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Poetry and medicine are related in multiple ways, including historical interests in healing, defined broadly, through words. More contemporary scholarship explores how poems, which include insights into the human condition, can enlarge our understanding of health, illness, mortality, and health care, including issues of diversity. Anesthesiology and poetry have particular affinities due to their structures, timeframes, and rhythms. Patients, physicians, and health care workers can benefit in terms of well-being by access to reading, reflecting on, and writing poetry., (Published by Elsevier Inc.)

Abstract Neuroendocrine (NE) transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor prognosis. Up to date, even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53 (TP53) and Retinoblastoma Transcriptional Corepressor 1 (RB1) mutations in their tumors, no therapeutic strategies are available to prevent or delay histological transformation. Upregulation of the cell cycle kinase Cell Division Cycle 7 (CDC7) occurred in tumors during the initial steps of NE transformation, already after TP53/RB1 co-inactivation, leading to induced sensitivity to the CDC7 inhibitor simurosertib. CDC7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYC Proto-Oncogen (MYC), implicated in stemness and histological transformation. Ectopic overexpression of a degradation-resistant MYC isoform reestablished the NE transformation phenotype observed on targeted therapy, even in the presence of simurosertib. CDC7 inhibition also markedly extended response to standard cytotoxics (cisplatin, irinotecan) in lung and prostate small cell carcinoma models. These results nominate CDC7 inhibition as a therapeutic strategy to constrain lineage plasticity, as well as to effectively treat NE tumors de novo or after transformation. As simurosertib clinical efficacy trials are ongoing, this concept could be readily translated for patients at risk of transformation.

Introduction: COVID-19 vaccinations reduce the severity and number of symptoms for acute SARS-CoV-2 infections and may reduce the risk of developing Long COVID, also known as post-acute sequelae of SARS-CoV-2 (PASC). Limited and heterogenous data exist on how these vaccinations received after COVID-19 infection might impact the symptoms and trajectory of PASC, once persistent symptoms have developed. Methods: We investigated the association of post-COVID-19 vaccination with any SARS-CoV-2 vaccine(s) on PASC symptoms in two independent cohorts: a retrospective chart review of self-reported data from patients (n = 128) with PASC seen in the Stanford PASC Clinic between May 2021 and May 2022 and a 2023 multinational survey assessment of individuals with PASC (n = 484). Findings: Within the PASC Clinic patient cohort (n = 128), 58.6% (n = 75) were female, and 41.4% (n = 53) were male; 50% (n = 64) were white, and 38.3% (n = 49) were non-white. A total of 60.2% (n = 77) of PASC Clinic patients reported no change in their PASC symptoms after vaccination, 17.2% (n = 22) reported improved symptoms, and 22.7% (n = 29) reported worsened symptoms. In the multinational survey cohort (n = 484), 380 were from the U.S., and 104 were from outside the U.S.; 88.4% (n = 428) were female, and 11.6% (n = 56) were male; and 88.8% (n = 430) were white, and 11.2% (n = 54) were non-white. The distribution of survey self-reported vaccine effects on PASC symptoms was 20.2% worsened (n = 98), 60.5% no effect (n = 293), and 19.2% improved (n = 93). In both cohorts, demographic features, including age, sex, and race/ethnicity, were not significantly associated with post-vaccination PASC symptom changes. There was also a non-significant difference in the median dates of COVID-19 infection among the different outcomes. BMI was significant for symptom improvement (p = 0.026) in the PASC Clinic cohort, while a history of booster doses was significant for symptom improvement (p < 0.001) in the survey cohort. Conclusions: Most individuals with PASC did not report significant changes in their overall PASC symptoms following COVID-19 vaccinations received after PASC onset. Further research is needed to better understand the relationship between COVID-19 vaccinations and PASC.

Abstract Objectives Medicaid and the Children’s Health Insurance Program (CHIP) provide health insurance coverage to more than 90 million Americans as of early 2023. There is substantial variation in eligibility criteria, application procedures, premiums, and other programmatic characteristics across states and over time. Analyzing changes in Medicaid policies is important for state and federal agencies and other stakeholders, but such analysis requires data on historical programmatic characteristics that are often not available in a form ready for quantitative analysis. Our objective is to fill this gap by synthesizing existing qualitative policy data to create a new data resource that facilitates Medicaid policy research. Data description Our source data were the 50-state surveys of Medicaid and CHIP eligibility, enrollment, and cost-sharing policies, and budgets conducted near annually by KFF since 2000, which we coded through 2020. These reports are a rich source of point-in-time information but not operationalized for quantitative analysis. Through a review of the measures captured in the KFF surveys, we developed five Medicaid policy domains with 122 measures in total, each coded by state-quarter—1) eligibility (28 measures), 2) enrollment and renewal processes (39 measures), 3) premiums (16 measures), 4) cost-sharing (26 measures), and 5) managed care (13 measures).

Abstract Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms. Methods: We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities. Results: By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18–100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates. Conclusion: This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.

