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Background Health literacy has been concerned a key factor for determining the use of health information and promoting health. The study aimed to explore adolescent health literacy, health-promoting lifestyle profile, and health status and related factors. Methods A cross-sectional study design was used; 918 first year junior college students were recruited in Taiwan. The measurements were the Chinese Health Literacy Survey Questionnaire (HLS-C-Q), the Chinese Health-Promoting Lifestyle Profile (HPLP-S), and the Health Status Questionnaire. Results The mean score for health literacy was 36.15 (±6.21), with 30.17% of the participants having insufficient or problematic health literacy. Further, 19.9% of participants were obese and 11.2% experienced emotional instability. Health literacy and health-promoting lifestyle profile showed significant positive and negative correlations with perceived health status and depression, respectively ( p  < 0.05). An exercise frequency of ≥3 times/week was a predictor of health literacy, health-promoting lifestyle profile, and emotional stability. Conclusions Adolescent health literacy, health-promoting lifestyle profile, and health status require careful consideration. In adolescents, developing regular exercise may increase health literacy, thereby developing healthy lifestyle profiles and ameliorating obesity and depression-related issues.

Mosunetuzumab is a CD20 × CD3 T-cell-engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. In a phase 1 study, mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to evaluate the safety and anti-tumour activity of fixed-duration mosunetuzumab in patients with relapsed or refractory follicular lymphoma who had received two or more previous therapies. We conducted a single-arm, multicentre, phase 2 study at 49 centres in seven countries (Australia, Canada, Germany, South Korea, Spain, UK, and USA). All patients were aged 18 years or older with histologically confirmed follicular lymphoma (grade 1–3a) and an Eastern Cooperative Oncology Group performance status of 0–1. Patients had disease that was relapsed or refractory to two or more previous lines of treatment, including an anti-CD20 therapy and an alkylating agent. Intravenous mosunetuzumab was administered in 21-day cycles with cycle 1 step-up dosing: 1 mg on cycle 1 day 1, 2 mg on cycle 1 day 8, 60 mg on cycle 1 day 15 and cycle 2 day 1, and 30 mg on day 1 of cycle 3 and onwards. Patients with a complete response by investigator assessment using the International Harmonisation Project criteria completed treatment after cycle 8, whereas patients with a partial response or stable disease continued treatment for up to 17 cycles. The primary endpoint was independent review committee-assessed complete response rate (as best response) in all enrolled patients; the primary efficacy analysis compared the observed IRC-assessed complete response rate with a 14% historical control complete response rate in a similar patient population receiving the pan class I PI3K inhibitor copanlisib. Safety was assessed in all enrolled patients. This study is registered with ClinicalTrials.gov, number NCT02500407, and is ongoing. Between May 2, 2019, and Sept 25, 2020, we enrolled 90 patients. As of the data cutoff date (Aug 27, 2021), the median follow-up was 18·3 months (IQR 13·8–23·3). According to independent review committee assessment, a complete response was recorded in 54 patients (60·0% [95% CI 49·1–70·2]). The observed complete response rate was significantly higher than the historical control complete response rate with copanlisib of 14% (p<0·0001), thereby meeting the primary study endpoint. Cytokine release syndrome was the most common adverse event (40 [44%] of 90 patients) and was predominantly grade 1 (23 [26%] of 90) and grade 2 (15 [17%]), and primarily confined to cycle 1. The most common grade 3–4 adverse events were neutropenia or neutrophil count decreased (24 [27%] of 90 patients), hypophosphataemia (15 [17%]), hyperglycaemia (seven [8%]), and anaemia (seven [8%]). Serious adverse events occurred in 42 (47%) of 90 patients. No treatment-related grade 5 (ie, fatal) adverse event occurred. Fixed-duration mosunetuzumab has a favourable safety profile and induces high rates of complete remissions, allowing potential administration as an outpatient regimen, in patients with relapsed or refractory follicular lymphoma and two or more previous therapies. F Hoffmann-La Roche and Genentech.

