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Abstract Background Dads and Daughters Exercising and Empowered (DADEE) is a program targeting fathers/father-figures to improve their daughters’ physical activity and well-being. Previous randomised controlled efficacy and effectiveness trials of DADEE demonstrated meaningful improvements in a range of holistic outcomes for both fathers and daughters in the short-term. This study aims to assess the long-term impact (12-months) of the program when delivered in the community by trained facilitators. Methods Fathers/father-figures and their primary school-aged daughters were recruited from Newcastle, Australia into a single-arm, non-randomised, pre-post study with assessments at baseline, 10-weeks (post-intervention) and 12-months. The 9-session program included weekly 90-min educational and practical sessions, plus home-based tasks. The primary outcome was fathers’ and daughters’ days per week meeting national physical activity recommendations (≥ 30 min/day of MVPA for fathers, ≥ 60 min/day MVPA for daughters). Secondary outcomes included physical activity, screen time, self-esteem, father-daughter relationship, social-emotional well-being, parenting measures, and process outcomes (including recruitment, attendance, retention and program acceptability). Results Twelve programs were delivered with 257 fathers (40.0 ± 9.2 years) and 285 daughters (7.7 ± 1.9 years). Mixed effects regression models revealed significant intervention effects for the primary outcome, with fathers increasing the days/week meeting physical activity recommendations by 27% at 10-weeks (p

Aims: Custom-made partial pelvis replacements (PPRs) are increasingly used in the reconstruction of large acetabular defects and have mainly been designed using a triflange approach, requiring extensive soft-tissue dissection. The monoflange design, where primary intramedullary fixation within the ilium combined with a monoflange for rotational stability, was anticipated to overcome this obstacle. The aim of this study was to evaluate the design with regard to functional outcome, complications, and acetabular reconstruction. Methods: Between 2014 and 2023, 79 patients with a mean follow-up of 33 months (SD 22; 9 to 103) were included. Functional outcome was measured using the Harris Hip Score and EuroQol five-dimension questionnaire (EQ-5D). PPR revisions were defined as an endpoint, and subgroups were analyzed to determine risk factors. Results: Implantation was possible in all cases with a 2D centre of rotation deviation of 10 mm (SD 5.8; 1 to 29). PPR revision was necessary in eight (10%) patients. HHS increased significantly from 33 to 72 postoperatively, with a mean increase of 39 points (p < 0.001). Postoperative EQ-5D score was 0.7 (SD 0.3; -0.3 to 1). Risk factor analysis showed significant revision rates for septic indications (p ≤ 0.001) as well as femoral defect size (p = 0.001). Conclusion: Since large acetabular defects are being treated surgically more often, custom-made PPR should be integrated as an option in treatment algorithms. Monoflange PPR, with primary iliac fixation, offers a viable treatment option for Paprosky III defects with promising functional results, while requiring less soft-tissue exposure and allowing immediate full weightbearing. Cite this article: Bone Jt Open 2024;5(8):688–696.

Young-Ran Kweon,1 Keum-Seong Jang,1 Myeong Back,2 Mikyoung Lee3 1Department of Nursing, Chonnam National University, Gwangju, South Korea; 2Myung Coaching Center, Gwangju, South Korea; 3Department of Nursing, Kwangju Women’s University, Gwangju, South KoreaCorrespondence: Mikyoung Lee, Department of Nursing, Dongshin University, 67, Dongshindae-gil, Naju-shi, Jeollanam-do, 58245, South Korea, Tel +82 61 330 4095, Email mikylee@dsu.ac.krPurpose: In South Korea, hospitalized patients’ experiences significantly impact satisfaction and treatment outcomes. This study developed and evaluated the Inpatients Experience Measurement Scale (IEMS) for its psychometric properties.Patients and Methods: Participants from three hospitals were recruited using convenience sampling. Scale item generation involved patient interviews and a Delphi survey with experts. Psychometric testing used Exploratory Factor Analysis (EFA) with 150 participants and Confirmatory Factor Analysis (CFA) with 151 participants.Results: A total of 301 patients participated, resulting in a 20-item scale across four factors: “Care Quality and Information Provision”, “Patient Safety and Dietary Services”, “Facility and Comfort Infrastructure”, and “Comprehensive Patient Support Services”. Rated on a 5-point Likert scale, the scale showed a high Content Validity Index (CVI) over 0.80. EFA explained 61.43% of the variance. The four-factor model was validated using CFA with favorable fit indices. The IEMS demonstrated strong convergent validity, supported by high composite reliability (CR) and average variance extracted (AVE) values. Significant correlations with the Patient Satisfaction Scale reinforced its convergent validity. Discriminant validity was confirmed, and all reliability measures exceeded the minimum threshold of 0.80.Conclusion: The IEMS effectively captures inpatients’ experiences, demonstrating robust reliability and validity. This scale is a valuable tool for assessing patient experiences, facilitating enhancements in patient care and satisfaction within hospital settings.Keywords: inpatients, experience, psychometrics, validation, factor analysis

Summary: Macrophages exhibit diverse phenotypes and respond flexibly to environmental cues through metabolic remodeling. In this study, we present a comprehensive multi-omics dataset integrating intra- and extracellular metabolomes with transcriptomic data to investigate the metabolic impact on human macrophage function. Our analysis establishes a metabolite-gene correlation network that characterizes macrophage activation. We find that the concurrent inhibition of tryptophan catabolism by IDO1 and IL4I1 inhibitors suppresses the macrophage pro-inflammatory response, whereas single inhibition leads to pro-inflammatory activation. We find that a subset of anti-inflammatory macrophages activated by Fc receptor signaling promotes glycolysis, challenging the conventional concept of reduced glycolysis preference in anti-inflammatory macrophages. We demonstrate that cholesterol accumulation suppresses macrophage IFN-γ responses. Our integrated network enables the discovery of immunometabolic features, provides insights into macrophage functional metabolic reprogramming, and offers valuable resources for researchers exploring macrophage immunometabolic characteristics and potential therapeutic targets for immune-related disorders.

IntroductionChronic insomnia is a substantial public health burden that often presents with co-occurring depression and anxiety. Randomized clinical trials and preliminary real-world evidence have shown that digitally delivered cognitive-behavioral therapy for insomnia (dCBT-I) is associated with improvements in insomnia, but real-world evidence is needed to determine the true impact of digital CBT-I. This pragmatic study aimed to evaluate the benefits of treating chronic insomnia with a tailored prescription digital therapeutic in a real-world population. MethodsThis prospective, single-arm clinical study involved adults aged 22-75 with chronic insomnia living in the US who had access to a mobile device. Participants accessed the FDA-cleared prescription digital therapeutic (PDT; Somryst®) over a 9-week intervention period. The PDT delivers cognitive-behavioral therapy for insomnia via six interactive treatment cores and daily sleep diaries used for tailoring treatment. Participants completed validated patient-reported instruments at baseline, before completing treatment cores, immediately post-intervention, and at 6-month and 1-year follow-ups. The Insomnia Severity Index [ISI], the 8-item Patient Health Questionnaire [PHQ-8], and the Generalized Anxiety Disorder-7 scale [GAD-7] were used to determine the effect of the PDT on insomnia, depression, and anxiety.ResultsAfter screening, 1565 adults accessed the PDT. 58% of those who began the program completed Core 4, established as exposure to all mechanisms of action in the digital therapeutic. For those who completed assessments for all 6 cores (48.4%), the ISI was lowered from 18.8 to a mean of 9.9 (P

Michelle Lee, Al-Rehan Dhanji, Periklis Perikleous, Ralitsa Baranowski, Kelvin Kar Wing Lau, David Waller Department of Thoracic Surgery, Barts Thorax Centre, St Bartholomew’s Hospital, London, UKCorrespondence: Michelle Lee, Department of Thoracic Surgery, St Bartholomew’s Hospital, West Smithfield, London, United Kingdom, Email m.lee7@nhs.netObjective: There is an assumption that because EBLVR requires less use of hospital resources, offsetting the higher cost of endobronchial valves, it should therefore be the treatment of choice wherever possible. We have tested this hypothesis in a retrospective analysis of the two in similar groups of patients.Methods: In a 4-year experience, we performed 177 consecutive LVR procedures: 83 patients underwent Robot Assisted Thoracoscopic (RATS) LVRS and 94 EBLVR. EBLVR was intentionally precluded by evidence of incomplete fissure integrity or intra-operative assessment of collateral ventilation. Unilateral RATS LVRS was performed in these cases together with those with unsuitable targets for EBLVR.Results: EBLVR was uncomplicated in 37 (39%) cases; complicated by post-procedure spontaneous pneumothorax (SP) in 28(30%) and required revision in 29 (31%). In the LVRS group, 7 (8%) patients were readmitted with treatment-related complications, but no revisional procedure was needed. When compared with uncomplicated EBLVR, LVRS had a significantly longer operating time: 85 (14– 82) vs 40 (15– 151) minutes (p< 0.001) and hospital stay: 7.5 (2– 80) vs 2 (1– 14) days (p< 0.01). However, LVRS had a similar total operating time to both EBLVR requiring revision: 78 (38– 292) minutes and hospital stay to EBLVR complicated by pneumothorax of 11.5 (6.5– 24.25) days. Use of critical care was significantly longer in RATS group, and it was also significantly longer in EBV with SP group than in uncomplicated EBV group.Conclusion: Endobronchial LVR does use less hospital resources than RATS LVRS in comparable groups if the recovery is uncomplicated. However, this advantage is lost if one includes the resources needed for the treatment of complications and revisional procedures. Any decision to favour EBLVR over LVRS should not be based on the assumption of a smoother, faster perioperative course.Keywords: lung volume reduction, lung volume reduction surgery, bronchoscopic lung volume reduction, endobronchial valve, emphysema