The impact of environmental uncertainty on locomotor adaptation remains unclear. Environmental uncertainty could either aid locomotor adaptation by prompting protective control strategies that stabilize movements to assist learning or impede adaptation by reducing error sensitivity and fostering hesitance to pursue corrective movements. To explore this, we investigated participants' adaptation to a consistent force field after experiencing environmental uncertainty in the form of unpredictable balance perturbations. We compared the performance of this group (Perturbation) to the adaptive performance of a group that did not experience any unpredictable perturbations (Non-Perturbation). Perturbations were delivered using a cable-driven robotic device applying lateral forces to the pelvis. We assessed whole-body center of mass (COM) trajectory (COM signed deviation), anticipatory postural adjustments (COM lateral offset), and first step width. The Perturbation group exhibited larger disruptions in COM trajectory (greater COM signed deviations) than the Non-Perturbation group when first walking in the force field. While the COM signed deviations of both groups decreased towards baseline values, only the Non-Perturbation group returned to baseline levels. The Perturbation groups COM signed deviations remained higher, indicating they failed to fully adapt to the force field before the end. The Perturbation group also did not adapt their COM lateral offset to counter the predictable effects of the force field as the Non-Perturbation group did, and their first step width increased more slowly. Our findings suggest that exposure to unpredictable perturbations impeded future sensorimotor adaptations to consistent perturbations.

Abstract Background: Members of many racial and ethnic population subgroups are underrepresented in clinical trials and research. We present perspectives on barriers and facilitators to study participation gathered from Hispanic participants in a population-based genetic screening study. Methods: Seven focus groups (five in English and two in Spanish) were conducted with self-identified Hispanic participants of the Healthy Oregon Project (HOP), a large population-based cohort of adults residing in Oregon. HOP study participants complete surveys about cancer and chronic disease risks with the option to donate a saliva sample for no-cost genetic risk screening for inherited disorders. HOP invited Hispanic participants via email to join a focus group about their experiences. Focus groups, generally lasting 60–90 minutes, occurred in person and virtually. Notes were coded and content-analyzed. Findings: 49 Hispanic adults participated in the focus groups (37 women; 9 men; 3 non-binary people). Identified facilitators for HOP study participation were trust in the academic medical center leading the study, having a family member who was impacted by cancer, and receiving free genetic screening. Identified barriers were difficulty completing the family history survey, lack of understanding or familiarity with research, immigration status, and navigating technology challenges. Recommendations to improve recruitment of Hispanic populations included promoting the study at community events, clinics, or schools, simplifying the consenting process and providing patient-focused videos to demonstrate study tasks, providing real-time sample tracking, and offering monetary incentives. Discussion: Our findings can inform strategies for bolstering recruitment of Hispanic adults in biomedical research studies.

BackgroundConversational agents (CA's) have shown promise in increasing accessibility to mental health resources. This study aimed to identify common themes of messages sent to a mental health CA (Wysa) related to ASD by general users and users that identify as having ASD.MethodsThis study utilized retrospective data. Two thematic analyses were conducted, one focusing on user messages including the keywords (e.g., ASD, autism, Asperger), and the second one with messages from users who self-identified as having ASD.ResultsFor the sample of general users, the most frequent themes were “others having ASD,” “ASD diagnosis,” and “seeking help.” For the users that self-identified as having ASD (n = 277), the most frequent themes were “ASD diagnosis or symptoms,” “negative reaction from others,” and “positive comments.” There were 3,725 emotion words mentioned by users who self-identified as having ASD. The majority had negative valence (80.3%), and few were positive (14.8%) or ambivalent (4.9%).ConclusionUsers shared their experiences and emotions surrounding ASD with a mental health CA. Users asked about the ASD diagnosis, sought help, and reported negative reactions from others. CA's have the potential to become a source of support for those interested in ASD and/or identify as having ASD.

Abstract Objective COVID-19 mitigation measures prompted many states to revise the administration of their welfare programs. States adopted policies that varied across the U.S. to respond to the difficulties in fulfilling program requirements, as well as increased financial need. This dataset captures the changes made to Temporary Assistance for Needy Families (TANF) programs during the COVID-19 pandemic, from March 2020 through December 2020. The authors created this dataset as part of a larger study that examined the health effects of TANF policy changes during the COVID-19 pandemic. Data description TANF is the main cash assistance program for low-income families in the U.S., but benefits are often conditional on work requirements and can be revoked if an individual is deemed noncompliant. Structural factors during the COVID-19 pandemic made meeting these criteria more difficult, so some states relaxed their rules and increased their benefits. This dataset captures 24 types of policies that state TANF programs enacted, which of the states enacted each of them, when the policies went into effect, and when applicable, when the policies ended. These data can be used to study the effects of TANF policy changes on various health and programmatic outcomes.

Persons with COVID-19–like illnesses are advised to stay home to reduce the spread of SARS-CoV-2. We assessed relationships between telework experience and COVID-19 illness with work attendance when ill. Adults experiencing fever, cough, or loss of taste or smell who sought healthcare or COVID-19 testing in the United States during March–November 2020 were enrolled. Adults with telework experience before illness were more likely to work at all (onsite or remotely) during illness (87.8%) than those with no telework experience (49.9%) (adjusted odds ratio 5.48, 95% CI 3.40–8.83). COVID-19 case-patients were less likely to work onsite (22.1%) than were persons with other acute respiratory illnesses (37.3%) (adjusted odds ratio 0.36, 95% CI 0.24–0.53). Among COVID-19 case-patients with telework experience, only 6.5% worked onsite during illness. Telework experience before illness gave mildly ill workers the option to work and improved compliance with public health recommendations to stay home during illness.