Recently developed solid-state catalysts can mediate carbon dioxide (CO 2 ) electroreduction to valuable products at high rates and selectivities. However, under commercially relevant current densities of > 200 milliamperes per square centimeter (mA cm −2 ), catalysts often undergo particle agglomeration, active-phase change, and/or element dissolution, making the long-term operational stability a considerable challenge. Here we report an indium sulfide catalyst that is stabilized by adding zinc in the structure and shows dramatically improved stability. The obtained ZnIn 2 S 4 catalyst can reduce CO 2 to formate with 99.3% Faradaic efficiency at 300 mA cm −2 over 60 h of continuous operation without decay. By contrast, similarly synthesized indium sulfide without zinc participation deteriorates quickly under the same conditions. Combining experimental and theoretical studies, we unveil that the introduction of zinc largely enhances the covalency of In-S bonds, which “locks” sulfur—a catalytic site that can activate H 2 O to react with CO 2 , yielding HCOO* intermediates—from being dissolved during high-rate electrolysis. Developing durable catalysts for carbon dioxide reduction to formate at commercial-scale current densities is challenging. This work reports that indium sulfide stabilized through zinc incorporation can produce formate efficiently and quickly at high current densities over long timescales.

Here we retrieve global daily 1 km gapless PM 2.5 concentrations via machine learning and big data, revealing its spatiotemporal variability at an exceptionally detailed level everywhere every day from 2017 to 2022, valuable for air quality monitoring, climate change, and public health studies. We find that 96%, 82%, and 53% of Earth’s populated areas are exposed to unhealthy air for at least one day, one week, and one month in 2022, respectively. Strong disparities in exposure risks and duration are exhibited between developed and developing countries, urban and rural areas, and different parts of cities. Wave-like dramatic changes in air quality are clearly seen around the world before, during, and after the COVID-19 lockdowns, as is the mortality burden linked to fluctuating air pollution events. Encouragingly, only approximately one-third of all countries return to pre-pandemic pollution levels. Many nature-induced air pollution episodes are also revealed, such as biomass burning. AI-driven daily 1-km gapless PM 2.5 data reveal the dynamics of unhealthy air around the world, stark disparities exist between nations and among neighbourhoods. Drastic air quality changes are associated with implementation and lifting of lockdown policies.

Vincristine plus dexamethasone pulses are generally used throughout maintenance treatment for childhood acute lymphoblastic leukaemia. However, previous studies remain inconclusive about the benefit of this maintenance therapy and the absence of randomised, controlled trials in patients with low-risk or high-risk acute lymphoblastic leukaemia provides uncertainty. We therefore aimed to determine if this therapy could be safely omitted beyond 1 year of treatment without leading to an inferior outcome in any risk subgroup of childhood acute lymphoblastic leukaemia. This open-label, multicentre, randomised, phase 3, non-inferiority trial involved 20 major medical centres across China. We enrolled patients who were aged 0–18 years with newly diagnosed acute lymphoblastic leukaemia that was subsequently in continuous remission for 1 year after initial treatment. Patients with secondary malignancy or primary immunodeficiency were excluded. Eligible patients were classified as having low-risk, intermediate-risk, or high-risk acute lymphoblastic leukaemia based on minimal residual disease and immunophenotypic and genetic features of leukaemic cells. Randomisation and analyses were done separately for the low-risk and intermediate-to-high-risk cohorts. Randomisation was generated by the study biostatistician with a block size of six. Stratification factors included participating centre, sex, and age at diagnosis; the low-risk cohort was additionally stratified for ETV6–RUNX1 status, and the intermediate-to-high-risk cohort for cell lineage. Patients in each risk cohort were randomly assigned (1:1) to either receive (ie, the control group) or not receive (ie, the experimental group) seven pulses of intravenous vincristine (1·5 mg/m2) plus oral dexamethasone (6 mg/m2 per day for 7 days) during the second year of treatment. The primary endpoint was difference in 5-year event-free survival between the experimental group and the control group for both the low-risk and intermediate-to-high-risk cohorts, with a non-inferiority margin of 0·05 (5%). The analysis was by intention to treat. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-14005706. Between Jan 1, 2015, and Feb 20, 2020, 6141 paediatric patients with newly diagnosed acute lymphoblastic leukaemia were registered to this study. Approximately 1 year after diagnosis and treatment, 5054 patients in continuous remission were randomly assigned, including 2923 (1442 in the control group and 1481 in the experimental group) with low-risk acute lymphoblastic leukaemia and 2131 (1071 control, 1060 experimental) with intermediate-to-high risk acute lymphoblastic leukaemia. Median follow-up for patients who were alive at the time of analysis was 3·7 years (IQR 2·8–4·7). Among patients with low-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (90·3% [95% CI 88·4–92·2] vs 90·2% [88·2–92·2]; p=0·90). The one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·024, establishing non-inferiority. Among patients with intermediate-to-high-risk acute lymphoblastic leukaemia, no difference was observed in 5-year event-free survival between the control group and the experimental group (82·8% [95% CI 80·0–85·7] vs 80·8% [77·7–84·0]; p=0·90), but the one-sided 95% upper confidence bound for the difference in 5-year event-free survival probability was 0·055, giving a borderline inferior result for those in the experimental group. In the low-risk cohort, we found no differences in the rates of infections, symptomatic osteonecrosis, or other complications during the second year of maintenance treatment between patients in the control and experimental groups. Patients with intermediate-to-high-risk acute lymphoblastic leukaemia in the control group were more likely to develop grade 3–4 pneumonia (26 [2·4%] of 1071 vs ten [0·9%] of 1060) and vincristine-related peripheral neuropathy (17 [1·6%] vs six [0·6%]) compared with the experimental group. Incidence of grade 5 fatal infection was similar between the control group and the experimental group in both the low-risk cohort (two [0·1%] of 1442 vs five [0·3%] of 1481) and intermediate-to-high risk cohort (six [0·6%] of 1071 vs five [0·5%] of 1060). Vincristine plus dexamethasone pulses might be omitted beyond 1 year of treatment for children with low-risk acute lymphoblastic leukaemia. Additional studies are needed for intermediate-to-high-risk acute lymphoblastic leukaemia. VIVA China Children's Cancer Foundation, the National Natural Science Foundation of China, the China fourth round of Three-Year Public Health Action Plan (2015–2017), Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities. For the Chinese translation of the abstract see Supplementary Materials section.

