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Low emittance tuning at the Cornell Electron Storage Ring (CESR) test accelerator depends on precision measurement of vertical dispersion and transverse coupling. The CESR beam position monitors (BPMs) consist of four button electrodes, instrumented with electronics that allow acquisition of turn-by-turn data. The response to the beam will vary among the four electrodes due to differences in electronic gain and/or misalignment. This variation in the response of the BPM electrodes will couple real horizontal offset to apparent vertical position, and introduce spurious measurements of coupling and vertical dispersion. To alleviate this systematic effect, a beam based technique to measure the relative response of the four electrodes has been developed. With typical CESR parameters, simulations show that turn-by-turn BPM data can be used to determine electrode gains to within ∼0.1%.

Measurement of the betatron phase in the vertical and horizontal planes as well as the transverse horizontal-vertical coupling is a standard procedure now used at the Cornell Electron/Positron Storage Ring. The measurement is made by shaking the beam and observing the phase of oscillation at detectors located around the ring. The measurements allow quadrupolar errors to be corrected.

MicroRNAs (miRNAs) have been implicated in human disorders, from cancers to infectious diseases. Targeting miRNAs or their target genes with small molecules offers opportunities to modulate dysregulated cellular processes linked to diseases. Yet, predicting small molecules associated with miRNAs remains challenging due to the small size of small molecule-miRNA datasets. Herein, we develop a generalized deep learning framework, sChemNET, for predicting small molecules affecting miRNA bioactivity based on chemical structure and sequence information. sChemNET overcomes the limitation of sparse chemical information by an objective function that allows the neural network to learn chemical space from a large body of chemical structures yet unknown to affect miRNAs. We experimentally validated small molecules predicted to act on miR-451 or its targets and tested their role in erythrocyte maturation during zebrafish embryogenesis. We also tested small molecules targeting the miR-181 network and other miRNAs using in-vitro and in-vivo experiments. We demonstrate that our machine-learning framework can predict bioactive small molecules targeting miRNAs or their targets in humans and other mammalian organisms., (© 2024. The Author(s).)

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing and transcriptomic analysis on 3D microvessel cell cultures exposed to simulated deep space radiation (0.5 Gy of Galactic Cosmic Radiation) with and without the antagonists to three microRNAs: miR-16-5p, miR-125b-5p, and let-7a-5p (i.e., antagomirs). Significant reduction of inflammation and DNA double strand breaks (DSBs) activity and rescue of mitochondria functions are observed after antagomir treatment. Using data from astronaut participants in the NASA Twin Study, Inspiration4, and JAXA missions, we reveal the genes and pathways implicated in the action of these antagomirs are altered in humans. Our findings indicate a countermeasure strategy that can potentially be utilized by astronauts in spaceflight missions to mitigate space radiation damage., (© 2024. The Author(s).)

Background: Low energy falls (LEF) in older adults constitute a relevant cause for emergency department (ED) visits, hospital admission and in-hospital mortality. Patient-reported outcome measures containing information about patients' medical, mental and social health problems might support disposition and therapy decisions. We investigated the value of a tablet-based (self-)assessment in predicting hospital admission and in-hospital mortality., Methods: Patients 65 years or older, consecutively presenting with LEF to our level I trauma center ED (from November 2020 to March 2021), were eligible for inclusion in this prospective observational study. The primary endpoint was hospital admission; secondary endpoints were in-hospital mortality and the use of the tablet for self-reported assessment. Multivariate logistic regression models were calculated to measure the association between clinical findings and endpoints., Results: Of 618 eligible patients, 201 patients were included. The median age was 82 years (62.7% women). The hospital admission rate was 45.3% (110/201), with an in-hospital mortality rate of 3.6% (4/110). Polypharmacy (odds ratio (OR): 8.48; 95% confidence interval (95%CI) 1.21-59.37, p = 0.03), lower emergency severity index (ESI) scores (OR: 0.33; 95%CI 0.17-0.64, p = 0.001) and increasing injury severity score (ISS) (OR: 1.54; 95%CI 1.32-1.79, p < 0.001) were associated with hospital admission. The Charlson comorbidity index (CCI) was significantly associated with in-hospital mortality (OR: 2.60; 95%CI: 1.17-5.81, p = 0.03). Increasing age (OR: 0.94; 95%CI: 0.89-0.99, p = 0.03) and frailty (OR: 0.71; 95%CI: 0.51-0.99, p = 0.04) were associated with the incapability of tablet use., Conclusions: The severity of fall-related injuries and the clinical acuity are easily accessible, relevant predictors for hospital admission. Tablet-based (self-)assessment may be feasible and acceptable during ED visits and might help facilitate comprehensive geriatric assessments during ED stay.

