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Small cell lung cancer comprises approximately 10% to 15% of all lung cancers but is associated with a high proliferation rate and poor prognosis. Treatment options for patients with small cell lung cancer have been limited and offer modest clinical benefit. Lurbinectedin, an approved treatment by the United States Food and Drug Administration for metastatic small cell lung cancer in adults with disease progression during or after platinum-based chemotherapy, was shown to have antitumor activity and a favorable safety profile in a phase II trial. Here, we present a case report of a patient who was treated with lurbinectedin for approximately 2 years and maintained stable disease while receiving a reduced dose. The patient developed grade 3 anemia which resolved following a dose reduction of lurbinectedin, allowing for mitigation of toxicity while maintaining the clinical efficacy of the drug. Clinicians who treat patients with small cell lung cancer should be aware of this extended use of lurbinectedin in a patient who relapsed following first-line treatment and maintained stable disease on a reduced dose for almost 2 years.

Abstract Background Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. Methods After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants’ receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. Results 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1–14.3%), and 8.9% (95%CI 5.6–12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12–5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38–13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07–3.87). Conclusion We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.

Purpose: Behcet's disease is an immune-mediated condition which can commonly have ocular involvement. We present a case of Behcet's associated neuroretinitis, which is a rare ocular manifestation of Behcet's disease. Observations: The patient experienced significant improvement in her neuroretinitis without initiation of treatment. After 28 days of observation there was spontaneous resolution of exam findings and return of Snellen visual acuity to 20/20. Conclusionand Importance: There are only two other cases reported in the literature of Behcet's associated neuroretinitis. Both cases report bilateral involvement with concomitant frosted branch angiitis. This is also the only reported case with spontaneous resolution of abnormal exam findings with return to 20/20 visual acuity. This case highlights the complexity of ocular involvement in Behcet's disease.

BackgroundSocial determinants of health (SDoH), such as financial resources and housing stability, account for between 30% and 55% of people’s health outcomes. While many studies have identified strong associations between specific SDoH and health outcomes, little is known about how SDoH co-occur to form subtypes critical for designing targeted interventions. Such analysis has only now become possible through the All of Us program. ObjectiveThis study aims to analyze the All of Us dataset for addressing two research questions: (1) What are the range of and responses to survey questions related to SDoH? and (2) How do SDoH co-occur to form subtypes, and what are their risks for adverse health outcomes? MethodsFor question 1, an expert panel analyzed the range of and responses to SDoH questions across 6 surveys in the full All of Us dataset (N=372,397; version 6). For question 2, due to systematic missingness and uneven granularity of questions across the surveys, we selected all participants with valid and complete SDoH data and used inverse probability weighting to adjust their imbalance in demographics. Next, an expert panel grouped the SDoH questions into SDoH factors to enable more consistent granularity. To identify the subtypes, we used bipartite modularity maximization for identifying SDoH biclusters and measured their significance and replicability. Next, we measured their association with 3 outcomes (depression, delayed medical care, and emergency room visits in the last year). Finally, the expert panel inferred the subtype labels, potential mechanisms, and targeted interventions. ResultsThe question 1 analysis identified 110 SDoH questions across 4 surveys covering all 5 domains in Healthy People 2030. As the SDoH questions varied in granularity, they were categorized by an expert panel into 18 SDoH factors. The question 2 analysis (n=12,913; d=18) identified 4 biclusters with significant biclusteredness (Q=0.13; random-Q=0.11; z=7.5; P

Abstract There is an increasing demand for the development of ion‐conducting electrolytes for energy storage systems. Much attention is directed toward deep eutectic solvents as potential candidates. In the search for highly conductive systems, the possibility of designing deep eutectic solvents with Grotthuss‐type proton transport is widely overlooked. Herein, ethaline, a mixture of choline chloride and ethylene glycol is used in a 1:2 molar ratio, to induce a significant conductivity increase with the addition of water and sulfuric acid (H2SO4). The achieved breakthrough conductivity is analyzed experimentally and simulated with ab initio molecular dynamics (AIMD). At sufficient water content, an H‐bonding network is formed that leads to a significant breakthrough conductivity based on H2SO4‐derived proton transfer following the long‐established Grotthuss proton transport mechanism. This result is substantiated by the positive deviation from the ideal KCl line in the Walden plot. Specifically, the data series positioned above the reference line indicates a Grotthuss mechanism in action. The AIMD simulations demonstrate proton transfer between water and ethylene glycol, supported by simulation frames captured at various times.

