Heterogeneous associations between interleukin-6 receptor variants and phenotypes across ancestries and implications for therapy.

The Phenome-Wide Association Study (PheWAS) is increasingly used to broadly screen for potential treatment effects, e.g., IL6R variant as a proxy for IL6R antagonists. This approach offers an opportunity to address the limited power in clinical trials to study differential treatment effects across patient subgroups. However, limited methods exist to efficiently test for differences across subgroups in the thousands of multiple comparisons generated as part of a PheWAS. In this study, we developed an approach that maximizes the power to test for heterogeneous genotype-phenotype associations and applied this approach to an IL6R PheWAS among individuals of African (AFR) and European (EUR) ancestries. We identified 29 traits with differences in IL6R variant-phenotype associations, including a lower risk of type 2 diabetes in AFR (OR 0.96) vs EUR (OR 1.0, p-value for heterogeneity = 8.5 × 10-3), and higher white blood cell count (p-value for heterogeneity = 8.5 × 10-131). These data suggest a more salutary effect of IL6R blockade for T2D among individuals of AFR vs EUR ancestry and provide data to inform ongoing clinical trials targeting IL6 for an expanding number of conditions. Moreover, the method to test for heterogeneity of associations can be applied broadly to other large-scale genotype-phenotype screens in diverse populations.

Transformation of (allo)securinine to (allo)norsecurinine via a molecular editing strategy.

Securinega alkaloids have intrigued chemists since the isolation of securinine in 1956. This family of natural products comprises a securinane subfamily with a piperidine substructure and norsecurinane alkaloids featuring a pyrrolidine core. From a biosynthetic perspective, the piperidine moiety in securinane alkaloids derives from lysine, whereas the pyrrolidine moiety in norsecurinane natural products originates from ornithine, marking an early biogenetic divergence. Herein, we introduce a single-atom deletion strategy that enables the late-stage conversion of securinane to norsecurinane alkaloids. Notably, for the first time, this method enabled the transformation of piperidine-based (allo)securinine into pyrrolidine-based (allo)norsecurinine. Straightforward access to norsecurinine from securinine, which can be readily extracted from the plant Flueggea suffruticosa, abundant across the Korean peninsula, holds promise for synthetic studies of norsecurinine-based oligomeric securinega alkaloids.

High-Precision Tailored Polymer Molecular Weights for Specific Photovoltaic Applications through Ultrasound-Induced Simultaneous Physical and Chemical Events.

It is highly challenging to reproducibly prepare semiconducting polymers with targeted molecular weight tailored for next-generation photovoltaic applications. Once such an easily accessible methodology is established, which can not only contribute to overcome the current limitation of the statistically determined nature of semiconducting polymers, but also facilitate rapid incorporation into the broad synthetic chemists' toolbox. Here, we describe a simple yet robust ultrasonication-assisted Stille polymerization for accessing semiconducting polymers with high-precision tailored molecular weights (from low to ultrahigh molecular weight ranges) while mitigating their interbatch variations. We propose that ultrasound-induced simultaneous physical and chemical events enable precise control of the semiconducting polymers' molecular weights with high reproducibility to satisfy all the optical/electrical and morphological demands of diverse types of high-performance semiconducting polymer-based devices; as demonstrated in in-depth experimental screenings in applications of both organic and perovskite photovoltaics. We believe that this methodology provides a fast development of new and existing semiconducting polymers with the highest-level performances possible on various photovoltaic devices.

Tethered Trimeric Small-molecular Acceptors through Aromatic-core Engineering for Highly Efficient and Thermally Stable Polymer Solar Cells.

