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This study characterizes the steroidal saponin diosgenin by theoretical and experimental spectroscopic techniques. Theoretical simulations were performed using the DFT/B3LYP/6-311++G(d,p) basis set to simulate spectroscopic, structural and other properties. Optimized geometries from simulations and experiments showed strong agreement, with R 2 value of 0.99846 for bond lengths and 0.88092 for bond angles. Vibrational spectra revealed distinctive peaks for the methyl, methylene, and methine groups in diosgenin. Solvent-solute interactions on the Frontier Molecular Orbitals (FMO), Molecular Electrostatic Potential (MEP) surfaces, and electronic spectra were analyzed, revealing insights into diosgenin's behavior in different environments. The FMO energy gap shows that polar solvents like acetone, ethanol, and water have wider band gaps (6.22-6.23 eV) than non-polar solvents like benzene, chloroform, and toluene (6.17-6.20 eV), indicating stronger interactions with polar groups, enhanced stability, and reduced reactivity. NBO analysis shows substantial stabilization energy (14.71 kJ/mol) when electrons from oxygen's (O 1 ) lone pair are donated to the anti-bonding orbital of O 2 C 15 through the transition of LP (2) → σ*. The carbon (C 15 ) situated between oxygen (O 1 ) and (O 2 ) exhibits increased electronegativity (-1.65605 e), confirming the electronegativity of the oxygen atoms. Hirshfeld surfaces shows that the crystal structure is mainly influenced by H…H (90.7 %) interaction. Topological analyses revealed molecular interactions and chemical bonding within diosgenin, highlighting its diverse chemical functionalities. Furthermore, molecular docking and ADME predictions underscores diosgenin's potential biological activity against human hexokinase (-8.09 kcal/mol) and phosphofructokinase (-8.35 kcal/mol), suggesting its efficacy as an antitumor drug., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Survivin is an inhibitor of apoptosis, and expressed in a large number of cancers. As Survivin expression is very low in normal tissues, it assumes significance as a prominent target for tumor diagnosis, prognosis and developing anti-cancer therapies. We report development of a novel triple fusion protein for a prospective vaccine against Survivin in targeted cancer immunotherapy. A gene was synthesized by combining the nucleotides encoding human origin Survivin and heat-labile enterotoxin of Escherichia coli (LTB). Further, nucleotides corresponding to single chain variable fragment (scFv) of a monoclonal having affinity for DEC205 receptor present on dendritic cells, were also incorporated into the gene sequence. This complete gene was expressed to a triple fusion recombinant protein using a bacterial expression vector under the control of robust bacteriophage T7 promoter. The recombinant DC Survivin-LTB protein, with a size of approximately 60 kDa, was purified from the inclusion bodies using affinity based Ni-NTA columns. The purified protein was confirmed by the Western blot, and further characterized with circular dichroism, fluorescence spectroscopy and mass spectroscopy. This molecularly adjuvanted Survivin fusion protein designed to deliver to the dendritic cells for better antigen processing, elicited a stronger anti-Survivin immune response compared to Survivin protein alone. It can be an effective vaccine in active and passive immunotherapies for Survivin expressing cancer cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Currently, abdominal aortic aneurysms (AAAs) are treated based on the diameter of the aorta, however, a more robust patient-specific marker is needed. The mean thickness of the wall is a potential indicator for AAA rupture risk, which varies significantly within and between patients. So far, regional thickness has not been used in previous rupture risk analysis studies, since it is challenging to measure in CT, MRI, and non-invasive ultrasound (US). This study shows how to map locally varying wall thickness of AAAs using intravascular ultrasound (IVUS). Since no ground truth of AAA wall thickness can be obtained in vivo, a novel ex vivo dataset was created of porcine, phantom and simulated aortas, of which ground truth data are available. A U-net model was trained on the ex vivo data and results show that the predicted wall segmentation is in good agreement with the ground truth (DSC = 0.86, HD = 0.97 mm). Wall thickness and geometry plots show that the variation in wall thickness can be recognized. The in vivo demonstration in patients shows that the diseased wall can be segmented, a regionally varying wall thickness can be measured, and detailed maps of AAA geometries can be created. The measured local wall thickness could be used for better general understanding of AAA wall properties resulting in more advanced rupture risk assessment of AAAs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Blood-related infections are a significant concern in healthcare. They can lead to serious medical complications and even death if not promptly diagnosed and treated. Throughout time, medical research has sought to identify clinical factors and strategies to improve the management of these conditions. The increasing adoption of electronic health records has led to a wealth of electronically available medical information and predictive models have emerged as invaluable tools. This manuscript offers a detailed survey of machine-learning techniques used for the diagnosis and prognosis of bacteraemia, bloodstream infections, and sepsis shedding light on their efficacy, potential limitations, and the intricacies of their integration into clinical practice., Methods: This study presents a comprehensive analysis derived from a thorough search across prominent databases, namely EMBASE, Google Scholar, PubMed, Scopus, and Web of Science, spanning from their inception dates to October 25, 2023. Eligibility assessment was conducted independently by investigators, with inclusion criteria encompassing peer-reviewed articles and pertinent non-peer-reviewed literature. Clinical and technical data were meticulously extracted and integrated into a registry, facilitating a holistic examination of the subject matter. To maintain currency and comprehensiveness, readers are encouraged to contribute manuscript suggestions and/or reports for integration into this living registry., Results: While machine learning (ML) models exhibit promise in advanced disease stages such as sepsis, early stages remain underexplored due to data limitations. Biochemical markers emerge as pivotal predictors during early stages such as bacteraemia, or bloodstream infections, while vital signs assume significance in sepsis prognosis. Integrating temporal trend information into conventional machine learning models appears to enhance performance. Unfortunately, sequential deep learning models face challenges, showing minimal performance improvements and significant drops in external datasets, potentially due to learning missing patterns within the scarce data available rather than understanding disease dynamics. Real-life implementation receives limited attention, as meeting design requirements proves challenging within existing healthcare infrastructure. The data collected in an event-based fashion during clinical practice is insufficient to fully harness the potential of these data-hungry models. Despite limitations, opportunities abound in leveraging flexible models and exploiting real-time non-invasive data collection technologies such as wearable devices or microneedles. Addressing research gaps in early disease stages, harnessing patient history data often underused, and embracing continual diagnostics beyond treatment initiation are crucial for improving healthcare decision-making support and adoption across the entire management pathway., Conclusions: This comprehensive survey illuminates the landscape of ML applications in blood-related infection management, offering insights for future research and clinical practice. Implementing clinical ML-based clinical decision support systems requires balancing research with practical considerations. Current methodologies often lead to complex models lacking transparency and practical validation. Integration into healthcare systems faces regulatory, privacy, and trust challenges. Clear presentations and adherence to standards are essential to boost confidence in machine learning models for real-world healthcare applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Hypospadias occurs sporadically in male livestock and is characterized by a non-fused urethra during fetal development. In this study, perineal hypospadias, a bifid scrotum, penile hypoplasia, and bilateral abdominal cryptorchidism were diagnosed in a neonatal Holstein male calf. Septicemia was also suspected due to hypothermia, blurred conjunctivae, and loss of sucking and swallowing reflexes. Gross pathology revealed that both testicles were located intraabdominally caudally to the kidneys. Histopathological examination of the hypospadias showed a urothelium-lined mucosal fold and parts of the corpus cavernosum penis and prepuce in the subcutis. Whole genome sequencing was performed on the affected calf. Analysis of short-read coverage depth along the chromosomes identified an entire extra copy of chromosome 26. Based on the comparison of available variant calling data from the sire, the identified trisomy 26 is due to non-disjunction of homologous chromosomes during the generation of paternal gametes. We have shown for the first time an association between bovine hypospadias and trisomy 26, which adds to the understanding of variation in fetal male sexual development., (© 2024 The Author(s). Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.)

