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Abstract Background The pretherapeutic differentiation of subtypes of primary intracranial germ cell tumours (iGCTs), including germinomas (GEs) and nongerminomatous germ cell tumours (NGGCTs), is essential for clinical practice because of distinct treatment strategies and prognostic profiles of these diseases. This study aimed to develop a deep learning model, iGNet, to assist in the differentiation and prognostication of iGCT subtypes by employing pretherapeutic MR T2-weighted imaging. Methods The iGNet model, which is based on the nnUNet architecture, was developed using a retrospective dataset of 280 pathologically confirmed iGCT patients. The training dataset included 83 GEs and 117 NGGCTs, while the retrospective internal test dataset included 31 GEs and 49 NGGCTs. The model’s diagnostic performance was then assessed with the area under the receiver operating characteristic curve (AUC) in a prospective internal dataset (n = 22) and two external datasets (n = 22 and 20). Next, we compared the diagnostic performance of six neuroradiologists with or without the assistance of iGNet. Finally, the predictive ability of the output of iGNet for progression-free and overall survival was assessed and compared to that of the pathological diagnosis. Results iGNet achieved high diagnostic performance, with AUCs between 0.869 and 0.950 across the four test datasets. With the assistance of iGNet, the six neuroradiologists’ diagnostic AUCs (averages of the four test datasets) increased by 9.22% to 17.90%. There was no significant difference between the output of iGNet and the results of pathological diagnosis in predicting progression-free and overall survival (P = .889). Conclusions By leveraging pretherapeutic MR imaging data, iGNet accurately differentiates iGCT subtypes, facilitating prognostic evaluation and increasing the potential for tailored treatment. Graphical Abstract

BackgroundFew individuals (

Evidence is increasing for digital health programs targeting the secondary prevention of stroke. We aimed to determine the feasibility of the novel Care Assistant and support Program for people after Stroke (CAPS) or transient ischaemic attack (TIA) by combining person-centred goal setting and risk-factor monitoring through a web-based clinician portal, SMS messages, a mobile application (app), and a wearable device. We conducted a 12-week mixed-methods, open-label feasibility study. Participants (6 months–3 years after stroke or TIA, access to the internet via a smartphone/tablet) were recruited via the Australian Stroke Clinical Registry. Participants set one or two secondary prevention goals with a researcher and provided access and training in technology use. Feasibility outcomes included recruitment, retention, usability, acceptability, and satisfaction. Secondary outcomes included goal attainment, health outcomes, and program costs. Following 600 invitations, 58 responded, 34/36 (94%) eligible participants commenced the program (one withdrawal; 97% retention), and 10 were interviewed. Participants (27% female, 33% TIA) generally rated the usability of the mobile application as ‘Good’ to ‘Excellent’ (System Usability Scale). Most (94%) agreed the program helped with engagement in health self-monitoring. Overall, 52 goals were set, predominantly regarding exercise (21/52), which were the most frequently achieved (9/21). At 12 weeks, participants reported significant improvements (p < 0.05) in self-efficacy (Cohen’s d = 0.40), cardiovascular health (d = 0.71), and the mental health domain of the PROMIS GH (d = 0.63). CAPS was acceptable, with good retention and engagement of participants. Evaluation of this program in a randomised controlled trial is warranted.

BackgroundMobile health (mHealth) technologies, such as wearable sensors, smart health devices, and mobile apps, that are capable of supporting pregnancy care are emerging. Although mHealth could be used to facilitate the tracking of health changes during pregnancy, challenges remain in data collection compliance and technology engagement among pregnant women. Understanding the interests, preferences, and requirements of pregnant women and those of clinicians is needed when designing and introducing mHealth solutions for supporting pregnant women’s monitoring of health and risk factors throughout their pregnancy journey. ObjectiveThis study aims to understand clinicians’ and pregnant women’s perceptions on the potential use of mHealth, including factors that may influence their engagement with mHealth technologies and the implications for technology design and implementation. MethodsA qualitative study using semistructured interviews was conducted with 4 pregnant women, 4 postnatal women, and 13 clinicians working in perinatal care. ResultsClinicians perceived the potential benefit of mHealth in supporting different levels of health and well-being monitoring, risk assessment, and care provision in pregnancy care. Most pregnant and postnatal female participants were open to the use of wearables and health monitoring devices and were more likely to use these technologies if they knew that clinicians were monitoring their data. Although it was acknowledged that some pregnancy-related medical conditions are suitable for an mHealth model of remote monitoring, the clinical and technical challenges in the introduction of mHealth for pregnancy care were also identified. Incorporating appropriate health and well-being measures, intelligently detecting any abnormalities, and providing tailored information for pregnant women were the critical aspects, whereas usability and data privacy were among the main concerns of the participants. Moreover, this study highlighted the challenges of engaging pregnant women in longitudinal mHealth monitoring, the additional work required for clinicians to monitor the data, and the need for an evidence-based technical solution. ConclusionsClinical, technical, and practical factors associated with the use of mHealth to monitor health and well-being in pregnant women need to be considered during the design and feasibility evaluation stages. Technical solutions and appropriate strategies for motivating pregnant women are critical to supporting their long-term data collection compliance and engagement with mHealth technology during pregnancy.

A major technological goal in neuroscience is to enable the interrogation of individual cells across the live brain. By creating a curved glass replacement to the dorsal cranium and surgical methods for its installation, we developed a chronic mouse preparation providing optical access to an estimated 800,000–1,100,000 individual neurons across the dorsal surface of neocortex. Post-surgical histological studies revealed comparable glial activation as in control mice. In behaving mice expressing a Ca2+ indicator in cortical pyramidal neurons, we performed Ca2+ imaging across neocortex using an epi-fluorescence macroscope and estimated that 25,000–50,000 individual neurons were accessible per mouse across multiple focal planes. Two-photon microscopy revealed dendritic morphologies throughout neocortex, allowed time-lapse imaging of individual cells, and yielded estimates of >1 million accessible neurons per mouse by serial tiling. This approach supports a variety of optical techniques and enables studies of cells across >30 neocortical areas in behaving mice.

Memory T cells are vital responders to skin inflammation, but cell localization and dynamics of exchange with the bloodstream are not clear. Here the authors use parabiosis and intravital microscopy to show that CD4+memory T cells equilibrate with the circulation and cluster around hair follicles in response to CCL5-dependent responses to viral infection or contact sensitization.

