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Understanding and improving passage by diadromous species at tidal barriers is less well advanced than that for non-tidal anthropogenic river barriers. This study assessed factors affecting upstream passage of anadromous river lamprey (Lampetra fluviatilis) at a tidal weir with pool-and-weir (PAW) and bypass (BP) fishways. A Continuous Time Markov Model (CTMM) was used to analyse migration behaviours of 120 acoustic- and PIT-tagged lamprey across 2 years. The weir was a major barrier to upstream migration with a mean time of 31.0 days taken to pass the weir compared to 2.5 days for the unobstructed reach immediately downstream. River stage was the most important variable associated with weir passage, with a 5.68 (CI = 3.95, 8.17) increase in passage probability for every 1 m river stage increase. Passage was predominately over the weir directly rather than by the fishways. Monitoring the fishways using additional PIT-tagged lamprey (n = 2814) suggested poor entrance efficiency (BP2018, 28.6%; BP2019, 53.1%; PAW2018, 37.0%). Successful fishway passage was estimated as 5.4% (BP2019)–9.0% (PAW2018) of lamprey that entered. Effective fishway entrance for lamprey is probably facilitated by high fishway discharge, yet high-velocity areas may have made it difficult for river lamprey to successfully ascend the fishways. [ABSTRACT FROM AUTHOR]

Passive acoustic monitoring (PAM) is an effective, non-intrusive method for studying ecosystems, but obtaining meaningful ecological information from its large number of audio files is challenging. In this study, we take advantage of the expected animal behavior at different times of the day (e.g., higher acoustic animal activity at dawn) and develop a novel approach to use these time-based patterns. We organize PAM data into 24-hour temporal blocks formed with sound features from a pretrained VGGish network. These features feed a 1D convolutional neural network with a class activation mapping technique that gives interpretability to its outcomes. As a result, these diel-cycle blocks offer more accurate and robust hour-by-hour information than using traditional ecological acoustic indices as features, effectively recognizing key ecosystem patterns. [ABSTRACT FROM AUTHOR]

Meniscus injuries are common and while surgical strategies have improved, there is a need for alternative therapeutics to improve long-term outcomes and prevent post-traumatic osteoarthritis. Current research efforts in regenerative therapies and tissue engineering are hindered by a lack of understanding of meniscus cell biology and a poorly defined meniscus cell phenotype. This study utilized bulk RNA-sequencing to identify unique and overlapping transcriptomic profiles in cartilage, inner and outer zone meniscus tissue, and passaged inner and outer zone meniscus cells. The greatest transcriptomic differences were identified when comparing meniscus tissue to passaged monolayer cells (> 4,600 differentially expressed genes (DEGs)) and meniscus tissue to cartilage (> 3,100 DEGs). While zonal differences exist within the meniscus tissue (205 DEGs between inner and outer zone meniscus tissue), meniscus resident cells are more similar to each other than to either cartilage or passaged monolayer meniscus cells. Additionally, we identified and validated LUM, PRRX1, and SNTB1 as potential markers for meniscus tissue and ACTA2, TAGLN, SFRP2, and FSTL1 as novel markers for meniscus cell dedifferentiation. Our data contribute significantly to the current characterization of meniscus cells and provide an important foundation for future work in meniscus cell biology, regenerative medicine, and tissue engineering. [ABSTRACT FROM AUTHOR]

Macrophages are pleiotropic and diverse cells that populate all tissues of the body. Besides tissue-specific resident macrophages such as alveolar macrophages, Kupffer cells, and microglia, multiple organs harbor at least two subtypes of other resident macrophages at steady state. During certain circumstances, like tissue insult, additional subtypes of macrophages are recruited to the tissue from the monocyte pool. Previously, a recruited macrophage population marked by expression of Spp1, Cd9, Gpnmb, Fabp5, and Trem2, has been described in several models of organ injury and cancer, and has been linked to fibrosis in mice and humans. Here, we show that Notch2 blockade, given systemically or locally, leads to an increase in this putative pro-fibrotic macrophage in the lung and that this macrophage state can only be adopted by monocytically derived cells and not resident alveolar macrophages. Using a bleomycin and COVID-19 model of lung injury and fibrosis, we find that the expansion of these macrophages before lung injury does not promote fibrosis but rather appears to ameliorate it. This suggests that these damage-associated macrophages are not, by themselves, drivers of fibrosis in the lung. Macrophages are pleiotropic and can have different functions and phenotypes. Here the authors show that a population of macrophages, previously described as pro-fibrotic, can be induced through Notch2 blockade and that in a mouse lung injury and fibrosis model this macrophage population does not promote inflammation or fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Restorative proctocolectomy (RPC) and total colectomy with ileorectal anastomosis (TC-IRA) are traditional surgical options for individuals with familial adenomatous polyposis (FAP). Re-appraisal and modification to these techniques, such as near-total colectomy with ileo-distal sigmoid anastomosis (NT-IDSA) and RPC with robotic intracorporeal single-stapled anastomosis (RPC-RiSSA), have been implemented in recent years. This study aimed to evaluate the early postoperative outcomes associated with novel techniques employed in a single centre for restorative surgery in patients with FAP. Methods: A retrospective analysis was conducted using data from patients with FAP who underwent prophylactic restorative surgery between January 2008 and December 2022 at St Mark's Hospital. Results: Two hundred fifty-three individuals underwent restorative surgery over the 15-year period; 102/253 (40.3%) underwent TC-IRA, 84 (33.2%) had NT-IDSA, and 67 (26.5%) underwent RPC. Laparoscopic approach was the most common (88.2%) operative access. Seventeen patients (6.7%) underwent robotic operations. For robotic-assisted procedures, no conversions were reported. No anastomotic leaks or 30-day reoperations were reported in the NT-IDSA group compared to 8% (0/84 vs 8/102, p = 0.009) and 11% (0/84 vs 11/102, p = 0.002), respectively, in the TC-IRA group. Regarding RPC, following the introduction of robotic RPC-RiSSA in 2019, no anastomotic leakage was observed compared with 9% (0/11 vs 5/56, p = 0.3) in those undergoing conventional RPC. Conclusion: Our institution has transitioned from TC-IRA to NT-IDSA since 2014 and conventional RPC to RPC-RiSSA in 2019. To date, since refinement of the techniques there have been no anastomotic failures amongst these cohorts. The reported results may offer future horizons for patients undergoing similar procedures for alternative colorectal diseases. [ABSTRACT FROM AUTHOR]

Lichen sclerosus is a chronic inflammatory condition of unknown etiology that affects the genital and extragenital skin, which can lead to sexual dysfunction and has been associated with vulvar cancer. The vaginal microbiome has a critical role in gynecologic health, but little is known about the microbiome in lichen sclerosus. This study investigated the vaginal and vulvar microbiomes of 27 post-menopausal women with lichen sclerosus. The most abundant genera detected in the vaginal microbiome were Lactobacillus, Gardnerella, and Anaerococcus, while Lactobacillus, Anaerococcus, and Staphylococcus were the most abundant in the vulvar microbiome. The vaginal samples clustered into two main groups, Lactobacillus dominant (n = 6, > 50% microbiome Lactobacillus) and polymicrobial (n = 21) with no dominant genus. The vulvar samples were mainly polymicrobial (n = 25). Actinomyces, Anaerococcus, and Ezakiella in the vaginal microbiome and Actinomyces and Ezakiella in the vulvar microbiome were significantly associated with lichen sclerosus symptoms (adjusted p < 0.05). In this population of post-menopausal women with lichen sclerosus the majority have diverse, non-Lactobacillus dominant microbiomes, which is considered less optimal for gynecologic health based on studies of pre-menopausal women. Actinomyces, Ezakiella, and Anaerococcus were associated with lichen sclerosus symptoms. Understanding the role of these bacteria in lichen sclerosus pathogenesis will be an essential future investigation. [ABSTRACT FROM AUTHOR]

