Tag: pubmed

Prostate Cancer Prostatic Dis. 2025 Nov 21. doi: 10.1038/s41391-025-01053-9. Online ahead of print.

ABSTRACT

BACKGROUND: AI is increasingly integrated within prostate cancer diagnosis pathway.

PURPOSE: To provide estimates of diagnostic accuracy of AI assistance for clinically significant prostate cancer (csPCa) via MRI.

MATERIALS AND METHODS: A systematic search of PubMed, Embase, Cochrane, Scopus and Web of Science from January 2017 to October 2024 was performed for studies on the diagnostic utility of AI for prostate MRI. Diagnostic performance metrics were synthesized through hierarchical summary receiver operating characteristic modeling with random-effects assumptions. Specially, to test inferiority and potential superiority of AI, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), cancer detection rate (CDR), and accuracy was pairwisely compared between AI and radiologists in study level using odds ratios (ORs) with Z-statistics.

RESULTS: 7398 patients from 29 studies with AI-vs-human pairwise comparison were included. When acting as an assistant to human readers, AI demonstrated superior performance compared to stand-alone human readers in diagnosing csPCa via MRI, specifically with higher sensitivity (86.5% vs 82.6%, P = 0.001), specificity (57.8% vs 50.0%, P = 0.028), PPV (64.3% vs 58.9%, P = 0.001), and NPV (82.9% vs 76.5%, P = 0.001) while maintaining comparable CDR (40.5% vs 38.6%, P = 0.093). When used as standalone readers, AI exhibited higher specificity (58.7% vs 48.7%, P = 0.026) but at the cost of reduced sensitivity (87.2% vs 90.1%, P = 0.017). Subgroup analysis indicated that readers of varying experience levels could all improve their diagnostic performance with AI assistance.

CONCLUSION: Integrating AI as an assistant in csPCa diagnostic workflows could enhance accuracy, particularly for less experienced readers.

CLINICAL TRIAL REGISTRATION INFORMATION: Trial Name: The efficiency comparison of radiologists with or without assistance of artificial intelligence in prostate cancer diagnosis: a meta-analysis. Registration date: April 17, 2024.

REGISTRATION NUMBER: CRD42024533016. Registration information available at: https://www.crd.york.ac.uk/PROSPERO/ .

PMID:41272268 | DOI:10.1038/s41391-025-01053-9

CNS Drugs. 2025 Nov 21. doi: 10.1007/s40263-025-01240-1. Online ahead of print.

ABSTRACT

BACKGROUND: Long-acting injectable antipsychotic (LAI) treatment is associated with improved adherence and reduced relapse and hospitalization rates, compared with oral antipsychotics, in patients with schizophrenia. TV-46000, an LAI formulation of risperidone, is approved for the treatment of schizophrenia in adults. TV-46000 administered once monthly (q1m) and once every 2 months (q2m) has previously been shown to be effective and safe in patients with schizophrenia in the phase 3 studies, RISE and SHINE. Here, the effect of long-term treatment with TV-46000 on psychopathological symptoms and severity of illness was evaluated.

METHODS: In RISE, patients were stabilized on oral risperidone for 12 weeks before randomization to subcutaneous treatment with TV-46000 q1m, q2m, or placebo (1:1:1) until study endpoint. Patients who successfully completed RISE (placebo and TV-46000 rollover cohorts) and newly recruited patients (de novo cohort) were eligible to enroll in SHINE to receive TV-46000 q1m or q2m for up to 56 weeks. Symptom severity was evaluated with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions-Severity (CGI-S) scale, and the Clinical Global Impressions-Improvement (CGI-I) scale, as prespecified exploratory endpoints from the RISE and SHINE studies.