Hepatitis B virus (HBV) DNA integration into the host cell genome is reportedly a major cause of liver cancer, and a source of hepatitis B surface antigen (HBsAg). High HBsAg levels can alter immune responses which therefore contributes to the progression of HBV-related disease. However, to what extent integration leads to the persistent circulating HBsAg is unclear. Here, we aimed to determine if the extent of HBV DNA integration is associated with the persistence of circulating HBsAg in people exposed to HBV. We established a digital droplet quantitative inverse PCR (dd-qinvPCR) method to quantify integrated HBV DNA in patients who had been exposed to HBV (anti-HBc positive and HBeAg-negative). Total DNA extracts from both liver resections (n = 32; 14 HBsAg-negative and 18 HBsAg-positive) and fine-needle aspirates (FNA, n = 10; 2 HBsAg-negative and 8 HBsAg-positive) were analysed. Using defined in vitro samples for assay establishment, we showed that dd-qinvPCR could detect integrations within an input of

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

Human skin contains various populations of memory T cells in permanent residence and in transit. Arguably, the best characterized of the skin subsets are the CD8(+) permanently resident memory T cells (TRM) expressing the integrin subunit, CD103. In order to investigate the remaining skin T cells, we isolated skin-tropic (CLA(+)) helper T cells, regulatory T cells, and CD8(+) CD103(-) T cells from skin and blood for RNA microarray analysis to compare the transcriptional profiles of these groups. We found that despite their common tropism, the T cells isolated from skin were transcriptionally distinct from blood-derived CLA(+) T cells. A shared pool of genes contributed to the skin/blood discrepancy, with substantial overlap in differentially expressed genes between each T cell subset. Gene set enrichment analysis further showed that the differential gene profiles of each human skin T cell subset were significantly enriched for previously identified TRM core signature genes. Our results support the hypothesis that human skin may contain additional TRM or TRM-like populations.

This paper presents the results of an experimental investigation of two gesture representations (overlaying hands and cursor pointer) in a video-mediated scenario—remote collaboration on physical task. Our study assessed the relative value of the two gesture representations with respect to their effectiveness in task performance, user's satisfaction, and user's perceived quality of collaboration in terms of the coordination and interaction with the remote partner. Our results show no clear difference between these two gesture representations in the effectiveness and user satisfaction. However, when considering the perceived quality of collaboration, the overlaying hands condition was statistically significantly higher than the pointer cursor condition. Our results seem to suggest that the value of a more expressive gesture representation is not so much a gain in performance but rather a gain in user's experience, more specifically in user's perceived quality of collaborative effort.

Abstract Background Older adults with cancer are vulnerable to declines in muscle performance (e.g., strength, speed, duration of muscular contraction), which are associated with worse cancer-related outcomes. Exercise-based interventions can mitigate these declines, but evidence of their effect among older adults with myeloid malignancies receiving outpatient treatment is limited. We explore change in muscle performance among patients in a single arm pilot study of a mobile health (mHealth) exercise intervention. Methods Patients ≥ 60 years old with myeloid malignancies receiving outpatient chemotherapy completed a home-based resistance band and walking exercise program [EXercise for Cancer Patients (EXCAP)©®] delivered via a mobile application with symptom monitoring [(Geriatric Oncology-EXCAP (GO-EXCAP)] lasting 2 cycles of chemotherapy (approximately 8–12 weeks). Clinical exercise physiologists provided instruction and ongoing support. Upper and lower extremity peak torque (maximum force, newton-meters, Nm), total work (force over entire movement, Nm), and average power (speed of force, watts, W) were assessed using the BIODEX System 4 isokinetic dynamometer. Muscle activation (motor recruitment, millivolts, mV) was captured using the BTS FREEEMG 1000. We report descriptive statistics and within-patient differences from baseline to post-intervention using Wilcoxon signed rank tests (α = 0.10) and effect size (ES, Cohen’s d, 0.20 ≤ small

Abstract Background Autonomy-supporting interventions may be a prerequisite to achieve better long-term management of type 2 diabetes. Evidence suggests that the guided self-determination (GSD) method might improve haemoglobin A1c and diabetes distress in people with type 1 diabetes. The evidence of an effect of a GSD intervention compared with an attention control group in adults with type 2 diabetes is unknown. Methods/design The trial is designed as a pragmatic, investigator-initiated, dual-centre, randomised, parallel-group, assessor-blinded, superiority clinical trial of persons with type 2 diabetes. A nurse will administer GSD intervention versus an attention control. The primary outcome is diabetes distress, and secondary outcomes are quality of life, depressive symptoms, and non-serious adverse events. Exploratory outcomes are haemoglobin A1c, motivation, and serious adverse events. Participants are assessed at baseline, 5-, and 12-month follow-up. Here, we present a detailed, comprehensive plan of all statistical analyses, including methods to handle missing data, and assessments of the underlying statistical assumptions. The statistical analyses will be conducted independently by two statisticians following the present plan. Discussion To mitigate the risk of analysis bias and increase the validity of the OVEROME trial, this statistical analysis plan was developed prior to unblinding of the trial results in concordance with the Declaration of Helsinki and the Conference on Harmonization of Good Clinical Practice Guidelines. Trial registration ClinicalTrials.gov NCT 04601311. Registered on October 2020.

Abstract The clinical manifestations and pathophysiology of clonal hematopoiesis (CH)‐associated immunological dysfunction are poorly understood. We describe an elderly woman with CH who developed various systemic inflammatory or autoimmune diseases (SIADs), including cutaneous Langerhans cell histiocytosis (LCH) and temporal arteritis. Sequencing of the LCH revealed somatic oncogenic mutations in MAP2K1, IDH2, and SRSF2, with enrichment of the latter two in her peripheral blood at high allele frequencies. These findings raise concern for the future development of a myeloid malignancy. Given the mounting evidence for adult‐onset autoinflammatory conditions caused by somatic blood mutations, we suspect CH‐mediated immune dysregulation is contributing to her multi‐organ involvement by a combination of SIADs.

