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Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.

Although intestinal microbiome have been established as an important biomarker and regulator of cancer development and therapeutic response, less is known about the role of microbiome at other body sites in cancer. Emerging evidence has revealed that the local microbiota make up an important part of the tumor microenvironment across many types of cancer, especially in cancers arising from mucosal sites, including the lung, skin and gastrointestinal tract. The populations of bacteria that reside specifically within tumors have been found to be tumor-type specific, and mechanistic studies have demonstrated that tumor-associated microbiota may directly regulate cancer initiation, progression and responses to chemo- or immuno-therapies. This review aims to provide a comprehensive review of the important literature on the microbiota in the cancerous tissue, and their function and mechanism of action in cancer development and treatment.

Background: Student-run free clinics provide an opportunity to shape medical student practices with and attitudes towards the medically underserved. Previous literature has shown mixed results on how student attitudes change over the course of medical education. The purpose of this mixed-method study is to determine the effect that participation in a student-run free clinic has on medical student attitudes towards the underserved as compared to attitudes of non-participating students. Methods: The validated Medical Attitudes Towards the Underserved (MSATU) survey was administered in cross-sectional study to student participants in a student-run free clinic and to non-participating medical students (n = 122). Additionally, first and fourth year participant students were interviewed via semi-structured interviews about results. Results: There was no statistically significant difference in overall MSATU scores between participant and non-participant medical students using Mann Whitney tests. In sub-score analyses, Mann Whitney tests demonstrated significantly higher scores among participants in the total services score (U = 1344.0, df = 115, p = 0.013) and the expensive procedures services sub-score (U = 1401.0, df = 115, p = 0.019). Interviews revealed that positive attitudes towards the underserved are not specific to student-run free clinic participants. Participants did not describe changes in their attitude from clinic participation, believing all medical students had a baseline positive attitude towards the underserved. They did, however, highlight that witnessing the reality of these patients influenced their perspective and future practice. Conclusions: There were limited significant differences in MSATU survey scores between participant and non-participant students. Interview results suggest that the survey tool was unable to capture changes in the perspectives of participant medical students or the changes in their projected practices but that, participation in a student-run free clinic had an overall positive effect on understanding of the barriers to care and empathy towards the underserved.

Background A range of services within Australia and internationally have been developed that are focused on the engagement of individuals who are of refugee background to work as a liaison between their communities and mental health services. The Community Liaison Worker (CLW) role at the Victorian Foundation for Survivors of Torture (VFST) was developed in 2008 in order to engage in such capacity-building initiatives. Aims To review and document the establishment, evolution and current status of the VFST CLW role, and examine the perspectives of CLWs on their role in trauma-informed community capacity-building. Methods The study comprised of two stages: a historical case study of the development of the CLW role, and a qualitative research study based on interviews with CLWs in order to identify key themes regarding various aspects of their role and understand the facilitators and barriers to their work of trauma-informed capacity-building with their respective communities. Results The CLW role has evolved from the provision of direct services through joint work with Counsellor Advocates at VFST to a broader role that is focused on building the capacity of community members. Thematic analysis of interviews with the seven current CLWs identified the complexity of their dual role as members of their community and employees of VFST, their role in addressing short-term goals to meet community needs, and the long-term objective of empowering their community to become integrated and self-sufficient. Conclusions CLWs at VFST demonstrate important work of liaison workers in facilitating trauma-informed capacity-building initiatives that are of benefit to members of their communities and also to service providers.

Background Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. Methods We investigated in vitro and in vivo effects of metformin in humans. Results Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in vitro cellular metabolism while inhibiting the mammalian target of rapamycin targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation and increased phagocytosis activity. Metformin administered to healthy human volunteers led to significant downregulation of genes involved in oxidative phosphorylation, mammalian target of rapamycin signaling, and type I interferon response pathways, particularly following stimulation with M. tuberculosis, and upregulation of genes involved in phagocytosis and reactive oxygen species production was increased. These in vivo effects were accompanied by a metformin-induced shift in myeloid cells from classical to nonclassical monocytes. At a functional level, metformin lowered ex vivo production of tumor necrosis factor α, interferon γ, and interleukin 1β but increased phagocytosis activity and reactive oxygen species production. Conclusion Metformin has a range of potentially beneficial effects on cellular metabolism, immune function, and gene transcription involved in innate host responses to M. tuberculosis., Metformin has shown beneficial effects in a murine model of tuberculosis. Using in-vitro and in-vivo studies we show that metformin has beneficial effects on cellular metabolism, immune function and genetranscription involved in innate host responses to M. tuberculosis in humans.