Major trade-offs often manifest as axes of diversity in organismal functional systems. Overarching trade-offs may result in high trait integration and restrict the trajectory of diversification to be along a single axis. Here, we explore the diversification of the feeding mechanism in coral reef fishes to establish the role of trade-offs and complexity in a spectacular ecological radiation. We show that the primary axis of variation in the measured musculo-skeletal traits is aligned with a trade-off between mobility and force transmission, spanning species that capture prey with suction and those that bite attached prey. We found weak or no covariation between about half the traits, reflecting deviations from the trade-off axis. The dramatic trophic range found among reef fishes occurs along the primary trade-off axis, with numerous departures that use a mosaic of trait combinations to adapt the feeding mechanism to diverse challenges. We suggest that morphological evolution both along and independent of a major axis of variation is a widespread mechanism of diversification in complex systems where a global trade-off shapes major patterns of diversity. Significant additional diversity emerges as systems use weak integration and complexity to assemble functional units with many trait combinations that meet varying ecological demands. The diversity of coral reef fishes' feeding apparatus aligns with the trade-off between mobility and force transmission, but weak trait covariation and complexity allow jaw traits to evolve independently to adapt to diverse ecological challenges. [ABSTRACT FROM AUTHOR]

Currently A(H5Nx) avian influenza viruses are globally widespread and continue to evolve. Since their emergence in 2020 novel highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b reassortant viruses have become predominant in the world and caused multiple infections in mammals. It was shown that some of A(H5N1) viruses mostly isolated from mammals contain an E627K mutation in the PB2 protein which can lead to adaptation of influenza viruses to mammalian cells. In 2023 in Russia we have isolated two highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b viruses from birds one of which contained an E627K mutation in the PB2 protein. This virus had increased virulence in mice. Limited airborne transmission of the virus with the PB2-E627K mutation was observed between ferrets, in which infectious virus was detected in the nasal washings of the three of the twelve recipient ferrets, and clinical symptoms of the disease were observed in one case. Both viruses showed dominant binding to avian-type sialoside receptors, which was most likely the reason for the limited transmissibility. Thus, this study indicates a possible limited increase in the pandemic potential of A(H5N1) 2.3.4.4b viruses and highlights the importance of continuous avian influenza surveillance for pandemic preparedness and response. [ABSTRACT FROM AUTHOR]

MBL is a precursor condition to chronic lymphocytic leukemia (CLL), characterized by monoclonal B-cells in blood. Mosaic chromosomal alterations (mCAs) are a form of clonal hematopoiesis that include gains, losses, and copy-neutral loss-of-heterozygosity of large DNA segments. Both MBL and mCAs have been found to increase the risk of CLL and lymphoid malignancies, and the aim of our study was to investigate how mCAs relate to MBL, which is currently unknown. We analyzed genetic, flow cytometric, and hematologic data from 4632 individuals from the Mayo Clinic Biobank and CLL Database. MBL was detected using flow cytometry and classified as high-count (HC) or low-count (LC) MBL based on clone size. mCAs were detected primarily from whole blood DNA using sensitive SNP-array-based analyses. mCAs commonly altered in CLL (deletion of 6q, 11q, 13q, 17p, and trisomy 12) were specific (>99%) to individuals with MBL and CLL. HC-MBL and LC-MBL individuals were 881-fold and 8-fold, respectively, more likely to harbor CLL-associated mCAs than those without MBL. The cell fraction bearing these mCAs typically exceeded the B-cell fraction, suggesting their origin prior to the B-cell lineage. Integrating genetic and blood count data enabled detecting HC-MBL with high specificity in a biobank sample. These results quantify the contribution of mCAs to MBL and could enable large studies of HC-MBL without the need for flow cytometric screening. [ABSTRACT FROM AUTHOR]

The purpose of this work is to study the structure of microbial communities, the physicochemical characteristics of the burozems' profiles, and the soil material infilling the humus pockets. Burozems (Cambisols) in the south of the Vitim Plateau are characterized by specific morphological features: presence of frost cracks, which form wedge-shaped humus pockets, sharply narrowing down the profile. Humus pockets are filled with dark brown humus-enriched material with black stripes that are sharply contrasting in color and properties with the enclosing soil. Compared to the profile of burozems at corresponding depths, the soil mass from humus pockets is less compacted. An increase in total porosity results in greater water permeability of the soil material in the frost cracks. Specific features of the microbial cenosis structure and of the microbial biomass carbon in the soil profile and in the soil material of pockets were revealed. The organic carbon and the absorbed bases are rather evenly distributed in the soil material of the pockets and their contents sharply decrease down the soil profile. The experimental data obtained during the study will replenish the database of the properties and status of microbial cenosis in burozems and in the soil material of their humus pockets in the south of the Vitim Plateau. [ABSTRACT FROM AUTHOR]

