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Coronavirus Disease 2019 (COVID-19) is an infectious respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease, first identified in the Chinese city of Wuhan in November 2019, has since spread worldwide, is the latest human pandemic and has officially infected over 800 million people and has caused nearly seven million deaths to date. Although SARS-CoV-2 belongs to the large family of coronaviruses, it has some unique biological characteristics in its interplay with the human host. Therefore, this narrative review aims to provide an up-to-date overview of the structure of the virus, incubation and shedding in the human host, infectivity and biological evolution over time, as well as the main mechanisms for invading human host cells and replicating within. We also proffer that ongoing epidemiological surveillance of newly emerged variants must always be accompanied by biological studies aimed at deciphering new advantageous traits that may contribute to increasing virulence and pathogenicity, such that the most appropriate strategies for establishing a (relatively) safe coexistence with the human host can be implemented.

Learning curves are a core analytical method employed by cost analysts to estimate weapon system production costs. This study examines United States Air Force aircraft programs and compares the traditional (e.g., Unit Theory) learning curve model to a production rate learning curve model. While there are some previous studies examining production rate models, one novelty of this research is the size of the dataset, which comprises the largest military examination to date. The results suggest the production rate model outperforms the traditional learning curve model. Additionally, the analysis identifies the post-Initial Operational Capability (IOC) time period as the preferred milestone in the life cycle to employ the production rate model.

The purpose of this proof-of-concept study was to investigate whether a commercially available urine dipstick may provide potentially useful information for screening plasma glucose and bilirubin in human plasma samples.

Purpose – The purpose of this study was to create an air movement operations planning model to rapidly generate air mission request (AMR) assignment and routing courses of action (COA) in order to minimize unsupported AMRs, aircraft utilization and routing cost. Design/methodology/approach – In this paper, the US Army Aviation air movement operations planning problem is modeled as a mixed integer linear program (MILP) as an extension of the dial-a-ride problem (DARP). The paper also introduces a heuristic as an extension of a single-vehicle DARP demand insertion algorithm to generate feasible solutions in a tactically useful time period. Findings – The MILP model generates optimal solutions for small problems (low numbers of AMRs and small helicopter fleets). The heuristic generates near-optimal feasible solutions for problems of various sizes (up to 100 AMRs and 10 helicopter team fleet size) in near real time. Research limitations/implications – Due to the inability of the MILP to produce optimal solutions for mid- and large-sized problems, this research is limited in commenting on the heuristic solution quality beyond the numerical experimentation. Additionally, the authors make several simplifying assumptions to generalize the average performance and capabilities of aircraft throughout a flight. Originality/value – This research is the first to solve the US Army Aviation air movement operations planning problem via a single formulation that incorporates multiple refuel nodes, minimization of unsupported demand by priority level, demand time windows, aircraft team utilization penalties, aircraft team time windows and maximum duration and passenger ride time limits.

Abstract Waist-to-hip circumference ratio (WHR) is now recognized as among the strongest shape biometrics linked with health outcomes, although use of this phenotypic marker remains limited due to the inaccuracies in and inconvenient nature of flexible tape measurements when made in clinical and home settings. Here we report that accurate and reliable WHR estimation in adults is possible with a smartphone application based on novel computer vision algorithms. The developed application runs a convolutional neural network model referred to as MeasureNet that predicts a person’s body circumferences and WHR using front, side, and back color images. MeasureNet bridges the gap between measurements conducted by trained professionals in clinical environments, which can be inconvenient, and self-measurements performed by users at home, which can be unreliable. MeasureNet’s accuracy and reliability is evaluated using 1200 participants, measured by a trained staff member. The developed smartphone application, which is a part of Amazon Halo, is a major advance in digital anthropometry, filling a long-existing gap in convenient, accurate WHR measurement capabilities.