Abstract Background Older adults with cognitive impairment exhibit different patterns of healthcare utilization compared to their cognitively healthy counterparts. Despite extensive research in high-income countries, similar studies in low- and middle-income countries are lacking. This study aims to investigate the population-level patterns in healthcare utilization among older adults with and without cognitive impairment in Mexico. Methods Data came from five waves (2001–2018) of the Mexican Health and Aging Study. We used self-reported measures for one or more over-night hospital stays, doctor visits, visits to homeopathic doctors, and dental visits in the past year; seeing a pharmacist in the past year; and being screened for cholesterol, diabetes, and hypertension in the past two years. Cognitive impairment was defined using a modified version of the Cross Cultural Cognitive Examination that assessed verbal memory, visuospatial and visual scanning. Total sample included 5,673 participants with cognitive impairment and 34,497 without cognitive impairment interviewed between 2001 and 2018. Generalized Estimating Equation models that adjusted for time-varying demographic and health characteristics and included an interaction term between time and cognitive status were used. Results For all participants, the risk for one or more overnight hospital stays, doctor visits, and dental visits in the past year, and being screened for diabetes, hypertension, and high cholesterol increased from 2001 to 2012 and leveled off or decreased in 2015 and 2018. Conversely, seeing a homeopathic doctor decreased. Cognitive impairment was associated with higher risk of hospitalization (RR = 1.13, 1.03–1.23) but lower risk of outpatient services (RR = 0.95, 0.93–0.97), cholesterol screening (RR = 0.93, 0.91–0.96), and diabetes screening (RR = 0.95, 0.92–0.97). No significant difference was observed in the use of pharmacists, homeopathic doctors, or folk healers based on cognitive status. Interaction effects indicated participants with cognitive impairment had lower risk for dental visits and hypertension screening but that these trajectories differed over time compared to participants without cognitive impairment. Conclusions We identified distinct population-level trends in self-reported healthcare utilization and differences according to cognitive status, particularly for elective and screening services. These findings highlight the necessity for policy interventions to ensure older adults with cognitive impairment have their healthcare needs met.

We present a genome assembly from an individual Tausonia pullulans (a basidiomycete yeast; Basidiomycota; Tremellomycetes; Cystofilobasidiales; Mrakiaceae). The genome sequence is 23.9 megabases in span. Most of the assembly is scaffolded into 20 chromosomal pseudomolecules. The mitochondrial genome has also been assembled and is 18.82 kilobases in length.

Polymerase β (POLB), with dual functionality as a lyase and polymerase, plays a critical role in the base excision repair (BER) pathway to maintain genomic stability. POLB knockout and rescue studies in BRCA1/2-mutant cancer cell lines revealed that inhibition of lyase and polymerase activity is required for the synthetic lethal interaction observed with PARP inhibitors, highlighting POLB as a valuable therapeutic target. Traditional biochemical assays to screen for enzyme inhibitors focus on a single substrate to product relationship and limit the comprehensive analysis of enzymes such as POLB that utilize multiple substrates or catalyze a multi-step reaction. This report describes the first high-throughput mass spectrometry-based screen to measure the two distinct biochemical activities of POLB in a single assay using a duplexed self-assembled monolayer desorption ionization (SAMDI) mass spectrometry methodology. A multiplexed assay for POLB dual enzymatic activities was developed optimizing for kinetically balanced conditions and a collection of 200,000 diverse small molecules was screened in the duplexed format. Small molecule modulators identified in the screen were confirmed in a traditional fluorescence-based polymerase strand-displacement assay and an orthogonal label-free binding assay using SAMDI affinity selection mass spectrometry (ASMS). This work demonstrates the flexibility of high-throughput mass spectrometry approaches in drug discovery and highlights a novel application of SAMDI technology that opens new avenues for multiplexed high-throughput screening.

