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Abstract Background Anabolic androgenic steroids (AAS) are synthetic forms of testosterone frequently used as performance enhancing drugs among gay, bisexual, and queer (GBQ) men. Despite widespread use, associated harms, and the likely existence of an AAS use disorder, there is no medical consensus on standards of care for people who use AAS, with most medical providers focusing exclusively on abstinence. Individuals using AAS have developed community-based harm reduction strategies to mitigate these harms. Methods This paper is a sub-analysis of qualitative data obtained through semi-structured interviews with GBQ men using AAS for 8 or more weeks recruited through convenience and snowball sampling from clinical sites and LGBTQ + venues in New York City as well as through social media. Interviews were coded with themes developed using reflexive thematic analysis. Data related to harm reduction techniques were then re-analyzed through a prevention strategies framework lens of primary, secondary, and tertiary harm prevention. Results Thematic saturation was reached at twelve interviews in the primary analysis, with men reporting frequent use of multiple harm reduction techniques. For primary prevention, men avoided oral steroids and simultaneous substance use, tried to obtain AAS from reputable sources, used “cycling” to dose steroids, and practiced sterile injection techniques. Secondary prevention methods included patient-directed lab testing for hematocrit, liver and kidney function, cholesterol, prostate specific antigen, testosterone, and self-performed blood pressure checks. Tertiary prevention included donating blood and the use of medications without a prescription, including aromatase inhibitors, selective estrogen receptor blockers, aspirin, statins, angiotensin receptor blockers, clomiphene, and human chorionic gonadotropin. Conclusions Despite many GBQ men experiencing harms from anabolic androgenic steroids, community members have often sought harm reduction techniques in lieu of abstinence. Though many of these techniques embrace clinical reasoning and may be more broadly applicable, additional research is needed to understand the impact of each intervention on the overall health of individuals using AAS.

Abstract Autologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34+ cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 106 cells/kg) and high (>2.5 × 106 cells/kg) CD34+ dose groups. We included 2479 patients, 95 in the low CD34+ group and 2384 in the high CD34+ group. Patients in the low CD34+ group were older (63.2 vs 61.1 years, p = 0.013), more often had R-ISS III (19% vs 9%, p = 0.014), received plerixafor (60% vs 35%, p 2.5 × 106 cells/kg. Multivariable analysis affirmed that CD34+ >2.5 × 106 cells/kg was associated with better PFS (HR 0.71, p = 0.008) and OS (0.59, p 2.5 × 106 cells/kg remained a predictor of better OS (0.42, p 2.5 × 106 cells/kg was associated with improved survival, without any additional benefit at incrementally higher doses.

Abstract The Phase 3 randomized controlled trial, TBTC Study 31/ACTG A5349 (NCT02410772) demonstrated that a 4-month rifapentine-moxifloxacin regimen for drug-susceptible pulmonary tuberculosis was safe and effective. The primary efficacy outcome was 12-month tuberculosis disease free survival, while the primary safety outcome was the proportion of grade 3 or higher adverse events during the treatment period. We conducted an analysis of demographic, clinical, microbiologic, radiographic, and pharmacokinetic data and identified risk factors for unfavorable outcomes and adverse events. Among participants receiving the rifapentine-moxifloxacin regimen, low rifapentine exposure is the strongest driver of tuberculosis-related unfavorable outcomes (HR 0.65 for every 100 µg∙h/mL increase, 95%CI 0.54–0.77). The only other risk factors identified are markers of higher baseline disease severity, namely Xpert MTB/RIF cycle threshold and extent of disease on baseline chest radiography (Xpert: HR 1.43 for every 3-cycle-threshold decrease, 95%CI 1.07–1.91; extensive disease: HR 2.02, 95%CI 1.07–3.82). From these risk factors, we developed a simple risk stratification to classify disease phenotypes as easier-, moderately-harder, or harder-to-treat TB. Notably, high rifapentine exposures are not associated with any predefined adverse safety outcomes. Our results suggest that the easier-to-treat subgroup may be eligible for further treatment shortening while the harder-to-treat subgroup may need higher doses or longer treatment.

Abstract Background The current understanding of climate anxiety among adolescents is sparse. This study identifies the characteristics of adolescents living in Quebec (Canada) who experience impairments induced by climate anxiety, who have feelings of self-efficacy and who adopt pro-environment behaviors. It also characterizes the association between climate anxiety, feelings of self-efficacy, and environmental actions. Methods We used a cross-sectional design to analyze data from the COMPASS study on adolescent health. Participants (n = 45 362) from 113 schools in Quebec (Canada) answered questions about climate anxiety, self-efficacy, behavioral engagement, and several indicators of well-being. Data were analyzed using ordered logistic regressions adjusted for potential confounders (age, gender, school type, material deprivation, etc.). Results 9% of adolescents reported that thinking about climate change made it difficult to sleep at least sometimes. 6% of adolescents reported that thinking about climate change interfered with their ability to get work or assignments done at least sometimes. Only 34% believed they could do something to address the problem, and 43% tried to reduce their behaviors that contribute to climate change at least sometimes. Adolescents who were boys or who were less anxious experienced less impairment and were less involved in the fight against climate change. Adolescents from less affluent families experienced more difficulty sleeping and interference with work but were not more engaged. Those with stronger school connectedness experienced less impairment and were more often involved in the fight against climate change. Adolescents who felt they could do something about climate change were more likely to try to reduce behaviors that contribute to climate change. Conclusion The findings are useful to identify and support vulnerable groups that are more likely to experience impairment due to climate anxiety. The feeling of climate self-efficacy was not well developed among some groups of adolescents. Improving adolescents’ beliefs in their capacity to help address climate change may be a key strategy to promote pro-environmental actions. As the threat of climate change increases, it will be important to follow the evolution of climate anxiety and engagement among adolescents.

Abstract Background The burden of chronic non-communicable diseases (NCDs) is a growing public health concern. The availability of cost-of-illness data, particularly public healthcare costs for NCDs, is limited in Sub-Saharan Africa (SSA), yet such data evidence is needed for policy action. Objective The objective of this study was to estimate the economic burden of type 2 diabetes (T2D) on Kenya’s public healthcare system in 2021 and project costs for 2045. Methods This was a cost-of-illness study using the prevalence-based bottom-up costing approach to estimate the economic burden of T2D in the year 2021. We further conducted projections on the estimated costs for the year 2045. The costs were estimated corresponding to the care, treatment, and management of diabetes and some diabetes complications based on the primary data collected from six healthcare facilities in Nairobi and secondary costing data from previous costing studies in low and middle-income countries (LMICs). The data capture and costing analysis were done in Microsoft Excel 16, and sensitivity analysis was conducted on all the parameters to estimate the cost changes. Results The total cost of managing T2D for the healthcare system in Kenya was estimated to be US$ 635 million (KES 74,521 million) in 2021. This was an increase of US$ 2 million (KES 197 million) considering the screening costs of undiagnosed T2D in the country. The major cost driver representing 59% of the overall costs was attributed to T2D complications, with nephropathy having the highest estimated costs of care and management (US$ 332 million (KES 36, 457 million). The total cost for T2D was projected to rise to US$ 1.6 billion (KES 177 billion) in 2045. Conclusion This study shows that T2D imposes a huge burden on Kenya’s healthcare system. There is a need for government and societal action to develop and implement policies that prevent T2D, and appropriately plan care for those diagnosed with T2D.

