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Intranasal dopamine stabilizes prefrontal cortical CaMKIIα-positive neuronal population dynamics during object discrimination
Abstract Dopamine (DA) is a key modulator of prefrontal cortex function, yet how distinct dopaminergic states shape the temporal organization of cortical population activity during behavior remains poorly understood. We combined in vivo fiber photometry of dorsomedial prefrontal cortex (dmPFC) putative glutamatergic neurons with an object-based attention (OBAT) task in male mice to examine this question. Intranasal DA (IN-DA), which accesses the brain directly via nose-to-brain pathways, left locomotion and exploratory behavior unchanged. Although both vehicle- and IN-DA- treated mice showed a preference for the novel object, this preference reached statistical significance only in the IN-DA group. IN-DA selectively amplified calcium activity within the familiar-object zone and enhanced movement-normalized calcium spike rates. Strikingly, IN-DA reduced both the mean and variability of calcium transient intervals, reflecting a shift toward more frequent and temporally regular events during object processing. To model the network consequences of supraphysiological dopaminergic drive, we administered the psychostimulant amphetamine as a proxy for dopaminergic excess. In contrast to the stabilizing effects of IN-DA, amphetamine induced locomotor hyperactivity accompanied by a collapse of temporal structure, characterized by prolonged inter-transient intervals and markedly increased variability. Together, these findings demonstrate that dopaminergic modulation shapes not only the magnitude but also the temporal organization of dmPFC population activity. At the network level, physiological DA promotes a temporally stable prefrontal state, whereas dopaminergic excess destabilizes it. This provides population-level evidence for the inverted-U relationship between DA signaling and prefrontal function.
UHRF1-regulated aerobic glycolysis mediates TOX lactylation to induce CD8⁺ T cell exhaustion in laryngeal cancer
Pharmacokinetics, bioequivalence, and safety of two formulations of Toremifene citrate tablets in healthy Chinese participants under fasted and fed conditions
Hypoglycemic exposure and glycemic variability are associated with surgical site infection after cardiac surgery
Increasing rainwater use efficiency and seed yield of chickpea and lentil using plastic mulch
Scalable Poisson regression via divide and recombine with asymptotic theory, Monte Carlo simulation, and application to cardiovascular risk factor burden in BRFSS
The effect of RISA on push out bond strength of an epoxy resin sealer and a bioceramic sealer: an in vitro study
Abstract This study aimed to evaluate the effect of Reduced Ionic Strength Agent (RISA), used as a final irrigant, on the push-out bond strength of resin-based and bioceramic root canal sealers compared with ethylenediaminetetraacetic acid (EDTA). Sixty extracted single-rooted mandibular premolars were prepared using Reciproc R40 instruments and randomly assigned to four groups according to the final irrigation protocol and sealer type: EDTA–resin, EDTA–bioceramic, RISA–resin, and RISA–bioceramic. After obturation using the single-cone technique, one 1-mm-thick slice was obtained from the middle third of each root. Push-out bond strength was measured using a universal testing machine. Data were analyzed using two-way analysis of variance and Bonferroni-adjusted post hoc tests. Failure modes were assessed under a stereomicroscope and compared using the chi-square test. The RISA–bioceramic group exhibited the highest mean push-out bond strength, whereas the EDTA–resin group showed the lowest mean value. Two-way ANOVA revealed significant main effects of both final irrigant and sealer type on push-out bond strength ( p < 0.001). Overall, RISA resulted in higher bond strength values than EDTA, and the tested bioceramic sealer exhibited higher bond strength than the tested epoxy resin-based sealer. No significant interaction was observed between irrigation protocol and sealer type. Failure mode distributions were predominantly mixed and did not differ significantly among the groups. Within the limitations of this in vitro study, RISA resulted in higher overall push-out bond strength than EDTA. Although these findings suggest that RISA may have the potential to enhance sealer adhesion, further studies incorporating aging protocols and clinically relevant experimental conditions are needed to determine the long-term durability and clinical relevance of the observed bond-strength advantage.
