COVID-19 patients. Here, we focus on the development and validation of a qPCR assay to accurately predict severe COVID-19 disease requiring intensive care unit (ICU) support and/or mechanical ventilation. From 200 original biomarker leads we established a classification model containing six markers. The markers were qualified and validated on 38 COVID-19 patients from an independent cohort. Overall, the six-marker model obtained a positive predictive value of 93% and balanced accuracy of 88% across 116 patients for the prognosis of COVID-19 severity requiring ICU care/ventilation support. The six-marker signature identifies individuals at the highest risk of developing severe complications in COVID-19 with high predictive accuracy and can assist in patient prognosis and clinical management decisions.
Rapid protocols to support Covid-19 clinical diagnosis based on hematological parameters
Authors: Gomes Juliana Carneiro , de Freitas Barbosa Valter Augusto , de Santana Maíra Araújo , de Lima Clarisse Lins , Calado Raquel Bezerra , Bertoldo Júnior Cláudio Roberto , de Almeida Albuquerque Jeniffer Emidio , de Souza Rodrigo Gomes , de Araújo Ricardo Juarez Escorel , Moreno Giselle Machado Magalhães , Soares Luiz Alberto Lira , Mattos Júnior Luiz Alberto Reis , de Souza Ricardo Emmanuel , dos Santos Wellington Pinheiro 
Published: June 2021

AbstractPurposeIn December 2019, the Covid-19 pandemic began in the world. To reduce mortality, in addiction to mass vaccination, it is necessary to massify and accelerate clinical diagnosis, as well as creating new ways of monitoring patients that can help in the construction of specific treatments for the disease.ObjectiveIn this work, we propose rapid protocols for clinical diagnosis of Covid-19 through the automatic analysis of hematological parameters using Evolutionary Computing and Machine Learning. These hematological parameters are obtained from blood tests common in clinical practice.MethodWe investigated the best classifier architectures. Then, we applied the particle swarm optimization algorithm (PSO) to select the most relevant attributes: serum glucose, troponin, partial thromboplastin time, ferritin, D-dimer, lactic dehydrogenase, and indirect bilirubin. Finally, we used decision trees to build four rapid protocols for Covid-19 clinical diagnosis.ResultsWe developed a web system for Covid-19 diagnosis support. Using a 100-tree Random Forest, we obtained results for accuracy, sensitivity and specificity superior to 99ConclusionBy using a reduced set of hematological parameters common in clinical practice, it was possible to achieve results of accuracy, sensitivity and specificity comparable to those obtained with RT-PCR. It was also possible to automatically generate clinical decision protocols, allowing relatively accurate clinical diagnosis even without the aid of the web decision support system.
RIC3 variants are not associated with Parkinson’s Disease in large European, Latin American, or East Asian cohorts
Authors: Brolin Kajsa , Bandres-Ciga Sara , Leonard Hampton , Makarious Mary B. , Blauwendraat Cornelis , Mata Ignacio F , Foo Jia Nee , Pihlstrøm Lasse , Swanberg Maria , Gan-Or Ziv , Tan Manuela MX ,   International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: June 2021

AbstractParkinson’s disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD, but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yielded inconsistent results. We further investigate the role of RIC3 variants in PD in European cohorts using individual-level genotyping data from 14,671 PD patients and 17,667 controls, as well as whole-genome sequencing data from 1,615 patients and 961 controls. We also investigated RIC3 using summary statistics from a Latin American cohort of 1,481 individuals, and from a cohort of 31,575 individuals of East Asian ancestry. We did not identify any association between RIC3 and PD in any of the cohorts. However, more studies of rare variants in non-European ancestry populations, in particular South Asian populations, are necessary to further evaluate the world-wide role of RIC3 in PD etiology.
Pre-activated anti-viral innate immunity in the upper airways controls early SARS-CoV-2 infection in children
Authors: Loske J , Röhmel J , Lukassen S , Stricker S , Magalhães VG , Liebig J , Chua RL , Thürmann L , Messingschlager M , Seegebarth A , Timmermann B , Klages S , Ralser M , Sawitzki B , Sander LE , Corman VM , Conrad C , Laudi S , Binder M , Trump S , Eils R , Mall M.A. , Lehmann I 
Published: June 2021

