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Objective Individuals who work on health data systems and services are uniquely positioned to understand the risks of health data collection and use. We designed and conducted a survey assessing the perceptions of those who work with health data around health data consent, sharing, and privacy practices in healthcare and clinical research. Methods A 43-item online survey was distributed via a market research firm to individuals (18+) who work with health data in the United States from March to April 2023. Descriptive statistics were calculated for all variables. Associations with demographic variables were assessed using Pearson's X 2 tests and ordinal logistic regression. Results Most of our respondents (61.7%) reported that they would trust people to use their health data across various sectors, but more respondents trusted those working in academic medical research (86.5%) and healthcare offices (89.9%) compared to those working in industry (68.2%). Despite this reported trust, a strong majority believed that individuals should have complete control over their health data (97.3%), specific consent should be obtained for each use of their health data (92.0%), and that there should be higher standards of consent and privacy for health records data than other types of data (93.7%). Conclusions Based on our findings, we might infer that people who work with health data generally trust institutions across sectors to protect their health data. However, many would prefer to have complete control over who has access to their health data and how it is used. These insights should be explored further through qualitative studies.

Abstract Intrathecal delivery of autologous culture-expanded adipose tissue-derived mesenchymal stem cells (AD-MSC) could be utilized to treat traumatic spinal cord injury (SCI). This Phase I trial (ClinicalTrials.gov: NCT03308565) included 10 patients with American Spinal Injury Association Impairment Scale (AIS) grade A or B at the time of injury. The study’s primary outcome was the safety profile, as captured by the nature and frequency of adverse events. Secondary outcomes included changes in sensory and motor scores, imaging, cerebrospinal fluid markers, and somatosensory evoked potentials. The manufacturing and delivery of the regimen were successful for all patients. The most commonly reported adverse events were headache and musculoskeletal pain, observed in 8 patients. No serious AEs were observed. At final follow-up, seven patients demonstrated improvement in AIS grade from the time of injection. In conclusion, the study met the primary endpoint, demonstrating that AD-MSC harvesting and administration were well-tolerated in patients with traumatic SCI.

When reviewing the safety of food packaging, safety assessors must determine the migration levels of a food contact substance (FCS) from the packaging into the contained food products. Migration values can be expressed relative to levels in food using a single ‘food mass-to-surface area (mF/A) ratio’, representative of the general food supply. Because no published literature has examined mF/A ratios for the current U.S. food supply, this study aimed to use food databases to develop a standard mF/A ratio representative of packaged foods in the current U.S. food supply. First, we obtained information on the food-contact surface area (A) and food mass (mF) for a selection of packaged foods sold in U.S. retail stores. To adequately represent the variation of food products on the market, we identified a representative product per food category, using a 95-category list that was derived from the USDA WWEIA Food Categories. The values for A and mF per package were determined for each representative product using product size information from the Syndigo Nutrition Database. These data were used to calculate the A/mF ratio for each of the 95 representative products, and the average A/mF ratio was determined. The average A/mF ratio was weighted using consumption data from the WWEIA component of NHANES, so that more weight was given to foods that are consumed in greater quantities. The final step was to then take the reciprocal of the averaged A/mF ratio to obtain the final mF/A ratio. The resulting mF/A ratio was 4.8 g/in2, which rounds to 5 g/in2. In summary, we determined that 5 g/in2 is representative of the current U.S. food supply and could be used as a standard mF/A ratio when estimating migration levels of an FCS from packaging into food.

Abstract Background The gut microbiome undergoes primary ecological succession over the course of early life before achieving ecosystem stability around 3 years of age. These maturational patterns have been well-characterized for bacteria, but limited descriptions exist for other microbiota members, such as fungi. Further, our current understanding of the prevalence of different patterns of bacterial and fungal microbiome maturation and how inter-kingdom dynamics influence early-life microbiome establishment is limited. Results We examined individual shifts in bacterial and fungal alpha diversity from 3 to 12 months of age in 100 infants from the CHILD Cohort Study. We identified divergent patterns of gut bacterial or fungal microbiome maturation in over 40% of infants, which were characterized by differences in community composition, inter-kingdom dynamics, and microbe-derived metabolites in urine, suggestive of alterations in the timing of ecosystem transitions. Known microbiome-modifying factors, such as formula feeding and delivery by C-section, were associated with atypical bacterial, but not fungal, microbiome maturation patterns. Instead, fungal microbiome maturation was influenced by prenatal exposure to artificially sweetened beverages and the bacterial microbiome, emphasizing the importance of inter-kingdom dynamics in early-life colonization patterns. Conclusions These findings highlight the ecological and environmental factors underlying atypical patterns of microbiome maturation in infants, and the need to incorporate multi-kingdom and individual-level perspectives in microbiome research to improve our understandings of gut microbiome maturation patterns in early life and how they relate to host health. Video Abstract

Rationale & Objective: Understanding national attitudes about living kidney donation will enable us to identify and address existing disincentives to living kidney donation. We performed a national survey to describe living kidney donation perceptions, perceived factors that affect the willingness to donate, and analyzed differences by demographic subgroups. Study Design: The survey items captured living kidney donation awareness, living kidney donation knowledge, willingness to donate, and barriers and facilitators to living kidney donation. Setting & Population: We surveyed 802 US adults (aged 25-65 years) in June 2021, randomly selected from an online platform with diverse representation. Analytical Approach: We developed summed, scaled indices to assess the association between the living kidney donation knowledge (9 items) and the willingness to donate (8 items) to self-reported demographic characteristics and other variables of interest using analysis of variance. All other associations for categorical questions were calculated using Pearson’s χ2 and Fisher exact tests. We inductively evaluated free-text responses to identify additional barriers and facilitators to living kidney donation. Results: Most (86.6%) of the respondents reported that they might or would definitely consider donating a kidney while they were still living. Barriers to living kidney donation included concerns about the risk of the surgery, paying for medical expenses, and potential health effects. Facilitators to living kidney donation included having information on the donation surgery’s safety, knowing that the donor would not have to pay for medical expenses related to the donation, and hearing living kidney donation success stories. Awareness of the ability to participate in kidney-paired donation was associated with a higher willingness to donate. Limitations: Potential for selection bias resulting from the use of survey panels and varied incentive amounts, and measurement error related to respondents’ attention level. Conclusions: Most people would consider becoming a living kidney donor. Increased rates of living kidney donation may be possible with investment in culturally competent educational interventions that address risks associated with donating, policies that reduce financial disincentives, and communication campaigns that raise awareness of kidney-paired donation and living kidney donation. Plain-Language Summary: Understanding what the general public thinks about living kidney donation will help to develop better education and increase the number of living kidney donors. We surveyed the public to find out: (1) how aware they are about the opportunity to donate a kidney while alive; (2) how much they know about living kidney donation; (3) whether they would be willing to donate; and (4) what would affect their willingness to donate. We found that teaching people about the risks of donating, decreasing costs related to donation, and raising awareness about it could increase the number of people willing to donate.

Abstract Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (βindirect = −2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.