Nicotinamide in a model of osteoarthritis: mechanism of analgesic action and its effect on cognition and reduction of oxidative stress in the rat heart
Correction: Pilot tests of continuous gas extraction with improved L-shaped wells from mining and goaf areas
Correction: Exploring the spatiotemporal evolution and spatial correlation network characteristics of cultivated land carbon emissions in China
Pharmaceutical payments to Australian health care professionals from 2015 to 2024
The generative creation in new media art under diffusion and ControlNet
Neuro-symbolic constraint verification for LLM-driven internet finance transaction execution
Abstract Large language model (LLM) agents cannot guarantee that their outputs satisfy the hard business rules that govern financial transactions. We present the Verifier-Actor Neuro-Symbolic Framework ( VA-NSF ), a dual-layer architecture that separates natural language understanding from formal constraint enforcement for internet finance transaction execution. A neural Actor parses financial instructions into a typed, schema-grounded abstract syntax tree (AST) through grammar-constrained decoding, and a symbolic Verifier evaluates each AST against Answer Set Programming (ASP) integrity constraints, issuing either a formal approval certificate or a structured violation report that drives targeted repair. On FinTxBench , a curated evaluation set of 8600 annotated financial instructions spanning three complexity tiers, VA-NSF attains 91.8% overall transaction accuracy (macro-averaged across the three tiers, with 94.7%, 91.2%, and 89.6% on the Simple, Compound, and Constrained tiers) at a constraint violation rate of at most 0.3%. It thereby outperforms four LLM baselines by 13 to 51 percentage points and reduces violations 30-fold, all within a median latency of 399 ms, of which ASP verification accounts for only 24 ms. Ablations confirm that each component contributes independently, and cross-domain experiments on payment processing, procurement, payroll, and inventory modules show at most 5.8 percentage points of degradation. All formal guarantees are relative to the fidelity of the encoded rule set, and the evaluation uses a curated benchmark with up to 80 rules; we therefore discuss explicitly the resulting limitations regarding noisy real-world language, rule-set scale, and human-escalation overhead.
Evaluation of plastid and nuclear DNA barcode regions for identifying gypsum endemic plants in Semnan Province, Iran
Geometric closure of classical nucleation theory for magnetic-field-controlled nanoparticle size across magnetic classes
Frequency-aware high-precision formation control of unmanned surface vehicle clusters
Undiagnosed hypertension and its determinants among adults in Rwanda in the 2021–2022 WHO STEPS survey
Abstract Hypertension remains a major public health concern in Rwanda, yet many affected adults remain undiagnosed. This study examined the extent and determinants of undiagnosed hypertension using data from the nationally representative 2021–2022 Rwanda STEPS Survey. A total of 1,223 adults aged 18–69 years who met clinical criteria for hypertension were included in this cross-sectional analysis. Survey-adjusted multivariable binary logistic regression was used to identify factors associated with being undiagnosed. Overall, 42.9% (95% CI: 39.1–46.9; n = 524 ) of hypertensive adults were unaware of their condition. Younger adults were significantly more likely to be undiagnosed, particularly those aged 18–24 years (AOR = 2.9, 95% CI: 1.30–6.30, p = 0.009) and 25–34 years (AOR = 1.9, 95% CI: 1.11–3.20, p = 0.020). Men had more than double the odds of being undiagnosed compared with women (AOR = 2.7, 95% CI: 1.82–3.96, p < 0.001). Higher education was protective, while residents of the Western Province showed elevated odds (AOR = 1.8, 95% CI: 1.07–3.05, p = 0.026). Not visiting a health worker in the past year was the strongest predictor of remaining undiagnosed (AOR = 3.2, 95% CI: 2.33–4.51, p < 0.001). These findings highlight the need to expand routine blood pressure screening to younger adults and men, and to strengthen community-based detection efforts across Rwanda.
Metformin combined with chemotherapy improved the treatment response of patients with high-grade B-cell lymphoma and diffuse large B-cell lymphoma
Abstract High-grade B-cell lymphomas (HGBCL) with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/TH) are aggressive and often resistant to standard chemotherapy, and metformin has shown promising anti-lymphoma effects. This study evaluated how lactate dehydrogenase (LDH), albumin (ALB), and oncogene expression levels affect outcomes in HGBCL and diffuse large B-cell lymphoma (DLBCL), and assessed the impact of adding metformin to chemotherapy. This prospective study, conducted between 2021 and 2024, involved HGBCL and DLBCL patients, of which 162 patients with DLBCL and 120 with DTH-HGBL were analyzed, focusing on their diabetes status and metformin use. Patients received 8 cycles of either CHOP or R-CHOP chemotherapy, and metformin use was monitored. Treatment response was evaluated after completion, with a median follow-up of 3 years. Serum levels of LDH and albumin were measured. Additionally, tissue samples were prepared and stained to detect bcl-2, c-myc, and bcl-6 proteins using immunohistochemistry. Among 282 lymphoma patients, 60–68% achieved complete remission, with better survival linked to 60.63% lower LDH, 68.08% higher ALB, and negative oncogene markers. Diabetic patients on metformin showed the best overall survival (OS), while those not on metformin had the worst ( p = 0.05). Metformin maintenance in diabetic lymphoma patients was linked to lower LDH (79.07%), higher ALB (86.04%), fewer relapses, and better survival (51.16%), in DTH-HGBCL patients, compared to those not on metformin. In 259 lymphoma patients, high c-myc and bcl-2/bcl-6 expression was linked to poorer treatment response and survival ( p < 0.001). Adding metformin to chemotherapy improved remission rates and 3-year survival, especially in patients with these protein expressions ( p < 0.001), suggesting metformin helps overcome chemotherapy resistance in high-risk cases. The study found that metformin improves remission and survival rates in high-risk lymphoma patients, and in diabetic DLBCL and DTH-HGBCL patients. It suggests metformin may be a helpful addition to standard lymphoma treatments.