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BackgroundOlder adults with type 2 diabetes mellitus (T2DM) or prediabetes are at increased risk of adverse changes in body composition, physical function, and aging-related biomarkers compared to those with normal glucose tolerance. Semaglutide is a glucagon-like peptide 1 receptor agonist that has been approved for T2DM and chronic weight management. Although semaglutide is effective for weight loss and T2DM management, its effects on lean body mass, physical function, and biomarkers of aging are understudied in older adults. ObjectiveThis study aims to compare the effects of lifestyle counseling with and that without semaglutide on body composition, physical function, and biomarkers of aging in older adults. MethodsThis is an open-label randomized controlled trial. A total of 20 adults (aged 65 years and older) with elevated BMI (27-40 kg/m2) and prediabetes or well-controlled T2DM (hemoglobin A1c 5.7%-7.5%) are recruited, stratified by sex, and randomized 1:1 to one of 2 groups (semaglutide plus lifestyle counseling vs lifestyle counseling alone) and followed up for 5 months. Those in the semaglutide group are titrated to 1 mg weekly, as tolerated, for 12 weeks. Lifestyle counseling is given by registered dietitians and based on the Diabetes Prevention Program Lifestyle Change Program. Our primary outcomes include changes in lean mass, physical function, and biomarkers of aging. Body composition is measured by dual-energy x-ray absorptiometry and includes total fat mass and lean mass. Physical function is measured by 6-minute walk distance, grip strength, and short physical performance battery. Biomarkers of aging are measured in blood, skeletal muscle, and abdominal adipose tissue to include C-reactive protein, interleukin-6, tumor necrosis factors α, and β galactosidase staining. ResultsThe study was funded in December 2021 with a projected data collection period from spring 2023 through summer 2024. ConclusionsDespite the elevated risk of adverse changes in body composition, physical function, and biomarkers of aging among older adults with glucose intolerance and elevated adiposity, the benefits and risks of commonly prescribed antihyperglycemic or weight loss medications such as semaglutide are understudied. This study aims to fill this knowledge gap to inform clinicians about the potential for additional clinically meaningful, nonglycemic effects of semaglutide. Trial RegistrationClinicalTrials.gov NCT05786521; https://clinicaltrials.gov/study/NCT05786521 International Registered Report Identifier (IRRID)DERR1-10.2196/62667

Abstract Clinical and preclinical studies established that supplementing diets with ω3 polyunsaturated fatty acids (PUFA) can reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) but molecular underpinnings of this action were elusive. Herein, we used multi‐omic network analysis that unveiled critical molecular pathways involved in ω3 PUFA effects in a preclinical mouse model of western diet induced NASH. Since NASH is a precursor of liver cancer, we also performed meta‐analysis of human liver cancer transcriptomes that uncovered betacellulin as a key EGFR‐binding protein upregulated in liver cancer and downregulated by ω3 PUFAs in animals and humans with NASH. We then confirmed that betacellulin acts by promoting proliferation of quiescent hepatic stellate cells, inducing transforming growth factor–β2 and increasing collagen production. When used in combination with TLR2/4 agonists, betacellulin upregulated integrins in macrophages thereby potentiating inflammation and fibrosis. Taken together, our results suggest that suppression of betacellulin is one of the key mechanisms associated with anti‐inflammatory and anti‐fibrotic effects of ω3 PUFA on NASH.

Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that exists in the Cannabis sativa plant. CBD has been found to act on various receptors, including both cannabinoid and non-cannabinoid receptors. In addition, CBD has antioxidant effects that are independent of receptors. CBD has demonstrated modulatory effects at different organ systems, such as the central nervous system, immune system, and the gastrointestinal system. Due to its broad effects within the body and its safety profile, CBD has become a topic of therapeutic interest. This literature review summarizes previous research findings with regard to the effect of CBD on the gastrointestinal (GI) system, including its effects at the molecular, cellular, organ, and whole-body levels. Both pre-clinical animal studies and human clinical trials are reviewed. The results of the studies included in this literature review suggest that CBD has significant impact on intestinal permeability, the microbiome, immune cells and cytokines. As a result, CBD has been shown to have therapeutic potential for GI disorders such as inflammatory bowel disease (IBD). Furthermore, through interactions with the gut, CBD may also be helpful in the treatment of disorders outside the GI system, such as non-alcoholic liver disease, postmenopausal disorders, epilepsy, and multiple sclerosis. In the future, more mechanistic studies are warranted to elucidate the detailed mechanisms of action of CBD in the gut. In addition, more well-designed clinical trials are needed to explore the full therapeutic potential of CBD on and through the gut.

FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (n = 530) of patients received treatment, and 47.5% (n = 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03, p = 0.001; HR 2.64, p = 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton’s tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and/or TP53 aberrations (HR 2.20, p = 0.001). The major cause of death in patients who received treatment was treatment/disease-related (32%, n = 42) and secondary malignancies (57%, n = 53) in those who were treatment-naïve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL.

Healthcare-associated viral respiratory infections (HA-VRIs) in a pediatric hospital decreased from 1.44 per 1000 patient days in 2019–0.43 and 0.38 in 2020–2021 during the SARS-CoV-2 pandemic but increased to 1.35 in 2022. The increase in HA-VRIs in 2022 coincided with the rise in community circulation of these organisms.