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) and Burkitt lymphoma (BL) are uncommon, highly aggressive diseases originating either from immature precursor T cells or from mature B cells in BL. We retrospectively analyzed the outcome of an early autologous and/or allogeneic stem cell transplantation (SCT) concept in 28 patients with advanced stage T-ALL/LBL and BL after three to four remission induction/consolidation chemotherapy cycles. Considering only patients in first complete remission (CR), the 5-year overall survival (OS) and event-free survival (EFS) was 91% in patients with BL and 73% in patients with T-ALL/LBL with a 5-year relapse incidence (RI) of 9% in patients with BL and 27% in patients with T-ALL/LBL. All relapsing patients finally succumbed to the disease (n = 10) or complications/toxicity after having received a salvage allogeneic transplant (n = 5). Despite the low patient number our retrospective single-centre analysis by incorporating an early intensive high-dose chemo-/radiotherapy strategy with either autologous or allogeneic stem cell transplantation, although preliminary, show promising long-term outcome. Further studies are highly warranted to better define those patients who might benefit most from such a treatment approach. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to identify risk factors for subsequent meniscal surgery following anterior cruciate ligament (ACL) reconstruction (ACLR) in patients without recurrent ACL injury. Methods: Patients aged ≥14 years who underwent primary ACLR with minimum 1‐year follow‐up and without recurrent ACL injury were retrospectively reviewed. Patient demographics and surgical data at the time of ACLR were collected. Postoperative radiographs were used to measure femoral and tibial tunnel position, and posterior tibial slope. Univariate and multivariate analyses were performed to identify risk factors for subsequent meniscal surgery. Results: Of 629 ACLRs that fulfilled the inclusion criteria, subsequent meniscal surgery was performed in 65 [10.3%] patients. Multivariate analysis revealed that medial meniscal repair at the time of ACLR, younger age, anterior femoral tunnel position and distal femoral tunnel position were significantly associated with subsequent meniscal surgery (p < 0.001, p = 0.016, p = 0.015, p = 0.035, respectively). The frequency of femoral tunnel placement >10% outside of the literature‐established anatomic position was significantly higher in those who underwent subsequent meniscal surgery compared to those who did not (38.3% vs. 20.3%, p = 0.006). Posterior tibial slope and ACL graft type were not significantly associated with subsequent meniscal surgery. Conclusion: Medial meniscal repair at the time of ACLR, younger age and nonanatomic femoral tunnel placement were risk factors for subsequent meniscal surgery in patients without recurrent ACL injury. Femoral tunnel placement <10% outside of the native anatomic position is important to reduce the risk of subsequent meniscal surgery. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Introduction: Prosthetic valve endocarditis (PVE) is a serious complication of prosthetic valve implantation, with an estimated yearly incidence of at least 0.4-1.0%. The Duke criteria and subsequent modifications have been developed as a diagnostic framework for infective endocarditis (IE) in clinical studies. However, their sensitivity and specificity are limited, especially for PVE. Furthermore, their most recent versions (ESC2015 and ESC2023) include advanced imaging modalities, e.g., cardiac CTA and [18F]FDG PET/CT as major criteria. However, despite these significant changes, the weighing system using major and minor criteria has remained unchanged. This may have introduced bias to the diagnostic set of criteria. Here, we aimed to evaluate and improve the predictive value of the modified Duke/ESC 2015 (MDE2015) criteria by using machine learning algorithms. Methods: In this proof-of-concept study, we used data of a well-defined retrospective multicentre cohort of 160 patients evaluated for suspected PVE. Four machine learning algorithms were compared to the prediction of the diagnosis according to the MDE2015 criteria: Lasso logistic regression, decision tree with gradient boosting (XGBoost), decision tree without gradient boosting, and a model combining predictions of these (ensemble learning). All models used the same features that also constitute the MDE2015 criteria. The final diagnosis of PVE, based on endocarditis team consensus using all available clinical information, including surgical findings whenever performed, and with at least 1 year follow up, was used as the composite gold standard. Results: The diagnostic performance of the MDE2015 criteria varied depending on how the category of 'possible' PVE cases were handled. Considering these cases as positive for PVE, sensitivity and specificity were 0.96 and 0.60, respectively. Whereas treating these cases as negative, sensitivity and specificity were 0.74 and 0.98, respectively. Combining the approaches of considering possible endocarditis as positive and as negative for ROC-analysis resulted in an excellent AUC of 0.917. For the machine learning models, the sensitivity and specificity were as follows: logistic regression, 0.92 and 0.85; XGBoost, 0.90 and 0.85; decision trees, 0.88 and 0.86; and ensemble learning, 0.91 and 0.85, respectively. The resulting AUCs were, in the same order: 0.938, 0.937, 0.930, and 0.941, respectively. Discussion: In this proof-of-concept study, machine learning algorithms achieved improved diagnostic performance compared to the major/minor weighing system as used in the MDE2015 criteria. Moreover, these models provide quantifiable certainty levels of the diagnosis, potentially enhancing interpretability for clinicians. Additionally, they allow for easy incorporation of new and/or refined criteria, such as the individual weight of advanced imaging modalities such as CTA or [18F]FDG PET/CT. These promising preliminary findings warrant further studies for validation, ideally in a prospective cohort encompassing the full spectrum of patients with suspected IE. [ABSTRACT FROM AUTHOR]

The article examines the usage patterns of SGLT2 inhibitors among high-risk CKM patients within the Mass General Brigham (MGB) healthcare system.

Thoracic spinal cord injury (SCI) profoundly impairs motor and sensory functions, significantly reducing life quality without currently available effective treatments for neuroprotection or full functional regeneration. This study investigated the neurotrophic and synaptic recovery potential of gonadotropin-releasing hormone (GnRH) and growth hormone (GH) treatments in ovariectomized rats subjected to thoracic SCI. Employing a multidisciplinary approach, we evaluated the effects of these hormones upon gene expression of classical neurotrophins (NGF, BDNF, and NT3) as well as indicative markers of synaptic function (Nlgn1, Nxn1, SNAP25, SYP, and syntaxin-1), together with morphological assessments of myelin sheath integrity (Klüver-Barrera staining and MBP immunoreactivity) and synaptogenic proteins (PSD95, SYP) by immunohystochemistry (IHC) , and also on the neuromotor functional recovery of hindlimbs in the lesioned animals. Results demonstrated that chronic administration of GnRH and GH induced notable upregulation in the expression of several neurotrophic and synaptogenic activity genes. Additionally, the treatment showed a significant impact on the restoration of functional synaptic markers and myelin integrity. Intriguingly, while individual GnRH application induced certain recovery benefits, the combined treatment with GH appeared to inhibit neuromotor recovery, suggesting a complex interplay in hormonal regulation post-SCI. GnRH and GH are bioactive and participate in modulating neurotrophic responses and synaptic restoration under neural damage conditions, offering insights into novel therapeutic approaches for SCI. However, the intricate effects of combined hormonal treatment accentuate the necessity for further investigation that conduce to optimal and novel therapeutic strategies for patients with spinal cord lesions. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the impact of posterior vitreous detachment (PVD) on the risk of developing neovascular glaucoma (NVG) in eyes with occlusions of the retinal artery (RAO) or retinal vein (RVO). Methods: Single-center retrospective case-control study of adults with a history of RVO/RAO. Cases (N = 101) who developed NVG were age and sex matched 1:2 to controls who did not develop NVG (N = 202). Multivariable logistic regression was used to estimate the association between history of PVD and risk of NVG while controlling for other related demographic or clinical factors. Results: In initial bivariate analyses, there was no difference in risk of NVG based on eye, lens status, hypertension, history of panretinal photocoagulation (PRP), or retinal surgery (all p > 0.10), a borderline difference based on diabetic retinopathy (DR) (p = 0.06) and prior anti-vascular endothelial growth factor (anti-VEGF) treatment (p = 0.08), and a significant difference based on race/ethnicity, type of vascular event, and PVD status (all p < 0.05). In the final multivariable model, patients without PVD were significantly more likely to develop NVG (OR = 3.07, p = 0.0001) independent of the other covariates. Risk of NVG was greater in those with DR (OR = 1.98, p = 0.0440) and in those with central RVO vs. branch RVO/hemiretinal RVO (OR = 5.77, p < 0.0001). Non-White/Non-Hispanics (OR = 2.56, p = 0.0051) and Hispanics (OR = 3.65, p = 0.0288) were more likely than White patients to develop NVG. Conclusions: Progression to NVG after retinal vascular occlusion is more likely in Non-White/Hispanic patients, those with concomitant DR, and those with CRVO/CRAO. The absence of PVD increases the risk for NVG. Further studies are necessary to understand this relationship. [ABSTRACT FROM AUTHOR]

