Light-driven C-H activation mediated by 2D transition metal dichalcogenides.

C-H bond activation enables the facile synthesis of new chemicals. While C-H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C-H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C-C coupling mediated by 2D TMDCs to promote C-H activation. Our results shed light on 2D materials for C-H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.

Volatile and Nonvolatile Resistive Switching Coexistence in Conductive Point Hexagonal Boron Nitride Monolayer.

Recently, we demonstrated the nonvolatile resistive switching effects of metal-insulator-metal (MIM) atomristor structures based on two-dimensional (2D) monolayers. However, there are many remaining combinations between 2D monolayers and metal electrodes; hence, there is a need to further explore 2D resistance switching devices from material selections to future perspectives. This study investigated the volatile and nonvolatile switching coexistence of monolayer hexagonal boron nitride (h-BN) atomristors using top and bottom silver (Ag) metal electrodes. Utilizing an h-BN monolayer and Ag electrodes, we found that the transition between volatile and nonvolatile switching is attributed to the thickness/stiffness of chain-like conductive bridges between h-BN and Ag surfaces based on the current compliance and atomristor area. Computations indicate a "weak" bridge is responsible for volatile switching, while a "strong" bridge is formed for nonvolatile switching. The current compliance determines the number of Ag atoms that undergo dissociation at the electrode, while the atomristor area determines the degree of electric field localization that forms more stable conductive bridges. The findings of this study suggest that the h-BN atomristor using Ag electrodes shows promise as a potential solution to integrate both volatile neurons and nonvolatile synapses in a single neuromorphic crossbar array structure through electrical and dimensional designs.

Health Care Costs With Sustained Oral Corticosteroid Use in Systemic Lupus Erythematosus.

PURPOSE: The goal of this study was to compare health care costs, health care resource utilization, and adverse events associated with sustained oral corticosteroid (OCS) use versus no OCS use in systemic lupus erythematosus. METHODS: This retrospective cohort study used claims data (January 1, 2006-July 31, 2019) from patients with systemic lupus erythematosus aged ≥5 years with ≥24 months of continuous enrollment. Health care costs, health care resource utilization, and OCS-related adverse events were assessed. The sustained OCS cohort (defined as ≥12 months of continuous OCS use) was divided into exposure categories based on the number of 6-month classification periods with >5 mg/d OCS (0, 1-2, or 3-4). FINDINGS: Of the 6234 patients in the sustained OCS use cohort, there were 1587 (25.5%) patients with 0 periods of >5 mg/d OCS use, 2087 (33.5%) patients with 1 to 2 periods of >5 mg/d OCS use, and 2560 (41.1%) patients with 3 to 4 periods of >5 mg/d OCS use; the no OCS use cohort included 7828 patients. Adjusted health care cost differences (95% CIs) were significantly greater for patients with 0, 1 to 2, and 3 to 4 periods of OCS use >5 mg/d versus the no OCS use cohort ($7774 [5426-10,223], $21,738 [18,898-25,321], and $30,119 [26,492-33,774], respectively). A higher proportion of patients in all OCS exposure categories required health care resource utilization (≥99.7% vs 93.4%) and experienced OCS-related adverse events (94.3%-96.8% vs 82.6%) versus the no OCS use cohort, with more periods of OCS use >5 mg/d associated with increased health care resource utilization and adverse events. IMPLICATIONS: Sustained OCS use in systemic lupus erythematosus was associated with high economic burden, health care resource utilization, and OCS-related adverse events. These data highlight the need for health care providers to carefully consider OCS use in systemic lupus erythematosus.

Clinical and Economic Burden in Patients With Systemic Lupus Erythematosus During the First Year After Initiating Oral Corticosteroids: A Retrospective US Database Study.

