bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coronavirus Disease 2019 as a Possible Cause of Severe Orbital Cellulitis
Authors: Carvalho Vinicius Almeida , Vergínio Vinícius Eduardo de Oliveira , Brito Gabriel Conceição , Pereira-Stabile Cecilia Luiz , Stabile Glaykon Alex Vitti 
Published: July 2021

Abstract
Infection by severe respiratory syndrome coronavirus 2 (coronavirus disease 2019) has been the most important public health event of the last 100 years. The number of cases and deaths caused by this disease, its potential to rapidly spread and the search for a vaccine have been the center of discussion all over the world for over 1 year. In addition to the number of cases and all social, economic, and public health consequences of the pandemic, the variety of symptoms and clinical signs presented by infected patients has been subject of several studies and case reports. At the time of this writing, even with promising research, the clinical outcome of some patients is still unpredictable. The purpose of this article is to report an unusual case, the diagnostic process, and early treatment of this severe and atypical clinical picture. The patient is a young man diagnosed with coronavirus disease 2019 who sought our hospital in Southern Brazil reporting a history of pansinusitis progressing to a severe orbital cellulitis, requiring immediate surgical intervention.
The Use of the Free Iliac Bone Flap by Shaping Like Puzzle for a Wide Alveolar Defect in a Bilateral Cleft Lip and Palate with Rudimentary Premaxilla
Authors: Altuntaş Selman Hakkı , Aydın Mustafa Asım 
Published: July 2021

Abstract
Secondary alveolar bone grafting may not be feasible in a considerable number of patients who have cleft lip and palate, mainly because of the requirement for sizeable bony restitution and the insufficient amount of soft tissue for reliable coverage. Bone transport distraction and free vascularized bone transfers are the salvage techniques for treating these deformities and accomplishing successful bone grafting. This report presents a case of bilateral cleft lip and palate with a large palatoalveolar fistula and a rudimentary premaxilla after prior failed attempts at bone grafting. The authors used the free vascularized iliac bone flap with the osteotomies like puzzle for definitive restoration of the deformity.
Esophagectomy Complications Impact Long-term Survival
Authors: Sachidananda Sandeep , Timsina Lava , Namburi Niharika , Birdas Thomas J. 
Published: July 2021

Objective:
To determine the effect of prolonged length of stay (LOS) after esophagectomy on long term survival.

Background:
Complications after esophagectomy have a significant impact in short-term survival. The specific effect of prolonged LOS after esophagectomy is unclear. We hypothesized that postoperative complications that occur after esophagectomy, resulting in prolonged LOS, have a detrimental effect on long term survival.

Methods:
All patients undergoing esophagectomy between 2004 and 2014 were identified in the National Cancer Database. To eliminate the confounding effect of short-term mortality, we included only patients who survived at least 90 days postoperatively. Demographics, disease characteristics, and perioperative outcomes were analyzed. Postoperative LOS was used as a surrogate for postoperative complications. The highest quintile of LOS was defined as excessive LOS (ELOS). Kaplan-Meier and Cox proportional hazards survival analyses were performed to examine survival.

Results:
A total of 20,719 patients were identified. Of those 3826 had ELOS, with median LOS 26days (range 18-168days). Their median survival was 30.6 months compared to 53.6 months in the entire non-ELOS group (P < 0.0001). After multivariate analysis ELOS (odds ratio 1.56, 95% confidence interval 1.46–1.67) was an independent predictor of overall mortality. Higher disease stage, higher age, male sex, higher Charlson/Deyo comorbidity score, and readmission after discharge were also significant negative predictors of long-term survival, whereas surgery in an academic institution, being at the highest income quartile and having private or Medicare insurance predicted longer survival (all P < 0.001).