Introduction  The surgical management that achieves minimal morbidity and mortality for patients with glomus and non-glomus tumors involving the jugular foramen (JF) region requires a comprehensive understanding of the complex anatomy, anatomic variability, and pathological anatomy of this region. Objective  The aim of this study is to propose a rational guideline to expose and preserve the lower cranial nerves (CNs) in the lateral approach of the JF. Methods  The technique utilized is the gross and microdissection of 4 fixed cadaveric heads to revise the JF's surgical anatomy and high part of the carotid sheath compared with surgical cases to understand and preserve the integrity of lower CNs. The method involves radical mastoidectomy, microdissection of the JF, facial nerve, and high neck just below the carotid canal and the JF. The CNs IX, X, XI, and XII are microscopically dissected and kept in sight up to the JF. Results  This study realized well the surgical and applied anatomy of the lower CNs with relation to the facial nerve and JF. Conclusions  The JF anatomy is complicated, and the key to safely operate on it and preserving the lower CNs is to find the posterior belly of the digastric muscle, to skeletonize the facial nerve, to remove the mastoid tip preserving the stylomastoid foramen, to skeletonize the sigmoid sinus and posterior fossa dura not only anterior but also posteroinferior to reach and drill the jugular tubercle., Competing Interests: Conflict of interests The authors have no conflict of interests to declare., (Fundação Otorrinolaringologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

We analyzed RNA sequencing data from nasal swabs used for SARS-CoV-2 testing. 13% of 317 PCR-negative samples contained over 100 reads aligned to multiple regions of the SARS-CoV-2 genome. Differential gene expression analysis compares the host gene expression in potential false-negative (FN: PCR negative, sequencing positive) samples to subjects with multiple SARS-CoV-2 viral loads. The host transcriptional response in FN samples was distinct from true negative samples (PCR & sequencing negative) and similar to low viral load samples. Gene Ontology analysis shows viral load-dependent changes in gene expression are functionally distinct; 23 common pathways include responses to viral infections and associated immune responses. GO analysis reveals FN samples had a high overlap with high viral load samples. Deconvolution of RNA-seq data shows similar cell content across viral loads. Hence, transcriptome analysis of nasal swabs provides an additional level of identifying SARS-CoV-2 infection., Competing Interests: Dr. Mason is a cofounder for Aevum (acquired by Onegevity), Biotia, BridgeOmics, Onegevity (acquired by Thorne HealthTech), as well as a current advisor, shareholder, or compensated speaker for Acuamark Diagnostics, Allen and Company, ArcBio, BGI/MGI, Bumrungrad International Hospital, Carverr, Color Genomics, Cowen, DNA Genotek, EdenRoc, Enzymetrics, Element Bio, Foresite Capital, F!nd Genomics, Genialis, GenPro, Ginger Network, Google, Homo Deus, iCareDx, JP Morgan, Illumina, Infectious Economics, Meenta, Merck, MilliporeSigma, Mirimus, Morgan Stanley, Nano-Lit, Nanostring, New England Biolabs, Nooma, Pandemic Response Lab, Promega, Pendulum Health, Poppy Health, QIAGEN, Roche, Seed, Tecan, Tempus Labs, Testing for America, Thermo Fisher, Torus, Twist Biosciences, UBS, Ursa Bio, WorldQuant, and Zymo Research., (© 2022 The Authors.)