OBJECTIVE: To characterize health care resource utilization (HCRU), health care costs, and adverse events (AEs) among patients with systemic lupus erythematosus (SLE) initiating oral corticosteroids (OCS) versus patients without OCS use. METHODS: In this retrospective cohort study (GSK Study 213061), eligible patients (aged ≥5 years at first OCS claim) with SLE from the IQVIA Real-World Data Adjudicated Claims-US database (January 2006 to July 2019) had continuous enrollment during the 6-month preindex (baseline) and 12-month postindex (observation) periods and one or more inpatient or emergency department SLE diagnosis codes or two or more outpatient SLE diagnosis codes during baseline. The "OCS-initiator cohort" comprised patients with one or more OCS pharmacy claims during the study period and no evidence of preindex OCS use and was classified into three exposure categories based on the number of 6-month periods of more than 5 mg/day of OCS use (0, 1, 2). The "no-OCS-use cohort" comprised patients without OCS claims, although patients may have received OCS prior to the study period. Clinical and economic outcomes were reported over the observation period. RESULTS: Adjusted health care costs differed significantly ($6542 [95% confidence interval (CI): $5761-$7368], $19,149 [95% CI: $16,954-$21,471], $28,985 [95% CI: $25,546-$32,885]). HCRU incidence rates were significantly greater for all OCS-initiator exposure categories (n = 16,216) versus the no-OCS-use cohort (n = 11,137; adjusted incidence rate ratios [95% CI]: 1.22 [1.19-1.24], 1.39 [1.34-1.43], 1.66 [1.60-1.73]). OCS-related AEs were experienced by 67.1% to 74.1% of patients with OCS initiation, most commonly affecting the immune system. CONCLUSION: Within 12 months of OCS initiation, patients with SLE experienced substantial clinical and economic burden, which may imply a need to minimize OCS use.

Time and personnel costs associated with adverse event (AE) management among patients with chronic lymphocytic leukemia (CLL).

OBJECTIVES: Novel therapies improve clinical outcomes in chronic lymphocytic leukemia (CLL), although adverse event (AE) profiles differ. This study evaluated time and personnel costs of AE management among healthcare professionals (HCPs) treating patients with CLL with novel therapies. METHODS: A non-interventional prospective survey was conducted over 2 months. Eligible HCPs reported the time per day spent performing AE management activities for CLL patients treated with acalabrutinib, ibrutinib, or venetoclax. Mean time and personnel costs (USD) per activity were summarized and used to estimate the total annual costs of AE management for an average-sized oncology practice. RESULTS: For an average-sized practice (28 HCPs with an average of 56 CLL patients), the mean annual personnel cost of AE management for CLL patients on novel agents was estimated at $115,733. The personnel cost associated with acalabrutinib ($20,912) was less than half that of ibrutinib ($53,801) and venetoclax ($41,884), potentially due to fewer severe AEs and less time spent by oncologists managing AEs compared to other HCP types. CONCLUSION: The substantial burden of AE management for patients with CLL may vary by treatment used. Acalabrutinib was associated with lower annual costs of AE management at an oncology practice level compared to ibrutinib and venetoclax.

Comparative Study between Sulfurized MoS2 from Molybdenum and Molybdenum Trioxide Precursors for Thin-Film Device Applications.

Two-dimensional (2D) materials have been studied as an emerging class of nanomaterials owing to their attractive properties in nearly every field of science and technology. Molybdenum disulfide (MoS2) is one of the more promising candidates of these atomically thin 2D materials for its technological potential. The facile synthesis of MoS2 remains a matter of broad interest. In this study, MoS2 was synthesized by chemical vapor deposition sulfurization at various temperatures (550 °C, 650 °C, and 750 °C) of either precursor molybdenum metal (Mo) or molybdenum trioxide (MoO3) deposited on silicon/silicon dioxide (Si/SiO2) via e-beam evaporation. Monolayer, bilayer, and few layers sulfurized samples have been grown and verified by Raman, photoluminescence spectroscopy, XRD, XPS, and AFM. MoO3 sulfurization provided monolayer growth in comparison to Mo sulfurization under the same conditions and precursor thicknesses. Optical microscopy showed the homogeneous nature of grown samples. A main finding of this work is that MoO3 sulfurization produced higher quality MoS2 as compared to those grown by an Mo precursor. Device characteristics based on monolayer MoO3 sulfurized MoS2-x include nonvolatile resistive switching with Ion/Ioff ≈ 104 at a relatively low operating bias of ±1 V. In addition, field-effect transistor characteristics revealed p-type material growth with a carrier mobility ∼ 41 cm2 V-1 s-1, which is in contrast to typically observed n-type characteristics.

Prolonged oral corticosteroid treatment in patients with systemic lupus erythematosus: An evaluation of 12-month economic and clinical burden.