The first phase of this study aimed to validate multi-scale approaches based on Representative Volume Elements (RVEs) for graphene–polyethylene nanocomposites. stress–strain curves of experimental results were compared with numerical homogenization results. The stress amplification obtained from these simulations was used to predict GNP aspect ratios, demonstrating good agreement with permeability results. After validation of the multiscale approach, this study investigates the adhesion between nanoparticles and matrix in anisotropic GNP-HDPE metamaterial nanocomposites, emphasizing the role of the carboxyl (COOH) functional group in improving adhesion. The RVE model is used to investigate the debonding initiation and progression in these anisotropic nanocomposites under tensile and shear loading. Results indicate a variance in debonding onset and growth depending on orientation relative to the GNP axis. In tensile loading, debonding initiates at higher strains along the GNP axis than perpendicularly. Under shear loading within an anisotropic distribution, debonding behaviour varies significantly between planes perpendicular and parallel to the GNP axis. GNP surfaces with fully debonded surfaces slightly exceed 0.6% perpendicular to the GNP axis but increase to over 10.5% parallel to it. [ABSTRACT FROM AUTHOR]

A complex of sedimentological, geochemical, and micropaleontological methods was used to study and compare five new sediment cores along a submeridional transect from the middle to the north of the Norwegian Sea. A combined analysis of the distribution of ice-rafted debris, polar/subpolar foraminifera, calcium carbonate, organic carbon, and continuous geochemical scanning records revealed an alternation of Middle–Late Quaternary glacial and interglacial intervals over the last 260 000 years. In the Late Middle Pleistocene glaciation (MIS 6, 8), the supply of terrigenous material had a much greater influence on regional sedimentation than in the Late Pleistocene (MIS 2–4). Local (between the central and northern parts of the Norwegian Sea) differences in glacial and interglacial sedimentation are shown. [ABSTRACT FROM AUTHOR]

Soil respiration (SR) is one of the largest fluxes in the global carbon cycle, exceeding anthropogenic CO2 emission by more than an order of magnitude. Estimation of the heterotrophic component of SR is necessary to assess the carbon balance on the ecosystem and on the regional, national, and global scales. Within the framework of the most important national innovation project "Development of a System of Ground-based and Remote Monitoring of Carbon Pools and Greenhouse Gas Fluxes on the Territory of the Russian Federation," the first Russian national network is organized to monitor CO2 emission from soils and other linked parameters. The SR values and the relationship with the temperature of the upper 5- to 10-cm layer of soil (TS) are analyzed for the first time on the territory of Russia based on methodologically identical field measurements conducted simultaneously in the summer period (June–August 2023) at 75 monitoring sites in the different ecosystems in the main Russian bioclimatic zones from the tundra to the semidesert. The positive effect of soil temperature on the mean summer SR rate and the maximum monthly SR values is observed in the interval of mean TS from 10 to 20°C. Among the ecosystems studied, the lowest SR values are recorded in tundra and bog ecosystems, while the highest values are in the forest–steppe. Amongst the forest ecosystems, the lowest SR rates are characteristic of larch forests, while the highest SR values are observed in broadleaved forests of the forest–steppe zone. To clarify the regularities obtained, it is necessary to expand studies in all bioclimatic zones, but mainly in agrocenoses, tundra, and steppe ecosystems. [ABSTRACT FROM AUTHOR]

Investigating evolutionary changes in frontal cortex microstructure is crucial to understanding how modifications of neuron and axon distributions contribute to phylogenetic variation in cognition. In the present study, we characterized microstructural components of dorsolateral prefrontal cortex, orbitofrontal cortex, and primary motor cortex from 14 primate species using measurements of neuropil fraction and immunohistochemical markers for fast-spiking inhibitory interneurons, large pyramidal projection neuron subtypes, serotonergic innervation, and dopaminergic innervation. Results revealed that the rate of evolutionary change was similar across these microstructural variables, except for neuropil fraction, which evolves more slowly and displays the strongest correlation with brain size. We also found that neuropil fraction in orbitofrontal cortex layers V–VI was associated with cross-species variation in performance on experimental tasks that measure self-control. These findings provide insight into the evolutionary reorganization of the primate frontal cortex in relation to brain size scaling and its association with cognitive processes. [ABSTRACT FROM AUTHOR]

Background: This study focuses on the role of lysosomal trafficking in prostate cancer, given the essential role of lysosomes in cellular homoeostasis. Methods: Lysosomal motility was evaluated using confocal laser scanning microscopy of LAMP-1-transfected prostate cells and spot-tracking analysis. Expression of lysosomal trafficking machinery was evaluated in patient cohort databases and through immunohistochemistry on tumour samples. The roles of vesicular trafficking machinery were evaluated through over-expression and siRNA. The effects of R1881 treatment on lysosome vesicular trafficking was evaluated by RNA sequencing, protein quantification and fixed- and live-cell microscopy. Results: Altered regulation of lysosomal trafficking genes/proteins was observed in prostate cancer tissue, with significant correlations for co-expression of vesicular trafficking machinery in Gleason patterns. The expression of trafficking machinery was associated with poorer patient outcomes. R1881 treatment induced changes in lysosomal distribution, number, and expression of lysosomal vesicular trafficking machinery in hormone-sensitive prostate cancer cells. Manipulation of genes involved in lysosomal trafficking events induced changes in lysosome positioning and cell phenotype, as well as differential effects on cell migration, in non-malignant and prostate cancer cells. Conclusions: These findings provide novel insights into the altered regulation and functional impact of lysosomal vesicular trafficking in prostate cancer pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia? Materials and methods: In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7 min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis. Results: We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24 years; range 17–33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76–0.97; circular ROI: ICC = 0.82, 95% CI 0.66–0.91) and interobserver agreement was adequate (manual ROI: LoA = 71 ms; circular ROI: LoA = 146 ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI − 0.06–0.94; circular RO: ICC = 0.99, 95% CI 0.98–0.99) and intraobserver agreement was good (manual ROI: LoA = 63 ms; circular ROI: LoA = 41 ms). Conclusion: T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the feasibility and efficacy of chemotherapy combined with irreversible electroporation (IRE) in patients with locally advanced gallbladder carcinoma (GBC) presenting as gallbladder masses. Materials and Methods: Patients with unresectable GBC masses of size greater than 2 cm and less than 6 cm without evidence of distant metastases and with no contraindication to general anaesthesia will be enrolled in the study. They will be randomized using computer generated table into two arms with 1:1 allocation ratio to include 15 patients in each group. Group I will be the chemotherapy alone arm and Group II will be the combined image-guided irreversible electroporation of the tumour and chemotherapy arm. The primary outcome assessed shall be the clinical benefit rate (complete response, CR; partial response, PR and stable disease, SD) based on the mRECIST criteria and overall survival. The secondary outcome shall be feasibility and safety of the procedure and quality of life pre and post procedure. The quality of life will be assessed by a questionnaire as given by EORTC-Quality of Life Group before starting therapy and 4 weeks after completion of therapy. Expected Gain of Knowledge: The combined local and systemic effects of irreversible electroporation and systemic chemotherapy respectively may improve the outcomes in inoperable cases of gallbladder carcinoma. Trial Registration: Clinical Trials Registry – India (https://ctri.nic.in/Clinicaltrials/advancesearchmain.php). Identifier: CTRI/2021/05/033803. Primary Register of the International Clinical Trials Registry Platform (WHO ICTRP) (http://www.who.int/ictrp/search/en/). [ABSTRACT FROM AUTHOR]