IntroductionLow back pain is the most common type of chronic pain. We examined pain-related behaviors across 18 weeks in rats that received injury to one or two lumbar intervertebral discs (IVD) to determine if multi-level disc injuries enhance/prolong pain.MethodsTwenty-three Sprague-Dawley adult female rats were used: 8 received disc puncture (DP) of one lumbar IVD (L5/6, DP-1); 8 received DP of two lumbar IVDs (L4/5 & L5/6, DP-2); 8 underwent sham surgery.ResultsDP-2 rats showed local (low back) sensitivity to pressure at 6- and 12-weeks post-injury, and remote sensitivity to pressure (upper thighs) at 12- and 18-weeks and touch (hind paws) at 6, 12 and 18-weeks. DP-1 rats showed local and remote pressure sensitivity at 12-weeks only (and no tactile sensitivity), relative to Sham DP rats. Both DP groups showed reduced distance traveled during gait testing over multiple weeks, compared to pre-injury; only DP-2 rats showed reduced distance relative to Sham DP rats at 12-weeks. DP-2 rats displayed reduced positive interactions with a novel adult female rat at 3-weeks and hesitation and freezing during gait assays from 6-weeks onwards. At study end (18-weeks), radiological and histological analyses revealed reduced disc height and degeneration of punctured IVDs. Serum BDNF and TNFα levels were higher at 18-weeks in DP-2 rats, relative to Sham DP rats, and levels correlated positively with remote sensitivity in hind paws (tactile) and thighs (pressure).DiscussionThus, multi-level disc injuries resulted in earlier, prolonged and greater discomfort locally and remotely, than single-level disc injury. BDNF and TNFα may have contributing roles.

BackgroundDigital health and telemedicine are potentially important strategies to decrease health care’s environmental impact and contribution to climate change by reducing transportation-related air pollution and greenhouse gas emissions. However, we currently lack robust national estimates of emissions savings attributable to telemedicine. ObjectiveThis study aimed to (1) determine the travel distance between participants in US telemedicine sessions and (2) estimate the net reduction in carbon dioxide (CO2) emissions attributable to telemedicine in the United States, based on national observational data describing the geographical characteristics of telemedicine session participants. MethodsWe conducted a retrospective observational study of telemedicine sessions in the United States between January 1, 2022, and February 21, 2023, on the doxy.me platform. Using Google Distance Matrix, we determined the median travel distance between participating providers and patients for a proportional sample of sessions. Further, based on the best available public data, we estimated the total annual emissions costs and savings attributable to telemedicine in the United States. ResultsThe median round trip travel distance between patients and providers was 49 (IQR 21-145) miles. The median CO2 emissions savings per telemedicine session was 20 (IQR 8-59) kg CO2). Accounting for the energy costs of telemedicine and US transportation patterns, among other factors, we estimate that the use of telemedicine in the United States during the years 2021-2022 resulted in approximate annual CO2 emissions savings of 1,443,800 metric tons. ConclusionsThese estimates of travel distance and telemedicine-associated CO2 emissions costs and savings, based on national data, indicate that telemedicine may be an important strategy in reducing the health care sector’s carbon footprint.

Background:. Due to variations in perforator vasculature, deep inferior epigastric artery perforator (DIEP) flap preoperative imaging can minimize operative time required to locate the most suitable perforators. Dedicated computed tomography angiography (CTA) has been the gold standard; however, many patients have already undergone a staging computed tomography (CT) per oncologic workup. The benefits from CTA may also be realized with a staging CT or CT with IV contrast. Methods:. Ten patients who underwent DIEP flap reconstruction with staging CT and CTA within 3 years of one another were included in this study. Reviewers evaluated axial views of both imaging modalities separately to identify each visible perforator in reference to the pubic symphysis from the xiphoid to the pubic symphysis. An intraclass correlation coefficient (ICC) was used to determine agreement in location of perforators between the two imaging studies. Statistical analysis was performed using an ICC and Wilcoxon signed rank-tests. Results:. The identified perforators within the patient cohort had an excellent correlation between their location on CT and CTA based upon ICC. The mean number of perforators identified in the CT group was 15.3 (SD 4.9) and in the CTA group was 18.8 (SD 6.4), which was not statistically different (P = 0.247). Conclusions:. CT has similar efficacy in identifying number of perforators and perforator location to dedicated CTA for preoperative planning in DIEP flaps. This has the potential for decreased patient contrast and ionizing radiation exposure as well as improved patient and healthcare resource utilization.