Polymer solar cells (PSCs) rely on a blend of small molecular acceptors (SMAs) with polymer donors, where thermodynamic relaxation of SMAs poses critical concerns on operational stability. To tackle this issue, tethered SMAs, wherein multiple SMA-subunits are connected to the aromatic-core via flexible chains, are proposed. This design aims to an elevated glass transition temperature (Tg) for a dynamical control. However, attaining an elevated Tg value with additional SMA subunits introduces complexity to the molecular packing, posing a significant challenge in realizing both high stability and power conversion efficiency (PCE). In this study, we initiate isomer engineering on the benzene-carboxylate core and find that meta-positioned dimeric BDY-ß exhibits more favorable molecular packing compared to its para-positioned counterpart, BDY-α. With this encouraging result, we expand our approach by introducing an additional SMA unit onto the aromatic core of BDY-ß, maintaining a meta-position relative to each SMA unit location in the tethered acceptor. This systematic aromatic-core engineering results in a star-shaped C3h-positioned molecular geometry. The supramolecular interactions of SMA units in the trimer contribute to enhancements in Tg value, crystallinity, and a red-shifted absorption compared to dimers. These characteristics result in a noteworthy increase in PCE to 18.24 %, coupled with a remarkable short-circuit current density of 27.06 mA cm-2. More significantly, the trimer-based devices delivered an excellent thermal stability with over 95 % of their initial efficiency after 1200 h thermal degradation. Our findings underscore the promise and feasibility of tethered trimeric structures in achieving highly ordered aggregation behavior and increased Tg value in PSCs, simultaneously improving in device efficiency and thermal stability.

Risk of fall or fracture with concomitant use of prescription opioids and other medications in osteoarthritis patients.

BACKGROUND: Osteoarthritis (OA) patients taking prescription opioids for pain are at increased risk of fall or fracture, and the concomitant use of interacting drugs may further increase the risk of these events. AIMS: To identify prescription opioid-related medication combinations associated with fall or fracture. MATERIALS & METHODS: We conducted a case-crossover-based screening of two administrative claims databases spanning 2003 through 2021. OA patients were aged 40 years or older with at least 365 days of continuous enrollment and 90 days of continuous prescription opioid use before their first eligible fall or fracture event. The primary analysis quantified the odds ratio (OR) between fall and non-opioid medications dispensed in the 90 days before the fall date after adjustment for prescription opioid dosage and confounding using a case-time-control design. A secondary analogous analysis evaluated medications associated with fracture. The false discovery rate (FDR) was used to account for multiple testing. RESULTS: We identified 41 693 OA patients who experienced a fall and 24 891 OA patients who experienced a fracture after at least 90 days of continuous opioid therapy. Top non-opioid medications by ascending p-value with OR > 1 for fall were meloxicam (OR 1.22, FDR = 0.08), metoprolol (OR 1.06, FDR >0.99), and celecoxib (OR 1.13, FDR > 0.99). Top non-opioid medications for fracture were losartan (OR 1.20, FDR = 0.80), alprazolam (OR 1.14, FDR > 0.99), and duloxetine (OR 1.12, FDR = 0.97). CONCLUSION: Clinicians may seek to monitor patients who are co-prescribed drugs that act on the central nervous system, especially in individuals with OA.

Three-in-One Strategy Enables Single-Component Organic Solar Cells with Record Efficiency and High Stability.

Single-component organic solar cells (SCOSCs) with covalently bonding donor and acceptor are becoming increasingly attractive because of their superior stability over traditional multicomponent blend organic solar cells (OSCs). Nevertheless, the efficiency of SCOSCs is far behind the state-of-the-art multicomponent OSCs. Herein, by combination of the advantages of three-component and single-component devices, this work reports an innovative three-in-one strategy to boost the performance of SCOSCs. In this three-in-one strategy, three independent components (PM6, D18, and PYIT) are covalently linked together to create a new single-component active layer based on ternary conjugated block copolymer (TCBC) PM6-D18-b-PYIT by a facile polymerization. Precisely manipulating the component ratios in the polymer chains of PM6-D18-b-PYIT is able to broaden light utilization, promote charge dynamics, optimize, and stabilize film morphology, contributing to the simultaneously enhanced efficiency and stability of the SCOSCs. Ultimately, the PM6-D18-b-PYIT-based device exhibits a power conversion efficiency (PCE) of 14.89%, which is the highest efficiency of the reported SCOSCs. Thanks to the aggregation restriction of each component and chain entanglement in the three-in-one system, the PM6-D18-b-PYIT-based SCOSC displays significantly higher stability than the corresponding two-component (PM6-D18:PYIT) and three-component (PM6:D18:PYIT). These results demonstrate that the three-in-one strategy is facile and promising for developing SCOSCs with superior efficiency and stability.

