LncRNA PRKCQ-AS1 regulates paclitaxel resistance in triple-negative breast cancer cells through miR-361-5p/PIK3C3 mediated autophagy.

Paclitaxel (PTX) resistance is a key cause of chemotherapy failure in patients with triple negative breast cancer (TNBC). The aim of this study is to investigate the effect and mechanism of long non-coding RNA (lncRNA) on the PTX resistance of TNBC cells through autophagy. MDA-MB-231 cells are used to induce the PTX-resistant TNBC cell line MDA-MB-231.PR (MDR) by increasing dose intermittently. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA levels of phosphoinositide-3-kinase class 3 (PIK3C3), miR-361-5p and lncRNA PRKCQ-AS1 in the cells, and Western blot analysis was used to detect the protein expressions of PIK3C3, autophagy-related, drug-resistant and apoptosis-related genes. MDC staining detected the formation of autophagic vacuoles. The interactions between miR-361-5p and PIK3C3 and between lncRNA PRKCQ-AS1 and miR-361-5p were verified by dual-luciferase assay. Cell viability, apoptosis, migration and invasion were assessed by performing MTT, flow cytometry assay, and transwell assay. The mRNA level of miR-361-5p and the autophagy and drug resistance levels of TNBC PTX-resistant cells were significantly up-regulated. miR-361-5p could target autophagy-related gene PIK3C3, and overexpression of miR-361-5p could down-regulate PIK3C3 protein expression and autophagy level and PTX resistance of MDR cells. LncRNA PRKCQ-AS1 was selected through bioanalysis, and miR-361-5p could target lncRNA PRKCQ-AS1. In addition, lncRNA PRKCQ-AS1 level was up-regulated in TNBC PTX-resistant cells, and knockdown of lncRNA PRKCQ-AS1 could weaken autophagy and drug resistance level and could promote cell apoptosis. Overexpression of lncRNA PRKCQ-AS1 reversed the pro-apoptotic effect and down-regulation of autophagy and resistance levels was induced by miR-361-5p. In vivo experiments were performed to verify the role of lncRNA PRKCQ-AS1. We demonstrate that down-regulation of lncRNA PRKCQ-AS1 weakened PTX resistance and promoted cell apoptosis by miR-361-5p/PIK3C3 mediated autophagy.

Lipid dysregulation associated with progression of silica-induced pulmonary fibrosis.

Silicosis is an irreversible, progressive, fibrotic lung disease caused by long-term exposure to dust-containing silica particles at the workplace. Despite the precautions enforced, the rising incidence of silicosis continues to occur globally, particularly in developing countries. A better understanding of the disease progression and potential metabolic reprogramming of silicosis is warranted. The low- or high-dose silica-induced pulmonary fibrosis in mice was constructed to mimic chronic or accelerated silicosis. Silica-induced mice lung fibrosis was analyzed by histology, lung function, and computed tomography scans. Non-targeted metabolomics of the lung tissues was conducted by ultra-high-performance liquid chromatography-mass spectrometry to show the temporal metabolic trajectory. The low-dose silica-induced silicosis characterized inflammation for up to 42 days, with the onset of cellular silicon nodules. Conversely, the high-dose silica-induced silicosis characterized inflammation for up to 14 days, after which the disease developed rapidly, with a large volume of collagen deposition, presenting progressive massive fibrosis. Both low- and high silica-induced fibrosis had aberrant lipid metabolism. Combined with the RNA-Seq data, this multiomics study demonstrated alterations in the enzymes involved in sphingolipid metabolism. Time-dependent metabolic reprogramming revealing abnormal glycerophospholipid metabolism was intimately associated with the process of inflammation, whereas sphingolipid metabolism was crucial during lung fibrosis. These findings suggest that lipid dysregulation, especially sphingolipid metabolism, was involved in the process of silicosis.

Multi-modal intermediate integrative methods in neuropsychiatric disorders: A review.