Homeostatic control of sleep is typically addressed through mechanical stimulation-induced forced wakefulness and the measurement of subsequent increases in sleep. A major confound attends this approach: biological responses to deprivation may reflect a direct response to the mechanical insult rather than to the loss of sleep. Similar confounds accompany all forms of sleep deprivation and represent a major challenge to the field. Here, we describe a new paradigm for sleep deprivation in Drosophila that fully accounts for sleep-independent effects. Our results reveal that deep sleep states are the primary target of homeostatic control and establish the presence of multi-cycle sleep rebound following deprivation. Furthermore, we establish that specific deprivation of deep sleep states results in state-specific homeostatic rebound. Finally, by accounting for the molecular effects of mechanical stimulation during deprivation experiments, we show that serotonin levels track sleep pressure in the fly’s central brain. Our results illustrate the critical need to control for sleep-independent effects of deprivation when examining the molecular correlates of sleep pressure and call for a critical reassessment of work that has not accounted for such non-specific effects.

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.

Abstract Acoustic structures associated with native-language phonological sequences are enhanced within auditory pathways for perception, although the underlying mechanisms are not well understood. To elucidate processes that facilitate perception, time–frequency (T–F) analyses of EEGs obtained from native speakers of English and Polish were conducted. Participants listened to same and different nonword pairs within counterbalanced attend and passive conditions. Nonwords contained the onsets /pt/, /pət/, /st/, and /sət/ that occur in both the Polish and English languages with the exception of /pt/, which never occurs in the English language in word onset. Measures of spectral power and inter-trial phase locking (ITPL) in the low gamma (LG) and theta-frequency bands were analyzed from two bilateral, auditory source-level channels, created through source localization modeling. Results revealed significantly larger spectral power in LG for the English listeners to the unfamiliar /pt/ onsets from the right hemisphere at early cortical stages, during the passive condition. Further, ITPL values revealed distinctive responses in high and low-theta to acoustic characteristics of the onsets, which were modulated by language exposure. These findings, language-specific processing in LG and acoustic-level and language-specific processing in theta, support the view that multi scale temporal processing in the LG and theta-frequency bands facilitates speech perception.

Abstract Objective: The goal of this pilot study was to identify changes associated with completion of a unique six-week hand exercise program in persons with carpometacarpal osteoarthritis. Methods: Twenty-four individuals, aged 55–80, with doctor-diagnosed carpometacarpal osteoarthritis participated in the study. Movement data from standard clinical motions and complex multi-planar motions were obtained using a motion capture system at three-time points: an initial visit, after two weeks of hand exercises, and after completion of the six-week exercise program. Results: This exercise program produced trends of improvement in complex multi-planar motions. Specifically, joint angle changes were seen during opposition and the formation of an “okay sign” that was included as part of the exercise program. Conclusion: Through the use of motion capture, changes were identified in thumb joint function after exercise. Specifically, motions associated with the more complex multi-planar tasks showed changes in individual joint contributions following the six-week exercise intervention. The results suggest that further exploration of this exercise program, particularly the inclusion of complex multi-planar tasks during osteoarthritis treatment and associated evaluations, should be considered in future clinical studies.

We report persistent severe acute respiratory syndrome coronavirus 2 infection in a patient with HIV/AIDS; the virus developed spike N terminal domain and receptor binding domain neutralization resistance mutations. Our findings suggest that immunocompromised patients can harbor emerging variants of severe acute respiratory syndrome coronavirus 2.

Abstract HLA-B27 is associated with increased susceptibility and disease activity of ankylosing spondylitis, but the effect of HLA-B27 on the activity of the broader category now called axial spondyloarthritis (AxSpA) is apparently the opposite. A modified Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was used to assess disease activity among 3435 patients with spondyloarthritis (SpA) who participated in a survey designed to assess the effect of their disease and its treatment on the susceptibility and severity of Covid-19. Chi square testing was used to compare BASDAI scores between HLA-B27 positive and negative subjects. 2836 survey respondents were HLA B27 positive. The average BASDAI for the HLA-B27 negative cohort was 4.92 compared to 4.34 for the HLA-B27 positive subjects. Based on linear regression, a subject’s sex could not fully account for the differing BASDAI score in HLA-B27 negative subjects compared to those who are HLA-B27 positive. The difference between B27 positive and negative subjects was skewed by those with a BASDAI score of one or two. HLA-B27 positive subjects were more than twice as likely to have a BASDAI score of 1 compared to HLA B27 negative subjects and about 60% more likely to have a BASDAI score of 2 (p

Abstract Background Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. Methods Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( https://pathogen.watch/ngonorrhoeae ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. Results AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. Conclusions The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