Abstract Learners’ metacognitive reading strategies support their attempts to draw meaning from texts and to overcome comprehension difficulties. For second language readers, such strategies may compensate for lack of language proficiency while reading. Taking a sample from a country that ranked last in the PISA 2018 reading assessment, this study aims to investigate potential discrepancies in how students evaluate the usefulness of specific reading strategies and how these conceptions are associated with related to the students’ reading proficiency. We explored the association between metacognitive reading strategies with reading proficiency by analysing data from a nationally representative sample of 15-year-old students who participated in the PISA 2018 (N = 6591). Awareness of different reading strategies was compared using repeated measures ANOVA; relationships with reading proficiency were examined using regression analysis. Self-reports on metacognitive reading strategies accounted for a significant portion of the variation in Filipino students’ English reading proficiency, after controlling for SES, sex, and number of books at home. The reading strategies perceived as most useful were not the most strongly associated with reading proficiency, suggesting that students may not be aware of which reading strategies are helpful in learning to read in English. The results indicate variations in the students’ awareness of which strategies aid in their reading comprehension and point to the need to better understand how effective reading strategy instruction is taught to and is engaged by Filipino students in their reading classes.

Rationale & Objective: Coronavirus disease (COVID)-19 has likely impacted accessibility to transplantation services among older adults (age ≥65 years). We quantified the impact of COVID-19 on kidney transplantation access for older kidney-only candidates registered on the United States (US) kidney waitlist. Study Design: Retrospective analysis of registry data. Setting & Participants: 57,222 older adults who were part of or added to the US kidney waitlist between January 1, 2016 and February 28, 2022, identified using the Scientific Registry of Transplant Recipients (SRTR). Exposures: Four COVID-19 waves and one nonwave period based on the national incidence of COVID-19 in the US (initial: March 15-May 30, 2020; winter 2020-2021: December 1, 2020-January 31, 2021; delta: August 1, 2021-September 30, 2021; omicron: December 1, 2021-February 28, 2022; nonwave: inter-wave periods). Outcomes: Waitlist registrations, deceased-donor kidney transplants, living-donor kidney transplants, waitlist mortality, and waitlist removals due to deteriorating condition (hereafter referred to as removals). Analytical Approach: Poisson regression for the adjusted incidence rate ratio (aIRR) of each outcome during the COVID-19 waves and the nonwave period relative to reference (January 1, 2016-December 31, 2019), adjusted for seasonality and secular trends. Results: Waitlist registrations initially declined and increased henceforth. Deceased-donor kidney transplants and living-donor kidney transplants remained below-expected levels during all waves. Waitlist mortality peaked during the winter 2020-2021 wave (aIRR: 1.701.982.30) and has declined since; mortality rates were 139%, 107%, and 251% above expected for Black candidates, men, and candidates aged ≥75 years, respectively, during the winter 2020-2021 wave. Removals increased from 22% below expected levels (initial wave) to 26% above expected levels (omicron wave); removals were nonsignificantly higher than expected during the omicron wave for older Black and Hispanic candidates. Limitations: The findings are not generalizable to those listed at earlier ages with prolonged waitlist times. Additionally, using national COVID-19 incidence does not consider local policy and health care variations. Lastly, aIRRs must be interpreted cautiously due to smaller daily event counts. Conclusions: COVID-19 was associated with fewer transplants and increased mortality and removals in older kidney transplant candidates. Transplant providers should consider this impact and implement policies and practices to ensure the continuity of care. Plain-Language Summary: The proportion of older adults on the kidney transplant waitlist is increasing, but the impact of COVID-19 on this population is not well characterized. In this study, we looked at incident waitlist registrations, deceased- and living-donor kidney transplants, and waitlist mortality and removals due to deteriorating condition over 4 waves of COVID-19. We found that transplantation services did not fully recover to prepandemic levels as of March 2022. Notably, racial/ethnic minorities and older men experienced lower rates of kidney transplants and higher rates of waitlist mortality, respectively, relative to White candidates and older women. Identifying vulnerable subpopulations affected by COVID-19 and its long-term impact is crucial for creating strategies to ensure the continuity of care in this population during public health emergencies.

BackgroundExploring the immune interface of follicular cell-derived thyroid cancer has prognostic and therapeutic potential. The available literature is lacking for comprehensive immunophenotyping in relation to clinical outcomes. In this study, we identify circulating immunophenotypes associated with thyroid cancer prognosis.MethodsWe conducted a pilot observational study of adults with follicular cell-derived thyroid cancer who underwent surgery at our tertiary care referral center and had consented for flow cytometry on peripheral blood collected at the time of thyroidectomy.ResultsOf the 32 included subjects, 20 (62%) had well differentiated, 5 (16%) had poorly differentiated, and 7 (22%) had anaplastic thyroid cancer. The most frequent AJCC stage was 4 (59%) and the ATA risk of recurrence category was high (56%). Patients with AJCC stage 3/4 demonstrated fewer circulating mononuclear cells (CD45+), more monocytes (CD14+), fewer total lymphocytes (CD14-), fewer T cells (CD3+), fewer CD4+ T cells, fewer gamma-delta T cells, fewer natural killer (NK) T-like cells, more myeloid-derived suppressor cells (MDSCs; Lin-CD33+HLADR-), and more effector memory T cells but similar CD8+ T cells compared to stage1/2. Immunophenotype comparisons by ATA risk stratification and course of thyroid cancer were comparable to those observed for stage, except for significant differences in memory T cell subtypes. The median follow-up was 58 months.ConclusionsAggressive follicular cell-derived thyroid cancer either at presentation or during follow-up is associated with down-regulation of the T cell populations specifically CD4+ T cells, gamma-delta T cells, and NK T-like cells but up-regulation of MDSCs and altered memory T cells. These immunophenotypes are potential prognostic biomarkers supporting future investigation for developing targeted immunotherapies against advanced thyroid cancer.

Objectives To assess the feasibility of conducting a pragmatic, multicentre randomised controlled trial (RCT) to test the clinical and cost-effectiveness of an informal caregiver training programme to support the recovery of people following hip fracture surgery.Design Two-arm, multicentre, pragmatic, open, feasibility RCT with embedded qualitative study.Setting National Health Service (NHS) providers in five English hospitals.Participants Community-dwelling adults, aged 60 years and over, who undergo hip fracture surgery and their informal caregivers.Intervention Usual care: usual NHS care. Experimental: usual NHS care plus a caregiver–patient dyad training programme (HIP HELPER). This programme comprised three, 1 hour, one-to-one training sessions for a patient and caregiver, delivered by a nurse, physiotherapist or occupational therapist in the hospital setting predischarge. After discharge, patients and caregivers were supported through three telephone coaching sessions.Randomisation and blinding Central randomisation was computer generated (1:1), stratified by hospital and level of patient cognitive impairment. There was no blinding.Main outcome measures Data collected at baseline and 4 months post randomisation included: screening logs, intervention logs, fidelity checklists, acceptability data and clinical outcomes. Interviews were conducted with a subset of participants and health professionals.Results 102 participants were enrolled (51 patients; 51 caregivers). Thirty-nine per cent (515/1311) of patients screened were eligible. Eleven per cent (56/515) of eligible patients consented to be randomised. Forty-eight per cent (12/25) of the intervention group reached compliance to their allocated intervention. There was no evidence of treatment contamination. Qualitative data demonstrated the trial and HIP HELPER programme was acceptable.Conclusions The HIP HELPER programme was acceptable to patient–caregiver dyads and health professionals. The COVID-19 pandemic impacting on site’s ability to deliver the research. Modifications are necessary to the design for a viable definitive RCT.Trial registration number ISRCTN13270387.