Bluetongue (BT) is a viral vector borne disease primarily affecting ruminants such as sheep, cattle, and goats. On 3 September 2023, the Netherlands reported the first case of bluetongue virus serotype 3 (BTV-3/NET2023)), after being BTV free for eleven years. Vaccination with inactivated BT vaccines for serotype 3 has been applied in the Netherlands since May 2024. Nonetheless, in late June/July 2024, BTV-3 re-emerged and spread over large parts of Europe. In October 2024, BTV-12 was identified by follow-up diagnostics after a BTV-3 vaccinated sheep with signs of BT was tested positive for BTV but negative for serotype 3. This marks a significant event, as BTV-12 had never been reported in Europe. Screening of farms in close proximity to the sheep farm and retrospective analysis of samples from clinically affected animals that were panBTV PCR positive resulted in the detection of nine BTV-12 affected farms in total. The emergence of BTV-12 in the Netherlands raises important questions about the route of introduction of BT in the Netherlands and mechanisms of viral spread of this specific serotype. Possible adaptation of new BTV serotypes to the European climatic and husbandry conditions prompts reconsideration of prevention, surveillance, and control strategies in relation to changing ecological conditions and vector dynamics. The initial findings, respective studies as well as the initial attempts to trace the origin of BTV-12/NET2024 are described., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Congenital malformations in cattle pose a diagnostic challenge with limited treatment options and are often associated with a guarded prognosis. The aim of this study was to characterize the clinicopathological phenotype of a viable calf with complex congenital heart defects and carpus valgus, and to identify a possible genetic cause using a whole genome sequencing trio approach. A 3-month-old female Holstein calf was referred for respiratory distress and congenital carpal deviation. Clinicopathologic findings included ventricular septal defect, ventricular dilatation, atrioventricular valve dysplasia, an overriding aorta, and unilateral carpus valgus. Genetic analysis revealed a private heterozygous missense variant in BRI3BP affecting an evolutionarily conserved residue (c.478G>A; p.Val160Ile). The variant was predicted to be deleterious and was present only in the affected calf and was absent in more than 5100 sequenced bovine genomes, including both parents, indicating a de novo origin. This study implicates an important role for the uncharacterized BRI3 binding protein in cardiac and possibly also bone development. By presenting the first BRI3BP-related disease model, this study demonstrates the potential to gain new insights into the function of individual genes by using phenotypically well-studied spontaneous mutants in large animals, and it provides a novel candidate gene for similar conditions in humans., (© 2024 The Author(s). Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics.)

We report the development of an immunotherapeutic molecule, a Humanized immunotoxin, for treating hCG-expressing advanced-stage cancers. PiPP, a high-affinity anti-hCG monoclonal antibody, is used in the immunotoxin for 'homing' hCG-positive cancer cells. The deimmunized (DI) form of α-Sarcin, a fungal-origin toxin that lacks functional T-cell epitopes, is used in the design to ensure minimal immunogenicity of the immunotoxin for repetitive use in humans. A single-chain variable fragment (scFv) of PiPP was constructed by linking the Humanized VH and VL regions of the antibody. The scFv part of the antibody was further linked to the toxin α-Sarcin (DI) at the gene level and expressed as a recombinant protein in E. coli . The immunotoxin was purified from the bacterial cell lysate and analysed for binding and cytotoxicity to hCG-secreting colorectal and pancreatic cancer cells. The results showed that the scFv(PiPP)-Sarcin immunotoxin was able to bind to colorectal and pancreatic cancer cells and killed approximately 85% of the cells. In vivo testing of the immunotoxin produced results similar to those of in vitro testing against colorectal adenocarcinoma-induced tumours. This immunotoxin could be a promising immunotherapeutic agent for treating colorectal, pancreatic and other terminal-stage hCG-expressing cancers.

In the previously created modular nanotransporter (MNT) capable of delivering a monobody to Keap1 into the cytosol, the endosomolytic module, translocation domain of diphtheria toxin (DTox), was replaced by the endosomolytic peptide GALA3. It was found that this substitution more than doubles the lifetime of MNT in the blood. Using confocal microscopy, it was shown that MNT with GALA3 was internalized into AML12 cells mainly due to binding to the epidermal growth factor receptor, and is also able to exit from endosomes into the cytosol. Using cellular thermal shift assay, it was shown that MNT with GALA3 and MNT with DTox are equally effective in disrupting the formation of the Nrf2 complex with Keap1, which led to similar protection of AML12 cells from the action of hydrogen peroxide. The obtained results allow not only optimizing the systemic use of MNT, but can also serve as a basis for creating agents aimed at treating diseases associated with oxidative stress., Competing Interests: ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Animal experiments were performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals ( http://oacu.od.nih.gov/regs/ index.htm ). Animal protocols were approved by the Bioethics Committee of the Institute of Gene Biology of the Russian Academy of Sciences, Moscow, Russia (Approval ID: no. 11, March 15, 2021). CONFLICT OF INTEREST: The authors of this work declare that they have no conflicts of interest., (© 2025. Pleiades Publishing, Ltd.)

Ex situ conservation of plant genetic resources (PGR) plays a crucial role in sustainable growth and development, as highlighted by the Global Strategy for Plant Conservation (GSPC). Seed genebanks, a key component of ex situ conservation, have been instrumental in preserving plant diversity. However, challenges arise with the conservation of non-orthodox (recalcitrant and intermediate) seeds and vegetative tissues, which are not amenable to storage in traditional genebanks at temperatures of -20 °C. Cryopreservation, the storage of biological materials at ultra-low temperatures in liquid nitrogen, has emerged as a viable solution for conserving such non-orthodox seeds, pollen, and dormant buds. This review presents insights into the National Cryogenebank Facility at ICAR-NBPGR, India, a pioneer in developing cryopreservation techniques and cryobanking of PGR. Established in 1987, the facility focuses on conserving difficult-to-conserve species of various agri-horticultural crops, including recalcitrant and intermediate species. With a capacity to hold a quarter of a million samples, the facility employs species-specific protocols to conserve rare, threatened, and endangered plant species, wild and weedy crop relatives, and genetic stocks. Over the past 3 decades, cryopreservation protocols have been developed at this facility using a diverse range of explants, including seeds, excised embryos, embryonic axes, pollen grains, and dormant buds. Successful cryopreservation protocols have been developed for temperate and tropical plant species important for horticultural, plantation, agro-forestry, and industrial use. Priority is given to conserving indigenous crop species and capturing the genetic diversity of indigenous tropical and temperate major and minor fruits. Additionally, the facility has successfully conserved pollen grains and dormant buds of tropical and temperate fruit crops, ensuring their viability and survival over extended periods of cryostorage. Furthermore, the cryobank regularly retests cryostored germplasm to assess viability and regrowth, with promising results indicating retention of seed viability even after 25-30 years of cryostorage. This highlights the potential of cryobanking as a long-term solution for conserving plant genetic resources. The National Cryogenebank Facility at ICAR-NBPGR exemplifies advancements in cryopreservation techniques applicable to plant genetic resource conservation, contributing significantly to national, regional and global efforts towards ex situ conservation of difficult-to-store plant species and overall sustainable agricultural development., Competing Interests: Declaration of interest None., (Copyright © 2025 Society for Cryobiology. Published by Elsevier Inc. All rights reserved.)

