Making Atomic-Level Magnetism Tunable with Light at Room Temperature

The capacity to manipulate magnetization in two-dimensional dilute magnetic semiconductors (2D-DMSs) using light, specifically in magnetically doped transition metal dichalcogenide (TMD) monolayers (M-doped TX2, where M = V, Fe, Cr; T = W, Mo; X = S, Se, Te), may lead to innovative applications in spintronics, spin-caloritronics, valleytronics, and quantum computation. This Perspective paper explores the mediation of magnetization by light under ambient conditions in 2D-TMD DMSs and heterostructures. By combining magneto-LC resonance (MLCR) experiments with density functional theory (DFT) calculations, we show that the magnetization can be enhanced using light in V-doped TMD monolayers (e.g., V-WS2, V-WSe2, V-MoS2). This phenomenon is attributed to excess holes in the conduction and valence bands, as well as carriers trapped in magnetic doping states, which together mediate the magnetization of the semiconducting layer. In 2D-TMD heterostructures such as VSe2/WS2 and VSe2/MoS2, we demonstrate the significance of proximity, charge-transfer, and confinement effects in amplifying light-mediated magnetism. This effect is attributed to photon absorption at the TMD layer (e.g., WS2, MoS2) that generates electron-hole pairs mediating the magnetization of the heterostructure. These findings will encourage further research in the field of 2D magnetism and establish a novel direction for designing 2D-TMDs and heterostructures with optically tunable magnetic functionalities, paving the way for next-generation magneto-optic nanodevices

Mapping for engagement: setting up a community based participatory research project to reach underserved communities at risk for Hepatitis C in Ho Chi Minh City, Vietnam

Background: Approximately 1. 07 million people in Vietnam are infected with hepatitis C virus (HCV). To address this epidemic, the South East Asian Research Collaborative in Hepatitis (SEARCH) launched a 600-patient cohort study and two clinical trials, both investigating shortened treatment strategies for chronic HCV infection with direct-acting antiviral drugs. We conducted ethnographic research with a subset of trial participants and found that the majority were aware of HCV infection and its implications and were motivated to seek treatment. However, people who inject drugs (PWID), and other groups at risk for HCV were under-represented, although injecting drug use is associated with high rates of HCV. Material and Methods: We designed a community-based participatory research (CBPR) study to engage in dialogues surrounding HCV and other community-prioritized health issues with underserved groups at risk for HCV in Ho Chi Minh City. The project consists of three phases: situation analysis, CBPR implementation, and dissemination. In this paper, we describe the results of the first phase (i.e., the situation analysis) in which we conducted desk research and organized stakeholder mapping meetings with representatives from local non-government and community-based organizations where we used participatory research methods to identify and analyze key stakeholders working with underserved populations. Results: Twenty six institutions or groups working with the key underserved populations were identified. Insights about the challenges and dynamics of underserved communities were also gathered. Two working groups made up of representatives from the NGO and CBO level were formed. Discussion: Using the information provided by local key stakeholders to shape the project has helped us to build solid relationships, give the groups a sense of ownership from the early stages, and made the project more context specific. These steps are not only important preliminary steps for participatory studies but also for other research that takes place within the communities

Differentiation of breast cancer stem cells by knockdown of CD44: promising differentiation therapy

<p>Abstract</p> <p>Background</p> <p>Breast cancer stem cells (BCSCs) are the source of breast tumors. Compared with other cancer cells, cancer stem cells show high resistance to both chemotherapy and radiotherapy. Targeting of BCSCs is thus a potentially promising and effective strategy for breast cancer treatment. Differentiation therapy represents one type of cancer stem-cell-targeting therapy, aimed at attacking the stemness of cancer stem cells, thus reducing their chemo- and radioresistance. In a previous study, we showed that down-regulation of CD44 sensitized BCSCs to the anti-tumor agent doxorubicin. This study aimed to determine if CD44 knockdown caused BCSCs to differentiate into breast cancer non-stem cells (non-BCSCs).</p> <p>Methods</p> <p>We isolated a breast cancer cell population (CD44⁺CD24^-cells) from primary cultures of malignant breast tumors. These cells were sorted into four sub-populations based on their expression of CD44 and CD24 surface markers. CD44 knockdown in the BCSC population was achieved using small hairpin RNA lentivirus particles. The differentiated status of CD44 knock-down BCSCs was evaluated on the basis of changes in CD44⁺CD24^-phenotype, tumorigenesis in NOD/SCID mice, and gene expression in relation to renewal status, metastasis, and cell cycle in comparison with BCSCs and non-BCSCs.</p> <p>Results</p> <p>Knockdown of CD44 caused BCSCs to differentiate into non-BCSCs with lower tumorigenic potential, and altered the cell cycle and expression profiles of some stem cell-related genes, making them more similar to those seen in non-BCSCs.</p> <p>Conclusions</p> <p>Knockdown of CD44 is an effective strategy for attacking the stemness of BCSCs, resulting in a loss of stemness and an increase in susceptibility to chemotherapy or radiation. The results of this study highlight a potential new strategy for breast cancer treatment through the targeting of BCSCs.</p