ABSTRACT The COVID-19 pandemic has likely influenced the epidemiology of bacterial infections through wide-ranging changes to clinical practices and infection control and prevention interventions. We sought to determine how the detection and incidence of bloodstream infections (BSIs) have been influenced by the pandemic. We performed a retrospective analysis of blood culture data in the province of Ontario, Canada, from 1 January 2017 to 31 December 2020. Outcomes included a weekly incidence of blood culture tests, BSIs, and contaminant results. Results were stratified by hospital, community, and long-term care (LTC) settings. An interrupted time series analysis using segmented regression models was used to determine changes in outcome incidence/prevalence during the pre- and peri-pandemic periods. Of the 14,083,853 individuals included, 129,329 (0.92%) developed a bloodstream infection. The blood culture ordering rate increased during the pandemic in the hospital setting only [Incidence rate ratio (IRR) 1.09, 95% confidence interval (CI) 1.01–1.19]. There was a decline in the incidence of community-acquired (IRR 0.95, 95% CI 0.91–0.99) and LTC-acquired (IRR 0.85, 95% CI 0.76–0.94) BSIs. Hospital-acquired BSIs were unchanged. The proportion of blood culture contaminants increased in the community (7% increase, P < 0.01) and LTC settings (14% increase, P < 0.05). There was decreased incidence of community-acquired Streptococcus pneumoniae (IRR 0.43, 95% CI 0.33–0.57) and Staphylococcus aureus (IRR 0.91, 95% CI 0.84–0.99) bacteremia. Pandemic-related changes in the performance of blood cultures and the epidemiology of BSIs have implications for current and future pandemic antimicrobial use, healthcare resource allocation, and hospital and laboratory policies. IMPORTANCE Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures.

# Background Current literature illustrates a disparity in trunk stability push up performance (TSPU), as measured by the Functional Movement Screen (FMSTM), in females throughout the lifespan when compared to their male counterparts. # Hypothesis/Purpose The purpose of this study was to evaluate the effectiveness of a novel exercise approach to a trunk stability (NEATS) program compared to a standard Pilates program on TSPU performance in active females aged 18-45 years. It was hypothesized that subjects in the NEATS program would have greater improvements on outcomes related to trunk stability than subjects in the Pilates program. # Study Design Randomized controlled trial # Methods All subjects were tested at baseline on Beighton criteria, the FMSTM, Y-Balance Test Upper Quarter and Lower Quarter, and grip strength by an evaluator blinded to group allocation. Subjects were randomized into the NEATS (n=17) or the Pilates group (n=19). The intervention period lasted eight weeks, with exercise progression at weeks two, four, and six. # Results The main outcome was between-group pass rates on the TSPU. At posttest, 41% (n=7) of the NEATS group and 42% (n=8) of the Pilates group passed the TSPU, though there was no difference between groups (p=0.97). Significant differences were noted on the TSPU (Pilates, NEATS p=0.01) and composite scores (Pilates p=0.01; NEATS p=0.03). No within-group improvements were noted on the individual scores of the FMSTM (p=0.05-0.66). Within-group differences were noted on the posterolateral reach on the Y-Balance Test Lower Quarter (p=0.03) in the Pilates group. Between-group posttest continuous measures were not significantly different (p=0.17-0.96). # Conclusion Improvements in trunk stability were comparable between the multi-planar NEATS program and a standard Pilates program suggesting that both can be used to improve trunk stability performance in active females. # Level of Evidence 2

This case details a 69-year-old female with a 3cm bladder mass on imaging who underwent transurethral resection of the bladder with pathology revealing non-Hodgkin follicular lymphoma to the bladder. The rarity and complexity of this presentation generated a challenging treatment dilemma regarding surveillance and active treatment.

Background: The Coronavirus Disease 2019 (COVID-19) is a global pandemic that has killed over 1.5 million people worldwide. A constellation of multisystem involvement with SARS-CoV-2 has been reported. COVID-19 has been shown to affect the human nervous system, however, both the extent and severity of involvement have yet to be fully elucidated. In this manuscript, we aimed to better understand the effect of COVID-19 on neuro-respiratory status by studying COVID-19 patients who presented with central apnea. Methodology: We analyzed patient characteristics, clinical outcomes, laboratory results, and imaging results of three patients with symptomatic, PCR-proven COVID-19 and episodes of central apnea. Results: Of the three patients included in this study, two patients developed new central apnea, and one patient developed an exacerbation of underlying central apnea despite COVID-19 treatments with systemic steroids and remdesivir. All occurred, on average, 15 days after the onset of COVID-19 symptoms. At 1-year follow-up, all patients experienced complete resolution of apneic breathing. Conclusions: Physicians should be vigilant for the presentation of COVID-19 with central apnea. Central apnea may be a complication in patients with severe COVID-19 infection. More research is warranted to further understand this association.

Abandoned and flooded ore mines are examples of hostile environments (cold, dark, oligotrophic, trace metal) with a potential vast diversity of microbial communities rarely characterized. This study aimed to understand the effects of depth, the source of water (surface or groundwater), and abiotic factors on the communities present in the old Forsyth iron mine in Quebec (Canada). Water and biofilm samples from the mine were sampled by a team of technical divers who followed a depth gradient (0 to 183 m deep) to study the planktonic and sessile communities’ diversity and structure. We used 16S/18S rRNA amplicon to characterize the taxonomic diversity of Bacteria, Archaea, and Eukaryotes. Our results show that depth was not a significant factor explaining the difference in community composition observed, but lifestyle (planktonic/sessile) was. We discovered a vast diversity of microbial taxa, with taxa involved in carbon- and sulfur-cycling. Sessile communities seem to be centered on C1-cycling with fungi and heterotrophs likely adapted to heavy-metal stress. Planktonic communities were dominated by ultra-small archaeal and bacterial taxa, highlighting harsh conditions in the mine waters. Microbial source tracking indicated sources of communities from surface to deeper layers and vice versa, suggesting the dispersion of organisms in the mine, although water connectivity remains unknown.