Background: One third of patients undergoing transcatheter aortic-valve implantation (TAVI) have an indication for oral anticoagulation owing to concomitant diseases. Interruption of oral anticoagulation during TAVI may decrease the risk of bleeding, whereas continuation may decrease the risk of thromboembolism., Methods: We conducted an international, open-label, randomized, noninferiority trial involving patients who were receiving oral anticoagulants and were planning to undergo TAVI. Patients were randomly assigned in a 1:1 ratio to periprocedural continuation or interruption of oral anticoagulation. The primary outcome was a composite of death from cardiovascular causes, stroke from any cause, myocardial infarction, major vascular complications, or major bleeding within 30 days after TAVI., Results: A total of 858 patients were included in the modified intention-to-treat population: 431 were assigned to continuation and 427 to interruption of oral anticoagulation. A primary-outcome event occurred in 71 patients (16.5%) in the continuation group and in 63 (14.8%) in the interruption group (risk difference, 1.7 percentage points; 95% confidence interval [CI], -3.1 to 6.6; P = 0.18 for noninferiority). Thromboembolic events occurred in 38 patients (8.8%) in the continuation group and in 35 (8.2%) in the interruption group (risk difference, 0.6 percentage points; 95% CI, -3.1 to 4.4). Bleeding occurred in 134 patients (31.1%) in the continuation group and in 91 (21.3%) in the interruption group (risk difference, 9.8 percentage points; 95% CI, 3.9 to 15.6)., Conclusions: In patients undergoing TAVI with a concomitant indication for oral anticoagulation, periprocedural continuation was not noninferior to interruption of oral anticoagulation during TAVI with respect to the incidence of a composite of death from cardiovascular causes, stroke, myocardial infarction, major vascular complications, or major bleeding at 30 days. (Funded by the Netherlands Organization for Health Research and Development and the St. Antonius Research Fund; POPular PAUSE TAVI ClinicalTrials.gov number, NCT04437303.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: The Pre-EMPT study aimed to determine if structured exercise could reduce length of stay, post-operative complications and improve fitness and health-related quality of life (HQRL) in patients undergoing neoadjuvant chemotherapy (NAC) and oesophagectomy., Methods: A prospective non-randomised trial compared a standard care pathway (control) to a structured prehabilitation exercise programme (intervention) commenced before NAC and surgery for oesophageal adenocarcinoma. Length of hospital stay and post-operative complications were recorded. Cardiopulmonary exercise testing (CPEX), body composition analyses, lymphocyte levels and HRQL questionnaires were performed at multiple time points., Results: Median length of stay was similar in both groups. There were 6 versus 11 complications observed (intervention vs control p = 0.086). Cardio-pulmonary fitness (VO2peak) declined after NAC, but less in the intervention group (intervention -13.54% vs control -21.40%, p = 0.02). Body composition improved in the intervention group (FMi/FFMi -5.5% intervention, 10.7% control p = 0.043). Performance, cognitive, sleep and emotional function scores improved following NAC in the intervention group. Lymphocyte subsets increased in the intervention group compared to the control group after chemotherapy (p = 0.034). Chemotherapy response was improved in the intervention group (p = 0.022)., Conclusion: A structured exercise programme may mitigate cardiopulmonary deconditioning, reduce sarcopenia and offset lymphopenia, during chemotherapy, in patients undergoing NAC and oesophagectomy., (© 2025 Wiley Periodicals LLC.)

Decentralized clinical trial (DCT) approaches - in which trial activities are conducted at participants' homes - have the potential to improve representativeness. We present a study that compared the demographics and cardiovascular risk factors of participants from a DCT (ASCEND) and a conventional trial with a similar trial objective (POPADAD) to those of patients in daily practice. We adjudicate that there are relevant differences when comparing the participants of the conventional trial and the DCT, with the latter providing better representativeness in terms of age, insulin use, smoking status, and body mass index, whereas conventional trial participants were more representative in terms of biological sex. Differences in these characteristics were not explained by the eligibility criteria, but are considered attributable to the operational trial approach., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Amos J. de Jong reports financial support was provided by Van Leersum Grant, KNAW Medical Sciences Fund. Mira G.P. Zuidgeest reports financial support and travel were provided by Innovative Health Initiative, SCOPE, DIA, EMA ACT-EU. Helga Gardarsdottir reports financial support was provided by Innovative Health Initiative. CEH is employed by the University of Copenhagen at the Copenhagen Centre for Regulatory Science (CORS). Novo Nordisk A/S and H. Lundbeck A/S have provided CORS with funding for research projects. Neither of the companies was involved in any aspect of the described work. The other authors declared no competing interests for this work. - CEH If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Gold nanoparticles are widely used in biomedical applications due to their unique properties. However, traditional synthesis methods generate contaminants that cause cytotoxicity and compromise the biocompatibility of the nanomaterials. Therefore, green synthesis methods are essential to produce pure and biocompatible nanoparticles, ensuring their effectiveness in biomedical applications. This study introduces a novel approach for synthesizing silica-coated gold nanoparticles (AuNP@SiO₂) using femtosecond laser ablation in water, eliminating the need for chemical reagents. The process involves three key laser-based steps: Si ablation, SiNP@SiO₂ fragmentation, and Au ablation, all conducted in a liquid environment. The resulting AuNP@SiO₂ were characterized using transmission electron microscopy (TEM), UV-Vis absorption spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), and zeta potential measurements. The results demonstrated that the AuNP@SiO₂ nanoparticles exhibit high colloidal stability, with a notably negative zeta potential of (-72.0 ± 0.3) mV, effectively preventing particle aggregation. TEM analysis confirmed predominantly spherical nanoparticles with an average diameter of (15.87 ± 0.70) nm, encapsulated by a SiO₂ layer ranging from 1 to 3 nm in thickness. The synthesis approach produced nanoparticles with an average size distribution below 35 nm. This green synthesis method not only produces stable and well-characterized AuNP@SiO₂ nanoparticles but also represents a significant step towards more sustainable nanomaterial production, with promising implications for biomedical applications., Competing Interests: Declarations. Competing  interests: The authors declare no competing interests., (© 2024. The Author(s).)