BACKGROUND Heart failure (HF) is a major public health problem that places a significant disease burden on society. Self-care is important in the management of HF because it averts disease progression and reduces the number of hospitalizations. Effective nursing interventions promote HF self-care. OBJECTIVE This study aims to explore participants’ perspectives on a nurse-led, home-based heart failure self-management program (HOM-HEMP) in a randomized controlled trial conducted in Singapore to gain insight into the effectiveness of the study intervention. METHODS A descriptive, qualitative approach was used. English- or Chinese-speaking participants from the intervention arms were recruited through a purposive sampling method from January 2019 to July 2019. Individual, face-to-face, semistructured interviews were conducted with 11 participants. All interviews were audio recorded and transcribed verbatim, with the participant identifiers omitted to ensure confidentiality. The thematic analysis approach was used to identify, analyze, and report patterns (themes) within the data. RESULTS A total of six themes emerged from the process evaluation interviews and were categorized according to the Donabedian structure-process-outcome framework as intervention structure, intervention process, and intervention outcome. These six themes were manageability of the intervention, areas for improvement, benefits of visiting, personal accountability in self-care, empowered with knowledge and skills in self-care after the intervention, and increased self-efficacy in cardiac care. CONCLUSIONS The findings of the process evaluation provided additional information on participants’ perceptions and experiences with the HOM-HEMP intervention. Although a home visit may be perceived as resource intensive, it remains to be the preferred way of engagement for most patients. Nurses play an important role in promoting HF self-care. The process of interaction with the patient can be an important process for empowering self-care behavior changes.

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

BACKGROUND Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. AMI is associated with poorer quality of life and other psychological symptoms (such as stress, depression and anxiety). Effective psychosocial interventions are essential to help patients post-AMI manage with the psychological symptoms. OBJECTIVE This study aimed to test the efficacy of a newly-developed symptom self-management program on health outcomes among inpatients post-AMI METHODS A pilot randomized, single-blinded, controlled trial was utilized. A convenient sample of 90 was recruited from a tertiary hospital in Singapore. Adult inpatients with stable post-AMI were randomly assigned to the following three groups: IManage-VR, IManage-FF or control group. The IManage-VR and IManage-FF groups received standard care and a symptom self-management program through virtual-reality device or face-to-face method respectively. Two researchers delivered the interventions and assisted with relaxation practice. The control group received only standard care. Data were collected through self-reported questionnaires and physiological instruments. Data analyses included univariate statistics, analysis of variance and repeated measure analysis of variance. RESULTS A total of 90 participants were recruited with 30 in each group. Results indicated that participants in the IManage-VR and IManage-FF group had significantly greater relaxation levels (Partial η2 = 0.11, 0.16), lower objective stress (Partial η2 =0.14, 0.06), and greater knowledge (Partial η2 = 0.62, 0.75) than those of the control group. The two intervention groups had lower subjective stress (Partial η2 = 0.04), depression (Partial η2 = 0.01), and anxiety (Partial η2 = 0.03) than the control but such differences did not achieve statistical significance. Furthermore, most participants (>90%) in the IManage-VR and IManage-FF groups reported that they were satisfied with the programs and they provided positive comments on the contents, educational materials and relaxation practice. CONCLUSIONS This pilot study supports the potential benefits and feasibility of the IManage-VR and IManage-FF interventions on stress, perceived relaxation, knowledge and patient satisfaction. Findings contribute to the current literature on psychosocial interventions for AMI where psychosocial educational materials could be added into the current cardiac rehabilitation programs. Future RCTs with multi-centered sites and larger sample size are required to further test the intervention. CLINICALTRIAL This study has been registered with International Standard Randomised Controlled Trial. Registration Number: ISRCTN61027816. http://www.controlled-trials.com/ ISRCTN61027816.

