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OBJECTIVES: To examine associations between regular statin use and the incidence of depression and anxiety. METHODS: This cohort was based on UK Biobank participants without depression/anxiety recruited between 2006 and 2010. The self-reported regular statin use was collected at baseline. Depression and anxiety outcomes were assessed by diagnostic interviews (international classification of diseases codes) and nondiagnostic scales (mental well-being questionnaires). Cox proportional hazards models adjusted for a wide range of confounders were used to estimate associations of statins with incident depression/anxiety. RESULTS: Among 363,551 eligible participants, 55,838 reported regular statin use. During a 13-year follow-up, 14,765 cases of depression and 15,494 cases of anxiety were identified. Compared with non-statin users, statin use was associated with reduced risk of depression (hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.81, 0.94) and anxiety (HR: 0.90, 95% CI: 0.84, 0.97). Effects of statins on depression were consistent in sensitivity analyses and may be less influenced by unmeasured confounders. However, results of online survey data showed that statin use might not be associated with incident anxiety (HR: 0.96, 95% CI: 0.85, 1.09). CONCLUSION: Regular statin use was associated with a lower risk of depression. No clear associations between statin use and anxiety were found.

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Three-dimensional-printed silicone rubber foams, with their designable and highly ordered pore structures, have shown exceptional potential for engineering applications, particularly in areas requiring energy absorption and cushioning. However, optimizing the mechanical properties of these foams through structural design remains a significant challenge. This study addresses this challenge by formulating the research question: How do different 3D-printed topologies and printing parameters affect the mechanical properties of silicone rubber foams, and how can we design a novel topological structure? To answer this, we explored the mechanical behavior of two common structures-simple cubic (SC) and face-centered tetragonal (FCT)-by varying printing parameters such as filament spacing, filament diameter, and layer height. Furthermore, we proposed a novel two-level 3D-printed structure, combining SC and FCT configurations to enhance performance. The results demonstrated that the two-level SC-SC structure exhibited a specific energy absorption of 8.2 to 21.0 times greater than the SC structure and 2.3 to 7.2 times greater than the FCT structure. In conclusion, this study provides new insights into the design of 3D-printed silicone rubber foams, offering a promising approach to developing advanced cushioning materials with superior energy absorption capabilities.

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Rapid DNA detection is a long-pursuing goal in molecular detection, especially in combating infectious diseases. Loop-mediated isothermal amplification (LAMP) is a robust and prevailing DNA detection method in pathogen detection, which has been drawing broad interest in improving its performance. Herein, we reported a new strategy and developed a new LAMP variant named TLAMP with a superior amplification rate. In this strategy, the turn-back loop primers (TLPs) were devised by ingeniously extending the 5' end of the original loop primer, which conferred the new role of being the inner primer for TLPs while retaining its original function as the loop primer. In theory, based on the bifunctional TLPs, a total of eight basic dumbbell-like structures and four cyclic amplification pathways were produced to significantly enhance the amplification efficiency of TLAMP. With the enhancing effect of TLPs, TLAMP exhibited a significantly reduced amplification-to-result time compared to the conventional six-primer LAMP (typically 1 h), enabling rapid DNA detection within 20 min. Furthermore, TLAMP proved to be about 10 min faster than the fast LAMP variants reported so far, while still presenting comparable sensitivity and higher repeatability. Finally, TLAMP successfully achieved an ultrafast diagnosis of Monkeypox virus (MPXV), capable of detecting as few as 10 copies (0.67copies/µL) of pseudovirus within 20 min using real-time fluorescence assay or within 30 min using a colorimetric assay, suggesting that the proposed TLAMP offers a sensitive, specific, reliable, and, most importantly, ultrafast DNA detection method when facing the challenges posed by infectious diseases.