The etiology of neuropsychiatric disorders involves complex biological processes at different omics layers, such as genomics, transcriptomics, epigenetics, proteomics, and metabolomics. The advent of high-throughput technology, as well as the availability of large open-source datasets, has ushered in a new era in system biology, necessitating the integration of various types of omics data. The complexity of biological mechanisms, the limitations of integrative strategies, and the heterogeneity of multi-omics data have all presented significant challenges to computational scientists. In comparison to early and late integration, intermediate integration may transform each data type into appropriate intermediate representations using various data transformation techniques, allowing it to capture more complementary information contained in each omics and highlight new interactions across omics layers. Here, we reviewed multi-modal intermediate integrative techniques based on component analysis, matrix factorization, similarity network, multiple kernel learning, Bayesian network, artificial neural networks, and graph transformation, as well as their applications in neuropsychiatric domains. We depicted advancements in these approaches and compared the strengths and weaknesses of each method examined. We believe that our findings will aid researchers in their understanding of the transformation and integration of multi-omics data in neuropsychiatric disorders.

Summarising data and factors associated with COVID-19 related conspiracy theories in the first year of the pandemic: a systematic review and narrative synthesis.

Conspiracy theories can have particularly harmful effects by negatively shaping health-related behaviours. A significant number of COVID-19 specific conspiracy theories emerged in the immediate aftermath of the pandemic outbreak. The aim of this study was to systematically review the literature on conspiracy theories related to COVID-19 during the first year of the pandemic (2020), to identify their prevalence, their determinants and their public health consequences. A comprehensive literature search was carried out in PubMed and PsycINFO to detect all studies examining any conspiracy theory related to COVID-19 between January 1st 2020, and January 10th 2021. Forty-three studies were included with a total of 61,809 participants. Between 0.4 and 82.7% of participants agreed with at least one conspiracy belief. Certain sociodemographic factors (young age, female gender, being non-white, lower socioeconomic status), psychological aspects (pessimism, blaming others, anger) and other qualities (political conservatism, religiosity, mistrust in science and using social media as source of information) were associated with increased acceptance of conspiracy theories. Conspiracy beliefs led to harmful health-related behaviours and posed a serious public health threat. Large-scale collaborations between governments and healthcare organizations are needed to curb the spread of conspiracy theories and their adverse consequences.

Association between physical activity and comorbid anxiety/depression in 46 low- and middle-income countries.

BACKGROUND: Evidence on the association of low physical activity (PA) with depression or anxiety is well established. Yet, evidence on the association between PA and comorbid anxiety/depression remains scarce, especially in low- and middle-income countries (LMICs). Thus, this study explored this relationship among adults aged ≥18 years from 46 LMICs. METHODS: Cross-sectional, community-based data were analyzed from the World Health Survey (WHS). Multivariable multinomial logistic regression analysis was conducted to examine the association between low PA and comorbid anxiety/depression with no anxiety or depression as the base category. RESULTS: 237,023 participants [mean (SD) age = 38.4 (16.0) years; 50.8 % female] were included in the analysis. Low PA was significantly associated with depression alone (OR = 1.33; 95%CI = 1.12-1.57) and anxiety alone (OR = 1.37; 95%CI = 1.23-1.53), while the OR was highest among those with comorbid anxiety/depression (OR = 1.75; 95%CI = 1.52-2.01). CONCLUSION: Low PA is associated with particularly increased odds for comorbid anxiety/depression. Increasing PA may have a beneficial effect on the prevention of comorbid anxiety/depression. However, future longitudinal research establishing the direction of this relationship is warranted.

Prognostic Predictive Characteristics in Patients With Fibrosing Interstitial Lung Disease: A Retrospective Cohort Study.

Background: Limited data are available regarding the entire spectrum of interstitial lung disease with a progressive fibrosing feature. We investigated the prevalence and prognostic predictive characteristics in patients with PF-ILD. Methods: This retrospective cohort study included patients with fibrosing ILD who were investigated between 1 January 2015 and 30 April 2021. We recorded clinical features and outcomes to identify the possible risk factors for fibrosing progression as well as mortality. Results: Of the 579 patients with fibrosing ILD, 227 (39.21%) met the criteria for progression. Clubbing of fingers [odds ratio (OR) 1.52, 95% confidence interval (CI) 1.03 to 2.24, p = 0.035] and a high-resolution computed tomography (HRCT)-documented usual interstitial pneumonia (UIP)-like fibrotic pattern (OR 1.95, 95% CI 1.33 to 2.86, p = 0.001) were risk factors for fibrosis progression. The mortality was worse in patients with PF with hypoxemia [hazard ratio (HR) 2.08, 95% CI 1.31 to 3.32, p = 0.002], in those with baseline diffusion capacity of the lung for carbon monoxide (DLCO) % predicted <50% (HR 2.25, 95% CI 1.45 to 3.50, p < 0.001), or in those with UIP-like fibrotic pattern (HR 1.68, 95% CI 1.04 to 2.71, p < 0.001). Conclusion: Clubbing of fingers and an HRCT-documented UIP-like fibrotic pattern were more likely to be associated with progressive fibrosing with varied prevalence based on the specific diagnosis. Among patients with progressive fibrosing, those with hypoxemia, lower baseline DLCO% predicted, or UIP-like fibrotic pattern showed poor mortality.