Conclusions and Relevance:
Postoperative complications after esophagectomy, resulting in ELOS, predict lower long-term survival independent of other factors. Counseling patients about surgery should include the detrimental long-term effects of postoperative complications and ELOS. Avoiding ELOS (LOS exceeding 18 days) could be considered a quality metric after esophagectomy.
Improving Outcome of Superior Mediastinal Lymph Node Dissection During Esophagectomy
Authors: Wong Ian Y. H. , Zhang Rui Qi , Tsang Raymond K. Y. , Kwok Jeanette Y. Y. , Wong Claudia L. Y. , Chan Desmond K. K. , Chan Fion S. Y. , Law Simon Y. K. 
Published: July 2021

Objective:
This study aimed at demonstrating the effects and learning curve of utilizing combined intermittent and continuous recurrent laryngeal nerve (RLN) monitoring for lymphadenectomy during esophagectomy.

Background:
RLN lymphadenectomy is oncologically important but is technically demanding. Vocal cord (VC) palsy as a result from RLN injury, carries significant morbidities.

Methods:
This is a retrospective study of consecutive esophageal squamous cell carcinoma (ESCC) patients who underwent transthoracic esophagectomy from 2010 to 2020. Combined nerve monitoring (CNM) included: CNM which involved a periodic stimulating left vagal electrode and intermittent nerve monitoring which utilized a stimulating probe to identify the RLNs. The integrity of the RLNs was assessed both intermittently and continuously. This technique was introduced in 2014. Patients were divided into “before CNM” and “CNM” groups. The primary outcome was the difference in number of RLN lymph nodes harvested and VC palsy rate. Learning curves were demonstrated by cumulative sum (CUSUM) analysis.

Results:
Two hundred and fifty-five patients were included with 157 patients in “CNM” group. The mean number of RLN lymph nodes harvested was significantly higher (4.31 vs 0.45, P < 0.0001) for the “CNM” group. VC palsy rates were significantly lower (17.8% vs 32.7%, P = 0.007). There was an initial increase in VC palsy rate, peaked at around 46 cases. The increase in lymph nodes harvested above the mean plateaued at around 96 cases.

Conclusions:
CNM helped improve bilateral RLN lymphadenectomy. Lymph node harvesting was increased with reduction of VC palsy after a learning curve.
Segmenting biological specimens from photos to understand the evolution of UV plumage in passerine birds
Authors: He Yichen , Cooney Christopher R. , Varley Zoë K. , Nouri Lara O. , Moody Christopher J. A. , Jardine Michael D. , Maddock Steve , Thomas Gavin H. 
Published: July 2021

AbstractUltraviolet (UV) colouration is thought to be an important signalling mechanism in many bird species, yet broad insights regarding the prevalence of UV plumage colouration and the factors promoting its evolution are currently lacking. Here, we develop a novel image segmentation pipeline based on deep learning that considerably outperforms classical (i.e. non-deep learning) segmentation methods, and use this to extract accurate information on whole-body plumage colouration from photographs of >24,000 museum specimens covering >4,500 species of passerine birds. Our results demonstrate that UV reflectance, particularly as a component of other colours, is widespread across the passerine radiation but is strongly phylogenetically conserved. We also find clear evidence in support of the role of light environment in promoting the evolution of UV plumage colouration, and a weak trend towards higher UV plumage reflectance among bird species with ultraviolet rather than violet-sensitive visual systems. Overall, our study provides important broad-scale insight into an enigmatic component of avian colouration, as well as demonstrating that deep learning has considerable promise for allowing new data to be bought to bear on long-standing questions in ecology and evolution.
Leveraging gene co-regulation to identify gene sets enriched for disease heritability
Authors: Siewert-Rocks Katherine M. , Kim Samuel S. , Yao Douglas W. , Shi Huwenbo , Price Alkes L. 
Published: July 2021