Background: Studies of adult populations in high-income countries have found an association between arthritis and myocardial infarction (MI) due to high levels of systemic inflammation. Our objectives were to examine the association between arthritis and MI among Mexican adults and to assess the mediating effect of C-reactive protein (CRP) on this association. Methods: Data came from the 2012, 2015, and 2018 observation waves of the Mexican Health and Aging Study. Our sample included 11,707 participants aged 50 and older with no prior MI before 2012. We used self-reported information for arthritis, joint pain, medication use, and limitations to daily activities in 2012. Logistic regression was used to model the association between arthritis and self-reported MI in 2015 or 2018. We used a sub-sample of 1602 participants to assess the mediating effect of CRP. Results: In the full sample, participants with arthritis that limited their daily activities had higher odds of MI than participants with no arthritis (OR = 1.40; 95 % CI = 1.04–1.88). In the sub-sample, arthritis that limited daily activities was associated with higher mean CRP (5.2 mg/dL; 95 % CI = 4.10–6.21) than arthritis with no limitations (3.5 mg/dL; 95 % CI = 2.93–4.01). However, CRP levels had a small mediating effect, and the relationship between arthritis with physical limitations and MI remained statistically significant. Conclusion: Mexican adults with arthritis that limits their daily activities are at an increased risk for MI. Continued research is needed to identify factors that contribute to this increased risk.

Societal Impact Statement Genetically modified (GM) crops have the potential to address multiple challenges for African smallholder farmers but are limited by several institutional constraints. Public–private partnerships (PPPs) are seen as an organizational fix to one such constraint, bringing privately held intellectual property rights on key crop technologies to African public institutions to develop GM crops for smallholder farmers. Here, a new comprehensive dataset of GM crops in Africa is used to understand the extent and efficacy of PPP‐led GM crop development for smallholder farmers and discuss what might limit their potential in the future. Summary Genetically modified (GM) crops are promoted as a key tool to address multiple challenges in Africa, including the impacts of climate change and food insecurity. Observers have noted, however, significant institutional challenges to achieving such goals, most notably, intellectual property rights (IPR) to key GM traits being held by private companies who have limited incentives to develop those technologies for smallholder farmers. To bridge the gap between privately held IPR and pro‐poor crop breeding, advocates have called for increased funding for institutional innovations such as public–private partnerships (PPPs) to facilitate the transfer of crop technologies from private companies to public research institutes. For the past two decades, donors and firms have invested considerable resources toward PPPs. However, to date, few research efforts have empirically examined the extent and effectiveness of PPPs at the continental scale. This study draws from a new comprehensive dataset on GM crop research and development in Africa to examine whether the anticipated advantages of PPPs have resulted in an improved ability to deliver GM crops to smallholder farmers. We find that although PPP research has focused on crops and traits more relevant for smallholder farmers, many of these efforts have been suspended, with only one crop thus far reaching the hands of farmers. PPPs can address some issues related to GM crop development but still appear constrained by other institutional challenges, which may limit their development, reach, and the achievement of targeted benefits for smallholder farmers.