Abstract Background During the 2021–22 academic year, Massachusetts supported several in-school testing programs to facilitate in-person learning. Additionally, COVID-19 vaccines became available to all school-aged children and many were infected with SARS-CoV-2. There are limited studies evaluating the impacts of these testing programs on SARS-CoV-2 cases in elementary and secondary school settings. The aim of this state-wide, retrospective cohort study was to assess the impact of testing programs and immunity on SARS-CoV-2 case rates in elementary and secondary students. Methods Community-level vaccination and cumulative incidence rates were combined with data about participation in and results of in-school testing programs (test-to-stay, pooled surveillance testing). School-level impacts of surveillance testing programs on SARS-CoV-2 cases in students were estimated using generalized estimating equations within a target trial emulation approach stratified by school type (elementary/middle/high). Impacts of immunity and vaccination were estimated using random effects linear regression. Results Here we show that among N = 652,353 students at 2141 schools participating in in-school testing programs, surveillance testing is associated with a small but measurable decrease in in-school positivity rates. During delta, pooled testing positivity rates are higher in communities with higher cumulative incidence of infection. During omicron, when immunity from prior infection became more prevalent, the effect reversed, such that communities with lower burden of infection during the earlier phases of the pandemic had higher infection rates. Conclusions Testing programs are an effective strategy for supporting in-person learning. Fluctuating levels of immunity acquired via natural infection or vaccination are a major determinant of SARS-CoV-2 cases in schools.

Abstract Background Childhood mortality persists as a significant public health challenge in low and middle-income countries and is uneven within countries, with poor communities such as urban informal settlements bearing the highest burden. There is limited literature from urban informal settlements on the risk factors of mortality. We assessed under-five mortality and associated risk factors from the period 2002 to 2018 in Nairobi urban informal settlements. Methods We used secondary data from the Nairobi Urban Health and Demographic Surveillance System (NUHDSS), a longitudinal surveillance platform that routinely collects individual and household-level data in two informal settlements (Viwandani and Korogocho) in Nairobi, Kenya. We used Kaplan-Meier curves to estimate overall survival and the Cox proportional hazard model with a frailty term to evaluate the impact of risk factors on survival time. Results Overall under-five survival rate was 96.8% and this improved from 82.6% (2002-2006) to 95% (2007-2012) and 98.4% (2012-2018). There was a reduced risk of mortality among children who had BCG vaccination, those born to a married mother or a mother not engaging in any income-generating activity (both from 2007 to 2011), children from singleton pregnancy, children born in Viwandani slum and ethnicity of the child. Conclusion Under-five mortality is still high in urban informal settlements. Targeted public health interventions such as vaccinations and interventions empowering women such as single mothers, those with multiple pregnancies, and more impoverished slums are needed to further reduce under-five mortality in urban informal settlements.

Abstract PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2. Ligands were identified that engage the C-degron binding site in KLHDC2, subjected to structure-based improvement, and linked to JQ1 for BET-family neo-substrate recruitment. Consideration of the exit vector emanating from the ligand engaged in KLHDC2’s U-shaped degron-binding pocket enabled generation of SJ46421, which drives formation of a remarkably cooperative, paralog-selective ternary complex with BRD3BD2. Meanwhile, screening pro-drug variants enabled surmounting cell permeability limitations imposed by acidic moieties resembling the KLHDC2-binding C-degron. Selectivity for BRD3 compared to other BET-family members is further manifested in ubiquitylation in vitro, and prodrug version SJ46420-mediated degradation in cells. Selectivity is also achieved for the ubiquitin ligase, overcoming E3 auto-inhibition to engage KLHDC2, but not the related KLHDC1, KLHDC3, or KLHDC10 E3s. In sum, our study establishes neo-substrate-specific targeted protein degradation via KLHDC2, and provides a framework for developing selective PROTAC protein degraders employing C-degron E3 ligases.

Abstract Cerebral dopamine neurotrophic factor (CDNF) is an unconventional neurotrophic factor that is a disease-modifying drug candidate for Parkinson’s disease. CDNF has pleiotropic protective effects on stressed cells, but its mechanism of action remains incompletely understood. Here, we use state-of-the-art advanced structural techniques to resolve the structural basis of CDNF interaction with GRP78, the master regulator of the unfolded protein response (UPR) pathway. Subsequent binding studies confirm the obtained structural model of the complex, eventually revealing the interaction site of CDNF and GRP78. Finally, mutating the key residues of CDNF mediating its interaction with GRP78 not only results in impaired binding of CDNF but also abolishes the neuroprotective activity of CDNF-derived peptides in mesencephalic neuron cultures. These results suggest that the molecular interaction with GRP78 mediates the neuroprotective actions of CDNF and provide a structural basis for development of next generation CDNF-based therapeutic compounds against neurodegenerative diseases.

Abstract Complexity is inherent in most biological phenomena, yet there is little effort to teach biological complexity per se in the classroom. Levels of organization and hierarchical complexity are familiar features of living systems and taken for granted in most instructional materials including the Next Generation Science Standards (NGSS) of the United States. However, the evolution of the hierarchical organization of life is not being taught because there has been no instructional framework for doing so until now. We seek to address this gap in instruction by translating recent research on evolutionary transitions in individuality (ETI theory) into an integrative, instructional framework for teaching the hierarchy of life that aligns with the three dimensions of the NGSS. ETI theory presents an evolutionary framework for teaching hierarchical complexity using the social principles of cooperation and conflict. These principles are intuitive for students because they are analogous to many of the social situations in their lives. By making use of the ETI framework, instructors can explicitly teach the evolution of the hierarchical organization of life, the organizing framework for all of biology.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated diseases. The pathophysiology of COVID-19 uses the following three mechanisms: (1) inflammasome activation mechanism; (2) cGAS–STING signaling mechanism; and (3) SAMHD1 tetramerization mechanism, which leads to IFN-I production. Interactions between the host and virus govern induction, resulting in multiorgan impacts. The NLRP3 with cGAS–STING constitutes the primary immune response. The expression of SARS-CoV-2 ORF3a, NSP6, NSP7, and NSP8 blocks innate immune activation and facilitates virus replication by targeting the RIG-I/MDA5, TRIF, and cGAS–STING signaling. SAMHD1 has a target motif for CDK1 to protect virion assembly, threonine 592 to modulate a catalytically active tetramer, and antiviral IFN responses to block retroviral infection. Plastic and allosteric nucleic acid binding of SAMHD1 modulates the antiretroviral activity of SAMHD1. Therefore, inflammasome activation, cGAS–STING signaling, and SAMHD1 tetramerization explain acute kidney injury, hepatic, cardiac, neurological, and gastrointestinal injury of COVID-19. It might be necessary to effectively block the pathological courses of diverse diseases.