AbstractIdentifying gene sets that are associated to disease can provide valuable biological knowledge, but a fundamental challenge of gene set analyses of GWAS data is linking disease-associated SNPs to genes. Transcriptome-wide association studies (TWAS) can be used to detect associations between the genetically predicted expression of a gene and disease risk, thus implicating candidate disease genes. However, causal disease genes at TWAS-associated loci generally remain unknown due to gene co-regulation, which leads to correlations across genes in predicted expression. We developed a new method, gene co-regulation score (GCSC) regression, to identify gene sets that are enriched for disease heritability explained by the predicted expression of causal disease genes in the gene set. GCSC regresses TWAS chi-square statistics on gene co-regulation scores reflecting correlations in predicted gene expression; GCSC determines that a gene set is enriched for disease heritability if genes with high co-regulation to the gene set have higher TWAS chi-square statistics than genes with low co-regulation to the gene set, beyond what is expected based on co-regulation to all genes. We verified via simulations that GCSC is well-calibrated, and well-powered to identify gene sets that are enriched for disease heritability explained by predicted expression. We applied GCSC to gene expression data from GTEx (48 tissues) and GWAS summary statistics for 43 independent diseases and complex traits (average N =344K), analyzing a broad set of biological pathways and specifically expressed gene sets. We identified many enriched gene sets, recapitulating known biology. For Alzheimer’s disease, we detected evidence of an immune basis, and specifically a role for antigen presentation, in analyses of both biological pathways and specifically expressed gene sets. Our results highlight the advantages of leveraging gene co-regulation within the TWAS framework to identify gene sets associated to disease.
Breakthrough Symptomatic COVID-19 Infections Leading to Long Covid: Report from Long Covid Facebook Group Poll
Authors: Massey Daisy , Berrent Diana , Krumholz Harlan 
Published: July 2021

AbstractVaccines have been shown to be extremely effective in preventing COVID-19 hospitalizations and deaths. However, a question remains whether vaccine breakthrough cases can still lead to Post-Acute Sequelae of SARS-CoV-2 (PASC), also known as Long Covid. To address this question, the Survivor Corps group, a grassroots COVID-19 organization focused on patient support and research, posted a poll to its 169,900 members that asked about breakthrough cases, Long Covid, and hospitalizations. 1,949 people who self-report being fully vaccinated have responded to date. While robust data are needed in a larger, unbiased sample to extrapolate rates to the population, we analyzed the results of this public poll to determine what people were reporting regarding Long Covid after breakthrough infection and to prompt discussion of how breakthrough cases are measured. The poll was posted in the Survivor Corps Facebook group (∼169,900 members). Of the 1,949 participants who responded to the poll, 44 reported a symptomatic breakthrough case and 24 of those reported that the case led to symptoms of Long Covid. 1 of these 24 cases was reported to have led to hospitalization in addition to Long Covid.
Epidemics of chikungunya, Zika, and COVID-19 reveal bias in case-based mapping
Authors: Bustos Carrillo Fausto Andres , Mercado Brenda Lopez , Monterrey Jairo Carey , Collado Damaris , Saborio Saira , Miranda Tatiana , Barilla Carlos , Ojeda Sergio , Sanchez Nery , Plazaola Miguel , Laguna Harold Suazo , Elizondo Douglas , Arguello Sonia , Gajewski Anna M. , Maier Hannah E. , Latta Krista , Carlson Bradley , Coloma Josefina , Katzelnick Leah , Sturrock Hugh , Balmaseda Angel , Kuan Guillermina , Gordon Aubree , Harris Eva 
Published: July 2021

ABSTRACTAccurate tracing of epidemic spread over space enables effective control measures. We examined three metrics of infection and disease in a pediatric cohort (N ≈ 3,000) over two chikungunya and one Zika epidemic, and in a household cohort (N=1,793) over one COVID-19 epidemic in Managua, Nicaragua. We compared spatial incidence rates (cases/total population), infection risks (infections/total population), and disease risks (cases/infected population). We used generalized additive and mixed-effects models, Kulldorf’s spatial scan statistic, and intracluster correlation coefficients. Across different analyses and all epidemics, incidence rates considerably underestimated infection and disease risks, producing large and spatially non-uniform biases distinct from biases due to incomplete case ascertainment. Infection and disease risks exhibited distinct spatial patterns, and incidence clusters inconsistently identified areas of either risk. While incidence rates are commonly used to infer infection and disease risk in a population, we find that this can induce substantial biases and adversely impact policies to control epidemics.Article summary lineInferring measures of spatial risk from case-only data can substantially bias estimates, thereby weakening and potentially misdirecting measures needed to control an epidemic.
Neuron-Glia Signaling Regulates the Onset of the Antidepressant Response
Authors: Yao Vicky , Aly Ammar , Kalik Salina , Gresack Jodi , Wang Wei , Handler Annie , Schaefer Anne , Troyanskaya Olga , Greengard Paul , Chottekalapanda Revathy U. 
Published: July 2021