BACKGROUND: Prolonged, high-dose corticosteroid treatment for systemic lupus erythematosus (SLE) is associated with substantial health care costs, health care resource utilization (HCRU), and adverse events (AEs). OBJECTIVE: To compare all-cause health care costs, HCRU, and oral corticosteroid (OCS)-related AEs among patients with prevalent OCS use and patients without OCS use. METHODS: This retrospective, longitudinal cohort study (GSK study 214100) used claims data from the IQVIA Real-World Data Adjudicated Claims - US, IQVIA, Inc, database between January 1, 2006, and July 31, 2019, to identify patients with SLE. Patients with at least 1 OCS pharmacy claim during the study period and continuous OCS use during the 6-month pre-index (baseline) period (index date is the date of the first OCS claim following 6 months' continuous use) formed the "prevalent OCS use cohort." This cohort was subdivided based on the level of OCS exposure during the 12-month observation period, ie, the number of 6-month periods of greater than 5 mg/day OCS use (0, 1, or 2). Patients without OCS claims formed the "no OCS use cohort." All patients had continuous enrollment during the baseline and observation periods, had at least 1 inpatient or at least 2 outpatient SLE diagnosis codes during baseline, and were aged at least 5 years at index. A 2-part model, a generalized linear regression model with a negative binomial distribution, and a multivariate logistic regression model were used to compare health care costs, HCRU, and the odds of developing an OCS-related AE between cohorts, respectively. RESULTS: The no OCS use and prevalent OCS use cohorts included 21,517 and 16,209 patients, respectively. Adjusted health care cost differences (95% CI) were significantly lower for the no OCS use cohort vs all prevalent OCS use exposure categories ($5,439 [$4,537-$6,371] vs $17,856 [$16,368-$19,498]), driven by inpatient stays and outpatient visits; HCRU was also significantly lower (adjusted incidence rate ratios vs no OCS use cohort [95% CI]: 1.20 [1.16-1.23] vs 1.47 [1.41-1.52]). Health care costs and HCRU increased with increasing length of OCS exposure. OCS-related AEs occurred more frequently for all prevalent OCS use exposure categories vs the no OCS use cohort (odds ratio [95% CI]: 1.39 [1.25-1.55] vs 2.32 [2.02-2.68]), driven by hematologic/oncologic and immune system-related AEs. The mean (SD) average daily dose of OCS increased with increasing periods of prevalent OCS use (2.5 [1.3], 6.9 [31.1], and 34.6 [1,717.3] mg/day, respectively, for patients with 0, 1, and 2 periods of OCS use). CONCLUSIONS: Prevalent OCS use incurs a substantial clinical and economic burden, highlighting the need for restricted OCS doses and durations. DISCLOSURES: This study (GSK Study 214100) was funded by GSK. GSK was involved in designing the study, contributing to the collection, analysis, and interpretation of the data, supporting the authors in the development of the manuscript, and funding the medical writing assistance. All authors, including those employed by GSK, approved the content of the submitted manuscript and were involved in the decision to submit the manuscript for publication. Dr DerSarkissian, Dr Duh, and Mr Benson are employees of Analysis Group, which received research funding from GSK to conduct this study. Dr Wang, Ms Gu, and Mr Vu are former employees of Analysis Group. Mr Bell is an employee of GSK and holds stocks and shares in the company. Ms Averell and Dr Huang are former employees of GSK and held stocks and shares in the company at the time of the study.

A 5-Year Retrospective, Observational Study Assessing Rheumatoid Arthritis Disease Outcome Measures to Characterize Systemic Lupus Erythematosus Burden in the USA.

INTRODUCTION: We evaluated the use of rheumatoid arthritis (RA) disease measures in patients with systemic lupus erythematosus (SLE) in a US community-based rheumatology physician network over 5 years. METHODS: This retrospective, observational cohort study (GSK Study 213818) of patients with SLE utilized electronic medical records (01 January 2010-31 December 2019) from the United Rheumatology Normalized Integrated Community Evidence database. The index was the date of first SLE diagnosis recorded in the database; the observation period was 5 years post-index. RA disease measures evaluated were: Pain Index, Multi-Dimensional Health Assessment Questionnaire (MD-HAQ), Patient Global Assessment (PtGA), Physician Global Assessment (PGA), Swollen Joint Count (SJC), Tender Joint Count (TJC), Routine Assessment of Patient Index Data 3 (RAPID3), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and Disease Activity Score 28 (DAS-28). The number of patients with measures utilized, the score on each measure, and proportion of patients per disease activity category were assessed. RESULTS: Overall, 5990 patients with SLE were included. The most frequently used measures were Pain Index, SJC, TJC, MD-HAQ, PtGA, RAPID3, and PGA (cumulative use over Years 1-5: 23.9-71.3%). For all measures, frequency of use was lowest in Year 1, followed by a general increase from Year 1 to Year 5. Scores remained relatively stable for most measures, and the proportion of patients in remission or with low/moderate disease activity per RAPID3 increased. CONCLUSION: RA disease measure utilization in SLE was generally infrequent but increased over time. Pain Index and MD-HAQ were the most commonly applied cumulatively across 5 years of follow-up. The rationale for the increased use of these measures in SLE over time requires further exploration. In the absence of a clinically applicable SLE-specific measure, the use of RA measures, for example in conjunction with SLE measures, may provide an alternative approach for measuring disease activity, representing an opportunity to improve patient outcomes.