RESULTS: Overall, 543 adult patients were enrolled in RISE (TV-46000 q1m, n = 183; q2m, n = 179; placebo, n = 181) and 333 in SHINE (TV-46000 q1m, n = 173 and q2m, n = 160; source groups: de novo, n = 106; placebo rollover, n = 55; TV-46000 rollover, n = 172). In RISE, PANSS total scores decreased after randomization to end of treatment (EoT) for TV-46000 (least squares mean [LSM] change [SE], q1m: -3.5 [0.69]; q2m, -4.9 [0.73]), but increased for placebo (1.1 [0.86]; P < 0.0001 for both TV-46000 q1m and q2m versus placebo). Corresponding changes from baseline to last assessment (LA) were -0.9 (0.97) for q1m, -0.2 (0.99) for q2m, and 7.4 (0.99) for placebo; P < 0.0001 for both versus placebo. Similar results were seen for the PANSS positive and general psychopathology subscales (P < 0.001 for both TV-46000 q1m and q2m versus placebo). These symptom improvements were maintained or improved in the TV-46000 q1m and q2m groups in SHINE, with notable improvements observed in patients without prior TV-46000 exposure. Similar results were observed in RISE and SHINE when PANSS scores were categorized by Marder factors of schizophrenia symptoms. CGI-I scores at EoT and LA were significantly better with TV-46000 than with placebo in RISE (LSM at EoT and LA: 3.3 and 3.6 for TV-46000 q1m, 3.2 and 3.6 for q2m; 3.9 and 4.4 for placebo, respectively [P < 0.0001 versus placebo]). These scores were maintained in the TV-46000 groups in SHINE, with larger improvements seen in the de novo cohort than in the placebo rollover and TV-46000 rollover cohorts.

CONCLUSIONS: Treatment with TV-46000 provided sustained overall symptom improvement in the RISE and SHINE studies in patients with schizophrenia who were stabilized on oral risperidone.

CLINICAL TRIALS REGISTRATION: RISE (ClinicalTrials.gov identifier: NCT03503318) and SHINE (ClinicalTrials.gov identifier: NCT03893825).

PMID:41272239 | DOI:10.1007/s40263-025-01240-1

Sci Rep. 2025 Nov 21;15(1):41165. doi: 10.1038/s41598-025-26521-z.

ABSTRACT

Corona discharge has been recognized for centuries, with sailors reporting the bluish glow of St. Elmo’s fire on ship masts during storms. In the early development of high-voltage engineering, researchers such as Townsend and Peek described the physical basis of this phenomenon as the ionization of air around a conductor when the electric field exceeds the strength of the surrounding medium. The result is a partial discharge that produces visible light, hissing sounds, ozone, and other reactive gases, while also creating radio interference and ultraviolet radiation. In modern transmission systems, these effects appear as wasted power, accelerated wear of insulators, shortened equipment lifetime, and environmental concerns. Although corona has been studied for decades, it continues to challenge the reliable and economical operation of high-voltage networks, particularly under changing weather conditions. This study investigates the phenomenon by analyzing its causes, effects, and mitigation strategies through a combination of theoretical modelling, simulation, and statistical analysis. Using MATLAB Simulink and Python, simulations were conducted under varying environmental conditions-including temperature, humidity, and pressure-as well as electrical parameters such as voltage and conductor design, using observed data to ensure practical relevance. Comparable data sources may be used in other national or regional contexts. Key statistical techniques, including linear and multiple regression, analysis of variance (ANOVA), t-tests, and Monte Carlo simulations, were applied to determine the most influential factors affecting corona discharge losses. Results confirmed that higher voltage levels and unfavorable environmental conditions significantly increase corona loss, while increased conductor spacing and the use of corona rings emerged as the most effective mitigation strategies. An economic analysis based on probabilistic modelling estimated potential annual savings of up to 455 million Egyptian pounds (EGP) for the Egyptian grid, serving as a representative case study. The analytical framework is general and can be applied to other national transmission systems with appropriate data. The findings offer data-driven insights for improving transmission efficiency, minimizing power losses, and enhancing the overall reliability and cost-effectiveness of high-voltage power systems.

PMID:41272217 | DOI:10.1038/s41598-025-26521-z

Surg Radiol Anat. 2025 Nov 21;48(1):9. doi: 10.1007/s00276-025-03778-7.