Changes in the microstructure of the aortic wall precede the progression of various aortic pathologies, including aneurysms and dissection. Current clinical decisions with regards to surgical planning and/or radiological intervention are guided by geometric features, such as aortic diameter, since clinical imaging lacks tissue microstructural information. The aim of this proof-of-concept work is to investigate a non-invasive imaging method, diffusion tensor imaging (DTI), in ex vivo aortic tissue to gain insights into the microstructure. This study examines healthy, aneurysm and a type B chronic dissection aortae, via DTI. DTI-derived metrics, such as the fractional anisotropy, mean diffusivity, helical angle and tractography, were examined in each morphology. The results from this work highlighted distinct differences in fractional anisotropy (healthy, 0.24 ± 0.008; aneurysmal, 0.19 ± 0.002; dissected, 0.13 ± 0.006) and a larger variation in the helical angle in the dissected aorta compared to healthy (39.28 ± 11.93° vs. 26.12 ± 4.60°, respectively). These differences were validated by histological characterisation. This study demonstrates the sensitivity of DTI to pathological changes in aortic tissue, highlighting the potential of this methodology to provide improved clinical insight., (© 2025 The Author(s). Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Proper nutrition is vital for maintaining good health for all people across their lifespan, especially children and mothers, who are especially vulnerable due to their specific nutrient needs. Despite the necessity of improved nutrition for these groups, some members do not fully meet their recommended daily micronutrient needs, a challenge exacerbated by different socioeconomic, cultural, and communal constraints resulting in malnutrition. Iron deficiency anaemia is a major concern among children and mothers, especially in pastoralist communities, due to poor nutrition and other related factors. Using a community-based cross sectional study, this study investigated factors associated with hemoglobin levels among children and women in Narok County, Kenya. Anthropometrics were estimated using body mass index measurements for mothers, and the nutritional status of children was calculated using Z -score measurements. Haemoglobin was measured using a rapid test (Hemocue 301). Multiple logistic regression models were fitted to assess the association between child and maternal risk factors and anaemia. Anaemia in children was associated with age (OR = 1.99, p  = 0.047), pastoralism (OR = 2.25, p  = 0.002), educational of the mother (OR = 0.74, p  = 0.008), severe and moderate undernourishment (OR = 1.14, p  = 0.049 and OR = 1.10, p  = 0.023), respectively, not meeting children dietary diversity (OR = 1.18, p  = 0.027), number of people in a household (OR = 1.84, p  = 0.003), and maternal age (OR = 0.30, p  = 0.010). On the other hand, the occurrence of anaemia in women was associated with pastoralism (OR = 2.22, p  = 0.001), having a primary school level of education (OR = 0.51, p  = 0.028), pregnancy status (OR = 5.36, p  = 0.002), not meeting maternal dietary diversity (OR = 1.39, p  = 0.026), number of household members (OR = 1.93, p  = 0.023), age of the mother (OR = 0.53, p  = 0.018), and having animals infected with East Coast Fever ( Theileria parva ) within the household (OR = 1.10, p  = 0.023). The results highlight the multifaceted nature of malnutrition, specifically anaemia in pastoral households, with interventions aimed at reducing disease infections in cattle, improved household dietary diversity, and community health education geared towards maternal and child nutrition being best placed to improve the overall household health outcomes relating to anaemia., Competing Interests: The authors declare no conflicts of interest., (© 2025 The Author(s). Food Science & Nutrition published by Wiley Periodicals LLC.)

Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM, FPD/AML, RUNX1 -FPD), caused by monoallelic deleterious germline RUNX1 variants, is characterized by bleeding diathesis and predisposition for hematologic malignancies, particularly myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Clinical data on FPDMM-associated AML (FPDMM-AML) are limited, complicating evidence-based clinical decision-making. Here, we present retrospective genetic and clinical data of the largest cohort of FPDMM patients reported to date. We describe 159 European patients (from 94 families) of whom 134 were evaluable for the development of malignant disease. Sixty developed a hematologic malignancy (44.8%), most frequently AML (36/134, 26.9%) or MDS (18/134, 13.4%). Somatic alterations of RUNX1 by gene mutation (48%) and chromosome 21 aberrations (14.3%) were the most common somatic genetic aberrations in FPDMM-AML, followed by FLT3-ITD mutations (24.1%). Somatic RUNX1 and FLT3-ITD mutations were not detected in FPDMM-associated MDS, suggesting important contributions to leukemic transformation. Remission-induction chemotherapy resulted in complete remission in 80% of FPDMM-AML patients with a 5-year overall survival (OS) of 50.4%. Survival outcome was non-inferior compared to a large cohort of newly diagnosed adult RUNX1 -mutated AML (5-year OS 36.6%, p  = 0.5), with relatively infrequent concurrent adverse risk somatic aberrations ( ASXL1 mutation, monosomal karyotype, monosomy 5/del 5q) in FPDMM-AML. Collectively, data support the notion that step-wise leukemic evolution in FPDMM is associated with distinct genetic events and indicate that a substantial subset of FPDMM-AML patients achieves prolonged survival with conventional AML treatment, including allogeneic stem cell transplant. These findings are anticipated to inform personalized clinical decision-making in this rare disorder., Competing Interests: The authors declare no conflict of interest., (© 2025 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Aims: Recent trials have shown that low-dose colchicine (0.5 mg once daily) reduces major cardiovascular events in patients with acute and chronic coronary syndromes. We aimed to estimate the cost-effectiveness of low-dose colchicine therapy in patients with chronic coronary disease when added to standard background therapy., Methods and Results: This Markov cohort cost-effectiveness model used estimates of therapy effectiveness, transition probabilities, costs, and quality of life obtained from the Low-Dose Colchicine 2 trial, as well as meta-analyses and public sources. In this trial, low-dose colchicine was added to standard of care and compared with placebo. The main outcomes were cardiovascular events, including myocardial infarction, stroke, and coronary revascularization, quality-adjusted life year (QALY), the cost per QALY gained (incremental cost-effectiveness ratio), and net monetary benefit. In the model, low-dose colchicine therapy yielded 0.04 additional QALYs compared with standard of care at an incremental cost of €455 from a societal perspective and €729 from a healthcare perspective, resulting in a cost per QALY gained of €12 176/QALY from a societal perspective and €19 499/QALY from a healthcare perspective. Net monetary benefit was €1414 from a societal perspective and €1140 from a healthcare perspective. Low-dose colchicine has a 96 and 94% chance of being cost-effective, from a societal and a healthcare perspective, respectively, when using a willingness to pay of €50 000/QALY. Net monetary benefit would decrease below zero when annual low-dose colchicine costs would exceed an annual cost of €221 per patient., Conclusion: Adding low-dose colchicine to standard of care in patients with chronic coronary disease is cost-effective according to commonly accepted thresholds in Europe and Australia and compares favourably in cost-effectiveness to other drugs used in chronic coronary disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Candida parapsilosis is a common human commensal and opportunistic fungal pathogen that is also found in non-human primates (NHPs). Here, we report the first draft sequence of C. parapsilosis NCYC 4418, a fecal isolate from an adult cynomolgus macaque., Competing Interests: The authors declare no conflict of interest.

Competing Interests: Competing interests: None declared.