Abstract The objective of this study was to examine the effect of consuming ketone monoester plus a high dose of carbohydrate from glucose (KE + CHO) on the change in erythropoietin (EPO) concentrations during load carriage exercise compared with carbohydrate (CHO) alone. Using a randomized, crossover design, 12 males consumed KE + CHO (573 mg KE/kg body mass, 110 g glucose) or CHO (110 g glucose) 30 min before 4 miles of self‐paced treadmill exercise (KE + CHO:51 ± 13%, CHO: 52 ± 12% V̇O2peak) wearing a weighted vest (30% body mass; 25 ± 3 kg). Blood samples for analysis were obtained under resting fasted conditions before (Baseline) consuming the KE + CHO or CHO supplement and immediately after exercise (Post). βHB increased (p

Abstract Background An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence. Aims The panel focused on multiple medical health and societal issues influencing effective treatment of obesity and identified several unmet needs in the definition, assessment, and care of obesity. Methods The panel was held in Leesburg, Virginia in September 2019. Results The panelists recommended addressing these unmet needs in obesity medicine through research, education, evaluation of delivery and payment of care, and updating clinical practice guidelines (CPG) to better reflect obesity’s pathophysiological basis and heterogeneity, as well as the disease’s health, sociocultural, and economic complications; effects on quality of life; need for standards for quantitative comparison of treatment benefits, risks, and costs; and the need to more effectively integrate obesity treatment guidelines into routine clinical practice and to facilitate more direct clinician participation to improve public understanding of obesity as a disease with a pathophysiological basis. The panel also recommended that professional organizations working to improve the care of people with obesity collaborate via a working group to develop an updated, patient‐focused, comprehensive CPG establishing standards of care, addressing identified needs, and providing for routine, periodic review and updating. Conclusions Unmet needs in the definition, assessment and treatment of obesity were identified and a blueprint to address these needs developed via a clinical practice guideline that can be utilized worldwide to respond to the increasing prevalence of obesity.

BackgroundAlthough most survivors of breast cancer report substantial sexual concerns following treatment, few receive support for these concerns. Delivering sexual health care to survivors of breast cancer via the internet could overcome many of the barriers to in-person treatment. Even when delivered remotely, survivor time constraints remain a leading barrier to sexual health intervention uptake. ObjectiveGuided by the multiphase optimization strategy methodological framework, the primary objective of this study is to identify the most efficient internet-delivered sexual health intervention package that is expected to provide survivors of breast cancer the greatest benefit with the fewest (and least-intensive) intervention components. This study aims to determine how intervention components work (mediators) and for whom they work best (moderators). MethodsPartnered, posttreatment adult female survivors of breast cancer (N=320) experiencing at least 1 bothersome sexual symptom (ie, pain with sex, vaginal dryness, low sexual desire, and difficulty with orgasm) related to their breast cancer treatment will be enrolled. Clinic-based recruitment will be conducted via the Wake Forest National Cancer Institute Community Oncology Research Program (NCORP) Research Base. Participants will be randomly assigned to 1 of 16 combinations of four intervention components with two levels each in this factorial trial: (1) psychoeducation about cancer-related sexual morbidity (receive either enhanced vs standard versions); (2) communication skills training for discussing concerns with health care providers (received vs not received); (3) communication skills training for discussing concerns with a partner (received vs not received); and (4) intimacy promotion skills training (received vs not received). Cores will be fully automated and implemented using a robust internet intervention platform with highly engaging elements such as animation, video, and automated email prompts. Survivors will complete web-based assessments at baseline (prerandomization time point) and again at 12 and 24 weeks later. The primary study aim will be achieved through a decision-making process based on systematically evaluating the main and interaction effects of components on sexual distress (Female Sexual Distress Scale–Desire, Arousal, Orgasm) and sexual functioning (Female Sexual Function Index) using a generalized linear model approach to ANOVA with effect coding. Mediation analyses will be conducted through a structural equation modeling approach, and moderation analyses will be conducted by extending the generalized linear model to include interaction effects. ResultsThis protocol has been reviewed and approved by the National Cancer Institute Central Institutional Review Board. Data collection is planned to begin in March 2024 and conclude in 2027. ConclusionsBy identifying the combination of the fewest and least-intensive intervention components likely to provide survivors of breast cancer the greatest sexual health benefit, this study will result in the first internet intervention that is optimized for maximum impact on the undertreated, prevalent, and distressing problem of breast cancer–related sexual morbidity. Trial RegistrationClinicalTrials.gov NCT06216574; https://clinicaltrials.gov/study/NCT06216574 International Registered Report Identifier (IRRID)PRR1-10.2196/57781

The Muwekma Ohlone Tribe has long been involved in the archaeology and stewardship of their ancestral homelands, both through their own cultural resource management (CRM) firm and though collaborations with academic and CRM archaeologists. In this article, we build on the past 40 years of archaeological collaborations in the southern San Francisco Bay region and offer examples of how archaeologists can support tribal heritage and environmental stewardship by using the traditional purview of material culture in combination with a broader array of evidence and concerns. As presented in our brief case studies, the Muwekma Ohlone Tribe and scholars are working together to reclaim tribal heritage and promote Native stewardship in a cultural landscape that has been marred by more than 250 years of dispossession. We examine this work in the context of the renaming of ancestral sites, the public interpretation of Native heritage associated with Mission Santa Clara de Asís, archival research into the history of Indigenous resistance, as well as collaborative efforts to awaken traditional ecological knowledge in service of the Tribe's stewardship and land management goals.

With the increasing use of electric vehicles, the demand for lithium iron phosphate batteries (LiFePO4) has risen sharply. Therefore, the recycling of metals from these batteries at the end of their life is necessary. In this study, a hydrometallurgical process for the recovery of lithium phosphate from spent LiFePO4 batteries was developed. The effects of the parameters on the recovery process, consisting of leaching, solvent extraction, and precipitation were investigated. The addition of H2O2 to the H2SO4 solution was ineffective for the selective leaching of Li(I) over iron. The results showed that Li(I) and iron were completely dissolved by 1.5 mol/L H2SO4, 100 g/L pulp density at 25 °C for 60 min at 300 rpm. After oxidation of Fe(II) in the leaching solution by addition of H2O2, Fe(III) was completely separated from the solution by five steps of cross-flow extraction with 1.0 mol/L D2EHPA at room temperature. The loaded Fe(III) was successfully separated by four steps of cross-current stripping with 50% (v/v) aqua regia solution. Finally, most Li(I) was recovered by precipitation of lithium phosphate from the iron-free raffinate by maintaining the pH of the solution at 11 and the temperature at 95 °C for 30 min. The optimum conditions for the complete dissolution of LiFePO4 batteries by sulfuric acid solution and for the separation of iron and lithium ions from the leaching solutions were determined. A hydrometallurgical process was proposed for the recovery of pure lithium phosphate from spent LiFePO4 batteries.

No Money No Time (NMNT) is a culinary nutrition website designed to optimize diet quality. The primary aim was to evaluate the impact of an online targeted nutrition challenge email campaign that encouraged engagement with NMNT and goal setting to improve diet quality and weekly food expenditure. A secondary aim was to assess NMNT engagement. Australian adults ≥18 years were recruited to the eHealth nutrition challenge delivered via weekly emails. Diet quality was assessed using the Healthy Eating Quiz (HEQ) diet quality tool. Engagement was assessed using email open and click-through rates. Intention-to-treat (ITT) analysis was conducted using mixed effects linear regression. Of 481 adults (49.7 ± 13.9 years, 84% female) who enrolled 79 (16%) completed the challenge. ITT results indicated statistically significant 6-week increases in diet quality score (+3.8 points p ≤ 0.001, d = 0.58) with sub-scale improvements in vegetables (+0.9 points, p = 0.01, d = 0.32), fruit (+1.2 points, p ≤ 0.001, d = 0.55), and dairy (+0.9 points, p ≤ 0.001, d = 0.58). There were significant post-challenge reductions in household spending on takeaway/snacks/coffee of AUD 8.9 per week (p = 0.01, d = 0.29), body weight reduction (−0.6 kg, p = 0.03, d = 0.26), and BMI (−0.2 kg/m2p = 0.02, d = 0.28). The email open rate remained constant at around 67% (56% to 75%), with an average click-through rate of 18% (7.1% to 37.9%). The eHealth nutrition challenge significantly improved diet quality while reducing BMI and money spent on discretionary foods. Strategies to scale the challenge should be tested as an innovative population strategy for improving diet quality, health indicators, and managing household food budgets.