Deep-immunophenotyping of the circulatory T cell compartment using mass cytometry and unsupervised clustering analysis, identifies phenotypic and functional differences in patients with atopic dermatitis (AD) and psoriasis, highlighting the stronger systemic component associated with AD.

With the rapid development in artificial intelligence, social computing has evolved beyond social informatics toward the birth of social intelligence systems. This paper, therefore, takes initiatives to propose a social behaviour understanding framework with the use of deep neural networks for social and behavioural analysis. The integration of information fusion, person and object detection, social signal understanding, behaviour understanding, and context understanding plays a harmonious role to elicit social behaviours. Three systems, including depression detection, activity recognition and cognitive impairment screening, are developed to evidently demonstrate the importance of social intelligence. The study considerably contributes to the cumulative development of social computing and health informatics. It also provides a number of implications for academic bodies, healthcare practitioners, and developers of socially intelligent agents.

Background Atrial fibrillation (AF) is the most common arrhythmia and has debilitating effects on patients' health-related quality of life (HRQoL) and psychological statuses. Aim To investigate the HRQoL, psychological distress, and symptom burden, and to identify the significant influencing factors of HRQoL among outpatients with AF in Singapore. Methods We conducted a cross-sectional descriptive correlational study of a sample of 116 outpatients with AF. Data were collected using 12-item Short Form Health Survey, Atrial Fibrillation Effect on Quality of Life scale, Patient Health Questionnaire-9 (PHQ-9), and University of Toronto Atrial Fibrillation Symptom Severity (AFSS) scale. Results Symptom burden and psychological distress significantly influenced the AF-specific HRQoL while symptom burden, unemployment and comorbidity of heart failure were significantly associated with poorer general physical health. Psychological distress was the only significant factor influencing the mental health. Conclusion Optimal symptom management is crucial for better HRQoL in patients with atrial fibrillation.

Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1–4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7–10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein–Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks of chronic antigen stimulation at the tumour site, supporting their classification as bystanders. Expression of CD39 varied markedly between patients, with some patients having predominantly CD39− CD8+ TILs. Furthermore, frequencies of CD39 expression among CD8+ TILs correlated with several important clinical parameters, such as the mutation status of lung tumour epidermal growth factor receptors. Our results demonstrate that not all tumour-infiltrating T cells are specific for tumour antigens, and suggest that measuring CD39 expression could be a straightforward way to quantify or isolate bystander T cells. Human lung and colorectal tumours contain a population of tumour-infiltrating lymphocytes that are specific for tumour-unrelated antigens and, unlike tumour-antigen-specific tumour-infiltrating lymphocytes, do not express CD39.

Pressure ulcers are a chronic problem for patients or the elderly who require extended periods of bed rest. The formation of ulcers is due to repeated cycles of ischemia-reperfusion (IR), which initiates an inflammatory response. Advanced ulcers disrupt the skin barrier, resulting in further complications. To date, the immunological aspect of skin IR has been understudied, partly due to the complexity of the skin immune cells. Through a combination of mass cytometry, confocal imaging and intravital multiphoton imaging, this study establishes a workflow for multidimensionality single cell analysis of skin myeloid cell responses in the context of IR injury with high spatiotemporal resolution. The data generated has provided us with previously uncharacterized insights into the distinct cellular behavior of resident dendritic cells (DCs) and recruited neutrophils post IR. Of interest, we observed a drop in DDC numbers in the IR region, which was subsequently replenished 48h post IR. More importantly, in these cells, we observe an attenuated response to repeated injuries, which may have implications in the subsequent wound healing process. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) We thank Dr. Michel Nussenzweig and Dr. Thomas Graf for providing us with the CD11c‐EYFP and LysM‐ eGFP mice, respectively. This research was funded by SIgN core funding, A*STAR, Singapore and National Health and Medical Research Council, Australia (1106439 to W.W. and L.G. NG).