We present an analysis method for determining signal amplitudes using a least squares method in combination with an optimally selected bandpass filter. This method has been developed to process heat and light signals obtained in the AMoRE-I experiment. We apply Butterworth filters with various combinations of passbands and filter orders to both the heat and light signals. Subsequently, we employ the least squares method to calculate signal amplitudes by comparing each signal template for the heat and light channels. Optimal filter conditions are identified to achieve the best resolution value. In this paper, we provide a detailed description of the signal processing approach, comparing it with the optimal filter method. [ABSTRACT FROM AUTHOR]

Using two-color planar laser-induced fluorescence (PLIF) of OH hydroxyl radicals excited at two wavelengths and coherent anti-Stokes Raman scattering (CARS) spectroscopy of H2 molecules in a laboratory burner, we have measured spatial temperature distributions in the central section of a stationary atmospheric laminar flame of a methane–air mixture with partial preliminary mixing of the components. The results of a comparative analysis of the data on two-dimensional PLIF and point CARS thermometry of a spatially inhomogeneous flame are presented, and possibilities of complementary application of these methods for diagnostics are shown. [ABSTRACT FROM AUTHOR]

This article presents a device for the storage and gasification of cryogenic working fluid, which is named a cryogenic fuelling tank. A cryogenic fuel tank can serve both as a fuel vessel and a pressure accumulator due to the regasification process that takes place inside. Application of this tank is slowed by the lack of theoretical and experimental research on its working process. This article deals with an investigation of the working process of the energy plant based on a cryogenic fuel tank coupled with a rotor-vane expander. Developed mathematical models include evaporation and condensation processes within the tank, heat exchange between gas chambers and between the tank and environment, and changes in energy due to incoming and leaving mass. Mechanical work used to determine the efficiency of a power plant is generated by a steam expander. Research shows that it is possible to achieve specific work outputs up to 110–160 kJ/kg with relative deviation of power and specific work determination equal to 1.4% and 1.9% correspondingly. [ABSTRACT FROM AUTHOR]

Sarcosphaera (Ascomycota: Pezizales) is a genus of rare spring fungi, currently encompassing a single species, S. coronaria, which is red-listed in many European countries. The genus is characterized by large bright-colored fruit-bodies and high arsenic content. This study investigates the genetic diversity across Europe and North America. Using integrated molecular techniques, including ITS and 28S rDNA sequencing, we aimed to resolve the taxonomic ambiguities and assess their arsenic hyperaccumulation capabilities, a rare trait among fungi. We identified the presence of two species in the Western Palearctic (S. coronaria, S. crassa) and at least 12 additional lineages in North America, indicating a more complex taxonomic structure than previously recognized. To consolidate the taxonomy and nomenclature of these fungi, we selected reference specimens for S. coronaria and S. crassa and discussed their morphological and ecological differences. Two genera, Caulocarpa (C. montana) and Hydnotryopsis (H. setchellii), a genus comprising hypogeous fungi, are newly placed in the genus Sarcosphaera. Sarcosphaera is thus another genus where the rapid evolution of hypogeous forms from their above-ground ancestors took place. Furthermore, two new Sarcosphaera species, S. columbiana and S. pacifica, are described from the Pacific Northwest. Investigation of arsenic content of Sarcosphaera species revealed that arsenic mass fractions in ascocarps vary significantly between species and even within species across different geographical locations. Our findings have important implications for the taxonomy and conservation of the S. coronaria species complex and also point to future directions for further research in the taxonomy, geomycology, and toxicology of this group of fungi. [ABSTRACT FROM AUTHOR]

This study investigated differences in electroencephalography (EEG) activity within motor-related brain areas during three phases of a single-leg squat (SLS)—i.e., descending, holding, and ascending phases. Specifically, utilizing advanced magnetic resonance imaging guided EEG source localization techniques and markerless motion capture technology, we explored the interplay between concurrently recorded lower-extremity biomechanics and brain activity. Among the phases of a nondominant leg SLS, differences in contralateral brain activity (right hemisphere) were found in the activity of the precentral gyrus, the postcentral gyrus, and the sensory motor area. Alternatively, during the dominant SLS leg, differences among the three SLS phases in contralateral brain activity were fewer. Hemispheric dependent brain activity also significantly correlated with participants' knee valgus angle range of motion (right hemisphere) and peak knee valgus angles (left hemisphere). In addition to the novel brain and biomechanical findings, this study sheds light on the technical feasibility of recording EEG during complex multi-joint movements and its potential applications in understanding sensorimotor behavior. [ABSTRACT FROM AUTHOR]

This paper presents statistical shape models of the four fingers of the hand, with an emphasis on anatomic analysis of the proximal and distal interphalangeal joints. A multi-body statistical shape modelling pipeline was implemented on an exemplar training dataset of computed tomography (CT) scans of 10 right hands (5F:5M, 27–37 years, free from disease or injury) imaged at 0.3 mm resolution, segmented, meshed and aligned. Model generated included pose neutralisation to remove joint angle variation during imaging. Repositioning was successful; no joint flexion variation was observed in the resulting model. The first principal component (PC) of morphological variation represented phalanx size in all fingers. Subsequent PCs showed variation in position along the palmar-dorsal axis, and bone breadth: length ratio. Finally, the models were interrogated to provide gross measures of bone lengths and joint spaces. These models have been published for open use to support wider community efforts in hand biomechanical analysis, providing bony anatomy descriptions whilst preserving the security of the underlying imaging data and privacy of the participants. The model describes a small, homogeneous population, and assumptions cannot be made about how it represents individuals outside the training dataset. However, it supplements anthropometric datasets with additional shape information, and may be useful for investigating factors such as joint morphology and design of hand-interfacing devices and products. The model has been shared as an open-source repository (https://github.com/abel-research/OpenHands), and we encourage the community to use and contribute to it. [ABSTRACT FROM AUTHOR]

Nuclear magnetic resonance (NMR), a technique mainly used for structure determination, has also been extensively used for mechanism elucidation. The study of the different steps involved in a chemical reaction is of utmost importance since it permits the optimization of reaction conditions to improve the yield of a synthesis or to obtain one possible product over another one, for example. This review is organized into two sections. Firstly, the experimental issues concerning the applications of NMR to the elucidation of reaction mechanisms are revised: advantages, limitations and challenges are discussed. The different techniques used for overcoming the difficulties concerning NMR (such as low sensitivity, peak resolution, and mixing time) are described (including stop-flow, rapid-injection, liquid chromatography-NMR, dynamic nuclear polarization, and parahydrogen-induced polarization, among others). In the second section, experiments specifically designed for obtaining mechanistic information by means of different NMR techniques are summarized: kinetic experiments, detection of reaction intermediates, isotope labeling, variable-temperature experiments, and variable-pH experiments. The main objective of this work is to give an overview on the relevance of NMR as a very useful tool for elucidating organic reaction mechanisms. [ABSTRACT FROM AUTHOR]