The conversion of organic matter to methane through anaerobic digestion (AD) process can be enhanced by different materials. However, literature reports show inconsistent results on the effect of materials in different AD systems. In this study, we evaluated the influence of the inoculum's activity on methane production (MP) efficiency in the presence of different materials (activated carbon (AC), magnetite (Mag), and zeolite (Zeo)). The inocula included pure cultures of methanogens, syntrophic cocultures, and complex microbial communities, and the kinetic parameters assessed were the lag phase duration and methane production rates (MPR). The results showed that the microbial activity of the inocula is an important factor determining materials' effect on MP kinetics. AC, Mag, and Zeo significantly enhanced the MP profiles of less active microbial communities or low-active microorganisms by decreasing lag phases duration up to 85 %, consequently increasing MPR up to 15 times. Contrarily, these materials did not affect highly active microbial communities or pure cultures, as MP profiles tend to be similar with and without materials. These results indicate that from an applied point of view, the addition of materials to anaerobic bioreactors should be considered only when the methanogenic activity of the sludge is low or compromised., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The loading of the bacterial replicative helicase DnaB is an essential step for genome replication and depends on the assistance of accessory proteins. Several of these proteins have been identified across the bacterial phyla. DciA is the most common loading protein in bacteria, yet the one whose mechanism is the least understood. We have previously shown that DciA from Vibrio cholerae is composed of a globular domain followed by an unfolded extension and demonstrated its strong affinity for DNA. Here, we characterize the condensates formed by VcDciA upon interaction with a short single-stranded DNA substrate. We demonstrate the fluidity of these condensates using light microscopy and address their network organization through electron microscopy, thereby bridging events to conclude on a liquid-liquid phase separation behavior. Additionally, we observe the recruitment of DnaB in the droplets, concomitant with the release of DciA. We show that the well-known helicase loader DnaC from Escherichia coli is also competent to form these phase-separated condensates in the presence of ssDNA. Our phenomenological data are still preliminary as regards the existence of these condensates in vivo, but open the way for exploring the potential involvement of DciA in the formation of non-membrane compartments within the bacterium to facilitate the assembly of replication players on chromosomal DNA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The exploration of extraterrestrial environments has become a focal point of scientific inquiry, driven by advancements in technology and a growing interest in the potential for life beyond Earth. This study investigates the adaptability of Antarctic nematodes, known for thriving in extreme cold and isolation, to simulated Martian (MGS-1) and Lunar (LMS-1) soils. The experiment revealed differential responses in nematode survivability to the two simulants, with Lunar soil demonstrating better adaptability compared to Martian soil. Our study provides valuable insights into the potential survivability of Antarctic nematodes on real Martian and Lunar substrates with the use of the MGS-1 and the LMS-1 under terrestrial conditions. The observed results suggest differential survival responses to Lunar (6.92 ± 0.74) and Martian (5.58 ± 1.91) regolith simulants and highlight the complexity of factors influencing organismal survival. Considering their crucial role in soil food webs, and their relation with nutrient cycling and carbon dioxide emissions, the observed capacity of nematodes to thrive in Martian and Lunar regoliths positions them as potential candidates to sustain human habitats, helping on the development of in-situ resource utilization (ISRU) systems, and forming the basis for a biological life-support system to facilitate human survival in extraterrestrial environments.

Here, we report the complete genome sequence of a new carlavirus causing mosaic on mint plants in Italy, which we have tentatively named "mint virus C" (MVC). Flexuous particles of around 600 nm were observed using transmission electron microscopy, and next-generation sequencing was performed to determine the nucleotide sequence of the MVC genome, which was found to be 8558 nt long, excluding the poly(A) tail, and shows the typical organization of a carlavirus. The putative proteins encoded by MVC are 44-56% identical to the closest matches in the NCBI database, suggesting that MVC should be considered a member of a new species in the genus Carlavirus. MVC was detected in independent mint samples from different regions of Italy, collected in 2023 and 2024. Two MVC isolates, identified in 2023 (Me1) and in 2024 (Me2), have been included in the Plant Virus Italy (PLAVIT) collection., Competing Interests: Declarations. Conflict of interest: Authors declare no conflict of interest., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Dyslipidaemia is among the major causes of severe diseases and, despite being well-established, the hypocholesterolaemic therapies still face significant concerns about potential side effects (such as myopathy, myalgia, liver injury digestive problems, or mental fuzziness in some people taking statins), interaction with other drugs or specific foods. Accordingly, this review describes the latest developments in the most effective therapies to control and regulate dyslipidaemia., Scope and Approach: Herein, the metabolic dynamics of cholesterol and their integration with the current therapies: statins, bile acid sequestrants, fibrates, niacin, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, reconstituted high-density lipoprotein (rHDL), or anti-inflammatory and immune-modulating therapies), were compared focusing their effectiveness, patients' adhesion and typical side-effects. Likewise, the interaction of these therapies with recommended dietary habits, focusing functional foods and nutraceuticals uptake were also considered., Key Findings and Conclusions: Since none of the current therapeutic alternatives represent an ideal solution (mainly due to side-effects or patients' tolerance), the potential adjuvant action of selected diets (and other healthy habits) was proposed as a way to improve the cholesterol-lowering effectiveness, while reducing the adverse effects caused by dose-increase or continuous uptake of alternating therapeutic agents. In general, the relevance of well-adapted diets must be acknowledged and their potential effects must be exhorted among patients, who need to be aware of the associated multifactorial advantages., Competing Interests: Declaration of competing interest Authors declare no conflict of interest of any kind., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

X-ray Diffraction Computed Tomography (XRD-CT) represents a cutting-edge method for non-destructive material analysis, offering the unique capability of providing molecular-level information with spatial resolution. In this study, we have applied XRD-CT to investigate pharmaceutically relevant tablets that have been subjected to a range of compression pressures typical in tablet manufacturing. By employing XRD-CT to pharmaceutical tablets, we reveal material changes without tablet destruction, thereby avoiding potential phase transformations during sample preparation that could lead to errors in the interpretation of the processes that have occurred. Utilizing a pressure-sensitive marker, glycolide, we have tracked changes within tablet structures induced by compression, pinpointing locations where glycolide undergoes pressure-induced transformation. Additionally, we conducted a follow-up study with analysis one month later, observing an in situ hydrolysis reaction of glycolide within the tablets. Through the complementary use of electron diffraction, we have elucidated the structure of the hydrolysis product, further enhancing our understanding of temporal changes in the tablets., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The human 15-lipoxygenase-2 (h15-LOX-2) catalyzes mainly the regio- and stereospecific oxygenation of arachidonate to its corresponding hydroperoxide (15( S )-HpETE). h15-LOX-2 is implicated in the biosynthesis of inflammatory lipid mediators and plays a role in the development of atherosclerotic plaques, but it is still underexploited as a drug target. Here, to search for novel h15-LOX-2 inhibitors, we used a virtual screening (VS) approach consisting of shape-based matching, two-dimensional (2D) structural "dissimilarity", docking, and visual inspection filters, which were applied to a "curated" ZINC database (∼8 × 10 6 compounds). The VS was experimentally validated, and six micromolar-range inhibitors were identified among 13 tested compounds (46.2%). The K i values could be determined for two inhibitors, compounds 10 ( K i = 16.4 ± 8.1 μM) and 13 ( K i = 15.1 ± 7.6 μM), which showed a mixed-type mechanism of inhibition. Overall, the identified inhibitors fulfill drug-like criteria and are structurally novel compared with known h15-LOX-2 inhibitors.