Abstract Background Tuberculosis (TB) preventive treatment (TPT) is a long-standing recommendation for children exposed to TB but remains poorly implemented. Home-based contact management may increase access and coverage of TPT among children exposed to TB in their households. Methods Sixty in-depth interviews were conducted with key informants including program managers, TB providers (known as TB focal persons), health extension workers and caregivers whose children had recently engaged with TB prevention services in Oromia, Ethiopia in 2021 to understand the barriers and facilitators to providing home-based TB prevention services for children aged

ABSTRACTSince the first genetically engineered or modified crops or organisms (GMO) were approved for commercial production in 1995, no new GMO has been proven to be a hazard or cause harm to human consumers. These modifications have improved crop efficiency, reduced losses to insect pests, reduced losses to viral and microbial plant pathogens and improved drought tolerance. A few have focused on nutritional improvements producing beta carotene in Golden Rice. Regulators in the United States and countries signing the CODEX Alimentarius and Cartagena Biosafety agreements have evaluated human and animal food safety considering potential risks of allergenicity, toxicity, nutritional and anti-nutritional risks. They consider risks for non-target organisms and the environment. There are no cases where post-market surveillance has uncovered harm to consumers or the environment including potential transfer of DNA from the GMO to non-target organisms. In fact, many GMOs have helped improve production, yield and reduced risks from chemical insecticides or fungicides. Yet there are generic calls to label foods containing any genetic modification as a GMO and refusing to allow GM events to be labeled as organic. Many African countries have accepted the Cartagena Protocol as a tool to keep GM events out of their countries while facing food insecurity. The rationale for those restrictions are not rational. Other issues related to genetic diversity, seed production and environmental safety must be addressed. What can be done to increase acceptance of safe and nutritious foods as the population increases, land for cultivation is reduced and energy costs soar?

Abstract The objective of this study was to evaluate the function, and usability of a novel automated software-guided cryostorage system in an active IVF laboratory setting. The investigational device (ID) was installed at 3 IVF laboratories (sites: α, β, and γ). A total of 15 embryologists were trained to use the ID. Mock patient specimens containing mirrored live patient data were handled using the ID. Temperature readings were recorded every minute. Successful identification, storage, and retrieval of mock patient specimens by the ID were evaluated. To assess an LN2 pressure builder, the frequency of use and events of workflow interruption were logged. Student’s t-test was used to determine statistical significance. The ID was in active use for 164 days total. During this time, 329 mock patient egg and embryo cohorts were handled by the ID. The mean ± SD temperatures during active use were: α, − 176.57 ± 1.83 °C; β, − 178.21 ± 2.75 °C; γ, − 178.98 ± 1.74 and did not differ significantly. The highest recorded temperatures were: α, − 165.14 °C; β, − 157.41 °C; γ, − 164.45 °C. A total of 1064 automation transactions on 409 specimen vessels were performed. Data was managed on 1501 eggs and embryos. The ID did not lose or misplace any specimen data or vessels, and no mock specimen was exposed to a detrimental (> − 150 °C) temperature excursion. Over the 25 LN2 pressure builder usages during 99 total days, there was 1 occurrence where usage interrupted workflow due to a lack of LN2 pressure. The ID has advantages over the current manual-based cryostorage systems, including radio frequency identification (RFID) tracking, automation of manual tasks, and software guidance to ensure accurate specimen storage and retrieval. The results of this study indicate that the ID can be integrated into active IVF laboratories.

Background and objective: Micro-ultrasound (MUS) uses a high-frequency transducer with superior resolution to conventional ultrasound, which may differentiate prostate cancer from normal tissue and thereby allow targeted biopsy. Preliminary evidence has shown comparable sensitivity to magnetic resonance imaging (MRI), but consistency between users has yet to be described. Our objective was to assess agreement of MUS interpretation across multiple readers. Methods: After institutional review board approval, we prospectively collected MUS images for 57 patients referred for prostate biopsy after multiparametric MRI from 2022 to 2023. MUS images were interpreted by six urologists at four institutions with varying experience (range 2–6 yr). Readers were blinded to MRI results and clinical data. The primary outcome was reader agreement on the locations of suspicious lesions, measured in terms of Light’s κ and positive percent agreement (PPA). Reader sensitivity for identification of grade group (GG) ≥2 prostate cancer was a secondary outcome. Key findings and limitations: Analysis revealed a κ value of 0.30 (95% confidence interval [CI] 0.21–0.39). PPA was 33% (95% CI 25–42%). The mean patient-level sensitivity for GG ≥2 cancer was 0.66 ± 0.05 overall and 0.87 ± 0.09 when cases with anterior lesions were excluded. Readers were 12 times more likely to detect higher-grade cancers (GG ≥3), with higher levels of agreement for this subgroup (κ 0.41, PPA 45%). Key limitations include the inability to prospectively biopsy reader-delineated targets and the inability of readers to perform live transducer maneuvers. Conclusions and clinical implications: Inter-reader agreement on the location of suspicious lesions on MUS is lower than rates previously reported for MRI. MUS sensitivity for cancer in the anterior gland is lacking. Patient summary: The ability to find cancer on imaging scans can vary between doctors. We found that there was frequent disagreement on the location of prostate cancer when doctors were using a new high-resolution scan method called micro-ultrasound. This suggests that the performance of micro-ultrasound is not yet consistent enough to replace MRI (magnetic resonance imaging) for diagnosis of prostate cancer.

Glioblastomas synthesize, bear receptors for, and respond to bradykinin, triggering migration and proliferation. Since centrifugal migration into uninvolved surrounding brain tissue occurs early in the course of glioblastoma, this attribute defeats local treatment attempts and is the primary reason current treatments almost always fail. Stopping bradykinin-triggered migration would be a step closer to control of this disease. The recent approval and marketing of an oral plasma kallikrein inhibitor, berotralstat (Orladeyo™), and pending FDA approval of a similar drug, sebetralstat, now offers a potential method for reducing local bradykinin production at sites of bradykinin-mediated glioblastoma migration. Both drugs are approved for treating hereditary angioedema. They are ideal for repurposing as a treatment adjunct in glioblastoma. Furthermore, it has been established that peritumoral edema, a common problem during the clinical course of glioblastoma, is generated in large part by locally produced bradykinin via kallikrein action. Both brain edema and the consequent use of corticosteroids both shorten survival in glioblastoma. Therefore, by (i) migration inhibition, (ii) growth inhibition, (iii) edema reduction, and (iv) the potential for less use of corticosteroids, berotralstat may be of service in treatment of glioblastoma, slowing disease progression. This paper recounts the details and past research on bradykinin in glioblastoma and the rationale of treating it with berotralstat.