Abstract In this contribution, we present some of the first data on the elemental signature of deep crustal fluids in a basalt-hosted, low-chloride magmatic-hydrothermal system. Down-hole fluid samples (850–1600 m) from wells in the Theistareykir and Krafla geothermal fields in the Northern Volcanic Zone of Iceland were combined with well-head samples of condensed vapor, cuttings of altered rock, and fresh basalt (being some of the first concentration data for volatile and semi-volatile elements (Sb, Tl, Bi, Cd and As) for this area of Iceland). Results show that the deep fluids are relatively enriched in base metals and (semi)-volatile metals (in particular Te, Hg, Re and Tl) compared to local basalt. We interpret this enrichment in volatile metals to reflect a significant element input from magma degassing. Boiling of this deep fluid results in a well-head fluid composition that is significantly depleted in most elements. This well-head fluid has a distinct elemental signature, including a depletion in Sb that is mirrored in the altered rocks, and a depletion in the base metals that shows their selective sequestration in scale minerals, likely sulphides. As expected, the element content and patterns in surface fluids can thus not be interpreted to directly reflect that of the deep reservoir fluid. The behaviour of elements in Theistareykir and Krafla fluids is consistent, and largely agrees with similar data obtained for the Reykjanes geothermal system in SW Iceland. We therefore posit that our results are representative for this geological setting and indicate a significant magmatic degassing cation input to deep fluids, variably modified by water–rock interaction.

MYC amplification is an independent prognostic factor for the most aggressive subgroup (Group 3) of pediatric medulloblastoma (G3 MB). Here, the authors highlight the role of the RNA-binding protein, Musashi-1 (MSI1) in G3 MB and identify MSI1-bound targets sharing MYC associated pathways.

We present an exceptionally rare scenario of obstructive uropathy secondary to a ureteral mass. This case details a 68-year-old female with metastatic stage IIID melanoma of the right heel found to have a two cm right proximal ureteral mass with associated hydronephrosis. Pathology from ureteroscopic biopsy revealed metastatic melanoma to the ureter, creating a unique treatment quandary.

The implementation of REDD+ (Reducing Emissions from Deforestation and Forest Degradation) projects has become a key Nature Based Solutions strategy to protect at-risk forests using the sale of verified emission reductions (carbon credits) as financing, generated by reducing forest loss against counterfactual baseline scenarios. Controversy over the reasonableness of such baseline scenarios has thrown this nascent market mechanism into disarray. While new technical approaches to baseline-setting that promise wider market acceptance are set to roll out in the coming years, existing projects are becoming unviable, as carbon credit buyers reduce investment due to lost confidence in the integrity of emissions reduction claims. Transparent, reproducible methods to assess existing REDD+ project baselines are needed in order to provide a clearer picture of the real impact of projects, and provide an objective basis on which investment decisions can be made today. Here we introduce such a method. In contrast to existing studies which utilize only one method to create a single ‘control,’ we integrate actual forest loss rates from a variety of control sites to establish a ‘zone of reasonable accuracy (or ZORA)’. Application of our method in Cambodia, using two geospatial datasets (one global and one locally calibrated), shows that all three project baselines fall within or below ZORA. This approach is fully reproducible, and provides a transparent way for analysts to assess REDD+ baselines during this critical time when investment in forest protection must increase dramatically and without delay.

Abstract Background Posterior Reversible Encephalopathy Syndrome (PRES) is a neurotoxic state characterized by seizures, headache, vision change, paresis, and altered mental status. PRES has an important place in medicine due to the wide variety of causative diseases, infections, and medications that precipitate its mysterious onset. Although exposure to medications, particularly immunosuppressants, cancer chemotherapy, and biologic drugs, is a common occurrence in patients who develop PRES, Mepolizumab has never before been associated. Case presentation This report of a 67-year-old male patient outlines the first reported case of Mepolizumab-induced PRES in the literature. Conclusions Treatment of severe asthma, asthma-exacerbations, and diseases such as eosinophilic granulomatosis with polyangiitis (formerly Churg-Strauss) with Mepolizumab is rapidly gaining popularity ever since the drug’s recent FDA-approval. This report aims to raise awareness of this potentially life-threatening and previously unreported side effect of Mepolizumab since early identification of the causative agent is the key to preventing the severe neurologic disability and possible death that may occur from the delayed treatment of PRES.

Abstract The BNT162b2 vaccine is highly effective against COVID-19 infection and was delivered with a 3-week time interval in registration studies1. However, many countries extended this interval to accelerate population coverage with a single vaccine. It is not known how immune responses are influenced by delaying the second dose. We provide the assessment of immune responses in the first 14 weeks after standard or extended-interval BNT162b2 vaccination and show that delaying the second dose strongly boosts the peak antibody response by 3.5-fold in older people. This enhanced antibody response may offer a longer period of clinical protection and delay the need for booster vaccination. In contrast, peak cellular-specific responses were the strongest in those vaccinated on a standard 3-week vaccine interval. As such, the timing of the second dose has a marked influence on the kinetics and magnitude of the adaptive immune response after mRNA vaccination in older people.

Developments in Artificial Intelligence (AI) are helping to solve complex physical problems that otherwise may be too computationally demanding to solve using traditional approaches. Universal Approximation Theorems tell us that we can model any physical system if we can approximate the system with some continuous function (i.e., compact convergence topology and algorithmically generated sets of functions, such as the convolutional neural network), whether for an arbitrary depth or arbitrary width neural network. We consider the problem of solving a set of $N$ coupled algebraic equations as $N$ becomes very large and apply machine learning (ML) to solve this problem for any value of $N$ . The physical problem we are focusing on is to model the equilibrium positions of ions in an ion trap. A storage ring quantum computer could contain well over tens of thousands of ions. Quickly determining the equilibrium positions will be important to minimize the time to target and observe each ion. As each ion serves as a single qubit, this is important for setting and measuring the individual qubit states. The phonon modes from a collection of ions acts as another qubit, useful for gate operations. Measuring the phonon modes, where ions are oscillating around their respective equilibrium positions also means understanding the equilibrium positions very well. Turning all of this into a virtual diagnostic allows real time prediction and comparison to ensure unique definition of each ion.

Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug-tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte-specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, microphthalmia-associated transcription factor (MITF) and SRY-box transcription factor 10 (SOX10), important in melanoma development and progression, have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation, and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF-methylated cultures were subdivided in 2 distinct subtypes. Examining mRNA levels of neural crest–associated genes, we found that 1 subtype had lost the expression of several lineage genes, including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF-methylated melanoma cells using CRISPR/Cas9 supported these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.

Summary: Background: There remains uncertainty about the epidemiology of SARS-CoV-2 among school students and staff and the extent to which non-pharmaceutical-interventions reduce the risk of school settings. Methods: We conducted an open cohort study in a sample of 59 primary and 97 secondary schools in 15 English local authority areas that were implementing government guidance to schools open during the pandemic. We estimated SARS-CoV-2 infection prevalence among those attending school, antibody prevalence, and antibody negative to positive conversion rates in staff and students over the school year (November 2020–July 2021). Findings: 22,585 staff and students participated. SARS-CoV-2 infection prevalence among those attending school was highest during the first two rounds of testing in the autumn term, ranging from 0.7% (95% CI 0.2, 1.2) among primary staff in November 2020 to 1.6% (95% CI 0.9, 2.3) among secondary staff in December 2020. Antibody conversion rates were highest in the autumn term. Infection patterns were similar between staff and students, and between primary and secondary schools. The prevalence of nucleoprotein antibodies increased over the year and was lower among students than staff. SARS-CoV-2 infection prevalence in the North-West region was lower among secondary students attending school on normal school days than the regional estimate for secondary school-age children. Interpretation: SARS-CoV-2 infection prevalence in staff and students attending school varied with local community infection rates. Non-pharmaceutical interventions intended to prevent infected individuals attending school may have partially reduced the prevalence of infection among those on the school site. Funding: UK Department of Health and Social Care.

Abstract Background The cell adhesion molecule transmembrane and immunoglobulin (Ig) domain containing1 (TMIGD1) is a novel tumor suppressor that plays important roles in regulating cell–cell adhesion, cell proliferation and cell cycle. However, the mechanisms of TMIGD1 signaling are not yet fully elucidated. Results TMIGD1 binds to the ERM family proteins moesin and ezrin, and an evolutionarily conserved RRKK motif on the carboxyl terminus of TMIGD1 mediates the interaction of TMIGD1 with the N-terminal ERM domains of moesin and ezrin. TMIGD1 governs the apical localization of moesin and ezrin, as the loss of TMIGD1 in mice altered apical localization of moesin and ezrin in epithelial cells. In cell culture, TMIGD1 inhibited moesin-induced filopodia-like protrusions and cell migration. More importantly, TMIGD1 stimulated the Lysine (K40) acetylation of α-tubulin and promoted mitotic spindle organization and CRISPR/Cas9-mediated knockout of moesin impaired the TMIGD1-mediated acetylation of α-tubulin and filamentous (F)-actin organization. Conclusions TMIGD1 binds to moesin and ezrin, and regulates their cellular localization. Moesin plays critical roles in TMIGD1-dependent acetylation of α-tubulin, mitotic spindle organization and cell migration. Our findings offer a molecular framework for understanding the complex functional interplay between TMIGD1 and the ERM family proteins in the regulation of cell adhesion and mitotic spindle assembly, and have wide-ranging implications in physiological and pathological processes such as cancer progression.

Epigenetic changes are implicated in Acute myeloid leukemia (AML) tumorigenesis. Here, the authors show that the ubiquitin ligase RNF5 and its substrate RBBP4 contribute to AML development by regulating epigenetic-controlled transcription which determines AML sensitivity to HDAC inhibitors.

Abstract Background Several SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8–12 week ‘extended interval’. Objectives We undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n = 54) or ChAdOx1 (n = 77) adenovirus vaccine. Blood samples were taken 2–3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-γ ELISpot. Results Antibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892–8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5–2543) in the 74 patients after the ChAdOx1 vaccine (p =

We describe results of testing blood donors in London, UK, for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) IgG before and after lockdown measures. Anonymized samples from donors 17–69 years of age were tested using 3 assays: Euroimmun IgG, Abbott IgG, and an immunoglobulin receptor-binding domain assay developed by Public Health England. Seroprevalence increased from 3.0% prelockdown (week 13, beginning March 23, 2020) to 10.4% during lockdown (weeks 15–16) and 12.3% postlockdown (week 18) by the Abbott assay. Estimates were 2.9% prelockdown, 9.9% during lockdown, and 13.0% postlockdown by the Euroimmun assay and 3.5% prelockdown, 11.8% during lockdown, and 14.1% postlockdown by the receptor-binding domain assay. By early May 2020, nearly 1 in 7 donors had evidence of past SARS-CoV-2 infection. Combining results from the Abbott and Euroimmun assays increased seroprevalence by 1.6%, 2.3%, and 0.6% at the 3 timepoints compared with Euroimmun alone, demonstrating the value of using multiple assays.