Ewing sarcoma (EWS) is the second most common bone tumor affecting children and young adults, with dismal outcomes for patients with metastasis at diagnosis. Mechanisms leading to metastasis remain poorly understood. To deepen our knowledge on EWS progression, we have profiled tumors and metastases from a spontaneous metastasis mouse model using a multi-omics approach. Combining transcriptomics, proteomics, and methylomics analyses, we identified signaling cascades and candidate genes enriched in metastases that could be modulating aggressiveness in EWS. Phenotypical validation of two of these candidates, cyclic AMP-responsive element-binding protein 1 (CREB1) and lipoxygenase homology domain-containing protein 1 (LOXHD1), showed an association with migration and clonogenic abilities. Moreover, previously described CREB1 downstream targets were present amongst the metastatic-enriched results. Combining the different omics datasets, we identified FYVE, RhoGEF, and PH domain-containing protein 4 (FGD4) as a CREB1 target interconnecting the different EWS biological layers (RNA, protein and methylation status) and whose high expression is associated with worse clinical outcome. Further studies will provide insight into EWS metastasis mechanisms and ultimately improve survival rates for EWS patients., (© 2025 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Human cancer cell lines are the mainstay of cancer research. Recent reports showed that highly mutated adult carcinoma cell lines (mainly HeLa and MCF-7) present striking diversity across laboratories and that long-term continuous culturing results in genomic/transcriptomic heterogeneity with strong phenotypical implications. Here, we hypothesize that oligomutated pediatric sarcoma cell lines mainly driven by a fusion transcription factor, such as Ewing sarcoma (EwS), are genetically and phenotypically more stable than the previously investigated adult carcinoma cell lines. A comprehensive molecular and phenotypic characterization of multiple EwS cell line strains, together with a simultaneous analysis during 12 months of continuous cell culture show that fusion-driven pediatric sarcoma cell line strains are genomically more stable than adult carcinoma strains, display remarkably stable and homogenous transcriptomes, and exhibit uniform and stable drug response. Additionally, the analysis of multiple EwS cell lines subjected to long-term continuous culture reveals that variable degrees of genomic/transcriptomic/phenotypic changes among fusion-driven cell lines, further exemplifying that the potential for reproducibility of in vitro scientific results may be rather understood as a spectrum, even within the same tumor entity., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To assess the outcomes of three surgical techniques in the management of simple gastroschisis., Materials and Methods: An observational, descriptive, retrospective, longitudinal study was carried out. Medical records of patients diagnosed with simple gastroschisis and treated with different surgical techniques -Simil-Exit, primary closure, and deferred closure- were reviewed., Results: 38 gastroschisis patients undergoing either the Simil-Exit (n= 10), the primary closure (n= 11), or the deferred closure (n= 17) techniques were analyzed. The Simil-Exit technique involved a shorter operating time than primary closure and deferred closure. Both Simil-Exit and primary closure patients required a shorter mechanical ventilation time, fewer days of parenteral nutrition, shorter time to oral feeding initiation, and a shorter hospital stay than deferred closure patients. The deferred closure technique had more frequent complications, such as sepsis., Conclusions: The Simil-Exit and the primary closure techniques demonstrated favorable outcomes in patients with simple gastroschisis. In addition, the former involved shorter operating times, it required less exposure of the small bowel loops to the environment, it was easily reproducible, and it provided a better cosmetic result.

This study investigates essential (Mg, Ca, Fe, Mn, Cu, Zn, Se, Ni) and non-essential (Li, Be, Cr, Rb, Sr, Cs, Cd, Sn, Ba, and Pb) element concentrations and stable isotope (δ 13 C, δ 15 N, δ 34 S) compositions in feathers of Brown Boobies (Sula leucogaster) from three distinct Atlantic islands: the Archipelagos of Saint Peter and Saint Paul (SPSP), Abrolhos, and Cagarras. We aimed to investigate the ecological and environmental factors influencing these seabird populations and assess potential variations in contaminant exposure and dietary habits based on location, sex, and maturity stages. Our finding revealed significant geographical differences in trace element concentrations. The Brown Boobies from Cagarras had higher concentrations (mean ± SD, μg g -1 ) of Fe (29 ± 20) and Mn (0.82 ± 0.82) than those from Abrolhos (Fe: 21 ± 20; Mn: 0.24 ± 0.09) and SPSP (Fe: 15 ± 16; Mn: 0.21 ± 0.06). Tin concentrations were also higher in Cagarras (Sn: 0.02 ± 0.01) than in SPSP (Sn: 0.01 ± 0.01). Our analyses revealed significant differences in Li, Mg, Rb, and Zn concentrations between adults and juveniles. However, there were no sex-related differences in element concentrations within each locality. SIBER analyses revealed distinct dietary differences among the three Brown Boobies populations, with the Cagarras seabirds occupying a higher trophic position compared to the SPSP population. This study highlights the importance of considering different populations to understand contaminant exposure and ecological dynamics in Brown Boobies along the South Atlantic. The Cagarras population shows significantly higher contaminant levels, likely due to proximity to anthropogenic activities. These results highlight the necessity for ongoing monitoring to evaluate long-term effects on the more impacted population and to ensure seabird health and sustainability in the Atlantic Ocean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Lung cancer remains the leading cause of cancer-related deaths worldwide due to its poor prognosis. Despite significant advancements in the understanding of cancer development, improvements in diagnostic methods, and multimodal therapeutic regimens, the prognosis of lung cancer has still not improved. Therefore, it is reasonable to look for newer and alternative medicines for treatment. Bhallataka nut extract, derived from the seeds of Semecarpus anacardium , is known for its anti-inflammatory and antioxidant properties, suggesting potential as a treatment for cancer. In this study, we investigated the molecular networks associated with the Bhallataka taila-mediated inhibition of lung adenocarcinoma. Treating lung cancer cell lines with Bhallataka taila resulted in decreased colony formation, proliferation, and migration, and increased apoptosis. Using a tandem mass tag (TMT)-based temporal quantitative proteomic analysis, we identified 173 overexpressed and 249 downregulated proteins among a total of 2879 proteins. Significantly altered proteins are associated with lung cancer progression, metastasis, invasion, migration, and epithelial-mesenchymal transition (EMT). The analysis of these altered proteins revealed molecular networks underlying the anticancer mechanisms of Bhallataka taila. Validation of these proteins and pathways affected by Bhallataka taila confirmed its utility in cancer treatment.

Low frequency noise (LFN) of unknown origin can be disturbing, especially at night, and affect sleep and relaxation. If reduction of the LFN is impossible, adding sound can mask the troubling noise or detract attention from it to reduce distress. To assess the effectiveness of this, a survey was set up consisting of three questionnaires: the first when a person requested a masking sound and follow-ups after 1 and 3 months. Distress reduction was based on self-assessment and on the tinnitus questionnaire (TQ). Out of 124 respondents, 69% reported that the masking sound contributed to a reduction in complaints, resulting in a reduction in TQ score. Respondents were mainly above 50 years of age and 31% were male. Most respondents (84%) denounce the possibility of an internal sound. However, demographic characteristics of respondents are more similar to tinnitus patients and less to residents annoyed by environmental noise. The number of respondents per capita rises with decreasing population density, indicating that a quiet environment enhances the hearing of LFN. Thus, absence of sound in the environment may induce the hearing of LFN., (© 2025 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

Socio-dynamic situations require a balance between response execution and action inhibition. Nonadaptive imbalance between response inhibition and execution exists in neurodevelopmental and neuropsychological disorders. To investigate the underlying neural mechanisms of cognitive control and the related deficits, comparative studies in human and nonhuman primates are crucial. Previous stop-signal tasks in humans and macaque monkeys have examined response execution (response time (RT) and accuracy in Go trials) and action inhibition (stop-signal reaction time (SSRT)). Even though marmosets are generally considered suitable translational animal models for research on social and cognitive deficits, their ability to inhibit behavior remains poorly characterized. We developed a marmoset stop-signal task, in which RT could be measured at millisecond resolution. All four marmosets performed many repeated Go trials with high accuracy (≥ 70%). Additionally, all marmosets successfully performed Stop trials. Using a performance-dependent tracking procedure, the accuracy in Stop trials was maintained around 50%, which enabled reliable SSRT estimates in marmosets for the first time. The mean SSRT values across sessions ranged between 677 and 1464 ms across the four marmosets. We also validated the suitability and practicality of this novel task for examining executive functions by testing the effects of a natural hormone, oxytocin, on response execution and action inhibition in marmosets. This marmoset model, for reliable (millisecond resolution) assessment of the balance between response execution and inhibition, will further facilitate studying the developmental alterations in inhibition ability and examining the effects of various contextual and environmental factors on marmosets' executive functions., (© 2025 The Author(s). American Journal of Primatology published by Wiley Periodicals LLC.)