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BACKGROUND: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear. METHODS: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources. RESULTS: The mean E24hUNa was 3.0 g (1st-99th percentile: 1.5 g-5.1 g). Over a mean follow-up of 13.6 years, 7886 (1.7 %) participants developed all-cause dementia, including 3763 (0.8 %) Alzheimer's disease and 1851 (0.4 %) vascular dementia. In the restricted cubic spline model, we identify a potential cutoff of 3.13 g for E24hUNa, below which each 1 g decrease in E24hUNa was associated with 21 % (95 % confidence interval [CI] 1.11-1.34) higher all-cause dementia risk and 35 % (95 % CI 1.11-1.63) higher vascular dementia risk (P-value <0.001 for non-linearity). The hazard ratios were 1.15 (95 % CI, 1.07-1.24) for all-cause dementia and 1.21 (95 % CI 1.04-1.40) for vascular dementia among individuals with E24hUNa below 3.13 g compared to those with E24hUNa higher than 3.13 g. LIMITATIONS: One of the major limitations is the estimation of 24-h urinary sodium with spot urine samples. CONCLUSIONS: An E24hUNa level below 3.13 g, equivalent to 3.37 g daily sodium intake, is associated with increased risks of all-cause and vascular dementia. This exploratory study suggests a potential lower limit below which the risk of dementia increases with a lower sodium level. Future studies are necessary to validate our findings.

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Background: How often hypertensive patients could achieve remission to normal blood pressure (BP) (i.e., <140/90 mmHg) in the absence of antihypertensive drugs, which is important for the management of hypertension, remains largely unknown. This observational study aimed to investigate the change of BP in older adults with hypertension who did not take antihypertensive drugs and preliminarily examine whether the remission from hypertension to normal BP observed in this setting was associated with lower risk of cardiovascular disease (CVD). Methods: 2760 participants aged 33-99 years (median 60 years, interquartile 54-68 years) from the Health and Retirement Study (wave 2006 to wave 2018) and the English Longitudinal Study of Ageing (wave 1998 to wave 2016), who had no major CVD, were hypertensive, and were not on antihypertensive drugs at the time of baseline BP measurement, and had at least one follow-up BP measurement before which no antihypertensive drugs were taken, were included for analysis. The main outcome was the proportion of patients who achieved remission of hypertension at the last wave of measurement. Findings: During a median follow-up of six years, 52% of the participants showed a reduction of ≥6 mmHg in systolic BP and 60% a reduction of ≥3 mmHg in diastolic BP. 1171 participants (42%, 95% CI: 41-44%) achieved remission at the last measurement, and by that time 67%, 43%, and 29% of them had maintained the normotensive state for around 4, 8, and 12 years, respectively. Various supplementary analyses that aimed to examine the impact of chance and bias yielded similar results. Preliminary analyses showed that being non-smokers at baseline, achieving a normal body mass index during follow-up, and quitting alcohol drinking during follow-up, among others, were associated with the remission of hypertension. Compared with the participants who remained hypertensive, those who achieved remission had a lower CVD risk (adjusted hazard ratio 0.66, 95% CI: 0.47-0.92). Interpretation: In many of this study population, hypertension could be reversed without the intervention of drug treatment in the first few years after diagnosis. This finding may have implications for more individualized management of hypertension. Further studies to identify the factors or algorithms predictive of such hypertension remission are warranted. Funding: The Chinese University of Hong Kong (7106452; 7105959),Shenzhen Science and Technology Program (KQTD20190929172835662), Strategic Priority Research Program of Chinese Academy of Sciences (XDB 38040200), National Institute on Aging (R01AG017644; NIA U01AG009740).

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Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GLP-1 RA (WMD -3.41 [-5.61, -1.21], p = 0.002), SGLT-2i (WMD -5.34 [-9.56, -1.13], p = 0.013), and DPP-4i (WMD -5.56 [-7.39, -3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP-1 RA (WMD -1.55 [-2.92, -0.18], p = 0.027), SGLT-2i (WMD -2.96 [-6.68, 0.77], p = 0.12), and DPP-4i (WMD -2.05 [-2.82, -1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP-1 RA (WMD -3.24 [-5.14, -1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP-1 RA (WMD -2.74 [-4.26, -1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP-1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia. Conclusions: The combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia. Trial Registration: CRD42023410345.