Abstract Rotational closures have potential fisheries benefits, yet their impact on coral cover is unknown. Research has shown that permanent closures can protect herbivorous fish, indirectly benefiting corals, but these observations may not apply when closed periods alternate with fishing. Here, we examine how rotational closures affect coral, focusing on systems with the potential to switch between alternative stable states, a context in which temporary closures may have persistent effects. We show that rotational closures can trigger coral recovery, and in some contexts lead to better coral recovery than fixed closures of similar size. Such benthic effects are only possible if closures last long enough for change to occur. We also note that very large fixed or rotating closures may concentrate fishing effort in areas where fishing remains permitted, leading to lower overall coral cover. Our findings offer crucial guidance to managers regarding rotational closures’ potential advantages and drawbacks.

Abstract This study investigated the effects of EPO on hemoglobin (Hgb) and hematocrit (Hct), time trial (TT) performance, substrate oxidation, and skeletal muscle phenotype throughout 28 days of strenuous exercise. Eight males completed this longitudinal controlled exercise and feeding study using EPO (50 IU/kg body mass) 3×/week for 28 days. Hgb, Hct, and TT performance were assessed PRE and on Days 7, 14, 21, and 27 of EPO. Rested/fasted muscle obtained PRE and POST EPO were analyzed for gene expression, protein signaling, fiber type, and capillarization. Substrate oxidation and glucose turnover were assessed during 90‐min of treadmill load carriage (LC; 30% body mass; 55 ± 5% V̇O2peak) exercise using indirect calorimetry, and 6‐6‐[2H2]‐glucose PRE and POST. Hgb and Hct increased, and TT performance improved on Days 21 and 27 compared to PRE (p

Purpose: To review the evidence for imaging modalities in assessing the vascular component of diabetic retinal disease (DRD), to inform updates to the DRD staging system. Design: Standardized narrative review of the literature by an international expert workgroup, as part of the DRD Staging System Update Effort, a project of the Mary Tyler Moore Vision Initiative. Overall, there were 6 workgroups: Vascular Retina, Neural Retina, Systemic Health, Basic and Cellular Mechanisms, Visual Function, and Quality of Life. Participants: The Vascular Retina workgroup, including 16 participants from 4 countries. Methods: Literature review was conducted using standardized evidence grids for 5 modalities: standard color fundus photography (CFP), widefield color photography (WFCP), standard fluorescein angiography (FA), widefield FA (WFFA), and OCT angiography (OCTA). Summary levels of evidence were determined on a validated scale from I (highest) to V (lowest). Five virtual workshops were held for discussion and consensus. Main Outcome Measures: Level of evidence for each modality. Results: Levels of evidence for standard CFP, WFCP, standard FA, WFFA, and OCTA were I, II, I, I, and II respectively. Traditional vascular lesions on standard CFP should continue to be included in an updated staging system, but more studies are required before they can be used in posttreatment eyes. Widefield color photographs can be used for severity grading within the area covered by standard CFPs, although these gradings may not be directly interchangeable with each other. Evaluation of the peripheral retina on WFCP can be considered, but the method of grading needs to be clarified and validated. Standard FA and WFFA provide independent prognostic value, but the need for dye administration should be considered. OCT angiography has significant potential for inclusion in the DRD staging system, but various barriers need to be addressed first. Conclusions: This study provides evidence-based recommendations on the utility of various imaging modalities for assessment of the vascular component of DRD, which can inform future updates to the DRD staging system. Although new imaging modalities offer a wealth of information, there are still major gaps and unmet research needs that need to be addressed before this potential can be realized. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Abstract Seismic ground motion creates low-frequency atmospheric sound (infrasound) that is detectable at remote sensor arrays. However, earthquake infrasound signal analysis is complicated by interference between multiple waves arriving at sensors simultaneously, reducing the accuracy and detail of ground motion detection. Here we show that individual waves in complicated wavefields can be resolved by recording infrasound on large-N arrays and processing with CLEAN beamforming. Examining both a local (ML3.5, purely tropospheric infrasound propagation) and regional earthquake (ML6.5, upper-atmospheric returns), we detect infrasound from tens of km away and up to several hundred km away respectively. Source regions span arcs of approximately 90°, indicating that although detection bias does occur (most likely from atmospheric winds) the recorded infrasound sources are widely dispersed and not simply epicentral. Infrasound-based remote detection of ground motion over wide areas can complement point measurements by seismometers and spur innovations in earthquake research and real-time hazard monitoring.

Abstract Background There is a lack of understanding of the potential utility of a chatbot integrated into a website to support healthy eating among young adults. Therefore, the aim was to interview key informants regarding potential utility and design of a chatbot to: (1) increase young adults’ return rates and engagement with a purpose-built healthy eating website and, (2) improve young adults’ diet quality. Methods Eighteen qualitative, semi-structured interviews were conducted across three stakeholder groups: (i) experts in dietary behaviour change in young adults (n = 6), (ii) young adult users of a healthy eating website (n = 7), and (iii) experts in chatbot design (n = 5). Interview questions were guided by a behaviour change framework and a template analysis was conducted using NVivo. Results Interviewees identified three potential roles of a chatbot for supporting healthy eating in young adults; R1: improving healthy eating knowledge and facilitating discovery, R2: reducing time barriers related to healthy eating, R3: providing support and social engagement. To support R1, the following features were suggested: F1: chatbot generated recommendations and F2: triage to website information or externally (e.g., another website) to address current user needs. For R2, suggested features included F3: nudge or behavioural prompts at critical moments and F4: assist users to navigate healthy eating websites. Finally, to support R3 interviewees recommended the following features: F5: enhance interactivity, F6: offer useful anonymous support, F7: facilitate user connection with content in meaningful ways and F8: outreach adjuncts to website (e.g., emails). Additional ‘general’ chatbot features included authenticity, personalisation and effective and strategic development, while the preferred chatbot style and language included tailoring (e.g., age and gender), with a positive and professional tone. Finally, the preferred chatbot message subjects included training (e.g., would you like to see a video to make this recipe?), enablement (e.g., healthy eating doesn’t need to be expensive, we’ve created a budget meal plan, want to see?) and education or informative approaches (e.g., “Did you know bananas are high in potassium which can aid in reducing blood pressure?”). Conclusion Findings can guide chatbot designers and nutrition behaviour change researchers on potential chatbot roles, features, style and language and messaging in order to support healthy eating knowledge and behaviours in young adults.

Background Knowledge of the base rate of signal changes consistent with distal biceps tendinopathy on magnetic resonance imaging (MRI) has the potential to influence strategies for diagnosis and treatment of people that present with elbow pain. The aim of this study is to measure the prevalence of distal biceps tendon signal changes on MRIs of the elbow by indication for imaging. Methods MRI data for 1,306 elbows were retrospectively reviewed for mention of signal change in distal biceps tendon. The reports were sorted by indication. Results Signal changes consistent with distal biceps tendinopathy were noted in 197 of 1,306 (15%) patients, including 34% of patients with biceps pain, 14% of patients with unspecified pain, and 8% of patients with a specific non-biceps indication. Distal biceps tendon changes noted on radiology reports were associated with older age, male sex, and radiologists with musculoskeletal fellowship training. Conclusions The finding that distal biceps MRI signal changes consistent with tendinopathy are common even in asymptomatic elbows reduces the probability that symptoms correlate with pathology on imaging. The accumulation of signal changes with age, also independent of symptoms, suggests that tendon pathology persists after symptoms resolve, that some degree of distal biceps tendinopathy is common in a human lifetime, and that tendinopathy may often be accommodated without seeking care. Level of evidenceIV.

Efforts to control and eliminate measles and rubella are aided by high-quality surveillance data—supported by laboratory confirmation—to guide decision-making on routine immunization strategies and locations for conducting preventive supplementary immunization activities (SIAs) and outbreak response. Important developments in rapid diagnostic tests (RDTs) for measles and rubella present new opportunities for the global measles and rubella surveillance program to greatly improve the ability to rapidly detect and respond to outbreaks. Here, we review the status of RDTs for measles and rubella Immunoglobulin M (IgM) testing, as well as ongoing questions and challenges regarding the operational use and deployment of RDTs as part of global measles and rubella surveillance. Efforts to develop IgM RDTs that can be produced at scale are underway. Once validated RDTs are available, clear information on the benefits, challenges, and costs of their implementation will be critical for shaping deployment guidance and informing country plans for sustainably deploying such tests. The wide availability of RDTs could provide new programmatic options for measles and rubella elimination efforts, potentially enabling improvements and flexibility for testing, surveillance, and vaccination.

