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Streptococcus intermedius is an oral commensal organism belonging to the Streptococcus anginosus group (SAG). S. intermedius causes periodontitis as well as invasive, pyogenic infection of the central nervous system, pleural space or liver. Compared with other SAG organisms, S. intermedius has a higher mortality as well as a predilection for intracranial infection, suggesting it is likely to possess virulence factors that mediate specific interactions with the host resulting in bacteria reaching the brain. The mechanisms involved are not well described. Intracranial suppuration (ICS) due to S. intermedius infection can manifest as an abscess within the brain parenchyma, or a collection of pus (empyema) in the sub- or extra-dural space. These infections necessitate neurosurgery and prolonged antibiotic treatment and are associated with a considerable burden of morbidity and mortality. The incidence of ICS is increasing in several settings, with SAG species accounting for an increasing proportion of cases. There is a paucity of published literature regarding S. intermedius pathogenesis as well as few published genomes, hampering molecular epidemiological research. This perspective evaluates what is known about the clinical features and pathogenesis of ICS due to S. intermedius and explores hypothetical explanations why the incidence of these infections may be increasing.

We report the intercalation of polyacrylonitrile nanoparticles in Ti 3 C 2 T x MXene layers through simple sonication. The use of polyacrylonitrile, which was synthesized via radical polymerization, offered dual benefits: (1) It increased the interlayer spacing of MXene, thereby exposing more surface area and enhancing ion transport channels during charge and discharge cycles, and (2) Integrating MXene with polyacrylonitrile enables the creation of a composite with conductive properties, following percolation principle. X-ray diffraction analysis showed an increase in the c-lattice parameter, indicative of the interlayer spacing, from 22.31 Å for the pristine MXene to 37.73 Å for the MXene-polyacrylonitrile composite. The intercalated polyacrylonitrile nanoparticles facilitated the delamination by weakening the interlayer interactions, especially during sonication. Electrochemical assessments revealed significant improvement in the properties of the MXene-polyacrylonitrile composite compared to the pristine MXene. The assembled asymmetric device achieved a good specific capacitance of 32.1 F/g, an energy density of 11.42 W h/kg, and 82.2% capacitance retention after 10,000 cycles, highlighting the practical potential of the MXene-polyacrylonitrile composite.

This study presents a simple and an environmentally friendly approach to make Laser-Induced Graphene (LIG) based supercapacitor electrodes anchored with abundant Silver Nanoparticles (AgNPs). LIG, was synthesized using a CO 2 laser writing technique on polyimide substrate. The LIG-Ag composite was prepared using two techniques, drop-coating, and screen-printing. Ag nanoparticles prepared using the plant extract of Swietenia Macrophylla was utilized to drop-coat AgNP on LIG substrate. Screen-printing was done by using a commercial Ag-ink and a suitable mesh. The supercapacitor made from screen-printed electrodes and supercapacitor made form drop-coated electrodes showed a high specific capacitance of 118 mF/cm 2 , 38 mF/cm 2 , and a high energy density of 2.42 mWh/cm 2 , 0.05 mWh/cm 2 respectively. The screen-printed composite of LIG and AgNP was further studied for its anti-fungal properties and proved to be effective against Candida sp., Competing Interests: Declarations Competing interests Authors have no competing interests. Ethics declarations The plant sample used throughout this work was collected from within the university premises while following the university guidelines pertaining to environment conservation. Any activity that would harm the ecosystem, such as deforestation, has not been entertained throughout the duration of this work., (© 2024. The Author(s).)

Objectives: Cancer diagnosis comes as a shock to many patients, and many of them feel unprepared to handle the complexity of the life-changing event, understand technicalities of the diagnostic reports, and fully engage with the clinical team regarding the personalized clinical decision-making., Materials and Methods: We develop Oncointerpreter.ai an interactive resource to offer personalized summarization of clinical cancer genomic and pathological data, and frame questions or address queries about therapeutic opportunities in near-real time via a graphical interface. It is built on the Mistral-7B and Llama-2 7B large language models trained on a local database trained using a large, curated corpus., Results: We showcase its utility with case studies, where Oncointerpreter.ai extracted key clinical and molecular attributes from deidentified pathology and clinical genomics reports, summarized their contextual significance and answered queries on pertinent treatment options. Oncointerpreter also provided personalized summary of currently active clinical trials that match the patients' disease status, their selection criteria, and geographic locations. Benchmarking and comparative assessment indicated that the model responses were generally consistent, and hallucination, ie, factually incorrect or nonsensical response was rare; treatment- and outcome related queries led to context-aware responses, and response time correlated with verbosity., Discussion: The choice of model and domain-specific training also affected the response quality., Conclusion: Oncointerpreter.ai can aid the existing clinical care with interactive, individualized summarization of diagnostics data to promote informed dialogs with the patients with new cancer diagnoses., Availability: https://github.com/Siris2314/Oncointerpreter., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Growth differentiation factor 9 ( GDF9) is an oocyte-specific paracrine factor involved in bidirectional communication, which plays an important role in oocyte developmental competence. In spite of its vital role in reproduction, there is insufficient information about exact transcriptional control mechanism of GDF9. Hence, present study was undertaken with the aim to study the expression of basic helix-loop-helix (bHLH) transcription factors (TFs) such as the factor in the germline alpha (FIGLA), twist-related protein 1 (TWIST1) and upstream stimulating factor 1 and 2 (USF1 and USF2), and nuclear receptor (NR) superfamily TFs like germ cell nuclear factor (GCNF) and oestrogen receptor 2 (ESR2) under three different in vitro maturation (IVM) groups [follicle-stimulating hormone (FSH), insulin-like growth factor-1 (IGF1) and oestradiol)] along with all supplementation group as positive control, to understand their role in regulation of GDF9 expression. Buffalo cumulus-oocyte complexes were aspirated from abattoir-derived ovaries and matured in different IVM groups. Following maturation, TFs expression was studied at 8 h of maturation in all four different IVM groups and correlated with GDF9 expression. USF1 displayed positive whereas GCNF, TWIST1 and ESR2 revealed negative correlation with GDF9 expression. TWIST1 & ESR2 revealing negative correlation with GDF9 expression were found to be positively correlated amongst themselves also. GCNF & USF1 revealing highly significant correlation with GDF9 expression in an opposite manner were found to be negatively correlated. The present study concludes that the expression of GDF9 in buffalo oocytes remains under control through the involvement of NR and bHLH TFs.

We study the dependence of alignment and confinement on the aggregate morphology of self-aligning soft disks(particles) in a planer box (two dimensional) geometry confined along y direction using Langevin dynamics simulations. We show that when the box width decreases, the aggregate wall accumulation becomes non-uniform and displays non-monotonic behaviour in terms of phase behavior and height of these aggregates with an increase in alignment strength. Additionally, we identify two distinct categories of wall aggregates: layered and non-layered structures each exhibiting distinct local structural properties. For non-layered structures, local speed of the particles stay nearly constant as we move away from the boundary, while for layered structures, it increases with distance from the boundary. Our analysis shows that active pressure difference is a useful indicator for different aggregate morphologies and the peaks in the pressure curve are indicative of the average and minimum height of the structure., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

We studied the frequency and quality factor of mechanical plasmonic nanoresonators as a function of temperature, ranging from ambient to 4 K. Our investigation focused on individual gold nanorods and nanodisks of various sizes. We observed that oscillation frequencies increase linearly as temperature decreases until saturation is reached at cryogenic temperatures. This behavior is explained by the temperature dependence of the elastic modulus, with a Debye temperature compatible with reported bulk values for gold. To describe the behavior of the quality factor, we developed a model considering the nanostructures as anelastic solids, identifying a dissipation peak around 150 K due to a thermally activated process, likely of the Niblett-Wilks mechanism type. Importantly, our findings suggest that external dissipation factors are more critical to improving quality factors than internal friction, which can be increased by modifying the nanoresonator's environment. Our results enable the future design of structures with high vibration frequencies and quality factors by effectively controlling external losses.