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BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

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Model-based meta-analysis (MBMA) can be used in assisting drug development and optimizing treatment in clinical practice, potentially reducing costs and accelerating drug approval. We aimed to assess the application and quality of MBMA studies. We searched multiple databases to identify MBMA in pharmaceutical research. Eligible MBMA should incorporate pharmacological concepts to construct mathematical models and quantitatively examine and/or predict drug effects. Relevant information was summarized to provide an overview of the application of MBMA. We used AMSTAR-2 and PRISMA 2020 checklists to evaluate the methodological and reporting quality of included MBMA, respectively. A total of 143 MBMA studies were identified. MBMA was increasingly used over time for one or more areas: drug discovery and translational research (n = 8, 5.6%), drug development decision making (n = 42, 29.4%), optimization of clinical trial design (n = 46, 32.2%), medication in special populations (n = 15, 10.5%), and rationality and safety of drug use (n = 71, 49.7%). The included MBMA covered 17 disease areas, with the top three being nervous system diseases (n = 19, 13.2%), endocrine/nutritional/metabolic diseases (n = 17, 11.8%), and neoplasms (n = 16, 11.1%). Of these MBMA studies, 138 (96.5%) were rated as very low quality. The average rate of compliance with PRISMA was only 51.4%. Our findings suggested that MBMA was mainly used to evaluate the efficacy and safety of drugs, with a focus on chronic diseases. The methodological and reporting quality of MBMA should be further improved. Given AMSTAR-2 and PRISMA checklists were not specifically designed for MBMA, adapted assessment checklists for MBMA should be warranted.

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The mechanical properties of metastable ß-titanium alloys are highly susceptible during the thermal mechanical processing (TMP). In this process, the recrystallization process plays an important role in determining the microstructure and texture evolution. The implementation of dynamic recrystallization (DRX), a process for achieving ß-grain refinement, is considered of great significance for the improvement of the properties of metastable ß-titanium alloys and their industrial production. Along these lines, in this work, an isothermal compression test of TB8 titanium alloy was carried out by using a Gleeble-3500 thermal simulator. As a result, the rheological stress behavior was analyzed, the thermal processing map was accurately established based on the stress-strain curve, and the optimal processing interval was determined. The DRX kinetic and the DRX grain size models were developed, on the basis of which a new DRX intrinsic model was established to improve the material parameters. Therefore, the actual situation in the working process could be better predicted. The microstructural evolution of TB8 titanium alloy during thermal deformation was comprehensively investigated using the electron backscatter diffraction (EBSD) technique. The obtained results demonstrate a close correlation between the diversity of DRX mechanisms in TB8 alloy and the distribution of dislocation density. Four microstructural textures during thermal deformation were identified, in which the cube texture of (001) <010> and the R-Gorss Nd texture of (110) <110> dominate. Due to the random orientation of the dynamically recrystallized grains, the strength of the R-Gorss Nd texture of (110) <110> increases with the increase in the volume fraction of DRX. On the contrary, it was verified that the dynamic recrystallization behavior has a significant weakening impact on the cube texture of (001) <010>.

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BACKGROUND & AIMS: The considerable disease burden of irritable bowel syndrome (IBS) has coincided with the increase of ultraprocessed food (UPF) consumption over the past few decades. However, epidemiologic evidence for an association is lacking. We aimed to examine the long-term risk of IBS associated with UPF consumption in a large-scale prospective cohort. METHODS: Participants who completed 24-hour dietary recalls during 2009 to 2012 from the UK Biobank, and free of IBS, celiac disease, inflammatory bowel disease, and any cancer at baseline, were included (N = 178,711; 53.1% female). UPF consumption was defined according to the NOVA food classification system, expressed as a percentage of UPF content in the total diet intake (as grams per day). The primary outcome was incident IBS. A Cox proportional hazard model was performed to estimate associated risk. RESULTS: The mean UPF consumption was 21.0% (SD, 11.0%) of the total diet. During a median of 11.3 years of follow-up, 2690 incident IBS cases were identified. An 8% higher risk of IBS (hazard ratio, 1.08; 95% CI, 1.04-1.12) was associated with every 10% increment of UPF consumption. Compared with the lowest quartile of UPF consumption, the highest quartile was associated with a significantly increased risk of incident IBS (hazard ratio, 1.19; 95% CI, 1.07-1.33; Ptrend < .001). Subgroup analyses by age, sex, body mass index, smoking, and alcohol drinking status also showed similar results, except for the never/previous drinking subgroup. Further sensitivity analyses confirmed the positive association with a higher UPF consumption. CONCLUSIONS: Our findings provide evidence that a higher UPF consumption is associated with an increased risk of incident IBS, with a significant dose-response relationship.