Abstract Filipino students’ performance in global assessments of science literacy has always been low, and this was confirmed again in the PISA 2018, where Filipino learners’ average science literacy scores ranked second to last among 78 countries. In this study, machine learning approaches were used to analyze PISA data from the student questionnaire to test models that best identify the poorest-performing Filipino students. The goal was to explore factors that could help identify the students who are vulnerable to very low achievement in science and that could indicate possible targets for reform in science education in the Philippines. The random forest classifier model was found to be the most accurate and more precise, and Shapley Additive Explanations indicated 15 variables that were most important in identifying the low-proficiency science students. The variables related to metacognitive awareness of reading strategies, social experiences in school, aspirations and pride about achievements, and family/home factors, include parents’ characteristics and access to ICT with internet connections. The results of the factors highlight the importance of considering personal and contextual factors beyond the typical instructional and curricular factors that are the foci of science education reform in the Philippines, and some implications for programs and policies for science education reform are suggested.

Introduction Many people quit smoking during pregnancy, but postpartum smoking relapse is common. Maintaining smoking abstinence achieved during pregnancy is key to improving maternal and child health. There are no evidence-based interventions for preventing postpartum smoking relapse. This trial aims to determine whether an intervention to prevent postpartum relapse is effective and cost-effective.Methods and analysis A randomised controlled trial of a complex intervention to prevent postpartum smoking relapse (BabyBreathe), with internal pilot, economic and process evaluations. Participants are adults who are pregnant and who report having quit smoking in the 12 months before, or during pregnancy. Participants are eligible if they read and understand English, and provide informed consent. Following consent and biochemical validation of smoking abstinence, participants are randomised to intervention or usual care/control (no specific relapse prevention support). The BabyBreathe intervention consists of manualised advice from a trained member of the health visiting service, health information leaflets for participants and partners, access to the BabyBreathe website and app. At the time of birth, participants are posted the BabyBreathe box and support is provided by text message for up to 12 months postpartum. Target sample size is 880, recruiting across midwifery services at four hubs in England and Scotland and through remote advertising in England, Scotland, Wales and Northern Ireland. Outcomes are collected at 6 and 12 months. The primary outcome is self-reported sustained smoking abstinence at 12 months, carbon monoxide verified. Secondary outcomes include self-reported abstinence, time to relapse, partner smoking status and quality of life.Ethics and dissemination The trial was approved by the North West Preston Research Ethics committee (21/NW/0017). Dissemination will include publication in peer-reviewed journals, presentation at academic and public conferences including patient and public involvement and to policymakers and practitioners.Trial registration number ISRCTN70307341

Objective: Heart transplants (HTs) from hepatitis C virus (HCV)-viremic donors to HCV-seronegative recipients (HCV D+/R–) have good 6-month outcomes, but practice uptake and long-term outcomes overall and among candidates on mechanical circulatory support (MCS) have yet to be established. Methods: Using the Scientific Registry of Transplant Recipients, we identified US adult HCV-seronegative HT recipients (R–) from 2015 to 2021. We classified donors as HCV-seronegative (D–) or HCV-viremic (D+). We used multivariable regression to compare post-HT extracorporeal membranous oxygenation, dialysis, pacemaker, acute rejection, and risk of post-HT mortality between HCV D+/R– and HCV D–/R–. Models were adjusted for donor, recipient, and transplant characteristics and center HT volume. We performed subgroup analyses of recipients bridged with MCS. Results: From 2015 to 2021, the number of HCV D+/R– HT increased from 1 to 181 and the number of centers performing HCV D+/R– HT increased from 1 to 60. Compared with HCV D–/R– recipients, HCV D+/R– versus D–/R– recipients overall and among patients bridged with MCS had similar odds of post-HT extracorporeal membranous oxygenation, dialysis, pacemaker, and acute rejection; and mortality risk at 30 days, 1 year, and 3 years (all P > .05). High center HT volume but not HCV D+/R– volume (5 in any year) was associated with lower mortality for HCV D+/R– HT. Conclusions: HCV D+/R– and D–/R– HT have similar outcomes at 3 years’ posttransplant. These results underscore the opportunity provided by HCV D+/R– HT, including among the growing population bridged with MCS, and the potential benefit of further expanding use of HCV+ allografts.

Introduction Over 50% of older adults are prescribed a medicine where the risk of harm outweighs the chances of benefit. During a hospital admission, older adults and carers expect medicines to be reviewed for appropriateness and any inappropriate medicines proactively deprescribed. While the principle of proactive deprescribing is an expectation of good prescribing practice, it is yet to become routine. The CompreHensive geriAtRician-led MEdication Review (CHARMER) study aims to develop and test a five-component behaviour change intervention to equip geriatricians and pharmacists to proactively deprescribe inappropriate medicines with older adults in hospital. This study aims to test the feasibility and acceptability of study processes and CHARMER implementation.Methods and analysis A two-arm purposive allocation feasibility study is being undertaken at four acute hospitals in England, UK (three intervention and one control). The target sample is 400 patients across all hospitals. Primary outcome measures are: (1) participant recruitment rate and (2) participant attrition rate. Secondary outcome measures are: (1) hospital readmission rate; (2) mortality rate and (3) quality of life. Quantitative data will be checked for completeness and quality, and practitioner and patient demographics descriptively analysed. We will undertake a rapid qualitative analysis on observations, interviews and study meeting minutes data. A subsequent thematic analysis will be undertaken with codes mapped to the Theoretical Domains Framework and Normalisation Process Theory. Triangulation of qualitative and quantitative data will be undertaken.Ethics and dissemination Ethics approval was obtained from Wales Research Ethics Committee 1 (IRAS ID 312494) and study approval from the Health Research Authority (22/WA/0087). Informed consent will be sought from all hospital staff involved in data collection activities and for patients involved in enhanced data collection activities. The findings of this study will be disseminated in peer-reviewed journals and conference presentations.Trial registration ISRCTN11899506.

Background. Incompatible living donor kidney transplant recipients (ILDKTr) require desensitization to facilitate transplantation, and this substantial upfront immunosuppression may result in serious complications, including cancer. Methods. To characterize cancer risk in ILDKTr, we evaluated 858 ILDKTr and 12 239 compatible living donor kidney transplant recipients (CLDKTr) from a multicenter cohort with linkage to the US transplant registry and 33 cancer registries (1997–2016). Cancer incidence was compared using weighted Cox regression. Results. Among ILDKTr, the median follow-up time was 6.7 y (maximum 16.1 y) for invasive cancers (ascertained via cancer registry linkage) and 5.0 y (maximum 16.1 y) for basal and squamous cell carcinomas (ascertained via the transplant registry and censored for transplant center loss to follow-up). Invasive cancers occurred in 53 ILDKTr (6.2%) and 811 CLDKTr (6.6%; weighted hazard ratio [wHR] 1.01; 95% confidence interval [CI], 0.76-1.35). Basal and squamous cell carcinomas occurred in 41 ILDKTr (4.8%) and 737 CLDKTr (6.0%) (wHR 0.99; 95% CI, 0.69-1.40). Cancer risk did not vary according to donor-specific antibody strength, and in an exploratory analysis, was similar between CLDKTr and ILDKTr for most cancer types and according to cancer stage, except ILDKTr had a suggestively increased risk of colorectal cancer (wHR 3.27; 95% CI, 1.23-8.71); however, this elevation was not significant after correction for multiple comparisons. Conclusions. These findings indicate that the risk of cancer is not increased for ILDKTr compared with CLDKTr. The possible elevation in colorectal cancer risk is unexplained and might suggest a need for tailored screening or prevention.