A major growing concern in the human and animal health sector is the emergence of antibiotic-resistant pathogenic bacteria due to the indiscriminate use of antibiotics. The exogenous application of bacteriophage endolysins causes abrupt lysis of the bacterial cell wall, which computes them as alternatives to antibiotics. Although naturally occurring endolysins may display limitations in solubility, lytic activity, and narrow lytic spectrum, novel strategies like developing chimeric endolysins and using endolysins in synergism with other antimicrobial agents are required to improve the lytic activity of natural endolysins. The modular structure of endolysins led to the development of novel chimeric endolysins via shuffling enzymatic and cell wall binding domains of different endolysins, using endolysins in a synergistic approach, and their applications in various in vitro and in vivo experiments and different applicable areas. This article aims to review the role of chimeric endolysins and their use in synergistic mode with other biofilm-reducing agents to control biofilm formation and deteriorating pre-formed biofilms in food, dairy, and medical industries. Promoting further development of phage technology and innovation in antibiotic therapy can achieve long-term sustainable development and economic returns., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The water channel aquaporin 4 (AQP4) contributes to water flow and waste removal across the blood-brain barrier and its levels, organization and localization are perturbed in various neurological diseases, including Alzheimer's Disease. This renders AQP4 a potentially valuable therapeutic target. However, most functional assays aimed at identifying modulators of AQP4 function are performed with primary rodent cells and do not consider inter-cellular variations in AQP4 abundance and presentation. To address this, we have established and applied a robust live cell microscopy assay that captures the contribution of AQP4 in the osmotically driven (de-)quenching of the vital dye Calcein-AM with single-cell resolution. Using human astrocytoma cells, we found that performing measurements on cellular regions instead of whole fields of view yielded a more sensitive readout of the osmotic response, which correlated with AQP4 abundance. Stable co-expression of the two major AQP4 isoforms, but not of the individual isoforms, provoked a faster adaptation to osmotic changes, while siRNA-mediated knockdown of AQP4 had the opposite effect. Post-hoc correlation with the canonical membrane marker CD44 revealed that the speed of the osmotic response scaled with AQP4 membrane enrichment. Coating the substrate with laminin promoted AQP4 membrane enrichment, while cell confinement with fixed-size micropatterns further increased the speed of osmoregulation, underscoring the influence of extracellular factors. The osmotic response of primary fetal astrocytes and human iPSC-derived astrocyte models was comparable to AQP4-deficient astrocytoma cells, in line with their low AQP4 levels and indicative of their immature state. In conclusion, a correlative single-cell approach based on the quantification of Calcein-AM quenching capacity, AQP4 abundance and AQP4 membrane enrichment, allows resolving osmoregulation in a more sensitive manner and reveals heterogeneity between and within human astrocyte (-like) cultures, which could prove crucial for future screens aimed at identifying AQP4 modulators., (© 2024 International Society for Advancement of Cytometry.)

Clostridioides difficile infection (CDI) is a common cause of antibiotic-associated colitis. C. difficile proliferates and produces toxins that damage the colonic epithelium, leading to symptoms ranging from mild diarrhea to severe pseudomembranous colitis. The host's innate response to CDI occurs in two phases: an early phase in which neutrophils reduce the bacterial load and a late phase involving repair mechanisms to restore epithelial integrity. Group 3 innate lymphoid cells (ILC3s) are crucial in protecting the gut from CDI. Previous studies have shown that ILC3-derived IL-22 is essential in the late phase of CDI for epithelial repair and maintaining an intestinal microbiota that competes with C. difficile , preventing its expansion. Our study finds that ILC3s also protect during the early stages of CDI by sustaining neutrophils through GM-CSF. Less neutrophil production, accumulation, and activation was evident in ILC3-deficient mice than in wild-type (WT) mice, which led to exacerbated symptoms, impaired pathogen clearance, a compromised epithelial barrier, and increased mortality. The adoptive transfer of ILC3s into ILC3-deficient mice restored neutrophil responses and improved disease outcomes. Both in vitro and in vivo experiments revealed that GM-CSF production by ILC3s is crucial for neutrophil production and effective resistance during CDI. Using mice lacking NKp46 + ILC3s, we found that this subset significantly contributes to GM-CSF production in CDI. These findings highlight the critical role of the ILC3-neutrophil connection in early innate responses to CDI. Enhancing ILC3 production of GM-CSF could be a promising strategy for improving host defense against CDI and other enteric infections., Competing Interests: Competing interests statement:The authors declare no competing interest.

Purpose: To investigate early changes in AMD by evaluating and comparing choriocapillaris (CC) flow in fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) and in healthy controls using swept-source optical coherence tomography angiography (SS-OCTA)., Methods: Patients with unilateral nAMD and no/early/intermediate AMD (no/e/iAMD) in their fellow eye and normal controls who underwent SS-OCT and OCTA where included. CC perfusion was assessed on MATLAB as percentage of flow deficits (FD%) in the central 4.5 × 4.5 mm macular region, after removing artifacts., Results: 81 eyes/patients (22 eyes with noAMD, 30 with eAMD, 29 with iAMD) with unilateral nAMD and 24 controls were analyzed. Median FD% was 8.97 (IQR 8.58-9.53) in AMD group, 8.92 (IQR 8.64-9.27) in noAMD group, 8.96 (IQR 8.46-9.38) in eAMD group, 9.05 (IQR 8.58-9.8) in iAMD group, and 8.22 (IQR 7.78-8.55) in controls. A statistically significant difference in FD% was observed between controls and AMD group (p < 0.001), as well as between each AMD subgroup and controls (noAMD vs controls p = 0.0037; eAMD vs control p = 0.0012; iAMD vs controls p = 0.0002)., Conclusion: This study suggests that CC dysfunction may occur in fellow eyes of patients with unilateral nAMD before visible AMD signs, potentially preceding RPE changes. Further longitudinal studies are needed to confirm these findings and explore the correlation with AMD development/progression.

Understanding all parameters contributing to enzyme activity is crucial in enzyme catalysis. For enzymatic PET degradation, this involves examining the formation of the enzyme-PET complex. In IsPETase (WT), a PET-degrading enzyme from Ideonella sakaiensis, mutating two non-catalytic residues (DM) significantly enhances activity. Such mutations, depending on their position in the tertiary structure, fine-tune enzyme function. However, detailed molecular insights into these mutations' structure-function relationship for PET degradation are lacking. This study characterizes IsPETase's catalytic ability compared to WT TfCut2 using molecular dynamics simulations and quantum mechanical methods. We explore the conformational landscape of the enzyme-PET complex and quantify residue-wise interaction energy. Notably, aromatic and hydrophobic residues Tyr, Trp, and Ile in the catalytic subsite S1, and aromatic Phe and polar Asn in the anchoring subsite S3, crucially optimize PET binding. These residues enhance PET specificity over non-aromatic plastics. Our findings suggest that the balance between binding at subsite S1 and subsite S3, which is influenced by cooperative mutations, underlies catalytic activity. This balance shows a positive correlation with experimentally obtained kcat/Km values: WT TfCut2