Background: Leishmaniasis is a neglected tropical disease whose available treatment has limitations. Hancornia speciosa Gomes, a tree native to Brazil, has been studied for its medicinal properties, including antimicrobial and healing properties. However, its effect on parasites of the Leishmania genus still needs to be elucidated. Purpose: To evaluate the leishmanicidal activity for potential therapeutic use of H. speciosa latex and its fractions on Leishmania (Leishmania) amazonensis promastigotes and amastigotes, as well as to analyze its cytotoxic effects on RAW264.7 cells and murine peritoneal macrophages. Methods: The anti-promastigote activity of latex and its fractions was evaluated by cell viability assays via MTT in L. (L.) amazonensis and monitoring the parasite's growth kinetics by counting under light microscopy. To evaluate anti-amastigote activity, RAW264.7 cells and murine peritoneal macrophages infected with amastigotes were analyzed using microscopy, immunofluorescence, and flow cytometry assays. The cytotoxicity of latex and its fractions was evaluated in these cells via MTT assay. Results: The H. speciosa latex and its fractions showed anti-promastigote activities in L. (L.) amazonensis, reducing its proliferation and viability and altering its morphology. These did not interfere with the viability of RAW264.7 cells and peritoneal macrophages. Crude latex and F < 10 kDa at 5 % reduced the infection of intracellular amastigotes in peritoneal macrophages to 32 % and 18 % after 24 h of treatment, respectively. Under the same conditions, the F > 10 kDa fraction showed 82 % of infected cells. The evaluation of the latex composition showed that the F > 10 kDa fraction has the highest concentration of carbohydrates, followed by phenolic compounds and proteins. In contrast, the F < 10k Da fraction presented fewer phenolic compounds and carbohydrates. Conclusions: These results indicate that H. speciosa crude latex and F < 10 kDa have intense leishmanicidal activity against L. (L.) amazonensis promastigotes and amastigotes internalized by macrophages. Additionally, the lack of cytotoxicity indicates that H. speciosa latex is a strong candidate for new alternative treatments for leishmaniasis.

Abstract Background Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections. Methods DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts. Conclusion We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility. Trial registration ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

The Gross Primary Productivity (GPP) is an important component in regional and global carbon budgets. Southeastern China has experienced vegetation greening and climate change. Yet, it remains unclear how these changes have impacted GPP in this region. As one of six special national parks in China with complex topography, high biodiversity, and little destructive human activities to the ecosystems, the Wuyi Mountain region is selected to study these impacts. In this study, we use a hydroecological model (BEPS-TerrainLab V2.0) to simulate the spatial and temporal variations of GPP in the Wuyi Mountain region over 2001–2018. We quantitatively separate the effects of vegetation greening and climate change on the trend and interannual variation in GPP through sensitivity experiments. The results show a significant increasing trend in Leaf Area Index (LAI) in the region over 2001–2018 (0.06 m2 m−2 yr−1, p

Abstract Events of stratospheric intrusions to the surface (SITS) can lead to severe ozone (O3) pollution. Still, to what extent SITS events impact surface O3 on a national scale over years remains a long-lasting question, mainly due to difficulty of resolving three key SITS metrics: frequency, duration and intensity. Here, we identify 27,616 SITS events over China during 2015-2022 based on spatiotemporally dense surface measurements of O3 and carbon monoxide, two effective indicators of SITS. An overview of the three metrics is presented, illustrating large influences of SITS on surface O3 in China. We find that SITS events occur preferentially in high-elevation regions, while those in plain regions are more intense. SITS enhances surface O3 by 20 ppbv on average, contributing to 30-45% of O3 during SITS periods. Nationally, SITS-induced O3 peaks in spring and autumn, while over 70% of SITS events during the warm months exacerbate O3 pollution. Over 2015-2022, SITS-induced O3 shows a declining trend. Our observation-based results can have implications for O3 mitigation policies in short and long terms.

Background: Research on improving psychotherapy for youths with obsessive-compulsive disorder (OCD), including cognitive behavioral therapy (CBT), should explore what works for whom and how by examining baseline moderators and potential mechanisms of change. Emotion dysregulation is proposed as an intermediate therapy factor in a transdiagnostic framework. This study investigates emotion dysregulation as an outcome, mechanism, and moderator of psychotherapy in youths aged 8–17 years with OCD. Methods: Data are from a randomized clinical trial and a parallel prospective study of healthy controls. Participants with OCD (n = 130; 121 in this study) were randomized to 14 sessions of either family-based CBT with exposure and response prevention versus family-based psychoeducation and relaxation training. We will; 1) assess if emotion dysregulation, measured by the Difficulties in Emotion Regulation Scale (DERS), decreases from baseline to end-of-treatment; 2) compare the proportion of participants with normative emotion regulation to a 90% reference interval from healthy controls (n = 90); 3) use linear regression to examine if baseline emotion dysregulation moderates treatment effects measured by the Children's Yale-Brown Obsessive-Compulsive Scale; 4) investigate if changes in emotion dysregulation mediate treatment effects; and 5) investigate the stability of emotion regulation over time in the healthy controls. Analyses 1–4 will be conducted for all OCD participants and separately for the two treatment groups. Two independent investigators will perform the analyses. Conclusion: This protocol and statistical analysis plan are presented to enhance analytical transparency and limit bias.

Im Zuge der zunehmenden Durchdringung von Lebenswelten mit digitalen Artefakten veränderte sich das Verhältnis zwischen Menschen und Medien sukzessive und befindet sich weiterhin in einem Transformationsprozess. Virtuelle Lebenswelten sind dabei nicht als Gegenwelten zu begreifen, sondern als unsere Alltagswelten, in denen das Virtuelle bereits ein legitimer Bestandteil geworden ist (vgl. Rieger et al. 2021). Bezogen auf das konkrete Phänomen Ernährungspraktiken haben wir mithilfe eines systematischen Reviews einschlägige Forschungsliteratur gesichtet, um Phänomene zu identifizieren, anhand derer sich dieser Transformationsprozess exemplarisch analysieren lässt. Im Beitrag konzentrieren wir uns auf virtuelle Influencer:innen in sozialen Medien und geben einen Einblick in das Material, bevor wir die Erkenntnisse theoretisch rahmen und einordnen. Abschliessend formulieren wir Implikationen für zukünftige medienpädagogische Forschungsfelder.

Monitoring turtle behavior is a conservation effort to preserve its habitat, and the detection process is a vital initial stage. On the other hand, robotics demands a deep learning network to automatically detect the presence of sea turtles that can operate in real-time. The need for increased model speed in the inference stage has led to many lightweight vision-based detectors. This work proposes a novel turtle detection to localize multiple sea turtles using a deep learning method. A lightweight primary extractor is applied to distinguish crucial features without producing a huge computational. An excited group attention is offered as an enhancement module that can capture essential turtle components in multi-level convolutional patches. A new turtle dataset is proposed that contains lighting, blur, occlusion, and complex background challenges. The evaluation results show that the proposed model performs higher accuracy than other lightweight object detection models. High-efficiency benefits models that can be implemented on low-end devices in terms of real-time data processing speed.