Pulmonary hypertension in patients with pneumoconiosis with progressive massive fibrosis.

OBJECTIVES: This study aims to explore the prevalence and clinical features of pulmonary hypertension (PH) in patients with progressive massive fibrosis (PMF) and its correlation with large opacities on CT scans. METHODS: This retrospective study collected 235 patients with PMF, and 199 were eligible for analysis. The probability of PH development was estimated based on tricuspid regurgitation velocity measured by echocardiogram. The size and the location of large opacities on chest CT were recorded. Potential risk factors for PH secondary to PMF were analysed using regression analysis. RESULTS: The prevalence of a high or intermediate probability of PH was 39.7% in patients with PMF. Type C of large opacities (OR 6.99, 95% CI 2.34 to 23.00, p<0.001) and central type of the large opacities (OR 8.12, 95% CI 2.89 to 24.71, p<0.001) were identified as the risk factors for PH secondary to PMF. Over a median follow-up of 32.8 months, the survival rate was 73.3% in the PH group, significantly lower than that in the non-PH group (96.6%, p<0.001). CONCLUSIONS: Over one-third of patients with PMF developed PH. The increased size and the central distribution of large opacities were identified as the risk factors.

High-resolution computed tomography features of asbestosis versus fibrotic hypersensitivity pneumonitis: an observational study.

BACKGROUND: Asbestosis and fibrotic hypersensitivity pneumonitis (FHP) share the pathogenetic mechanisms induced bronchiolocentric fibrotic process secondary to inhalation exposure. Under the occupational and environmental mixed exposures, asbestosis and FHP are needed to make the differential diagnoses on high-resolution computed tomography (HRCT), especially in the countries still using asbestos. The study aimed to analyze the HRCT features of asbestosis versus FHP. METHODS: The patients with asbestosis or with HP were sequentially recruited in this comparative study at Beijing Chaoyang Hospital between January 2006 and December 2016. Patients' clinical data were obtained from a predesigned charts. The international classification of HRCT for occupational and environmental respiratory diseases was used to categorize chest imaging findings in patients. The calculation of test statistics was used to compare the imaging features of asbestosis and FHP. RESULTS: 341 patients with asbestosis and 158 patients with HP were sequentially recruited, among which 204 patients with asbestosis and 74 patients with FHP were eligible for data analysis. Patients with asbestosis were older and had a longer latent period until disease manifestation than those with FHP. Asbestosis was characterized by irregular and/or linear opacities, with lower lung preponderance, accompanied by ground-glass opacities and mosaic attenuation. Notably, 98.5% of patients with asbestosis showed benign pleural abnormalities, and 39.7% of these patients had diffuse pleural thickening with parenchymal bands and/or rounded atelectasis. Abnormalities of the mediastinal and diaphragmatic pleura were observed only in cases of asbestosis, and this finding showed high specificity for the diagnosis for asbestosis compared with that for FHP. Subpleural dots or diaphragmatic pleural abnormalities showed moderate sensitivity and high specificity for diagnosis of asbestosis compared with that for FHP. Interobserver reliability was good for evaluation of imaging findings including honeycombing, pleural calcification, lymphadenectasis, and lymph node calcification. CONCLUSIONS: HRCT-based imaging findings can distinguish between asbestosis and FHP to a certain extent, particularly with regard to subpleural dots and diaphragmatic pleural abnormalities that characterize the former.

Loneliness and the onset of new mental health problems in the general population.