The Integrator is a multi-subunit protein complex that catalyzes the maturation of snRNA transcripts via 3' cleavage, a step required for snRNA incorporation with snRNP for spliceosome biogenesis. Here we developed a GFP based in vivo snRNA misprocessing reporter as a readout of Integrator function and performed a genome-wide RNAi screen for Integrator regulators. We found that loss of the Argonaute encoding csr-1 gene resulted in widespread 3' misprocessing of snRNA transcripts that is accompanied by a significant increase in alternative splicing. Loss of the csr-1 gene down-regulates the germline expression of Integrator subunits 4 and 6 and is accompanied by a reduced protein translation efficiency of multiple Integrator catalytic and non-catalytic subunits. Through isoform and motif mutant analysis, we determined that CSR-1's effect on snRNA processing is dependent on its catalytic slicer activity but does not involve the CSR-1a isoform. Moreover, mRNA-sequencing revealed high similarity in the transcriptome profile between csr-1 and Integrator subunit knockdown via RNAi. Together, our findings reveal CSR-1 as a new regulator of the Integrator complex and implicate a novel role of this Argonaute protein in snRNA 3' processing.

Objectives/hypothesisThis study utilizes a large population national database to comprehensively analyze prognosticators and overall survival (OS) outcomes of varying treatment modalities in a large cohort of sinonasal diffuse large B-cell lymphoma (SN-DLBCL) patients.Study designRetrospective database study.MethodsThe National Cancer Database was queried for all SN-DLBCL cases diagnosed from 2004 to 2015. Kaplan-Meier log-rank test determined differences in OS based on clinical covariates. Cox proportional-hazards analysis was used to determine clinical and sociodemographic covariates predictive of mortality.ResultsA total of 2,073 SN-DLBCL patients were included, consisting of 48% female with a mean age of 66.0 ± 16.2 years. Overall, 82% of patients were Caucasian, 74% had early-stage disease, and 49% had primary tumors in the paranasal sinuses. Early-stage patients were more likely to receive multi-agent chemoradiotherapy compared to multi-agent chemotherapy alone (P

BackgroundNo study to date has analyzed the progression of sinonasal symptoms over time in COVID-19 patients. The purpose of this study is to analyze the progression of sinonasal symptoms and risk factors for olfactory dysfunction in the mild severity COVID-19 patient.MethodsAn internet survey was used to assess sinonasal symptoms in patients with COVID-19. Changes in rhinologic domain and symptom-specific Sinonasal Outcome Test (SNOT-22) scores were compared at five time points: two weeks before diagnosis, at diagnosis, two weeks after diagnosis, four weeks after diagnosis, and six months after diagnosis.Results521 responses were collected. Rhinologic domain SNOT-22 scores increased significantly (p  0.999). Taste-specific SNOT-22 scores also peaked at diagnosis (2.06, p  0.999). There were no significant differences in sense of smell or taste between 1-month and 6-month timepoints.ConclusionSinonasal symptoms, particularly loss of smell and taste, may be important presenting symptoms in the mild severity COVID-19 patient. Our findings support incorporating these symptoms into screening protocols.Level of evidence4.

ObjectiveTo examine neurotologists' 2013 to 2016 Medicare Part-D data and evaluate commonly prescribed medications, longitudinal changes in prescribing patterns, presumed associated pathologies, and cost distribution across United States.MethodsComprehensive prescription data of Part-D-participating neurotologists was quiered from the 2013 to 2016 Medicare Part-D database. Outcome variables consisted of the 25 most commonly prescribed + refilled medications, cost distribution per medication, presumed associated pathologies, and standardized prescription cost across United States.ResultsOf the 594 available U.S. neurotologists, 336 (57%) were found in the Medicare Part-D database. In 2016, total prescription costs were $4 483 268 with an averaged $13 343 ± $18 698 per neurotologist. The three most frequently filled drugs were fluticasone propionate, ciprofloxacin, and triamterene-hydrochlorothiazide. From 2013 to 2016, the greatest change in prescription pattern was observed with azelastine (+188%), montelukast sodium (+104%), mupirocin (+63%), and mometasone (-91%), whereas the greatest change in relative drug cost distribution was seen in ofloxacin, (+695.7%) neomycin-polymyxin-hydrocortisone (+262.1%), and mometasone (-83%). Triamterene-hydrochlorothiazide, prednisone, montelukast, amoxicillin-clavulanate, azelastine, spironolactone, and mupirocin had statistically significant increases in average number of prescriptions per physician, whereas ofloxacin and mometasone had significant decreases. Medications presumably treating Eustachian tube dysfunction, Meniere's disease, and vestibular migraine had the greatest percent changes across years. Cost distribution of four drugs increased upwards of 100%. Geographic analysis demonstrated that Southern and Midwest regions had higher standardized prescription costs.ConclusionsThis study is the first to analyze neurotologists' trends in prescribing patterns, regional prescription cost distributions, and commonly treated pathologies. This can lead to better standardization of prescribing patterns and cost in the future.