Comparative Effectiveness of Cognitive Behavioral Therapy and Behavioral Therapy in Obesity: A Systematic Review and Network Meta-Analysis.

We aimed to evaluate the effects of obesity treatment with behavioral therapy (BT) and cognitive behavioral therapy (CBT) interventions compared with multiple comparators and find effective techniques or combinations of techniques in BT and CBT interventions for weight loss. We systematically searched electronic databases and selected randomized controlled trials using CBT or BT intervention for obesity treatment in overweight adults or adults with obesity without psychological symptoms. Both pairwise meta-analysis and network meta-analysis were performed to comprehensively evaluate the comparative effects between interventions. We classified the techniques used in BT and CBT interventions and compared the treatment effects between techniques. Compared with no treatment as a common comparator, CBT was most effective for weight loss, followed by BT, usual care (UC), and minimal care (MC). CBT was a more effective intervention than BT, but the effect of CBT compared to BT was not remarkable in network estimates. The most used BT techniques were feedback and monitoring, and the most used CBT technique was cognitive restructuring. Our results indicated that CBT and BT are effective interventions for weight loss, and that successful weight loss requires more aggressive interventions such as BT or CBT than MC and UC.

Improving the accuracy of automated gout flare ascertainment using natural language processing of electronic health records and linked Medicare claims data.

BACKGROUND: We aimed to determine whether integrating concepts from the notes from the electronic health record (EHR) data using natural language processing (NLP) could improve the identification of gout flares. METHODS: Using Medicare claims linked with EHR, we selected gout patients who initiated the urate-lowering therapy (ULT). Patients' 12-month baseline period and on-treatment follow-up were segmented into 1-month units. We retrieved EHR notes for months with gout diagnosis codes and processed notes for NLP concepts. We selected a random sample of 500 patients and reviewed each of their notes for the presence of a physician-documented gout flare. Months containing at least 1 note mentioning gout flares were considered months with events. We used 60% of patients to train predictive models with LASSO. We evaluated the models by the area under the curve (AUC) in the validation data and examined positive/negative predictive values (P/NPV). RESULTS: We extracted and labeled 839 months of follow-up (280 with gout flares). The claims-only model selected 20 variables (AUC = 0.69). The NLP concept-only model selected 15 (AUC = 0.69). The combined model selected 32 claims variables and 13 NLP concepts (AUC = 0.73). The claims-only model had a PPV of 0.64 [0.50, 0.77] and an NPV of 0.71 [0.65, 0.76], whereas the combined model had a PPV of 0.76 [0.61, 0.88] and an NPV of 0.71 [0.65, 0.76]. CONCLUSION: Adding NLP concept variables to claims variables resulted in a small improvement in the identification of gout flares. Our data-driven claims-only model and our combined claims/NLP-concept model outperformed existing rule-based claims algorithms reliant on medication use, diagnosis, and procedure codes.

Thickness Tolerance in Large-Area Organic Photovoltaics with Fluorine-Substituted Regioregular Conjugated Polymer.

Large areas and simple processing methods are necessary for the commercialization of organic photovoltaics (OPVs). However, the efficiency drop due to the variation in thickness of OPVs limits their large-scale applications. Regioregular polymers with good crystallinity and packing properties that exhibit high charge mobility and extraction ability can help overcome these limitations. In this study, a regioregular polymer named PDBD-2FBT was synthesized. The crystallinity and packing properties of PDBD-2FBT were enhanced by a simple thermal treatment. Using PDBD-2FBT material as a donor and Y6-HU as an acceptor, we fabricated binary blend OPV devices. The devices with optimized active layer thickness achieved a power conversion efficiency (PCE) of 14.14%. A PCE of 13.18% was maintained even in thick-film conditions (400 nm), and thickness tolerance was observed. Based on the thickness tolerance, a 5-line module measuring 36 cm2 was fabricated via the bar-coating method, and a PCE of approximately 10% was achieved.

Moracin E and M isolated from Morus alba Linné induced the skeletal muscle cell proliferation via PI3K-Akt-mTOR signaling pathway.

Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p < 0.001) and 57% (p < 0.05), respectively, which have more than 2- and 1.5-fold stronger effects compared to the control. Furthermore, both increased the expression level of proteins involved in the PI3K-Akt-mTOR signaling pathway and myogenic proteins, including myogenin and MyoD. This study demonstrated that moracin E and M exhibit cell proliferative effects on skeletal muscle cells through the PI3K-Akt-mTOR signaling pathway.

Unraveling prokaryotic diversity distribution and functional pattern on nitrogen and methane cycling in the subtropical Western North Pacific Ocean.

Prokaryotes play an important role in marine nitrogen and methane cycles. However, their community changes and metabolic modifications to the concurrent impact of ocean warming (OW), acidification (OA), deoxygenation (OD), and anthropogenic­nitrogen-deposition (AND) from the surface to the deep ocean remains unknown. We examined here the amplicon sequencing approach across the surface (0-200 m; SL), intermediate (200-1000 m; IL), and deep layers (1000-2200 m; DL), and characterized the simultaneous impacts of OW, OA, OD, and AND on the Western North Pacific Ocean prokaryotic changes and their functional pattern in nitrogen and methane cycles. Results showed that SL possesses higher ammonium oxidation community/metabolic composition assumably the reason for excess nitrogen input from AND and modification of their kinetic properties to OW adaptation. Expanding OD at IL showed hypoxic conditions in the oxygen minimum layer, inducing higher microbial respiration that elevates the dimerization of nitrification genes for higher nitrous oxide production. The aerobic methane-oxidation composition was dominant in SL presumably the reason for adjustment in prokaryotic optimal temperature to OW, while anaerobic oxidation composition was dominant at IL due to the evolutionary changes coupling with higher nitrification. Our findings refocus on climate-change impacts on the open ocean ecosystem from the surface to the deep-environment integrating climate-drivers as key factors for higher nitrous-oxide and methane emissions.

Regulation of σB-Dependent Biofilm Formation in Staphylococcus aureus through Strain-Specific Signaling Induced by Diosgenin.

Staphylococcus aureus is a commensal skin bacterium and a causative agent of infectious diseases. Biofilm formation in S. aureus is a mechanism that facilitates the emergence of resistant strains. This study proposes a mechanism for the regulation of biofilm formation in S. aureus through strain-specific physiological changes induced by the plant steroid diosgenin. A comparison of diosgenin-induced changes in the expression of regulatory genes associated with physiological changes revealed the intracellular regulatory mechanisms involved in biofilm formation. Diosgenin reduced biofilm formation in S. aureus ATCC 6538 and methicillin-resistant S. aureus (MRSA) CCARM 3090 by 39% and 61%, respectively. Conversely, it increased biofilm formation in S. aureus ATCC 29213 and MRSA CCARM 3820 by 186% and 582%, respectively. Cell surface hydrophobicity and extracellular protein and carbohydrate contents changed in a strain-specific manner in response to biofilm formation. An assessment of the changes in gene expression associated with biofilm formation revealed that diosgenin treatment decreased the expression of icaA and spa and increased the expression of RNAIII, agrA, sarA, and sigB in S. aureus ATCC 6538 and MRSA CCARM 3090; however, contrasting gene expression changes were noted in S. aureus ATCC 29213 and MRSA CCARM 3820. These results suggest that a regulatory mechanism of biofilm formation is that activated sigB expression sequentially increases the expression of sarA, agrA, and RNAIII. This increased RNAIII expression decreases the expression of spa, a surface-associated adhesion factor. An additional regulatory mechanism of biofilm formation is that activated sigB expression decreases the expression of an unknown regulator that increases the expression of icaA. This in turn decreases the expression of icaA, which decreases the synthesis of polysaccharide intercellular adhesins and ultimately inhibits biofilm formation. By assessing strain-specific contrasting regulatory signals induced by diosgenin in S. aureus without gene mutation, this study elucidated the signal transduction mechanisms that regulate biofilm formation based on physiological and gene expression changes.

Occupational Risk Factors for Stroke: A Comprehensive Review.

