Boosting cuckoo optimization algorithm via Gaussian mixture model for optimal power flow problem in a hybrid power system with solar and wind renewable energies.

This paper presents a novel approach, the Gaussian Mixture Method-enhanced Cuckoo Optimization Algorithm (GMMCOA), designed to optimize power flow decision parameters, with a specific focus on minimizing fuel cost, emissions, network loss, and voltage deviation. GMMCOA integrates the strengths of COA and GMM while mitigating their individual limitations. While COA offers robust search capabilities, it suffers from initial parameter dependency and the risk of getting trapped in local optima. Conversely, GMM delivers high-speed performance but requires guidance to identify the best solution. By combining these methods, GMMCOA achieves an intelligent approach characterized by reduced parameter dependence and enhanced convergence speed. The effectiveness of GMMCOA is demonstrated through extensive testing on both the IEEE 30-bus and the large-scale 118-bus test systems. Notably, for the 118-bus test system, GMMCOA achieved a minimum cost of $129,534.7529 per hour and $103,382.9225 per hour in cases with and without the consideration of renewable energies, respectively, surpassing outcomes produced by alternative algorithms. Furthermore, the proposed method is benchmarked against the CEC 2017 test functions. Comparative analysis with state-of-the-art algorithms, under consistent conditions, highlights the superior performance of GMMCOA across various optimization functions. Remarkably, GMMCOA consistently outperforms its competitors, as evidenced by simulation results and Friedman examination outcomes. With its remarkable performance across diverse functions, GMMCOA emerges as the preferred choice for solving optimization problems, emphasizing its potential for real-world applications.

Efficacy, reactogenicity, and safety of the adjuvanted recombinant zoster vaccine for the prevention of herpes zoster in Chinese adults ≥ 50 years: A randomized, placebo-controlled trial.

Phase III multi-country studies (ZOE-50/70) demonstrated that the adjuvanted recombinant zoster vaccine (RZV) was well tolerated and prevented herpes zoster (HZ) in healthy ≥ 50-year-olds, with a vaccine efficacy (VE) > 90% across age groups. These pivotal trials did not enroll participants from mainland China where RZV is licensed, therefore similar clinical data are missing for this population. In this phase IV observer-blind study (NCT04869982) conducted between 2021 and 2023 in China, immunocompetent and medically stable ≥ 50-year-olds were randomized 1:1 to receive two RZV or placebo doses, 2 months apart. This study assessed the VE (overall, as confirmatory objective, and descriptively by age category [50-69-year-olds/≥ 70-year-olds]), reactogenicity, and safety of RZV in this Chinese population. Of the 6138 enrolled participants, 99.2% completed the study. During a mean follow-up period of 15.2 (±1.1) months, 31 HZ episodes were confirmed (RZV = 0; placebo = 31) for an incidence rate of 0.0 vs 8.2 per 1000 person-years and an overall VE of 100% (89.82-100). The descriptive VE was 100% (85.29-100) for 50-69-year-olds and 100% (60.90-100) for ≥ 70-year-olds. Solicited adverse events (AEs) were more frequent in the RZV vs the placebo group (median duration: 1-3 days for both groups). Pain and fatigue were the most frequent local and general AEs (RZV: 72.1% and 43.4%; placebo: 9.2% and 5.3%). The frequencies of unsolicited AEs, serious AEs, potential immune-mediated diseases, and deaths were similar between both groups. RZV is well tolerated and efficacious in preventing HZ in Chinese ≥ 50-year-olds, consistent with efficacy studies including worldwide populations with similar age and medical characteristics.

What is the context? Herpes zoster, commonly known as shingles, is a painful rash resulting from the reactivation of the dormant virus causing chickenpox.Vaccines preventing shingles, such as Shingrix, were shown to be well tolerated and efficacious in healthy adults over 50 years of age from Europe, North and Latin America, Australia, and Asia (Taiwan, Hong Kong, Korea, Japan).However, data on real-world protective effect of Shingrix are limited in some regions where the vaccine is licensed for use, such as mainland China.What is new? We analyzed data from Chinese adults aged 50 years or older to determine the efficacy and safety of Shingrix.Around 6000 participants were divided in two equal groups to receive two doses of Shingrix or two doses of a placebo, given 2 months apart.We found that, during the study period, the vaccine was 100% efficacious in preventing shingles.We showed that the vaccine had an acceptable safety profile in this Chinese population.What is the impact? Shingrix is efficacious and well tolerated in Chinese adults over 50 years of age, as it is in similarly aged populations from other evaluated regions.

Knowledge, Attitude, and Practice of Organ Donation Among the Population of Al-Majma'ah Region, Saudi Arabia.