This article focuses on the unique needs and concerns of nursing educators and nursing students in the face of the COVID-19 pandemic. During social distancing, interacting with other human beings has been restricted. This would undermine the experiential learning of nursing students. Hence, it is important to develop and evaluate an experiential learning program (ELP) for nursing education. A pre-test and post-test design were used. The study was conducted in a university in Central Taiwan. A total of 103 nursing students participated in the study from February to June 2019. The study intervention was the experiential learning program (ELP), including bodily experiences and nursing activities with babies, pregnant women, and the elderly. After the intervention, the students completed the self-reflection and insight scale (SRIS) and Taiwan Critical Thinking Disposition Inventory (TCTDI) as outcome measures. An independent t-test showed that there was a significant difference between pre-test and post-test in both SRIS and TCTDI (p < 0.01). The Pearson product–moment correlation analysis showed that SRIS and TCTDI were significantly positively correlated (p < 0.01). ELP has a significant impact on the self-reflection and critical thinking of first-year nursing students, which can be used as a reference for the education of nursing students. During these turbulent times, it is especially vital for faculties to provide experiential learning instead of the traditional teaching concept.

Recurrent and hormone-refractory prostate cancer (PCA) exhibits aggressive behaviors while current therapeutic approaches show little effect of prolonging the survival of patients with PCA. Thus, a deeper understanding of the patho-molecular mechanisms underlying the disease progression in PCA is crucial to identify novel diagnostic and/or therapeutic targets to improve the outcome of patients. Recent evidence suggests that activation of Wnt signaling in cancer stem cells (CSCs) contributes to cancer progression in malignant tumors. Here, we report that a novel Wnt co-activator ASPM (abnormal spindle-like microcephaly associated) maintains the prostate CSC subpopulation by augmenting the Wnt-β-catenin signaling in PCA. ASPM expression is incrementally upregulated in primary and metastatic PCA, implicating its potential role in PCA progression. Consistently, downregulation of ASPM expression pronouncedly attenuated the proliferation, colony formation, and the invasive behavior of PCA cells, and dramatically reduced the number of ALDH + CSCs and inhibited cancer stemness and tumorigenicity. Mechanistically, ASPM interacts with disheveled-3 (Dvl-3), a cardinal upstream regulator of canonical Wnt signaling, and inhibits its proteasome-dependent degradation, thereby increasing its protein stability and enabling the Wnt-induced β-catenin transcriptional activity in PCA cells. In keeping with the role of ASPM as a CSC-regulator, ASPM co-localizes with ALDH in PCA tissues and its expression exhibits high intra-tumoral heterogeneity. The proportion of high-ASPM-expressing cells in the tumor inversely correlates with the relapse-free survival of PCA patients. Collectively, our data points to ASPM as a novel oncoprotein and an essential regulator of Wnt signaling and cancer stemness in PCA, which has important clinical and therapeutic significance.

