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摘要： QuestionDo kidney outcomes differ between initiating treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) vs glucagon-like peptide-1 receptor agonist (GLP-1RA) in individuals with type 2 diabetes?FindingsIn this comparative effectiveness study with a target trial emulation including 36 279 SGLT2i initiators and 18 782 GLP-1RA initiators, SGLT2i initiation was associated with a lower 5-year risk of chronic kidney disease and a lower 5-year count of acute kidney injury compared with GLP-1RA initiation. Findings were consistent across subgroups and most pronounced among individuals without preexisting kidney *** findings suggest that initiating treatment with an SGLT2i, compared with a GLP-1RA, is associated with improved kidney outcomes in individuals with type 2 diabetes. This comparative effectiveness research study examines whether kidney outcomes differ with sodium-glucose cotransporter-2 (SGLT2) inhibitor vs glucagon-like peptide-1 (GLP-1) receptor agonist treatment in individuals with type 2 diabetes. ImportanceNo randomized clinical trial has directly compared the effectiveness of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment in reducing acute and chronic kidney *** examine the comparative effectiveness of SGLT2i and GLP-1RA treatment for acute and chronic kidney outcomes in individuals with type 2 ***, Setting, and ParticipantsThis comparative effectiveness study with a target trial emulation design used nationwide, population-based data from Denmark. Participants were individuals with metformin-treated type 2 diabetes who initiated SGLT2i or GLP-1RA treatment from January 2014 to November 2020, with follow-up through October *** of an SGLT2i or a *** Outcomes and MeasuresThe 2 coprimary outcomes were chronic kidney disease (CKD;40% reduction in estimated glomerular filtration rate [eGFR], severe albuminu

关键词： Classical hodgkin lymphoma   Programmed death ligand 1 (PD-L1)  

摘要： Classical Hodgkin lymphoma (CHL) has an overall favourable prognosis. However, relapse/refractory CHL cases are associated with an unfavourable outcome. Targeted immunotherapy based on PD-1 and PD-L1 pathway inhibitors have shown improvement in the treatment of relapsed/refractory CHL cases. The objective of this study was to assess Programmed death ligand (PD-L1) expression before and after antineoplastic treatment in primary refractory (P/R) Classical Hodgkin lymphoma and relapsed/ refractory (R/R) Classical Hodgkin lymphoma cases. Slides and blocks of 30 paired biopsies of Classical Hodgkin Lymphoma cases during the five year study period which have been refractory or have relapsed post antineoplastic treatment were retrieved and reviewed. PD-L1 expression in Hodgkin Reed Sternberg (HRS) cells and micro environment (ME) at primary diagnosis and at relapse/refractory disease were analysed by staining with PD-L1 (SP263) antibody. Tumour cells and peritumoral microenvironment were evaluated separately. More than 5% expression with 2+/3+ intensity in HRS cells and/or in microenvironment were accepted as positive. In our patient population we found that the PD-L1 expression in relapse/refractory lymphoma biopsy in comparison to primary diagnosis biopsy remains largely unchanged in HRS cells and in the microenvironment. This stable expression of PD-L1 expression in paired biopsies suggests that PD-L1 inhibitors can be used as second line therapy in all relapsed Classical Hodgkin lymphoma patients without PD-L1 testing.

关键词： Generalized divisor problem   number theoretic error term   Dirichlet series of error term   Perron's formula   exponential sums   exponent pairs   sum of Chowla and Walum  

摘要： Let E-a(x) be the error term of the sum of sigma(a)(n) for n <= x, where sigma(a)(n) =& sum;d|nd(a). In this paper we study the behavior of & sum;(n <= x)Ea(n) in the case 1/ 2 < a <= 1 by applying analytic properties of the Dirichlet series & sum;E-infinity(n=1)a(n)/ n(s). Especially, we shall give an explicit upper bound for the error term of & sum;E-n <= x(a)(n) by means of exponent pairs.