Abstract The present paper examines longitudinally how subjective perceptions about COVID-19, one’s community, and the government predict adherence to public health measures to reduce the spread of the virus. Using an international survey (N = 3040), we test how infection risk perception, trust in the governmental response and communications about COVID-19, conspiracy beliefs, social norms on distancing, tightness of culture, and community punishment predict various containment-related attitudes and behavior. Autoregressive analyses indicate that, at the personal level, personal hygiene behavior was predicted by personal infection risk perception. At social level, social distancing behaviors such as abstaining from face-to-face contact were predicted by perceived social norms. Support for behavioral mandates was predicted by confidence in the government and cultural tightness, whereas support for anti-lockdown protests was predicted by (lower) perceived clarity of communication about the virus. Results are discussed in light of policy implications and creating effective interventions.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive pulmonary disease characterized by aberrant tissue remodeling, formation of scar tissue within the lungs and continuous loss of lung function. The areas of fibrosis seen in lungs of IPF patients share many features with normal aging lung including cellular senescence. The contribution of the immune system to the etiology of IPF remains poorly understood. Evidence obtained from animal models and human studies suggests that innate and adaptive immune processes can orchestrate existing fibrotic responses. Currently, there is only modest effective pharmacotherapy for IPF. Mesenchymal stem cells (MSCs)-based therapies have emerged as a potential option treatment of IPF. This study characterizes the functionality of autologous MSCs for use as an IPF therapy and presents an attempt to determine whether the disease occurring in the lungs is associated with an alterated immune system. Methods Comprehensive characterization of autologous adipose-derived MSCs (aMSCs) from 5 IPF patient and 5 age- and gender-matched healthy controls (HC) was done using flow cytometry, PCR (ddPCR), multiplex Luminex xMAP technology, confocal microscopy self-renewal capacity and osteogenic differentiation. Additionally, multi-parameter quantitative flow cytometry of unmanipulated whole blood of 15 IPF patients and 87 (30 age- and gender-matched) HC was used to analyze 110 peripheral phenotypes to determine disease-associated changes in the immune system. Results There are no differences between autologous aMSCs from IPF patients and HC in their stem cell properties, self-renewal capacity, osteogenic differentiation, secretome content, cell cycle inhibitor marker levels and mitochondrial health. IPF patients had altered peripheral blood immunophenotype including reduced B cells subsets, increased T cell subsets and increased granulocytes demonstrating disease-associated alterations in the immune system. Conclusions Our results indicate that there are no differences in aMSC properties from IPF patients and HC, suggesting that autologous aMSCs may be an acceptable option for IPF therapy. The altered immune system of IPF patients may be a valuable biomarker for disease burden and monitoring therapeutic response,

Pathogenic Escherichia coli and Salmonella enterica pose serious public health threats due to their ability to cause severe gastroenteritis and life-threatening sequela, particularly in young children. Moreover, the emergence and dissemination of antibiotic resistance in these bacteria have complicated control of infections. Alternative strategies that effectively target these enteric pathogens and negate or reduce the need of antibiotics are urgently needed. Such an alternative is the CRISPR-Cas9 system because it can generate sequence-specific lethal double stranded DNA breaks. In this study, two self-transmissible broad host range conjugative plasmids, pRK24 and pBP136, were engineered to deliver multiplexed CRSIPR-Cas9 systems that specifically target Enterohemorrhagic and Enteropathogenic strains of E. coli (EHEC and EPEC), S. enterica, and blaCMY-2 antibiotic resistance plasmids. Using in vitro mating assays, we show that the conjugative delivery of pRK24-CRISPR-Cas9 carrying guide RNAs to the EPEC/EHEC eae (intimin) gene can selectively kill enterohemorrhagic E. coli O157 eae+ cells (3 log kill at 6 h) but does not kill the isogenic Δeae mutant (P

Objectives To determine if a newer design of total knee replacement (TKR) (Journey II BCS) produces superior patient-reported outcomes scores and biomechanical outcomes than the older, more established design (Genesis II).Setting Patients were recruited from an NHS University Hospital between July 2018 and October 2019 with surgery at two sites. Biomechanical and functional capacity measurements were at a University Movement and Exercise Laboratory.Participants 80 participants undergoing single-stage TKR.Interventions Patients were randomised to receive either the Journey II BCS (JII-BCS) or Genesis II TKR.Primary and secondary outcome measures Primary outcome was the Oxford Knee Score (OKS), at 6 months. Secondary outcomes were: OKS Activity and Participation Questionnaire, EQ-5D-5L and UCLA Activity scores, Timed Up and Go Test, 6 min walk test, lower limb kinematics and lower limb muscle activity during walking and balance.Results This study found no difference in the OKS between groups. The OKS scores for the JII-BCS and Genesis II groups were mean (SD) 42.97 (5.21) and 43.13 (5.20) respectively, adjusted effect size 0.35 (-2.01,2.71) p=0.771In secondary outcome measures, the Genesis II group demonstrated a significantly greater walking range-of-movement (50.62 (7.33) vs 46.07 (7.71) degrees, adjusted effect size, 3.14 (0.61,5.68) p=0.02) and higher peak knee flexion angular velocity during walking (mean (SD) 307.69 (38.96) vs 330.38 (41.40) degrees/second, adjusted effect size was 21.75 (4.54,38.96), p=0.01) and better postural control (smaller resultant centre of path length) during quiet standing than the JII-BCS group (mean (SD) 158.14 (65.40) vs 235.48 (176.94) mm, adjusted effect size, 59.91 (–105.98, –13.85) p=0.01.).Conclusions In this study population, the findings do not support the hypothesis that the Journey II BCS produces a better outcome than the Genesis II for the primary outcome of the OKS at 6 months after surgery.Trial registration number ISRCTN32315753.

Introduction Chronic musculoskeletal (bone, joint or muscle) pain is disabling. People with it frequently have difficulties in managing everyday activities. Individuals may rely on family members or friends to support them. These people are known as informal caregivers. No interventions have previously addressed the health needs of people with chronic musculoskeletal pain and their caregivers. In response, the JOINT SUPPORT programme was developed. In this study, we will assess the feasibility and acceptability of conducting a pragmatic, multicentre, randomised controlled trial (RCT) to test the clinical and cost-effectiveness of the JOINT SUPPORT programme to support these individuals.Methods and analysis This will be a mixed-methods feasibility RCT. We will recruit 80 patients with chronic musculoskeletal pain with their informal caregivers. Patients will be randomised to usual National Health Service (NHS) care OR usual NHS care plus a caregiver–patient dyad training programme (JOINT SUPPORT). This programme comprises of five, 1-hour, group-based sessions for patients and caregivers, delivered by trained physiotherapists or occupational therapists. It includes developing skills in: understanding pain, pacing, graded activity, fear avoidance and goal-setting, understanding benefits of physical activity and skills in medication management. This will be re-enforced with a workbook. After the group-based sessions, patients and caregivers will be supported through three telephone sessions with a therapist. Data collected at baseline and 3 months will include: screening logs, intervention logs, fidelity checklists and clinical outcomes on quality of life, physical and emotional outcomes, adverse events and resource use. Qualitative research with 24 patient–caregiver dyads and 12 healthcare professionals will explore the acceptability of trial processes. Stop–go criteria will inform the progression to a full trial.Ethics and dissemination Ethical approval was obtained on 22 February 2022 (National Research Ethics Committee Number: 22/NW/0015). Results will be reported at conferences, peer-review publications and across social media channels.Trial registration number ISRCTN78169443.