Phase I oncology clinical trials often comprise a limited number of patients representing different disease subtypes who are divided into cohorts receiving treatment(s) at different dosing levels and schedules. Here, we leverage a previously developed quantitative systems pharmacology model of the anti‐CD20/CD3 T‐cell engaging bispecific antibody, mosunetuzumab, to account for different dosing regimens and patient heterogeneity in the phase I study to inform clinical dose/exposure‐response relationships and to identify biological determinants of clinical response. We developed a novel workflow to generate digital twins for each patient, which together form a virtual population (VPOP) that represented variability in biological, pharmacological, and tumor‐related parameters from the phase I trial. Simulations based on the VPOP predict that an increase in mosunetuzumab exposure increases the proportion of digital twins with at least a 50% reduction in tumor size by day 42. Simulations also predict a left‐shift of the exposure‐response in patients diagnosed with indolent compared to aggressive non‐Hodgkin's lymphoma (NHL) subtype; this increased sensitivity in indolent NHL was attributed to the lower inferred values of tumor proliferation rate and baseline T‐cell infiltration in the corresponding digital twins. Notably, the inferred digital twin parameters from clinical responders and nonresponders show that the potential biological difference that can influence response include tumor parameters (tumor size, proliferation rate, and baseline T‐cell infiltration) and parameters defining the effect of mosunetuzumab on T‐cell activation and B‐cell killing. Finally, the model simulations suggest intratumor expansion of pre‐existing T‐cells, rather than an influx of systemically expanded T‐cells, underlies the antitumor activity of mosunetuzumab.

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major metabolic disorder and is frequently accompanied by liver steatosis. Apolipoprotein J (ApoJ) is a glucose-regulated molecular chaperone that has been implicated in hepatic lipid deposition under nutrient overload. This study aimed to investigate the role of hepatocyte-specific ApoJ deletion in hepatic metabolism under diabetic conditions. Methods: A T2DM mouse model with hepatocyte-specific ApoJ knockout (HKO) was established through a high-fat diet combined with streptozotocin injection. Hepatic metabolic profiles were analyzed using untargeted metabolomics with UHPLC–MS/MS. Differential metabolites were subjected to KEGG pathway and Sankey diagram analyses to identify biologically relevant pathways. Results: In total, 140 metabolites showed significant differential abundance in HKO mouse liver, primarily encompassing organic acids and derivatives as well as lipids and lipid-like molecules. KEGG analysis revealed that ApoJ deletion enhanced pathways related to vitamin digestion and absorption, thiamine metabolism, amino acid biosynthesis, lysine degradation, and 2-oxocarboxylic acid metabolism. In contrast, pathways associated with galactose metabolism, cysteine and methionine metabolism, purine metabolism, and the pentose phosphate pathway were suppressed. Sankey diagram analysis further demonstrated that ApoJ deletion markedly reshapes hepatic metabolic networks in T2DM. Conclusions: Given the central role of hepatic dysmetabolism in the pathogenesis of diabetes and its complications, targeting ApoJ may represent a promising therapeutic approach for restoring hepatic metabolic homeostasis and preventing diabetes-associated steatosis.

Angiogenesis is a critical process in the formation of new capillaries and a key participant in rheumatoid arthritis (RA) pathogenesis. The chemokine (C-X-C motif) ligand 13 (CXCL13) plays important roles in several cellular functions such as infiltration, migration, and motility. We report significantly higher levels of CXCL13 expression in collagen-induced arthritis (CIA) mice compared with controls and also in synovial fluid from RA patients compared with human osteoarthritis (OA) samples. RA synovial fluid increased endothelial progenitor cell (EPC) homing and angiogenesis, which was blocked by the CXCL13 antibody. By interacting with the CXCR5 receptor, CXCL13 facilitated vascular endothelial growth factor (VEGF) expression and angiogenesis in EPC through the PLC, MEK, and AP-1 signaling pathways. Importantly, infection with CXCL13 short hairpin RNA (shRNA) mitigated EPC homing and angiogenesis, articular swelling, and cartilage erosion in ankle joints of mice with CIA. CXCL13 is therefore a novel therapeutic target for RA.