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BACKGROUND: Under the global risk of epidemic rebound of influenza after COVID-19 outbreak, the study aimed to provide a comprehensive evaluation of the seasonal influenza vaccine effectiveness (IVE) and to explore the potential effect modifiers. METHODS: We searched for test-negative design studies with IVE estimates published between January 1, 2017 and December 31, 2022. We estimated pooled IVE using random-effects meta-analysis, and conducted meta-regression with study site, age, sex and comorbidity as explanatory variables. RESULTS: We identified 2429 publications and included 191 in the meta-analysis. The pooled IVE was 41.4 % (95 % CI: 39.2-43.5 %) against any influenza. For specific strains, the IVE was 55.4 % (95 % CI: 52.7-58.1 %) against A/H1N1, 26.8 % (95 % CI: 23.5-29.9 %) against A/H3N2, 47.2 % (95 % CI: 38.1-54.9 %) against B/Yamagata, and 40.6 % (95 % CI: 23.7-53.7 %) against B/Victoria, and the effectiveness against A/H3N2 was significantly lower than A/H1N1 (p < 0.0001) and B/Yamagata (p < 0.0001). The pooled IVE was 39.2 % (95 % CI: 36.5-41.9 %) in preventing influenza-associated outpatient visit and 43.7 % (95 % CI: 39.7-47.4 %) in preventing influenza-related hospitalization. The IVE against any influenza was 48.6 % (95 % CI: 44.7-52.2 %) for children aged < 18 years, 36.7 % (95 % CI: 31.9-41.1 %) for adults aged 18-64 years, and 30.6 % (95 % CI: 26.2-34.8 %) for elderly aged ≥65 years. Meta-regression revealed that the IVE was associated with the average age of study participants, in which both young adults [relative odds ratio (ROR) = 1.225, 95 % confidence interval (CI): 1.099-1.365, p = 0.0002] and elderly (ROR = 1.245, 95 % CI: 1.083-1.431, p = 0.002) manifested a significantly decreased effectiveness compared with children. CONCLUSIONS: Influenza vaccines provided moderate protection against laboratory-confirmed influenza and related outpatient visit and hospitalization. However, the effectiveness may vary substantially by virus type and age group, suggesting the necessity to tailor vaccination strategies especially for older individuals and against the A/H3N2 strain, and to promote annual immunization and annual analysis of vaccine effectiveness.

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Background: Constipation is generally considered a common physical symptom of depression or a side effect of antidepressant treatments. However, according to the gut-brain axis hypothesis, the association between depression and constipation might be bi-directional. This study investigated the association between premorbid constipation and depression. Methods: We conducted a retrospective cohort study using data from UK Biobank. Individuals free of depression between 2006 and 2010 were included. Constipation status was determined using diagnostic codes from electronic health records or a baseline questionnaire. Data on covariates, including socio-demographic characteristics, lifestyle factors, health conditions, and regular medication use, were also collected through a baseline questionnaire. The primary outcome is incident depression, which was extracted from hospital inpatient admissions, primary care, self-report, and death data from baseline to 2022. The secondary outcome is depressive symptoms, which was assessed by Patient Health Questionnaire-9 (PHQ-9) from an online survey in 2016. Cox proportional hazard regression models were employed to assess the prospective association between constipation and incident depression. Logistic regression models were used to assess its association with depressive symptoms. Findings: Among the 449,459 participants included in the study, 18,596 (4.1%) experienced constipation at baseline, and 18,576 (4.1%) developed depression over a median follow-up period of 12.3 years. Premorbid constipation is associated with a 2.28-fold higher risk of depression. After adjusting the covariates, we found those with constipation still had a 48% higher risk of developing depression (adjusted hazard ratio [aHR] 1.48; 95% CI, 1.41-1.56) than those without constipation. Self-reported and diagnosed constipation were both associated with a higher risk of depression, with the aHR being 1.42 (95% CI: 1.34-1.51) and 1.66 (95% CI: 1.51-1.82), respectively. Participants with constipation were more likely to report depressive symptoms than people without (adjusted odds ratio 2.18; 95% CI, 1.97-2.43). These findings remained consistent in sensitivity analyses. Interpretation: Diagnosed and self-reported constipation are both prospectively associated with an elevated risk of depression. These explorative findings suggest that constipation may be an independent risk factor or a prodromal symptom of depression. Gastroenterologists and primary care physicians should pay more attention to the depressive symptoms of their constipation patients. Funding: The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences.