ABSTRACT

This study constructed a statistical shape model (SSM) of the full ankle joint-including the tibia, talus, calcaneus, and fibula-in healthy Chinese males and analyzed the variation patterns of joint space width (JSW). Computed tomography scans of 108 asymptomatic ankle joints were collected from healthy Chinese males and used to construct a statistical shape model based on principal component analysis. Anatomical variations were evaluated using spatial mapping and least-squares regression. The statistical shape model satisfied the validation criteria for accuracy, compactness, generalization, and specificity, and participants demonstrated high conformity in joint surface coverage and congruency. The first principal component explained more than 22% of the total variance. The minimum joint space widths for the tibiotalar, talofibular, and talocalcaneal joints ranged from 0.85 to 1.95 mm, 0.87 to 2.39 mm, and 0.90 to 3.32 mm, respectively, while the average joint space widths ranged from 2.81 to 3.35 mm, 1.36 to 3.36 mm, and 2.12 to 4.95 mm, respectively. Regression analysis showed that the first five principal modes of variation were strongly correlated with anatomical variations in ankle JSW. This study will provide theoretical support for the early diagnosis and personalized treatment of ankle joint diseases, as well as important morphological references for prosthesis design and biomechanical simulation research.

PMID:41272216 | DOI:10.1007/s00276-025-03778-7

Sci Rep. 2025 Nov 21;15(1):41186. doi: 10.1038/s41598-025-28886-7.

ABSTRACT

Additive manufacturing based on photopolymer resins requires additional light curing during postprocessing to achieve the final mechanical properties. The present in-vitro study aimed to evaluate the impact of the curing temperature during postprocessing on the fracture resistance and accuracy of both additively manufactured four-unit fixed dental prostheses (FDPs) and bar-shaped, ISO-conform specimens. All samples were fabricated by either additive manufacturing using two different light-curing resins or subtractive manufacturing using polymethyl methacrylate. Three different curing temperatures were evaluated (40 °C, 60 °C, 80 °C). All bars (n = 136) were subjected to a three-point bending test after 68 of them had been stored in water for 24 h. All bridges (n = 90) were analyzed for dimensional accuracy and afterwards subjected to static loading until fracture. Additively manufactured bar-shaped specimens exhibited significantly higher flexural strength compared to the subtractively manufactured counterparts. In contrast, all but one group (p = 0.082) of the additively manufactured four-unit FDPs demonstrated significantly lower fracture strength than the subtractively manufactured bridges (p < 0.024). Post-curing temperature had no significant effect on accuracy for the temporary resin (p > 0.469), whereas the permanent resin showed significant differences for some regions of interest and temperature combinations. For the recommended curing duration of 40 min, the lowest tested curing temperature of 40 °C already resulted in a sufficient degree of cure and mechanical properties with no general benefit to higher curing temperatures, indicating their use to be unnecessary.

PMID:41272215 | DOI:10.1038/s41598-025-28886-7

Diabetologia. 2025 Nov 21. doi: 10.1007/s00125-025-06593-2. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become an important option in clinical use for type 2 diabetes due to their dual benefits of glycaemic management and metabolic improvements. Efsubaglutide alfa, a novel long-acting GLP-1RA, was developed for sustained glycaemic management. This study aimed to confirm its recommended clinical dose and evaluate its efficacy and safety in drug-naive individuals with type 2 diabetes that was inadequately managed through lifestyle interventions.

METHODS: This two-stage Phase IIb/III trial employed an operationally seamless adaptive design and enrolled adults who had been newly diagnosed with type 2 diabetes and whose diabetes was inadequately managed by diet and exercise. In the Phase IIb stage, participants were randomised in a 2:2:2:1 ratio to receive once-weekly subcutaneous injections of efsubaglutide alfa (1, 2 or 3 mg) or placebo for 12 weeks. Based on an interim analysis, two recommended Phase III doses (RP3Ds) were selected by an independent data monitoring committee. In the Phase III stage, participants were randomised in a 2:2:1 ratio to receive efsubaglutide alfa at one of the two RP3Ds or to receive placebo. Participants, investigators and sponsors were masked to drug/placebo allocation throughout the trial. The primary endpoint was the change in HbA_1c from baseline to week 24. Secondary endpoints included changes in body weight and metabolic parameters at weeks 24 and 52. Safety was monitored throughout.