Abstract Background Transcutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects. Methods/design The study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p

Abstract One of the most used self-administered instruments to assess persecutory delusions is the Persecutory Ideation Questionnaire (PIQ). Individual differences in PIQ scores are important because they predict the severity of symptoms associated with psychosis-related disorders. The current research demonstrates that PIQ is associated with two new outcomes: Satisfaction with life (Studies 1 and 2) and therapy length needed for hospital discharge (Study 2). Most relevant, we introduce meta-cognitive confidence in one’s scale responses as a construct capable of improving the predictive validity of the PIQ. Across two studies, participants from the general population (Study 1) and from a clinical sample (Study 2) completed the PIQ and then reported the confidence in their responses. As expected, the PIQ was associated with satisfaction with life in both cases and duration of therapy required to receive hospital discharge for the clinical sample. Most importantly, confidence further moderated the extent to which the PIQ scores were linked with both outcomes, with greater consistency between the PIQ and the dependent measures obtained for those with higher confidence. Therefore, asking a single item about the confidence associated with responses to the PIQ enhances the association of PIQ scores and relevant consequences across domains.

Lavandula angustifolia Mill., lavender, is an aromatic plant in the Lamiaceae family. Lavender is an important economic plant that is cultivated throughout the world. Previous studies have shown that the primary pollinators of lavender in Europe and North Africa are bee species, specifically Bombus spp. However, similar studies have not been previously performed in North America. The current study, on cultivated population lavender (grown from seed) in Utah (USA), found a diverse community of bees visiting lavender over a 4-week sequential and successive blooming period. The observed and identified bees were distinguished across 8 genera and 12 species, of which 3 were species not native to North America. The most observed bees were Apis mellifera (88.3%), Bombus fervidus (4.2%), and B. huntii (3.7%). To investigate seed production and viability, lavender plants were either caged off and their access withheld from pollinators, or selectively granted access to various pollinators, to determine (1) if lavender is capable of self-pollination, (2) if pollination increases both the seed production rates and seed viability of lavender, and (3) which bee species are the most efficient pollinators of lavender. The findings from this study demonstrate the ecological interactions between pollinators both native and non-native to North America on lavender, a plant native to the Mediterranean region.

Abstract Introduction Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. Methods This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019–2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants’ experiences with AEs also were collected for the COVID-19 vaccine recipients. Results Females were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. Conclusions Our findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women.

BackgroundCurrent diving physiology postulates that SCUBA divers’ arterial blood gas (ABG) levels vary proportionally to environmental pressure, but, to date, ABGs have only been obtained during simulated dives. Also, recent evidence supports the use of the arterial/alveolar (a:A) partial pressures of oxygen (PO2) ratio to predict the arterial PO2 (PaO2) under hyperbaric conditions from measurements obtained at 1 atmosphere absolute (ATA). This work summarizes ABGs obtained in SCUBA divers in real underwater conditions and aims to validate the a:A ratio in predicting PaO2 in this subset of individuals at depth.MethodsThe study was approved by the local ethics committee. After cannulating the radial artery of the non-dominant limb, ABGs were sampled at the surface before the dive (A), at depth (15 meters of freshwater (mfw) or 42 mfw) before (B) and after (C) pedaling on a submersed bicycle for 10 minutes, and back at surface (D). After calculating the surface alveolar PO2 for each subject, the a:A ratio was obtained and used to predict PaO2 at depth. A linear regression between measured and predicted PaO2 was reported, along with the goodness-of-fit F test.ResultsSix subjects performed the dive at 15 mfw, and four others at 42 mfw. The PaO2 proportionally increased at both depths, remaining stable before and after pedaling. The a:A calculated from the baseline ABG obtained at rest, out of the water, adequately predicted the PaO2 at depth (R2 = 0.97, p

Abstract Objective Learning Health Systems (LHSs) have not directly informed evidence‐based policymaking. The Translation‐to‐Policy (T2P) Learning Cycle aligns scientists, end‐users, and policymakers to support a repeatable roadmap of innovation and quality improvement to optimize effective policies toward a common public health goal. We describe T2P learning cycle components and provide examples of their application. Methods The T2P Learning Cycle is based on the U.S. Department of Veterans Affairs (VA) Office of Research and Development and Quality Enhancement Research Initiative (QUERI), which supports research and quality improvement addressing national public health priorities to inform policy and ensure programs are evidence‐based and work for end‐users. Incorporating LHS infrastructure, the T2P Learning Cycle is responsive to the Foundations for Evidence‐based Policymaking Act, which requires U.S. government agencies to justify budgets using evidence. Results The learning community (patients, providers, clinical/policy leaders, and investigators) drives the T2P Learning Cycle, working toward one or more specific, shared priority goals, and supports a repeatable cycle of evidence‐building and evaluation. Core T2P Learning Cycle functions observed in the examples from housing/economic security, precision oncology, and aging include governance and standard operating procedures to promote effective priority‐setting; complementary research and quality improvement initiatives, which inform ongoing data curation at the learning system level; and sustainment of continuous improvement and evidence‐based policymaking. Conclusions The T2P Learning Cycle integrates research translation with evidence‐based policymaking, ensuring that scientific innovations address public health priorities and serve end‐users through a repeatable process of research and quality improvement that ensures policies are scientifically based, effective, and sustainable.

Abstract Long‐lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long‐term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with 89Zr‐labeled bioadhesive nanoparticles (BNPs) in non‐human primates. We additionally examined the safety of repeated BNP application. BNPs administered vaginally to cynomolgus monkeys were still detected after 24 h (1.7% retention) and 120 h (0.1% retention). BNPs did not translocate to the uterus or into systemic circulation. Analysis of inflammatory biomarkers in the vaginal fluid and plasma suggest that BNPs are safe and biocompatible, even after multiple doses. BNPs are a promising delivery vehicle for vaginally administered therapeutics. Further studies using the non‐human primate imaging materials and methods developed here could help advance clinical translation of BNPs and other long‐lasting vaginal dosage forms.

Objective:. To identify factors associated with incident alcohol consumption, hazardous drinking, alcohol-related problems, and substance use up to 8 years following metabolic and bariatric surgery (MBS) during adolescence. Background:. In this cohort, nearly half of those who underwent MBS as adolescents screened positive for alcohol use disorder, symptoms of alcohol-related harm, or alcohol-related problems within 8 years post-surgery. Moreover, persistent or heavy marijuana use following MBS during adolescence is higher than national data. Methods:. This study includes 217 adolescents (aged 13–19 years) enrolled in a 5-center prospective cohort study who underwent Roux-en-Y gastric bypass or vertical sleeve gastrectomy between 2007 and 2011 and were followed for up to 8 years. Participants self-reported alcohol use via the Alcohol Use Disorders Identification Test and substance use for up to 8 years. Results:. Female sex, pre-surgery lower body mass index, and pre-surgery substance use were independently associated with increased risk of incident post-surgery hazardous drinking. Pre-surgery psychiatric counseling was significantly associated with increased risk for new-onset substance use post-surgery. Starting substance use post-surgery or continuing pre- to post-surgery was independently associated with a higher risk of post-surgery hazardous drinking. Greater percent weight loss, starting post-surgery or continuing pre- to post-surgery psychiatric counseling, using alcohol, and hazardous drinking were independently associated with a higher risk of post-surgery substance use. Conclusions:. Future research with a nonsurgical control group should be examined to further elucidate the relationships between MBS and alcohol and substance use following surgery during adolescence.