Background: Assessment of the pattern of the RV outflow tract Doppler provides insights into the hemodynamics of chronic thromboembolic pulmonary hypertension (CTEPH). We studied whether pre-operative assessment of timing of the pulmonary flow systolic notch by Doppler echocardiography is associated with long-term survival after pulmonary endarterectomy (PEA) for CTEPH. Methods: Fifty-nine out of 61 consecutive CETPH patients (mean age 53 ± 14 years, 34% male) whom underwent PEA between June 2002 and June 2005 were studied. Clinical, echocardiographic and hemodynamic variables were assessed pre-operatively and repeat echocardiography was performed 3 months after PEA. Notch ratio (NR) was assessed with pulsed Doppler and calculated as the time from onset of pulmonary flow until notch divided by the time from notch until end of pulmonary flow. Long-term follow-up was obtained between May 2021 and February 2022. Results: Pre-operative mean pulmonary artery pressure (mPAP) was 45 ± 15 mmHg and pulmonary vascular resistance (PVR) was 646 ± 454 dynes.s.cm-5. Echocardiography before PEA showed that 7 patients had no notch, 33 had a NR < 1.0 and 19 had a NR > 1.0. Three months after PEA, echocardiography revealed a significant decrease in sPAP in long-term survivors with a NR < 1.0 and a NR > 1.0, while a significant increase in TAPSE/sPAP was only observed in the NR < 1.0 group. Mean long-term clinical follow-up was 14 ± 6 years. NR was significantly different between survivors and non-survivors (0.73 ± 0.25 vs. 1.1 ± 0.44, p < 0.001) but no significant differences were observed in mPAP or PVR. Long-term survival at 14 years was significantly better in patients with a NR < 1.0 compared to patients with a NR > 1.0 (83% vs. 37%, p = < 0.001). Conclusion: Pre-operative assessment of NR is a predictor of long-term survival in CTEPH patients undergoing PEA, with low mortality risk in patients with NR < 1.0. Long-term survivors with a NR < 1.0 and NR > 1.0 had a significant decrease in sPAP after PEA. However, the TAPSE/sPAP only significantly increased in the NR < 1.0 group. In the NR < 1.0 group, the 6-min walk test increased significantly between pre-operative and at 1-year post-operative follow-up. NR is a simple echocardiographic parameter that can be used in clinical decision-making for PEA. [ABSTRACT FROM AUTHOR]

We present direct eddy covariance measurements of the surface heat flux in sea ice over a wide range of conditions across the Arctic Ocean made during two research cruises. Photographic imagery of the surface around the ship provides a local, in situ estimate of the ice fraction. Aerodynamically rough conditions prevail for the majority of the time in the consolidated pack ice. The results are analyzed in the framework of a recently-developed parameterization scheme in which the exchange coefficients over ice are functions of a roughness Reynolds number, R*, hence account for aerodynamic roughness variability. This parameterization accurately represents the measured fluxes under all conditions, while under aerodynamically rough conditions the existing parameterizations from both the Met Office Unified Model, and ECMWF Integrated Forecast System overestimate the fluxes. The results corroborate those of a previous airborne study over the marginal ice zone, and encompass a wider range of atmospheric stability conditions. [ABSTRACT FROM AUTHOR]

Invasive species' plasticity and latitudinal spread have become an increasing matter of concern in rapidly changing climate. The brush-clawed shore crab (Hemigrapsus takanoi), native along northwestern Pacific shores, has established dense populations in northern European coasts. Detrimental effects in natura have been reported, such as displacement of native species and competition for shelter, rasing concerns regarding shellfish early life stages and food webs-posing a threat to wild stocks' recruitment and aquaculture. The species has not yet been observed in southern European countries (e.g., Portugal), where niche habitats such as harbours, mudflats, and lagoons reach higher temperatures than the invaded northern range. The aims of this study were to determine H. takanoi potential to acclimate to a southern thermal range, assess thermal performance, and identify potential competitive advantages over the native shore crab Carcinus maenas. This was accomplished through individual exposure to one of three treatments, resembling a southern European thermal range (17 °C, 21 °C, or 25 °C), for 30 days. H. takanoi thrived in temperatures as high as 25 °C, a realistic thermal scenario in Óbidos Lagoon (the biggest Portuguese lagoon)—while the native shore crab C. maenas underperformed at that treatment, showing lower survival, growth, and feed intake than H. takanoi. These results suggest that H. takanoi may be able to colonise southern and warmer European locations and have higher plasticity than the native species already inhabiting areas close to its upper thermal limits. Under global warming scenarios, inferences of further latitudinal spread and increased invaded range may also be taken to the invaded northern European habitats. [ABSTRACT FROM AUTHOR]

Background: Rockfalls pose a serious threat along the main road network, representing a major hazard in mountainous territory and causing damage and victims. Currently, susceptibility mapping represents a starting point to identify areas more susceptible to rockfall occurrence, a key approach in land use planning and risk management. Despite the extensive use of these maps by decision makers and administrators, the usability of such maps over time and their reliability represent a poorly discussed and examined feature. Methods: Here, we proposed a-posteriori analysis of a three-year-old rockfall susceptibility map, generated along the main road network of the Aosta Valley, an alpine region of north-western Italy. To verify map consistency over time, we implemented a dual-analysis in GIS-environment and by text mining, to respectively analyse the geocoded data and textual information derivable from the regional landslide inventory. The first one allowed us to extract rockfall events occurred after the susceptibility map generation. By this way, we operated to spatially and temporally verify the map consistency. Jointly, the textual information reported in the Event Description Form, linked to each geocoded event, are being exploited. This allowed us to derive relevant information about occurred damage and their degree, presence of protective measures or secondary roads, i.e. involvement of, farm or forestry, road. Results: The implemented approach allowed us to prove the quality of the previous map in terms of reliability, robustness and degree of fitting respect to the succession of rockfall occurrence over time. After only three years as many as 198 rockfall events have been occurred and collected since the map was generated. Particularly, 80% of rockfall fit with "high" and "very high" susceptibility classes, and pointed out large involvement of main roads in rockfall occurrence, representing the most affected target with damage to road pavement and vehicles, as well as a relevant involvement of existing rockfall barriers and of the dense network of forestry roads and footpaths that characterize this alpine region. Results: The proposed approach representing a starting point in landslide susceptibility map verification and usability as valid instrument for a reliable land planning. [ABSTRACT FROM AUTHOR]

Ageing impairs the ability of neural stem cells (NSCs) to transition from quiescence to proliferation in the adult mammalian brain. Functional decline of NSCs results in the decreased production of new neurons and defective regeneration following injury during ageing1–4. Several genetic interventions have been found to ameliorate old brain function5–8, but systematic functional testing of genes in old NSCs—and more generally in old cells—has not been done. Here we develop in vitro and in vivo high-throughput CRISPR–Cas9 screening platforms to systematically uncover gene knockouts that boost NSC activation in old mice. Our genome-wide screens in primary cultures of young and old NSCs uncovered more than 300 gene knockouts that specifically restore the activation of old NSCs. The top gene knockouts are involved in cilium organization and glucose import. We also establish a scalable CRISPR–Cas9 screening platform in vivo, which identified 24 gene knockouts that boost NSC activation and the production of new neurons in old brains. Notably, the knockout of Slc2a4, which encodes the GLUT4 glucose transporter, is a top intervention that improves the function of old NSCs. Glucose uptake increases in NSCs during ageing, and transient glucose starvation restores the ability of old NSCs to activate. Thus, an increase in glucose uptake may contribute to the decline in NSC activation with age. Our work provides scalable platforms to systematically identify genetic interventions that boost the function of old NSCs, including in vivo, with important implications for countering regenerative decline during ageing.CRISPR–Cas9 screens in cultures of young and old neural stem cells (NSCs) and in vivo in old mice identify gene knockouts that can boost old NSC activation and neurogenesis, with Slc2a4, which encodes the glucose transporter GLUT4, showing particular efficacy. [ABSTRACT FROM AUTHOR]