关键词： depression   complexity   biomarkers   electroencephalography   d & eacute   pression   complexit & eacute   biomarqueurs   eacute   lectroenc & eacute   phalographie  

摘要： Objectives Current pharmacological antidepressant treatments suffer from low remission rates and slow initiation of therapeutic effects. In addition, the development of new antidepressant treatments is confounded by the lack of consensus on efficient and valid neurophysiological targets. Temporal complexity is an alternative measure of dynamic brain activity that estimates brain signal variability at several timescales. It can be easily extracted from non-invasive brain recordings and provides new insights into pathophysiological mechanisms. We aim to assess the potential of brain temporal complexity as a novel neuromarker to predict the effectiveness of antidepressant *** We measured longitudinal changes in temporal complexity of electroencephalography signals in patients undergoing 8 weeks of escitalopram treatment through a Canadian Biomarker Integration Network in Depression (CAN-BIND) *** As early as 2 weeks after the start of treatment, reduction of complexity in fine timescales was associated with improvement in depressive symptoms. After 8 weeks of treatment, the treatment-related effect shifted towards an increase in coarse timescale complexity, linked to symptom *** These results suggest a relative shift away from local, segregated information processing, measured by complexity at fine timescales, in the short term, potentially in favour of a higher long-range communication across networks, as indicated by higher complexity measures at coarse timescales in the long term. Further research into the modulation of multiscale temporal complexity by antidepressant treatments could open new possibilities for faster-acting and more efficient treatments.

摘要： This narrative review discusses the current landscape of glucagon-like peptide-1 therapies in the context of alcohol and other substance use disorders, mental health considerations, and gaps and opportunities in this field. ImportanceGlucagon-like peptide-1 (GLP-1) therapies have revolutionized the management of chronic conditions like obesity and diabetes. Consistent with the overlap between feeding and metabolic pathways and those mediating addictive behaviors, growing evidence suggests that GLP-1 therapies may also be beneficial for treating alcohol and other substance use disorders (ASUDs). This review discusses the current landscape of GLP-1 therapies in the context of ASUDs, mental health considerations, and gaps and opportunities in this *** evidence across several experimental models and species consistently shows that GLP-1 receptor agonists (GLP-1RAs) reduce drug intake and other addictive behaviors. Research to date has primarily focused on alcohol;however, nicotine, opioids, and psychostimulants have also been studied. Observational cohort studies using electronic health records suggest improvements in ASUD-related outcomes among people treated with GLP-1RAs for other indications. Randomized clinical trials (RCTs) have been limited, yielding mixed results but overall promising signals. Several RCTs are ongoing or about to start. Despite some early pharmacovigilance alarms, GLP-1RAs do not seem to cause or increase the risk of psychopathology (eg, depression, suicidal ideation and/or behavior). Some recent studies suggest beneficial effects of GLP-1RAs on mental health outcomes, but more work is *** and RelevanceThe rationale for studying GLP-1 therapies for ASUDs is supported by preclinical and observational clinical evidence. RCTs are emerging and critically needed at this juncture to determine the safety and efficacy of GLP-1 therapies in people with ASUDs. Pending results from RCTs, GLP-1 therapies have the pot

关键词： galaxies: evolution   galaxies: formation   galaxies: general   galaxies: kinematics and dynamics   galaxies: nuclei   galaxies: supermassive black holes  

摘要： Current spatially resolved kinematic measurements of supermassive black hole (SMBH) masses are largely confined to the local Universe (distances less than or similar to 100 Mpc). We investigate the potential of the Extremely Large Telescope's (ELT) first-light instruments, MICADO and HARMONI, to extend these dynamical measurements to galaxies at redshift 1 less than or similar to z less than or similar to 2 . We select a sample of five bright, massive, quiescent galaxies at these redshifts, adopting their S & eacute;rsic profiles, from HST photometry, as their intrinsic surface brightness distributions. Based on these intrinsic models, we generate mock MICADO images using SIMCADO and mock HARMONI integral-field spectroscopic data cubes using HSIM. The HAR-MONI simulations utilize input stellar kinematics derived from Jeans Anisotropic Models (JAM). We then process these mock observations: the simulated MICADO images are fitted with Multi-Gaussian Expansion (MGE) to derive stellar mass models, and stellar kinematics are extracted from mock HARMONI cubes with PPXF. Finally, these derived stellar mass models and kinematics are used to constrain JAM dynamical models within a Bayesian framework. Our analysis demonstrates that SMBH masses can be recovered with an accuracy of similar to 10 per cent. We find that MICADO can provide detailed stellar mass models with similar to 1 hour of on-source exposure. HARMONI requires longer minimum integrations for reliable stellar kinematic measurements of SMBHs. The required on-source time scales with apparent brightness, ranging from 5-7.5 hours for galaxies at z approximate to 1(F814W, 20-20.5 mag) to 5 hours for galaxies at 1 < z less than or similar to 2 (F160W, 20.8 mag). These findings highlight the ELT's capability to push the frontier of SMBH mass measurements to z approximate to 2 , enabling crucial tests of SMBH-galaxy co-evolution at the top end of the galaxies mass function.