Ecosystem health assessments are crucial to protect the ecological environment and ensure the sustainable ecological functions of alpine ecoregions. At present, few studies evaluating the ecosystem health of the Gannan alpine grassland, China, an ecologically fragile area, based on a remote sensing theoretical framework exist. As such, this study assessed the ecosystem health of the Gannan alpine grassland based on the Remote Sensing-based Ecological Index (RSEI) and provided a comparative analysis of the RSEI and Gross Primary Productivity (GPP), extending the study of their spatiotemporal patterns and influencing factors. The results suggested that RSEI and GPP showed strong comparability in an ecological sense, with the RSEI better reflecting changes in ecosystem health of the Gannan alpine grassland than the GPP. Overall, the health of the Gannan alpine grassland ecosystem was good (RSEI of 0.61–0.76) and a slow, fluctuating upward trend was seen from 2000 (RSEI = 0.66) to 2020 (RSEI = 0.72). Notably, the RSEI was high in the south and low in the north of the region. Over the past 21 years, 43.92% of the ecologically healthy grassland in the southwest of Gannan has been degrading, while the poor ecological health of 39.04% of the grasslands in the southeast and northeast improved. The model test results show that RSEI could reasonably evaluate the ecosystem health of Gannan alpine grassland. Our assessment results provide important scientific data and information on health monitoring and targeted ecological restoration efforts in the Gannan region.

Toxoplasmosis is a neglected disease that represents a significant public health problem. The antigenic profile of T. gondii is complex, and the immune response can lead to either susceptibility or resistance. Some antigens, such as surface antigen glycoprotein (SAG), are expressed on the surface of tachyzoite stages and interact with the host immune cells. In this study, we investigated the potential of the recombinant SAG2A protein of T. gondii to control parasitism and modulate the immune response in the peritoneal exudate cells (PECs) of both susceptible (C57BL/6) and resistant (BALB/c) mice using an in vitro infection model, gene expression, proteomic analysis, and bioinformatic tools. Our results showed that rSAG2A-treated PECs presented a lower parasitism in C57BL/6 mice but not in the PECs from BALB/c mice, and induced a pro-inflammatory cytokine profile in C57BL/6 mice (iNOS, TNF-α, and IL-6). rSAG2A modulated different exclusive proteins in each mouse lineage, with PECs from the C57BL/6 mice being more sensitive to modulation by rSAG2A. Additionally, biological processes crucial to parasite survival and immune response were modulated by rSAG2A in the C57BL/6 PECs, including fatty acid beta-oxidation, reactive oxygen species metabolism, interferon production, and cytokine-mediated signaling pathways. Together, our study indicates that rSAG2A controls T. gondii parasitism in susceptible C57BL/6 PECs through the modulation of pro-inflammatory cytokines and enhanced expression of proteins involved in the cytotoxic response.

This study investigates the key antecedents and mechanisms that influence customer identification in healthcare contexts, based on two studies from different stakeholders: healthcare workers and patients (customers) of healthcare organisations. The first study (N = 788) explored a positive relationship between a hospital’s service tangibility and service reliability. The second (N = 657) affirmed and expanded this finding, and revealed that the service reliability of a hospital was positively related to customer identification with the hospital. This service reliability further mediated the positive relationship between service tangibility and customer identification. Our results highlight the role of service tangibility and reliability in enhancing customer identification in healthcare contexts. Implications for theory and practice are discussed. [ABSTRACT FROM AUTHOR]

Background Asia hosts the second-largest international migrant population in the world. In Southeast Asia (SEA), key types of migration are labour migration, forced migration, and environmental migration. This scoping review seeks to identify key themes and gaps in current research on the ethics of healthcare for mobile and marginalised populations in SEA, and the ethics of research involving these populations. Methods We performed a scoping review using three broad concepts: population (stateless population, migrants, refugees, asylum seekers, internally displaced people), issues (healthcare and ethics), and context (11 countries in SEA). Three databases (PubMed, CINAHL, and Web of Science) were searched from 2000 until May 2023 over a period of four months (February 2023 to May 2023). Other relevant publications were identified through citation searches, and six bioethics journals were hand searched. All searches were conducted in English, and relevant publications were screened against the inclusion and exclusion criteria. Data were subsequently imported into NVivo 14, and thematic analysis was conducted. Results We identified 18 papers with substantial bioethical analysis. Ethical concepts that guide the analysis were ‘capability, agency, dignity’, ‘vulnerability’, ‘precarity, complicity, and structural violence’ (n=7). Ethical issues were discussed from the perspective of research ethics (n=9), clinical ethics (n=1) and public health ethics (n=1). All publications are from researchers based in Singapore, Thailand, and Malaysia. Research gaps identified include the need for more research involving migrant children, research from migrant-sending countries, studies on quality of migrant healthcare, participatory health research, and research with internal migrants. Conclusions More empirical research is necessary to better understand the ethical issues that exist in the domains of research, clinical care, and public health. Critical examination of the interplay between migration, health and ethics with consideration of the diverse factors and contexts involved is crucial for the advancement of migration health ethics in SEA.

BackgroundSerious illness conversations may help patients avoid unwanted treatments. We previously piloted the telehealth Serious Illness Care Program (SICP) for older adults with acute myeloid leukemia and myelodysplastic syndrome. ObjectiveIn this study, we aimed to understand the experience of the telehealth SICP from the clinician’s perspective. MethodsWe studied 10 clinicians who delivered the telehealth SICP to 20 older adults with acute myeloid leukemia or myelodysplastic syndrome. Quantitative outcomes included confidence and acceptability. Confidence was measured using a 22-item survey (range 1-7; a higher score is better). Acceptability was measured using an 11-item survey (5-point Likert scale). Hypothesis testing was performed at α=.10 (2-tailed) due to the pilot nature and small sample size. Clinicians participated in audio-recorded qualitative interviews at the end of the study to discuss their experience. ResultsA total of 8 clinicians completed the confidence measure and 7 clinicians completed the acceptability measure. We found a statistically significant increase in overall confidence (mean increase of 0.5, SD 0.6; P=.03). The largest increase in confidence was in helping families with reconciliation and goodbye (mean 1.4, SD 1.5; P=.04). The majority of clinicians agreed that the format was simple (6/7, 86%) and easy to use (6/7, 86%). Clinicians felt that the telehealth SICP was effective in understanding their patients’ values about end-of-life care (7/7, 100%). A total of three qualitative themes emerged: (1) the telehealth SICP deepened relationships and renewed trust; (2) each telehealth SICP visit felt unique and personal in a positive way; and (3) uninterrupted, unrushed time optimized the visit experience. ConclusionsThe telehealth SICP increased confidence in having serious illness conversations while deepening patient-clinician relationships. Trial RegistrationClinicalTrials.gov NCT04745676; https://www.clinicaltrials.gov/study/NCT04745676