PURPOSE: Loneliness is associated with poor health including premature mortality. There are cross-sectional associations with depression, anxiety, psychosis, and other mental health outcomes. However, it is not known whether loneliness is causally linked with the new onset of mental health problems in the general population. Longitudinal studies are key to understanding this relationship. We synthesized evidence from longitudinal studies investigating the relationship between loneliness and new onset of mental health problems, in the general population. METHOD: We systematically searched six electronic databases, unpublished sources, and hand-searched references, up to August 2021. We conducted a meta-analysis of eight independent cohorts and narrative synthesis of the remaining studies. RESULTS: We included 32 studies, of which the majority focused on depression. Our narrative synthesis found most studies show loneliness at baseline which is associated with the subsequent new onset of depression. The few studies on anxiety and self-harm also showed a positive association. Our meta-analysis found a pooled adjusted odds ratio of 2.33 (95% CI 1.62-3.34) for risk of new onset depression in adults who were often lonely compared with people who were not often lonely. This should be interpreted with caution given evidence of heterogeneity. CONCLUSION: Loneliness is a public mental health issue. There is growing evidence it is associated with the onset of depression and other common mental health problems. Future studies should explore its impact across the age range and in more diverse populations, look beyond depression, and explore the mechanisms involved with a view to better informing appropriate interventions.

Multimorbidity clusters among people with serious mental illness: a representative primary and secondary data linkage cohort study.

BACKGROUND: People with serious mental illness (SMI) experience higher mortality partially attributable to higher long-term condition (LTC) prevalence. However, little is known about multiple LTCs (MLTCs) clustering in this population. METHODS: People from South London with SMI and two or more existing LTCs aged 18+ at diagnosis were included using linked primary and mental healthcare records, 2012-2020. Latent class analysis (LCA) determined MLTC classes and multinominal logistic regression examined associations between demographic/clinical characteristics and latent class membership. RESULTS: The sample included 1924 patients (mean (s.d.) age 48.2 (17.3) years). Five latent classes were identified: 'substance related' (24.9%), 'atopic' (24.2%), 'pure affective' (30.4%), 'cardiovascular' (14.1%), and 'complex multimorbidity' (6.4%). Patients had on average 7-9 LTCs in each cluster. Males were at increased odds of MLTCs in all four clusters, compared to the 'pure affective'. Compared to the largest cluster ('pure affective'), the 'substance related' and the 'atopic' clusters were younger [odds ratios (OR) per year increase 0.99 (95% CI 0.98-1.00) and 0.96 (0.95-0.97) respectively], and the 'cardiovascular' and 'complex multimorbidity' clusters were older (ORs 1.09 (1.07-1.10) and 1.16 (1.14-1.18) respectively). The 'substance related' cluster was more likely to be White, the 'cardiovascular' cluster more likely to be Black (compared to White; OR 1.75, 95% CI 1.10-2.79), and both more likely to have schizophrenia, compared to other clusters. CONCLUSION: The current study identified five latent class MLTC clusters among patients with SMI. An integrated care model for treating MLTCs in this population is recommended to improve multimorbidity care.

Small airway dysfunction in pneumoconiosis: a cross-sectional study.

BACKGROUND: Although several histological studies have documented airway inflammation and remodelling in the small airways of dust-exposed workers, little is known regarding the prevalence and risk factors of small airway dysfunction (SAD) in pneumoconiosis. The present study investigated the prevalence and characteristics of spirometry-defined SAD in pneumoconiosis and assessed the risk factors for associated with SAD. METHODS: A total of 1255 patients with pneumoconiosis were invited to participate, of whom 1115 patients were eligible for final analysis. Spirometry was performed to assess SAD using the following three indicators: maximal mid-expiratory flow and forced expiratory flow 50% and 75%. SAD was defined as at least two of these three indicators being less than 65% of predicted value. Logistic regression analyses were used to analyse the relationships between clinical variables and SAD. RESULTS: Overall, 66.3% of patients with pneumoconiosis had SAD, among never-smokers the prevalence of SAD was 66.7%. The proportion of SAD did not differ among the subtypes of pneumoconiosis. In addition, SAD was present across the patients with all stages of pneumoconiosis. Even among those with forced expiratory volume in 1 s (FEV1) ≥ 80% and FEV1/forced vital capacity ratio ≥ 70%, 40.8% of patients had SAD. Patients with SAD were older than patients without SAD, more likely to be women and heavy smokers. Importantly, patients with SAD had more severe airflow obstruction, air trapping, and diffusion dysfunction. All patients with both pneumoconiosis and chronic obstructive pulmonary disease had SAD. Based on multivariate analysis, overall, aged 40 years and older, female sex, heavy smoking, body mass index ≥ 25.0 kg/m2 and pneumoconiosis stage III were significantly associated with increased risk of SAD. Among the never smokers, risk factors for SAD included female sex, BMI ≥ 25.0 kg/m2, pneumoconiosis stage II and stage III CONCLUSION: Spirometry-defined SAD is one of the common functional abnormalities caused by occupational dust exposure and should be taken into account when monitoring respiratory health of workers to guide the early precautions and management in pneumoconiosis.