Carbon nanomaterials-based electric double-layer capacitors (EDLCs) are reliable and appealing energy-storage systems offering high power density and long cycling stability. However, these energy storage devices are plagued with critical shortcomings, such as low specific capacitance, inefficient physical/chemical activation process, and self-discharge of electrode materials, hindering their future application. In this work, we use a self-activation process, an environmentally benign and low-cost process, to produce high-performance activated carbon (AC). Novel activated carbon from pecan shells (PS) was successfully synthesized through a single-step self-activation process, which combines the carbonization and activation processes. The as-synthesized pecan shell-derived activated carbon (PSAC) provides a high-porosity, low-resistance, and ordered pore structure with a specific pore volume of 0.744 cm3/g and BET surface area of 1554 m2/g. The supercapacitors fabricated from PSAC demonstrate a specific capacitance of 269 F/g at 2 A/g, excellent cycling stability over 15,000 cycles, and energy and power density of 37.4 Wh/kg and of 2.1 kW/kg, respectively. It is believed that the high-efficiency PSAC synthesized from the novel self-activation method could provide a practical route to environmentally friendly and easily scalable supercapacitors.

Kichan Yoon,1 Han-Kyoul Kim,2,3 Mankyu Choi,4,5,&ast; Munjae Lee,6,&ast; Mihajlo Jakovljevic7– 9 1The Institute for Democracy, Seoul, Republic of Korea; 2Department of Rehabilitation Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 3National Traffic Injury Rehabilitation Research Institute, National Traffic Injury Rehabilitation Hospital, Yang-Pyeong, Republic of Korea; 4Department of Health Policy & Management, College of Health Science, Korea University, Seoul, Republic of Korea; 5BK21 FOUR R&E Center for Learning Health Systems, Korea University, Seoul, Republic of Korea; 6Department of Medical Science, Ajou University School of Medicine, Suwon, Republic of Korea; 7Institute of Advanced Manufacturing Technologies, Peter the Great St. Petersburg Polytechnic University, St Petersburg, 195251, Russia; 8Institute of Comparative Economic Studies, Hosei University, Tokyo, 194-0298, Japan; 9Department of Global Health Economics and Policy, University of Kragujevac, Kragujevac, 34000, Serbia&ast;These authors contributed equally to this workCorrespondence: Munjae Lee, Department of Medical Science, Ajou University School of Medicine, Suwon, Republic of Korea, Email emunjae@ajou.ac.kr Mankyu Choi, Department of Health Policy & Management, College of Health Science, Korea University, Seoul, Republic of Korea, Email mkchoi@korea.ac.krPurpose: The purpose of this study lies in verifying the effectiveness of the health promotion project which the public health center at the local level conducted by systematically linking the health examination results from the Health Insurance Corporation. We intend to emphasize the importance of linking the health-related public data.Methods: A survey was conducted to measure the effect of improving health behavior using EQ-5D-5L and demographic variables.Results: As a result of the analysis, the residents (3.13) who had experienced the use of public health centers recognized more necessity for the service linked systematically with health checkup data than those (2.93) who had not. In addition, the residents who had experienced the use of public health centers responded that their chronic diseases had improved compared to a year ago (2.78→ 2.93). Next, those (3.04) who had experienced the services linked with health checkup data recognized that their chronic diseases and health conditions had been improved compared to those (2.81) who had not. However, in EQ-5D-5L, after using the service, mobility showed no difference between those who had used the service and those who had not. Furthermore, even in terms of self-management, daily life, etc., the management ability was further improved compared to those who had not used it, before using the service.Conclusion: This study showed the improved health level when the health promotion service of the public health center was provided by systematically linking the health checkup data of the Health Insurance Corporation in Korea. In order to increase the effectiveness of health data-linked projects, it is necessary to prepare guidelines for linking the public health data and to expand the data-linked project. It will be needed to further subdivide the health checkup results to provide customized services, and to secure dedicated personnel to reinforce the system link.Keywords: subjective quality of life, EQ-5D-5L, regional health institutions, public data-linked services, South Korea

IntroductionDespite increasing survival of children following hospitalization, hospitalization may increase iatrogenic risk for mental health (MH) disorders, including acute stress, post-traumatic stress, anxiety, or depression. Using a population-based retrospective cohort study, we assessed the rates of new MH diagnoses during the 12 months after hospitalization, including the moderating effects of ICU exposure.Study design/methodsThis was a retrospective case control study using the Truven Health Analytics insurance database. Inclusion criteria included children aged 3–21 years, insurance enrollment for >12 months before and after hospital admission. We excluded children with hospitalization 2 years prior to index hospitalization and those with prior MH diagnoses. We extracted admission type, ICD-10 codes, demographic, clinical, and service coordination variables from the database. We established age- and sex-matched cohorts of non-hospitalized children. The primary outcome was a new MH diagnosis. Multivariable regression methods examined the risk of incident MH disorder(s) between hospitalized and non-hospitalized children. Among hospitalized children, we further assessed effect modification from ICU (vs. non-ICU) stay, admission year, length of stay, medical complexity, and geographic region.ResultsNew MH diagnoses occurred among 19,418 (7%) hospitalized children, 3,336 (8%) ICU-hospitalized children and 28,209 (5%) matched healthy controls. The most common MH diagnoses were anxiety (2.5%), depression (1.9%), and stress/trauma (2.2%) disorders. Hospitalization increased the odds of new MH diagnoses by 12.3% (OR: 1.123, 95% CI: 1.079–1.17) and ICU-hospitalization increased these odds by 63% (OR: 1.63, 95% CI: 1.483–1.79) as compared to matched, non-hospitalized children. Children with non-complex chronic diseases (OR: 2.91, 95% CI: 2.84–2.977) and complex chronic diseases (OR: 5.16, 95% CI: 5.032–5.289) had a substantially higher risk for new MH diagnoses after hospitalization compared to patients with acute illnesses.ConclusionPediatric hospitalization is associated with higher, long-term risk of new mental health diagnoses, and ICU hospitalization further increases that risk within 12 months of the acute episode. Acute care hospitalization confers iatrogenic risks that warrant long-term mental and behavioral health follow-up.

Limb salvage procedures can be complicated by large segmental defects. Aggressive tibio-talar debridement or possible talectomy, hardware removal, and revisional surgery often leave a large void. An ideal graft that is mechanically strong, readily available, disease free, capable of maintaining length, and possesses all three biologic properties (osteoinductive, osteoconductive and osteogenic) is difficult to find. 3D printed implants and allografts, such as femoral head, are viable options but may present with pitfalls such as increased cost and risk of nonunion. This case report outlines a novel limb salvage surgical technique for tibiocalcaneal arthrodesis with an ipsilateral fibular strut autograft. The harvested fibula is divided into struts, which are then assembled into a circular configuration and used to fill a large defect. This technique offers an accessible and affordable solution of providing both substantial bone graft to assist in tibiocalcaneal arthrodesis, while also maintaining length.

Summary: Generating large-scale, high-fidelity sequencing data is challenging and, furthermore, not much has been done to characterize adjuvants’ effects at the repertoire level. Thus, we introduced an IgSeq pipeline that standardized library prep protocols and data analysis functions for accurate repertoire profiling. We then studied systemically effects of CpG and Alum on the Ig heavy chain repertoire using the ovalbumin (OVA) murine model. Ig repertoires of different tissues (spleen and bone marrow) and isotypes (IgG and IgM) were examined and compared in IGHV mutation, gene usage, CDR3 length, clonal diversity, and clonal selection. We found Ig repertoires of different compartments exhibited distinguishable profiles at the non-immunized steady state, and distinctions became more pronounced upon adjuvanted immunizations. Notably, Alum and CpG effects exhibited different tissue- and isotype-preferences. The former led to increased diversity of abundant clones in bone marrow, and the latter promoted the selection of IgG clones in both tissues.