For primary prevention, it is important for public health and clinical medicine to identify and characterize modifiable risk factors of stroke. In existing literature, the impact of occupational variables on ischemic and hemorrhagic stroke has been extensively studied. This review summarizes the available data on the significance of occupational variables in stroke. The results of this review suggest that there is sufficient evidence for the relationship between increased risk of stroke and job stress, working in extreme temperatures, long working hours, and/or shift work. The association between long working hours and occupational exposure to noise and chemicals remains inconclusive although several studies have reported this finding. This review will act as a step toward future research and provide information that may serve as a baseline for developing targeted interventions to prevent stroke in the working population.

Real-World Treatment Effectiveness of Disease-Modifying Antirheumatic Drugs by Serostatus Among Patients With Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to compare the clinical effectiveness of biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase inhibitors (JAKi) among seropositive versus seronegative patients with rheumatoid arthritis (RA) in a real-world setting. METHODS: We used Optum's deidentified Clinformatics Data Mart Database (January 1, 2004, to March 31, 2021) linked with outpatient laboratory test results. The study population was adult patients with RA who initiated a bDMARD or JAKi. The index date was the dispensing of the first-ever study drug. At least 1-year continuous enrollment before and after the index date was required. Disenrollment due to death after the index date was allowed. Serostatus was defined using laboratory test results or the International Classification of Diseases, 10th Revision code M05x or M06.0x any time prior to the index date. Treatment effectiveness was measured based on a claims-based composite endpoint at 1-year post index, including nonoccurrence of any of the following: addition of conventional synthetic DMARDs, addition of or switching to new bDMARDs/JAKi, initiation of glucocorticoids, increased glucocorticoid dose, or death. Log-binomial regression models were constructed to estimate the risk ratio (RR) with 95% confidence interval (CI) comparing seropositive patients with seronegative patients, adjusting for more than 60 baseline covariates. RESULTS: We identified a total of 7813 seropositive patients and 4202 seronegative patients. The mean (±SD) age was 56.7 (±14.0) years; 77.9% were female. The risk of 1-year treatment effectiveness was 70.2% among seropositive patients and 69.8% among seronegative patients. The adjusted RR (95% CI) was 1.00 (0.98-1.02). CONCLUSION: In this real-world cohort study, seropositive and seronegative patients with RA had similar 1-year treatment effectiveness after initiating a bDMARD/JAKi.

Associations between post-traumatic stress disorders and psychotic symptom severity in adult survivors of developmental trauma: a multisite cross-sectional study in the UK and South Korea.

BACKGROUND: Childhood maltreatment is a risk factor for the development of post-traumatic stress disorders and psychosis. However, the association between post-traumatic stress disorder (PTSD), including complex PTSD, and psychotic symptoms is unknown. We investigated whether the presence of PTSD and complex PTSD was associated with psychotic symptom severity within survivors of developmental trauma. METHODS: As part of the Investigating Mechanisms underlying Psychosis Associated with Childhood Trauma (IMPACT) study, from Aug 20, 2020, to Jan 24, 2021, and from Sept 9, 2022, to Feb 21, 2023, using study advertisement on online platforms we recruited adult (≥18 years) participants who had experienced developmental trauma without a psychiatric diagnosis in the UK and South Korea. We measured whether participants met diagnostic thresholds for PTSD and complex PTSD using the self-reported International Trauma Questionnaire, and psychotic symptoms using the self-reported Community Assessment of Psychic Experiences. We used linear regression, adjusting for sociodemographic variables such as age, sex, ethnicity, educational attainment, and socioeconomic status, to examine whether there was an association between PTSD and complex PTSD and psychotic symptoms. The study is registered in the UK (University College London Research Ethics Committee [14317/001] and the National Health Service Research Ethics Committee [22/YH/0096]) and South Korea (Institutional Review Board of Seoul National University Bundang Hospital [B-2011-648-306]), and is ongoing. FINDINGS: Of the 2675 participants who took part in the study, 1273 had experienced developmental trauma and were included in the study in the UK (n=475) and South Korea (n=798), comprising 422 (33%) men and 851 (67%) women with a mean age of 26·9 years (SD 6, range 18-40), mostly of White British (n=328) or South Korean (n=798) ethnicity. We found no significant association between PTSD and psychotic symptom severity (total severity ß=-2·40 [SE 3·28], p=0·47), compared with participants who did not meet PTSD or complex PTSD caseness. We found a significant relationship between complex PTSD and psychotic symptom severity (total severity ß=22·62 [SE 1·65], p<0·0001), including for positive (ß=12·07 [SE 0·99], p<0·0001) and negative symptoms (ß=10·5 [SE 0·95], p<0·0001), compared with participants who did not meet PTSD or complex PTSD caseness. INTERPRETATION: Health systems must assess individuals with previous developmental trauma for complex PTSD and treat those affected. These individuals should also be assessed for psychotic symptoms, and if necessary, preventative measures should be taken to reduce risk of conversion. Further work should assess whether treating complex PTSD modifies the risk of conversion to psychosis. FUNDING: UKRI Future Leaders Fellowship, British Medical Association Margaret Temple Award for Schizophrenia Research, and the National Research Foundation of Korea-Korea Government.