BackgroundAll federal agencies are required to support appropriation requests with evidence and evaluation (US Public Law 115-435; the Evidence Act). The StrAtegic PoLicy EvIdence-Based Evaluation CeNTer (SALIENT) is 1 of 6 centers that help the Department of Veterans Affairs (VA) meet this requirement. ObjectiveWorking with the existing VA evaluation structure, SALIENT evaluations will contribute to (1) optimize policies and programs for veteran populations; (2) improve outcomes regarding health, equity, cost, and provider well-being; (3) advance the science of dissemination and knowledge translation; and (4) expand the implementation and dissemination science workforce. MethodsWe leverage the Lean Sprint methodology (iterative, incremental, rule-governed approach to clearly defined, and time-boxed work) and 3 cores to develop our evaluation plans collaboratively with operational partners and key stakeholders including veterans, policy experts, and clinicians. The Operations Core will work with evaluation teams to develop timelines, facilitate work, monitor progress, and guide quality improvement within SALIENT. The Methods Core will work with evaluation teams to identify the most appropriate qualitative, quantitative, and mixed methods approaches to address each evaluation, ensure that the analyses are conducted appropriately, and troubleshoot when problems with data acquisition and analysis arise. The Knowledge Translation (KT) Core will target key partners and decision makers using a needs-based market segmentation approach to ensure that needs are incorporated in the dissemination of knowledge. The KT Core will create communications briefs, playbooks, and other materials targeted at these market segments to facilitate implementation of evidence-based practices and maximize the impact of evaluation results. ResultsThe SALIENT team has developed a center infrastructure to support high-priority evaluations, often to be responsive to shifting operational needs and priorities. Our team has engaged in our core missions and operations to rapidly evaluate a high-priority areas, develop a comprehensive Lean Sprint systems redesign approach to training, and accelerate rapid knowledge translation. ConclusionsWith an array of interdisciplinary expertise, operational partnerships, and integrated resources, SALIENT has an established and evolving infrastructure to rapidly develop and implement high-impact evaluations. Projects are developed with sustained efficiency approaches that can pivot to new priorities as needed and effectively translate knowledge for key stakeholders and policy makers, while creating a learning health system infrastructure to foster the next generation of evaluation and implementation scientists. International Registered Report Identifier (IRRID)PRR1-10.2196/59830

IntroductionThe goal of this study is to determine whether two commonly used generative learning activities for text-based lessons—writing a summary or creating a drawing—help students learn from a multimedia lesson involving animations with short text captions without prior training in the generative activities.MethodsStudents viewed a series of four annotated animations on greenhouse gases. During pauses between the animations, students were asked to generate a written summary, to create a drawing, or to do both, whereas a control group viewed the lesson without any generative learning activities. Students were tested immediately (Experiment 1) or after a one-week delay (Experiment 2).ResultsIn both experiments, students who produced written summaries scored significantly higher on the posttest than those who engaged in no generative learning activities (d = 0.48 in Experiment 1, d = 0.54 in Experiment 2), but there was no significant difference on the posttest for students who generated drawings compared to those who engaged in no generative learning activities. In addition, those who engaged in drawing and summarizing did not have significantly different posttest performance than those engaged in summarizing alone.DiscussionWe conclude that writing summaries during a highly visual animated lesson is effective for learning, possibly because it encourages students to engage in generative processing during learning more than drawing and we discuss potential reasons for this in the discussion. This work helps extend generative learning theory by pinpointing potential boundary conditions for learning by drawing and learning by summarizing.

Abstract Background Since the 1990s, evidence has accumulated that macrophages promote peripheral nerve regeneration and are required for enhancing regeneration in the conditioning lesion (CL) response. After a sciatic nerve injury, macrophages accumulate in the injury site, the nerve distal to that site, and the axotomized dorsal root ganglia (DRGs). In the peripheral nervous system, as in other tissues, the macrophage response is derived from both resident macrophages and recruited monocyte-derived macrophages (MDMs). Unresolved questions are: at which sites do macrophages enhance nerve regeneration, and is a particular population needed. Methods Ccr2 knock-out (KO) and Ccr2 gfp/gfp knock-in/KO mice were used to prevent MDM recruitment. Using these strains in a sciatic CL paradigm, we examined the necessity of MDMs and residents for CL-enhanced regeneration in vivo and characterized injury-induced nerve inflammation. CL paradigm variants, including the addition of pharmacological macrophage depletion methods, tested the role of various macrophage populations in initiating or sustaining the CL response. In vivo regeneration, measured from bilateral proximal test lesions (TLs) after 2 d, and macrophages were quantified by immunofluorescent staining. Results Peripheral CL-enhanced regeneration was equivalent between crush and transection CLs and was sustained for 28 days in both Ccr2 KO and WT mice despite MDM depletion. Similarly, the central CL response measured in dorsal roots was unchanged in Ccr2 KO mice. Macrophages at both the TL and CL, but not between them, stained for the pro-regenerative marker, arginase 1. TL macrophages were primarily CCR2-dependent MDMs and nearly absent in Ccr2 KO and Ccr2 gfp/gfp KO mice. However, there were only slightly fewer Arg1+ macrophages in CCR2 null CLs than controls due to resident macrophage compensation. Zymosan injection into an intact WT sciatic nerve recruited Arg1+ macrophages but did not enhance regeneration. Finally, clodronate injection into Ccr2 gfp KO CLs dramatically reduced CL macrophages. Combined with the Ccr2 gfp KO background, depleting MDMs and TL macrophages, and a transection CL, physically removing the distal nerve environment, nearly all macrophages in the nerve were removed, yet CL-enhanced regeneration was not impaired. Conclusions Macrophages in the sciatic nerve are neither necessary nor sufficient to produce a CL response.

Abstract Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p

Abstract Purpose To characterize current lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI +) health-related undergraduate medical education (UME) curricular content and associated changes since a 2011 study and to determine the frequency and extent of institutional instruction in 17 LGBTQI + health-related topics, strategies for increasing LGBTQI + health-related content, and faculty development opportunities. Method Deans of medical education (or equivalent) at 214 allopathic or osteopathic medical schools in Canada and the United States were invited to complete a 36-question, Web-based questionnaire between June 2021 and September 2022. The main outcome measured was reported hours of LGBTQI + health-related curricular content. Results Of 214 schools, 100 (46.7%) responded, of which 85 (85.0%) fully completed the questionnaire. Compared to 5 median hours dedicated to LGBTQI + health-related in a 2011 study, the 2022 median reported time was 11 h (interquartile range [IQR], 6–16 h, p