关键词： E)-N'-(2-(2-hydroxynaphthalen-1-yl)ethylidene)-2,5-diphenyl-2H-1,2,3-triazole-4-carbohydrazide   Fluorescent probe   Aluminium ions   Biological applications  

摘要： In this study, a novel fluorescent "turn-on" probe, (E)-N'-(2-(2-hydroxynaphthalen-1-yl) ethylidene)-2,5-diphenyl-2 H-1,2,3-triazole-4-carbohydrazide (G4), was designed and synthesized, and fully characterized by various analytical techniques. Spectroscopic investigations revealed that G4 exhibits excellent selectivity and sensitivity toward Al3+, with a 1:1 binding stoichiometry and a detection limit of 1.623 nM. Its advantages over existing probes include the lower detection limit and a distinct color reaction under UV light, which facilitates straightforward qualitative detection with lower cytotoxicity. The sensing mechanism was elucidated through density functional theory (DFT) and quantum chemical calculations. Then the practical utility of G4 was demonstrated through recovery experiments in real water samples and its development into a portable test kit. Furthermore, cell experiments and zebrafish imaging confirmed its biocompatibility and applicability in biological systems with lower cytotoxicity. As a candidate drug that may be developed and utilized, the interactions of G4 with two serum proteins (HSA and HIgG) were also investigated through spectrofluorometric and molecular docking analysis, revealing hydrogen bond or van der Waals forces as the main mode of action, suggesting potential for further biomedical applications. These results highlight G4 as a highly sensitive, selective, and dual-functional fluorescent probe with significant potential for environmental monitoring and biological sensing.

关键词： diabetes mellitus type 1   disease management   health-related quality of life   social support   stress   treatment adherence  

摘要： Aims To examine the associations among diabetes-related stress, treatment adherence, perceived social support, and health-related quality of life (HRQoL) in adults with type 1 diabetes mellitus (DM1), and to explore the mediating roles of support and adherence in this *** A cross-sectional observational study using self-report standardised measures and mediation *** A total of 772 Spanish adults with DM1 completed validated instruments measuring diabetes-related distress, perceived social support, treatment adherence, and HRQoL. Hierarchical multiple regression and serial mediation analysis (PROCESS Model 6, 10,000 bootstraps) were conducted, controlling for age, sex, and time since *** Sources Not applicable (primary data collection, not a review).Results Diabetes-related stress was the strongest predictor of lower HRQoL. Perceived social support and treatment adherence also contributed significantly. Mediation analyses indicated that the impact of stress on HRQoL was partially mediated by perceived social support and, in sequence, by treatment adherence. The indirect path through social support alone and the sequential path involving both mediators were *** Stress and social support are critical in understanding and improving HRQoL in adults with DM1. Treatment adherence appears to be influenced by perceived support, highlighting an indirect mechanism linking stress to quality of *** for the Profession and/or Patient Care Healthcare professionals should integrate psychosocial assessments and interventions into routine diabetes care. Targeting stress reduction and enhancing social support may improve adherence and overall well-being in adults with *** What problem did the study address? The study addressed the need to understand how psychosocial factors-specifically stress, perceived social support, and treatment adherence-contribute to HRQoL in adults with DM1. While prior research oft