Background: People with aphasia commonly experience depression and anxiety. The individual therapy program, Aphasia PRevention Intervention and Support in Mental health (Aphasia PRISM) offers low intensity psychotherapeutic interventions using communication supports. Trained stroke clinicians from disciplines other than psychology (e.g., allied health professional, nurse, doctor) can deliver such interventions. The aim of the planned studies is to test the acceptability, feasibility and preliminary effectiveness of Aphasia PRISM for preventing depression and anxiety and supporting wellbeing in people with aphasia after stroke. Method: This protocol describes two feasibility studies of the Aphasia PRISM using parallel, convergent, mixed methods designs. Participants will be adults with aphasia after stroke from a metropolitan healthcare site (Study A, pre-post case series, approximate n = 6) and two regional/rural sites (Study B, randomised controlled trial, n = 30; random allocation to either: treatment arm Aphasia PRISM + usual care; or attention control of secondary stroke prevention information + usual care) in Victoria, Australia. Eligible participants will be offered 7 weekly intervention sessions (via telehealth or in person). Other participant groups include stroke clinicians / site managers and family members. Feasibility will be assessed with treatment acceptability ratings (primary outcome) and secondary outcomes such as recruitment rate and participant clinical response. Participant clinical responses to intervention will be collected pre-intervention (baseline), concurrently (4 week acceptability measure), immediately post (8 weeks), follow-up (3 months) and follow-up at 6 months (Study B only). Descriptive statistics will be used to analyse quantitative data based on the type and distribution of data. Reflexive thematic analysis, an inductive approach will be used to analyse qualitative data. Discussion: Aphasia PRISM offers the potential for trained stroke clinicians to deliver low intensity psychotherapeutic interventions with communication supports to people with aphasia. Studies A and B were registered with the Australian New Zealand Clinical Trials registry under one registration (ACTRN12620000209998) 20th February 2020. [ABSTRACT FROM AUTHOR]

Topologically nontrivial magnetic structures such as skyrmion lattices are well known in materials lacking lattice inversion symmetry, where antisymmetric exchange interactions are allowed. Only recently, topological multi-q magnetic textures that spontaneously break the chiral symmetry, for example, three-dimensional hedgehog lattices, were discovered in centrosymmetric compounds, where they are instead driven by frustrated interactions. Here we show that the bilayer perovskite Sr3Fe2O7, previously believed to adopt a simple single-q spin-helical order, hosts two distinct types of multi-q spin textures. Its ground state represents a novel multi-q spin texture with unequally intense spin modulations at the two ordering vectors. This is followed in temperature by a new "spin meta-cholesteric" phase, in which the chiral symmetry is spontaneously broken along one of the crystal directions, but the weaker orthogonal modulation melts, giving rise to intense short-range dynamical fluctuations. Shortly before the transition to the paramagnetic state, vortex-crystal order spanned by two equivalent q vectors emerges. This renders Sr3Fe2O7 an ideal material to study transitions among multiple-q spin textures in a centrosymmetric host. [ABSTRACT FROM AUTHOR]

Glass durability is one of the properties that can be affected by surface treatments such as coatings or chemical attacks. These treatments can be used to reduce the quantities of potentially toxic elements contained in glass that may be released in solution. Five surface treatments were selected: three different coatings (SnO2, TiO2, SiO2) and two acidic attacks (SO2 dealkalization and acid polishing). These treatments were performed on five glass compositions (soda-lime, borosilicate, barium silicate, opal, and lead crystal). Their effects on alteration rates and mechanisms were investigated through a single protocol (acetic acid 4%, 70 °C) simulating accelerated aging conditions for containers of beverages or food. The data collected over 1.3 years showed significant reduction of lead leaching with all treatments except acid polishing. The best reduction factor was obtained with SO2 dealkalization, which also demonstrated beneficial effects towards the retention of Ba by reducing the diffusion of alkalis. [ABSTRACT FROM AUTHOR]

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks1–5. The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities6–8 or interacting with a stellar object in a close orbit9–11. It has been suggested that this disk could be created when the SMBH disrupts a passing star8,11, implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions13,14. TDEs and QPEs also occur preferentially in similar galaxies15. However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE16. We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs.The detection and modelling of nine X-ray quasi-periodic eruptions from a nearby tidal disruption event shows that these eruptions arise in accretion disks around massive black holes, left behind by tidally disrupted stars, and that an orbiting body colliding with this disk is a plausible explanation for the X-ray variability. [ABSTRACT FROM AUTHOR]

Vaccines to the Plasmodium falciparum reticulocyte binding-like protein homologue 5 (PfRH5) target the blood-stage of the parasite life cycle. PfRH5 has the potential to trigger the production of strain-transcendent antibodies and has proven its efficacy both in pre-clinical and early clinical studies. Vaccine-induced monoclonal antibodies (mAbs) to PfRH5 showed promising outcomes against cultured P. falciparum laboratory strains from distinct geographic areas. Here, we assessed the functional impact of vaccine-induced anti-PfRH5 mAbs on more genetically diverse P. falciparum clinical isolates. We used mAbs previously isolated from single B cells of UK adult PfRH5 vaccinees and used ex-vivo growth inhibition activity (GIA) assays to assess their efficacy against P. falciparum clinical isolates. Next-generation sequencing (NGS) was used to assess the breadth of genetic diversity in P. falciparum clinical isolates and to infer the genotype/phenotype relationship involved in antibody susceptibility. We showed a dose-dependent inhibition of clinical isolates with three main GIA groups: high, medium and low. Except for one isolate, our data show no significant differences in the mAb GIA profile between P. falciparum clinical isolates and the 3D7 reference strain, which harbors the vaccine allele. We also observed an additive relationship for mAb combinations, whereby the combination of GIA-low and GIA-medium antibodies resulted in increased GIA, having important implications for the contribution of specific clones within polyclonal IgG responses. While our NGS analysis showed the occurrence of novel mutations in the pfrh5 gene, these mutations were predicted to have little or no functional impact on the antigen structure or recognition by known mAbs. Our present findings complement earlier reports on the strain transcendent potential of anti-PfRH5 mAbs and constitute, to our knowledge, the first report on the susceptibility of P. falciparum clinical isolates from natural infections to vaccine-induced human mAbs to PfRH5. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) care has evolved during the past decades. Advances in care have contributed to improved survival among CHD patients. Children with CHD are requiring interventions for non-CHD related medical issues that occur in the general pediatric population. Methods: A retrospective review of the Pediatric Health Information System (PHIS) database from January 1, 2004, to July 31, 2023. Discharges of patients with an admitting/principal diagnosis of appendicitis were evaluated and categorized as CHD or non-CHD. Results: A total of 319,228 patients were identified with 1,25,858(39.4%) female, 1,38,966(43.5%) white, and median age of 11[IQR:8–14] years. 708(0.2%) had CHD with 85(12%) of them having a diagnosis consistent with single-ventricle CHD (SV-CHD). In univariate analysis, CHD patients were more likely to undergo conservative treatment (n = 172(24.2%)vs n = 59,358(18.6%)) and less likely to undergo laparoscopic appendectomy (n = 483(68.2%) vs n = 2,35,324(73.8%))(p < 0.001) compared to non-CHD. After adjustment, CHD patients had increased odds of undergoing open appendectomy compared to non-CHD. CHD patients were more likely to have an ICU admission (OR:8.36(95%CI 6.35–10.00),p < 0.001) and had a 77.6%(95%CI 40.89–123.93) increase in length of stay (LOS) (p < 0.001). Conclusion: CHD patients are more likely to have an open appendectomy than non-CHD patients. These findings suggest a distinctive pattern in the care of CHD patients compared to non-CHD. Overall, CHD patients had a more intense level of care with longer LOS and increased ICU admissions. Further work is needed to evaluate drivers of management decisions, the role of conservative treatment with antibiotics alone in the CHD population, and the potential impacts and safety of a laparoscopic approach. [ABSTRACT FROM AUTHOR]