The discovery of new therapeutic alternatives for cancer treatment is essential for improving efficacy and specificity, overcoming resistance, and enabling a more personalized approach for each patient. We investigated the antitumor activity of the crude ethanolic extract of the fungus Trichoderma asperelloides (ExtTa) and its interaction with chemotherapeutic drugs. It was observed, by MTT cytotoxicity assay, that ExtTa significantly reduced cell viability in breast adenocarcinoma, glioblastoma, lung carcinoma, melanoma, colorectal carcinoma, and sarcomas cell lines. The highest efficacy and selectivity of ExtTa were found against glioblastoma T98G and colorectal HCT116 cell lines. ExtTa is approximately four times more cytotoxic to those tumor cells than to non-cancer cell lines. A synergistic effect between ExtTa and doxorubicin was found in the treatment of osteosarcoma Saos-2 cells, as well as with 5-fluorouracil in the treatment of HCT116 colorectal carcinoma cells using CompuSyn software. Our data unravel the presence of bioactive compounds with cytotoxic effects against cancer cells present in T. asperelloides ethanolic crude extract, with the potential for developing novel anticancer agents.

We present the case of a 75-year-old female with simultaneous EGFR-mutated stage IV lung cancer and advanced BRCA2-mutated ovarian cancer, treated with a unique regimen. In this case report, the patient was treated with alternating months of osimertinib and olaparib to control her lung and ovarian cancers, respectively. When both diseases showed progression, the patient underwent a trial of concurrent therapy with both drugs, yet this was discontinued due to patient-reported adverse side effects. Combination targeted drug therapy may be required to treat complex diagnoses such as dual malignancies. However, combination drug therapy consisting of osimertinib and olaparib has not previously been explored. This case report represents the first to demonstrate osimertinib and olaparib combination therapy as a unique treatment regimen for concurrent lung and ovarian cancers. These two drugs can either be given in an alternating way or given together, short-term, with a higher but tolerable toxicity profile.

AbstractObjective To evaluate an experiential student clinical addiction research program by analyzing its components, evaluation survey data, and scientific outputs.Methods In 1995, we established a summer research program supporting trainees to gain exposure to clinical addiction research careers. This curriculum employed a three-pronged approach that combined mentored research training, didactic education, and clinical observerships for medical students and other trainees to acquire experience with addiction medicine and research. Utilizing the Kirkpatrick model as program evaluation framework, we analyzed evaluation data from programmatic surveys (didactic seminar evaluations, overall program surveys) and conducted qualitative feedback exploration.Results Between 2007 and 2019, 56 trainees and 26 faculty mentors participated in the curriculum. To date, 25 students published 38 papers with their faculty mentor. Analysis of the past 12 years of program evaluation data demonstrated that students highly valued individually-mentored research experiences. They indicated that seminars familiarized them with the foundations of different clinical care models and career trajectories in addiction medicine. Clinical observerships provided students with patient contacts in various multidisciplinary addiction treatment settings. These experiences, perhaps most importantly hearing about patients’ lived experiences, meaningfully informed various research and didactic activities.Conclusions This summer student research program successfully introduced students to addiction medicine and research, manifested by high peer-reviewed publication productivity. While our program engaged and involved committed mentors and inspired mentees to pursue professional paths in addiction research, it did not specifically incorporate attention to equity and diversity into program planning and implementation. Going forward, the program will improve equity by increasing the recruitment of trainees from disadvantaged groups and engaging underrepresented faculty.KEY MESSAGESSummer programs can be effective in engaging medical students and trainees in research early in their trajectory and inspire them to incorporate research into their careers.Programs that integrate experiential addiction research learning, i.e. mentored research activities, didactic sessions, and clinical observerships, can provide trainees with a profound understanding of substance use disorder treatment and research.

Abstract Background Autonomy-supporting interventions, such as self-determination theory and guided self-determination interventions, may improve self-management and clinical and psychosocial outcomes in people with diabetes. Such interventions have never been systematically reviewed assessing both benefits and harms and concurrently controlling the risks of random errors using trial sequential analysis methodology. This systematic review investigates the benefits and harms of self-determination theory-based interventions compared to usual care in people with diabetes. Methods We used the Cochrane methodology. Randomized clinical trials assessing interventions theoretically based on guided self-determination or self-determination theory in any setting were eligible. A comprehensive search (latest search April 2022) was undertaken in CENTRAL, MEDLINE, Embase, LILACS, PsycINFO, SCI-EXPANDED, CINAHL, SSCI, CPCI-S, and CPCI-SSH to identify relevant trials. Two authors independently screened, extracted data, and performed risk-of-bias assessment of included trials using the Cochrane risk-of-bias tool 1.0. Our primary outcomes were quality of life, all-cause mortality, and serious adverse events. Our secondary outcomes were diabetes distress, depressive symptoms, and nonserious adverse events not considered serious. Exploratory outcomes were glycated hemoglobin and motivation (autonomy, controlled, amotivation). Outcomes were assessed at the end of the intervention (primary time point) and at maximum follow-up. The analyses were conducted using Review Manager 5.4 and Trial Sequential Analysis 0.9.5.10. Certainty of the evidence was assessed by GRADE. Results Our search identified 5578 potentially eligible studies of which 11 randomized trials (6059 participants) were included. All trials were assessed at overall high risk of bias. We found no effect of self-determination theory-based interventions compared with usual care on quality of life (mean difference 0.00 points, 95% CI −4.85, 4.86, I 2 = 0%; 225 participants, 3 trials, TSA-adjusted CI −11.83, 11.83), all-cause mortality, serious adverse events, diabetes distress, depressive symptoms, adverse events, glycated hemoglobulin A1c, or motivation (controlled). The certainty of the evidence was low to very low for all outcomes. We found beneficial effect on motivation (autonomous and amotivation; low certainty evidence). Conclusions We found no effect of self-determination-based interventions on our primary or secondary outcomes. The evidence was of very low certainty. Systematic review registration PROSPERO CRD42020181144