Labyrinth seals (LSs) in turbomachinery are used to minimize leaks. This study presents an experimental setup designed to test and validate LS designs. The test bench (TB) described in this paper can evaluate different LS designs obtained through various methods to find better solutions to mitigate greenhouse gas (GHG) emissions. Prototypes with conventional geometry, such as straight-through and interlaced LSs, are initially implemented and tested. A measurement procedure and experimental methodology for collecting leakage data are defined. The experimental methodology includes a measurement TB that supports a pressure difference of up to 5 bar. The leakage rate is measured in g/s using instrumentation that corrects the mass flow rate based on pressure and temperature measurements. The experimental results are compared to the Computational Fluid Dynamics results. Thus, the setup given in this article is a new and versatile TB setup focused on leakage measurement, which allows being used for analyzing various types of LS (with or without rotor structures) and is effective for evaluating the performance of LSs, helping the development of new LS geometries that can reduce GHG emissions., (© 2025 Author(s). Published under an exclusive license by AIP Publishing.)

Little is known regarding the effects high-intensity training performed in hypoxia on the oxidative stress and antioxidant systems. The aim of this study was to assess the potential effect of 4 weeks of repeated sprint training in hypoxia (RSH) on the redox balance. Forty male well-trained cyclists were matched into two different interventions (RSH, n  = 20) or in normoxia, RSN, n  = 20) and tested twice (before (Pre-) and after (Post-) a 4-week of training) for performance (repeated sprint ability (RSA) test), oxidative stress, and antioxidant status. Antioxidant enzyme activity (Superoxide Dismutase, Glutathione Peroxidase, and catalase), NO metabolites (NOx: nitrites and nitrates), ferric reducing antioxidant power, Malondialdehyde (MDA), nitrotyrosine, and carbonyls were measured in plasma. At Post-, MDA, and carbonyls increased ( p  < 0.05) in the RSN group both at rest (+90.6%) and also acutely in response to RSA (+22.9%); but not in RSH. At Post-, in the RSH group, catalase increased ( p  < 0.05) both at rest (+44.7%) and in response to the RSA test (+66.3%). At Post-, SOD, and nitrotyrosine decreased after RSA and at rest, regardless of the group ( p  = 0.0012 and p  = 0.0413, respectively). At Post-, NOx decreased after the RSA test, regardless of the group ( p  < 0.05). In conclusion, several weeks of RSH training limits the increase in oxidative stress markers both at rest and in response to RSA test. Moreover, such training downregulated SOD activity, possibly due to an overproduction of reactive oxygen species. These findings could constitute a paradigm shift with a better enzymatic adaptation after RSH concomitant with a distinct reactive oxygen species (ROS) production between RSH and RSN.

Errors during cell division lead to aneuploidy, which is associated with genomic instability and cell transformation. In response to aneuploidy, cells activate the tumour suppressor p53 to elicit a surveillance mechanism that halts proliferation and promotes senescence. The molecular sensors that trigger this checkpoint are unclear. Here, using a tunable system of chromosome mis-segregation, we show that mitotic errors trigger nuclear deformation, nuclear softening, and lamin and heterochromatin alterations, leading to rapid p53/p21 activation upon mitotic exit in response to changes in nuclear mechanics. We identify mTORC2 and ATR as nuclear deformation sensors upstream of p53/p21 activation. While triggering mitotic arrest, the chromosome mis-segregation-induced alterations of nuclear envelope mechanics provide a fitness advantage for aneuploid cells by promoting nuclear deformation resilience and enhancing pro-invasive capabilities. Collectively, this work identifies a nuclear mechanical checkpoint triggered by altered chromatin organization that probably plays a critical role in cellular transformation and cancer progression., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Osteoporotic fragility fractures (FF), particularly those affecting the hip, represent a major clinical and socio-economic concern. These fractures can lead to various adverse outcomes, which may be exacerbated by the presence of sarcopenia, especially among older and frail patients. Early identification of patients with FF is crucial for implementing effective diagnostic and therapeutic strategies to prevent subsequent fractures and their associated consequences., Methods: The Hip-POS program, implemented at Azienda Ospedale-Università Padova, is a Fracture Liaison Service (FLS) program to evaluate patients aged > 50 years old admitted with fragility hip fractures, involving an interdisciplinary team. After the identification of patients with hip fractures in the Emergency Department, a comprehensive evaluation is conducted to identify risk factors for further fractures, and to assess the main domains of multidimensional geriatric assessment, including muscle status. Patients are then prescribed with anti-fracture therapy, finally undergoing periodic follow-up visits., Results: During the first five months, a total of 250 patients were evaluated (70.4% women, median age 85 years). Following assessment by the Hip-POS team, compared to pre-hospitalization, the proportion of patients not receiving antifracture therapy decreased significantly from 60 to 21%. The prescription rates of vitamin D and calcium increased markedly from 29.6% to 81%., Conclusions: We introduced the Hip-POS program for the care of older adults with hip fractures. We aspire that our model will represent a promising approach to enhancing post-fracture care by addressing the multifactorial nature of osteoporosis and its consequences, bridging the gap in secondary fracture prevention, and improving patient outcomes., Competing Interests: Declarations. Conflicts of interest: The authors have no competing interests to declare that are relevant to the content of this article. Research involving human participants and/or animals: All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Institutional and National) and with the Helsinki Declaration of 1964 and later versions. Informed consent: Informed consent was obtained from all patients for being included in the study., (© 2024. The Author(s).)

Effects on physiology were evaluated in 49 free-ranging moose (Alces alces), 11 adult males, 36 females, two of unknown sex) in Minnesota, USA, immobilized by helicopter darting with thiafentanil (10 mg) and xylazine (30 mg) in February 2020 and March 2021. Pursuit time (PT), induction time (IT), recumbency time (RT), recovery time (RC), temperature (T), and body position were recorded. For 14 females, respiratory rate (RR), pulse rate (PR), and pulse oximetry (SpO2) were obtained before and at 1, 5, and 10 min after 4 L/min nasal oxygen supplementation was started; pH, lactate (Lac), arterial oxygen (PaO2), and carbon dioxide (PaCO2) tensions were obtained pre-treatment and 5 min post-treatment. Immobilizations were reversed with naltrexone (200 mg) and tolazoline (800 mg) intramuscularly. Median PT and IT were 4 min; a longer dart needle significantly reduced IT (P=0.0274). Most (98%) remained sternal; 77% held their head upright. Median RC was 3 min. Temperature remained ≤41.2 C. Median RR, PR, and SpO2 were RR=20 breaths/min, PR=70 beats/min, SpO2=91% pre-treatment and RR=30 breaths/min, PR=72 beats/min, SpO2=97% 5-min post-treatment. Median blood gas values were pH=7.45, Lac=5.62 mmol/L, PaCO2=44 mmHg, and PaO2=65 mmHg pre-treatment and pH=7.48, Lac=4.99 mmol/L, PaCO2=41.1 mmHg, and PaO2=78 mmHg 5-min post-treatment. Physiologic improvement from oxygen supplementation was clinically relevant but not statistically significant. All moose survived immobilization. Thiafentanil and xylazine combination provided safe and effective immobilization in free-ranging moose., (© Wildlife Disease Association 2025.)