Introduction Attendees of emergency departments (EDs) have a higher than expected prevalence of smoking. ED attendance may be a good opportunity to prompt positive behaviour change, even for smokers not currently motivated to quit. This study aims to determine whether an opportunist smoking cessation intervention delivered in the ED can help daily smokers attending the ED quit smoking and is cost-effective.Methods and analysis A two-arm pragmatic, multicentred, parallel-group, individually randomised, controlled superiority trial with an internal pilot, economic evaluation and mixed methods process evaluation. The trial will compare ED-based brief smoking cessation advice, including provision of an e-cigarette and referral to local stop smoking services (intervention) with the provision of contact details for local stop smoking services (control). Target sample size is 972, recruiting across 6 National Health Service EDs in England and Scotland. Outcomes will be collected at 1, 3 and 6 months. The primary outcome at 6 months is carbon monoxide verified continuous smoking abstinence.Ethics and dissemination The trial was approved by the South Central—Oxford B Research Committee (21/SC/0288). Dissemination will include the publication of outcomes, and the process and economic evaluations in peer-reviewed journals. The findings will also be appropriately disseminated to relevant practice, policy and patient representative groups.Trial registration number NCT04854616; protocol V.4.2.

Background. Following the outbreak of coronavirus disease 2019 (COVID-19) in the United States, the number of kidney waitlist additions and living-donor and deceased-donor kidney transplants (LDKT/DDKT) decreased substantially but began recovering within a few months. Since then, there have been several additional waves of infection, most notably, the Delta and Omicron surges beginning in August and December 2021, respectively. Methods. Using SRTR data, we compared observed waitlist registrations, waitlist mortality, waitlist removal due to deteriorating condition, LDKT, and DDKT over 5 distinct pandemic periods to expected events based on calculations from preepidemic data while accounting for seasonality and secular trends. Results. Although the number of daily waitlist additions has been increasing since May 2020, the size of the active waitlist has consistently declined, reaching a minimum of 52 556 on February 27, 2022. The recent Omicron surge knocked LDKT from 25% below baseline (incidence rate ratio [IRR] = 0.690.750.81) during the Delta wave to 38% below baseline (IRR = 0.580.620.67). DDKT, however, was less affected by the Omicron wave (IRR = 0.850.890.93 and 0.880.920.96 during the Delta and Omicron waves, respectively). Waitlist death decreased from 56% above baseline (IRR = 1.431.561.70) during Delta to 41% above baseline during Omicron, whereas waitlist removal due to deteriorating condition remained at baseline/expected levels during the Delta wave (IRR = 0.931.021.12) and the Omicron wave (IRR = 0.991.071.16). Conclusions. Despite exceptionally high COVID-19 incidence during the Omicron wave, the transplant system responded similarly to prior waves that imposed a lesser disease burden, demonstrating the transplant system’s growing adaptations and resilience to this now endemic disease.

ABSTRACT Background Engagement frameworks provide the conceptual structure for consumer engagement in healthcare decision making, but the level to which these frameworks support culturally and linguistically diverse (CALD) consumer engagement is not known. Objective This study aimed to investigate how consumer engagement is conceptualised and operationalized and to determine the implications of current consumer engagement frameworks for engagement with CALD consumers. Method Altheide's document analysis approach was used to guide a systematic search, selection and analytic process. Australian Government health department websites were searched for eligible publicly available engagement frameworks. A narrative synthesis was conducted. Results Eleven engagement frameworks published between 2007 and 2019 were identified and analysed. Only four frameworks discussed engagement with CALD consumers distinctly. Organisational prerequisites to enhance engagement opportunities and approaches to enable activities of engagement were highlighted to improve CALD consumers' active participation in decision making; however, these largely focused on language, with limited exploration of culturally sensitive services. Conclusion There is limited discussion of what culturally sensitive services look like and what resources are needed to enhance CALD consumer engagement in high‐level decision making. Health services and policy makers can enhance opportunities for engagement with CALD consumers by being flexible in their approach, implementing policies for reimbursement for participation and evaluating and adapting the activities of engagement in collaboration with CALD consumers. Patient/Public Contribution This study is part of a wider ‘CanEngage’ project, which includes a consumer investigator, and is supported by a consumer advisory group. The study was conceived with inputs from the consumer advisory group, which continued to meet regularly with the project team to discuss the methodology and emerging findings.

The HIV latent viral reservoir (LVR) remains a major challenge in the effort to find a cure for HIV. There is interest in lymphocyte-depleting agents, used in solid organ and bone marrow transplantation to reduce the LVR. This study evaluated the LVR and T cell receptor repertoire in HIV-infected kidney transplant recipients using intact proviral DNA assay and T cell receptor sequencing in patients receiving lymphocyte-depleting or lymphocyte-nondepleting immunosuppression induction therapy. CD4+ T cells and intact and defective provirus frequencies decreased following lymphocyte-depleting induction therapy but rebounded to near baseline levels within 1 year after induction. In contrast, these biomarkers were relatively stable over time in the lymphocyte-nondepleting group. The lymphocyte-depleting group had early TCRβ repertoire turnover and newly detected and expanded clones compared with the lymphocyte-nondepleting group. No differences were observed in TCRβ clonality and repertoire richness between groups. These findings suggest that, even with significant decreases in the overall size of the circulating LVR, the reservoir can be reconstituted in a relatively short period of time. These results, while from a relatively unique population, suggest that curative strategies aimed at depleting the HIV LVR will need to achieve specific and durable levels of HIV-infected T cell depletion.

Background. ABO type B and O kidney transplant candidates have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival. Methods. We used weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i versus ABO-compatible (ABOc) recipients. Results. Using Scientific Registry of Transplant Recipients data 2000–2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1-/5-/10-y mortality was 0.9%/6.5%/24.2%, respectively, among A2i LDKT recipients versus 1.4%/7.7%/22.2%, respectively, among ABOc LDKT recipients (weighted hazard ratio [wHR], 0.811.041.33; P = 0.8). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1-/5-/10-y graft failure was 5.7%/11.6%/22.4% for A2i versus 1.7%/7.5%/17.2% for ABOc recipients (wHR in year 1 = 2.243.565.66; through year 5 = 1.251.782.53; through year 10 = 1.151.552.07). By comparison, 1-/5-/10-y wHRs for A1-incompatible recipients were 0.631.966.08/0.390.942.27/0.390.831.74. Conclusions. A2i LDKT is generally safe, but A2i donor/recipient pairs should be counseled about the increased risk of graft failure and be monitored as closely as their A1-incompatible counterparts posttransplant.