Serum Oncomarkers in Patients with MPO-ANCA-Positive Vasculitis: Diagnostic and Prognostic Predictive Values for Interstitial Lung Disease.

PURPOSE: To explore in myeloperoxidase-antineutrophil cytoplasmic autoantibody-associated vasculitis (MPO-AAV) the value of circulating oncomarkers in identifying interstitial lung disease (ILD) and predicting prognosis. METHODS: Newly diagnosed MPO-AAV patients were evaluated retrospectively at a single center. The serum levels of carbohydrate antigen (CA) 19-9, CA125, cytokeratin fraction 21-1 (CYFRA21-1), carcinoembryonic antigen, squamous cell carcinoma antigen, and neuron-specific enolase were compared between patients with and without ILD. The strength of the oncomarkers in identifying ILD was assessed through logistic regression and receiver operating characteristic (ROC) curves. Correlation analysis was applied to detect the associations between oncomarkers and ILD severity. The significance of serum oncomarkers as prognosis predictors for MPO-AAV associated ILD was evaluated by survival analysis. RESULTS: 169 MPO-AAV patients were included and ILD was found in 101 patients. Serum CA125, CA19-9, and CYFRA21-1 were significantly higher in patients with ILD than those without ILD. The area under the ROC curve of CA19-9, CA125, and CYFRA21-1 for identifying ILD was 0.701, 0.660, and 0.711, respectively. A specificity of 98.5% for diagnosing ILD was found for CA19-9 at the recommended normal level. CA19-9 was positively correlated with HRCT fibrosis score (r = 0.498, p < 0.001) and CYFRA21-1 was correlated with ground-glass score (r = 0.316, p = 0.002). Both CA19-9 and CYFRA21-1 were independent risk factors for all-cause mortality in patients with ILD. CONCLUSION: Serum CA19-9 and CYFRA21-1 might be useful markers in the diagnosis, disease severity evaluation, and prognosis prediction of MPO-AAV-associated ILD.

Exploring High Thermal Conductivity Amorphous Polymers Using Reinforcement Learning.

Developing amorphous polymers with desirable thermal conductivity has significant implications, as they are ubiquitous in applications where thermal transport is critical. Conventional Edisonian approaches are slow and without guarantee of success in material development. In this work, using a reinforcement learning scheme, we design polymers with thermal conductivity above 0.400 W/m·K. We leverage a machine learning model trained against 469 thermal conductivity data calculated from high-throughput molecular dynamics (MD) simulations as the surrogate for thermal conductivity prediction, and we use a recurrent neural network trained with around one million virtual polymer structures as a polymer generator. For all generated polymers with thermal conductivity ≥0.400 W/m·K, we have evaluated their synthesizability by calculating the synthetic accessibility score and validated the thermal conductivity of selected polymers using MD simulations. The best thermally conductive polymer designed has an MD-calculated thermal conductivity of 0.693 W/m·K, which is also estimated to be easily synthesizable. Our demonstrated inverse design scheme based on reinforcement learning may advance polymer development with target properties, and the scheme can also be generalized to other material development tasks for different applications.

Predictors of falls and fractures leading to hospitalisation in 36 101 people with affective disorders: a large representative cohort study.

OBJECTIVES: To investigate predictors of falls and fractures leading to hospitalisation in people with affective disorders. DESIGN: Cohort study. SETTING: The South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register. PARTICIPANTS: A large cohort of people with affective disorders (International Classification of Diseases- 10th version [ICD-10] codes F30-F34) diagnosed between January 2008 and March 2016 was assembled using data from the SLaM BRC Case Register. PRIMARY AND SECONDARY OUTCOME MEASURES: Falls and fractures leading to hospitalisation were ascertained from linked national hospitalisation data. Multivariable Cox proportional hazards analyses were administrated to identify predictors of first falls and fractures. RESULTS: Of 36 101 people with affective disorders (mean age 44.4 years, 60.2% female), 816 (incidence rate 9.91 per 1000 person-years) and 1117 (incidence rate 11.92 per 1000 person-years) experienced either a fall or fracture, respectively. In multivariable analyses, older age, analgesic use, increased physical illness burden, previous hospital admission due to certain comorbid physical illnesses and increase in attendances to accident and emergency services following diagnosis were significant risk factors for both falls and fractures. Having a history of falls was a strong risk factor for recurrent falls, and a previous fracture was also associated with future fractures. CONCLUSIONS: Over a mean 5 years' follow-up, approximately 8% of people with affective disorders were hospitalised with a fall or fracture. Several similar factors were found to predict risk of falls and fracture, for example, older age, comorbid physical disorders and analgesic use. Routine screening for bone mineral density and fall prevention programmes should be considered for this clinical group.