Background Patients with neuromyelitis optica spectrum disorder (NMOSD) are often seropositive for antibodies against aquaporin-4 (AQP4). The importance of MRI monitoring in this disease requires evaluation. Purpose To profile MRI features from a large international cohort with AQP4 immunoglobulin G (IgG)-seropositive NMOSD (from the Parallel MRI in NMOSD [PAMRINO] study) and to evaluate and confirm existing knowledge regarding the incidence, location, and longitudinal development of characteristic lesions in the central nervous system associated with AQP4-IgG-seropositive NMOSD. Materials and Methods In this retrospective study (from August 2016 to January 2019), MRI and clinical data were collected from 17 NMOSD expert sites in 11 countries across four continents. Clinical features and lesions identified at cross-sectional and longitudinal MRI were assessed. No formal statistical tests were used to compare observations; however, means, SDs, and 95% CIs are reported when evaluating lesion frequencies. Results Available T1-weighted and T2-weighted MRI scans in patients with AQP4-IgG-seropositive NMOSD ( n = 525) were read. Among the 525 patients, 320 underwent cerebral MRI examinations with T2-weighted hyperintense cerebral (264 of 320; 82.5%), cerebellar (44 of 320; 13.8%), and brainstem (158 of 321 [49.2%], including one lesion observed at cervical spinal cord [SC] MRI) lesions. Lesions in the optic nerves, analyzed from 152 MRI examinations, were mainly found in the central (81 of 92; 88%) and posterior (79 of 92; 86%) sections (bilaterally in 39 of 92; 42%). Longitudinally extensive transverse myelitis was the predominant SC lesion pattern (upper compartment from 322 MRI examinations, 133 of 210 [63.3%]; and lower compartment from 301 MRI examinations, 149 of 212 [70.3%]). However, nonlongitudinal extensive transverse myelitis lesions were also observed frequently (105 of 210; 50.0%) in the cervical SC. Clinical data ( n = 349; mean age, 44 years ± 14 [SD]; 202 female patients) and acute lesions at contrast-enhanced (CE) MRI ( n = 58, performed within 30 days of the last attack) were evaluated. CE lesions were detected in the cerebrum (eight of 13; 62%), optic nerves (14 of 19; 74%), or chiasm (three of four; 75%) within 15 days of any relapse. In the upper SC (29 of 44; 66%), CE lesions were frequently observed up to 20 days after a clinical myelitis event. Conclusion A high incidence of abnormal brain MRI examinations and nonlongitudinal extensive SC lesions was found in patients in PAMRINO with AQP4-IgG-seropositive NMOSD. © RSNA, 2024 Supplemental material is available for this article.

Aquaporins (AQPs) are essential membrane proteins facilitating water and small solute transport across cell membranes. Mammals have approximately 13 paralogs of AQPs that may have evolved through gene duplication events. These genes are present in two separate clusters within the genome. In the present study, comprehensive 13 AQP genes (AQP0-12) were cloned and characterized in buffalo and goat. The protein coding region of AQPs in both species ranged from 729 to 990 bps, corresponding to 263-330 amino acid residues. Two important residues including NPA motifs and ar/R selectivity filter were found conserved in all AQPs, except for AQP7, 11 and 12. AQP0, 2, 4, 5, 7, 9, 12 showed tissue-restricted expression, whereas AQP1, 3, 8, and 11 exhibited ubiquitous expression across several tissues. AQP10 was identified as a pseudogene in all artiodactyls. Transcript variants were identified in buffalo and goat, where some variants of goat AQP5 and 6 lacked important motifs. Evolutionary analysis indicated positive selection at or near the NPA motifs and ar/R selectivity filter of AQP0, 3, 6, 7, and 10 that may alter its structure and function. This study is crucial for future investigations aiming to study the molecular mechanisms of AQPs in response to various physiological conditions., Competing Interests: Declaration of competing interest The authors declare that they have read and approve the present manuscript and there is 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.)

Aim: To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis., Methods: This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes., Results: Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05)., Conclusion: We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

In vitro embryo production is one of the main reproductive techniques used in dairy Gyr cattle. In addition, linear type measures are well characterized and have been used in dairy Gyr breed selection for the last 4 decades. The estimation of genetic parameters for the number of aspirated oocytes and in vitro-produced embryos associated with the linear type measures would support genetic progress for animal breeding programs toward embryo production. This study aimed to estimate genetic parameters for aspirated oocytes, embryo in vitro production, and linear type traits, exploring the association between them. The repeatability model was applied to 14,251 ovum pick-up events from 1,916 Gyr donors. A subset of 604 donors from the same group had their body measurements taken. Single- and 2-trait analyses were carried out using the BLUPF90 family programs. Heritability estimates of 0.38, 0.34, and 0.20 were obtained for total oocytes, viable oocytes, and embryos, respectively, and the heritability of the linear type traits ranged from 0.22 to 0.40. High genetic correlations between total oocytes and viable oocytes (0.99), and between oocytes (total and viable) and embryos (0.83) were obtained. Low to high genetic (-0.07 to 0.92) and phenotypic (0.32-0.86) correlations were obtained between the linear type traits. Moreover, low phenotypic correlations (0.01-0.13) were observed for oocytes (total and viable) and embryos with the linear type traits, whereas low to moderate genetic correlations (0.07-0.42) were observed between the same traits, especially for ilium width (0.42), rump area (0.38), and hip height (0.33). Thus, selection for in vitro production is achievable in Gyr dairy cattle, and superior genetic progress is associated with the selection of oocytes (total and viable). Furthermore, the moderate genetic association between oocytes and embryos with linear type traits, especially ilium width suggests that progress on in vitro embryo production may be achieved by accessing these measurements., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Cellular senescence, a state of persistent growth arrest, is closely associated with aging and age-related diseases. Deciphering the heterogeneity within senescent cell populations and identifying therapeutic targets are paramount for mitigating senescence-associated pathologies. In this study, proteins on the surface of cells rendered senescent by replicative exhaustion and by exposure to ionizing radiation (IR) were identified using mass spectrometry analysis, and a subset of them was further studied using single-cell CITE-seq (Cellular Indexing of Transcriptomes and Epitopes by Sequencing) analysis. Based on the presence of proteins on the cell surface, we identified two distinct IR-induced senescent cell populations: one characterized by high levels of CD109 and CD112 (cluster 3), the other characterized by high levels of CD112, CD26, CD73, HLA-ABC, CD54, CD49A, and CD44 (cluster 0). We further found that cluster 0 represented proliferating and senescent cells in the G1 phase of the division cycle, and CITE-seq detection of cell surface proteins selectively discerned those in the senescence group. Our study highlights the heterogeneity of senescent cells and underscores the value of cell surface proteins as tools for distinguishing senescent cell programs and subclasses, paving the way for targeted therapeutic strategies in disorders exacerbated by senescence., (© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Germline mutations of homologous-recombination (HR) genes are among the top contributors to medulloblastomas. A significant portion of human medulloblastomas exhibit genomic signatures of HR defects. Whether ablation of Brca2 and Palb2, and their related Brca1 and Bccip genes, in the mouse brain can differentially initiate medulloblastomas was explored here. Conditional knockout mouse models of these HR genes and a conditional knockdown of Bccip (shBccip-KD) were established. Deletion of any of these genes led to microcephaly and neurologic defects, with Brca1 - and Bccip - producing the worst defects. Trp53 co-deletion significantly rescued the microcephaly with Brca1, Palb2, and Brca2 deficiency but exhibited limited impact on Bccip - mice. For the first time, inactivation of either Brca1 or Palb2 with Trp53 was found to induce medulloblastomas. Despite shBccip-CKD being highly penetrative, Bccip/Trp53 deletions failed to induce medulloblastomas. The tumors displayed diverse immunohistochemical features and chromosome copy number variation. Although there were widespread up-regulations of cell proliferative pathways, most of the tumors expressed biomarkers of the sonic hedgehog subgroup. The medulloblastomas developed from Brca1 - , Palb2 - , and Brca2 - mice were highly sensitive to a poly (ADP-ribose) polymerase inhibitor but not the ones from shBccip-CKD mice. These models recapitulate the spontaneous medulloblastoma development with high penetrance and a narrow time window, providing ideal platforms to test therapeutic agents with the ability to differentiate HR-defective and HR-proficient tumors., Competing Interests: Disclosure Statement None declared., (Copyright © 2024 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Clinical genomic profiling of cell-free nucleic acids (e.g. cell-free DNA or cfDNA) from blood and other body fluids has ushered in a new era in non-invasive diagnostics and treatment monitoring strategies for health conditions and diseases such as cancer. Genomic analysis of cfDNAs not only identifies disease-associated mutations, but emerging findings suggest that structural, topological, and fragmentation characteristics of cfDNAs reveal crucial information about the location of source tissues, their epigenomes, and other clinically relevant characteristics, leading to the burgeoning field of fragmentomics. The field has seen rapid developments in computational and genomics methodologies for conducting large-scale studies on health conditions and diseases - that have led to fundamental, mechanistic discoveries as well as translational applications. Several recent studies have shown the clinical utilities of the cfDNA fragmentomics technique which has the potential to be effective for early disease diagnosis, determining treatment outcomes, and risk-free continuous patient monitoring in a non-invasive manner. In this article, we outline recent developments in computational genomic methodologies and analysis strategies, as well as the emerging insights from cfNA fragmentomics. We conclude by highlighting the current challenges and opportunities., 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. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for Translational Oncology and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024. Published by Elsevier Inc.)

Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention. At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy. The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention. Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients' associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients' associations - invert the pyramid order. In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

With the alarming rise in cases of arterial hypertension worldwide, there is an urgent need to develop combined therapies to mitigate this scenario. Rose oxide (RO), a monoterpene with anti-inflammatory and hypotensive properties, emerges as an alternative. The present study is the first to evaluate the effect of RO administered chronically and combined with physical exercise (swimming) since both have been reported to have beneficial impacts on hypertension. Male SHR and Wistar rats (aged 12 weeks) received RO for 34 consecutive days (orally; 100 mg/kg). The progression of systolic arterial pressure (SAP) was monitored through tail-cuff plethysmography. Twenty-four hours before the end of the treatment, the animals were anesthetized, and the femoral artery and vein were cannulated to record the pulsatile arterial pressure and to administer drugs, respectively. Hemodynamic and autonomic parameters and baroreflex sensitivity and intrinsic heart rate (IHR) were evaluated. Treatment with RO, administered alone or combined with exercise, reduced SAP and mean arterial pressure in SHR. The swimming protocol did not prevent increases in BP, but when combined with RO, it improved autonomic control, assessed through heart rate variability and parasympathetic tone. IHR was attenuated in SHR, and none of the treatments reversed this response. Therefore, combining RO with physical exercise may enhance their antihypertensive effects, improving autonomic function, reducing oxidative stress and inflammation, providing synergistic cardiovascular benefits, improving metabolic health, promoting a comprehensive lifestyle intervention, and potentially allowing for reduced medication dosages. This multifaceted approach could offer a more effective and sustainable strategy for managing hypertension., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Long non-coding RNAs (lncRNAs) are highly versatile in their modes of action and play critical roles in both normal physiological and disease processes. The dysregulation of lncRNA expression has been implicated in aging and many neurological disorders, including Alzheimer's disease (AD). Here, we report a spatial expression atlas of 7,634 lncRNA genes in aged human brains, covering 258,987 microdomains from 78 postmortem brain sections of 21 ROSMAP participants. We detected a greater proportion of lncRNAs expressed specifically in distinct cortical subregions than mRNAs, and most belong to antisense and lincRNA biotypes. We generated 193 gene modules from gene networks of 8 subregions and identified lncRNA-enriched gene modules implicated in multiple AD-relevant biological processes. By cross-referencing published snRNA-seq data, we detected a partially overlapping but independent pattern between sub-region and cell-type specificity of lncRNA expression. We mapped spatially differentially expressed (SDE) lncRNAs and mRNAs in AD brains and observed that SDE lncRNAs encompass more subregion-specific transcripts. Gene set enrichment analysis indicates that AD SDE lncRNAs are involved in epigenetic regulation, chromatin remodeling, RNA metabolism, synaptic signaling, and apoptosis. Particularly relevant to AD therapeutic potentials is an enrichment for HDAC target genes, including OIP5-AS1 , a lncRNA extensively studied in cancer and, most recently, in AD. We then applied multivariate fine-mapping to the expression quantitative trait loci (eQTLs) proximal to the OIP5-AS1 loci and identified rs1655558 as a potential genetic driver of OIP5-AS1 expression. Using statistical modeling, we inferred that the interaction between OIP5-AS1 and HDAC proteins, especially HDAC11, is associated with tau tangles in excitatory neurons and plaque burden in microglia. Our study represents a valuable resource of lncRNA spatial expression in the aged human brain, shedding mechanistic insights into their functional roles in AD and neurodegeneration.

Background: The MDS-UPDRS has been available in English since 2008, showing satisfactory clinimetric results and being proposed as the new official benchmark scale for Parkinson's disease (PD), being cited as a core instrument for PD in the National Institutes of Neurological Disorders and Stroke Common Data Elements program. For this reason, the MDS created guidelines for development of MDS-UPDRS official, clinimetrically validated translations., Objective: This study presents the formal process used to obtain the officially approved Portuguese version of the MDS-UPDRS., Methods: The study consisted of three phases: (1) Independent translation by Portuguese and Brazilian teams followed by a challenging consensus process that this article particularly emphasizes; (2) Cognitive pretest involving raters and patients from both Portugal and Brazil; (3) Validation test with a sample of 367 native Portuguese-speaking PD patients., Results: The overall factor structure of the Portuguese version was consistent with the English version based on a comparative fit index ≥0.96 for all four parts of the MDS-UPDRS., Conclusion: This version can be designated as the official Portuguese version of the MDS-UPDRS., (© 2024 International Parkinson and Movement Disorder Society.)

Objective: To verify the effect of the educational intervention TIV-Disinfect (Intravenous Therapy-Disinfect) on the knowledge of nursing professionals in pediatric inpatient units., Method: Quasi-experimental study, with a dependent sample of 65 nursing professionals from pediatric inpatient units. A questionnaire with objective questions regarding the disinfection of venous devices was used, and pre- and post-tests were applied. Data collection was conducted in two public hospitals in southern Brazil, between April and July 2022. For data analysis, descriptive statistics and McNemar's test were used., Results: There was a statistically significant difference between the pre- and post-tests regarding variables of passive disinfection, and recommended antiseptics and materials, rubbing and drying. A lower frequency of incorrect alternatives was noted after the intervention., Conclusion: The educational intervention had a positive effect. Better results were observed in the knowledge of nursing professionals regarding the disinfection of venous devices, as well as allowing the professionals to reinforce already consolidated knowledge. This intervention can be used as a tool for updating and/or continuing training of nursing professionals, aiming at the safety of pediatric patients and care practices.

The fruit of Spondias mombin (cajazeira) is widely consumed in the northeast region of Brazil. In this work, three different extraction methods, namely ultrasound-assisted extraction (UAE), turbo-extraction (TE) and pressurized hot water extraction (PHWE), were evaluated in order to investigate the potential of cajazeira leaves as an alternative source of bioactive compounds. The extraction methods were compared in terms of yield, chemical composition and total phenolic content (TPC) of the extracts. The highest yields and TPC values were obtained by TE with a mixture ethanol: water (70:30%, v/v) as the solvent. PHWE has not yet been applied for the extraction of cajazeira leaves. Thus, it was evaluated as one alternative for the recovery of phenolic compounds under conditions of 80, 100 and 120 °C and 100 and 120 bar. A modeling study of PHWE kinetics was investigated at 80 °C and 200 bar. Furthermore, a biorefinery approach considering integrated processes to recover bioactive compounds was investigated and the results showed that combining processes may enhance the valorization of agricultural waste.