Abstract In a previous report, we demonstrated that Cbx1, PurB and Sp3 inhibited cardiac muscle differentiation by increasing nucleosome density around cardiac muscle gene promoters. Since cardiac and skeletal muscle express many of the same proteins, we asked if Cbx1, PurB and Sp3 similarly regulated skeletal muscle differentiation. In a C2C12 model of skeletal muscle differentiation, Cbx1 and PurB knockdown increased myotube formation. In contrast, Sp3 knockdown inhibited myotube formation, suggesting that Sp3 played opposing roles in cardiac muscle and skeletal muscle differentiation. Consistent with this finding, Sp3 knockdown also inhibited various muscle-specific genes. The Cbx1, PurB and Sp3 proteins are believed to influence gene-expression in part by altering nucleosome position. Importantly, we developed a statistical approach to determine if changes in nucleosome positioning were significant and applied it to understanding the architecture of muscle-specific genes. Through this novel statistical approach, we found that during myogenic differentiation, skeletal muscle-specific genes undergo a set of unique nucleosome changes which differ significantly from those shown in commonly expressed muscle genes. While Sp3 binding was associated with nucleosome loss, there appeared no correlation with the aforementioned nucleosome changes. In summary, we have identified a novel role for Sp3 in skeletal muscle differentiation and through the application of quantifiable MNase-seq have discovered unique fingerprints of nucleosome changes for various classes of muscle genes during myogenic differentiation.

Abstract Carbon-based nanomaterials, such as carbon nanoplatelets, graphene oxide, and carbon quantum dots, have many possible end-use applications due to their ability to impart unique mechanical, electrical, thermal, and optical properties to cement composites. Despite this potential, these materials are rarely used in the construction industry due to high material costs and limited data on performance and durability. In this study, domestic coal is used to fabricate low-cost carbon nanomaterials that can be used economically in cement formulations. A range of chemical and physical processing approaches are employed to control the size, morphology, and chemical functionalization of the carbon nanomaterial, which improves its miscibility with cement formulations and its impact on mechanical properties and durability. At loadings of 0.01 to 0.07 wt.% of coal-derived carbon nanomaterial, the compressive and flexural strength of cement samples are enhanced by 24% and 23%, respectively, in comparison to neat cement. At loadings of 0.02 to 0.06 wt.%, the compressive and flexural strength of concrete composites increases by 28% and 21%, respectively, in comparison to neat samples. Additionally, the carbon nanomaterial additives studied in this work reduce cement porosity by 36%, permeability by 86%, and chloride penetration depth by 60%. These results illustrate that low-loadings of coal-derived carbon nanomaterial additives can improve the mechanical properties, durability, and corrosion resistance of cement composites.

Abstract Sexually transmitted infections (STIs) are common among adolescents. According to the Health Belief Model, cues to action influence preventive behaviors. Cues to action can include health experiences such as being diagnosed with an STI. The impact of a history of STIs on subsequent condom use among adolescents remains largely unexamined, despite high rates of recurrence and their health impacts. This project aimed to systematically review the literature on the association between curable STIs and subsequent condom use among adolescents. The systematic review, reported following PRISMA guidelines, was conducted using the Joanna Briggs Institute method. Eligible studies, in the form of cohort studies, case-control studies, or cross-sectional studies, targeted adolescents aged 10 to 24, with or without a history of curable STIs; the outcome was subsequent condom use. MEDLINE (Ovid), Embase (Elsevier), and Web of Science were searched from January 2012 to December 2022 with the assistance of an information specialist. Two reviewers independently selected articles and extracted data. Risk of bias analysis was performed using ROBINS-E. The review explores results, with tables, based on population characteristics, exposure, and outcome, and addresses the influence of gender, ethnicity, and age. Of 3088 articles identified, seven studies were retained. Almost all the studies focused on African-American, Nigerian, or Rwandan adolescents, and several included only girls. Among girls, a history of STI increased subsequent condom use in combination with other contraceptive methods (n = 4). Among boys and older adolescents of both genders, a history of STI was associated with a decrease in condom use (n = 3). No study distinguished between different STIs. While all the studies (n = 7) presented a high risk of bias, six did not present a threat to conclusion validity. All the studies indicated that a history of STI could influence subsequent protective behaviors, possibly by acting as a cue to action, as posited by the Health Belief Model. This information enhances our understanding of factors leading to the adoption of preventive health measures among adolescents and could apply to other infectious experiences. Registration The protocol is registered in PROSPERO (CRD42023397443).

Abstract Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive “transient” and “durable” expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination.

Abstract Background Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP. Methods/design This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2–125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p

Rice is the dominant food staple and an important economic resource throughout Asia. Lowland rice production also provides important wetland habitats in support of biodiversity that may provide ecosystem services back to the rice agroecosystems. This review summarizes the literature on the ecosystem benefits that amphibians, birds, bats, and rodents support in the context of the Southeast Asia rice agroecosystems. The literature provides evidence that these taxonomic groups contribute to cultural, regulatory, and provisioning services in support of smallholder farmers and may allow for economic benefits through reduced use of chemical inputs into crops. We encourage a multipronged research approach to bring stakeholders together to provide structured and scalable education programs that will lead to improved human and agroecosystem health through the promotion of understanding the positive feedbacks from biodiversity in these important agricultural wetland habitats.

Abstract Sickle cell disease (SCD) is a genetic disorder causing painful and unpredictable Vaso-occlusive crises (VOCs) through blood vessel blockages. In this study, we propose explosive synchronization (ES) as a novel approach to comprehend the hypersensitivity and occurrence of VOCs in the SCD brain network. We hypothesized that the accumulated disruptions in the brain network induced by SCD might lead to strengthened ES and hypersensitivity. We explored ES's relationship with patient reported outcome measures (PROMs) as well as VOCs by analyzing EEG data from 25 SCD patients and 18 matched controls. SCD patients exhibited lower alpha frequency than controls. SCD patients showed correlation between frequency disassortativity (FDA), an ES condition, and three important PROMs. Furthermore, stronger FDA was observed in SCD patients with a higher frequency of VOCs and EEG recording near VOC. We also conducted computational modeling on SCD brain network to study FDA's role in network sensitivity. Our model demonstrated that a stronger FDA could be linked to increased sensitivity and frequency of VOCs. This study establishes connections between SCD pain and the universal network mechanism, ES, offering a strong theoretical foundation. This understanding will aid predicting VOCs and refining pain management for SCD patients.

Abstract Prostate cancer pathology plays a crucial role in clinical management but is time-consuming. Artificial intelligence (AI) shows promise in detecting prostate cancer and grading patterns. We tested an AI-based digital twin of a pathologist, vPatho, on 2603 histological images of prostate tissue stained with hematoxylin and eosin. We analyzed various factors influencing tumor grade discordance between the vPatho system and six human pathologists. Our results demonstrated that vPatho achieved comparable performance in prostate cancer detection and tumor volume estimation, as reported in the literature. The concordance levels between vPatho and human pathologists were examined. Notably, moderate to substantial agreement was observed in identifying complementary histological features such as ductal, cribriform, nerve, blood vessel, and lymphocyte infiltration. However, concordance in tumor grading decreased when applied to prostatectomy specimens (κ = 0.44) compared to biopsy cores (κ = 0.70). Adjusting the decision threshold for the secondary Gleason pattern from 5 to 10% improved the concordance level between pathologists and vPatho for tumor grading on prostatectomy specimens (κ from 0.44 to 0.64). Potential causes of grade discordance included the vertical extent of tumors toward the prostate boundary and the proportions of slides with prostate cancer. Gleason pattern 4 was particularly associated with this population. Notably, the grade according to vPatho was not specific to any of the six pathologists involved in routine clinical grading. In conclusion, our study highlights the potential utility of AI in developing a digital twin for a pathologist. This approach can help uncover limitations in AI adoption and the practical application of the current grading system for prostate cancer pathology.