As mobile and wearable devices continue to grow in popularity, there is strong yet unrealized potential to harness people's mobile sensing data to improve our understanding of their cellular and biologically-based diseases. Breakthrough technical innovations in tumor modeling, such as the three dimensional tumor microenvironment system (TMES), allow researchers to study the behavior of tumor cells in a controlled environment that closely mimics the human body. Although patients' health behaviors are known to impact their tumor growth through circulating hormones (cortisol, melatonin), capturing this process is a challenge to rendering realistic tumor models in the TMES or similar tumor modeling systems. The goal of this paper is to propose a conceptual framework that unifies researchers from digital health, data science, oncology, and cellular signaling, in a common cause to improve cancer patients' treatment outcomes through mobile sensing. In support of our framework, existing studies indicate that it is feasible to use people's mobile sensing data to approximate their underlying hormone levels. Further, it was found that when cortisol is cycled through the TMES based on actual patients' cortisol levels, there is a significant increase in pancreatic tumor cell growth compared to when cortisol levels are at normal healthy levels. Taken together, findings from these studies indicate that continuous monitoring of people's hormone levels through mobile sensing may improve experimentation in the TMES, by informing how hormones should be introduced. We hope our framework inspires digital health researchers in the psychosocial sciences to consider how their expertise can be applied to advancing outcomes across levels of inquiry, from behavioral to cellular.

Here, we introduce the Early Relational Health (ERH) Learning Community's bold, large-scale, collaborative, data-driven and practice-informed research agenda focused on furthering our mechanistic understanding of ERH and identifying feasible and effective practices for making ERH promotion a routine and integrated component of pediatric primary care. The ERH Learning Community, formed by a team of parent/caregiver leaders, pediatric care clinicians, researchers, and early childhood development specialists, is a workgroup of Nurture Connection—a hub geared toward promoting ERH, i.e., the positive and nurturing relationship between young children and their parent(s)/caregiver(s), in families and communities nationwide. In response to the current child mental health crisis and the American Academy of Pediatrics (AAP) policy statement promoting ERH, the ERH Learning Community held an in-person meeting at the AAP national headquarters in December 2022 where members collaboratively designed an integrated research agenda to advance ERH. This agenda weaves together community partners, clinicians, and academics, melding the principles of participatory engagement and human-centered design, such as early engagement, co-design, iterative feedback, and cultural humility. Here, we present gaps in the ERH literature that prompted this initiative and the co-design activity that led to this novel and iterative community-focused research agenda, with parents/caregivers at the core, and in close collaboration with pediatric clinicians for real-world promotion of ERH in the pediatric primary care setting.

Background: Histological grade has been regarded as the most important prognostic factor in conventional central chondrosarcoma. To evaluate whether the presence of an extraosseous tumour component is associated with a decreased metastasis-free survival or disease-specific survival and alternatively to develop a simple prognostic and clinical decision-making tool. Material and methods: We searched two prospectively maintained international sarcoma centre databases for primary non metastatic central conventional chondrosarcomas of all grades in pelvis, scapula or long bone location, undergoing curative treatment, diagnosed between 2000 and 2020. Pre-treatment MRI scans were reviewed for the presence of an extraosseous mass. The metastasis-free survival (MFS) and disease-specific survival (DSS) were estimated by the Kaplan-Meier method from surgery to event, death or last follow-up. Results: 336 patients were identified between 2000 and 2020, undergoing surgical treatment for conventional central chondrosarcoma. 111 patients (33 %) had grade 1 tumours, 149 patients (44 %) had grade 2, and 76 patient (23 %) had grade 3 chondrosarcomas determined as the highest grade in the final resected specimen. An extraosseous soft tissue component was more frequent in higher grade tumours (p

ABSTRACT.High daily energy expenditure without compensatory increases in energy intake results in severe energy deficits during cold-weather military operations. The severity of energy deficits has been proportionally linked to declines in body mass, negative protein balance, suppression of androgen hormones, increases in systemic inflammation and degraded physical performance. Food availability does not appear to be the predominant factor causing energy deficits; providing additional rations or supplement snack bars does not reduce the severity of the energy deficits. Nutrition interventions that allow greater energy intake could be effective for reducing energy deficits during cold-weather military operations. One potential intervention is to increase energy density (i.e. energy per unit mass of food) by increasing dietary fat. Our laboratory recently reported that self-selected higher energy intakes and reductions in energy deficits were primarily driven by fat intake (r = 0.891, r2 = 0.475), which, of the three macronutrients. Further, soldiers who ate more fat lost less body mass, had lower inflammation, and maintained net protein balance compared to those who ate less fat. These data suggest that consuming high-fat energy-dense foods may be a viable nutritional intervention that mitigates the negative physiological effects of energy deficit and sustains physical performance during cold-weather military operations.

Abstract Bacterial symbioses allow annelids to colonise extreme ecological niches, such as hydrothermal vents and whale falls. Yet, the genetic principles sustaining these symbioses remain unclear. Here, we show that different genomic adaptations underpin the symbioses of phylogenetically related annelids with distinct nutritional strategies. Genome compaction and extensive gene losses distinguish the heterotrophic symbiosis of the bone-eating worm Osedax frankpressi from the chemoautotrophic symbiosis of deep-sea Vestimentifera. Osedax’s endosymbionts complement many of the host’s metabolic deficiencies, including the loss of pathways to recycle nitrogen and synthesise some amino acids. Osedax’s endosymbionts possess the glyoxylate cycle, which could allow more efficient catabolism of bone-derived nutrients and the production of carbohydrates from fatty acids. Unlike in most Vestimentifera, innate immunity genes are reduced in O. frankpressi, which, however, has an expansion of matrix metalloproteases to digest collagen. Our study supports that distinct nutritional interactions influence host genome evolution differently in highly specialised symbioses.

Objective: Two brief computerized motivational interventions for excessive-drinking university students were evaluated. Method: Participants (N = 88, females = 61.5%, mean age = 21.05 years) were randomly assigned to a control group or one of two experimental groups: Computerized Brief Intervention (CBI) or Computerized Brief Intervention-Enhanced (CBI-E). CBI followed the principles of Motivational Interviewing to motivate participants to change their drinking behavior. CBI-E additionally used the principles of Systematic Motivational Counseling to identify and discuss with participants their dysfunctional motivational patterns that were interfering with their attainment of emotional satisfaction. At baseline and a three-month follow-up, the participants completed a battery of measures of alcohol consumption and related problems. Results: At baseline, the participants were confirmed to be heavy drinkers with many drink-related negative consequences. Males and females responded differently to the interventions. During follow-up, males’ alcohol use was ordered: CBI-E < CBI < Controls. The females in all three groups reduced their alcohol use, but there were no significant group differences. Conclusions: Males responded to the interventions as expected. For females, the assessment itself seemed to serve as an effective intervention, and there were no post-intervention differences among the three groups. Suggestions for future research using CBI and CBI-E are discussed.

Chondrosarcomas (CSs) consist of a heterogenous group of primary bone cancers arising from malignant cells which produce cartilaginous matrix. As the second most common primary bone cancer, CS are often resistant to systemic chemotherapy due to poor vascularization, slow proliferation, and expression of multidrug-resistant pumps. Immune checkpoint inhibitors have transformed the field of oncology and are now designated as frontline therapy for many solid tumor cancers. Several studies have demonstrated increased expression of programed cell death 1 (PD-1) and PD-L1 in CS tissue in vitro , which has led to the development of multiple clinical trials for immunotherapy in patients with aggressive CS. In this review, we highlight the ongoing investigation into the role for immunotherapy in CS. We also report the case of a 44-year-old female with a history of stage IV primary CS of the right shoulder who underwent radical resection with recurrence and demonstrated a spectacular sustained response to pembrolizumab at our center. Our review highlights the need for further studies investigating the role of immunotherapy in the treatment of aggressive bone sarcomas that are resistant to standard surgical resection, chemotherapy, and radiation treatment.

The aim of this survey was to identify, (1) use of Dietitians Australia best practice guidelines, (2) contemporary practices/knowledge, and (3) professional development needs of Australian dietitians in relation to management of clients with overweight or obesity. A cross-sectional online survey consisting of 67 multiple choice and Likert scale questions on the three survey aims was administered. Data were collected between 2020–2021 and reported descriptively as frequency (%). Of 178 survey attempts, 80 respondents completed all questions (45%). Most respondents spent >50% of their time working with individuals with overweight/obesity, usually in private practice (47%). Two thirds of respondents had accessed best practice guidelines, but only 12% had completely read best practice guidelines. General healthy eating was the most frequent dietary approach used (77%). Seventy-five percent (n = 56) of dietitians reported that dietary interventions were selected based on client preference. Almost half of dietitians rated their knowledge and level of skill in management of obesity as good. Approximately 60% (n = 41) dietitians reported their skill gap was related to providing behavioural therapy/counselling. Results of the current survey indicate that use of best practice guidelines is low. However, dietitians surveyed reported that they had a good understanding of obesity management and choose a client centred approach to management, which is in line with current recommendations. Professional development activities, particularly regarding behavioural counselling are of particular interest to dietitians working with individuals with obesity.