Climate change and growing population and their strain on animal production are the impending challenges that the developing countries, like India, need to tackle in the coming days. This study aimed to detect and analyze the uncharacterized variation in the gene expression patterns with the change of condition, from thermoneutral to chronic hot-humid, in the Sahiwal cattle, one of the best breeds of milk-producing cattle in India, known for being heat-tolerant. Using RNA-Seq analysis on peripheral blood mononuclear cells (PBMCs), 4021 differentially expressed mRNAs (2772 upregulated, 1249 downregulated) and 1303 differentially expressed long non-coding RNAs (769 upregulated, 534 downregulated) were identified, with the thresholds of false discovery rate < 0.05 and|log 2 (fold change)| > 2. Significantly (p-adjusted < 0.05) overrepresented Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathways were analyzed, revealing upregulation of processes like pyruvate metabolic process, gluconeogenesis, ion transmembrane transport, neuropeptide signaling pathway, and animal organ development, with genes like SHH, GRK1, CHRM3, CAMK2A, and HSPB7 were upregulated, while translation and immune responses, with genes like RPS3, EEF1A1, TNF, BoLA-DRB3, and UBB were downregulated. Analysis of cis-mRNAs of DE-lncRNAs showed presence of both up- and down-regulated cis-mRNAs for both up- and down-regulated lncRNAs indicating existence of positive and negative regulation of mRNA expression by lncRNAs. Managemental nudges that decrease metabolic heat generation, like betaine and chromium supplementation, and increase heat dissipation, like microenvironment cooling, should be utilized. This study highlights the role of pyruvate metabolism and gluconeogenesis in coping up with heat stress and offers an improved understanding of the heat stress response of Sahiwal cattle along with the genes and pathways responsible for it., (© 2024. The Author(s) under exclusive licence to International Society of Biometeorology.)

Leishmaniasis is a diverse group of clinical diseases caused by protozoan parasites of the Leishmania genus. Species-specific identification of Leishmania spp. is challenging due to the high number of different pathogenic species that sometimes co-circulate in the same foci, hampering efforts to effectively control the disease. Multiplex PCR is an attractive alternative for rapid differentiation of Leishmania species with high sensitivity and specificity. We aimed to generate a panel of primers optimized for a multiplex PCR assay capable of identifying different Leishmania species in a single reaction. Species-specific primers were designed based on genomic data using the TipMT tooL. Potential non-specific amplifications of other trypanosomatids as well as human, dog, and sandfly hosts were first evaluated in silico using the Primer-Blast tooL. Species-specific primers for Leishmania amazonensis, Leishmania braziliensis, Leishmania donovani, Leishmania infantum, Leishmania mexicana and for the Leishmania guyanensis complex were tested in vitro. The primers have a limit of detection ranging from 1 to 0.01 ng of parasite gDNA using the same annealing temperature of 66 °C. The primers were specific for their targets when tested against 13 species of Leishmania, six trypanosomatids, and Babesia sp., and to detect the target species in a prepared pool with gDNA of six pathogenic Leishmania species. The designed primers were optimized for multiplex PCR, enabling species-specific identification of all five Leishmania species and one species complex. This new primer set could allow for efficient, fast, and reliable identification of Leishmania parasites., 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. Published by Elsevier B.V.)

Microbial biofilms constitute a significant virulence factor and a substantial challenge in clinical environments due to their role in promoting antimicrobial resistance and their resilience to eradication efforts. Methicillin-resistant Staphylococcus aureus (MRSA) infections substantially increase healthcare costs, extend hospitalizations, and elevate morbidity and mortality rates. Therefore, developing innovative strategies to target and eliminate these bacteria and their biofilms effectively is imperative for robust epidemiological control. In this study, we evaluated the antibacterial and antibiofilm activities of cell-free supernatant (CFS) obtained from the Bacillus velezensis 1273 strain culture. Our data showed that CFS inhibited the growth of S. aureus ATCC 29213 and MRSA (clinical strain), with greater efficacy observed against S. aureus (1:16 dilution). Furthermore, CFS showed substantial potential in reducing biofilm formation in both strains (∼30 %) at subinhibitory concentrations. Additionally, the antibacterial activity against biofilm-formed cells showed that pure CFS treatment decreased the viability of S. aureus (60 %) and MRSA (45 %) sessile cells. We further demonstrated that CFS treatment induces the production of reactive oxygen species (ROS) and damages the membranes and cell walls of the pathogen cells. Genome analysis revealed the presence of genes encoding bacteriocins and secondary metabolites with antibacterial activity in the B. velezensis 1273 genome. These findings highlight the potential of probiotic bacterial metabolites as antibiofilm and anti-multidrug-resistant pathogens., 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 Ltd. All rights reserved.)

Introduction: Pediatric pelvic and acetabular fractures are rare but potentially devastating injuries and significant management variation exists across the United States. This study sought to elucidate treatment decision-making trends, involvement of adult trauma fellowship-trained surgeons in pediatric care, and pre- and postoperative transfer patterns., Methods: Pediatric orthopaedic surgeons who serve as trauma liaisons at 20 PTCs were surveyed regarding training, practice volume, and factors contributing to institutional management of pelvic and acetabular injuries. Five clinical scenarios of pelvic ring and acetabular fractures that varied by injury pattern, age, and sex were presented. Descriptive statistics were used to summarize the results., Results: Eighteen institutions responded to the survey (90% response rate, 16 Level, 1 PTC). All surgeons were pediatric fellowship-trained (77.7% in practice >5 y). The four most common factors affecting whether surgeons independently managed both pelvic ring and acetabular fractures were patient age, fracture characteristics, displacement and need for surgery. The majority reported managing <10 acetabular (72.2%) but >10 pelvic ring (77.8%) injuries per year. In the clinical scenarios, patients <10 were more likely to have treatment decisions made by a pediatric orthopaedic surgeon. Older patients were more likely to be transferred to another institution for surgery but were often transferred back to the PTC postoperatively. In all clinical scenarios other than posterior hip dislocation, a trauma fellowship-trained surgeon was more likely to be the operative surgeon, even when the patient was not transferred., Conclusions: There is substantial variation in the management of pediatric and adolescent pelvic and acetabular fractures. Even at tertiary care PTCs, volumes are low, and trauma fellowship-trained surgeons are often involved in decision-making and operative management. Age and injury pattern seem to play a large role in variation, and patient transfers between facilities are common., Level of Evidence: V., Competing Interests: J.S. is a consultant for OrthoPediatrics. I.S. is a consultant for OrthoPediatrics. W.T. is currently receiving grants from the National Institutes of Health and the Gillette Foundation. The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The intricate healing mechanism of chronic wounds and their multitude of healing-related obstacles, such as infections, compromised cellular processes, and impediments to the healing process, pose a significant healthcare problem. Exploration of metal oxide nanoparticles, such as yttrium oxide (Y 2 O 3 ) nanoparticles, can lead to innovative discoveries in the field of chronic wound healing by offering cues that promote cell proliferation in the scaffolds. To achieve this, Y 2 O 3 nanoparticles were synthesized and incorporated within poly(vinyl alcohol) (PVA) nanofibrous scaffolds. Moreover, lysine was infused in the nanofibrous scaffolds to tune its cell adhesion and antimicrobial property. The structure and morphology of the synthesized nanofibers were confirmed through various physicochemical characterizations. Notably, all the fabricated scaffolds have remarkably tuned WVTR values within the range of 2000-2500 g/m 2 /day, favorable for removing the wound exudate, which facilitate the healing process. The scaffolds exhibited substantial antimicrobial property of approximately 68% and 72.2% against both E. coli and S. aureus at optimized Y 2 O 3 loading. They further prevented the formation of biofilm by 68.6% for S. aureus and 51.2% for P. aeruginosa , suggesting the inhibition of recurrent wound infection. The scaffolds illustrated good blood biocompatibility, cytocompatibility, and cell adhesion capabilities. In vitro ROS inhibition study also corroborated the antioxidant property of the scaffold. Similarly, the wound scratching experiment showed high proliferative capability of a yttria-loaded PVA/lysine (S3) sample through the development of an extracellular matrix support. Molecular insight of wound healing was also validated through flow cytometry analysis and immunocytochemistry imaging studies. The findings revealed increased collagen I (Col-I) expression of approximately 19.48% in cultured fibrocytes. The findings are validated from immunocytochemistry imaging. In summary, the results furnish a captivating paradigm for the use of these scaffolds as a therapeutic biomaterial and to foster their potential efficacy toward wound care management.