Tumor necrosis factor (TNF)α is a major regulator of inflammation. However, the epigenetic regulation of TNFα in the context of an exercise intervention among older adults with cancer is understudied. In this exploratory analysis, we used data from a single-arm mobile health (mHealth) exercise intervention among older adults with myeloid malignancies to 1) assess changes in TNFα promoter methylation, TNFα mRNA expression, serum TNFα and other related-cytokine levels after intervention; and 2) assess correlations between blood markers and exercise levels. Twenty patients were included. From baseline to post-intervention, there was no statistical changes in TNFα promoter methylation status at seven CpG sites, TNFα mRNA expression, and serum TNFα levels. Effect sizes, however, were moderate to large for several CpG sites (−120, −147, −162, and −164; Cohen's d = 0.44–0.75). Median serum TNFα sR1 levels increased (83.63, IQR 130.58, p = 0.06; Cohen's d = 0.18) but not the other cytokines. Increases in average daily steps were correlated with increases in TNFα promoter methylation at CpG sites −147 (r = 0.48; p = 0.06) and −164 (r = 0.51; p = 0.04). Resistance training minutes were negatively correlated with TNFα promoter methylation at CpG site −120 (r = −0.62; p = 0.02). All effect sizes were moderate to large. In conclusion, after a mHealth exercise intervention, we demonstrated changes with moderate to large effect sizes in several CpG sites in the TNFα promoter region. Exercise levels were correlated with increases in TNFα promoter methylation. Larger exercise trials are needed to better evaluate TNFα regulation to inform interventions to augment TNFα regulation in order to improve outcomes in older adults with cancer.

BackgroundOpioids are a key component of pain management among patients with metastatic cancer pain. However, the evidence base available to guide opioid-related decision-making in individuals with advanced cancer is limited. Patients with advanced cancer or cancer that is unlikely to be cured frequently experience pain. Opioids are a key component of pain management among patients with metastatic cancer pain. Many individuals with advanced cancer are now living long enough to experience opioid-related harm. Emerging evidence from chronic noncancer pain literature suggests that longer-term opioid therapy may have limited benefits for pain and function, and opioid-related harms are also a major concern. However, whether these benefits and harms of opioids apply to patients with cancer-related pain is unknown. ObjectiveThis manuscript outlines the protocol for the “Opioid Therapy for Pain in Individuals With Metastatic Cancer: The Benefits, Harms, and Stakeholder Perspectives (BEST) Study.” The study aims to better understand opioid decision-making in patients with advanced cancer, along with opioid benefits and harms, through prospective examination of patients’ pain experiences and opioid side effects and understanding the decision-making by patients, care partners, and clinicians. MethodsThis is a multicenter, prospective cohort study that aims to enroll 630 patients with advanced cancer, 20 care partners, and 20 clinicians (670 total participants). Patient participants must have an advanced solid cancer diagnosis, defined by the American Cancer Society as cancer that is unlikely to be cured. We will recruit patient participants within 12 weeks after diagnosis so that we can understand opioid benefits, harms, and perspectives on opioid decision-making throughout the course of their advanced cancer (up to 2 years). We will also specifically elicit information regarding long-term opioid use (ie, opioids for ≥90 consecutive days) and exclude patients on long-term opioid therapy before an advanced cancer diagnosis. Lived-experience perspectives related to opioid use in those with advanced cancer will be captured by qualitative interviews with a subset of patients, clinicians, and care partners. Our data collection will be grounded in a behavioral decision research approach that will allow us to develop future interventions to inform opioid-related decision-making for patients with metastatic cancer. ResultsData collection began in October 2022 and is anticipated to end by November 2024. ConclusionsUpon successful execution of our study protocol, we anticipate the development of a comprehensive evidence base on opioid therapy in individuals with advanced cancer guided by the behavioral decision research framework. The information gained from this study will be used to guide interventions to facilitate opioid decisions among patients, clinicians, and care partners. Given the limited evidence base about opioid therapy in people with cancer, we envision this study will have significant real-world implications for cancer-related pain management and opioid-related clinical decision-making. International Registered Report Identifier (IRRID)DERR1-10.2196/54953

Background The posterior ledge (PL) is a vital structure that supports the implant posteriorly during orbital floor reconstruction. This study describes a technique for mapping the PL in relation to the infraorbital margin (IM) in patients with orbital floor blowout fractures. This study establishes the location of the optic foramen in relation to the PL.

Abstract Surface ozone increased unexpectedly over northern China during the COVID-19 lockdown (CLD) period (23 January–29 February 2020), which was characterized by vigorous emission reduction. The reasons for this ozone enhancement have been speculated from perspectives of chemical responses to the emissions and meteorology. As known, the processes of natural stratospheric ozone injecting to the troposphere are most active in winter and spring. Yet, little attention was paid to stratospheric influences on this ozone enhancement. Here we report a stratospheric intrusion (SI) that reached the surface over northern China on 15–17 February during the CLD. The coevolution of enhanced ozone and sharply declined carbon monoxide and relative humidity (RH) was indicative of the SI occurrence. We show that the SI was facilitated by a cutoff low system that led to abnormally high surface ozone in most part of northern China. We estimate that over the SI period, the injected stratospheric ozone constituted up to 40–45% of the surface ozone over northern China. If the stratospheric ozone inputs were scaled over the entire CLD period, these inputs would account for 4–8% of the surface ozone. In view of the unexpected ozone increase during the CLD, this SI event could explain up to 18% of the ozone increase in some cities, and average 5–10% over larger areas that were affected. Hence, the nonnegligible stratospheric influences urge extra consideration of natural ozone sources in disentangling the role of emission reduction and meteorological conditions during the CLD in China and elsewhere in the world.