Background: Compared to other occupational groups, first responders (FR) experience worse mental health outcomes due to duty-related trauma and occupational stressors. Despite their best efforts, they bring this stress home to friends and family. Consequently, FR and their supporters suffer from increased psychosocial difficulties and experience stigma and other barriers to help-seeking. Prior work offers little opportunity for open dialogue and shared understanding of the repercussions of this occupation for all members of the first responder community.In this qualitative study, we aimed to: (i) explore the lived experience of Irish FR and their family members (FM) related to occupational stressors, and (ii) identify opportunities to engage FM with existing organizational supports available for FR. Methods: Using a community based participatory research (CBPR) approach, we conducted six focus groups involving a total of fourteen participants comprising FR, organizational representatives, and FM. All focus groups were audio recorded, transcribed, and analyzed using reflexive thematic analysis. Findings: FR and FM shared their experiences of both joining and learning to live as members of the FR community in Ireland. Through our analysis, we identified a main theme of ‘crossing thresholds’, characterizing their transformative learning experiences. This learning experience includes recognizing the consequences of this new role for them as individuals and for their relationships. Participants also shared how they have learned to cope with the consequences of their roles and what they need to better support each other. Conclusions: FM are often unheard, hidden members of the first responder community in Ireland, highlighting an unmet need for FR organizations to acknowledge FM role in supporting FR and to provide them with the appropriate training and resources required. Training for new recruits needs to move beyond the tokenistic involvement of FM and encourage knowledge sharing among experienced and novice members. Cultural change is required to support help-seeking among FR and foster a sense of peer support and community among families.

El priapismo es una erección dolorosa y prolongada del pene que persiste en ausencia de actividad o deseo sexual. La mayoría de los casos se clasifican como bajo flujo o isquémicos. Se considera una emergencia urológica cuando la erección dura más de cuatro a seis horas. El objetivo es presentar una alternativa en el manejo del priapismo refractario. Presentamos nuestra experiencia en un paciente utilizando el procedimiento Grayhack. Consiste en un bypass safeno-cavernoso después de que el manejo conservador y los procedimientos quirúrgicos de primera línea no resuelven el priapismo. Posterior a la derivación safeno-cavernosa, el paciente describe una actividad sexual normal y complicaciones leves.

Biodiversity genomics research requires reliable organismal identification, which can be difficult based on morphology alone. DNA-based identification using DNA barcoding can provide confirmation of species identity and resolve taxonomic issues but is rarely used in studies generating reference genomes. Here, we describe the development and implementation of DNA barcoding for the Darwin Tree of Life Project (DToL), which aims to sequence and assemble high quality reference genomes for all eukaryotic species in Britain and Ireland. We present a standardised framework for DNA barcode sequencing and data interpretation that is then adapted for diverse organismal groups. DNA barcoding data from over 12,000 DToL specimens has identified up to 20% of samples requiring additional verification, with 2% of seed plants and 3.5% of animal specimens subsequently having their names changed. We also make recommendations for future developments using new sequencing approaches and streamlined bioinformatic approaches.

Abstract Background The post-acute patient standardized functional items (Section GG) include non-response options such as refuse, not attempt and not applicable. We examined non-response patterns and compared four methods to address non-response functional data in Section GG at nation-wide inpatient rehabilitation facilities (IRF). Methods We characterized non-response patterns using 100% Medicare 2018 data. We applied four methods to generate imputed values for each non-response functional item of each patient: Monte Carlo Markov Chains multiple imputations (MCMC), Fully Conditional Specification multiple imputations (FCS), Pattern-mixture model (PMM) multiple imputations and the Centers for Medicare and Medicaid Services (CMS) approach. We compared changes of Spearman correlations and weighted kappa between Section GG and the site-specific functional items across impairments before and after applying four methods. Results One hundred fifty-nine thousand six hundred ninety-one Medicare fee-for-services beneficiaries admitted to IRFs with stroke, brain dysfunction, neurologic condition, orthopedic disorders, and debility. At discharge, 3.9% (self-care) and 61.6% (mobility) of IRF patients had at least one non-response answer in Section GG. Patients tended to have non-response data due to refused at discharge than at admission. Patients with non-response data tended to have worse function, especially in mobility; also improved less functionally compared to patients without non-response data. Overall, patients coded as ‘refused’ were more functionally independent in self-care and patients coded as ‘not applicable’ were more functionally independent in transfer and mobility, compared to other non-response answers. Four methods showed similar changes in correlations and agreements between Section GG and the site-specific functional items, but variations exist across impairments between multiple imputations and the CMS approach. Conclusions The different reasons for non-response answers are correlated with varied functional status. The high proportion of patients with non-response data for mobility items raised a concern of biased IRF quality reporting. Our findings have potential implications for improving patient care, outcomes, quality reporting, and payment across post-acute settings.