RESULTS: In the Phase IIb stage, 140 participants were randomised to efsubaglutide alfa (1 mg, n=41; 2 mg, n=39; 3 mg, n=41) or placebo (n=19). Based on interim analysis, 1 and 3 mg were selected as the RP3Ds. In the Phase III stage, 297 participants were randomised to efsubaglutide alfa (1 mg, n=118; 3 mg, n=117) or placebo (n=62). At week 24, the HbA_1c reductions from baseline were -18.91 mmol/mol (1.73%) (95% CI -20.98, -16.83) with the 1 mg dose, and -23.50 mmol/mol (2.15%) (95% CI -25.68, -21.31) with 3 mg. The estimated treatment difference vs placebo was -13.71 mmol/mol (-1.26%) (95% CI -17.39, -10.06) for the 1 mg dose and -18.36 mmol/mol (-1.68%) (95% CI -22.08, -14.64) for 3 mg. Additionally, 56% of participants receiving the 1 mg dose (95% CI 47, 65; p<0.001) and 68% of participants receiving the 3 mg dose (95% CI 59, 76; p<0.001) achieved an HbA_1c <53.0 mmol/mol (7.0%). There were significant reductions of fasting plasma glucose from baseline: 2.04 mmol/l (95% CI -2.40, -1.68) for the 1 mg dose, and 2.49 mmol/l (95% CI -2.87, -2.11) for 3 mg (estimated treatment difference vs placebo: -1.71 mmol/l [95% CI-2.34, -1.07] for the 1 mg dose, and -2.16 mmol/l [95% CI -2.80, -1.52] for 3 mg). There were also significant reductions in 2 h postprandial plasma glucose compared with the baseline: 3.7 mmol/l (95% CI -4.42, -3.03] for the 1 mg dose, and 4.6 mmol/l (95% CI -5.36, -3.86) for 3 mg (estimated treatment difference vs placebo: -3.2 mmol/l [95% CI -4.41, -1.98] for the 1 mg dose, and -4.1 mmol/l [95% CI -5.28, -2.88] for 3 mg). Body weight decreased by 0.97% (95% CI -1.76, -0.18) with the 1 mg dose and by 3.14% (95% CI -3.98, -2.31) with 3 mg (estimated treatment difference vs placebo: 0.97% [95% CI -0.41, 2.35] for the 1 mg dose, and -2.18% [95% CI -3.30, -1.05] for 3 mg). Gastrointestinal symptoms, including nausea, vomiting, diarrhoea and decreased appetite, were the most common adverse events, and were mostly mild to moderate in severity.

CONCLUSIONS/INTERPRETATION: Efsubaglutide alfa significantly improved glycaemic management and promoted weight loss in drug-naive individuals with type 2 diabetes, with a favourable safety profile. These results establish efsubaglutide alfa as a promising therapeutic option for type 2 diabetes and related metabolic disorders.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04994288 FUNDING: This study was sponsored by Innogen Pharmaceutical Co. Ltd.

PMID:41272211 | DOI:10.1007/s00125-025-06593-2

Support Care Cancer. 2025 Nov 21;33(12):1110. doi: 10.1007/s00520-025-10144-1.

ABSTRACT

PURPOSE: Lymphoma survivors face long-term treatment-related side effects that impact their quality of life (QOL) and needs. Yet, evidence on their specific challenges in the five years following diagnosis remains limited. Existing research has often examined unmet needs and QOL separately or within broader cancer populations, lacking a comprehensive analysis of their interconnections. This study explored the link between lymphoma survivors’ unmet needs and quality of life.

METHODS: A cross-sectional survey study recruited lymphoma survivors from the outpatient haematology-oncology services of five hospitals. The questionnaire comprised validated instruments for unmet needs (Short-Form Survivor Unmet Needs) and QOL (FACT-LYM and EQ 5D-5L). Descriptive statistics, hierarchical multiple regression and canonical correlation analyses were performed to analyse the data.

RESULTS: A survey was completed by 205 lymphoma survivors one to five years post-diagnosis. An increase in QOL was significantly associated with decreased unmet needs. Female and younger survivors were more likely to report higher unmet needs. The top two most frequently unmet needs items were ‘dealing with feeling tired’ (72.5%, n = 145) and ‘coping with having a bad memory or lack of focus’ (67.2%, n = 135).

CONCLUSION: The relationship between unmet needs and QOL among lymphoma survivors is complex, highlighting the need to address specific unmet needs and well-being dimensions to improve longer-term outcomes. This study supports the use of instruments to measure unmet needs, which help to identify survivors who may benefit from clinical attention or enhanced supportive care. The study findings suggest that interventions targeting unmet needs could improve survivors’ QOL.

PMID:41272209 | DOI:10.1007/s00520-025-10144-1

Sci Rep. 2025 Nov 21;15(1):41398. doi: 10.1038/s41598-025-25371-z.