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BACKGROUND: Which life satisfaction components could be a target of positive psychological interventions for longevity is largely unknown. We aimed to investigate association of the composite measure of life satisfaction and its individual components with mortality. METHODS: This cohort study included UK Biobank participants who responded to questions concerning five components of life satisfaction at baseline. We generated a composite score representing overall life satisfaction, ranging from 0 (lowest) to 5 (highest). The outcomes were all-cause and cause-specific mortality. We used multivariable Cox regression to estimate hazard ratios (HR) for the associations of interest. RESULTS: Among 165,842 eligible participants, 12,261 all-cause deaths were observed over a median of 12.9-year follow-up. Overall life satisfaction was inversely associated with all-cause mortality (adjusted HR 0.94 [95% CI: 0.93-0.95] per 1 score increment). Health satisfaction showed the strongest association with all-cause mortality, with a fully adjusted HR of 0.52 (95% CI: 0.49-0.55) for high/extreme satisfaction and 0.63 (95% CI: 0.59-0.66) for moderate satisfaction, compared with unsatisfaction (P-trend<0.001), independent of other satisfaction components, regardless of physical health and sociodemographics. The association for family, friendship, work and financial satisfaction was attenuated when adjusted for other life satisfaction components. Similar findings were observed for cause-specific mortality. LIMITATIONS: Observational study with single baseline measurement of life satisfaction precludes the ability to establish causal relationship. CONCLUSIONS: Higher overall life satisfaction was associated with lower mortality. As the major contributor to lower mortality regardless of physical health and sociodemographics, health satisfaction could be an important target of positive psychological interventions for longevity.

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BACKGROUND: Vitamin B12 is essential to human but the implications of serum vitamin B12 level for mortality in clinical practice remain unclear. We conducted a systematic review and dose-response meta-analysis to quantify the relationship between vitamin B12 levels and the risk of all-cause, cardiovascular, and cancer mortality. METHODS: Electronic databases of PubMed, Embase, and the Cochrane Library Central Register of Controlled Trials were searched from inception through May 2023. Two reviewers independently extracted individual study data and evaluated the risk of bias among the studies using the Newcastle‒Ottawa Scale. To examine a potential nonlinear relationship between the vitamin B12 levels and all-cause mortality, we performed a two-stage random effects dose‒response meta-analysis. RESULTS: Twenty-two cohort studies (92,346 individuals with 10,704 all-cause deaths) were included. A linear trend dose-response analysis showed that each 100 pmol/L increase in serum vitamin B12 concentration was associated with a 4 % higher risk of all-cause mortality in the general population (adjusted HR 1.04, 95 % confidence interval CI 1.01 to 1.08; n = 8; P non-linearity = 0.11) and a 6 % higher risk for all-cause mortality in older adults (adjusted HR 1.06, 95 % CI 1.01 to 1.13; n = 4; P non-linearity = 0.78). Current evidence was mixed for the association between serum vitamin B12 concentration and cardiovascular mortality and was limited for cancer mortality. The meta-analysis of cohort studies showed a positive association between a high serum vitamin B12 concentration (>600 pmol/L) and all-cause mortality (adjusted HR 1.50, 95 % CI 1.29 to 1.74; n = 10; p < 0.01), CVD mortality (adjusted HR 2.04, 95 % CI 0.99 to 4.19; n = 2; p = 0.02), except cancer mortality (adjusted HR 1.56, 95 % CI 0.82 to 2.95; n = 3). Similarly, serum vitamin B12 concentrations (400-600 pmol/L) were associated with increased all-cause mortality (adjusted HR 1.34, 95 % CI 1.10 to 1.64; n = 9; p < 0.01). CONCLUSIONS: Serum vitamin B12 concentration was positively associated with the risk of all-cause mortality, especially among older adults, with a linear increasing trend. These findings suggested the primary cause of elevated level of serum vitamin B12 concentration should be timely identified and effectively managed in clinical practice.