The World Health Organization recently defined hypertension and type 2 diabetes (T2D) as modifiable comorbidities leading to dementia and Alzheimer's disease. In the United States (US), hypertension and T2D are health disparities, with higher prevalence seen for Black and Hispanic minority groups compared to the majority White population. We hypothesized that elevated prevalence of hypertension and T2D risk factors in Black and Hispanic groups may be associated with dementia disparities. We interrogated this hypothesis using a cross-sectional analysis of participant data from the All of Us (AoU) Research Program, a large observational cohort study of US residents. The specific objectives of our study were: (1) to compare the prevalence of dementia, hypertension, and T2D in the AoU cohort to previously reported prevalence values for the US population, (2) to investigate the association of hypertension, T2D, and race/ethnicity with dementia, and (3) to investigate whether race/ethnicity modify the association of hypertension and T2D with dementia. AoU participants were recruited from 2018 to 2019 as part of the initial project cohort (R2019Q4R3). Participants aged 40-80 with electronic health records and demographic data (age, sex, race, and ethnicity) were included for analysis, yielding a final cohort of 125,637 individuals. AoU participants show similar prevalence of hypertension (32.1%) and T2D (13.9%) compared to the US population (32.0% and 10.5%, respectively); however, the prevalence of dementia for AoU participants (0.44%) is an order of magnitude lower than seen for the US population (5%). AoU participants with dementia show a higher prevalence of hypertension (81.6% vs. 31.9%) and T2D (45.9% vs. 11.4%) compared to non-dementia participants. Dominance analysis of a multivariable logistic regression model with dementia as the outcome shows that hypertension, age, and T2D have the strongest associations with dementia. Hispanic was the only race/ethnicity group that showed a significant association with dementia, and the association of sex with dementia was non-significant. The association of T2D with dementia is likely explained by concurrent hypertension, since > 90% of participants with T2D also had hypertension. Black race and Hispanic ethnicity interact with hypertension, but not T2D, to increase the odds of dementia. This study underscores the utility of the AoU participant cohort to study disease prevalence and risk factors. We do notice a lower participation of aged minorities and participants with dementia, revealing an opportunity for targeted engagement. Our results indicate that targeting hypertension should be a priority for risk factor modifications to reduce dementia incidence., (© 2022. The Author(s).)

In this study, we characterize biophysical changes in NMDA receptor function in response to brief non-injurious ischemic stress (ischemic preconditioning). Electrophysiological studies show NMDA receptor function is reduced following preconditioning in cultured rat cortical neurons. This functional change is not due to changes in the reversal potential of the receptor, but an increase in desensitization. We performed concentration-response analysis of NMDA-evoked currents, and demonstrate that preconditioned neurons show a reduced potency of NMDA to evoke currents, an increase in Mg 2+ sensitivity, but no change in glycine sensitivity. Antagonists studies show a reduced inhibition of GluN2B antagonists that have an allosteric mode of action (ifenprodil and R-25-6981), but competitive antagonists at the GluR2A and 2B receptor (NVP-AMM077 and conantokin-G) appear to have similar potency to block currents. Biochemical studies show a reduction in membrane surface GluN2B subunits, and an increased co-immunoprecipitation of GluN2A with GluN2B subunits, suggestive of tri-heteromeric receptor formation. Finally, we show that blocking actin remodeling with jasplakinolide, a mechanism of rapid ischemic tolerance, prevents NMDA receptor functional changes and co-immunoprecipitation of GluN2A and 2B subunits. Together, this study shows that alterations in NMDA receptor function following preconditioning ischemia are associated with neuroprotection in rapid ischemic tolerance.