Osteoporosis referral and treatment among people with severe mental illness: A ten-year data linkage study.

INTRODUCTION: People with severe mental illness (SMI) are at increased risk of osteoporosis but minimal information is available on their treatment and referral. We investigated differences in these outcomes between patients with/without SMI in linked primary and specialist care data. METHODS: People with SMI aged 18+ at diagnosis with both primary and mental healthcare records between 1st May 2009 and 31st May 2019 from a south London catchment were matched 1:4 to randomly selected controls on gender, age and duration of primary care follow-up. Outcomes included prescription of osteoporosis medications and referrals for osteoporosis, analysed using multivariable logistic regression analyses. RESULTS: The study included 2269 people with SMI and 9069 matched non-SMI controls. People with SMI were more likely to have a recorded prescription of osteoporosis medications (odds ratio [OR] = 3.54, 95% confidence interval [CI] 2.87, 4.35) and be referred for osteoporosis (OR = 1.51, 95% CI 1.09, 2.08) within 2 years after the date of first SMI diagnosis after adjusting for ethnicity, deprivation and Charlson Comorbidity Index. Factors including older age (osteoporosis medications: OR = 1.04, 95% CI 1.03, 1.05; osteoporosis referral: OR = 1.05, 95% CI 1.04, 1.07) and being prescribed with Class A analgesics (osteoporosis medications: OR = 1.91, 95% CI 1.31, 2.77; osteoporosis referral: OR = 1.77, 95% CI 1.02, 3.07) are significant predictors for osteoporosis management pathways within SMI patients. CONCLUSION: People with SMI are more frequently prescribed medications for osteoporosis and referred to osteoporosis screening than the general population. Given the many risk factors for osteoporosis in this group, this increased rate of referrals may well be warranted, and there is need to pay more attention to this at-risk group. Screening studies are needed to determine whether the rate of referral is proportional to the need.

Multimorbidity and obesity in older adults from six low- and middle-income countries.

Prevalence of multimorbidity (i.e., ≥2 chronic conditions), chronic diseases, and obesity is increasing in low- and middle-income countries (LMICs), posing a potential threat to the health of older adults living in these areas. This study hence investigates the unexplored association between obesity and multimorbidity among older adults from LMICs. Cross-sectional, community-based data from the WHO Study on global Ageing and adult health (SAGE) were analysed. The sample consisted of 20,198 individuals aged ≥60 years [Mean age (SD) = 69.3 (13.1) years; 54.1% female] from China, India, Ghana, Mexico, Russia, South Africa. Twelve chronic conditions were assessed. Multivariable logistic regression was conducted to assess the association between BMI ≥ 30 kg/m2, high waist circumference (WC, cut-points > 102 cm for males and > 88 cm for females) and multimorbidity. After adjusting for potential confounders, overall, BMI ≥ 30 kg/m2 was associated with 1.43 (95%CI = 1.21-1.69) times higher odds for multimorbidity, while this estimate for high WC was 1.50 (95%CI = 1.21-1.86). Significant associations emerged between obesity measures and five out of twelve chronic conditions. Results from this study underline the need to reduce obesity among older adults in areas where its prevalence is increasing, as it is associated with increased odds for multimorbidity. Future longitudinal research in this setting is required to assess the impact of obesity reduction on multimorbidity incidence.

Light-intensity physical activity and mental ill health: a systematic review of observational studies in the general population.