BACKGROUND: Organ donation plays a pivotal role in addressing the global demand for transplantable organs and saving lives. The success of organ transplantation relies not only on medical advancements but also on the willingness of communities to participate in organ donation programs. In Saudi Arabia, specifically within the Al-Majma'ah region, understanding the dynamics of knowledge, attitudes, and practices related to organ donation is crucial for promoting a sustainable and ethical organ donation system. METHODS: A cross-sectional, retrospective study was utilized in this research, employing data from a sample of 564 participants from the general population of the Al-Majma'ah region, Saudi Arabia. The participants completed a self-administered questionnaire and ensured anonymity. RESULTS: About 545 (96.6%) respondents were familiar with the concept of organ donation, and 455 (80.7%) participants recognized the necessity for the blood groups of the donor and recipient to match before the transplant process. About 412 (73.0%) participants agreed with the practice of organ donation with 326 (57.8%) expressing support for the practice. About 417 (73.9%) participants reported that their religion permits or endorses organ donation/transplantation. A total of 151 individuals (26.8%) had a low knowledge level, with total scores below 50% (6 or lower). In contrast, 280 people (4.7%) demonstrated a moderate level of knowledge (scoring between 50% and 75%) (7 to 9). Additionally, 133 individuals (23.5%) showcased a high level of knowledge, with scores exceeding 75% (10 or higher). The study established a statistically significant association between age, marital status with p-values < 0.05 (0.001*), and the knowledge score toward organ donation. However, gender and monthly household income were not significantly associated with knowledge score toward organ transplant with p-values (p-value > 0.05). CONCLUSION: The research findings indicated a moderate level of knowledge and a positive attitude toward organ donation among the general population of the Al-Majma'ah region in Saudi Arabia. Age and marital status were found to be significantly associated with the knowledge score toward organ donation. The study noted the desire and willingness to save lives through organ donation by the residents of the Al-Majma'ah region in Saudi Arabia.

Hedgehog signaling mastery: R51211's promise in augmenting the therapeutic efficacy of sorafenib.

Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer.

Vascular service provision during the COVID-19 pandemic worsened major amputation rates in socially deprived diabetic populations.

Introduction: The Coronavirus Disease - 2019 (COVID-19) pandemic significantly impacted healthcare service provision and put diabetic patients at increased risk of adverse health outcomes. We aimed to assess the impact of the COVID-19 pandemic on the incidence and demographic shift of major lower-limb amputation in diabetic patients. Methods: We performed a retrospective analysis of diabetic patient records undergoing major lower-limb amputation between 01/03/2019 and 01/03/2021 at the Royal Sussex County Hospital, the regional arterial hub for Sussex. Primary outcomes were amputation incidence rates and patient demographics compared between the prepandemic and pandemic cohorts. Results: The incidence rate ratio of major lower-limb amputations shows a drop in amputations during the pandemic compared to pre-pandemic (IRR 0.82; 95% CI 0.57-1.18). Data suggests a shift in the social deprivation background of patients receiving amputations to disproportionately affect those in the more deprived 50% of the population (p=0.038). Younger patients received more amputations during the pandemic compared to prepandemic levels (p=0.001). Conclusion: Results suggest that during the COVID-19 pandemic there was a paradoxical reduction in amputations compared to prepandemic levels. However, changes to the demographic makeup of patient's receiving amputations are alarming as younger, and more deprived patients have been disproportionately affected by the pandemic.

Ion Trap LC/MS reveals the generation of reactive intermediates in acalabrutinib metabolism: phase I metabolic profiling and bioactivation pathways elucidation.

Acalabrutinib (CALQUENCE; ACB) is a Bruton tyrosine kinase inhibitor (BTKI) used to treat mantle cell lymphoma, small lymphocytic lymphoma (SLL), and chronic lymphocytic leukemia (CLL). On 21 November 2019, ACB was approved by the U.S. FDA for the use as a single therapy for the treatment of CLL/SLL. In silico studies were first done to propose vulnerable sites of metabolism and reactivity pathways by StarDrop software and Xenosite online software; respectively. ACB metabolites and stable adducts were characterized in vitro from rat liver microsomes (RLMs) using Ion Trap LC/MS. Generation of reactive intermediates (RIs) in the in vitro metabolism of ACB was investigated using glutathione, potassium cyanide, and methoxylamine as trapping nucleophiles for the RIs including iminopyridinone, iminium, and aldehyde, respectively, to form stable adducts that can be identified and characterized by Ion Trap LC/MS. Five phase I metabolites, seven 6-iminopyridin-3(6H)-one and five aldehyde RIs of ACB were identified. Based on literature reviews, the generation of RIs of ACB, and the subsequent drug-induced organ toxicity (DIOT) reactions may provide an explanation of ACB ADRs. Additional drug discovery investigations can be performed to facilitate the creation of novel medications with improved safety characteristics.

Bifunctional Co3O4/g-C3N4 Hetrostructures for Photoelectrochemical Water Splitting.