Abstract Forest biomass harvesting guidelines help ensure the ecological sustainability of forest residue harvesting for bioenergy and bioproducts, and hence contribute to social license for a growing bioeconomy. Guidelines, typically voluntary, provide a means to achieve outcomes often required by legislation, and must address needs related to local or regional context, jurisdictional compatibility with regulations, issues of temporal and spatial scale, and incorporation of appropriate scientific information. Given this complexity, comprehensive reviews of existing guidelines can aid in development of new guidelines or revision of existing ones. We reviewed 32 guidelines covering 43 jurisdictions in the USA, Canada, Europe and East Asia to expand upon information evaluated and recommendations provided in previous guideline reviews, and compiled a searchable spreadsheet of direct quotations from documents as a foundation for our review. Guidelines were considered in the context of sustainable forest management (SFM), focusing on guideline scope and objectives, environmental sustainability concerns (soils, site productivity, biodiversity, water and carbon) and social concerns (visual aesthetics, recreation, and preservation of cultural, historical and archaeological sites). We discuss the role of guidelines within the context of other governance mechanisms such as SFM policies, trade regulations and non-state market-driven (NSMD) standards, including certification systems. The review provides a comprehensive resource for those developing guidelines, or defining sustainability standards for market access or compliance with public regulations, and/or concerned about the sustainability of forest biomass harvesting. We recommend that those developing or updating guidelines consider (i) the importance of well-defined and understood terminology, consistent where possible with guidelines in other jurisdictions or regions; (ii) guidance based on locally relevant research, and periodically updated to incorporate current knowledge and operational experience; (iii) use of indicators of sensitive soils, sites, and stands which are relevant to ecological processes and can be applied operationally; and (iv) incorporation of climate impacts, long-term soil carbon storage, and general carbon balance considerations when defining sustainable forest biomass availability. Successful implementation of guidelines depends both on the relevance of the information and on the process used to develop and communicate it; hence, appropriate stakeholders should be involved early in guideline development.

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.

The ubiquitin ligase Siah2 has been implicated in immune responses. Here, the authors show that Siah2 null immune cells have an increased inflammatory response to inoculated melanoma cells, along with a reduced number of infiltrating immunosuppressive regulatory T cells, resulting in inhibition of tumour growth.

Background and ObjectiveThe cochlear implant (CI) electrode insertion process is a key step in CI surgery. One of the aims of advances in robotic-assisted CI surgery (RACIS) is to realize better cochlear structure preservation and to precisely control insertion. The aim of this literature review is to gain insight into electrode selection for RACIS by acquiring a thorough knowledge of electrode insertion and related complications from classic CI surgery involving a manual electrode insertion process.MethodsA systematic electronic search of the literature was carried out using PubMed, Scopus, Cochrane, and Web of Science to find relevant literature on electrode tip fold over (ETFO), electrode scalar deviation (ESD), and electrode migration (EM) from both pre-shaped and straight electrode types.ResultsA total of 82 studies that include 8,603 ears implanted with a CI, i.e., pre-shaped (4,869) and straight electrodes (3,734), were evaluated. The rate of ETFO (25 studies, 2,335 ears), ESD (39 studies, 3,073 ears), and EM (18 studies, 3,195 ears) was determined. An incidence rate (±95% CI) of 5.38% (4.4–6.6%) of ETFO, 28.6% (26.6–30.6%) of ESD, and 0.53% (0.2–1.1%) of EM is associated with pre-shaped electrodes, whereas with straight electrodes it was 0.51% (0.1–1.3%), 11% (9.2–13.0%), and 3.2% (2.5–3.95%), respectively. The differences between the pre-shaped and straight electrode types are highly significant (p < 0.001). Laboratory experiments show evidence that robotic insertions of electrodes are less traumatic than manual insertions. The influence of round window (RW) vs. cochleostomy (Coch) was not assessed.ConclusionConsidering the current electrode designs available and the reported incidence of insertion complications, the use of straight electrodes in RACIS and conventional CI surgery (and manual insertion) appears to be less traumatic to intracochlear structures compared with pre-shaped electrodes. However, EM of straight electrodes should be anticipated. RACIS has the potential to reduce these complications.

Infectious disease transmission models often stratify populations by age and geographic patches. Contact patterns between age groups and patches are key parameters in such models. Arenas et al. (2020) develop an approach to simulate contact patterns associated with recurrent mobility between patches, such as due to work, school, and other regular travel. Using their approach, mixing between patches is greater than mobility data alone would suggest, because individuals from patches A and B can form contacts if they meet in patch C. We build upon their approach to address three potential gaps that remain, outlined in the bullets below. We describe the steps required to implement our approach in detail, and present step-wise results of an example application to generate contact matrices for SARS-CoV-2 transmission modelling in Ontario, Canada. We also provide methods for deriving the mobility matrix based on GPS mobility data (appendix). • Our approach includes a distribution of contacts by age that is responsive to the underlying age distributions of the mixing populations. • Our approach maintains different age mixing patterns by contact type, such that changes to the numbers of different types of contacts are appropriately reflected in changes to overall age mixing patterns. • Our approach distinguishes between two mixing pools associated with each patch, with possible implications for the overall connectivity of the population: the home pool, in which contacts can only be formed with other individuals residing in the same patch, and the travel pool, in which contacts can be formed with some residents of, and any other visitors to the patch.

# Background Trunk stability is a risk factor commonly associated with lower extremity injuries, particularly in females. Performance on trunk stability tasks, such as the Trunk Stability Push Up (TSPU), is less than optimal in females. Current corrective programs include few females, and clinically, improvements for females have been minimal. # Purpose/Hypothesis The purpose of this pilot study was to determine the effectiveness of a novel trunk stability intervention program in improving TSPU performance in a cohort of active female participants. It was hypothesized that ≥60% of participants would improve their TSPU scores to ≥2 via Functional Movement Screen™ (FMS™) criteria following a novel six-week intervention program. # Study Design Pilot Cohort Study # Methods Participants were screened for pain with lumbar and shoulder clearing tests and hypermobility was assessed using Beighton scores. Additional testing included a breathing screen, the FMS™, Y-Balance Test-Lower Quarter and Y-Balance Test-Upper Quarter. Participants who scored a 1 on the TSPU received a home exercise program instructed by student physical therapists. Exercises focused on improving awareness of lumbar spine position and thoracic spine mobility. Participants returned for follow-ups after two and four weeks for instruction in exercise progression, which increased postural demand on the lumbar spine and upper extremities, and utilized closed-chain, multiplanar stability strategies. # Results Nine of 20 participants (45%) scored ≥2 on the TSPU at posttest. Due to the COVID-19 pandemic, only 12 participants were able to complete all posttest outcome measures. No significant differences were noted in the remaining outcome measures. Conclusion: The results of this study indicate that a multiplanar exercise approach, combining anti-extension and anti-rotation training, was beneficial for inducing trunk stability improvements in some active females. # Level of Evidence 2b