Aqueous lithium chloride solution as a non-toxic bactericidal and fungicidal disinfectant for air-conditioning systems: Efficacy and mechanism.

Airborne pathogenic bacteria and fungi transmitted through air-conditioning (AC) systems have been identified as a major public health risk. Air scrubbing is a promising liquid-based air disinfection technique that captures and inactivates airborne pathogens in liquid disinfectants. However, owing to the drawbacks of irritating odor and toxicity, the commonly-used chemical disinfectants cannot be employed for AC systems. This study aimed to unveil the inactivation performance and mechanism of non-toxic and chemically stable aqueous lithium chloride (LiCl) solution-the popular liquid desiccant in the AC systems-as a user-friendly disinfectant. Four prominent airborne pathogenic bacteria and fungi were exposed to the LiCl solution under various conditions. The inactivation effects were quantified with fluorescence-staining-based confocal microscopy and verified with the pathogens' membrane integrity variations, intracellular substance leakage, and morphological changes. Results showed that LiCl solution was remarkably efficient in inactivating the pathogens within 60 min, with an efficacy of 35.2-96.2%. The solution's inactivation ability was promoted by increasing the temperatures and concentrations; however, it appeared insensitive to exposure time over 30 min. We then explored the inactivation mechanism of LiCl solution by assessing cellular protein leakages and compared the inactivation rates with those of NaCl solution. The extracellular protein increased by over 470% after being exposed to LiCl solution. The inactivation rate was also considerably higher than in NaCl solution under the same osmotic pressure (24.79 MPa). We suggest that apart from osmotic pressure, the inactivation is reinforced by Li+-specific properties, including its strong water attraction that deprived the solvation shells of microbial protein and caused protein denaturation. We propose that aqueous LiCl solution may act as a user-friendly disinfectant for air-scrubbing due to its attractive characteristics, including its non-toxicity, odorless nature, and chemical stability. These findings may open up a "green" way to disinfect airborne pathogens and safeguard public health.

Portable ultrasonic humidifier exacerbates indoor bioaerosol risks by raising bacterial concentrations and fueling pathogenic genera.

Portable ultrasonic humidifiers are frequently used in heating rooms to ease air dryness. However, it has also posed serious health concerns such as "humidifier fever" because the bioaerosol concentration and community in the humidified space may alter quickly before the occupants could even notice. We compared the microbial proliferation rates in the humidifiers' reservoirs filled with three commonly used water types and investigated the impacts of the ultrasonic humidifiers on the temporal concentration, size distribution, and community variations of indoor bacterial and fungal aerosols during two-week humidification. The concentration of indoor bacterial aerosols increased exponentially, concentrating in the respiratory size ranges (≤1.1 µm), and was proportional to the humidification level, which soon exceeded 1000 CFU/m3 in one week (at RH = 70%), while the fungal concentration always remained low (≤177 CFU/m3 ). The indoor bioaerosol community, significantly associated with the humidifier water, was substantially distorted after humidification and dominated by the pathogenic Pseudomonas spp. (40.50%), Brevundimonas spp. (3.02%), Acinetobacter spp. (0.98%) and Legionella spp. (0.69%). Our results show that ultrasonic humidification contaminates indoor air by raising bacterial concentrations and fueling the pathogenic genera. To minimize the exposure risks, occupants should avoid long-term and excessive humidification (RH ≥ 70%) and clean the ultrasonic humidifier weekly.

A Library of Atomically Thin 2D Materials Featuring the Conductive-Point Resistive Switching Phenomenon.