Abstract Tumor histology is an important predictor of therapeutic response and outcomes in lung cancer. Tissue sampling for pathologist review is the most reliable method for histology classification, however, recent advances in deep learning for medical image analysis allude to the utility of radiologic data in further describing disease characteristics and for risk stratification. In this study, we propose a radiomics approach to predicting non-small cell lung cancer (NSCLC) tumor histology from non-invasive standard-of-care computed tomography (CT) data. We trained and validated convolutional neural networks (CNNs) on a dataset comprising 311 early-stage NSCLC patients receiving surgical treatment at Massachusetts General Hospital (MGH), with a focus on the two most common histological types: adenocarcinoma (ADC) and Squamous Cell Carcinoma (SCC). The CNNs were able to predict tumor histology with an AUC of 0.71(p = 0.018). We also found that using machine learning classifiers such as k-nearest neighbors (kNN) and support vector machine (SVM) on CNN-derived quantitative radiomics features yielded comparable discriminative performance, with AUC of up to 0.71 (p = 0.017). Our best performing CNN functioned as a robust probabilistic classifier in heterogeneous test sets, with qualitatively interpretable visual explanations to its predictions. Deep learning based radiomics can identify histological phenotypes in lung cancer. It has the potential to augment existing approaches and serve as a corrective aid for diagnosticians.

The circadian clock orchestrates daily changes in physiology and behavior to ensure internal temporal order and optimal timing across the day. In animals, a central brain clock coordinates circadian rhythms throughout the body and is characterized by a remarkable robustness that depends on synaptic connections between constituent neurons. The clock neuron network of Drosophila, which shares network motifs with clock networks in the mammalian brain yet is built of many fewer neurons, offers a powerful model for understanding the network properties of circadian timekeeping. Here, we report an assessment of synaptic connectivity within a clock network, focusing on the critical lateral neuron (LN) clock neuron classes within the Janelia hemibrain dataset. Our results reveal that previously identified anatomical and functional subclasses of LNs represent distinct connectomic types. Moreover, we identify a small number of non-clock cell subtypes representing highly synaptically coupled nodes within the clock neuron network. This suggests that neurons lacking molecular timekeeping likely play integral roles within the circadian timekeeping network. To our knowledge, this represents the first comprehensive connectomic analysis of a circadian neuronal network.

Background Only a few recent reports have examined longitudinal adherence patterns in US clinics and its impact on immunological and virological outcomes among large cohorts initiating contemporary antiretroviral therapy (ART) in US clinics. Methods We followed all persons with HIV (PLWH) in a California clinic population initiating ART between 2010 and 2017. We estimated longitudinal adherence for each PLWH by calculating the medication possession ratio within multiple 6-month intervals using pharmacy refill records. Results During the study, 2315 PWLH were followed for a median time of 210.8 weeks and only 179 (7.7%) were lost-to-follow-up. The mean adherence was 84.9%. Age (Hazard Ratio (HR): (95% confidence interval): 1.25 (1.20–1.31) per 10-year increase) and Black race (HR: 0.62 (0.53–0.73) vs. White) were associated with adherence in the cohort. A 10% percent increase in adherence increased the odds of being virally suppressed by 37% (OR and 95% CI: 1.37 [1.33–1.41]) and was associated with an increase in mean CD4 count by 8.54 cells/ul in the next 6-month interval (p-value Conclusions Our study shows that despite large improvements in retention in care, demographic disparities in adherence to ART persist. Adherence was lower among younger patients and black patients. Our study confirmed the strong association between adherence to ART and viral suppression but could only establish a weak association between adherence and CD4 count. These findings reaffirm the importance of adherence and retention in care and further highlight the need for tailored patient-centered HIV Care Models as a strategy to improve PLWH’s outcomes.

As novel SARS-CoV-2 variants with different patterns of spike protein mutations have emerged, the susceptibility of these variants to neutralization by antibodies has been rapidly assessed. However, neutralization data are generated using different approaches and are scattered across different publications making it difficult for these data to be located and synthesized. The Stanford Coronavirus Resistance Database (CoV-RDB; https://covdb.stanford.edu) is designed to house comprehensively curated published data on the neutralizing susceptibility of SARS-CoV-2 variants and spike mutations to monoclonal antibodies (mAbs), convalescent plasma (CP), and vaccinee plasma (VP). As of December 31, 2021, CoV-RDB encompassed 257 publications including 91 (35%) containing 9,070 neutralizing mAb susceptibility results, 131 (51%) containing 16,773 neutralizing CP susceptibility results, and 178 (69%) containing 33,540 neutralizing VP results. The database also records which spike mutations are selected during in vitro passage of SARS-CoV-2 in the presence of mAbs and which emerge in persons receiving mAbs as treatment. The CoV-RDB interface interactively displays neutralizing susceptibility data at different levels of granularity by filtering and/or aggregating query results according to one or more experimental conditions. The CoV-RDB website provides a companion sequence analysis program that outputs information about mutations present in a submitted sequence and that also assists users in determining the appropriate mutation-detection thresholds for identifying non-consensus amino acids. The most recent data underlying the CoV-RDB can be downloaded in its entirety from a GitHub repository in a documented machine-readable format.