Abstract Shared decision-making involves patients engaging with their physicians to make informed decisions regarding treatment selection, a process that empowers patients and ensures that treatment decisions reflect their individual values and preferences. However, shared decision-making can be challenging to implement for various reasons, including time, staffing, or resource limitations at community practices and differences in patients’ cultural backgrounds or health literacy. In this podcast, we discuss how to ensure that individual patients’ needs and concerns are addressed, including an overview of different approaches for initial consultations, strategies for tailoring conversations based on a patient’s background or health literacy, and trustworthy resources that can help improve patients’ understanding. As an illustrative example, we focus on how to implement shared decision-making to address the needs of a patient with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer who is eligible for combination therapy with a cyclin-dependent kinase 4/6 inhibitor plus an aromatase inhibitor. Overall, this podcast illustrates how shared decision-making is an achievable goal, even in small or underresourced practices, and provides an instructive guide on how to facilitate shared decision-making for patients with HR+/HER2− metastatic breast cancer. Podcast Discussion (MP4 29880 KB) Infographic

Abstract Fungal conservation is gaining momentum globally, but many challenges remain. To advance further, more data are needed on fungal diversity across space and time. Fundamental information regarding population sizes, trends, and geographic ranges is also critical to accurately assess the extinction risk of individual species. However, obtaining these data is particularly difficult for fungi due to their immense diversity, complex and problematic taxonomy, and cryptic nature. This paper explores how citizen science (CS) projects can be leveraged to advance fungal conservation efforts. We present several examples of past and ongoing CS‐based projects to record and monitor fungal diversity. These include projects that are part of broad collecting schemes, those that provide participants with targeted sampling methods, and those whereby participants collect environmental samples from which fungi can be obtained. We also examine challenges and solutions for how such projects can capture fungal diversity, estimate species absences, broaden participation, improve data curation, and translate resulting data into actionable conservation measures. Finally, we close the paper with a call for professional mycologists to engage with amateurs and local communities, presenting a framework to determine whether a given project would likely benefit from participation by citizen scientists.

BackgroundOlder cancer survivors likely experience physical function limitations due to cancer and its treatments, leading to disability and early mortality. Existing studies have focused on factors associated with surgical complications and mortality risk rather than factors associated with the development of poor disability status (DS), a proxy measure of poor performance status, in cancer survivors. We aimed to identify factors associated with the development of poor DS among older survivors of colorectal cancer (CRC) and compare poor DS rates to an age-sex-matched, non-cancer cohort.MethodsThis retrospective cohort study utilized administrative data from the Texas Cancer Registry Medicare-linked database. The study cohort consisted of 13,229 survivors of CRC diagnosed between 2005 and 2013 and an age-sex-matched, non-cancer cohort of 13,225 beneficiaries. The primary outcome was poor DS, determined by Davidoff’s method, using predictors from 12 months of Medicare claims after cancer diagnosis. Multivariable Cox proportional hazards regression was used to identify risk factors associated with the development of poor DS.ResultsAmong the survivors of CRC, 97% were 65 years or older. After a 9-year follow-up, 54% of survivors of CRC developed poor DS. Significant factors associated with future poor DS included: age at diagnosis (hazard ratio [HR] = 3.50 for >80 years old), female sex (HR = 1.50), race/ethnicity (HR = 1.34 for Hispanic and 1.21 for Black), stage at diagnosis (HR = 2.26 for distant metastasis), comorbidity index (HR = 2.18 for >1), and radiation therapy (HR = 1.21). Having cancer (HR = 1.07) was significantly associated with developing poor DS in the pooled cohorts; age and race/ethnicity were also significant factors.ConclusionsOur findings suggest that a CRC diagnosis is independently associated with a small increase in the risk of developing poor DS after accounting for other known factors. The study identified risk factors for developing poor DS in CRC survivors, including Hispanic and Black race/ethnicity, age, sex, histologic stage, and comorbidities. These findings underscore the importance of consistent physical function assessments, particularly among subsets of older survivors of CRC who are at higher risk of disability, to prevent developing poor DS.