AbstractCommonly prescribed antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) take weeks to achieve therapeutic benefits1, 2. The underlying mechanisms of why antidepressants take weeks or months to reverse depressed mood are not understood. Using a single cell sequencing approach, we analyzed gene expression changes in mice subjected to stress-induced depression and determined their temporal response to antidepressant treatment in the cerebral cortex. We discovered that both glial and neuronal cell populations elicit gene expression changes in response to stress, and that these changes are reversed upon treatment with fluoxetine (Prozac), a widely prescribed selective serotonin reuptake inhibitor (SSRI). Upon reproducing the molecular signaling events regulated by fluoxetine3 in a cortical culture system, we found that these transcriptional changes are serotonin-dependent, require reciprocal neuron-glia communication, and involve temporally-specified sequences of autoregulation and cross-regulation between FGF2 and BDNF signaling pathways. Briefly, stimulation of Fgf2 synthesis and signaling directly regulates Bdnf synthesis and secretion cell-non-autonomously requiring neuron-glia interactions, which then activates neuronal BDNF-TrkB signaling to drive longer-term neuronal adaptations4–6 leading to improved mood. Our studies highlight temporal and cell type specific mechanisms promoting the onset of the antidepressant response, that we propose could offer novel avenues for mitigating delayed onset of antidepressant therapies.
Delineating Medical Education: Bibliometric Research Approach(es)
Authors: Maggio Lauren A. , Ninkov Anton , Frank Jason R. , Costello Joseph A. , Artino Anthony R. 
Published: July 2021

AbstractBackgroundThe field of medical education remains poorly delineated such that there is no broad consensus of the articles and journals that comprise “the field.” This lack of consensus has implications for conducting bibliometric studies and other research designs (e.g., systematic reviews); it also challenges the field to compare citation scores in the field and across others and for an individual to identify themselves as “a medical education researcher.” Other fields have utilized bibliometric field delineation, which is the assigning of articles or journals to a certain field in an effort to define that field.ProcessIn this Research Approach, three bibliometric field delineation approaches -- information retrieval, core journals, and journal co-citation -- are introduced. For each approach, the authors describe their attempt to apply it in the medical education context and identify related strengths and weaknesses. Based on co-citation, the authors propose the Medical Education Journal List 24 (MEJ-24), as a starting point for delineating medical education and invite the community to collaborate on improving and potentially expanding this list.PearlsAs a research approach, field delineation is complicated, and there is no clear best way to delineate the field of medical education. However, recent advances in information and computer science provide potentially more fruitful approaches to deal with the complexity of the field. When considering these emerging approaches, researchers should consider collaborating with bibliometricians.Bibliometric approaches rely on available metadata for articles and journals, which necessitates that researchers examine the metadata prior to analysis to understand its strengths and weaknesses, and to assess how this might affect their data interpretation. While using bibliometric approaches for field delineation is valuable, it is important to remember that these techniques are only as good as the research team’s interpretation of the data, which suggests that an expanded research approach is needed to better delineate medical education, an approach that includes active discussion within the medical education community.
Low dose rate γ-irradiation protects Drosophila melanogaster chromosomes from double strand breaks and telomere fusions by modulating the expression of the esi-RNA biogenesis factor Loquacious
Authors: Porrazzo A. , Cipressa F. , De Gregorio A. , De Pittà C. , Sales G. , Ciapponi L. , Morciano P. , Esposito G. , Tabocchini M.A. , Cenci G. 
Published: July 2021