This protocol aims to demonstrate the surgical technique for transferring cloned pig embryos to the oviduct, a method widely used in the production of genetically modified pigs for biomedical research. Nine gilts underwent hormonal synchronization and laparotomy for the transfer of cloned embryos produced by somatic cell nuclear transfer (SCNT) at stages of up to 4 cells on day 2 to the oviduct. Gestational diagnosis was conducted via ultrasound examination 30 days post-transfer surgery. Six out of the nine operated gilts exhibited signs of pregnancy on ultrasound examination. However, as there was no progression in fetal development as assessed by echography, the gilts underwent necropsy at 60 days for the collection of biological material and assessment of the reproductive system. Adhesions were observed in the uterine horns, ovaries, and oviducts. From the uterine lumen of two of the euthanized gilts, one and four embryonic structures with gestational ages ranging between 12 to 20 days were obtained. Despite the absence of live piglets, likely attributed to the low-efficiency rate of transferring cloned pig embryos, which is influenced by various factors, including the number and quality of transferred embryos, the presented surgical technique proved to be rapid and safe.

Objective: To compare neonatal outcomes following URS, stent, or PCN in pregnant women presenting with suspected renal colic., Methods: Women undergoing a procedure for suspected renal colic during pregnancy at a large multi-center institution between 2008 and 2022 were retrospectively reviewed and categorized by initial intervention. Neonatal outcomes were recorded and linked to maternal and obstetric data. Groups were compared by a Kruskal-Wallis, ANOVA, or Fisher's Exact test, followed by pairwise post-hoc testing as appropriate (α = 0.05). Multivariate analyses were also conducted., Results: 95 patients were analyzed, of whom 32 were managed with PCN, 47 with stent, and 16 with URS. Maternal baseline characteristics were similar between groups, except for lower gravidity and parity in the stent group. Rates of premature delivery did not differ, but gestational age at delivery was lower in the PCN group versus the stent and URS groups (p = 0.006 and p = 0.025, respectively). Neonatal Intensive Care Unit (NICU) admission rates were higher in the PCN group versus the stent and URS groups (p = 0.006 and 0.036, respectively). Respiratory distress syndrome significantly differed between groups (p = 0.041). Neonatal birth weight, Apgar scores, and other complications did not significantly differ., Conclusion: This study demonstrated higher rates of NICU admissions and lower gestational age at delivery for neonates born to mothers managed with PCN compared to stent and URS. Larger multi-institutional studies are warranted to further explore these associations., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Smita De reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. Sri Sivalingam reports a relationship with Fortec medical that includes: consulting or advisory and travel reimbursement. Sri Sivalingam reports a relationship with BD Urology that includes: consulting or advisory and travel reimbursement. Sri Sivalingam reports a relationship with Karl Storz Endoscopy America Inc that includes: consulting or advisory and travel reimbursement. Sri Sivalingam reports a relationship with Cook Medical Inc that includes: consulting or advisory and travel reimbursement. 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 Elsevier B.V. All rights reserved.)

Examination of all publicly available Oryctolagus cuniculus (rabbit) ribosome cryo-EM structures reveals numerous confusing inconsistencies. First, there are a plethora of single nucleotide differences among the various rabbit 28S and 18S rRNA structures. Second, two nucleotides are absent from the NCBI Reference Sequence for the 18S rRNA gene. Moving forward, we propose using the Broad Institute's rabbit whole genome shotgun sequence and numbering to reduce modeling ambiguity and improve consistency between ribosome models.

By integrating dielectric and metallic components, hybrid nanophotonic devices present promising opportunities for manipulating nanoscale light-matter interactions. Here, we investigate hybrid nanoparticle-on-mirror optical cavities, where semiconductor WS 2 monolayers are positioned between gallium phosphide (GaP) nanoantennas and a gold mirror, thereby establishing extreme confinement of optical fields. Prior to integration of the mirror, we observe an intermediate coupling regime from GaP nanoantennas covered with WS 2 monolayers. Upon introduction of the mirror, enhanced interactions lead to modal splitting in the exciton photoluminescence spectra, spatially localized within the dielectric-metallic gap. Using a coupled harmonic oscillator model, we extract an average Rabi splitting energy of 22.6 meV at room temperature, at the onset of the strong coupling regime. Moreover, the characteristics of polaritonic emission are revealed by the increasing Lorentzian linewidth and energy blueshift with increasing excitation power. Our findings highlight hybrid nanophotonic structures as novel platforms for controlling light-matter coupling with atomically thin materials.

Background: Social Communication Disorder (SCD), introduced in the DSM-5, is distinguished from Autism Spectrum Disorder (ASD) by the absence of restricted and repetitive behaviors or interests (RRBIs)., Aim: To compare the adaptive, sensory, communication, and cognitive profiles of children with ASD and SCD., Methods: The assessments of nine children with SCD and ten with ASD were compared with either Fisher's Exact Test or the Mann-Whitney Test. Assessments included the Vineland Adaptive Behavior Scales, the Autism Diagnostic Observation Schedule (ADOS), the Short Sensory Profile, Bishop's Children's Communication Checklist, a pragmatics evaluation, and the Wechsler Intelligence Scale for Children IV., Results: The total ADOS score and the second subtotal "Restricted and Repetitive Behaviors" were significantly higher ( p = 0.022) in the ASD group than in the SCD group. The Vineland standard score for the "Socialization" domain was significantly lower ( p = 0.037) in the ASD group (mean: 51 +/- 19) than in the SCD group (mean: 80 +/- 28). The working memory index score was also significantly lower ( p = 0.013) in the ASD group compared to the SCD group., Conclusions: While ASD and SCD share similarities in communication and pragmatic difficulties, some distinctions have been identified, e.g. in executive functioning and the impact on socialization, which may be linked to the absence of RRBIs in SCD. These findings highlight the challenges posed by this nosographic separation during diagnostic evaluations due to the scarcity of discriminative tools.

Background: Transcarotid artery revascularization (TCAR) has emerged as an alternative therapeutic modality to carotid endarterectomy (CEA) and transfemoral carotid artery stenting (TFCAS) for the management of patients with carotid artery stenosis. However, certain issues regarding the indications and contraindications of TCAR remain unanswered or unresolved. The aim of this international, expert-based Delphi consensus document was to attempt to provide some guidance on these topics., Methods: A 3-round Delphi consensus process was performed, including 29 experts. The aim of round 1 was to investigate the differing views and opinions of the participants. Round 2 was carried out after the results from the literature on each topic were provided to the participants. During round 3, the participants had the opportunity to finalize their vote., Results: Most participants agreed that TCAR can or can probably or possibly be performed within 14 days of a cerebrovascular event, but it is best to avoid it in the first 48 hr. It was felt that TCAR cannot or should not replace TFCAS or CEA, as each procedure has specific indications and contraindications. Symptomatic patients >80 years should probably be treated with TCAR rather than with TFCAS. TCAR can or can probably be used for the treatment of restenosis following CEA or TFCAS. Finally, there is a need for a randomized controlled trial (RCT) to provide better evidence for the unresolved issues., Conclusions: This Delphi consensus document attempted to assist the decision-making of physicians or interventionalists or vascular surgeons involved in the management of carotid stenosis patients. Furthermore, areas requiring additional research were identified. Future studies and RCTs should provide more evidence to address the unanswered questions regarding TCAR., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The role of the emergency medical service (EMS) is changing globally as ambulance crews respond to a shifting burden of disease, as well as societal stressors such as violence and inequality. New ways of thinking about how to provide emergency care are required to shift EMS from a role primarily focused on clinical care and transporting patients to hospital. In this paper, we present the experience of the Philippi Project (PP), an innovative community-based model of care developed by front line ambulance crews in a low-income neighbourhood in Cape Town, South Africa. Our insights were developed through observational, interview and document review work, within an overall embedded research approach. Our analysis draws on the everyday health systems resilience (EHSR) framework, which sees resilience as an emergent process that may be stimulated through response to stress and shock. Responses take the form of absorptive, adaptive or transformative strategies and are underpinned by system capacities (cognitive, behavioural and contextual). We consider the PP as a potentially transformative resilience strategy, defined as a new way of working that offered the promise of long-term health system gains. We found that the PP's initial development was supported by a range of system capacity attributes (such as the intentional development of relationships, a sense of collective purpose and creating spaces for constructive sense-making). However, the PP was hard to sustain over time because emergent ways of working were undermined both by other capacity attributes rooted in pre-existing organizational routines and two contextual shocks (Coronavirus and a violent incident). The paper adds a new empirical contribution to the still-small EHSR literature. In addition, the PP experience offers globally relevant lessons for developing community-based models of EMS care. It demonstrates that front line staff can develop creative solutions to their stressful daily realities, but only if space is created and protected., (© The Author(s) 2024. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