Background The COVID-19 pandemic affected healthcare delivery globally, impacting care access and delivery of essential services. Objectives We investigated the pandemic’s impact on care for patients with type 2 diabetes and factors associated with care disruption in Kenya and Tanzania. Methods A cross-sectional study was conducted among adults diagnosed with diabetes pre-COVID-19. Data were collected in February–April 2022 reflecting experiences at two time-points, three months before and the three months most affected by the COVID-19 pandemic. A questionnaire captured data on blood glucose testing, changes in medication prescription and access, and healthcare provider access. Results We recruited 1000 participants (500/country). Diabetes care was disrupted in both countries, with 34.8% and 32.8% of the participants reporting change in place and frequency of testing in Kenya, respectively. In Tanzania, 12.4% and 17.8% reported changes in location and frequency of glucose testing, respectively. The number of health facility visits declined, 14.4% (p

Purpose: To characterize the early postoperative complications following outpatient tibial tubercle osteotomy (TTO) to determine its safety in this setting. Methods: Patients undergoing TTO by a single surgeon between July 2017 and August 2022 for patellar instability or patellofemoral chondromalacia and achieving a minimum of 3 months of clinical and radiographic follow-up were evaluated for inclusion. Although an inclusion criterion was a minimum follow-up of 3 months, if evidence of a healed osteotomy was observed sooner, final follow-up was accepted at 2 months. Patient demographics, perioperative risk factors, and incidence of complications were collected retrospectively. Categorical data were analyzed using χ2 and Fisher exact tests. Continuous data were analyzed using 2-tailed t tests and Mann-Whitney U data for parametric and nonparametric data, respectively. Results: A total of 195 knees in 167 patients met inclusion criteria, with a mean age of 24.7 ± 9.2 years and mean follow-up time of 10.9 months (range, 2-69 months). Fifty-one early postoperative complications occurred in 47 (24.1%) knees in 42 (25.1%) patients. Ten major and 41 minor complications occurred. Major complications were associated with older age (P = .015), smoking (P = .038), and smaller preoperative patellar tendon–lateral trochlear ridge distance (P = .012). Forty-four reoperations occurred in 42 (21.5%) knees in 37 (22.2%) patients. The most common reasons for reoperation included removal of symptomatic hardware (31 knees; 15.9%) and arthrofibrosis requiring lysis of adhesions and manipulation under anesthesia (8 knees; 4.1%). The mean time to reoperation was 13.0 months (range, 1-42 months). Smaller body mass index was associated with increased risk of reoperation (P = .002). Conclusions: Outpatient TTO is safe when performed with the described technique, but the later development of minor complications is not infrequent following surgery. Patients should be counseled regarding a relatively high incidence of hardware irritation, arthrofibrosis, and eventual reoperation. Level of Evidence: Level IV, case series.

Introduction COVID-19 affected healthcare access, utilisation and affordability, especially for patients suffering from chronic diseases, including type 2 diabetes (T2D). This study measured the occurrence and magnitude of changes in healthcare and broader societal costs among patients with T2D before and during COVID-19 in Kenya and Tanzania to understand whether and how COVID-19 affected T2D management in countries implementing different policies during the pandemic.Methods A cross-sectional study was conducted in Kenya and Tanzania in March–April 2022 among 500 patients with T2D in each country. We interviewed patients on direct healthcare costs (eg, inpatient and outpatient costs), societal costs (eg, productivity loss) and patients’ characteristics before and during the COVID-19 pandemic. We estimated changes over time using the Generalised Linear Model in Kenya and a two-part model in Tanzania, adjusting for patient-level covariates.Results The overall costs of management of T2D in most categories increased in both countries during COVID-19, but some of the increase was not significant. Transport and testing costs increased significantly in Tanzania (I$0.33, p

Research inspired by collective action theory has provoked a rethinking of premodern governance, including state formation. We briefly summarize key elements of this theoretical turn, first, by demonstrating that, as predicted by the existing theory, political collective action is enhanced when the provision of good government motivates taxpayer compliance. Beyond that key process, our cross-cultural comparative investigation identified a suite of corollary social and cultural factors, including civic ritual, that, side-by-side with good government, served to undergird the institution of political collective action. We investigate, in particular, policies and practices that fostered the transformation of what had been a dominated and socially fragmented subaltern into a politically engaged and conditionally compliant citizenry. We discuss this process in relation to administrative policies and practices and in relation to evidence we found for directed cultural change purposed to enhance consensus and forbearance in the face of social divisiveness and political inequality.

Herein, the stabilization of 2D single‐atom high gold rafts containing up to ≈60 Au atoms on amorphous carbon, fabricated by sputtering of atoms and imaged by aberration‐corrected scanning transmission electron microscopy, is demonstrated. These rafts deviate from the established cluster transition from 2D to 3D Au structural motifs in free clusters, which occurs in the region of 10–14 atoms. The experimental findings are supported by explicit ab initio calculations of Aun (n = 3–147) clusters on graphene and the role of cluster–surface interactions in the stabilization of the 2D single‐atom high Au cluster rafts on graphene is revealed. The transition from equilibrium 2D–3D structures is delayed to n = 19, while metastable 2D single‐atom high rafts compete with 3D structures up to about n = 60 atoms. The catalytic activity of supported nanoclusters depends strongly on their structure (and carbon‐based supports are used for a number of reactions); therefore these results are relevant to the catalytic performance of nanocluster‐based catalysts.

Body condition score (BCS) has been a useful tool in estimating the health of cattle for many years now. This categorical metric requires experienced observers to visually inspect cows and assess body fat deposits regularly via a time consuming, subjective process. Low cost RGB+depth cameras have been used alongside machine learning algorithms in the past and have shown great promise, however, more advanced techniques are projected to yield better performance. In this work, a vision transformer (ViT) is pretrained using a recently developed self-supervised pretraining method, masked image modeling, and then fine-tuned on RGB+depth BCS data with the objective of improving performance. Model accuracy was found to be highly dependent on dataset curation, ranging from 64% to 92% accuracy. These discrepancies are attributed to non-unique data in the training and test splits and an inherently unbalanced dataset, both of which are discussed in detail. It is recommended that engineers and animal scientists collaborate more closely, as certain details related to dataset curation are critical to thoroughly assess performance and robustness of automated methods for BCS determination.