DO19-ordered Mn3Ga gained much attention recently due to their potential application in spintronic devices. However, there still remain several challenges to overcome before their practical application. We have studied the structural, magnetic, and transport properties of polycrystalline Mn3Ga0.8Ge0.2. It was found that Ge-doped Mn3Ga ingot undergoes a spin reorientation transition from a coplanar antiferromagnetic to a noncoplanar configuration of Mn moments at around 200 K, accompanied by the competition among magnetocrystalline anisotropy, ferromagnetic interaction, and antiferromagnetic coupling. Compared with other reports on polycrystalline Mn3Ga, the Mn3Ga0.8Ge0.2 alloy in our work has a higher spin reorientation transition temperature, which is related to the lattice distortion caused by Ge doping. The anomalous Hall effect can be observed from 10 to 350 K and the Hall resistivity at room temperature is 0.641 μΩ cm. An apparent topological Hall effect (THE) was observed simultaneously in the hexagonal non-collinear polycrystalline Mn3Ga0.8Ge0.2 ingots below 200 K. The origin of the present THE is attributed to the non-collinear triangular magnetic configuration with slight distortion. The maximum value of topological Hall resistivity can reach a value of about 0.242 μΩ cm at 120 K. Our work provides an approach for topological spintronics applications using Mn3X-based alloys. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has posed significant challenges to global healthcare systems, particularly impacting individuals with pre-existing conditions like hypertension. This study sought to assess the impact of the antihypertensive medications, losartan and enalapril maleate on SARS-CoV-2 infected cells. Vero E6 cells were infected and treated in vitro, evaluating cell viability via the MTT colorimetric assay. Additionally, the study measured relative levels of viral RNA and selected gene messenger RNAs using reverse transcriptase followed by quantitative real-time polymerase chain reaction. Results: The findings revealed that losartan substantially reduced nucleocapsid RNA levels of SARS-CoV-2 to nearly undetectable levels, while enalapril maleate did not demonstrate a significant effect. In response to viral infection, the expression of il-18, p53, p21, and p62 increased compared to uninfected-untreated cells. Notably, il-6 expression was upregulated by both infection and treatments. A comparison between infected cells treated with losartan or enalapril maleate highlighted the presence of distinct profiles in the expression of il-6, p53, p21, and p62. Conclusions: The data from our study suggest that these medications could interfere with certain effects triggered by SARS-CoV-2 infection in Vero E6 cells. However, their influence appears to vary both quantitatively and qualitatively in the modulation of metabolic and signal transduction pathways. [ABSTRACT FROM AUTHOR]

Introduction: Despite advantages for patients with ulcerative colitis, Crohn's disease, and familial adenomatous polyposis, restorative proctocolectomy with ileal pouch-anal anastomosis carries a risk of pouch failure, necessitating pouch excision. The traditional open approach is associated with potential complications. Robotic and laparoscopic techniques are emerging, but comparative outcome data are limited. Methods: We conducted a retrospective study of consecutive adult patients undergoing robotic, laparoscopic, and open ileal pouch excision at Mayo Clinic, Rochester, MN, between January 2015 and December 2023. We analyzed data on patient characteristics, perioperative variables, and postoperative outcomes, focusing on short-term complications. Statistical analysis included appropriate tests. Results: The study included 123 patients: 23 underwent robotic-assisted pouch excision, 12 laparoscopic, and 82 open. The robotic approach had the longest median operative time (334 ± 170 min, p = 0.03). However, it demonstrated significantly lower estimated blood loss than open (150 ± 200 ml vs. 350 ± 300 ml, p = 0.002) and laparoscopic surgery (250 ± 250 ml, p = 0.005). Robotic and laparoscopic groups required fewer preoperative ureteral stents than the open group (p = 0.001). Additionally, the robotic approach utilized fewer pelvic drainages (p < 0.0001) and had a lower rate of lysis of adhesions > 60 min compared to open surgery (p = 0.003). Robotic procedures had significantly lower 30-day postoperative complications than the open approach (30.4% vs. 65.9%, p = 0.002) while also demonstrating fewer 30-day reoperations than the laparoscopic group (p = 0.04). Conclusions: Robotic-assisted pouch excision offered significant benefits, including decreased EBL, reduced need for preoperative ureteral stents, and significantly fewer 30-day postoperative complications compared to open surgery. [ABSTRACT FROM AUTHOR]

Patients' beliefs about their illness are of central importance in understanding how a person adjusts to their condition and adheres to self-management recommendations. No previous studies have set out to quantitatively examine Illness beliefs in patients with kidney stones (KS). 112 patients with radiological confirmation of KS (59% male, mean (x̄) age = 50.1 years [sd14.15 years], 50.5% previous surgical treatment) attending for clinical consultation completed the Brief-Illness Perception Questionnaire alongside a range of demographic and illness related variables. Template analysis was undertaken on the free text responses of patients' beliefs about what had caused their KS. Almost a third (31.2%) of patients did not know what had caused their KS. Of those who cited a cause, dietary factors, fluid intake, medical risk factors (e.g. Inflammatory bowel disease), genetics, and psychological factors were ranked as the most important. Patients generally believed they had a reasonable understanding of KS (x̄=6.32 [sd3.21]), but reported poor levels of personal control over their KS (x̄=2.90 [sd2.93]) and high confidence in the effectiveness of treatments (x̄=8.64 [sd1.90]). Patients with a recurrence believed KS had a significantly greater impact on their life (z=-2.56, p = 0.01) and had greater emotional consequences (z=-2.77, p < 0.01). Perceptions of poor personal control over KS and a strong belief in medical/surgical treatment was evident regardless of first or recurrent stone, gender, age, previous surgical management of KS or time since diagnosis. Results highlight the need to actively increase patients' perceptions of personal control in the management and prevention of KS. [ABSTRACT FROM AUTHOR]