AbstractIt is still continuously debated whether the low-dose/dose-rate (LDR) of ionizing radiation represents a hazard for humans. Model organisms, such as fruit flies, are considered valuable systems to reveal insights into this issue. We found that, in wild-type Drosophila melanogaster larval neuroblasts, the frequency of Chromosome Breaks (CBs), induced by acute γ-irradiation, is significantly reduced when flies are previously exposed to a protracted dose of 0.4Gy delivered at a dose rate of 2.5mGy/h. This indicates that this exposure, which is associated with an increased expression of DNA damage response proteins, induces a radioadaptive response (RAR) that protects Drosophila from extensive DNA damage. Interestingly, the same exposure reduces the frequency of telomere fusions (TFs) from Drosophila telomere capping mutants suggesting that the LDR can generally promote a protective response on chromatin sites that are recognized as DNA breaks. Deep RNA sequencing revealed that RAR is associated with a reduced expression of Loquacious D (Loqs-RD) gene that encodes a well-conserved dsRNA binding protein required for esiRNAs biogenesis. Remarkably, loss of Loqs mimics the LDR-mediated chromosome protection as it decreases the IR-induced CBs and TF frequency. Thus, our molecular characterization of RAR identifies Loqs as a key factor in the cellular response to LDR and unveils unprecedented epigenetic routes involved in radioresistance.
Transcriptomic Analysis of Human Sensory Neurons in Painful Diabetic Neuropathy Reveals Inflammation and Neuronal Loss
Authors: Hall Bradford E. , Macdonald Emma , Cassidy Margaret , Yun Sijung , Sapio Matthew R. , Ray Pradipta , Doty Megan , Nara Pranavi , Burton Michael D. , Shiers Stephanie , Ray-Chaudhury Abhik , Mannes Andrew J. , Price Theodore J. , Iadarola Michael J. , Kulkarni Ashok B. 
Published: July 2021

AbstractPathological sensations caused by peripheral painful neuropathy occurring in Type 2 diabetes mellitus (T2DM) are often described as ‘sharp’ and ‘burning’ and are commonly spontaneous in origin. Proposed etiologies implicate dysfunction of nociceptive sensory neurons in dorsal root ganglia (DRG) induced by generation of reactive oxygen species, microvascular defects, and ongoing axonal degeneration and regeneration. To investigate the molecular mechanisms contributing to diabetic pain, DRGs were acquired postmortem from patients who had been experiencing painful diabetic peripheral neuropathy (DPN) and subjected to transcriptome analyses to identify genes contributing to pathological processes and neuropathic pain. DPN occurs in distal extremities resulting in the characteristic “glove and stocking” pattern. Accordingly, the L4 and L5 DRGs, which contain the perikarya of primary afferent neurons innervating the foot, were analyzed from five DPN patients and compared with seven controls. Transcriptom e analyses identified 844 differentially expressed genes. We observed increases in levels of inflammation-associated genes from macrophages in DPN patients that may contribute to increased pain hypersensitivity and, conversely, there were frequent decreases in neuronally-related genes. The elevated inflammatory gene profile and the accompanying downregulation of multiple neuronal genes provide new insights into intraganglionic pathology and mechanisms causing neuropathic pain in DPN patients with T2DM.
Accelerated epigenetic aging and inflammatory/immunological profile (ipAGE) in patients with chronic kidney disease
Authors: Yusipov Igor , Kondakova Elena , Kalyakulina Alena , Krivonosov Mikhail , Lobanova Nadezhda , Bacalini Maria Giulia , Franceschi Claudio , Vedunova Maria , Ivanchenko Mikhail 
Published: July 2021

AbstractChronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). This failure can be related to a phenotype of accelerated aging. In this work we considered 76 subjects with end-stage renal disease (ESRD) and 83 healthy controls. We evaluated two measures that can be informative of the rate of aging, i.e. whole blood DNA methylation using the Illumina Infinium EPIC array and plasma levels of a selection of inflammatory/immunological proteins using Multiplex Immunoassays. We demonstrated accelerated aging in terms of the most common epigenetic age estimators in CKD patients. We developed a new predictor of age based on inflammatory/immunological profile (ipAGE) and confirmed age acceleration in CKD patients. Finally, we evaluated the relationship between epigenetic age predictors and ipAGE and further identified the inflammatory/immunological biomarkers differentially expressed between cases and controls. In summary, our data show an accelerated aging phenotype in CKD patients sustained by inflammatory processes.