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on the function of viral components versus the cellular defenses. Non-coding RNAs (ncRNAs) are important cellular modulators, either promoting or preventing the progression of viral infections. Among these ncRNAs, the long non-coding RNA (lncRNA) family is especially relevant due to their intrinsic functional properties and ubiquitous biological roles. Specific lncRNAs have been recently characterized as modulators of the cellular response during infection of human host cells by single stranded RNA viruses. However, the role of host lncRNAs in the infection by human RNA coronaviruses such as SARS-CoV-2 remains uncharacterized. Methods: In the present work, we have performed a transcriptomic study of a cohort of patients with different SARS-CoV-2 viral load and analyzed the involvement of lncRNAs in supporting regulatory networks based on their interaction with RNA-binding proteins (RBPs). Results: Our results revealed the existence of a SARS-CoV-2 infection-dependent pattern of transcriptional up-regulation in which specific lncRNAs are an integral component. To determine the role of these lncRNAs, we performed a functional correlation analysis complemented with the study of the validated interactions between lncRNAs and RBPs. This combination of in silico functional association studies and experimental evidence allowed us to identify a lncRNA signature composed of six elements - NRIR, BISPR, MIR155HG, FMR1-IT1, USP30-AS1, and U62317.2 - associated with the regulation of SARS-CoV-2 infection. Conclusions: We propose a competition mechanism between the viral RNA genome and the regulatory lncRNAs in the sequestering of specific RBPs that modulates the interferon response and the regulation of RNA surveillance by nonsense-mediated decay (NMD)., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Whole transcriptome RNA-sequencing was performed to quantify RNA expression changes in whole blood samples collected from steady state sickle cell anemia (SCA) and control subjects. Pediatric SCA and control subjects were recruited from Atlanta (GA)-based hospital(s) systems and consented for RNA sequencing. RNA sequencing was performed on an Ion Torrent S5 sequencer, using the Ion Total RNA-seq v2 protocol. Data were aligned to the hg19 reference genome and analyzed in the Partek Genomics studio package (v7.0). 223 genes were differentially expressed between SCA and controls (± 1.5 fold change FDR p < 0.001) and 441 genes show differential transcript expression (± 1.5 fold FDR p < 0.001). Differentially expressed RNA are enriched for hemoglobin associated genes and ubiquitin-proteasome pathway genes. Further analysis shows higher gamma globin gene expression in SCA (33-fold HBG1 and 49-fold HBG2, both FDR p < 0.05), which did not correlate with hemoglobin F protein levels. eQTL analysis identified SNPs in novel non-coding RNA RYR2 gene as having a potential regulatory role in HBG1 and HBG2 expression levels. Gene expression correlation identified JHDM1D-AS1(KDM7A-DT), a non-coding RNA associated with angiogenesis, enhanced GATA1 and decreased JAK-STAT signaling to correlate with HBG1 and HBG2 mRNA levels. These data suggest novel regulatory mechanisms for fetal hemoglobin regulation, which may offer innovative therapeutic approaches for SCA., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Gee, Pearson, Buchanan-Perry, Simon, Archer and Meller.)

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provide an exciting avenue toward antiviral therapeutics. From patient transcriptomic data, we determined that a circulating miRNA, miR-2392, is directly involved with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) machinery during host infection. Specifically, we show that miR-2392 is key in driving downstream suppression of mitochondrial gene expression, increasing inflammation, glycolysis, and hypoxia, as well as promoting many symptoms associated with coronavirus disease 2019 (COVID-19) infection. We demonstrate that miR-2392 is present in the blood and urine of patients positive for COVID-19 but is not present in patients negative for COVID-19. These findings indicate the potential for developing a minimally invasive COVID-19 detection method. Lastly, using in vitro human and in vivo hamster models, we design a miRNA-based antiviral therapeutic that targets miR-2392, significantly reduces SARS-CoV-2 viability in hamsters, and may potentially inhibit a COVID-19 disease state in humans., Competing Interests: Declaration of interests A.C., P.N., S.V.C., and A.B. have a provisional patent based on the antiviral discovery and design. A.C., P.N., and S.S. are part of the company (Sachi Bioworks Inc.) that has filed a patent on the Nanoligomer technology., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

With the development of transcriptomic technologies, we are able to quantify precise changes in gene expression profiles from astronauts and other organisms exposed to spaceflight. Members of NASA GeneLab and GeneLab-associated analysis working groups (AWGs) have developed a consensus pipeline for analyzing short-read RNA-sequencing data from spaceflight-associated experiments. The pipeline includes quality control, read trimming, mapping, and gene quantification steps, culminating in the detection of differentially expressed genes. This data analysis pipeline and the results of its execution using data submitted to GeneLab are now all publicly available through the GeneLab database. We present here the full details and rationale for the construction of this pipeline in order to promote transparency, reproducibility, and reusability of pipeline data; to provide a template for data processing of future spaceflight-relevant datasets; and to encourage cross-analysis of data from other databases with the data available in GeneLab., Competing Interests: The authors declare no competing interests.