BACKGROUND: Most of theevidence has focused on examining the influence of moderate-to-vigorous intensity physical activity on mental health, but he role of light intensity physical activity (LIPA) is less understood. The purpose of this systematic review was to assess the relationship between time spent in LIPA and mental ill health across the lifespan. METHODS: Data were obtained from online databases (Medline, Embase, Scopus, PsychInfo and CINAHL). The search and collection of eligible studies was conducted up to May 28, 2020. Observational studies conducted in the general population and reporting on the association between LIPA (1.6-2.9 metabolic equivalents; either self-reported or device-based measured) and mental ill health were included. RESULTS: Twenty-two studies were included in the review (16 cross-sectional and 6 longitudinal). In older adults (≥ 65 years) and adults (18-64 years), the evidence examining the relationship between LIPA and depressive symptoms is mixed. Data on anxiety, psychological distress and overall mental health are scarce, and results are inconclusive. There is no evidence suggesting favorable associations between LIPA and anxiety in college students. Finally, very limited data was found in adolescents (11-17 years) (n = 2 studies) and children (6-10 years) (n = 2 studies), but the evidence suggests that LIPA does not influence mental health outcomes in these age groups. CONCLUSIONS: This review provided mostly cross-sectional evidence indicating that LIPA may not be associated with mental health outcomes across age groups. Future research efforts employing prospective research designs are warranted to better understand the role of LIPA on mental ill health across age groups.

Impact of surface and pore characteristics on fatigue life of laser powder bed fusion Ti-6Al-4V alloy described by neural network models.

In this study, the effects of surface roughness and pore characteristics on fatigue lives of laser powder bed fusion (LPBF) Ti-6Al-4V parts were investigated. The 197 fatigue bars were printed using the same laser power but with varied scanning speeds. These actions led to variations in the geometries of microscale pores, and such variations were characterized using micro-computed tomography. To generate differences in surface roughness in fatigue bars, half of the samples were grit-blasted and the other half were machined. Fatigue behaviors were analyzed with respect to surface roughness and statistics of the pores. For the grit-blasted samples, the contour laser scan in the LPBF strategy led to a pore-depletion zone isolating surface and internal pores with different features. For the machined samples, where surface pores resemble internal pores, the fatigue life was highly correlated with the average pore size and projected pore area in the plane perpendicular to the stress direction. Finally, a machine learning model using a drop-out neural network (DONN) was employed to establish a link between surface and pore features to the fatigue data (logN), and good prediction accuracy was demonstrated. Besides predicting fatigue lives, the DONN can also estimate the prediction uncertainty.

Trajectories of loneliness and objective social isolation and associations between persistent loneliness and self-reported personal recovery in a cohort of secondary mental health service users in the UK.

BACKGROUND: Loneliness is a frequent and distressing experience among people with mental health problems. However, few longitudinal studies have so far investigated the trajectories of loneliness and objective social isolation, and the extent to which both issues may impact mental health outcomes among mental health service users. Therefore, this study aims to describe the trajectories of loneliness and objective social isolation and their associations with self-rated personal recovery among people leaving crisis resolution teams (CRTs). METHODS: A total of 224 participants receiving care from CRTs (recruited for a large multi-site randomised controlled trial) were included in this longitudinal cohort study. They completed the eight-item University of California at Los Angeles Loneliness Scale (ULS-8), Lubben-Social Network Scale (LNSN-6), and the Questionnaire about the Process of Recovery (QPR) (primary outcome) at baseline, 4- and 18-month follow-up, as well as baseline sociodemographic and clinical variables. RESULTS: We compared groups who were persistently lonely (at all time points), intermittently lonely (at one or two time points) and never lonely. After adjusting for all potential confounders and baseline predictive variables, persistent severe loneliness was associated with worse personal recovery at 18-month follow-up compared with the never lonely (reference group) (coef. = - 12.8, 95% CI -11.8, - 3.8, p < .001), as was being intermittently lonely (coef. = - 7.8, 95% CI -18.8, - 6.8, p < .001). The persistently objectively social isolated group (coef. = - 9.8, 95% CI -15.7, - 3.8, p = .001) also had poorer self-rated recovery at 18-month follow-up than those who were not socially isolated at any timepoint (i.e., reference category). CONCLUSION: Results suggest that both persistent loneliness and objective social isolation are associated with poorer self-rated recovery following a crisis, compatible with a causal relationship. These findings suggest a potential role for interventions aimed at alleviating loneliness and objective social isolation in improving recovery outcomes for people with mental health symptoms. Increased awareness of both issues among health practitioners is also warranted.