Abstract Background Older adults with myeloid malignancies are susceptible to treatment-related toxicities. Accelerated DNAm age, or the difference between DNA methylation (DNAm) age and chronological age, may be used as a biomarker of biological age to predict individuals at risk. In addition, cancer treatment can also lead to accelerated DNAm age. Exercise is a promising intervention to reduce or prevent functional, psychological, and cognitive impairments in older patients with myeloid malignancies, yet there is little evidence of the effects of exercise on DNAm age. We explored (1) the associations of accelerated DNAm age with physical, psychological, and cognitive functions at baseline; (2) changes in DNAm age from baseline to post-intervention; and (3) the associations of changes in accelerated DNAm age with changes in functions from baseline to post-intervention. Methods We enrolled older patients with myeloid malignancies to a single-arm pilot study testing a mobile health (mHealth) exercise intervention that combines an exercise program (EXCAP©®) with a mobile application over 2 cycles of chemotherapy (8–12 weeks). Patients completed measures of physical, psychological, and cognitive functions and provided blood samples for analyses of DNAm age at baseline and post-intervention. Paired t-tests or Wilcoxon signed rank tests assessed changes in DNAm ages, and Spearman’s correlation assessed the relationships between accelerated ages and functions. Results We included 20 patients (mean age: 72 years, range 62–80). Accelerated GrimAge, accelerated PhenoAge, and DunedinPACE were stable from baseline to post-intervention. At baseline, DunedinPACE was correlated with worse grip strength (r = -0.41, p = 0.08). From baseline to post-intervention, decreases in accelerated GrimAge (r = -0.50, p = 0.02), accelerated PhenoAge (r = − 0.39, p = 0.09), and DunedinPace (r = − 0.43, p = 0.06) were correlated with increases in distance walked on 6-min walk test. Decreases in accelerated GrimAge (r = − 0.49, p = 0.03), accelerated PhenoAge (r = − 0.40, p = 0.08), and DunedinPace (r = − 0.41, p = 0.07) were correlated with increases in in grip strength. Conclusions Among older adults with myeloid malignancies receiving chemotherapy, GrimAge and PhenoAge on average are stable after a mHealth exercise intervention. Decreases in accelerated GrimAge, accelerated PhenoAge, and DunedinPACE over 8–12 weeks of exercise were correlated with increased physical performance. Future trials assessing the effects of exercise on treatment-related toxicities should evaluate DNAm age. Trial registration Clinicaltrials.gov identifier: NCT04981821.

Urban tree classification enables informed decision-making processes in urban planning and management. This paper introduces a novel data reformation method, pseudo tree crown (PTC), which enhances the feature difference in the input layer and results in the improvement of the accuracy and efficiency of urban tree classification by utilizing artificial intelligence (AI) techniques. The study involved a comparative analysis of the performance of various machine learning (ML) classifiers. The results revealed a significant enhancement in classification accuracy, with an improvement exceeding 10% observed when high spatial resolution imagery captured by an unmanned aerial vehicle (UAV) was utilized. Furthermore, the study found an impressive average classification accuracy of 93% achieved by a classifier built on the PyTorch framework, with ResNet50 leveraged as its convolutional neural network layer. These findings underscore the potential of AI-driven approaches in advancing urban tree classification methodologies for enhanced urban planning and management practices.

Climate change has caused more frequent instances of extreme climatic events around the world, being an influential factor on the occurrence of wildfires in China on large scale. However, the impact of changes in extreme climate on the occurrence of wildfires in different climate zones remains unclear. In the present study, 26 extreme climate indices were selected to analyze the thereof relationship with wildfire occurrences from 2005 to 2018 in different regions of China. Wildfires in China primarily occur in the south, with a measurable presence in the north. On an annual scale, the wildfire occurrences in southwestern China show stronger correlations with mean temperature than extreme temperature indices, but show stronger correlations with extreme precipitation indices than the total precipitation. On the contrary, the wildfire occurrences in southeastern China show stronger correlations with the total precipitation than extreme precipitation indices, but show stronger correlations with extreme temperature indices than the mean temperature. In Northeast China, wildfires show a more significant correlation with mean temperature than with any extreme climate indices, indicating a minimal impact from extreme climatic conditions. The fire-climate relationships in the main fire season (January-April) are similar to those in the annual scale. The wildfire occurrences in the southwestern, south-central, and southeastern China, which are located in the same latitudes, were affected by extreme climate indices of different types and on different time scales. Furthermore, we recommend that consecutive dry days (CDD) and diurnal temperature range (DTR) should be considered first when studying the relationship between wildfire occurrence and extreme climate in southwestern and southeastern China respectively.

Background Asia hosts the second-largest international migrant population in the world. In Southeast Asia (SEA), key types of migration are labour migration, forced migration, and environmental migration. This scoping review seeks to identify key themes and gaps in current research on the ethics of healthcare for mobile and marginalised populations in SEA, and the ethics of research involving these populations. Methods We performed a scoping review using three broad concepts: population (stateless population, migrants, refugees, asylum seekers, internally displaced people), issues (healthcare and ethics), and context (11 countries in SEA). Three databases (PubMed, CINAHL, and Web of Science) were searched from 2000 until May 2023 over a period of four months (February 2023 to May 2023). Other relevant publications were identified through citation searches, and six bioethics journals were hand searched. All searches were conducted in English, and relevant publications were screened against the inclusion and exclusion criteria. Data were subsequently imported into NVivo 14, and thematic analysis was conducted. Results We identified 18 papers with substantial bioethical analysis. Ethical concepts that guide the analysis were ‘capability, agency, dignity’, ‘vulnerability’, ‘precarity, complicity, and structural violence’ (n=7). Ethical issues were discussed from the perspective of research ethics (n=9), clinical ethics (n=1) and public health ethics (n=1). All publications are from researchers based in Singapore, Thailand, and Malaysia. Research gaps identified include the need for more research involving migrant children, research from migrant-sending countries, studies on quality of migrant healthcare, participatory health research, and research with internal migrants. Conclusions More empirical research is necessary to better understand the ethical issues that exist in the domains of research, clinical care, and public health. Critical examination of the interplay between migration, health and ethics with consideration of the diverse factors and contexts involved is crucial for the advancement of migration health ethics in SEA.