Spaceflight is known to impose changes on human physiology with unknown molecular etiologies. To reveal these causes, we used a multi-omics, systems biology analytical approach using biomedical profiles from fifty-nine astronauts and data from NASA's GeneLab derived from hundreds of samples flown in space to determine transcriptomic, proteomic, metabolomic, and epigenetic responses to spaceflight. Overall pathway analyses on the multi-omics datasets showed significant enrichment for mitochondrial processes, as well as innate immunity, chronic inflammation, cell cycle, circadian rhythm, and olfactory functions. Importantly, NASA's Twin Study provided a platform to confirm several of our principal findings. Evidence of altered mitochondrial function and DNA damage was also found in the urine and blood metabolic data compiled from the astronaut cohort and NASA Twin Study data, indicating mitochondrial stress as a consistent phenotype of spaceflight., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed involvement in immune system dysregulation. Furthermore, a large astronaut cohort showed elevated inflammation during low-Earth orbit missions, thereby supporting our simulated ground experiments in mice. Herein, circulating immune biomarkers are defined by distinct deep space irradiation types coupled to simulated microgravity and could be targets for future space health initiatives., Competing Interests: All authors declare no competing interests., (© 2020 The Author(s).)

Background: In the setting of complete distal biceps tendon rupture, surgical repair has become the standard of care to restore optimal elbow function, but the optimal approach and method of tendon fixation are still subjects of debate and have remained controversial for more than half a century., Purpose: To evaluate patient-reported long-term outcomes after distal biceps tendon repair using a modified double-incision technique., Study Design: Case series; Level of evidence, 4., Methods: We reviewed primary distal biceps tendon repairs after isolated tendon rupture using the modified muscle-splitting double-incision approach and transosseous suture fixation technique described by Morrey et al (1985), which had been performed at our level 1 trauma center between January 2000 and December 2013. Outcome measures included the subjective elbow value (SEV), the Oxford Elbow Score (OES) with its 3 domains (function, pain, and social-psychological), a self-performed hook test, and the 3-level version of the EuroQoL 5-dimensional instrument (EQ-5D-3L) as a measure of health status. Levels of overall satisfaction were determined by asking whether the patient would consent to the operation again. In addition, patients were asked to report any complications., Results: A total of 30 patients met the inclusion criteria, and 25 patients were available for the survey. Mean age at the time of rupture was 47 years. All patients were male. Mean follow-up was 120 months (range, 57-207 months). The follow-up rate was 83.34%. The following outcome results were obtained: SEV, 88.16% ± 25.18%; OES, 43.80 ± 10.56 out of 48 points; OES Pain, 92.50% ± 23.03%; OES Function, 92.25% ± 22.19%; OES Social-Psychological, 89% ± 23.68%; EQ-5D-3L, 0.93 ± 0.21. All patients described a negative hook test. Patient-reported complications included painless limitation in forearm rotation in 8% of patients (n = 2); reduced flexion and forearm rotation strength with and without pain in 8% (n = 2) and 4% (n = 1), respectively; synostosis after 1 year requiring revision surgery in 4% (n = 1); and transient wrist drop in 4% (n = 1). The overall complication rate was 28% (7/25), and 96% (n = 24) would consent to the operation again., Conclusion: Despite the cited approach-related morbidity, we report an excellent patient-reported long-term outcome for the double-incision distal biceps repair technique., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Mitochondrial fission catalyzed by dynamin-related protein 1 (Drp1) is necessary for mitochondrial biogenesis and maintenance of healthy mitochondria. However, excessive fission has been associated with multiple neurodegenerative disorders, and we recently reported that mice with smaller mitochondria are sensitized to ischemic stroke injury. Although pharmacological Drp1 inhibition has been put forward as neuroprotective, the specificity and mechanism of the inhibitor used is controversial. Here, we provide genetic evidence that Drp1 inhibition is neuroprotective. Drp1 is activated by dephosphorylation of an inhibitory phosphorylation site, Ser637. We identify Bβ2, a