Non-volatile resistive switching (NVRS) is a widely available effect in transitional metal oxides, colloquially known as memristors, and of broad interest for memory technology and neuromorphic computing. Until recently, NVRS was not known in other transitional metal dichalcogenides (TMDs), an important material class owing to their atomic thinness enabling the ultimate dimensional scaling. Here, various monolayer or few-layer 2D materials are presented in the conventional vertical structure that exhibit NVRS, including TMDs (MX2 , M = transitional metal, e.g., Mo, W, Re, Sn, or Pt; X = chalcogen, e.g., S, Se, or Te), TMD heterostructure (WS2 /MoS2 ), and an atomically thin insulator (h-BN). These results indicate the universality of the phenomenon in 2D non-conductive materials, and feature low switching voltage, large ON/OFF ratio, and forming-free characteristic. A dissociation-diffusion-adsorption model is proposed, attributing the enhanced conductance to metal atoms/ions adsorption into intrinsic vacancies, a conductive-point mechanism supported by first-principle calculations and scanning tunneling microscopy characterizations. The results motivate further research in the understanding and applications of defects in 2D materials.

Suicidal ideation and attempts in the United States of America among stimulant-treated, non-stimulant-treated, and untreated patients with a diagnosis of attention-deficit/hyperactivity disorder.

BACKGROUND: Studies of the association between attention-deficit/hyperactivity disorder (ADHD) drug therapy and suicidal ideation and attempts (SIA) have conflicting results. METHODS: Cohorts of patients with ADHD aged 6 years or older with at least one pharmacy claim for a central nervous system (CNS) stimulant or a non-stimulant, or with no claims for ADHD pharmacotherapy, were identified in the US IBM® MarketScan® Research Database from January 2008 to March 2018. Incidence density rates (IDRs) of SIA (i.e., claims for suicide and self-inflicted poisoning, suicide and self-inflicted injuries, or suicidal ideation) were calculated. Cohorts were compared (CNS stimulants vs non-stimulants; CNS stimulants vs no pharmacotherapy) using hazard ratios (HRs) estimated from Cox proportional hazards models. Inverse-probability-of-treatment weighting (IPTW) was used to control for confounding. RESULTS: The study included 797,189 patients (CNS stimulants, 622,536; non-stimulants, 54,615; no pharmacotherapy, 120,038). IDRs of SIA (per 1000 patient-years) were: CNS stimulants, 5.8; non-stimulants, 10.5; and no pharmacotherapy, 10.0. The overall SIA risk was significantly lower with CNS stimulants than with non-stimulants (IPTW-adjusted HR = 0.70, 95% confidence interval = 0.61-0.81, p < 0.001) and no pharmacotherapy (0.62, 0.57-0.67, p < 0.001). LIMITATIONS: SIA assessment was based on diagnostic codes; suicidal ideation may not have been reported; completed suicides were generally not captured; and treatment was not verified. CONCLUSIONS: In this population-based study of patients with ADHD, SIA risk was significantly lower in those receiving CNS stimulants relative to those receiving non-stimulants or no pharmacotherapy, suggesting that CNS stimulants may attenuate SIA risk.

Achieving Remarkable Activity and Durability toward Oxygen Reduction Reaction Based on Ultrathin Rh-Doped Pt Nanowires.

The research of active and sustainable electrocatalysts toward oxygen reduction reaction (ORR) is of great importance for industrial application of fuel cells. Here, we report a remarkable ORR catalyst with both excellent mass activity and durability based on sub 2 nm thick Rh-doped Pt nanowires, which combine the merits of high utilization efficiency of Pt atoms, anisotropic one-dimensional nanostructure, and doping of Rh atoms. Compared with commercial Pt/C catalyst, the Rh-doped Pt nanowires/C catalyst shows a 7.8 and 5.4-fold enhancement in mass activity and specific activity, respectively. The combination of extended X-ray absorption fine structure analysis and density functional theory calculations reveals that the compressive strain and ligand effect in Rh-doped Pt nanowires optimize the adsorption energy of hydroxyl and in turn enhance the specific activity. Moreover, even after 10000 cycles of accelerated durability test in O2 condition, the Rh-doped Pt nanowires/C catalyst exhibits a drop of 9.2% in mass activity, against a big decrease of 72.3% for commercial Pt/C. The improved durability can be rationalized by the increased vacancy formation energy of Pt atoms for Rh-doped Pt nanowires.