BackgroundIn contrast to the current broad dissemination of telemedicine across medical specialties, previous research focused on the effectiveness of telemedicine in special populations and for behavioral health encounters, demonstrating that both physician and patient factors impact the efficacious use of telemedicine. ObjectiveWe aim to evaluate physician perceptions of the appropriateness of telemedicine for patients attending the primary care practices of a federally qualified health center in New York City. MethodsWe used an anonymous cross-sectional survey including closed- and open-ended questions. We used chi-square to test whether providers from certain specialties were more likely to state they would use telemedicine in the future. We used t tests to compare age between those who would versus would not use telemedicine. We then used logistic regression to test whether age and specialty were both correlated with the desire to use telemedicine in the future. We used thematic content analysis to describe the reasons providers felt they would not want to use telemedicine in the future and to describe the situations for which they felt telemedicine would be appropriate. ResultsOf 272 health care providers who were sent the electronic survey, 157 (58%) responded within the 2-week survey time frame. The mean age of providers was 45 (range 28-75) years. Overall, 80% (126/157) stated they would use telemedicine in the future. Compared to the family medicine, internal medicine, behavioral health, dental, and obstetrics and gynecology specialties, providers from pediatrics, med-peds, subspecialties, and surgery (protelemedicine specialties) were more likely to believe telemedicine would be useful post pandemic (61/67 [91%] vs 65/90 [72%]; P

ObjectivesThe unprecedented worldwide social distancing response to COVID-19 resulted in a quick reversal of escalating case numbers. Recently, local governments globally have begun to relax social distancing regulations. Using the situation in Manitoba, Canada as an example, we estimated the impact that social distancing relaxation may have on the pandemic.MethodsWe fit a mathematical model to empirically estimated numbers of people infected, recovered, and died from COVID-19 in Manitoba. We then explored the impact of social distancing relaxation on: (a) time until near elimination of COVID-19 (< one case per million), (b) time until peak prevalence, (c) proportion of the population infected within one year, (d) peak prevalence, and (e) deaths within one year.ResultsAssuming a closed population, near elimination of COVID-19 in Manitoba could have been achieved in 4-6 months (by July or August) if there were no relaxation of social distancing. Relaxing to 15% of pre-COVID effective contacts may extend the local epidemic for more than two years (median 2.1). Relaxation to 50% of pre-COVID effective contacts may result in a peak prevalence of 31-38% of the population, within 3-4 months of initial relaxation.ConclusionSlight relaxation of social distancing may immensely impact the pandemic duration and expected peak prevalence. Only holding the course with respect to social distancing may have resulted in near elimination before Fall of 2020; relaxing social distancing to 15% of pre-COVID-19 contacts will flatten the epidemic curve but greatly extend the duration of the pandemic.

Abstract Introduction: Urothelial carcinoma (UCC) develops in both humans and dogs and tracks to regions of high industrial activity. We hypothesize that dogs with UCC may act as sentinels for human urothelial carcinogen exposures. The aim of this pilot study was to determine whether healthy people and dogs in the same households share urinary exposures to potentially mutagenic chemical carcinogens. Methods: We measured urinary concentrations of acrolein (as its metabolite 3-HPMA), arsenic species, 4-aminobiphenyl, and 4-chlorophenol (a metabolite of the phenoxyherbicide 2,4-D) in healthy dogs and their owners. We assessed possible chemical sources through questionnaires and screened for urothelial DNA damage using the micronucleus assay. Results: Biomarkers of urinary exposure to acrolein, arsenic, and 4-chlorophenol were found in the urine of 42 pet dogs and 42 owners, with 4-aminobiphenyl detected sporadically. Creatinine-adjusted urinary chemical concentrations were significantly higher, by 2.8- to 6.2-fold, in dogs compared to humans. Correlations were found for 3-HPMA (r = 0.32, P = 0.04) and monomethylarsonic acid (r = 0.37, P = 0.02) between people and their dogs. Voided urothelial cell yields were inadequate to quantify DNA damage, and questionnaires did not reveal significant associations with urinary chemical concentrations. Conclusions: Healthy humans and pet dogs have shared urinary exposures to known mutagenic chemicals, with significantly higher levels in dogs. Higher urinary exposures to acrolein and arsenic in dogs correlate to higher exposures in their owners. Follow-up studies will assess the mutagenic potential of these levels in vitro and measure these biomarkers in owners of dogs with UCC.

Tissue homeostasis relies on the fine regulation between stem and progenitor cell maintenance and lineage commitment. In the adult prostate, stem cells have been identified in both basal and luminal cell compartments. However, basal stem/progenitor cell homeostasis is still poorly understood. We show that basal stem/progenitor cell maintenance is regulated by a balance between BMP5 self-renewal signal and GATA3 dampening activity. Deleting Gata3 enhances adult prostate stem/progenitor cells self-renewal capacity in both organoid and allograft assays. This phenotype results from a local increase in BMP5 activity in basal cells as shown by the impaired self-renewal capacity of Bmp5-deficient stem/progenitor cells. Strikingly, Bmp5 gene inactivation or BMP signaling inhibition with a small molecule inhibitor are also sufficient to delay prostate and skin cancer initiation of Pten-deficient mice. Together, these results establish BMP5 as a key regulator of basal prostate stem cell homeostasis and identifies a potential therapeutic approach against Pten-deficient cancers.

A transcription factor helps young flies to sleep longer by delaying the maturation of a neural network that controls sleep.