Background A person’s self-efficacy plays a critical role during the chronic management process of a health condition. Assessment of self-efficacy for patients with heart diseases is essential for healthcare professionals to provide tailored interventions to help patient to manage the disease. Objective To translate and test the psychometric properties of the Chinese version of Cardiac Self-efficacy Scale (C-CSES) as a disease-specific instrument for patients with coronary heart disease (CHD) in mainland China. Methods The original English version of the CSES was translated into Chinese using a forward-backward translation approach. A convenience sample consisting of 224 Chinese patients with CHD were recruited from a university-affiliated hospital in Shiyan, China. The C-CSES and the General Self-efficacy Scale (GSES) were used in this study. The factor structure, convergent and discriminative validities, and internal consistency of the C-CSES were evaluated. Results The confirmatory factor analysis (CFA) supported a three-factor high-order structure of the C-CSES with model fit indexes (RMSEA = 0.084, CFI = 0.954, NNFI = 0.927, IFI = 0.954 and χ 2 /df = 2.572). The C-CSES has good internal consistency with a Cronbach’s alpha of 0.926. The convergent validity of the C-CSES was established with significantly moderate correlations between the C-CSES and the Chinese version of the GSES (p

The “craniofacial orthodontist” (CO) plays a vital and integral role in the management of craniofacial anomalies such as cleft lip and palate, and craniofacial syndromes. The COs involvement in the management of craniofacial deformity begins right from birth (e.g., cleft lip and palate) up to complete cessation of active biological growth (adult life). The long-term association of patient–doctor relationship not only demands a consistent understanding of the complexities involved in the multidisciplinary management of the anomaly but also provides a unique opportunity for the CO to work in tandem with other specialties in delivering a holistic treatment. Furthermore, the CO, as a member of the craniofacial team, could make use of the remarkable advancements in the diagnosis and management of craniofacial anomalies. This paper provides an overview of the synergistic management of cleft lip and palate and craniofacial anomalies, with a specific focus on the COs contribution in the craniofacial team with case illustrations, author's favored treatment protocols and integration of recent advancements.

Although important, heart failure self-care remains a challenge for many patients. This study aimed to evaluate the effect of a nurse-led, home-based self-management psychosocial education intervention (HOM-HEMP). The primary outcome was patient's HF self-care in terms of maintenance, management and confidence. The secondary outcomes were cardiac self-efficacy, psychological wellbeing in terms of perceived social support, health related quality of life and levels of anxiety and depression. The clinical outcomes included New York Heart Association (NYHA) functional class and numbers of unplanned health service visits due to cardiac-related reasons.A three-arm stratified randomized controlled trial was conducted (Clinical trial registration number: NCT03108235).A total of 213 participants admitted for heart failure were recruited from the inpatient wards of a tertiary public hospital in Singapore. They were randomly allocated to the control group, the experimental group A or the experimental group B. All participants received the usual care provided by the hospital. Participants in experimental groups A and B received the HOM-HEMP intervention, and those in experimental group B received an additional supplemental smartphone application. Data were collected at baseline, 6 weeks, 3 months and 6 months from baseline.Compared to the control groups, participants in either of the experimental group had significantly higher levels of heart failure self-care maintenance (F = 4.222, p = 0.001), self-care confidence (F = 5.796, p 0.001) and self-care management (p 0.05) at 6-week, 3-month and 6-month follow-ups. In addition, both experimental groups had significantly higher levels of cardiac self-efficacy, better health related quality of life and lower depression levels than the control group after the study intervention. A higher proportion of participants in both experimental groups had a better New York Heart Association functional class at 6-week and 3-month follow-ups. Participants in the experimental group B also had significantly fewer cardiac-related unplanned hospital admissions and emergency room visits than the control group at 6-month follow-up. Results on perceived social support were not significant. The study outcomes in experimental group A and B were not significantly different at any of the post intervention follow-up.The findings suggested that HOM-HEMP is an effective intervention for patients with heart failure in Singapore.