Mingyu Lee,1 Min Chul Kim,2 Jae Young Lee1 1School of Materials Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea; 2Division of Cardiology, Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of KoreaCorrespondence: Jae Young Lee, Tel +82 62 715 2358, Email jaeyounglee@gist.ac.krAbstract: Cardiovascular disease is one of major causes of deaths, and its incidence has gradually increased worldwide. For cardiovascular diseases, several therapeutic approaches, such as drugs, cell-based therapy, and heart transplantation, are currently employed; however, their therapeutic efficacy and/or practical availability are still limited. Recently, biomaterial-based tissue engineering approaches have been recognized as promising for regenerating cardiac function in patients with cardiovascular diseases, including myocardial infarction (MI). In particular, materials mimicking the characteristics of native cardiac tissues can potentially prevent pathological progression and promote cardiac repair of the heart tissues post-MI. The mechanical (softness) and electrical (conductivity) properties of biomaterials as non-biochemical cues can improve the cardiac functions of infarcted hearts by mitigating myocardial cell death and subsequent fibrosis, which often leads to cardiac tissue stiffening and high electrical resistance. Consequently, electrically conductive hydrogels that can provide mechanical strength and augment the electrical activity of the infarcted heart tissue are considered new functional materials capable of mitigating the pathological progression to heart failure and stimulating cardiac regeneration. In this review, we highlight nanomaterial-incorporated hydrogels that can induce cardiac repair after MI. Nanomaterials, including carbon-based nanomaterials and recently discovered two-dimensional nanomaterials, offer great opportunities for developing functional conductive hydrogels owing to their excellent electrical conductivity, large surface area, and ease of modification. We describe recent results using nanomaterial-incorporated conductive hydrogels as cardiac patches and injectable hydrogels for cardiac repair. While further evaluations are required to confirm the therapeutic efficacy and toxicity of these materials, they could potentially be used for the regeneration of other electrically active tissues, such as nerves and muscles.Graphical Abstract: Keywords: nanomaterials, conductive, hydrogel, cardiac tissue engineering

Introduction: Studies assessing the management of laryngopharyngeal reflux by otolaryngologists have reported an important heterogeneity regarding the definition, diagnosis, and treatment, which leads to discrepancies in the management of the patient. Information about the current knowledge and practices of Brazilian otolaryngologists in laryngopharyngeal reflux is lacking. Objective: To investigate the trends in management of laryngopharyngeal reflux disease among Brazilian otolaryngologists. Methods: A survey was sent by email to the members of the Brazilian Association of Otolaryngology-Head Neck Surgery. This survey has initially been conducted by the laryngopharyngeal reflux study group of young otolaryngologists of the International Federation of Otolaryngological Societies. Results: According to the survey responders, the prevalence of laryngopharyngeal reflux was estimated to be 26.8% of patients consulting in otolaryngology and the most common symptoms were globus sensation, throat clearing, cough and stomach acid reflux. Nasal obstruction, Eustachian tube dysfunction, acute and chronic otitis media, vocal fold nodules and hemorrhage were considered not associated with laryngopharyngeal reflux by the majority of responders. About 2/3 of Brazilian otolaryngologists based the diagnosis of laryngopharyngeal reflux on the assessment of both symptoms and findings and a positive response to empiric therapeutic trials. Proton pump inhibitor utilized once or twice daily, was the most commonly used therapeutic scheme. Only 21.4% of Brazilian otolaryngologists have heard about nonacid and mixed laryngopharyngeal reflux and the awareness about the usefulness of multichannel intraluminal impedance pH monitoring (MII-pH) was minimal; 30.5% of responders did not consider themselves as well-informed about laryngopharyngeal reflux. Conclusion: Although the laryngopharyngeal reflux-related symptoms, main diagnostic and treatment approaches referred by Brazilian otolaryngologists are consistent with the literature, the survey identified some limitations, such as the insufficient awareness of the role of laryngopharyngeal reflux in many otolaryngological conditions and of the possibility of non-acid or mixed reflux in refractory cases. Future studies are needed to establish international recommendations for the management of laryngopharyngeal reflux disease.

ABSTRACT Osedax, the deep-sea annelid found at sunken whalefalls, is known to host Oceanospirillales bacterial endosymbionts intracellularly in specialized roots, which help it feed exclusively on vertebrate bones. Past studies, however, have also made mention of external bacteria on their trunks. During a 14-yr study, we reveal a dynamic, yet persistent, shift of Campylobacterales integrated into the epidermis of Osedax, which change over time as the whale carcass degrades on the sea floor. The Campylobacterales associated with seven species of Osedax, which comprise 67% of the bacterial community on the trunk, appear initially dominated by the genus Arcobacter (at early time points 140 mo) of whale carcass decomposition. Metagenome analysis of the epibiont metabolic capabilities suggests potential for a transition from heterotrophy to autotrophy and differences in their capacity to metabolize oxygen, carbon, nitrogen, and sulfur. Compared to free-living relatives, the Osedax epibiont genomes were enriched in transposable elements, implicating genetic exchange on the host surface, and contained numerous secretions systems with eukaryotic-like protein (ELP) domains, suggesting a long evolutionary history with these enigmatic, yet widely distributed deep-sea worms. IMPORTANCE Symbiotic associations are widespread in nature and we can expect to find them in every type of ecological niche. In the last twenty years, the myriad of functions, interactions and species comprising microbe-host associations has fueled a surge of interest and appreciation for symbiosis. During this 14-year study, we reveal a dynamic population of bacterial epibionts, integrated into the epidermis of 7 species of a deep-sea worm group that feeds exclusively on the remains of marine mammals. The bacterial genomes provide clues of a long evolutionary history with these enigmatic worms. On the host surface, they exchange genes and appear to undergo ecological succession, as the whale carcass habitat degrades over time, similar to what is observed for some free-living communities. These, and other annelid worms are important keystone species for diverse deep-sea environments, yet the role of attached external bacteria in supporting host health has received relatively little attention.

Summary: Among all RNA viruses, coronavirus RNA transcription is the most complex and involves a process termed “discontinuous transcription” that results in the production of a set of 3′-nested, co-terminal genomic and subgenomic RNAs during infection. While the expression of the classic canonical set of subgenomic RNAs depends on the recognition of a 6- to 7-nt transcription regulatory core sequence (TRS), here, we use deep sequence and metagenomics analysis strategies and show that the coronavirus transcriptome is even more vast and more complex than previously appreciated and involves the production of leader-containing transcripts that have canonical and noncanonical leader-body junctions. Moreover, by ribosome protection and proteomics analyses, we show that both positive- and negative-sense transcripts are translationally active. The data support the hypothesis that the coronavirus proteome is much vaster than previously noted in the literature.

Coeliac disease (CD) is associated with hyposplenism, an acquired impairment of spleen function associated with reduced IgM memory B cells and increased susceptibility to serious pneumococcal infection. Little is known about the immune implications of hyposplenism in CD or the optimal pneumococcal vaccination strategy. In this study, the immune effects of hyposplenism in CD, and the accuracy of screening approaches and protective responses induced by two different pneumococcal vaccines were examined. Active and treated CD cohorts, and healthy and surgically splenectomised controls underwent testing for the presence of Howell–Jolly bodies and pitted red cells, spleen ultrasound, and immune assessment of IgM memory B cell frequency and IgM memory B cell responses to T cell-dependent (TD) or T cell-independent (TI) stimulation. Responses following conjugate (TD) and polysaccharide (TI) pneumococcal vaccination were compared using ELISA and opsonophagocytic assays. Although hyposplenism is rare in treated CD (5.1%), functional B cell defects are common (28–61%) and are not detected by current clinical tests. Conjugate pneumococcal vaccination induced superior and sustained protection against clinically relevant serotypes. Clinical practice guidelines in CD should recommend routine pneumococcal vaccination, ideally with a conjugate vaccine, of all patients in lieu of hyposplenism screening.

Monitoring adherence to a gluten-free diet is an important goal of coeliac disease management. Urine and stool gluten immunogenic peptide (GIP) assays provide an objective readout of gluten ingestion, with the former favoured due to its convenience and acceptability. This study assessed stool GIP excretion after low-dose gluten challenge designed to mimic accidental gluten exposure. A total of 52 coeliac participants undertook a randomised, double-blind gluten (50–1000 mg) or placebo challenge. Stool and urinary GIP, serology, dietary adherence and symptoms were assessed. Stool GIP was 100% sensitive for gluten intake ≥250 mg and 71% for 50 mg. Peak GIP detection was 12–36 h after gluten exposure. The mean stool GIP after 1000 mg gluten ingestion remained above the limit of quantification for 5 days. Urine GIP assessment had poor sensitivity for GIP excretion compared to stool. Serology, dietary adherence score and symptoms did not correlate with gluten excretion during lead-in. We conclude that stool GIP detection is highly sensitive, with levels related to gluten dose and time from ingestion. Weekly or bi-weekly testing will detect low-level exposure more effectively than urine GIP assessments or traditional methods. In this seronegative, apparently well-treated cohort, a high frequency of baseline-positive GIP suggests ongoing gluten exposure, but the assessment of patient behaviour and assay specificity is needed.

Gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae, poses a significant global public health threat. Infection in women can be asymptomatic and may result in severe reproductive complications. Escalating antibiotic resistance underscores the need for an effective vaccine. Approaches being explored include subunit vaccines and outer membrane vesicles (OMVs), but an ideal candidate remains elusive. Meningococcal OMV-based vaccines have been associated with reduced rates of gonorrhea in retrospective epidemiologic studies, and with accelerated gonococcal clearance in mouse vaginal colonization models. Cross-protection is attributed to shared antigens and possibly cross-reactive, bactericidal antibodies. Using a Candidate Antigen Selection Strategy (CASS) based on the gonococcal transcriptome during human mucosal infection, we identified new potential vaccine targets that, when used to immunize mice, induced the production of antibodies with bactericidal activity against N. gonorrhoeae strains. The current study determined antigen recognition by human sera from N. gonorrhoeae-infected subjects, evaluated their potential as a multi-antigen (combination) vaccine in mice and examined the impact of different adjuvants (Alum or Alum+MPLA) on functional antibody responses to N. gonorrhoeae. Our results indicated that a stronger Th1 immune response component induced by Alum+MPLA led to antibodies with improved bactericidal activity. In conclusion, a combination of CASS-derived antigens may be promising for developing effective gonococcal vaccines.

Yoonseo Park,1 Sewon Park,2 Munjea Lee2 1Department of Bio Medial Engineering, Ajou University, Suwon, Republic of Korea; 2Department of Medical Humanities and Social Medicine, Ajou University School of Medicine, Suwon, Republic of KoreaCorrespondence: Munjea Lee, Department of Medical Humanities and Social Medicine, Ajou University School of Medicine, Suwon, South Korea, Tel +82-31-219-5289, Email emunjae@ajou.ac.krPurpose: This study utilized text mining to analyze research trends around community care, which focuses on improving patients’ quality of life by lessening the financial burden on caregivers and relieving patient discomfort.Methods: To examine research trends by community care stage, Section 1 is set from 2017 to 2019, when the community care was implemented, and Section 2 from 2020 to 2021, after the end of the community care. Papers used for the analysis were extracted using the Korea Citation Index (KCI); a total of 132 articles were selected and subjected to text mining analysis.Results: First, the main community care research areas included work, housing, economy, disability, and mind. Second, from 2017 to 2019, there was considerable interest in community care centered on households, and main keywords, such as nursing, family, and experience, appeared. Third, from 2020 to the present, there was high interest in community care centered on disabilities, and keywords, such as space, business, and Seoul City, appeared.Conclusion: The results reveal the changing issues, with the implementation of community care. Overall, research has tended to focus on social and welfare systems, rather than health and medical systems. In the future, local, community-integrated health and medical care systems should be restructured and regional delivery systems established to make them more accessible.Keywords: community care, integrated care, local community, elderly care, text mining, network analysis

Abstract Background Targeting fathers may be a key strategy to increase physical activity among their preschool-aged children, but limited research exists in this area. The primary study aim was to examine the impact of a lifestyle program for fathers and their preschool-aged children on child physical activity levels. Methods A total of 125 fathers (aged: 38 ± 5.4 years, BMI: 28.1 ± 4.9 kg/m2) and 125 preschool-aged children (aged: 3.9 ± 0.8 years, BMI z-score: 0.3 ± 0.9, 39.2% girls) recruited from Newcastle, Australia, NSW were randomised to (i) the Healthy Youngsters, Healthy Dads (HYHD) program, or (ii) wait-list control group. The program included two fathers-only workshops (2 h each) and eight father-child weekly educational and practical sessions (75 min each), plus home-based activities targeting family physical activity and nutrition. Assessments took place at baseline, 10-weeks (post-intervention) and 9-months follow-up. The primary outcome was the children’s mean steps/day at 10-weeks. Secondary outcomes included: co-physical activity, fathers’ physical activity levels and parenting practices for physical activity and screen time behaviours, children’s fundamental movement skill (FMS) proficiency, plus accelerometer based light physical activity (LPA) and moderate-to-vigorous physical activity (MVPA), screen time and adiposity for fathers and children. Process measures included; attendance, satisfaction, fidelity and retention. Linear mixed models estimated the treatment effect at all time-points for all outcomes. Results Intention-to-treat analyses revealed a significant group-by-time effect for steps per day at 10-weeks (+ 1417, 95%CI: 449, 2384) and 9-months follow-up (+ 1480, 95%CI: 493, 2467) in intervention children compared to control. There were also favourable group-by-time effects for numerous secondary outcomes including fathers’ physical activity levels, children’s FMS proficiency, and several parenting constructs. No effects were observed for both fathers’ and children’s accelerometer based LPA or MVPA, co-physical activity, screen-time and adiposity measures. Process evaluation data revealed very high levels of satisfaction, attendance, retention, and intervention fidelity. Conclusion Engaging fathers in a lifestyle program is a promising strategy to increase physical activity among preschool-aged children. Additional benefits to fathers’ physical activity levels, children’s FMS proficiency and parenting practices further support the importance of engaging fathers to improve family health outcomes. Trial Registration Australian New Zealand Clinical Trials Registry: ACTRN12619000105145 . Registered 24/01/2019.

The discovery of gasdermin D (GSDMD) as the terminal executioner of pyroptosis provided a large piece of the cell death puzzle, whilst simultaneously and firmly putting the gasdermin family into the limelight. In its purest form, GSDMD provides a connection between the innate alarm systems to an explosive, inflammatory form of cell death to jolt the local environment into immunological action. However, the gasdermin field has moved rapidly and significantly since the original seminal work and novel functions and mechanisms have been recently uncovered, particularly in response to infection. Gasdermins regulate and are regulated by mechanisms such as autophagy, metabolism and NETosis in fighting pathogen and protecting host. Importantly, activators and interactors of the other gasdermins, not just GSDMD, have been recently elucidated and have opened new avenues for gasdermin-based discovery. Key to this is the development of potent and specific tool molecules, so far a challenge for the field. Here we will cover some of these recently discovered areas in relation to bacterial infection before providing an overview of the pharmacological landscape and the challenges associated with targeting gasdermins.

IntroductionInsects share intimate relationships with microbes that play important roles in their biology. Yet our understanding of how host-bound microbial communities assemble and perpetuate over evolutionary time is limited. Ants host a wide range of microbes with diverse functions and are an emerging model for studying the evolution of insect microbiomes. Here, we ask whether phylogenetically related ant species have formed distinct and stable microbiomes.MethodsTo answer this question, we investigated the microbial communities associated with queens of 14 Formica species from five clades, using deep coverage 16S rRNA amplicon sequencing.ResultsWe reveal that Formica species and clades harbor highly defined microbial communities that are dominated by four bacteria genera: Wolbachia, Lactobacillus, Liliensternia, and Spiroplasma. Our analysis reveals that the composition of Formica microbiomes mirrors the phylogeny of the host, i.e., phylosymbiosis, in that related hosts harbor more similar microbial communities. In addition, we find there are significant correlations between microbe co-occurrences.DiscussionOur results demonstrate Formica ants carry microbial communities that recapitulate the phylogeny of their hosts. Our data suggests that the co-occurrence of different bacteria genera may at least in part be due to synergistic and antagonistic interactions between microbes. Additional factors potentially contributing to the phylosymbiotic signal are discussed, including host phylogenetic relatedness, host-microbe genetic compatibility, modes of transmission, and similarities in host ecologies (e.g., diets). Overall, our results support the growing body of evidence that microbial community composition closely depends on the phylogeny of their hosts, despite bacteria having diverse modes of transmission and localization within the host.