BackgroundDistress is common immediately after diagnosis of testicular cancer. It has historically been difficult to engage people in care models to alleviate distress because of complex factors, including differential coping strategies and influences of social gender norms. Existing support specifically focuses on long-term survivors of testicular cancer, leaving an unmet need for age-appropriate and sex-sensitized support for individuals with distress shortly after diagnosis. ObjectiveWe evaluated a web-based intervention, Nuts & Bolts, designed to provide support and alleviate distress after diagnosis of testicular cancer. MethodsUsing a mixed methods design to evaluate the acceptability, feasibility, and impact of Nuts & Bolts on distress, we randomly assigned participants with recently diagnosed testicular cancer (1:1) access to Nuts & Bolts at the time of consent (early) or alternatively, 1 week later (day 8; delayed). Participants completed serial questionnaires across a 4- to 5-week period to evaluate levels of distress (measured by the National Comprehensive Cancer Network Distress Thermometer [DT]; scored 0-10), anxiety, and depression (Hospital Anxiety and Depression Score [HADS]–Anxiety and HADS-Depression; each scored 0-21). The primary end point was change in distress between consent and day 8. Secondary end points of distress, anxiety, and depression were assessed at defined intervals during follow-up. Optional, semistructured interviews occurring after completion of quantitative assessments were thematically analyzed. ResultsOverall, 39 participants were enrolled in this study. The median time from orchidectomy to study consent was 14.8 (range 3-62) days. Moderate or high levels of distress evaluated using DT were reported in 58% (23/39) of participants at consent and reduced to 13% (5/38) after 1 week of observation. Early intervention with Nuts & Bolts did not significantly decrease the mean DT score by day 8 compared with delayed intervention (early: 4.56-2.74 vs delayed: 4.47-2.74; P=.85), who did not yet have access to the website. A higher baseline DT score was significantly predictive of reduction in DT score during this period (P

This study explored people’s estimation of cooperative intention when paired with people with different types of relationships, and the mediating roles of trust and responsibility between guanxi perception and the estimation of cooperative intention. We recruited 398 university students from the Greater Bay Area of China to complete two public goods dilemma experiments. Study 1 manipulated the type of partner to be either family member, classmate, and stranger, representing different types of guanxi. Study 2 manipulated the type of partner to be either stranger with intermediary, stranger within ingroup, and complete stranger. In both studies, the mediating roles of trust and responsibility in the relationship between guanxi perception and the estimation of cooperative intention were tested. The results of study 1 showed that the participants’ estimation of cooperative intention with a family member was higher than with acquaintances or with strangers. In study 2, the estimation of cooperative intention with stranger with intermediary was higher than with a stranger within one’s ingroup or with a complete stranger. Multivariate analysis verified the mediating effects. The results are discussed with reference to why Chinese people treat different types of guanxi distinctly, especially to different types of strangers, and how guanxi perception, trust, and responsibility work together to the influence of the estimation of cooperative intention.

2016年，菲律賓國會頒布法律實施新的高中計畫，將基礎教育週期增加了兩年。作為這項國家改革的一部分，學校必須招募和培養第一批高中教師以實施新課程。本研究採用混合方法，通過分析馬尼拉大都會私立學校的新高中教師在應對新要求、新義務和新增的不確定性時的感受（統稱為「需求感知」），來探索國家教育改革的微觀影響。本研究採用聚合平行設計的混合研究方法，由焦點小組討論的質性數據和問卷調查的量化數據得知，與需求感知有關的領域包括職業規劃、教學任務和經濟考量。量化數據進一步表明，高職業相關的需求感知與較低積極應對策略及低自尊有關。本研究的結果指出了職業相關的需求感知負荷是如何與教師的應對機制相關聯的。本文最後重點討論了在分析改革對教師的微觀影響時運用由社會變化而產生的需求感知的可行性，及可能的執行策略。 In 2016, the Philippine Congress enacted a law that added 2 years to the basic education cycle by implementing a new Senior High School (SHS) program. As part of this national reform effort, schools were required to recruit, orient, and train the first batch of SHS teachers to implement the new curriculum. This mixed methods study explored the microlevel effects of national education reform by analyzing the experiences of new SHS teachers at private schools in Metro Manila regarding new requirements, novel obligations, and increased uncertainties; these are collectively referred to as “perceived demand.” A convergent parallel design for mixed methods research was employed, and qualitative data from focus group discussions and quantitative data from a questionnaire revealed that several domains were related to perceived demand, including career plans, instructional tasks, and financial concerns. Quantitative data further indicated how heavy, career-related perceived demand was associated with less positive coping strategies and reduced self-esteem. The results demonstrate how the burden of career-related perceived demand relates to teachers’ coping mechanisms. The discussion focused on the viability of applying perceived demand caused by social change in analyzing the microlevel effects of reform on teachers, and possible strategies for implementation were discussed.

Background. Automation of deceased donor referrals with standardized clinical triggers allows organ procurement organizations to be rapidly aware of medically eligible potential donors without the need for manual reporting and subjective decision-making of otherwise very busy hospital staff. In October 2018, 3 Texas hospitals (pilot hospitals) began using an automated referral system; our goal was to evaluate the impact of this system on eligible donor referral. Methods. We studied ventilated referrals (n = 28 034) in a single organ procurement organization from January 2015 to March 2021. We estimated the change in referral rate in the 3 pilot hospitals due to the automated referral system using a difference-in-differences analysis with Poisson regression. Results. Ventilated referrals from the pilot hospitals increased from mean 11.7 per month pre-October 2018 to 26.7 per month post-October 2018. The difference-in-differences analysis estimated that automated referral was associated with a 45% increase in referrals (adjusted incidence rate ratio [aIRR] = 1.30 1.45 1.62), an 83% increase in approaches for authorization (aIRR = 1.34 1.83 2.48), a 73% increase in authorizations (aIRR = 1.18 1.73 2.55), and a 92% increase in organ donors (aIRR = 1.13 1.92 3.09). Conclusions. Following deployment of an automated referral system that did not require any actions by the referring hospital, referrals, authorizations, and organ donors increased substantially in the 3 pilot hospitals. Broader deployment of automated referral systems may lead to increases in the deceased donor pool.

Literature from worldwide revealed that poor mental health is evident among youths living with HIV (YLHIV). However, literature exploring their mental health in the Philippines is limited despite the alarming increase of HIV cases among young people. Hence, this descriptive phenomenological study purported to characterize the mental health of a select group of Filipino YLHIV. In-depth interviews with ten fully consented male participants aged 18-30 were conducted. Field texts were subjected to Collaizi's (1978) seven-step data analysis method. Interestingly, the Mental Health Tower of Youth Living with HIV emerged after thoroughly analyzing the data. This model typifies the mental health of YLHIV, which operates in an environment where both internal and external pressures make them experience (a) disruptive thoughts, (b) depressive mood, and (c) deteriorative behavior. The study has vividly described the instability of the YLHIV's mental health. Therefore, it is vital to develop a mental health program specifically designed for youth living with HIV.

Today, more than ever, there is a need to uncover the patterns of thinking that shape the rationality of the leader cohort to aid them in their role-making of the challenging niche truly. This Husserlian phenomenological inquiry purported to explore the individual and collective lived experiences of nine (9) purposively selected Filipino academic managers regarding the essence of Dweck's growth and fixed mindsets in their leadership preparation. A semi-structured interview was employed as the main data gathering tool. Field texts were analyzed using Colaizzi's Procedural Steps to abstract the phenomenon's essence and were validated through the member checking procedure and critical friend technique. Interestingly, the study debuts an insightful Taxonomy of Cognitive Personas, which typifies the dynamic nature of the leader cohort's mindsets. Embedded in the Perennial Learner, Proactive Player, and Pragmatic Leader personas are cognitive tools and value priorities utilized in various influencing and regulating experiences in academic organizations. Academic organizations can use the findings of this study to focus on the cognitive preparation of millennial managers for higher leadership roles. Such findings are expected to complement the skill-based preparation that the millennials can employ for their role-making efforts in school leadership.