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BACKGROUND: The COVID-19 pandemic has sparked increased interest in telework as a means of reducing the spread of the virus and maintaining social distance. OBJECTIVE: This study aims to generate a bibliometric analysis of research progress and trends in telework over the past 20 years. METHOD: A search of key terms was conducted in the Social Science Citation Index, Science Citation Index Expanded, and Arts and Humanities Citation Index categories for documents published on telework from 2000-2023. A total of 3,446 studies were analyzed using VOSviewer for co-citation, co-word, and cluster analysis. RESULTS: Bibliometric analysis revealed that telework research has experienced a significant increase during the COVID-19 pandemic, with the number of publications in 2022 being more than 15 times higher than that in 2019. The analysis revealed that the most commonly researched areas related to telework were applied psychology, management and business. The knowledge base focuses on the antecedents, moderators, mediators, and consequences of telework, and the research primarily centers around seven directions of well-being, mental health, and work-family conflict. A conceptual framework for telework research and suggestions for future investigation are proposed based on the results of the bibliometric analysis. CONCLUSION: This study provides an overview of telework research over the past two decades, highlighting the current status and hot topics in the field. It calls for wider and more active participation of researchers globally to advance the understanding of telework.

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OBJECTIVES: Negative controls are considered an important tool to mitigate biases in observational studies. The aim of this scoping review was to summarize current methodologies of negative controls (both negative control exposure [NCE] and negative control outcome [NCO]). STUDY DESIGN AND SETTING: We searched PubMed, Web of Science, Embase, and Cochrane Library (up to March 9, 2023) for articles on methodologies of negative controls. Two reviewers selected eligible studies and collected relevant data independently and in duplicate. We reported total numbers and percentages, and summarized methodologies narratively. RESULTS: A total of 37 relevant methodological articles were included in our review. These publications covered NCE (n = 11, 29.8%), NCO (n = 13, 35.1%), or both (n = 13, 35.1%), with most focused on bias detection (n = 14, 37.8%), bias correction (n = 16, 43.3%), and P value or confidence interval (CI) calibration (n = 5, 13.5%). For the two remaining articles (5.4%), one discussed bias detection and P value or CI calibration and the other covered all the three functions. For bias detection, the existence of an association between the NCE (NCO) and outcome (exposure) variables of interest simply indicates that results may suffer from confounding bias, selection bias and/or information bias. For bias correction, however, the algorithms of negative control methods need more stringent assumptions such as rank preservation, monotonicity, and linearity. CONCLUSION: Negative controls can be leveraged for bias detection, P value or CI calibration, and bias correction, among which bias correction has been the most studied methodologically. The current available methods need some stringent assumptions to detect or remove bias. More methodological research is needed to optimize the use of negative controls.

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DNA molecules commonly exhibit wide interactions between the nucleobases. Modeling the interactions is important for obtaining accurate sequence-based inference. Although many deep learning methods have recently been developed for modeling DNA sequences, they still suffer from two major issues: 1) most existing methods can handle only short DNA fragments and fail to capture long-range information; 2) current methods always require massive supervised labels, which are hard to obtain in practice. We propose a new method to address both issues. Our neural network employs circular dilated convolutions as building blocks in the backbone. As a result, our network can take long DNA sequences as input without any condensation. We also incorporate the neural network into a self-supervised learning framework to capture inherent information in DNA without expensive supervised labeling. We have tested our model in two DNA inference tasks, the human variant effect and the open chromatin region of plants, where the experimental results show that our method outperforms five other deep learning models. Our code is available at https://github.com/wiedersehne/cdilDNA.