Posterior sternoclavicular joint dislocation is a rare injury requiring prompt diagnosis as it has been associated with the compression of the subclavian and brachiocephalic arteries. We report the case of a 27-year-old male presenting with altered mental status and left hemiparesis found to have life-altering neurologic damage caused by severe orthopedic injury after a fall while intoxicated. Imaging revealed a posteriorly displaced right medial clavicle with surrounding hematoma compressing the brachiocephalic artery causing local thrombus formation and distal embolization, ultimately resulting in malignant cerebral infarction. His hospital course was complicated by cerebral edema requiring decompressive craniectomy, hemorrhagic transformations, brachiocephalic pseudoaneurysm, and the development of remote embolic ischemic infarctions.

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

RNF5 is a ubiquitin ligase regulating ER stress response. Here the authors show that Rnf5 deficiency potentiates immune response against melanoma via altered microbiota, and isolate bacterial strains that confer the same phenotype to wild type mice.

Medulla compression from vertebral artery abnormality is a very rare occurrence with few cases present in the literature. It has been documented to present with a very wide spectrum of clinical symptomatology ranging from asymptomatic to full hemiplegia. There is currently no treatment algorithm in place to guide clinicians encountering such patients but treatments have historically involved major posterior compartment surgical interventions. This case outlined a patient evaluated for dizziness without any other neurological symptoms or signs, found to have abnormal dilatation, elongation, and tortuosity of the vertebral artery with resultant compression of the medulla oblongata. The patient was managed conservatively after discussion of surgical options. This report outlined an important consideration for management of medullar compression by vertebral artery based on symptom severity with the possibility of postponing surgical or endovascular interventions and opting for conservative management with an anti-platelet regimen, particularly in the short term.

Background: Care homes have been disproportionately affected by the COVID-19 pandemic. We investigated the potential role of asymptomatic infection and silent transmission in London care homes that reported no cases of COVID-19 during the first wave of the pandemic. Methods: Five care homes with no cases and two care homes reporting a single case of COVID-19 (non-outbreak homes) were investigated with nasal swabbing for SARS-CoV-2 RT-PCR and serology for SARS-CoV-2 antibodies five weeks later. Whole genome sequencing (WGS) was performed on RT-PCR positive samples. Serology results were compared with those of six care homes with recognised outbreaks. Findings: Across seven non-outbreak homes, 718 (387 staff, 331 residents) individuals had a nasal swab and 651 (386 staff, 265 residents) had follow-up serology. Sixteen individuals (13 residents, 3 staff) in five care homes with no reported cases were RT-PCR positive (care home positivity rates, 0 to 7.6%) compared to 13 individuals (3.0 and 10.8% positivity) in two homes reporting a single case.Seropositivity across these seven homes varied between 10.7-56.5%, with four exceeding community seroprevalence in London (14.8%). Seropositivity rates for staff and residents correlated significantly (rs 0.84, [95% CI 0.51-0.95] p

Background: We investigated six London care homes experiencing a COVID-19 outbreak and found high rates of SARS-CoV-2 infection among residents and staff. Here we report follow-up investigations including antibody testing in the same care homes five weeks later. Methods: Residents and staff in the initial investigation had a repeat nasal swab for SARS-CoV-2 RT-PCR and a blood test for SARS CoV-2 antibodies using ELISA based on SARS-CoV-2 native viral antigens derived from infected cells and virus neutralisation. Findings: Of the 518 residents and staff in the initial investigation, 186/241 (77.2%) surviving residents and 208/254 (81.9%) staff underwent serological testing. Almost all SARS-CoV-2 RT-PCR positive residents and staff were seropositive five weeks later, whether symptomatic (residents 35/35, 100%; staff, 22/22, 100%) or asymptomatic (residents 32/33, 97.0%; staff 21/22, 95.5%). Symptomatic but SARS-CoV-2 RT-PCR negative residents and staff also had high seropositivity rates (residents 23/27, 85.2%; staff 18/21, 85.7%), as did asymptomatic RT-PCR negative individuals (residents 61/91, 67.0%; staff 95/143, 66.4%). Neutralising antibody was detected in 118/132 (89.4%) seropositive individuals and was not associated with age or symptoms. Ten residents (10/79 re-tested, 12.7%) remained RT-PCR positive but with higher RT-PCR cycle threshold values; 7/10 had serological testing and all were seropositive. New infections were detected in three residents and one staff. Interpretation: RT-PCR provides a point prevalence of SARS-CoV-2 infection but significantly underestimates total exposure in outbreak settings. In care homes experiencing large COVID-19 outbreaks, most residents and staff had neutralising SARS-CoV-2 antibodies, which was not associated with age or symptoms. Funding: PHE

Background: Care homes are experiencing large outbreaks of COVID-19 associated with high case-fatality rates. We conducted detailed investigations in six London care homes reporting suspected COVID-19 outbreaks during April 2020.Methods: Residents and staff had nasal swabs for SARS CoV-2 testing using RT-PCR and were followed-up for 14 days. They were categorized as symptomatic, post-symptomatic or pre-symptomatic if they had symptoms at the time of testing, in the two weeks before or two weeks after testing, respectively, or asymptomatic throughout. Virus isolation and whole genome sequencing (WGS) was also performed.Findings: Across the six care homes, 105/264 (39.8%) residents were SARS CoV-2 positive, including 28 (26.7%) symptomatic, 10 (9.5%) post-symptomatic, 21 (20.0%) pre-symptomatic and 46 (43.8%) who remained asymptomatic. Case-fatality at 14-day follow-up was highest among symptomatic SARS-CoV-2 positive residents (10/28, 35.7%) compared to asymptomatic (2/46, 4.3%), post-symptomatic (2/10, 20.0%) or pre-symptomatic (3/21,14.3%) residents. Among staff, 53/254 (20.9%) were SARS-CoV-2 positive and 26/53 (49.1%) remained asymptomatic. RT-PCR cycle-thresholds and live-virus recovery were similar between symptomatic/asymptomatic residents/staff. Higher RT-PCR cycle threshold values (lower virus load) samples were associated with exponentially decreasing ability to recover infectious virus (P

