CD4+ NKG2D+ T cells are associated with tumour, infection and autoimmune diseases. Some CD4+ NKG2D+ T cells secrete IFN‐γ and TNF‐α to promote inflammation, but others produce TGF‐β and FasL to facilitate tumour evasion. Here, murine CD4+ NKG2D+ T cells were further classified into NK1.1− CD4+ NKG2D+ and NK1.1+ CD4+ NKG2D+ subpopulations. The frequency of NK1.1− CD4+ NKG2D+ cells decreased in inflamed colons, whereas more NK1.1+ CD4+ NKG2D+ cells infiltrated into colons of mice with DSS‐induced colitis. NK1.1− CD4+ NKG2D+ cells expressed TGF‐β and FasL without secreting IFN‐γ, IL‐21 and IL‐17 and displayed no cytotoxicity. The adoptive transfer of NK1.1− CD4+ NKG2D+ cells suppressed DSS‐induced colitis largely dependent on TGF‐β. NK1.1− CD4+ NKG2D+ cells did not expressed Foxp3, CD223 (LAG‐3) and GITR. The subpopulation was distinct from NK1.1+ CD4+ NKG2D+ cells in terms of surface markers and RNA transcription. NK1.1− CD4+ NKG2D+ cells also differed from Th2 or Th17 cells because the former did not express GATA‐3 and ROR‐γt. Thus, NK1.1− CD4+ NKG2D+ cells exhibited immune regulatory functions, and this T cell subset could be developed to suppress inflammation in clinics.

Regulatory T cells play critical roles in self-tolerance and tumor evasion. CD4NKG2D cells with regulatory activity are present in patients with NKG2DL tumors and juvenile systemic lupus erythematosus. We previously showed that TGF-β-producing CD4NKG2D T cells are present in pCD86-Rae-1ε transgenic mice. Here, we performed both ex vivo and in vivo studies on pCD86-Rae-1ε transgenic mice and an MC38 tumor-bearing mouse model and show that NK1.1CD4NKG2D T cells have regulatory activity in pCD86-Rae-1ε transgenic mice. Furthermore, this T-cell subset was induced in mice transplanted with NKG2DL tumor cells and produced TGF-β and FasL, and secreted low amounts of IFN-γ. This T-cell subset downregulated the function of effector T cells and dendritic cells, which were abolished by anti-TGF-β antibody. In vivo, adoptive transfer of NK1.1CD4NKG2D T cells promoted TGF-β-dependent tumor growth in mice. We further found that ex vivo induction of NK1.1CD4NKG2D T cells was dependent on both anti-CD3 and NKG2DL stimulation. Furthermore, regulatory NK1.1CD4NKG2D T cells did not express Foxp3 or CD25 and expressed intermediate levels of T-bet. Western-blotting showed that STAT3 signaling was activated in NK1.1CD4NKG2D T cells of MC38 tumor-bearing and pCD86-Rae-1ε transgenic mice. In conclusion, we describe a regulatory NK1.1CD4NKG2D T-cell population, different from other regulatory T cells and abnormally elevated in pCD86-Rae-1ε transgenic and MC38 tumor-bearing mice.

Previous evidence suggests that temperature is associated with the number of emergency department (ED) visits. A predictive system for ED visits, which takes local temperature into account, is therefore needed. This study aimed to compare the predictive performance of various machine learning methods with traditional statistical methods based on temperature variables and develop a daily ED attendance rate predictive model for Hong Kong. We analyzed ED utilization among Hong Kong older adults in May to September from 2000 to 2016. A total of 103 potential predictors were derived from 1- to 14-day lag of ED attendance rate and meteorological and air quality indicators and 0-day lag of holiday indicator and month and day of week indicators. LASSO regression was used to identify the most predictive temperature variables. Decision tree regressor, support vector machine (SVM) regressor, and random forest regressor were trained on the selected optimal predictor combination. Deep neural network (DNN) and gated recurrent unit (GRU) models were performed on the extended predictor combination for the previous 14-day horizon. Maximum ambient temperature was identified as a better predictor in its own value than as an indicator defined by the cutoff. GRU achieved the best predictive accuracy. Deep learning methods, especially the GRU model, outperformed conventional machine learning methods and traditional statistical methods.

Introduction Older patients are vulnerable to falls after discharge as hospitalization could induce declines in physical function, mobility, and muscle strength. Falls may cause readmissions and subsequent healthcare burden. However, such incidence rates and costs have not been understudied. This study aimed to investigate the incidence and costs of fall-related readmissions in older patients. Method A population-based retrospective cohort study was conducted among patients aged 65 or over and discharged from public hospitals in Hong Kong from 2007 to 2017. The administrative data for inpatient admission were obtained from the Hospital Authority Data Collaboration Lab. The fall-related readmissions within 12 months following discharge were identified by the International Classification of Diseases code of diagnosis. The incidence rates were calculated in terms of person-years. The costs were computed based on the public ward maintenance fees adopted since 2007. Results In total, 611,349 older patients with a mean (SD) age of 75.3(7.6) were analyzed. Within 12 months after discharge, 18,608 patients (3.0%) had 20,666 fall-related readmissions, giving an incidence rate of 35.2 per 1000 person-years. Meanwhile, such rates (per 1000 person-years) were 44.7 for women, 25.5 for men, 20.5 for patients aged 65-74, 41.0 for patients aged 75-84, and 76.2 for patients aged ≥85. The annual cost exceeded HKD 145.6 million (23.9 million USD PPP in 2018) for older patients, and the mean cost per fall-related readmission was HKD 7,827 (1,286 USD PPP). Conclusion The fall-related hospital readmissions were important adverse events during the transitional period and caused a considerable healthcare burden to the patients, family caregivers, and the health system. Health professionals are suggested to implement interventions during hospitalizations or at the early stage after discharge to reduce falls, particularly for women and patients aged ≥85. For instance, increase physical activity during the hospital stay can be considered for fall prevention.