Pyronaridine-Artesunate versus Chloroquine in Patients with Acute Plasmodium vivax Malaria: A Randomized, Double-Blind, Non-Inferiority Trial

BACKGROUND: New antimalarials are needed for P. vivax and P. falciparum malaria. This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria. METHODS AND FINDINGS: This phase III randomized, double-blind, non-inferiority trial included five centers across Cambodia, Thailand, India, and Indonesia. In a double-dummy design, patients (aged >3-≤ 60 years) with microscopically confirmed P. vivax mono-infection were randomized (1:1) to receive pyronaridine-artesunate (target dose 7.2:2.4 mg/kg to 13.8:4.6 mg/kg) or chloroquine (standard dose) once daily for three days. Each treatment group included 228 randomized patients. Outcomes for the primary endpoint, Day-14 cure rate in the per-protocol population, were 99.5%, (217/218; 95%CI 97.5, 100) with pyronaridine-artesunate and 100% (209/209; 95%CI 98.3, 100) with chloroquine. Pyronaridine was non-inferior to chloroquine: treatment difference -0.5% (95%CI -2.6, 1.4), i.e., the lower limit of the 2-sided 95%CI for the treatment difference was greater than -10%. Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21, 28, 35 and 42. Parasite clearance time was shorter with pyronaridine-artesunate (median 23.0 h) versus chloroquine (32.0 h; p<0.0001), as was fever clearance time (median 15.9 h and 23.8 h, respectively; p = 0.0017). Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5% with pyronaridine-artesunate, 6.1% with chloroquine (p = 0.048, log-rank test). Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8% and 12.4%, respectively (p = 0.022, log rank test). There were no deaths. Adverse events occurred in 92/228 (40.4%) patients with pyronaridine-artesunate and 72/228 (31.6%) with chloroquine. Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate. CONCLUSION: Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine. As pyronaridine-artesunate is also efficacious against P. falciparum malaria, this combination has potential utility as a global antimalarial drug. TRIAL REGISTRATION: Clinicaltrials.gov NCT00440999

Associations of Underlying Health Conditions With Anxiety and Depression Among Outpatients: Modification Effects of Suspected COVID-19 Symptoms, Health-Related and Preventive Behaviors

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB).Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18–85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety.Results: People with UHC had higher odds of depression (OR = 2.11; p &lt; 0.001) and anxiety (OR = 2.86; p &lt; 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p &lt; 0.001); and were significantly lower for those had UHC and interacted with “unchanged/more” physical activity (p &lt; 0.001), or “unchanged/more” drinking (p &lt; 0.001 for only anxiety), or “unchanged/healthier” eating (p &lt; 0.001), and high PB score (p &lt; 0.001), as compared to those without UHC and without S-COVID-19-S, “never/stopped/less” physical activity, drinking, “less healthy” eating, and low PB score, respectively.Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p&lt;0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p&lt;0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

BLOOM: A 176B-Parameter Open-Access Multilingual Language Model

Large language models (LLMs) have been shown to be able to perform new tasks based on a few demonstrations or natural language instructions. While these capabilities have led to widespread adoption, most LLMs are developed by resource-rich organizations and are frequently kept from the public. As a step towards democratizing this powerful technology, we present BLOOM, a 176B-parameter open-access language model designed and built thanks to a collaboration of hundreds of researchers. BLOOM is a decoder-only Transformer language model that was trained on the ROOTS corpus, a dataset comprising hundreds of sources in 46 natural and 13 programming languages (59 in total). We find that BLOOM achieves competitive performance on a wide variety of benchmarks, with stronger results after undergoing multitask prompted finetuning. To facilitate future research and applications using LLMs, we publicly release our models and code under the Responsible AI License