Abstract Purpose To determine whether scapular morphology could predict isolated supraspinatus tendon tear propagation after exercise therapy. We hypothesised that a larger critical shoulder angle (CSA) and type III acromial morphology predict a positive change in tear size. Methods Fifty‐nine individuals aged 40–70 years with isolated symptomatic high‐grade partial or full‐thickness supraspinatus tendon tears were included. Individuals participated in a structured, individualised 12‐week exercise therapy programme and underwent ultrasound to measure tear size at baseline and 12 months following therapy. Computed tomography images were segmented to create three‐dimensional subject‐specific bone models and reviewed by three trained clinicians to measure CSA and to determine acromion morphology based on the Bigliani classification. A binary logistic regression was performed to determine the predictive value of CSA and acromion morphology on tear propagation. Results The CSA was 30.0 ± 5.4°. Thirty‐one individuals (52.5%) had type II acromial morphology, followed by type III and type I morphologies (25.4% and 22.0%, respectively); 81.4% experienced no change in tear size, four (6.8%) individuals experienced tear propagation and seven (11.9%) individuals had a negative change in tear size. No significant difference in tear propagation rates based on CSA or acromion morphology (not significant [NS]) was observed. The model predicted tear size status in 81.4% of cases but only predicted tear propagation 8.3% of the time. Overall, CSA and acromion morphology only predicted 24.3% (R2 = 0.243) of variance in tear propagation (NS). Conclusions CSA and acromion morphology were NS predictors of tear propagation of the supraspinatus tendon 12 months following an individualised exercise therapy programme. Level of Evidence II.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p

BackgroundDengue is an increasing health burden that has spread throughout the tropics and sub-tropics. There is currently no effective vaccine and control is only possible through integrated vector management. Early warning systems (EWS) to alert potential dengue outbreaks are currently being explored but despite showing promise are yet to come to fruition. This study addresses the association of meteorological variables with both mosquito indices and dengue incidences and assesses the added value of additionally using mosquito indices for predicting dengue incidences.Methodology/principal findingsEntomological surveys were carried out monthly for 14 months in six sites spread across three environmentally different cities of the Philippines. Meteorological and dengue data were acquired. Non-linear generalized additive models were fitted to test associations of the meteorological variables with both mosquito indices and dengue cases. Rain and the diurnal temperature range (DTR) contributed most to explaining the variation in both mosquito indices and number of dengue cases. DTR and minimum temperature also explained variation in dengue cases occurring one and two months later and may offer potentially useful variables for an EWS. The number of adult mosquitoes did associate with the number of dengue cases, but contributed no additional value to meteorological variables for explaining variation in dengue cases.Conclusions/significanceThe use of meteorological variables to predict future risk of dengue holds promise. The lack of added value of using mosquito indices confirms several previous studies and given the onerous nature of obtaining such information, more effort should be placed on improving meteorological information at a finer scale to evaluate efficacy in early warning of dengue outbreaks.

Abstract We report a rare regime of Earth's magnetosphere interaction with sub‐Alfvénic solar wind in which the windsock‐like magnetosphere transforms into one with Alfvén wings. In the magnetic cloud of a Coronal Mass Ejection (CME) on 24 April 2023, NASA's Magnetospheric Multiscale mission distinguishes the following features: (a) unshocked and accelerated low‐beta CME plasma coming directly against Earth's dayside magnetosphere; (b) dynamical wing filaments representing new channels of magnetic connection between the magnetosphere and foot points of the Sun's erupted flux rope; (c) cold CME ions observed with energized counter‐streaming electrons, evidence of CME plasma captured due to by reconnection between magnetic‐cloud and Alfvén‐wing field lines. The reported measurements advance our knowledge of CME interaction with planetary magnetospheres, and open new opportunities to understand how sub‐Alfvénic plasma flows impact astrophysical bodies such as Mercury, moons of Jupiter, and exoplanets close to their host stars.

Introduction Even with recent treatment advances, type 2 diabetes (T2D) remains poorly controlled for many patients, despite the best efforts to adhere to therapies and lifestyle modifications. Although estimates vary, studies indicate that in >10% of individuals with difficult-to-control T2D, hypercortisolism may be an underlying contributing cause. To better understand the prevalence of hypercortisolism and the impact of its treatment on T2D and associated comorbidities, we describe the two-part Hypercortisolism in Patients with Difficult to Control Type 2 Diabetes Despite Receiving Standard-of-Care Therapies: Prevalence and Treatment with Korlym® (Mifepristone) (CATALYST) trial.Methods and analysis In part 1, approximately 1000 participants with difficult-to-control T2D (haemoglobin A1c (HbA1c) 7.5%–11.5% despite multiple therapies) are screened with a 1 mg dexamethasone suppression test (DST). Those with post-DST cortisol >1.8 µg/dL and dexamethasone level ≥140 ng/dL are identified to have hypercortisolism (part 1 primary endpoint), have morning adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS) measured and undergo a non-contrast adrenal CT scan. Those requiring evaluation for elevated ACTH are referred for care outside the study; those with ACTH and DHEAS in the range may advance to part 2, a randomised, double-blind, placebo-controlled trial to evaluate the impact of treating hypercortisolism with the competitive glucocorticoid receptor antagonist mifepristone (Korlym®). Participants are randomised 2:1 to mifepristone or placebo for 24 weeks, stratified by the presence/absence of an abnormal adrenal CT scan. Mifepristone is dosed at 300 mg once daily for 4 weeks, then 600 mg daily based on tolerability and clinical improvement, with an option to increase to 900 mg. The primary endpoint of part 2 assesses changes in HbA1c in participants with hypercortisolism with or without abnormal adrenal CT scan. Secondary endpoints include changes in antidiabetes medications, cortisol-related comorbidities and quality of life.Ethics and dissemination The study has been approved by Cleveland Clinic IRB (Cleveland, Ohio, USA) and Advarra IRB (Columbia, Maryland, USA). Findings will be presented at scientific meetings and published in peer-reviewed journals.Trial registration number NCT05772169.

IntroductionPrior to the introduction of novel food ingredients into the food supply, safety risk assessments are required, and numerous prediction models have been developed and validated to evaluate safety.MethodsThe allergenic risk potential of Helaina recombinant human lactoferrin (rhLF, Effera™), produced in Komagataella phaffii (K. phaffii) was assessed by literature search, bioinformatics sequence comparisons to known allergens, glycan allergenicity assessment, and a simulated pepsin digestion model.ResultsThe literature search identified no allergenic risk for Helaina rhLF, K. phaffii, or its glycans. Bioinformatics search strategies showed no significant risk for cross-reactivity or allergenicity between rhLF or the 36 residual host proteins and known human allergens. Helaina rhLF was also rapidly digested in simulated gastric fluid and its digestibility profile was comparable to human milk lactoferrin (hmLF), further demonstrating a low allergenic risk and similarity to the hmLF protein. ConclusionCollectively, these results demonstrate a low allergenic risk potential of Helaina rhLF and do not indicate the need for further clinical testing or serum IgE binding to evaluate Helaina rhLF for risk of food allergy prior to introduction into the food supply.