This study explored the synergistic potential of photoelectrochemical water splitting through bifunctional Co3O4/g-C3N4 heterostructures. This novel approach merged solar panel technology with electrochemical cell technology, obviating the need for external voltage from batteries. Scanning electron microscopy and X-ray diffraction were utilized to confirm the surface morphology and crystal structure of fabricated nanocomposites; Co3O4, Co3O4/g-C3N4, and Co3O4/Cg-C3N4. The incorporation of carbon into g-C3N4 resulted in improved catalytic activity and charge transport properties during the visible light-driven hydrogen evolution reaction and oxygen evolution reaction. Optical properties were examined using UV-visible spectroscopy, revealing a maximum absorption edge at 650 nm corresponding to a band gap of 1.31 eV for Co3O4/Cg-C3N4 resulting in enhanced light absorption. Among the three fabricated electrodes, Co3O4/Cg-C3N4 exhibited a significantly lower overpotential of 30 mV and a minimum Tafel slope of 112 mV/dec This enhanced photoelectrochemical efficiency was found due to the established Z scheme heterojunction between Co3O4 and gC3N4. This heterojunction reduced the recombination of photogenerated electron-hole pairs and thus promoted charge separation by extending visible light absorption range chronoamperometric measurements confirmed the steady current flow over time under constant potential from the solar cell, and thus it provided the effective utilization of bifunctional Co3O4/g-C3N4 heterostructures for efficient solar-driven water splitting.

Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia.

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

Germline Variants in Sporadic Pituitary Adenomas.

Context: Data on germline genetics of pituitary adenomas (PAs) using whole-exome sequencing (WES) are limited. Objective: This study investigated the germline genetic variants in patients with PAs using WES. Methods: We studied 134 consecutive functioning (80.6%) and nonfunctioning (19.4%) PAs in 61 female (45.5%) and 73 male patients (54.5%). Their median age was 34 years (range, 11-85 years) and 31 patients had microadenomas (23.0%) and 103 macroadenomas (77%). None of these patients had family history of PA or a known PA-associated syndrome. Peripheral blood DNA was isolated and whole-exome sequenced. We used American College of Medical Genetics and Genomics (ACMG) criteria and a number of in silico analysis tools to characterize genetic variant pathogenicity levels and focused on previously reported PA-associated genes. Results: We identified 35 variants of unknown significance (VUS) in 17 PA-associated genes occurring in 40 patients (29.8%). Although designated VUS by the strict ACGM criteria, they are predicted to be pathogenic by in silico analyses and their extremely low frequencies in 1000 genome, gnomAD, and the Saudi Genome Project databases. Further analysis of these variants by the Alpha Missense analysis tool yielded 8 likely pathogenic variants in 9 patients in the following genes: AIP:c.767C>T (p.S256F), CDH23:c.906G>C (p.E302D), CDH23:c.1096G>A (p.A366T), DICER1:c.620C>T (p.A207V), MLH1:c.955G>A (p.E319K), MSH2:c.148G>A (p.A50T), SDHA:c.869T>C (p.L290P) and USP48 (2 patients): c.2233G>A (p.V745M). Conclusion: This study suggests that about 6.7% of patients with apparently sporadic PAs carry likely pathogenic variants in PA-associated genes. These findings need further studies to confirm them.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Checklist for Artificial Intelligence in Medical Imaging (CLAIM): 2024 Update.

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. ©RSNA, 2024.

The association between caesarean section delivery and obesity at age 17 years. Evidence from a longitudinal cohort study in the United Kingdom.

BACKGROUND: Childhood and adolescent obesity are major, preventable public health concerns. Studies to date are inconclusive regarding an association between caesarean section (CS) delivery and offspring obesity, with fewer studies conducted in late adolescence. This study examined the association between CS delivery, with a specific focus on planned CS, and induction of labour and adolescent body mass index (BMI) and body fat percentage (BF%) at age 17 years. METHODS: Data on 8,880 mother-child pairs from the United Kingdom Millennium Cohort Study were analysed. The exposures were mode of delivery (normal vaginal delivery (VD) (reference), assisted VD, planned CS and emergency CS) and mode of delivery by induction of labour status. Crude and adjusted binary logistic regression and linear regression models were fitted examining BMI and BF% at age 17 years respectively, adjusting for several potential confounders. RESULTS: Adolescents born by CS did not have an elevated BMI or BF% compared to those born by normal VD. The fully adjusted results for overweight and obesity in children born by planned CS, compared to VD, were 1.05 (95% CI: 0.86-1.28) and 0.94 (95% CI: 0.72-1.23), respectively. The results were similar for the associations between CS and BF%, and between induction of labour and BMI. CONCLUSION: Overall, this large longitudinal study did not support an association between CS or induction of labour and overweight, obesity or BF%. It is possible that previously reported associations are due to residual or unmeasured confounding and/or underlying indications for CS delivery.

Origins and diversity of pan-isotype human bone marrow plasma cells.

Bone marrow plasma cells (BMPCs) produce durable, protective IgM, IgG, and IgA antibodies, and in some cases, pro-allergic IgE antibodies, but their properties and sources are unclear. We charted single BMPC transcriptional and clonal heterogeneity in food-allergic and non-allergic individuals across CD19 protein expression given its inverse correlation to BMPC longevity. Transcriptional and clonal diversity revealed distinct functional profiles. Additionally, distribution of somatic hypermutation and intraclonal antibody sequence variance suggest that CD19low and CD19high BMPCs arise from recalled memory and germinal center B cells, respectively. Most IgE BMPCs were from peanut-allergic individuals; two out of 32 from independent donors bound peanut antigens in vitro and in vivo. These findings shed light on BMPC origins and highlight the bone marrow as a source of pathogenic IgE in peanut allergy.