mitochondria-localized protein phosphatase 2A (PP2A) regulatory subunit, as a neuron-specific Drp1 activator in vivo Bβ2 KO mice of both sexes display elongated mitochondria in neurons and are protected from cerebral ischemic injury. Functionally, deletion of Bβ2 and maintained Drp1 Ser637 phosphorylation improved mitochondrial respiratory capacity, Ca 2+ homeostasis, and attenuated superoxide production in response to ischemia and excitotoxicity in vitro and ex vivo Last, deletion of Bβ2 rescued excessive stroke damage associated with dephosphorylation of Drp1 S637 and mitochondrial fission. These results indicate that the state of mitochondrial connectivity and PP2A/Bβ2-mediated dephosphorylation of Drp1 play a critical role in determining the severity of cerebral ischemic injury. Therefore, Bβ2 may represent a target for prophylactic neuroprotective therapy in populations at high risk of stroke. SIGNIFICANCE STATEMENT With recent advances in clinical practice including mechanical thrombectomy up to 24 h after the ischemic event, there is resurgent interest in neuroprotective stroke therapies. In this study, we demonstrate reduced stroke damage in the brain of mice lacking the Bβ2 regulatory subunit of protein phosphatase 2A, which we have shown previously acts as a positive regulator of the mitochondrial fission enzyme dynamin-related protein 1 (Drp1). Importantly, we provide evidence that deletion of Bβ2 can rescue excessive ischemic damage in mice lacking the mitochondrial PKA scaffold AKAP1, apparently via opposing effects on Drp1 S637 phosphorylation. These results highlight reversible phosphorylation in bidirectional regulation of Drp1 activity and identify Bβ2 as a potential pharmacological target to protect the brain from stroke injury., (Copyright © 2020 the authors.)

Background: Ionizing radiation from galactic cosmic rays (GCR) is one of the major risk factors that will impact the health of astronauts on extended missions outside the protective effects of the Earth's magnetic field. The NASA GeneLab project has detailed information on radiation exposure using animal models with curated dosimetry information for spaceflight experiments. Methods: We analyzed multiple GeneLab omics datasets associated with both ground-based and spaceflight radiation studies that included in vivo and in vitro approaches. A range of ions from protons to iron particles with doses from 0.1 to 1.0 Gy for ground studies, as well as samples flown in low Earth orbit (LEO) with total doses of 1.0 mGy to 30 mGy, were utilized. Results: From this analysis, we were able to identify distinct biological signatures associating specific ions with specific biological responses due to radiation exposure in space. For example, we discovered changes in mitochondrial function, ribosomal assembly, and immune pathways as a function of dose. Conclusions: We provided a summary of how the GeneLab's rich database of omics experiments with animal models can be used to generate novel hypotheses to better understand human health risks from GCR exposures., Competing Interests: The authors declare no conflict of interest.

The tumor immune microenvironment (TIME) consists of multiple cell types that contribute to the heterogeneity and complexity of prostate cancer (PCa). In this study, we sought to understand the gene-expression signature of patients with primary prostate tumors by investigating the co-expression profiles of patient samples and their corresponding clinical outcomes, in particular "disease-free months" and "disease reoccurrence". We tested the hypothesis that the CXCL13-CXCR5 axis is co-expressed with factors supporting TIME and PCa progression. Gene expression counts, with clinical attributes from PCa patients, were acquired from TCGA. Profiles of PCa patients were used to identify key drivers that influence or regulate CXCL13-CXCR5 signaling. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expression patterns among CXCL13-CXCR5, associated genes, and key genetic drivers within the CXCL13-CXCR5 signaling pathway. The processing of downloaded data files began with quality checks using NOISeq, followed by WGCNA. Our results confirmed the quality of the TCGA transcriptome data, identified 12 co-expression networks, and demonstrated that CXCL13, CXCR5 and associated genes are members of signaling networks (modules) associated with G protein coupled receptor (GPCR) responsiveness, invasion/migration, immune checkpoint, and innate immunity. We also identified top canonical pathways and upstream regulators associated with CXCL13-CXCR5 expression and function.