Summary: Background: The optimal timing for SARS-CoV-2 vaccines within the first year after allogeneic hematopoietic cell transplant (HCT) is poorly understood. Methods: We conducted a prospective, multicentre, observational study of allogeneic HCT recipients who initiated SARS-CoV-2 vaccinations within 12 months of HCT. Participants were enrolled at 22 academic cancer centers across the United States. Participants of any age who were planning to receive a first post-HCT SARS-CoV-2 vaccine within 12 months of HCT were eligible. We obtained blood prior to and after each vaccine dose for up to four vaccine doses, with an end-of-study sample seven to nine months after enrollment. We tested for SARS-CoV-2 spike protein (anti-S) IgG; nucleocapsid protein (anti-N) IgG; neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains; and SARS-CoV-2-specific T-cell receptors (TCRs). The primary outcome was a comparison of anti-S IgG titers at the post-V2 time point in participants initiating vaccinations

ClpP activators ONC201 and related small molecules (TR compounds, Madera Therapeutics), have demonstrated significant anti-cancer potential in vitro and in vivo studies, including clinical trials for refractory solid tumors. Though progress has been made in identifying specific phenotypic outcomes following ClpP activation, the exact mechanism by which ClpP activation leads to broad anti-cancer activity has yet to be fully elucidated. In this study, we utilized a multi-omics approach to identify the ClpP-dependent proteomic, transcriptomic, and metabolomic changes resulting from ONC201 or the TR compound TR-57 in triple-negative breast cancer cells. Applying mass spectrometry-based methods of proteomics and metabolomics, we identified ∼8,000 proteins and 588 metabolites, respectively. From proteomics data, 113 (ONC201) and 191 (TR-57) proteins significantly increased and 572 (ONC201) and 686 (TR-57) proteins significantly decreased in this study. Gene ontological (GO) analysis revealed strong similarities between proteins up- or downregulated by ONC201 or TR-57 treatment. Notably, this included the downregulation of many mitochondrial processes and proteins, including mitochondrial translation and mitochondrial matrix proteins. We performed a large-scale transcriptomic analysis of WT SUM159 cells, identifying ∼7,700 transcripts (746 and 1,100 significantly increasing, 795 and 1,013 significantly decreasing in ONC201 and TR-57 treated cells, respectively). Less than 21% of these genes were affected by these compounds in ClpP null cells. GO analysis of these data demonstrated additional similarity of response to ONC201 and TR-57, including a decrease in transcripts related to the mitochondrial inner membrane and matrix, cell cycle, and nucleus, and increases in other nuclear transcripts and transcripts related to metal-ion binding. Comparison of response between both compounds demonstrated a highly similar response in all -omics datasets. Analysis of metabolites also revealed significant similarities between ONC201 and TR-57 with increases in α-ketoglutarate and 2-hydroxyglutaric acid and decreased ureidosuccinic acid, L-ascorbic acid, L-serine, and cytidine observed following ClpP activation in TNBC cells. Further analysis identified multiple pathways that were specifically impacted by ClpP activation, including ATF4 activation, heme biosynthesis, and the citrulline/urea cycle. In summary the results of our studies demonstrate that ONC201 and TR-57 induce highly similar and broad effects against multiple mitochondrial processes required for cell proliferation.

Immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) therapy may vary substantially in their clinical presentation, including natural history, outcomes to treatment, and patterns. The application of clinical guidelines for irAE management can be challenging for practitioners due to a lack of common or consistently applied terminology. Furthermore, given the growing body of clinical experience and published data on irAEs, there is a greater appreciation for the heterogeneous natural histories, responses to treatment, and patterns of these toxicities, which is not currently reflected in irAE guidelines. Furthermore, there are no prospective trial data to inform the management of the distinct presentations of irAEs. Recognizing a need for uniform terminology for the natural history, response to treatment, and patterns of irAEs, the Society for Immunotherapy of Cancer (SITC) convened a consensus panel composed of leading international experts from academic medicine, industry, and regulatory agencies. Using a modified Delphi consensus process, the expert panel developed clinical definitions for irAE terminology used in the literature, encompassing terms related to irAE natural history (ie, re-emergent, chronic active, chronic inactive, delayed/late onset), response to treatment (ie, steroid unresponsive, steroid dependent), and patterns (ie, multisystem irAEs). SITC developed these definitions to support the adoption of a standardized vocabulary for irAEs, which will have implications for the uniform application of irAE clinical practice guidelines and to enable future irAE clinical trials.

Objective This study investigates a 6-month short message service (SMS) intervention to reduce adolescent sugar-sweetened beverage (SSB) intake. The objectives are to describe caregiver retention and SMS engagement as well as explore differences by caregiver characteristics. Methods Caregivers completed a baseline survey then messages were sent two times per week. Message types included the following: SSB intake assessments, educational information, infographic URLs, and strategies. Engagement was measured through interaction with these messages and included: assessment completion, reminders needed, number of strategies chosen, and URLs clicked. Results Caregivers (n = 357) had an average baseline SSB intake of 23.9 (SD = 26.8) oz/day. Of those, 89% were retained. Caregivers with a greater income and education were retained at a higher rate. Average engagement included: 4.1 (SD = 1.3) of 5 assessments completed with few reminders needed [4.1 (SD = 3.7) of 14 possible], 3.2 (SD = 1.1) of 4 strategies selected, and 1.2 (SD = 1.6) of 5 URLs clicked. Overall, average engagement was relatively high, even where disparities were found. Demographic characteristics that were statistically related to lower engagement included younger age, lower income, lower educational attainment, single caregivers, lower health literacy. Furthermore, caregivers with a reduced intention to change SSB behaviors completed fewer assessments and needed more reminders. Higher baseline SSB intake was associated with lower engagement across all indicators except URL clicks. Conclusions Results can be used to develop targeted retention and engagement strategies (e.g., just-in-time and/or adaptive interventions) in rural SMS interventions for identified demographic subsets. Trial registration Clincialtrials.gov: NCT03740113.

Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different sites with very limited information on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we have analyzed the gut microbiome (both fungal and bacterial communities) in patients with metastatic GEP-NENs. Fecal samples were collected and compared with matched healthy control samples using logistic regression distances utilizing R package MatchIt (version 4.2.0, Daniel E. Ho, Stanford, CA, USA). We examined differences in microbiome profiles between GEP-NENs and control samples using small subunit (SSU) rRNA (16S), ITS1, ITS4 genomic regions for their ability to accurately characterize bacterial and fungal communities. We correlated the results with different behavioral and dietary habits, and tumor features including differentiation, grade, primary site, and therapeutic response. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Gut samples of 34 patients (12 males, 22 females, median age 64 years) with metastatic GEP-NENs (22 small bowel, 10 pancreatic, 1 gall bladder, and 1 unknown primary) were analyzed. Twenty-nine patients had well differentiated GEP-neuroendocrine tumors (GEP-NETs), (G1 = 14, G2 = 12, G3 = 3) and five patients had poorly differentiated GEP-neuroendocrine carcinomas (GEP-NECs). Patients with GEP-NENs had significantly decreased bacterial species and increased fungi (notably Candida species, Ascomycota, and species belonging to saccharomycetes) compared to controls. Patients with GEP-NECs had significantly enriched populations of specific bacteria and fungi (such as Enterobacter hormaechei, Bacteroides fragilis and Trichosporon asahii) compared to those with GEP-NETs (p = 0.048, 0.0022 and 0.034, respectively). In addition, higher grade GEP-NETs were associated with significantly higher Bacteroides fragilis (p = 0.022), and Eggerthella lenta (p = 0.00018) species compared to lower grade tumors. There were substantial differences associated with dietary habits and therapeutic responses. This is the first study to analyze the role of the microbiome environment in patients with GEP-NENs. There were significant differences between GEP-NETs and GEP-NECs, supporting the role of the gut microbiome in the pathogenesis of these two distinct entities.

Abstract Background Parents frequently seek parental advice online and on social media; thus, these channels should be better utilized in child health interventions. The Parents in Child Nutrition Informing Community (PICNIC) program aims to facilitate peer-to-peer sharing of evidence-based child feeding information and support parents within their social networks. The present study aimed to explore web and social media analytics to evaluate reach and user engagement with the PICNIC online components. Methods Online user activity data from the PICNIC Facebook closed group and public Page were collected through Facebook Insights, and program-specific website traffic data through Google Analytics. Analytics data from Nov-2019 to April-2021 was evaluated through visualisation and summary statistics to obtain insights into program growth and current reach in Australia, compare demographics of audience reached through the online channels, and explore parents’ use and engagement in PICNIC content. Results Results showed steady program growth in the 18 months of recruitment; participant numbers grew from 102 to 261 peer educators while the Facebook Page audience increased threefold, totalling 1615 followers. Intervention posts shared on Facebook (4–5 posts/week) typically reached only a portion of PICNIC Page followers each week, but also reached a wider audience through their friends. Throughout the evaluated period, Facebook users actively engaged in PICNIC posts, although the level of engagement varied considerably from post to post. Furthermore, results from this study suggest the strategy of directing potentially interested parents from social media to the website for program sign-up was successful. Finally, the explored data gave insights into users’ availability, demographics and engagement, which will be used to inform refinement of the PICNIC website and social media strategies. Conclusions Our findings confirm the benefits of using a peer education approach and existing social network channels to disseminate evidence-based child feeding information to parents. This study also demonstrates the usefulness of web and social media analytics to be used as part of a continuous evaluation for gaining insight to inform further development and improvement of program strategies. Trial registration The PICNIC project was retrospectively submitted for registration with the Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12622000230752 (09/02/2022).

Evidence exists that the typically antiviral signaling mediator STING is, counterintuitively, needed for optimal human rhinovirus infection. Here the authors confirm this finding and show how human rhinovirus can reduce stored Ca2+ levels to drive this effect.