BackgroundThis study evaluates the influence of facility case-volume on nasopharyngeal carcinoma (NPC) treatments and overall survival (OS).MethodsThe 2004-2015 National Cancer Database was queried for patients with NPC receiving definitive treatment.ResultsA total of 8260 patients (5-year OS: 63.4%) were included. The 1114 unique facilities were categorized into 854 low-volume (treating 1-8 patients), 200 intermediate-volume (treating 9-23 patients), and 60 high-volume (treating 24-187 patients) facilities. Kaplan-Meier log-rank analysis demonstrated significantly improved OS with high-volume facilities (p

The objective of this study is to evaluate the impact of preoperative frailty on short-term outcomes following intradural resection of skull base lesions. The 2005-2017 ACS-NSQIP database was queried for 30-day post-operative outcomes of patients undergoing intradural resection of the skull base, extracted by CPT codes 61601, 61606, 61608, and 61616. Five-item modified frailty index (mFI) was calculated based on the history of diabetes mellitus, chronic obstructive pulmonary disease, congestive heart failure, chronic hypertension, and functional status. A total of 701 patients (58.8% female, 72.0% white) were included with a mean age of 51.8 ± 14.7 years. Compared to patients with mFI = 0 (n = 403), patients with mFI ≥ 1 (n = 298) were more likely to have higher rates of reoperation (13.4% vs. 8.7%, p = 0.045), medical complications (20.5% vs. 9.2%, p

Non-genetic mechanisms have recently emerged as important drivers of cancer therapy failure1, where some cancer cells can enter a reversible drug-tolerant persister state in response to treatment2. Although most cancer persisters remain arrested in the presence of the drug, a rare subset can re-enter the cell cycle under constitutive drug treatment. Little is known about the non-genetic mechanisms that enable cancer persisters to maintain proliferative capacity in the presence of drugs. To study this rare, transiently resistant, proliferative persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell's clonal origin and proliferative and transcriptional states. Here we show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Upregulation of antioxidant gene programs and a metabolic shift to fatty acid oxidation are associated with persister proliferative capacity across multiple cancer types. Impeding oxidative stress or metabolic reprogramming alters the fraction of cycling persisters. In human tumours, programs associated with cycling persisters are induced in minimal residual disease in response to multiple targeted therapies. The Watermelon system enabled the identification of rare persister lineages that are preferentially poised to proliferate under drug pressure, thus exposing new vulnerabilities that can be targeted to delay or even prevent disease recurrence.

ObjectiveTo review overall survival (OS), recurrence patterns, and prognostic factors of de novo sinonasal squamous cell carcinoma (DN-SCC).Data sourcesPubMed, Scopus, OVID Medline, and Cochrane databases from 2006 to December 23, 2020.Review methodsThe study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Articles were required to report either recurrence patterns or survival outcomes of adults with DN-SCC. Case reports, books, reviews, meta-analyses, and database studies were all excluded.ResultsForty-one studies reported on survival or recurrence outcomes. The aggregate 5-year OS was 54.5% (range, 18%-75%) from 35 studies (n = 1903). Patients undergoing open surgery were more likely to receive radiation therapy and present at an advanced stage compared to those receiving endoscopic surgery (all P < .001). Advanced T stage, presence of cervical nodal metastases, maxillary sinus primary site, and negative human papillomavirus (HPV) status were all correlated with significantly worse 5-year OS. Direct meta-analysis of 8 studies demonstrated patients with surgery were more likely to be alive at 5 years compared to those who did not receive surgery (odds ratio, 2.26; 95% CI, 1.48-3.47; P < .001). Recurrence was reported in 628 of 1471 patients from 26 studies (42.7%) with an aggregate 5-year locoregional control rate of 67.1% (range, 50.4%-93.3%).ConclusionThis systematic review and meta-analysis suggests that the 5-year OS rate for DN-SCC may approach 54.5% and recurrence rate approaches 42.7%. In addition, various tumor characteristics including advanced T stage, positive nodal status, maxillary sinus origin, and negative HPV status are all associated with decreased survival.