Purpose: MR-guided Radiation Therapy (MRgRT) allows for high-precision radiotherapy under real-time MR visualization. This enables margin reduction and subsequent dose escalation which may lead to higher tumor control and less toxicity. The Unity MR-linac (Elekta AB, Stockholm, Sweden) integrates a linear accelerator with a 1.5T diagnostic quality MRI and an online adaptive workflow. A prospective international registry was established to facilitate the evidence-based implementation of the Unity MR-linac into clinical practice, to systemically evaluate long-term outcomes, and to aid further technical development of MR-linac-based MRgRT.Methods and Results: In February 2019, the Multi-OutcoMe EvaluatioN of radiation Therapy Using the MR-linac study (MOMENTUM) started within the MR-linac Consortium. The MOMENTUM study is an international academic-industrial partnership between several hospitals and industry partner Elekta. All patients treated on the MR-linac are eligible for inclusion in MOMENTUM. For participants, we collect clinical patient data (e.g., patient, tumor, and treatment characteristics) and technical patient data which is defined as information generated on the MR-linac during treatment. The data are captured, pseudonymized, and stored in an international registry at set time intervals up to two years after treatment. Patients can choose to provide patient-reported outcomes and consent to additional MRI scans acquired on the MR-linac. This registry will serve as a data platform that supports multicenter research investigating the MR-linac. Rules and regulations on data sharing, data access, and intellectual property rights are summarized in an academic-industrial collaboration agreement. Data access rules ensure secure data handling and research integrity for investigators and institutions. Separate data access rules exist for academic and industry partners. This study is registered at ClinicalTrials.gov with ID: NCT04075305 (https://clinicaltrials.gov/ct2/show/NCT04075305).Conclusion: The multi-institutional MOMENTUM study has been set up to collect clinical and technical patient data to advance technical development, and facilitate evidenced-based implementation of MR-linac technology with the ultimate purpose to improve tumor control, survival, and quality of life of patients with cancer.

Background and purpose: Several studies have investigated multi leaf collimator (MLC) leaf design. We performed a systematic review and meta-analysis of those studies to compare the impact of MLC leaf width used for different radiotherapy techniques. Materials and methods: We decided to focus on 2.5, 3.0 and 5.0 mm leaf width MLCs as it appeared to be the most contentious area from literature. We adopted Cochrane and PRISMA guidelines and computed the association between MLC leaf width and conformity index (CI) across the selected studies as pooled mean difference (PMD) with 95% confidence interval. Results: A total of 43 papers were selected from the literature search, of which ten compare MLC leaf width of 2.5 mm or 3.0 mm (MLC2.5 mm) versus 5.0 mm (MLC5 mm) in terms of CI. There was a slight, but significant, difference between MLC2.5 mm and MLC5 mm in favor of the former (mean difference −0.036; 95% confidence interval: −0.068 to −0.005). A subgroup analysis was performed by comparing techniques (intensity modulated radiation therapy vs conformal). In the intensity modulated radiation therapy (IMRT) subgroup, the difference between MLC2.5 mm and MLC5 mm appeared to be negligible (mean difference: −0.006; 95% confidence interval: −0.013 to 0.001) and not significantly different from zero. In the subgroup of studies which used conformal techniques, there was a significant difference between MLC2.5 mm and MLC5 mm (mean difference: −0.054; 95% confidence interval: −0.096 to −0.012). Conclusions: Introduction of IMRT produced comparable target coverage (CI) between 2.5 or 5.0 mm leaf width MLCs. Keywords: Multi leaf collimators, Treatment planning system, Intensity modulated radiation therapy, Systematic review, Meta-analysis

Multidisciplinary team (MDT) diagnosis of interstitial lung disease (ILD) has been proposed as a gold standard, but there are no formal recommendations for MDT process or composition and limited knowledge regarding prevalence in routine practice. We performed a systematic evaluation of ILD diagnostic practice across a range of healthcare settings around the world. Electronic questionnaires were distributed across all global regions via society and collaborators networks. Responses from 457 unique centres across 64 countries were included in the analysis. Of the 350 (76.6%) centres holding formal meetings, the majority held face-to-face MDT meetings (80%), for a minimum of 30 min (93%), and discussed diagnosis (96.9%) and patient management (94.9%) at the meetings. Compared with non-academic and academic non-ILD centres, ILD academic centres reported a higher ILD caseload, held more formal MDT meetings, and were more likely to include histopathology and rheumatology specialists in their diagnostic team. Of the centres holding MDT meetings, 5.5% routinely discussed all new cases at such meetings. An MDT approach to ILD diagnosis is consistently interpreted and widely implemented across a range of routine care settings around the world. This observation will inform future ILD diagnostic agreement studies and diagnostic pathway recommendations.