Skin Test-Guided Strategy to Select Alternative Iodinated Contrast Media in Patients With Immediate Hypersensitivity Reaction: A Prospective Confirmative Study.

BACKGROUND: Iodinated contrast media (ICM) are a common cause of drug-induced immediate hypersensitivity reaction (IHR). Repeated use of ICM is often necessary; therefore, a standardized protocol to prevent recurrence of IHR is required. OBJECTIVE: We aimed to propose an intradermal skin test (IDT)-guided strategy for previous reactors to prevent recurrence of IHR. METHODS: We conducted a prospective multicenter study from May 2018 to December 2020 and recruited patients who had experienced IHR to ICM. Once enrolled, the participants underwent IDT with a causative ICM. The alternatives for reexposure were selected using the following protocol: (1) if the IDT with the culprit ICM was positive, further skin tests with other available ICM were conducted to choose IDT-negative agents as alternatives, and (2) if the IDT with the culprit ICM was negative, a randomly changed ICM was used without additional skin tests. The recurrence and severity of hypersensitivity were assessed in subsequent computed tomography examinations. Premedication was administered according to the severity of the index event in all cases. RESULTS: A total of 496 participants were enrolled, and 299 were reexposed to ICM. Among 269 participants who followed the protocol, 228 (84.8%) completed computed tomography examinations without adverse reactions, and IHR recurred in 16 of 30 participants (53.3%) who did not follow the protocol (P < .001). In addition, application of the protocol reduced the severity of IHR in recurred cases (P = 0.003). CONCLUSIONS: Our IDT-guided strategy not only reduced recurrence of IHR to ICM but also mitigated the severity in recurred cases. This provides evidence for recommending an IDT to diagnose ICM allergy and find safe alternatives.

Contemporary trends in the utilization of second-line pharmacological therapies for type 2 diabetes in the United States and the United Kingdom.

AIM: To examine trends of second-line glucose-lowering therapies among patients with type 2 diabetes (T2D) initiating first-line metformin in the United States and the United Kingdom, overall and by subgroups of cardiovascular disease (CVD) and calendar time. METHODS: Using the US Optum Clinformatics and the UK Clinical Practice Research Datalink, we identified adults with T2D who initiated first-line metformin or sulphonylurea monotherapy, separately, from 2013 to 2019. Within both cohorts, we identified patterns of second-line medications through June 2021. We stratified patterns by CVD and calendar time to investigate the impact of rapidly evolving treatment guidelines. RESULTS: We identified 148 511 and 169 316 patients initiating treatment with metformin monotherapy in the United States and the United Kingdom, respectively. Throughout the study period, sulphonylureas and dipeptidyl peptidase-4 inhibitors were the most frequently initiated second-line medications in the United States (43.4% and 18.2%, respectively) and the United Kingdom (42.5% and 35.8%, respectively). After 2018, sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists were more commonly used as second-line agents in the United States and the United Kingdom, although these agents were not preferentially prescribed among patients with CVD. Initiation of first-line sulphonylureas was much less common, and most sulphonylurea initiators had metformin added as the second-line agent. CONCLUSIONS: This international cohort study shows that sulphonylureas remain the most common second-line medications prescribed following metformin in both the United States and the United Kingdom. Despite recommendations, the use of newer glucose-lowering therapies with cardiovascular benefits remains low.