Mild traumatic brain injury (mTBI) is a complex, neurophysiological condition that can have detrimental outcomes. Yet, to date, no objective method of diagnosis exists. Physical damage to the blood-brain-barrier and normal waste clearance via the lymphatic system may enable the detection of biomarkers of mTBI in peripheral circulation. Here we evaluate the accuracy of whole transcriptome analysis of blood to predict the clinical diagnosis of post-concussion syndrome (PCS) in a military cohort. Sixty patients with clinically diagnosed chronic concussion and controls (no history of concussion) were recruited (retrospective study design). Male patients (46) were split into a training set comprised of 20 long-term concussed (> 6 months and symptomatic) and 12 controls (no documented history of concussion). Models were validated in a testing set (control = 9, concussed = 5). RNA&#95;Seq libraries were prepared from whole blood samples for sequencing using a SOLiD5500XL sequencer and aligned to hg19 reference genome. Patterns of differential exon expression were used for diagnostic modeling using support vector machine classification, and then validated in a second patient cohort. The accuracy of RNA profiles to predict the clinical diagnosis of post-concussion syndrome patients from controls was 86% (sensitivity 80%; specificity 89%). In addition, RNA profiles reveal duration of concussion. This pilot study shows the potential utility of whole transcriptome analysis to establish the clinical diagnosis of chronic concussion syndrome.

Background: Arthroscopic debridement represents a salvage procedure for irreparable rotator cuff tears. It is important to accurately diagnose the patient for irreparable rotator cuff tears. The diagnosis and the therapeutic options must be explained to the patient. It is mandatory that the patient understands the primary goal of the arthroscopic debridement being reduction of pain, not improving strength or function., Methods: The procedure consists of 7 distinct steps to debride the soft tissues and alleviate pain., Results: Even though there is a lack of evidence that this procedure is superior to other therapeutic options, it has shown good results in patients with the main complaint of pain., Conclusion: The results reported in some studies should, however, be interpreted with caution, taking into consideration the substantial structural damage in irreparable defects.

Objective: Molecular diagnostic medicine holds much promise to change point of care treatment. An area where additional diagnostic tools are needed is in acute stroke care, to assist in diagnosis and prognosis. Previous studies using microarray-based gene expression analysis of peripheral blood following stroke suggests this approach may be effective. Next-generation sequencing (NGS) approaches have expanded genomic analysis and are not limited to previously identified genes on a microarray chip. Here, we report on a pilot NGS study to identify gene expression and exon expression patterns for the prediction of stroke diagnosis and prognosis., Methods: We recruited 28 stroke patients and 28 age- and sex-matched hypertensive controls. RNA was extracted from 3 mL blood samples, and RNA-Seq libraries were assembled and sequenced., Results: Bioinformatical analysis of the aligned RNA data reveal exonic (30%), intronic (36%), and novel RNA components (not currently annotated: 33%). We focused our study on patients with confirmed middle cerebral artery occlusion ischemic stroke (n = 17). On the basis of our observation of differential splicing of gene transcripts, we used all exonic RNA expression rather than gene expression (combined exons) to build prediction models using support vector machine algorithms. Based on model building, these models have a high predicted accuracy rate >90% (spec. 88% sen. 92%). We further stratified outcome based on the improvement in NIHss scores at discharge; based on model building we observe a predicted 100% accuracy rate., Interpretation: NGS-based exon expression analysis approaches have a high potential for patient diagnosis and outcome prediction, with clear utility to aid in clinical patient care.