Ritonavir-boosted atazanavir is an option for second-line therapy in low- and middle-income countries (LMICs). We analyzed publicly available HIV-1 protease sequences from previously PI-naïve patients with virological failure (VF) following treatment with atazanavir. Overall, 1497 patient sequences were identified, including 740 reported in 27 published studies and 757 from datasets assembled for this analysis. A total of 63% of patients received boosted atazanavir. A total of 38% had non-subtype B viruses. A total of 264 (18%) sequences had a PI drug-resistance mutation (DRM) defined as having a Stanford HIV Drug Resistance Database mutation penalty score. Among sequences with a DRM, nine major DRMs had a prevalence >5%: I50L (34%), M46I (33%), V82A (22%), L90M (19%), I54V (16%), N88S (10%), M46L (8%), V32I (6%), and I84V (6%). Common accessory DRMs were L33F (21%), Q58E (16%), K20T (14%), G73S (12%), L10F (10%), F53L (10%), K43T (9%), and L24I (6%). A novel nonpolymorphic mutation, L89T occurred in 8.4% of non-subtype B, but in only 0.4% of subtype B sequences. The 264 sequences included 3 (1.1%) interpreted as causing high-level, 14 (5.3%) as causing intermediate, and 27 (10.2%) as causing low-level darunavir resistance. Atazanavir selects for nine major and eight accessory DRMs, and one novel nonpolymorphic mutation occurring primarily in non-B sequences. Atazanavir-selected mutations confer low-levels of darunavir cross resistance. Clinical studies, however, are required to determine the optimal boosted PI to use for second-line and potentially later line therapy in LMICs.

Abstract Background There is a strong and growing interest in biomedical ethics and medical humanities (BEMH) within medical education for facilitating key components of medical professionalism and ethics, clinical communication and observational skills, and self-care and reflective practices. Consequently, United States (US) medical institutions have begun to incorporate BEMH through formal Scholarly Concentrations (SCs). This is the first study to examine the impact of a US BEMH SC, from student experience in medical school to post-graduate development, as perceived by graduate physicians. Methods Graduated students who participated in the BEMH SC or did extensive BEMH research prior to the BEMH SC’s establishment (n = 57) were sampled for maximum variation across graduating years. In telephone surveys and interviews, participants discussed the perceived impact of the BEMH SC on (a.) student experience during medical school and (b.) post-graduate development. Interviews were audiotaped, transcribed, and de-identified. The authors iteratively generated a codebook; two raters coded independently, adjudicated codes, and completed inter-rater reliability (IRR) tests. The authors subsequently conducted a team-based thematic analysis, identifying emergent themes. Results Nineteen BEMH graduates were interviewed. Results were analyzed according to (a.) student experience and (b.) post-graduate development. Overall, respondents perceived impacts in reinforcing knowledge and skills in clinical ethics; solidifying self-care and reflective practices; refining a sense of professional identity and integrity for ethically challenging situations; and promoting student skills, productivity, and later careers involving BEMH. Conclusion A comprehensive US BEMH SC achieved the purported aims of BEMH in medical education, with graduate physicians perceiving persisting effects into clinical practice. Furthermore, the structure and format of a SC may offer additional advantages in promoting student scholarly skill and productivity, career development, and professional identity formation—core competencies identified across clinical training and ethics programs. Our findings indicate that a BEMH SC is effective in achieving a range of desired immediate and post-graduate effects and represent a particularly promising venue for BEMH in medical education. We believe these findings to be of critical significance to medical educators and administrators when considering how best to incorporate BEMH into SCs and medical curricula.

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 – A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F – were more common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMs will be important for monitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

BackgroundThe Affordable Care Act led to improvements in reporting a usual source of care, but it is unclear whether patients are changing their usual source of care in response to coverage gains. We assess whether prior insurance instability is associated with changes in use of emergency and office-based care after the Marketplace and Medicaid expansion were introduced.MethodsOur study draws from the 2013-14 Medical Expenditure Panel Survey, identifying a cohort of non-elderly adults with full-year health insurance coverage in 2014. We use linear and multinomial logistic regression to assess the relationship between insurance instability prior to 2014 (uninsured for 1-11 months, ≥12 months) and person-level changes in use of health care after gaining coverage (change in ED and office visits from 2013 to 2014) with continuously insured individuals serving as a comparison group.ResultsBeing uninsured for at least one year prior to gaining full-year coverage in 2014 was associated with a 33% increase in ED visits (0.06 visits, pConclusionThe long-term uninsured may have substantial health needs and pent-up demand for health care, seeing more physicians across multiple settings in the year after gaining coverage as they seek to get unmanaged conditions under control. Closing the gap in primary care use between the previously uninsured and those with health insurance coverage may help improve long-term health outcomes.

As newer single-cell protocols generate increasingly more cells at reduced sequencing depths, the value of a higher read depth may be overlooked. Using data from three different single-cell RNA-seq protocols that lend themselves to having either higher read depth (Smart-seq) or many cells (MARS-seq and 10X), we evaluate their ability to recapitulate biological signals in the context of spatial reconstruction. Overall, we find gene expression profiles after spatial reconstruction analysis are highly reproducible between datasets despite being generated by different protocols and using different computational algorithms. While UMI-based protocols such as 10X and MARS-seq allow for capturing more cells, Smart-seq's higher sensitivity and read-depth allow for analysis of lower expressed genes and isoforms. Additionally, we evaluate trade-offs for each protocol by performing subsampling analyses and find that optimizing the balance between sequencing depth and number of cells within a protocol is necessary for efficient use of resources. Our analysis emphasizes the importance of selecting a protocol based on the biological questions and features of interest.