Abstract This paper examines whether compliance with COVID-19 mitigation measures is motivated by wanting to save lives or save the economy (or both), and which implications this carries to fight the pandemic. National representative samples were collected from 24 countries (N = 25,435). The main predictors were (1) perceived risk to contract coronavirus, (2) perceived risk to suffer economic losses due to coronavirus, and (3) their interaction effect. Individual and country-level variables were added as covariates in multilevel regression models. We examined compliance with various preventive health behaviors and support for strict containment policies. Results show that perceived economic risk consistently predicted mitigation behavior and policy support—and its effects were positive. Perceived health risk had mixed effects. Only two significant interactions between health and economic risk were identified—both positive.

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

Abstract Background Transplantation of HIV-positive (HIV+) donor organs for HIV+ recipients (HIV D+/R+) is now being performed as research in the United States, but raises ethical concerns. While patient-reported outcome measures are increasingly used to evaluate clinical interventions, there is no published measure to aptly capture patients’ experiences in the unique context of experimental HIV D+/R+ transplantation. Therefore, we developed PROMETHEUS (patient-reported measure of experimental transplants with HIV and ethics in the United States). To do so, we created a conceptual framework, drafted a pilot battery using existing and new measures related to this context, and refined it based on cognitive and pilot testing. PROMETHEUS was administered 6-months post-transplant in a clinical trial evaluating these transplants. We analyzed data from the first 20 patient-participants for reliability and validity by calculating Cronbach’s alpha and reviewing item performance characteristics. Results PROMETHEUS 1.0 consisted of 29 items with 5 putative subscales: Emotions; Trust; Decision Making; Transplant; and Decision Satisfaction. Overall, responses were positive. Cronbach’s alpha was > 0.8 for all subscales except Transplant, which was 0.38. Two Transplant subscale items were removed due to poor reliability and construct validity. Conclusions We developed PROMETHEUS to systematically capture patient-reported experiences with this novel experimental transplantation program, nested it in an actual clinical trial, and obtained preliminary data regarding its performance.

It was hypothesized that mesenchymal stem cells (MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance® Nerve Grafts or NeuraGen® Nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance® Nerve Grafts and 30 NeuraGen® Nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), pleiotrophin (PTN), growth associated protein 43 (GAP43) and brain-derived neurotrophic factor (BDNF)], myelination [peripheral myelin protein 22 (PMP22) and myelin protein zero (MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1 (PECAM1/CD31) and vascular endothelial cell growth factor alpha (VEGFA)], extracellular matrix (ECM) [collagen type alpha I (COL1A1), collagen type alpha III (COL3A1), Fibulin 1 (FBLN1) and laminin subunit beta 2 (LAMB2)] and cell surface marker cluster of differentiation 96 (CD96) gene expression was quantified. Unseeded Avance® Nerve Grafts and NeuraGen® Nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance® Nerve Grafts led to a short-term upregulation of neurotrophic (NGF, GDNF and BDNF), myelination (PMP22 and MPZ) and angiogenic genes (CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the NeuraGen® Nerve Guide led to short term upregulation of neurotrophic (NGF, GDNF and BDNF) myelination (PMP22 and MPZ), angiogenic (CD31 and VEGFA), ECM (COL1A1) and cell surface (CD96) genes and long-term upregulation of neurotrophic (GDNF and BDNF), angiogenic (CD31 and VEGFA), ECM genes (COL1A1, COL3A1, and FBLN1) and cell surface (CD96) genes. Analysis demonstrated MSCs seeded onto NeuraGen® Nerve Guides expressed significantly higher levels of neurotrophic (PTN), angiogenic (VEGFA) and ECM (COL3A1, FBLN1) genes in the long term period compared to MSCs seeded onto Avance® Nerve Grafts. Overall, the interaction between human MSCs and both nerve graft substitutes resulted in a significant upregulation of the expression of numerous genes important for nerve regeneration over time. The in vitro interaction of MSCs with the NeuraGen® Nerve Guide was more pronounced, particularly in the long term period (> 14 days after seeding). These results suggest that MSC-seeding has potential to be applied in a clinical setting, which needs to be confirmed in future in vitro and in vivo research.

The professional development of teachers is an important component of quality standards for any educational system, as teachers’ engagement in continuing professional development (CPD) activities are related with aspects of professional commitment and satisfaction. In this study, we explore how perceived demands of a national educational reform in the Philippines are associatedwithdifferent indicators of senior high school teachers’ professional development.A survey of 289teachers recruited to teach senior high school for the first time in the Philippines indicated that perceived demand was not associated with CPD participation intentions,but thatperceived demand related to job requirement and to career planning had different associations with attitudes towards CPD. These different associations can be viewed as adaptive responding to the uncertainties in their changing work environment. The implications for conceptualizing the context of teachers’ professional development, and the external factors that strengthen or weaken teachers’ positive attitudes towards CPD are discussed.

Abstract Background Live kidney donors (LKDs) account for nearly a third of kidney transplants in the United States. While donor nephrectomy poses minimal post-surgical risk, LKDs face an elevated adjusted risk of developing chronic diseases such as hypertension, diabetes, and end-stage renal disease. Routine screening presents an opportunity for the early detection and management of chronic conditions. Transplant hospital reporting requirements mandate the submission of laboratory and clinical data at 6-months, 1-year, and 2-years after kidney donation, but less than 50% of hospitals are able to comply. Strategies to increase patient engagement in follow-up efforts while minimizing administrative burden are needed. We seek to evaluate the effectiveness of using small financial incentives to promote patient compliance with LKD follow-up. Methods/design We are conducting a two-arm randomized controlled trial (RCT) of patients who undergo live donor nephrectomy at The Johns Hopkins Hospital Comprehensive Transplant Center (MDJH) and the University of Maryland Medical Center Transplant Center (MDUM). Eligible donors will be recruited in-person at their first post-surgical clinic visit or over the phone. We will use block randomization to assign LKDs to the intervention ($25 gift card at each follow-up visit) or control arm (current standard of care). Follow-up compliance will be tracked over time. The primary outcome will be complete (all components addressed) and timely (60 days before or after expected visit date), submission of LKD follow-up data at required 6-month, 1-year, and 2-year time points. The secondary outcome will be transplant hospital-level compliance with federal reporting requirements at each visit. Rates will be compared between the two arms following the intention-to-treat principle. Discussion Small financial incentivization might increase patient compliance in the context of LKD follow-up, without placing undue administrative burden on transplant providers. The findings of this RCT will inform potential center- and national-level initiatives to provide all LKDs with small financial incentives to promote engagement with post-donation monitoring efforts. Trial registration ClinicalTrials.gov number: NCT03090646 Date of registration: March 2, 2017 Sponsors: Johns Hopkins University, University of Maryland Medical Center Funding: The Living Legacy Foundation of Maryland

The folate receptor alpha (FRα) is overexpressed in the majority of high-grade serous ovarian cancers and has been proposed as a candidate vaccine antigen. Here the authors report the safety and immunogenicity of Th17-inducing dendritic cells pulsed with FRα-derived epitopes in an early phase I clinical trial with ovarian cancer patients.