AbstractChildren are consistently reported to have reduced SARS-CoV-2 infection rates and a substantially lower risk for developing severe COVID-19. However, the molecular mechanisms underlying protection against COVID-19 in younger age groups remain widely unknown. Here, we systematically characterized the single-cell transcriptional landscape in the upper airways in SARS-CoV-2 negative and age-matched SARS-CoV-2 positive children (n=42) and corresponding samples from adults (n=44), covering an age range of four weeks to 77 years. Children displayed higher basal expression of the relevant pattern recognition receptor (PRR) pathways in upper airway epithelial cells, macrophages, and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection compared to adults. We further detected distinct immune cell subpopulations with an overall dominance of neutrophils and a population of cytotoxic T cells occurring predominantly in children. Our study provides evidence that the airway epithelial and mucosal immune cells of children are pre-activated and primed for virus sensing, resulting in a stronger early innate antiviral responses to SARS-CoV-2 infection compared to adults.
Ipsilesional motor cortex activation with high-force unimanual handgrip contractions of the less-affected limb in participants with stroke
Authors: Andrushko Justin W. , Gould Layla , Renshaw Doug W. , Forrester Shannon , Kelly Michael E. , Linassi Gary , Mickleborough Marla , Oates Alison , Hunter Gary , Borowsky Ron , Farthing Jonathan P. 
Published: June 2021

AbstractStroke is a leading cause of severe disability that often presents with unilateral motor impairment. Conventional rehabilitation approaches focus on motor practice of the affected limb and aim to suppress brain activity in the contralesional hemisphere to facilitate ipsilesional hemispheric neuroplasticity subserving motor recovery. Previous research has also demonstrated that exercise of the less-affected limb can promote motor recovery of the affected limb through the interlimb transfer of the trained motor task, termed cross-education. One of the leading theories for cross-education proposes that the interlimb transfer manifests from ipsilateral cortical activity during unimanual motor tasks, and that this ipsilateral cortical activity results in motor related neuroplasticity giving rise to contralateral improvements in motor performance. Conversely, exercise of the less-affected limb promotes contralesional brain activity which is typically viewed as contraindicated in stroke recovery due to the interhemispheric inhibitory influence onto the ipsilesional hemisphere. High-force unimanual handgrip contractions are known to increase ipsilateral brain activation in control participants, but it remains to be determined if this would be observed in participants with stroke. Therefore, this study aimed to determine how parametric increases in handgrip force during repeated contractions with the less-affected limb impacts brain activity bilaterally in participants with stroke and in a cohort of neurologically intact controls. In this study, higher force contractions were found to increase brain activation in the ipsilesional/ipsilateral hemisphere in both groups (p = .002), but no between group differences were observed. These data suggest that high-force exercise with the less-affected limb may promote ipsilesional cortical plasticity to promote motor recovery of the affected-limb in participants with stroke.
Chronic adolescent stress increases exploratory behavior but does not change the acute stress response in adult male C57BL/6 mice
Authors: Sturman Oliver , von Ziegler Lukas , Privitera Mattia , Waag Rebecca , Duss Sian , Vermeiren Yannick , de Deyn Peter , Bohacek Johannes 
Published: June 2021

AbstractChronic stress exposure in adolescence can lead to a lasting change in stress responsiveness later in life and is associated with increased mental health issues in adulthood. Here we investigate whether the Chronic Social Instability (CSI) paradigm in mice influences the behavioural and molecular responses to novel acute stressors, and whether it alters physiological responses influenced by the noradrenergic system. Using large cohorts of mice, we show that CSI mice display a persistent increase in exploratory behaviors in the open field test alongside small but widespread transcriptional changes in the ventral hippocampus. However, both the transcriptomic and behavioural responses to novel acute stressors are indistinguishable between groups. In addition, the pupillometric response to a tail shock, known to be mediated by the noradrenergic system, remains unaltered in CSI mice. Ultra-high performance liquid chromatography analysis of monoaminergic neurotransmitter levels in the ventral hippocampus also shows no differences between control or CSI mice at baseline or in response to acute stress. We conclude that CSI exposure during adolescence leads to persistent changes in exploratory behavior and gene expression in the hippocampus, but it does not alter the response to acute stress challenges in adulthood and is unlikely to alter the function of the noradrenergic system.