Bio-oil from Hibiscus cannabinus seeds was extracted with four solvents: acetone, benzene, isopropanol, and hexane. Solvent extraction techniques have less oil residue than other methods. The primary factors that influence the extraction processes such as extraction time, particle size, seed ageing, and solvent suitability were optimised to enhance the bio-oil yield. The extracted bio-oil was tested by GC-MS, FTIR, and 1 H-NMR. Physicochemical properties (free fatty acid, specific gravity, acid value, calorific value, saponification number, iodine number, etc.) of hibiscus cannabinus oil were also analysed on a dry weight basis. The hexane solvent gave the highest yield (25.37%) followed by acetone (21.32%), Benzene (16.98%), and Isopropanol (14.20%) over 3.5 h. It is also predicted that the cost of Hibiscus cannabinus seed bio-oil per litre is Rs. 230 which is moderately economical Hibiscus cannabinus oil has a calorific value of 39,895 kJ/kg, making it a better fuel choice.

Time-resolved three-dimensional ultrasound (3D + t US) is a promising imaging modality for monitoring abdominal aortic aneurysms (AAAs), providing their 3D geometry and motion. The lateral contrast of US is poor, a well-documented drawback which multi-perspective (MP) imaging could resolve. This study aims to show the feasibility of in vivo multi-perspective 3D + t ultrasound imaging of AAAs for improving the image contrast and displacement accuracy. To achieve this, single-perspective (SP) aortic ultrasound images from three different angles were spatiotemporally registered and fused, and the displacements were compounded. The fused MP had a significantly higher wall-lumen contrast than the SP images, for both patients and volunteers ( P  < .001). MP radial displacements patterns are smoother than SP patterns in 67% of volunteers and 92% of patients. The MP images from three angles have a decreased tracking error ( P  < .001 for all participants), and an improved SNR e compared to two out of three SP images ( P  < .05). This study has shown the added value of MP 3D + t US, improving both image contrast and displacement accuracy in AAA imaging. This is a step toward using multiple or large transducers in the clinic to capture the 3D geometry and strain more accurately, for patient-specific characterization of AAAs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study aimed to evaluate the feasibility of performing multiple testicular biopsies in rams using Tru-cut® needles, assessing histological structure, gene expression, and potential complications such as effects on semen quality, testicular blood flow, and ultrasonographic echotexture. In Exp. 1, six mature rams underwent testicular biopsies at intervals (0, 3, 6, 12, 24, and 48 h) using a 16 G Tru-cut® needle, with alternating testes for each collection. Benzathine benzylpenicillin and flunixin meglumine were administered for infection and inflammation control. Local anesthesia and post-biopsy care included lidocaine, digital pressure, and ice application. Testicular samples were analyzed for gene expression related to inflammation, oxidative stress, and steroidogenesis. Semen quality was assessed pre-biopsy and 28 days post-biopsy. Ultrasonographic evaluations of the scrotum and testes were conducted before biopsies and on days 5, 9, 13, 17, and 21 post-biopsies. In Exp. 2, a second group of six mature rams underwent biopsies using 14 G needles, with two samples taken from each testis. Samples were histologically examined for structural preservation. Scrotal skin temperature was measured using infrared thermography, and testicular blood flow was assessed via color Doppler ultrasonography, with measurements taken before and on days 1, 2, 4, 6, 8, 10, 25, 50, 75, and 100 post-biopsies. Semen collection followed the same schedule as in Exp. 1. In Exp. 3, biopsies were performed on different testicular regions (upper, middle, lower) using 12 G, 14 G, and 16 G needles to compare structural preservation. Samples were histologically analyzed. No clinical signs of injury, inflammation, or fluid accumulation were observed. Scrotal pain, increased temperature, swelling, and bleeding were absent, and behavioral signs indicative of pain were not detected. Gene expression remained unchanged, and no significant alterations in seminal characteristics or testicular echogenicity were observed. A slight increase in resistivity and pulsatility indices was noted in Exp. 2. Biopsies with 14 G and 16 G needles resulted in structural disruptions, while 12 G needles better preserved testicular parenchyma. Multiple testicular biopsies using Tru-cut® needles did not cause significant morphological changes, alter transcriptional profiles, or affect semen or ultrasonographic characteristics, demonstrating that this method is viable for monitoring acute molecular changes in the testes., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction and Importance: Neglected posterior hip dislocations in adults are rare, particularly when untreated for years. In developing nations, patients often rely on traditional bone setters, leading to delayed diagnosis and increased complications. Adult hip dislocations carry a higher risk of avascular necrosis and require complex treatments. This case illustrates a five-year delayed posterior hip dislocation with a false acetabulum, managed with skeletal traction and total hip replacement. This case report is written in compliance with the SCARE guideline., Case Presentation: A 64-year-old Minahasa woman presented with six years of hip pain, gait issues, and functional limitations post-fall. Initially treated by a bone setter, the patient had an 8 cm limb length discrepancy, restricted hip motion, and a Harris Hip Score of 39 %. Imaging showed a high-displaced hip with a false acetabulum and acetabular fracture. Treatment involved a two-staged procedure: skeletal traction and reconstruction followed by cemented total hip replacement, resulting in significant recovery and a Harris Hip Score of 90 % after four years., Clinical Discussion: Chronic hip dislocations present challenges due to fibrous tissue and muscle contractures. Skeletal traction facilitated the reduction of the dislocation and provided stabilization prior to the replacement surgery. Total hip replacement was required due to the extent of joint damage. A Staged management skeletal traction and reconstruction before surgery improve outcomes in such cases, making total hip replacement an optimal solution for chronic dislocations., Conclusion: Total hip replacement is effective for neglected hip dislocations, restoring function and mobility, as demonstrated by this case's successful long-term outcome., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) available for type 2 diabetes mellitus (T2DM) management, whose effectiveness and tolerability have extensively been demonstrated in the PIONEER clinical trial program. Nevertheless, data from real-world are crucial to evaluate treatment performance under routine care. The aim of this narrative review is to summarize available evidence regarding real-world utilization patterns of oral semaglutide, and discuss efficacy, safety, and dosing regimen data in routine scenarios., Methods: We searched PubMed for real-world studies evaluating oral semaglutide up to August 2024, and specific search terms were: "oral semaglutide," and "real-world studies" or "observational studies" or "retrospective studies"., Findings: 19 real-world studies were included in the narrative review. In real-world settings, oral semaglutide provided significant glycemic (median HbA1c reduction at 6 months of 1%) and weight (median body weight reduction of 2 to 3 kg) benefits across the spectrum of T2DM, aligning with pre-clinical evidence from the PIONEER program. No new tolerability and safety issue has emerged from oral semaglutide administration in routine clinical practice., Implications: Oral semaglutide constitutes an effective and safe option for T2DM management, and its increased acceptance has the potential to favor the early introduction of GLP-1RAs along the disease course. Nevertheless, continuous evaluation of real-world data is critical to better define the optimal positioning of oral semaglutide along T2DM trajectory and fully exploit its potential in everyday clinical practice., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Gian Paolo Fadini reports a relationship with Abbott, AstraZeneca, Boehringer, Lilly, MSD, Novo Nordisk, Novaartis, Sanofi, Servier, Takeda that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Participant recruitment for studies investigating neurodevelopmental conditions can be difficult, limited, and resource intensive. In this study, caregivers were surveyed to learn about the factors influencing their decision to enroll their neurodivergent child in research. Method: Data were collected through an online survey from caregivers of neurodivergent children who were signing up for a research recruitment database (n = 46). Results: Participants indicated the most important motives were to help achieve better outcomes for other children and to contribute to scientific understanding. Personal curiosities, such as the caregiver or child learning more about their condition, were identified as important for some parents. The most influential barrier to enrollment noted by participants was a heightened possibility of a significant negative side effect. Conclusion: These findings provide essential insight that can inform study design and associated research support that could overcome barriers and ensure families are aware of the benefits of participating in research.