IntroductionAt low mutation-detection thresholds, next generation sequencing (NGS) for HIV-1 genotypic resistance testing is susceptible to artifactual detection of mutations arising from PCR error and APOBEC-mediated G-to-A hypermutation.MethodsWe analyzed published HIV-1 pol Illumina NGS data to characterize the distribution of mutations at eight NGS mutation detection thresholds: 20%, 10%, 5%, 2%, 1%, 0.5%, 0.2%, and 0.1%. At each threshold, we determined proportions of amino acid mutations that were unusual (defined as having a prevalence ResultsEight studies, containing 855 samples, in the NCBI Sequence Read Archive were analyzed. As detection thresholds were lowered, there was a progressive increase in the proportion of positions with usual and unusual mutations and in the proportion of all mutations that were unusual. The median proportion of positions with an unusual mutation increased gradually from 0% at the 20% threshold to 0.3% at the 1% threshold and then exponentially to 1.3% (0.5% threshold), 6.9% (0.2% threshold), and 23.2% (0.1% threshold). In two of three studies with available plasma HIV-1 RNA levels, the proportion of positions with unusual mutations was negatively associated with virus levels. Although the complete set of signature APOBEC mutations was much smaller than that of unusual mutations, the former outnumbered the latter in one-sixth of samples at the 0.5%, 1%, and 2% thresholds.ConclusionsThe marked increase in the proportion of positions with unusual mutations at thresholds below 1% and in samples with lower virus loads suggests that, at low thresholds, many unusual mutations are artifactual, reflecting PCR error or G-to-A hypermutation. Profiling the numbers of unusual and signature APOBEC pol mutations at different NGS mutation detection thresholds may be useful to avoid selecting a threshold that is too low and poses an unacceptable risk of identifying artifactual mutations.

Objectives China has a high burden of gonorrhea, but an imbalanced male-to-female (M/F) ratio of reported cases. Therefore, the prevalence of gonorrhea in China may be underestimated due to inadequate testing of potentially infected females. The objective of this study is to investigate the cause of this imbalanced M/F ratio and develop strategies to enhance gonorrhea surveillance, particularly among females. Methods The national center for STD control (NCSTDC) of China CDC collected data in Zhongshan city over the year 2018 from the National Notifiable Disease Report System (NNDRS) and the Hospital and Laboratory Information Systems (HIS and LIS) that obtains information from 24 hospitals. Results Analysis of 1,542 reported cases of gonorrhea and the case distribution among different hospitals showed that most of the female cases (80.31%) were reported by gynecological clinics. The M/F ratio of reported cases varied between different hospitals and was dependent on the intensity of testing of females by their gynecological clinics. Conclusions This study showed a significant correlation between M/F ratios and the relative contribution of female gonorrhea testing, especially in gynecology clinics. Enhancing gonorrhea testing among females should be advocated to improve surveillance in China.

BackgroundThere is a need for a rapid diagnostic point of care test to detect Neisseria gonorrhoeae (NG) infection to prevent incorrect, lack or excess of treatment resulting from current syndromic management in low-resource settings. An assay to identify NG antimicrobial resistance (AMR) is also highly desirable to facilitate antibiotic stewardship. Here we describe the development of two target product profiles (TPPs): one for a test for etiological diagnosis of NG and Chlamydia trachomatis (CT) (TPP1) and one for the detection of NG AMR/susceptibility (TPP2).MethodsDraft TPPs were initially developed based on a landscape analysis of existing diagnostics and expert input. TPPs were refined via an online Delphi survey with two rounds of input from 68 respondents. TPP characteristics on which ResultsThe need for a test to identify NG in patients with urethral or vaginal discharge was identified as a minimal requirement of TPP1, with a test that can diagnose NG in asymptomatic patients as the optimal requirement. A sensitivity of 80% was considered acceptable, either in context of syndromic management or screening high-risk populations. For TPP2, the agreed minimal requirement was for a test to be used at level 2 healthcare facilities and above, with an optimal requirement of level 1 or above. A lateral flow format was preferred for TPP1, while it was considered likely that TPP2 would require a molecular format. A total of 31 test characteristics were included in TPP1 and 27 in TPP2.ConclusionsFollowing the working group revisions, TPPs were posted online for public feedback for two months, and are now finalized. The final TPPs are currently guiding the development of new diagnostics that meet the defined characteristics to reach the market within two years.