This study investigated the physicochemical, low glycemic index, and mineral uptake of functional noodles added with varying concentrations (0-10 %) of Lentinus edodes (also known as shiitake) powder. Noodles with 4 % mushroom powder (L3) exhibited comparable sensory attributes in comparison with control noodles. The L3 showed significantly higher protein (1.92 ± 0.035 %), decreased carbohydrate content, improved cooking characteristics. The L3 exhibited darker color with lower hardness, adhesiveness, higher mineral content and bioavailability of iron (59.22 ± 0.49 %). As well, L3 showed a significantly higher mineral transport, retention, and uptake of minerals followed by increased ferritin content (29.17 ± 0.52 ng/mg cell protein). Mushroom powder incorporation in noodles significantly decreased the area under the curve of reducing sugar release correlating with lower glycemic index and thus a potential impact on blood sugar levels. This study illustrates the efficacy of mushroom powder as a functional component in noodles, offering both augmented nutritional advantages and increased glycemic regulation., Competing Interests: 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., (© 2024 The Authors.)

Background: The ethical challenges faced by undergraduate nursing students and nurses may lead to moral distress, negatively affecting learning capacity and self-confidence and potentially influencing the quality of patient care. Objective: To examine the state of knowledge regarding the moral distress among undergraduate nursing students during clinical practice. Methods: This scoping review followed JBI guidelines. First, the LILACS, Web of Science, Scopus, CINAHL, PubMed/MEDLINE, PsycINFO, Embase, and ProQuest databases were consulted. Next, the reference lists of the studies included in the sample were checked. Studies exploring moral distress among undergraduate nursing students during clinical practice were included regardless of language or date of publication. Two independent reviewers simultaneously selected the studies. Results: The sample included 12 articles with different research designs. Three conditions that trigger moral distress among undergraduate nursing students emerged: Interpersonal relationships between students and preceptors/supervisors and multidisciplinary teams; interpersonal relationships between students and patients; and the relationship between students and health services. Conclusions: This review identified the various circumstances that lead to moral distress among undergraduate nursing students. Therefore, these results highlight the importance of preventing moral distress in this group through teaching, especially before students begin their clinical practices., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: One of the authors is a member of the Editorial Board.

Equal access to health initiatives and services under the principles of universal and comprehensive care remains a challenge in Brazil. The realization of public health policies is further intricate when one examines the health situation of people deprived of liberty. This study showcases the "Prison System: Beyond the Walls" educational pathway, available on the Virtual Learning Environment of the Brazilian National Health System (AVASUS). The action research methodological strategy guided the pathway development, emphasizing dialogic learning. The goal was to address the need for massive training on the topic of prison health, with the model focusing on engagement through spontaneous, non-mandatory participation in the pathway courses. The pathway comprised four modules, whose educational offerings were based on the self-learning model. Students were free to choose which courses to take and in what order, as there was no prerequisite for participating in modules. Hence, students could either take all the courses or only those with which they identify their learning needs, regardless of work demands or personal interests. Structuring the pathway through action research facilitated a massive, cohesive, and continuous training process. This approach expanded knowledge and established meaningful relationships among the related topics and the key players involved: health professionals, prison officers, and people deprived of liberty. Notably, the pathway courses have surpassed the 50,000-enrollment mark, spanning all five regions of Brazil. In this context, this article presents and discusses the development of the "Prison System: Beyond the Walls" pathway, emphasizing the massive improvement of health within Brazil's prison system and highlighting the results achieved.

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/ personal relationships, which may be considered as potential competing interests: Louisa Ho and Smita De are paid consultants to Boston Scientific.

Flo8 is a main transcriptional regulator of flocculation and pseudohyphal growth in yeast. Disruption of FLO8 in the popular recombinant protein production host Komagataella phaffii (Pichia pastoris) prevents pseudohyphal growth and reduces cell-to-surface adherence, making the mutant an interesting platform for research and industry. However, knowledge of the physiological impact of the mutation remained scarce. In-depth analysis of transcriptome data from FLO8-deficient K. phaffii revealed that Flo8 affects genes involved in cell cycle, mating, respiration, and catabolite repression additionally to flocculation targets. One gene with considerably increased expression in flo8 was GTH1, encoding a high-affinity glucose transporter in K. phaffii. Its promoter (P G1 ) was previously established as a strong, glucose-regulatable alternative to methanol-induced promoters. P G1 and its improved derivatives P G1 - 3 , D-P GS4 and D-P GS5 , proved to be promising candidates for controlling recombinant protein production in the FLO8-deficient background. In small-scale screenings, P G1 3 -controlled intracellular EGFP levels were 2.8-fold higher, and yields of different secreted recombinant proteins were up to 4.8-fold increased. The enhanced productivity of the flo8 mutant in combination with the P G1 variants was transferrable to glucose-limited fed-batch processes and could largely be attributed to higher transcriptional activity of the promoter, leading to a much higher productivity per chromosomally integrated gene copy. K. phaffii flo8 has many advantageous characteristics, such as reduced surface growth and increased transcriptional strength of glucose-regulatable promoters. These features turn the flo8 strain into a valuable new base strain for various experimental designs and establish flo8 as an excellent strain background for methanol-free recombinant protein production processes., Competing Interests: Declaration of Competing Interest All authors have read the manuscript and agree with its publication. The authors declare that they have no conflict of interest. WO2015158800A1 patent family covers the use of flo8 for protein production in K. phaffii (inventors B. Gasser, D. Mattanovich, M. Buchetics; application by Lonza Ltd, Boehringer Ingelheim RCV GmbH, Sandoz GmbH and Validogen GmbH). Some of the authors (B. Gasser, C. Rebnegger, D. Mattanovich, M. Flores-Villegas) are inventors, but not owners, of the patent family covering the surprising effect of the flo8 deletion on the P(G)-promoter variants (WO2020144313A1 by Lonza Ltd)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Anesthesia choice during the procedural management of suspected renal colic during pregnancy may vary based on available resources and patient or provider preferences, as there are no specific recommendations. Our objective was to evaluate whether preterm birth (<37 weeks) was associated with anesthesia type, anesthesia timing by trimester, or procedure type., Methods: We retrospectively identified pregnant patients who required procedural management with ureteral stent, percutaneous nephrostomy (PCN), or ureteroscopy (URS) for suspected renal colic based on laboratory and imaging findings from 2009-2021 at our center. Analyzed data included anesthesia type (local analgesia only, monitored anesthesia care [MAC], spinal anesthesia, or general anesthesia), trimester of procedure, procedure type, and obstetric outcomes including preterm birth., Results: The study cohort included 96 patients who underwent 231 total procedures, including primary URS, PCN, stent, as well as PCN and stent change. The median gestational age was 38.7 (37.1-39.5) weeks, and preterm birth rate was 15.8%. The most common anesthetic used across all procedures and trimesters was MAC. PCN was associated with the use of less invasive analgesia or anesthesia, whereas endoscopic procedures were more commonly performed with spinal or general anesthesia. Using multivariable logistic regression, procedure type was associated with preterm birth, but not anesthesia type or timing by trimester., Conclusions: Anesthesia type and timing were not associated with preterm birth, and selection may be influenced by resources, clinical scenario, or patient and provider preferences.