Abstract Background In a single‐arm pilot study, we assessed the feasibility and usefulness of an innovative patient‐centered communication tool (UR‐GOAL tool) that addresses aging‐related vulnerabilities, patient values, and prognostic awareness for use in treatment decision making between older adults with newly diagnosed acute myeloid leukemia (AML), their caregivers, and oncologists. Methods Primary feasibility metric was retention rate; >50% was considered feasible. We collected recruitment rate, usefulness, and outcomes including AML knowledge (range 0–14) and perceived efficacy in communicating with oncologists (range 5–25). Due to the pilot nature and small sample size, hypothesis testing was performed at α = 0.10. Results We included 15 patients (mean age 76 years, range 64–88), 12 caregivers, and 5 oncologists; enrollment and retention rates for patients were 84% and 73%, respectively. Patients agreed that the UR‐GOAL tool helped them understand their AML diagnosis and treatment options, communicate with their oncologist, and make more informed decisions. From baseline to post‐intervention, patients and caregivers scored numerically higher on AML knowledge (patients: +0.6, p = 0.22; caregivers: +1.1, p = 0.05) and perceived greater efficacy in communicating with their oncologists (patients: +1.5, p = 0.22; caregivers: +1.2, p = 0.06). Conclusion We demonstrated that it is feasible to incorporate the UR‐GOAL tool into treatment decision making for older patients with AML, their caregivers, and oncologists.

Abstract Objective: To assess the clustering properties of residential urban food environment indicators across neighbourhoods and to determine if clustering profiles are associated with diet outcomes among adults in Brooklyn, New York. Design: Cross-sectional. Setting: Five neighbourhoods in Brooklyn, New York. Participants: Survey data (n 1493) were collected among adults in Brooklyn, New York between April 2019 and September 2019. Data for food environment indicators (fast-food restaurants, bodegas, supermarkets, farmer’s markets, community kitchens, Supplemental Nutrition Assistance Program application centres, food pantries) were drawn from New York databases. Latent profile analysis (LPA) was used to identify individuals’ food access-related profiles, based on food environments measured by the availability of each outlet within each participant’s 800-m buffer. Profile memberships were associated with dietary outcomes using mixed linear regression. Results: LPA identified four residential urban food environment profiles (with significant high clusters ranging from 17 to 57 across profiles): limited/low food access, (n 587), bodega-dense (n 140), food swamp (n 254) and high food access (n 512) profiles. Diet outcomes were not statistically different across identified profiles. Only participants in the limited/low food access profile were more likely to consume sugar-sweetened beverages (SSB) than those in the bodega-dense profile (b = 0·44, P < 0·05) in adjusted models. Conclusions: Individuals in limited and low food access neighbourhoods are vulnerable to consuming significant amounts of SSB compared with those in bodega-dense communities. Further research is warranted to elucidate strategies to improve fruit and vegetable consumption while reducing SSB intake within residential urban food environments.

Abstract Background Endoscopic retrograde cholangiography (ERC) with stone extraction and papillotomy with subsequent laparoscopic cholecystectomy—the two-step approach—is the standard treatment of common bile duct stones in many countries. However, ERC is associated with a high risk of complications and more than half of patients require multiple ERCs. Meta-analyses of randomised clinical trials find no major differences of the two-step approach in comparison with laparoscopic cholecystectomy with intraoperative laparoscopic stone clearance—the one-step approach. Currently, there are insufficient data to ascertain superiority. Methods The preGallstep trial is an investigator-initiated, multicentre randomised feasibility and pilot clinical trial with blinded outcome assessment. Eligible patients are patients with common bile duct stones (identified by magnetic resonance cholagiopancreatography), age 18 years or above with the possibility to perform both interventions within a reasonable time. We intent to randomise 150 participants allocated 1:1. The experimental intervention is the one-step approach. This consists of laparoscopic common bile duct exploration plus laparoscopic cholecystectomy. The control intervention is the two-step approach which consists of ERC plus sphincterotomy (first step) and subsequent laparoscopic cholecystectomy (second step). Feasibility outcomes include the proportion of eligible patients not wanting to participate, reasons for rejection to participate, difficulties during the informed consent procedure, difficulties with randomisation, difficulties with data management, difficulties with blinding patient charts and forms and difficulties with maintaining blinding for the outcome assessors. The primary pilot outcome is the proportion of participants with at least one postoperative complication according to the Clavien-Dindo score grade II and above until 90 days after randomisation. This outcome will be used for a future sample size calculation of a larger pragmatic trial. Further, a range of clinical explorative outcomes will be assessed. Discussion As no sample size is estimated in this trial, there is a risk of wrongly assessing the effect on the patient-related outcome. The surgical procedures cannot be blinded. However, blinding will be employed in all other aspects of the trial, including the establishment of a blinded outcome adjudication committee with three independent assessors. Heterogeneity in screening, randomisation, diagnostics, treatment procedures, interventions and follow-up across trial sites may cause challenges in conducting a larger pragmatic trial. To monitor inter-site differences, we have implemented a central data monitoring scheme. Trial registration ClinicalTrials.gov identification: NCT04801238 , Registered on 16 March 2021

Dystrophic calcinosis cutis can be associated with severe pain, decreased mobility, increased risk of infection and significantly decreased quality of life. We report a case of recalcitrant calcinosis cutis on the background of eosinophilic fasciitis, which achieved rapid reduction in calcium deposits following a novel injecting protocol of intralesional sodium thiosulfate. [ABSTRACT FROM AUTHOR]

Background: Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on adverse events in psychotherapy for youth with OCD. Methods: This is an analysis plan for a convergent mixed methods study within a randomized clinical trial (the TECTO trial). We include at least 128 youth aged 8–17 years with obsessive-compulsive disorder (OCD). Participants are randomized to either family-based cognitive behavioral therapy (FCBT) or family-based psychoeducation and relaxation training (FPRT). Adverse events are monitored quantitatively with the Negative Effects Questionnaire. Furthermore, we assess psychiatric symptoms, global functioning, quality of life, and family factors to investigate predictors for adverse events. We conduct semi-structured qualitative interviews with all youths and their parents on their experience of adverse events in FCBT or FPRT. For the mixed methods analysis, we will merge 1) a qualitative content analysis with descriptive statistics comparing the types, frequencies, and severity of adverse events; 2) a qualitative content analysis of the perceived causes for adverse events with prediction models for adverse events; and 3) a thematic analysis of the participants’ treatment evaluation with a correlational analysis of adverse events and OCD severity. Discussion: The in-depth mixed methods analysis can inform 1) safer and more effective psychotherapy for OCD; 2) instruments and guidelines for monitoring adverse events; and 3) patient information on potential adverse events. The main limitation is risk of missing data. Trial registration: ClinicalTrials.gov identifier: NCT03595098. Registered on July 23, 2018.