Abstract Background Fungi constitute an important yet frequently neglected component of the human microbiota with a possible role in health and disease. Fungi and bacteria colonise the infant gastrointestinal tract in parallel, yet most infant microbiome studies have ignored fungi. Milk is a source of diverse and viable bacteria, but few studies have assessed the diversity of fungi in human milk. Results Here we profiled mycobiota in milk from 271 mothers in the CHILD birth cohort and detected fungi in 58 (21.4%). Samples containing detectable fungi were dominated by Candida, Alternaria, and Rhodotorula, and had lower concentrations of two human milk oligosaccharides (disialyllacto-N-tetraose and lacto-N-hexaose). The presence of milk fungi was associated with multiple outdoor environmental features (city, population density, and season), maternal atopy, and early-life antibiotic exposure. In addition, despite a strong positive correlation between bacterial and fungal richness, there was a co-exclusion pattern between the most abundant fungus (Candida) and most of the core bacterial genera. Conclusion We profiled human milk mycobiota in a well-characterised cohort of mother-infant dyads and provide evidence of possible host-environment interactions in fungal inoculation. Further research is required to establish the role of breastfeeding in delivering fungi to the developing infant, and to assess the health impact of the milk microbiota in its entirety, including both bacterial and fungal components.

Abstract Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of ‘personalized’ therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is

Background. Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. Methods. We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March–May 2020, 21 patients; and Era 2: June–November 2020, 56 patients) and 52 solid organ transplant outpatients. Results. In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post–COVID-19 renal and liver function were comparable between eras, out to 90 d. Conclusions. Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

Background: Falls in care home residents are common, unpleasant, costly and difficult to prevent. Objectives: The objectives were to evaluate the clinical effectiveness and cost-effectiveness of the Guide to Action for falls prevention in Care Homes (GtACH) programme. Design: A multicentre, cluster, parallel, 1 : 1 randomised controlled trial with embedded process evaluation and economic evaluation. Care homes were randomised on a 1 : 1 basis to the GtACH programme or usual care using a secure web-based randomisation service. Research assistants, participating residents and staff informants were blind to allocation at recruitment; research assistants were blind to allocation at follow-up. NHS Digital data were extracted blindly. Setting: Older people’s care homes from 10 UK sites. Participants: Older care home residents. Intervention: The GtACH programme, which includes care home staff training, systematic use of a multidomain decision support tool and implementation of falls prevention actions, compared to usual falls prevention care. Outcomes: The primary trial outcome was the rate of falls per participating resident occurring during the 90-day period between 91 and 180 days post randomisation. The primary outcome for the cost-effectiveness analysis was the cost per fall averted, and the primary outcome for the cost–utility analysis was the incremental cost per quality adjusted life-year. Secondary outcomes included the rate of falls over days 0–90 and 181–360 post randomisation, activity levels, dependency and fractures. The number of falls per resident was compared between arms using a negative binomial regression model (generalised estimating equation). Results: A total of 84 care homes were randomised: 39 to the GtACH arm and 45 to the control arm. A total of 1657 residents consented and provided baseline measures (mean age 85 years, 32% men). GtACH programme training was delivered to 1051 staff (71% of eligible staff) over 146 group sessions. Primary outcome data were available for 630 GtACH participants and 712 control participants. The primary outcome result showed an unadjusted incidence rate ratio of 0.57 (95% CI 0.45 to 0.71; p

Objective: While primary cytoreductive surgery (PCS) is considered the standard of care for women who present with stage IV endometrial cancer, neoadjuvant chemotherapy (NACT) followed by interval cytoreductive surgery (ICS) has emerged as an alternative treatment strategy. We summarized the literature and compared outcomes of PCS compared to NACT and ICS. Methods: We conducted a systematic search on PubMed, Embase, Web of Science, and Scopus for articles published from January 1, 1990 to December 31, 2020. Key search terms included multiple descriptors of advanced disease status in combination with “endometrial cancer” and “neoadjuvant chemotherapy”. Our review included studies that examined survival and surgical outcomes of patients with stage III or IV endometrial cancer treated with neoadjuvant chemotherapy followed by interval cytoreductive surgery versus those who received primary cytoreductive surgery. We excluded studies examining only patients with leiomyosarcomas, carcinosarcomas, and stromal sarcomas due to the biologic heterogeneity of these malignancies. Results: The nine included studies encompassed 5,844 patients, of which 1,317 (22.5%) received NACT and 4,527 received PCS (77.5%). With the exception of a single study, all were retrospective observational studies or case series. Use of NACT in patients with stage IV EC increased from 16.0% in 2010 to 23.9% in 2015. Five studies analyzed median overall survival and all but one reported no significant difference between NACT + ICS vs. PCS. Optimal cytoreduction (

Background. The coronavirus disease 2019 (COVID-19) pandemic has had a variable course across the United States. Understanding its evolving impact on heart and lung transplantation (HT and LT) will help with planning for next phases of this pandemic as well as future ones. Methods. We used Scientific Registry of Transplant Recipients data from before the pandemic to predict the number of waitlist registrations and transplants expected to occur between March 15, 2020, and December 31, 2020 (if no pandemic had occurred), and compared these expectations to observed rates. The observed era was divided into wave 1 (March 15–May 31), wave 2 (June 1–September 30), and wave 3 (October 1–December 31). We used multilevel Poisson regression to account for center- and state-level COVID-19 incidence. Results. During wave 1, rates of heart registrations and transplants were 28% (incidence rate ratio [IRR]: 0.72 [95% confidence interval (CI), 0.67-0.77]) and 13% (IRR: 0.87 [95% CI, 0.80-0.93]) lower than expected; lung registrations and transplants were 40% (IRR: 0.60 [95% CI, 0.54-0.66]) and 28% (IRR: 0.72 [95% CI, 0.66-0.79]) lower. Decreases were greatest in states with the highest incidence where registrations were 53% (IRR: 0.47 [95% CI, 0.36-0.62]) and 59% (IRR: 0.41 [95% CI, 0.29-0.58]) and transplants were 57% (IRR: 0.43 [95% CI, 0.31-0.60]) and 58% (IRR: 0.42 [95% CI, 0.29-0.62]) lower than expected. Whereas HT largely recovered during waves 2 and 3, LT continued to fall short of expectations through the end of the year. Conclusions. The COVID-19 pandemic in the US substantially reduced thoracic transplant access. Ongoing evaluation of the risks and benefits of this dramatic practice change is critical to inform clinical decision-making moving forward.

The positive education movement has called attention to the importance of student well-being and the role of positive constructs, such as hope, in the educational process. The external locus-of-hope dimensions, or positive cognitions about the role of external actors in the pursuit of important goals, positively predict student well-being, learning approaches, and achievement. However, external locus-of-hope dimensions were found to be associated with maladaptive coping styles among Asian students. In this study, we revisit this relationship between external locus-of-hope dimensions and coping among students, by focusing on collectivist coping strategies that are assumed to be more relevant to Asian students. A total of 780 university students from three Asian cities (Hong Kong, n = 295; Macau, n = 225; Manila, n = 260) were asked to complete a questionnaire on collectivist coping styles, internal and external locus-of-hope dimensions. Separate multiple regression analyses indicated that the coping style of acceptance/reframing/striving was mainly predicted by internal locus-of-hope in the three groups, but the coping styles of family support and religious coping were consistently predicted by external locus-of-hope dimensions in all three groups of students. The two other coping styles of avoidance/detachment and personal emotional outlets were also predicted by specific external locus-of-hope dimensions, but only in particular groups. The results are discussed in terms of how external locus-of-hope dimensions might evoke both adaptive and maladaptive coping among Asian students, which may be associated with primary and secondary control dimensions of the collectivist coping styles.