Abstract Introduction Patient engagement in patient‐oriented research (POR) is described as patients collaborating as active and equal research team members (patient research partners [PRPs]) on the health research projects and activities that matter to them. The Canadian Institutes of Health Research (CIHR), Canada's federal funding agency for health research, asks that patients be included as partners early, often and at as many stages of the health research process as possible. The objective of this POR project was to co‐build an interactive, hands‐on training programme that could support PRPs in understanding the processes, logistics and roles of CIHR grant funding applications. We also conducted a patient engagement evaluation, capturing the experiences of the PRPs in co‐building the training programme. Methods This multiphased POR study included a Working Group of seven PRPs with diverse health and health research experiences and two staff members from the Patient Engagement Team. Seven Working Group sessions were held over the 3‐month period from June to August 2021. The Working Group worked synchronously (meeting weekly online via Zoom) as well as asynchronously. A patient engagement evaluation was conducted after the conclusion of the Working Group sessions using a validated survey and semi‐structured interviews. Survey data were analysed descriptively and interview data were analysed thematically. Results The Working Group co‐built and co‐delivered the training programme about the CIHR grant application process for PRPs and researchers in five webinars and workshops. For the evaluation of patient engagement within the Working Group, five out of seven PRPs completed the survey and four participated in interviews. From the survey, most PRPs agreed/strongly agreed to having communication and supports to engage in the Working Group. The main themes identified from the interviews were working together‐communication and supports; motivations for joining and staying; challenges to contributing; and impact of the Working Group. Conclusion This training programme supports and builds capacity for PRPs to understand the grant application process and offers ways by which they can highlight the unique experience and contribution they can bring to each project. Our co‐build process presents an example and highlights the need for inclusive approaches, flexibility and individual thinking and application. Patient or Public Contribution The objective of this project was to identify the aspects of the CIHR grant funding application that were elemental to having PRPs join grant funding applications and subsequently funded projects, in more active and meaningful roles, and then to co‐build a training programme that could support PRPs to do so. We used the CIHR SPOR Patient Engagement Framework, and included time and trust, in our patient engagement approaches to building a mutually respectful and reciprocal co‐learning space. Our Working Group included seven PRPs who contributed to the development of a training programme. We suggest that our patient engagement and partnership approaches, or elements of, could serve as a useful resource for co‐building more PRP‐centred learning programmes and tools going forward.

Abstract Background The opioid crisis continues in full force, as physicians and caregivers are desperate for resources to help patients with opioid use and chronic pain disorders find safer and more accessible non-opioid tools. Main body The purpose of this article is to review the current state of the opioid epidemic; the shifting picture of cannabinoids; and the research, policy, and current events that make opioid risk reduction an urgent public health challenge. The provided table contains an evidence-based clinical framework for the utilization of cannabinoids to treat patients with chronic pain who are dependent on opioids, seeking alternatives to opioids, and tapering opioids. Conclusion Based on a comprehensive review of the literature and epidemiological evidence to date, cannabinoids stand to be one of the most interesting, safe, and accessible tools available to attenuate the devastation resulting from the misuse and abuse of opioid narcotics. Considering the urgency of the opioid epidemic and broadening of cannabinoid accessibility amidst absent prescribing guidelines, the authors recommend use of this clinical framework in the contexts of both clinical research continuity and patient care.