Biodegradation of polystyrene by intestinal symbiotic bacteria isolated from mealworms, the larvae of Tenebrio molitor.

Objectives: Polystyrene is a plastic that leads to environmental pollution. In particular, expanded polystyrene is very light and takes up much space, causing additional environmental problems. The aim of this study was to isolate new symbiotic bacteria which degraded polystyrene from mealworms. Methods: The population of polystyrene degrading bacteria was increased by enrichment culture of intestinal bacteria from mealworms with polystyrene as a sole carbon source. The degradation activity of isolated bacteria was evaluated by morphological change of micro-polystyrene particles and the surface change of polystyrene films. Results: Eight isolated species (Acinetobacter septicus, Agrobacterium tumefaciens, Klebsiella grimontii, Pseudomonas multiresinivorans, Pseudomonas nitroreducens, Pseudomonas plecoglossicida, Serratia marcescens, and Yokenella regensburgei) were identified that degrade polystyrene. Conclusion: Bacterial identification shows that a broad spectrum of bacteria decomposing polystyrene coexists in the intestinal tract of mealworms.

Validation of the Korean Version of the Community Assessment of Psychic Experiences in General Population.

OBJECTIVE: The Community Assessment of Psychic Experiences has been widely translated and commonly used as a measure for psychotic experiences and psychosis proneness in clinical and research environments worldwide. This study aimed to establish the psychometric properties (reliability and validity) and factor structure of a Korean version of the Community Assessment of Psychic Experiences (K-CAPE) in the general population. METHODS: A total of 1,467 healthy participants completed K-CAPE and other psychiatric symptom-related scales (Paranoia scale, Patient Health Questionnaire-9, Dissociative Experiences Scale-II, and Oxford-Liverpool Inventory of Feelings and Experiences) via online survey. K-CAPE's internal reliability was analyzed using Cronbach's alpha coefficient. Confirmatory factor analysis (CFA) was performed to investigate whether the original three-factor model (positive, negative, and depressive) and other hypothesized multidimensional models (including positive and negative subfactors) were suitable for our data. Exploratory factor analysis (EFA) was conducted to explore better alternative factor solutions with a follow-up CFA. To assess convergent and discriminant validity, we examined correlations between K-CAPE subscales with other established measures of psychiatric symptoms. RESULTS: K-CAPE showed good internal consistency in all original three subscales (all greater than α=0.827). The CFA demonstrated that the multidimensional models exhibited relatively better quality than the original three-dimensional model. Although the model fit indices did not reach their respective optimal thresholds, they were within an acceptable range. Results from the EFA indicated 3-5 factor solutions. In 3-factor solution, "negative-avolition" items were founded to be loaded more consistently with depressive items than with the negative dimension. In 4-factor solution, positive items were divided into two subfactors: "positive-bizarre experiences" and "positive-delusional thoughts," while negative symptoms were separated into two distinct subfactors in 5-factor solution: "negative-avolition (expressive)," and "negative-social (experiential)." The correlation coefficients between K-CAPE subscales and corresponding measurements were significant (p<0.001), confirming the convergent and discriminant validity. CONCLUSION: Our study provides evidence to support the reliability and validity of the K-CAPE and its use as a measure of psychotic symptoms in the Korean population. Although alternative factor structures did not improve the model fit, our EFA findings implicate the use of subfactors to investigate more specific domains of positive and negative symptoms. Given the heterogeneous nature of psychotic symptoms, this may be useful in capturing their different underlying mechanisms.

An electron acceptor with an intrinsic quinoidal core for bulk-heterojunction organic solar cells and photodetectors.

An electron acceptor based on a quinoidal dipyrrolopyrazinedione core was synthesized for organic solar cells and photodetectors. A power conversion efficiency of 6.7% and a specific detectivity of 4.1 × 1013 Jones at 800 nm have been obtained, suggesting the promising prospects of quinoidal molecules for optoelectronic devices.