Canine malignant melanoma, a significant cause of mortality in domestic dogs, is a powerful comparative model for human melanoma, but little is known about its genetic etiology. We mapped the genomic landscape of canine melanoma through multi-platform analysis of 37 tumors (31 mucosal, 3 acral, 2 cutaneous, and 1 uveal) and 17 matching constitutional samples including long- and short-insert whole genome sequencing, RNA sequencing, array comparative genomic hybridization, single nucleotide polymorphism array, and targeted Sanger sequencing analyses. We identified novel predominantly truncating mutations in the putative tumor suppressor gene PTPRJ in 19% of cases. No BRAF mutations were detected, but activating RAS mutations (24% of cases) occurred in conserved hotspots in all cutaneous and acral and 13% of mucosal subtypes. MDM2 amplifications (24%) and TP53 mutations (19%) were mutually exclusive. Additional low-frequency recurrent alterations were observed amidst low point mutation rates, an absence of ultraviolet light mutational signatures, and an abundance of copy number and structural alterations. Mutations that modulate cell proliferation and cell cycle control were common and highlight therapeutic axes such as MEK and MDM2 inhibition. This mutational landscape resembles that seen in BRAF wild-type and sun-shielded human melanoma subtypes. Overall, these data inform biological comparisons between canine and human melanoma while suggesting actionable targets in both species.

Summary: Inflammatory bowel disease (IBD) is prevalent, but the mechanisms underlying disease development remain elusive. We identify a role for the E3 ubiquitin ligase RNF5 in IBD. Intestinal epithelial cells (IECs) express a high level of RNF5, while the colon of Rnf5−/− mice exhibits activated dendritic cells and intrinsic inflammation. Rnf5−/− mice exhibit severe acute colitis following dextran sodium sulfate (DSS) treatment. S100A8 is identified as an RNF5 substrate, resulting in S100A8 ubiquitination and proteasomal-dependent degradation that is attenuated upon inflammatory stimuli. Loss of RNF5 from IECs leads to enhanced S100A8 secretion, which induces mucosal CD4+ T cells, resulting in Th1 pro-inflammatory responses. Administration of S100A8-neutralizing antibodies to DSS-treated Rnf5−/− mice attenuates acute colitis development and increases survival. An inverse correlation between RNF5 and S100A8 protein expression in IECs of IBD patients coincides with disease severity. Collectively, RNF5-mediated regulation of S100A8 stability in IECs is required for the maintenance of intestinal homeostasis. : Fujita et al. show that RNF5 regulation of S100A8 stability in intestinal epithelial cells defines the degree of pro-inflammatory response, culminating in severe intestinal inflammation following DSS treatment to Rnf5−/− mice. Neutralizing S100A8 antibodies attenuates acute colitis phenotypes, and inverse RNF5/S100A8 expression coincides with clinical severity in IBD patients. Keywords: ubiquitin ligase, RNF5, S100A8, intestinal inflammation, IBD, acute colitis, intestinal epithelial cells

Defining protein interaction networks can provide key insights into how protein complexes govern complex biological problems. Here we define a method for proximity based labeling using permissive biotin ligase to define protein networks in the intracellular parasite Toxoplasma gondii. When combined with CRISPR/Cas9 based tagging, this method provides a robust approach to defining protein networks. This approach detects interaction within intact cells, it is applicable to both soluble and insoluble components, including large proteins complexes that interact with the cytoskeleton and unique microtubule organizing center that comprises the apical complex in apicomplexan parasites.

Toxoplasma gondii is a member of the deadly phylum of protozoan parasites called Apicomplexa. As a model apicomplexan, there is a great wealth of information regarding T. gondii’s 8,000+ protein coding genes including sequence variation, expression, and relative contribution to parasite fitness. However, new tools are needed to functionally investigate hundreds of putative essential protein coding genes. Accordingly, we recently implemented the auxin-inducible degron (AID) system for studying essential proteins in T. gondii. Here we provide a step-by-step protocol for examining protein function in T. gondii using the AID system in a tissue culture setting.

While the underrepresentation of women in the fast-growing STEM field of computer science (CS) has been much studied, no consensus exists on the key factors influencing this widening gender gap. Possible suspects include gender differences in aptitude, interest, and academic environment. Our study contributes to this literature by applying student engagement research to study the experiences of college students studying CS, to assess the degree to which differences in men and women's engagement may help account for gender inequity in the field. Specifically, we use the Experience Sampling Method (ESM) to evaluate in real-time the engagement of college students during varied activities and environments. Over the course of a full week in fall semester and a full week in spring semester, 165 students majoring in CS at two Research I universities were “beeped” several times a day via a smartphone app prompting them to fill out a short questionnaire including open-ended and scaled items. These responses were paired with administrative and over 2 years of transcript data provided by their institutions. We used mean comparisons and logistic regression analysis to compare enrollment and persistence patterns among CS men and women. Results suggest that despite the obstacles associated with women's underrepresentation in computer science, women are more likely to continue taking computer science courses when they felt challenged and skilled in their initial computer science classes. We discuss implications for further research.

Just as oncogene activation and tumor suppressor loss are hallmarks of tumor development, emerging evidence indicates that tumor microenvironment-mediated changes in glycosylation play a crucial functional role in tumor progression and metastasis. Hypoxia and inflammatory events regulate protein glycosylation in tumor cells and associated stromal cells in the tumor microenvironment, which facilitates tumor progression and also modulates a patient’s response to anti-cancer therapeutics. In this review, we highlight the impact of altered glycosylation on angiogenic signaling and endothelial cell adhesion, and the critical consequences of these changes in tumor behavior.

Abstract Although microarray analysis has provided information regarding the dynamics of gene expression during development of the mouse lung, no extensive correlations have been made to the levels of corresponding protein products. Here, we present a global survey of protein expression during mouse lung organogenesis from embryonic day E13.5 until adulthood using gel‐free two‐dimensional liquid chromatography coupled to shotgun tandem mass spectrometry (MudPIT). Mathematical modeling of the proteomic profiles with parallel DNA microarray data identified large groups of gene products with statistically significant correlation or divergence in coregulation of protein and transcript levels during lung development. We also present an integrative analysis of mRNA and protein expression in Nmyc loss‐ and gain‐of‐function mutants. This revealed a set of 90 positively and negatively regulated putative target genes. These targets are evidence that Nmyc is a regulator of genes involved in mRNA processing and a repressor of the imprinted gene Igf2r in the developing lung.