ABSTRACT

Hypomyelinating leukodystrophies (HLDs) are genetic disorders characterized by deficient myelination. While TMEM63A variants are associated with HLD19, the specific lipid alterations in affected brain regions remain to be fully characterized. This study aimed to investigate the spatial distribution of lipid changes in a Tmem63a mutant rat model of hypomyelination. A homozygous Tmem63a c.500G > A p.(G167E) knock-in rat model (Tmem63a^G167E/G167E) was established. Brain sections from Tmem63a^G167E/G167E and Tmem63a^WT rats (n = 3/group) were analyzed using MALDI-MSI for lipid profiling across nine distinct brain regions. Myelin structure was characterized by transmission electron microscopy (TEM) and g-ratio quantification. Statistical analyses included Mann-Whitney U tests for g-ratio distributions and ROC analysis for feature screening. Out of 702 analyzed features, 124 were differentially expressed. Lipids constituted the most altered class (43 features), including 22 glycerophospholipid, 9 fatty acid, 5 sphingolipid, 5 sterol lipid, and 2 prenol lipid species. These alterations were predominantly observed in white matter-rich regions and gray-white matter junctions. TEM revealed thinner and less dense myelin sheaths in Tmem63a^G167E/G167E rats, with a reduced proportion of optimal g-ratios. This study provides a comprehensive spatial lipidomic characterization in a Tmem63a mutant rat model, revealing significant lipid alterations associated with hypomyelination. These findings offer new insights into the pathology of hypomyelination and highlight specific lipid species for future investigation.

PMID:41272208 | DOI:10.1038/s41598-025-25371-z

Commun Chem. 2025 Nov 21. doi: 10.1038/s42004-025-01803-9. Online ahead of print.

ABSTRACT

Stereoselective synthesis of cis- and trans- configurations remain challenging in molecular systems. Here, asymmetric 90^o Pt(II) acceptors enable stereoselective coordination-driven self-assembly of configuration-specific [Pt₂L₂] metallacycles. The coordination of trimethylphosphine or triethylphosphine (PR₃) and phosphangulene (Phang) to the Pt(II) centers yielded two asymmetric cis-PtCl₂(PR₃)(Phang) complexes. Upon ligand exchange, these acceptors assemble with the bispyridyl ligands to form statistical mixtures of cis- and trans- metallacycles. Stereoselective self-assembly is achieved by modifying the bis-pyridyl ligand with N-ortho-bismethyl groups, leveraging intramolecular C-H···π interactions with Phang, steric effects, and 90^o Pt(II) heteroligation to selectively generate trans- or cis- isomers. The stereochemistry is confirmed by NMR spectrometry, investigation of the mass spectrometry, density functional theory calculations, and single-crystal X-ray diffraction. Notably, hierarchical self-assembly in the crystalline state revealed stark structural divergences between trans- and cis- metallacycles, offering key insights into stereo-controlled supramolecular design.

PMID:41272184 | DOI:10.1038/s42004-025-01803-9

Sci Rep. 2025 Nov 21;15(1):41353. doi: 10.1038/s41598-025-25329-1.

ABSTRACT

The objective of this study was to investigate symptoms after vaccination with different COVID-19 vaccines reported from employees in an Austrian University hospital. A paper-based survey was conducted among adult employees of an Austrian University Hospital after receiving a first, second or booster dose of a COVID-19 vaccine during January 2021 and January 2022 to identify any side effects reported by participants. The survey further inquired about the participants’ demographic information, sick leave or hospitalisation due to the symptoms. Out of the approximately 5000 persons who have been vaccinated, 1093 participants completed the survey. A total of 818 of 1029 employees (79%) reported symptoms after the first, 613 of 1007 employees (61%) reported symptoms after the second and a total of 814 of 974 employees (84%) reported symptoms after booster vaccination. There were differences in the type of vaccination in relation to and number of different symptoms, sick leave as well as anxiety. In conclusion, according to the COVID-19 vaccine type, different side effects might occur following the first, second and booster doses of vaccination. These findings assist in addressing problems of vaccination hesitancy.Trial registration: ClinicalTrials.gov: NCT06035926, 2023-08-28 (retroactively registered).

PMID:41272132 | DOI:10.1038/s41598-025-25329-1