Objective: To decrease the electronic health record (EHR) clerical burden and improve patient/clinician satisfaction, allied health staff were trained as visit facilitators (VFs) to assist the physician in clinical and administrative tasks. Patients and Methods: From December 7, 2020, to October 11, 2021, patients with complex medical conditions were evaluated by an internal medicine physician in an outpatient general internal medicine (GIM) consultative practice at a tertiary care institution. A VF assisted with specific tasks before, during, and after the clinical visit. Presurvey and postsurvey assessments were performed to understand the effect of the VF on clinical tasks as perceived by the physician. Results: A total of 57 GIM physicians used a VF, and 41 (82%) physicians and 39 (79%) physicians completed the pre-VF and post-VF surveys, respectively. Physicians reported a significant reduction in time reviewing outside materials, updating pertinent information, and creating/modifying EHR orders (P

Playful learning has seen a resurgence of interest in the past decade, particularly in contexts where play is not traditionally part of a teacher’s repertoire. Teachers interested in exploring the integration of play in their classrooms need formative tools and resources that help them to reflect and assess their own practice and their ability to create a playful learning experience for their students. This study presents the results of two rounds of pilot testing in three countries for Teacher RePlay, a new open-source toolkit designed to support teachers interested in reflecting on and deepening their learning through play practice. The toolkit includes the main Teacher RePlay observation protocol for teachers, as well as Children ReAct, a complementary protocol for a photo-elicited focus group discussion with children, intended to directly assess children’s experiences and reflections on learning through play. Upon observation, teachers receive customized coaching suggestions and tips designed to strengthen their learning through play practice. Initial results from the piloting indicate that the toolkit holds strong potential for teachers interested in better understanding and deepening their playful learning practice. This paper discusses the development, validation, successes, and challenges of the Teacher RePlay toolkit, and identifies future directions for its use.

Genetic modification of cells using viral vectors has shown huge therapeutic benefit in multiple diseases. However, inefficient transduction contributes to the high cost of these therapies. Several transduction-enhancing small molecules have previously been identified; however, some may be toxic to the cells or patient, otherwise alter cellular characteristics, or further increase manufacturing complexity. In this study, we aimed to identify molecules capable of enhancing lentiviral transduction of T cells from available small-molecule libraries. We conducted a high-throughput flow-cytometry-based screen of 27,892 compounds, which subsequently was narrowed down to six transduction-enhancing small molecules for further testing with two therapeutic lentiviral vectors used to manufacture GSK’s clinical T cell therapy products. We demonstrate enhanced transduction without a negative impact on other product attributes. Furthermore, we present results of transcriptomic analysis, suggesting alteration of ribosome biogenesis, resulting in reduced interferon response, as a potential mechanism of action for the transduction-enhancing activity of the lead compound. Finally, we demonstrate the ability of the lead transduction enhancer to produce a comparable T cell product using a 3-fold reduction in vector volume in our clinical manufacturing process, resulting in a predicted 15% reduction in the overall cost of goods.

ABSTRACTAs more cities implement cycling infrastructure, there is a growing need to both learn best practices from other places through a detailed understanding of the lived and embodied experiences of cycling. However, this is rarely the case. On the one hand, planners and policymakers rely on incomplete (quantitative) data and policy tours that are unable to document the full extent of cycling or how it is experienced. While recent studies have expanded to include qualitative methods, they are predominantly conducted in one place, limiting our ability to draw international comparisons. The Netherlands is a popular destination for such tours and is generally regarded as one of the best places in the world for cycling. But what about people who, for a variety of reasons, have lived in different countries? Their knowledge, experiences and reflections on cycling are rarely featured in planning. To redress this, we interviewed participants who have international experience, capturing beyond aspects of policy tourism, illuminating how: (1) mixed land-use patterns, (2) incentivizing cycling as a mode choice, and (3) cycle networks and safety are vital to cycling participation. We advance the cycling research agenda by examining these findings and proposing changes best suited to low-cycling cities.

Many nursing homes operated at thin profit margins prior to the COVID-19 pandemic. This study examines the role of nursing homes’ financial performance and chain affiliation in shortages of personal protection equipment (PPE) during the first year of the COVID-19 pandemic. We constructed a longitudinal file of 79 868 nursing home-week observations from 10 872 unique facilities. We found that a positive profit margin was associated with a 21.0% lower probability of reporting PPE shortages in chain-affiliated nursing homes, but not in non-chain nursing homes. Having adequate financial resources may help nursing homes address future emergencies, especially those affiliated with a multi-facility chain.