Diffusion magnetic resonance images may suffer from geometric distortions due to susceptibility induced off resonance fields, which cause geometric mismatch with anatomical images and ultimately affect subsequent quantification of microstructural or connectivity indices. State-of-the art diffusion distortion correction methods typically require data acquired with reverse phase encoding directions, resulting in varying magnitudes and orientations of distortion, which allow estimation of an undistorted volume. Alternatively, additional field maps acquisitions can be used along with sequence information to determine warping fields. However, not all imaging protocols include these additional scans and cannot take advantage of state-of-the art distortion correction. To avoid additional acquisitions, structural MRI (undistorted scans) can be used as registration targets for intensity driven correction. In this study, we aim to (1) enable susceptibility distortion correction with historical and/or limited diffusion datasets that do not include specific sequences for distortion correction and (2) avoid the computationally intensive registration procedure typically required for distortion correction using structural scans. To achieve these aims, we use deep learning (3D U-nets) to synthesize an undistorted b0 image that matches geometry of structural T1w images and intensity contrasts from diffusion images. Importantly, the training dataset is heterogenous, consisting of varying acquisitions of both structural and diffusion. We apply our approach to a withheld test set and show that distortions are successfully corrected after processing. We quantitatively evaluate the proposed distortion correction and intensity-based registration against state-of-the-art distortion correction (FSL topup). The results illustrate that the proposed pipeline results in b0 images that are geometrically similar to non-distorted structural images, and more closely match state-of-the-art correction with additional acquisitions. In addition, we show generalizability of the proposed approach to datasets that were not in the original training / validation / testing datasets. These datasets included varying populations, contrasts, resolutions, and magnitudes and orientations of distortion and show efficacious distortion correction. The method is available as a Singularity container, source code, and an executable trained model to facilitate evaluation.

ABSTRACT IMPACT: This project aims to better understand mechanisms of sensory and motor deficits in individuals with ASD with the goal of informing diagnosis and treatment development. OBJECTIVES/GOALS: Over-reliance on both visual and proprioceptive feedback have both been observed during motor behavior in persons with Autism Spectrum Disorders (ASD), suggesting that separate sensory feedback processes may be selectively altered during different behaviors. The objective of this study is to clarify sensory mechanisms of fine motor control in ASD. METHODS/STUDY POPULATION: Participants with ASD (N=43) and controls (N=23) matched on age (10-20 yrs) and non-verbal IQ completed tests of precision gripping. Participants were instructed to press on force sensors with their index finger and thumb so that a moving bar corresponding to their force output reached and stayed as stable as possible at the level of a stationary target bar. Visual feedback was manipulated by changing the visual gain of the force bar (low, medium and high). The force bar moved more per change in force output at higher gains. Proprioceptive feedback was manipulated by applying 80 Hz tendon vibration at the wrist to induce an illusion of muscle contraction. This was compared to a condition with the tendon vibrator turned off. Force variability (standard deviation) and regularity (sample entropy) were examined. RESULTS/ANTICIPATED RESULTS: Controls showed increased force variability with the tendon vibration on compared to off (t = -3.372, p < 0.001); however, the ASD group showed no difference in force variability between the tendon vibration conditions (t = -0.960, p = 0.338). Individuals with ASD had stronger age-associated reductions in force variability relative to controls across tendon vibrator and gain conditions (Group x Age: t = -4.05, p < .001). The ASD group also had greater age-associated increases in force regularity relative to controls, especially at higher gain levels (Group x Gain Level x Age: t = -3.22, p = 0.001). Unlike the ASD group for whom regularity increased with age in both tendon vibration conditions, controls only showed these age-related gains when the tendon vibrator was off (Group x Vibration Frequency x Age: t = 2.46, p = .014). DISCUSSION/SIGNIFICANCE OF FINDINGS: Our findings indicate that while controls integrate proprioceptive and visual feedback online to accurately adjust fine motor behavior, persons with ASD rely mostly on visual feedback. Our results suggest delayed development of sensory integration and reduced reliance on multisensory feedback during online fine motor control in persons with ASD.

OBJECTIVES/GOALS: Sensorimotor integration deficits are common in Autism Spectrum Disorders (ASD). There is evidence for both an over-reliance on visual and proprioceptive feedback during motor control in ASD, suggesting deficits in the ability to modulate sensory feedback processing in order to use the most reliable input. This study aims to test this hypothesis. METHODS/STUDY POPULATION: 40 persons with ASD (ages 10-33 yrs) and 25 age-, sex- and nonverbal IQ-matched controls completed precision gripping tasks under multiple proprioceptive and visual feedback conditions. Participants squeezed a force sensor with their index finger and thumb and tried to match their force output to a target force. Visual feedback of the target force (stationary bar) and their force output (bar that moved up/down with increased/decreased force) were displayed on a computer screen. Visual feedback was presented across low, medium, and high gain levels; the force bar moved a greater distance per change in force at higher gains. Proprioceptive feedback was manipulated using 80Hz tendon vibration at the wrist to create an illusion that the muscle is contracted. Force regularity (approximate entropy; ApEn) was examined. RESULTS/ANTICIPATED RESULTS: We have scored data from 18 participants with ASD and 13 control participants to date. Preliminary results from these participants indicate a Group x Tendon Vibration x Visual Gain interaction for ApEn (F = 1.559, p = 0.023). Individuals with ASD show slight increases in ApEn with 80Hz tendon vibration relative to no tendon vibration in all visual conditions. Controls showed increased ApEn during 80Hz compared to no tendon vibration at low visual gain but decreased ApEn with tendon vibration at high visual gain. These preliminary results indicate that controls shift to using a secondary source of sensory feedback (e.g., proprioception) when the primary source (e.g., vision) is degraded. However, persons with ASD do not reweight different sensory feedback processes as feedback inputs are degraded or magnified. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary results reveal that sensorimotor issues in ASD result from deficits in the reweighting of sensory feedback. Namely, persons with ASD fail to dynamically recalibrate feedback processes across visual and proprioceptive systems when feedback conditions change. Our results may aid treatment development for sensorimotor issues in ASD.