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To examine the effectiveness of azvudine and nirmatrelvir-ritonavir in treating hospitalized patients with moderate-to-severe COVID-19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate-to-severe COVID-19 without contraindications for azvudine or nirmatrelvir-ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir-ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all-cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent-to-treat analyses, azvudine reduced all-cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12-0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24-0.92). Nirmatrelvir-ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17-1.05), and its composite with all-cause death (HR: 0.38; 95% CI: 0.18-0.81). The study did not identify credible subgroup effects. The per-protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir-ritonavir improved the prognosis of hospitalized adults with moderate-to-severe COVID-19.

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Importance: Assessment of additional protection of a booster dose with an inactivated SARS-CoV-2 vaccine is key to developing vaccination strategies for billions of people worldwide who have received the primary 2-dose regimen. Objective: To estimate the relative effectiveness of a booster dose of an inactivated SARS-CoV-2 vaccine against Omicron infection. Design, Setting, and Participants: This cohort study was conducted among primary close contacts without previous SARS-CoV-2 infection identified in Shenzhen, China, between February and October 2022. Multiple strict nucleic acid testing and symptom surveillance for SARS-CoV-2 infection were regularly conducted during the 7-day centralized plus 7-day home-based quarantine. Exposure: A booster with an inactivated SARS-CoV-2 vaccine vs no booster after receipt of the primary 2-dose inactivated SARS-CoV-2 vaccine regimen. Main Outcomes and Measures: The primary outcomes were overall, symptomatic, and asymptomatic infections. Secondary outcomes were length of incubation and level of cycle threshold values. All the outcomes were assessed during the quarantine period. Results: Among 119 438 eligible participants (mean [SD] age, 37.6 [12.0] years; 66 201 men [55.4%]), 86 251 (72.2%) received a booster dose of an inactivated SARS-CoV-2 vaccine and 33 187 (27.8%) did not. A total of 671 cases infected with Omicron BA.2 were confirmed (464 symptomatic and 207 asymptomatic), and no severe infection or death events were observed. At a median (IQR) duration of 111 (75 to 134) days after booster vaccination, the relative effectiveness of a booster was 32.2% (95% CI, 11.3% to 48.2%) for overall infection, 23.8% (95% CI, -8.2% to 46.4%) for symptomatic infection, and 43.3% (95% CI, 12.3% to 63.3%) for asymptomatic infection. The effectiveness against overall infection changed nonlinearly over time following booster vaccination: 44.9% (95% CI, 4.9% to 68.1%) within 60 days, 50.4% (95% CI, 23.7% to 67.7%) at 61 to 120 days, 29.1% (95% CI, -4.8% to 52.1%) at 121 to 180 days, and 19.4% (95% CI, -14.4% to 43.2%) after 180 days (nonlinear P = .03). The effectiveness did not vary significantly according to the interval between booster vaccination and completion of primary vaccination. There was no association of booster vaccination with incubation or cycle threshold values. Conclusions and Relevance: In this cohort study, a booster dose of an inactivated SARS-CoV-2 vaccine provided additional moderate protection against mild infection for 120 days after receipt, but more research is needed to determine the optimal timing of a booster and its effectiveness in preventing severe infection for a longer duration.

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Armillaria luteo-virens (A. luteo-virens) is a kind of edible fungus mainly exists in Qinghai-Tibet of China, but at present only very few studies focus on the bioactivities of its polysaccharides. This study aimed to purify and characterize the structure features of a novel intracellular polysaccharide (ALP-A) derived from A. luteo-virens and explore its potential anti-tumor and immunomodulatory activities. Through systematic separation and purification, we obtained a homogeneous ALP-A with an average molecular weight of 23693Da. Structural analysis indicated that ALP-A was mainly composed of glucose and mannose with a molar ratio of 6.02:1. The repeating unit of ALP-A was →4) -α-D-Glcp-(1→ backbone with α-Glcp-(1→ and α-Manp-(6→ side chains which branched at O-2 position. The anti-tumor assays in vivo suggested that ALP-A could effectively restrain S180 solid tumor growth, protect immune organs and promote the secretion of cytokines (IL2, IL6 and TNF-α) in serum. Besides, in vitro immunomodulatory assays indicated that ALP-A could improve proliferation, phagocytic capacity and raise the level of NO and cytokines in Raw264.7 cells. These results demonstrate that ALP-A which possess potential antitumor and immunomodulatory abilities can be developed as a new functional food.

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