The Atlantic Forest Biome (AFB) creates an ideal environment for the proliferation of vector mosquitoes, such as Haemagogus and Sabethes species, which transmit the Yellow Fever virus (YFV) to both human and non-human primates (NHP) (particularly Alouatta sp. and Callithrix sp.). From 2016 to 2020, 748 fatal cases of YF in humans and 1,763 in NHPs were reported in this biome, following several years free from the disease. This underscores the imminent risk posed by the YFV. In this study, we examined the spatiotemporal distribution patterns of YF cases in both NHPs and humans across the entire AFB during the outbreak period, using a generalized linear mixed regression model (GLMM) at the municipal level. Our analysis examined factors associated with the spread of YFV, including environmental characteristics, climate conditions, human vaccination coverage, and the presence of two additional YFV-affected NHP species. The occurrence of epizootics has been directly associated with natural forest formations and the presence of species within the Callithrix genus. Additionally, epizootics have been shown to be directly associated with human prevalence. Furthermore, human prevalence showed an inverse correlation with urban areas, temporary croplands, and savannah and grassland areas. Further analyses using Moran's Index to incorporate the neighborhoods of municipalities with cases in each studied host revealed additional variables, such as altitude, which showed a positive correlation. Additionally, the occurrence of the disease in both hosts exhibited a spatio-temporal distribution pattern. To effectively mitigate the spread of the virus, it is necessary to proactively expand vaccination coverage, refine NHP surveillance strategies, and enhance entomological surveillance in both natural and modified environments., Competing Interests: We declare that we have no known competing personal relationships or financial interests that could appear to have influenced the work reported in this paper., (Copyright: © 2024 Kersul et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No approved therapies have been proven to augment the strength of a detrusor voiding contraction., Methods: This subject was discussed by a think-tank at the International Consultation on Incontinence- Research Society (ICI-RS) meeting held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This first part discusses molecular and stem cell therapies targeting the urinary bladder and the neural axis., Results: Senescence of the urothelium and extracellular ATP acting through P2X3 receptors might be important in detrusor underactivity. Several molecules such as parasympathomimetics, acotiamide, ASP8302, neurokinin-2 agonists have been explored but none has shown unequivocal clinical benefit. Different stem cell therapy approaches have been used, chiefly in neurogenic dysfunction, with some studies showing benefit. Molecular targets for the neural axis have included TRPV-4, Bombesin, and serotoninergic receptors and TAC-302 which induces neurite growth., Conclusions: Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive., Clinical Trial Registration: Not necessary. Not a clinical trial., (© 2024 Wiley Periodicals LLC.)

Introduction: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No clinical therapy has been proven to augment the strength of a detrusor contraction., Methods: This subject was discussed at a think-tank at the International Consultation on Incontinence-Research Society (ICI-RS) held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This second part discusses the role of electrical stimulation therapies, treatment of bladder outlet obstruction, constipation, and pelvic floor disorders, in the enhancement of strength of a detrusor contraction., Results: Electrical stimulation therapies, specifically sacral neuromodulation, have long been used in the salvage of patients with refractory nonobstructive voiding dysfunction. Clinical improvements can be noted in men following bladder outlet resistance reduction surgery especially, though not limited to those with demonstrable obstruction. Some patients may also show improvement with pelvic floor relaxation therapies and constipation care. However, there is a lack of high-quality urodynamic data to demonstrate an improvement in the strength of a detrusor contraction with these therapies. The think-tank recommends standards for future clinical studies examining treatments aimed at improving an underactive detrusor., Conclusions: Studies need to examine whether clinical improvement following treatment of patients with an underactive detrusor is associated with improvement in strength of the detrusor contraction. New therapeutic options should apply specified standards for assessing and reporting the impact on detrusor contraction., (© 2024 Wiley Periodicals LLC.)

Purpose: Normative ADC values of the pineal gland in young children are currently lacking, however, these are potentially useful in the differential diagnosis of pineal involvement in trilateral retinoblastoma, which is challenging when the size of the tumor is less than 10-15 mm. The main objective of this study was to establish ADC reference values of the normal pineal gland in a large cohort of children between 0 and 4 years., Methods: This retrospective study was conducted in a tertiary pediatric hospital. We collected 64 patients with normal MRI examination (between 2017 and 2024) and clinical indication unrelated to the pineal gland, and divided them into 5 age groups (0 to 4 years). Gland size and mean ADC values were calculated, using the ellipsoid formula and ROI/histogram analysis, respectively. The established values were tested in three cases of trilateral retinoblastoma (10 to 20 months)., Results: Mean ADC values were always above 1000 × 10 - 6 mm 2 /s, while in patients with trilateral retinoblastoma they were around 800 × 10 - 6 mm 2 /s. Pineal ADC values were identical in both genders. The volume of the pineal gland showed a tendency to increase with age., Conclusions: We present ADC reference data for the pineal gland in children under 4 years of age. The distribution of mean ADC values of trilateral retinoblastoma was significantly different from the normative values, hence, the use DWI/ADC may help to identify small trilateral retinoblastoma in children with ocular pathology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Sleep is vital for health. It has regenerative and protective functions. Its disruption reduces the quality of life and increases susceptibility to disease. During sleep, there is a cyclicity of distinct phases that are studied for clinical purposes using polysomnography (PSG), a costly and technically demanding method that compromises the quality of natural sleep. The search for simpler devices for recording biological signals at home addresses some of these issues. We have reworked a single-channel in-ear electroencephalography (EEG) sensor grounded to a commercially available memory foam earplug with conductive tape. A total of 14 healthy volunteers underwent a full night of simultaneous PSG, in-ear EEG and actigraphy recordings. We analysed the performance of the methods in terms of sleep metrics and staging. In another group of 14 patients evaluated for sleep-related pathologies, PSG and in-ear EEG were recorded simultaneously, the latter in two different configurations (with and without a contralateral reference on the scalp). In both groups, the in-ear EEG sensor showed a strong correlation, agreement and reliability with the 'gold standard' of PSG and thus supported accurate sleep classification, which is not feasible with actigraphy. Single-channel in-ear EEG offers compelling prospects for simplifying sleep parameterisation in both healthy individuals and clinical patients and paves the way for reliable assessments in a broader range of clinical situations, namely by integrating Level 3 polysomnography devices. In addition, addressing the recognised overestimation of the apnea-hypopnea index, due to the lack of an EEG signal, and the sparse information on sleep metrics could prove fundamental for optimised clinical decision making., (© 2024 European Sleep Research Society.)

Objective: This study aimed to describe the use of etonogestrel (ENG) implants for menstrual management (i.e., management of bleeding and symptoms associated with menstruation) in individuals with intellectual disabilities., Methods: This study retrospectively analyzed a cohort of individuals with intellectual disabilities who began using ENG implants between 2003 and 2018, in Joinville, Brazil. We collected sociodemographic, clinical, and reproductive data from the medical records, along with information related to ENG implant use., Results: In total, 369 implants were placed in 130 individuals with intellectual disabilities. The median age at the first implant was 20 (interquartile range [IQR], 17-26) years, and 43.8% of the patients were adolescents. By December 2018, 90 patients had received two or more subsequent implants. The median duration of current ENG implant use was 19 (IQR, 12.8-22) months. More than 40% of the patients had comorbidities, with epilepsy being the most common. During the use of the current implant, 80% of the patients had a favorable bleeding profile (no bleeding or ≤1 bleeding episode per month), and 53.8% (70/130) had no bleeding within 3 months before their last medical visit. Among patients experiencing dysmenorrhea and premenstrual syndrome (PMS), 79% (64/81) and 82% (54/66) reported complete improvement, respectively. The premature implant removal rate was 8.9% (33/369). Unfavorable bleeding was the main reason for premature implant removal (20 out 33 removals)., Conclusions: ENG implants might be a suitable option for individuals with intellectual disabilities who require management of menstrual bleeding and symptoms associated with menstruation. Most patients had a favorable bleeding profile and experienced significant improvements in dysmenorrhea and PMS, contributing to the high continuation rates of ENG implants., (© 2024 International Federation of Gynecology and Obstetrics.)