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Abstract The interplay between spin-orbit interaction and magnetic order is one of the most active research fields in condensed matter physics and drives the search for materials with novel, and tunable, magnetic and spin properties. Here we report on a variety of unique and unexpected observations in thin multiferroic Ge1−x Mn x Te films. The ferrimagnetic order parameter in this ferroelectric semiconductor is found to switch direction under magnetostochastic resonance with current pulses many orders of magnitude lower as for typical spin-orbit torque systems. Upon a switching event, the magnetic order spreads coherently and collectively over macroscopic distances through a correlated spin-glass state. Utilizing these observations, we apply a novel methodology to controllably harness this stochastic magnetization dynamics.

Abstract Background Pelvic organ prolapse (POP) is a condition affecting more than half of the women above age 40. The estimated lifetime risk of needing surgical management for POP is 11%. In patients undergoing POP surgery of the anterior vaginal wall, the re-operation rate is 30%. The recurrence risk is especially high in women with a levator ani defect. Such defect is present if there is a partially or completely detachment of the levator ani from the inferior ramus of the symphysis. Detecting levator ani defects is relevant for counseling, and probably also for treatment. Levator ani defects can be imaged with MRI and also with Translabial 3D ultrasonography of the pelvic floor. The primary aim of this study is to assess the diagnostic accuracy of translabial 3D ultrasonography for diagnosing levator defects in women with POP with Magnetic Resonance Imaging as the reference standard. Secondary goals of this study include quantification of the inter-observer agreement about levator ani defects and determining the association between levator defects and recurrent POP after anterior repair. In addition, the cost-effectiveness of adding translabial ultrasonography to the diagnostic work-up in patients with POP will be estimated in a decision analytic model. Methods/Design A multicentre cohort study will be performed in nine Dutch hospitals. 140 consecutive women with a POPQ stage 2 or more anterior vaginal wall prolapse, who are indicated for anterior colporapphy will be included. Patients undergoing additional prolapse procedures will also be included. Prior to surgery, patients will undergo MR imaging and translabial 3D ultrasound examination of the pelvic floor. Patients will be asked to complete validated disease specific quality of life questionnaires before surgery and at six and twelve months after surgery. Pelvic examination will be performed at the same time points. Assuming a sensitivity and specificity of 90% of 3D ultrasound for diagnosing levator defects in a population of 120 women with POP, with a prior probability of levator ani defects of 40%, we will be able to estimate predictive values with good accuracy (i.e. confidence limits of at most 10% below or above the point estimates of positive and negative predictive values). Anticipating 3% unclassifiable diagnostic images because of technical reasons, and a further safety margin of 10% we plan to recruit 140 patients. Trial registration Nederlands trial register NTR2220.

Abstract Van der Waals heterostructures composed of multiple few layer crystals allow the engineering of novel materials with predefined properties. As an example, coupling graphene weakly to materials with large spin–orbit coupling (SOC) allows to engineer a sizeable SOC in graphene via proximity effects. The strength of the proximity effect depends on the overlap of the atomic orbitals, therefore, changing the interlayer distance via hydrostatic pressure can be utilized to enhance the interlayer coupling between the layers. In this work, we report measurements on a graphene/WSe2 heterostructure exposed to increasing hydrostatic pressure. A clear transition from weak localization to weak antilocalization is visible as the pressure increases, demonstrating the increase of induced SOC in graphene.

Here, the authors report on the large twist-angle susceptibility of excitons involving upper conduction bands in transition metal dichalcogenide bilayers. These high-lying excitons couple with band-edge excitons, and give rise to nonlinear quantum-optical processes that become tuneable by twisting.

Transition metal dichalcogenides (TMDCs) are ideal candidates to explore the manifestation of spin-valley physics under external stimuli. In this study, we investigate the influence of strain on the spin and orbital angular momenta, effective g -factors, and Berry curvatures of several monolayer TMDCs (Mo and W based) using a full ab initio approach. At the K -valleys, we find a surprising decrease of the conduction band spin expectation value for compressive strain, consequently increasing the dipole strength of the dark exciton by more than one order of magnitude (for $\sim 1\%-2\%$ strain variation). We also predict the behavior of direct excitons g -factors under strain: tensile (compressive) strain increases (decreases) the absolute value of g -factors. Strain variations of ∼1% modify the bright (A and B) excitons g -factors by ∼0.3 (0.2) for W (Mo) based compounds and the dark exciton g -factors by ∼0.5 (0.3) for W (Mo) compounds. Our predictions could be directly visualized in magneto-optical experiments in strained samples at low temperature. Additionally, our calculations strongly suggest that strain effects are one of the possible causes of g -factor fluctuations observed experimentally. By comparing the different TMDC compounds, we reveal the role of spin–orbit coupling (SOC): the stronger the SOC, the more sensitive are the spin-valley features under applied strain. Consequently, monolayer WSe _2 is a formidable candidate to explore the role of strain on the spin-valley physics. We complete our analysis by considering the side valleys, Γ and Q points, and by investigating the influence of strain in the Berry curvature. In the broader context of valley- and strain-tronics, our study provides fundamental microscopic insights into the role of strain in the spin-valley physics of TMDCs, which are relevant to interpret experimental data in monolayer TMDCs as well as TMDC-based van der Waals heterostructures.

OBJECTIVES: To reexamine a health-protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOE epsilon2-containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (> or = 65) men and women and to examine how diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration, and atherosclerosis may mediate these connections. DESIGN: Retrospective cross-sectional study. SETTING: The unique disability-focused data from a genetic subsample of the 1999 National Long Term Care Survey linked with Medicare service use files. PARTICIPANTS: One thousand seven hundred thirty-three genotyped individuals interviewed regarding IADL disabilities. MEASUREMENTS: Indicators of IADL impairments, five geriatric disorders, and epsilon2-containing genotypes. RESULTS: The epsilon2/3 genotype is a major contributor to adverse associations between the epsilon2 allele and IADL disability in men (odds ratio (OR)=3.09, 95% confidence interval (CI)=1.53-6.26), although it provides significant protective effects for CHD (OR=0.55, 95% CI=0.33-0.92), whereas CHD is adversely associated with IADL disability (OR=2.18, 95% CI=1.28-3.72). Adjustment for five diseases does not significantly alter the adverse association between epsilon2-containing genotypes and disability. Protective effects of the epsilon2/3 genotype for CHD (OR=0.52, 95% CI=0.27-0.99) and deleterious effects for IADLs (OR=3.50, 95% CI=1.71-7.14) for men hold in multivariate models with both these factors included. No significant associations between the epsilon2-containing genotypes and IADL are found in women. CONCLUSION: The epsilon2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that epsilon2-containing genotypes can be unfavorable factors for the health and well-being of aging men. [ABSTRACT FROM AUTHOR]

Spin-orbit coupling underlies many important spintronic concepts, and is strongly influenced by crystal symmetry. Here, the authors demonstrate a strong enhancement of spin-orbit coupling in core/shell semiconductor nanowires induced by the large interfacial surface areas

By measuring the spin polarization of GeTe films as a function of light polarization we observed that the bulk states are fully spin polarized in the initial state, in strong contrast with observations for other systems with a strong spin-orbit interaction and the surface derived states in the same system. In agreement with state-of-the-art theory, our experimental results show that fully spin-polarized bulk states are an intrinsic property of the ferroelectric Rashba semiconductor α-GeTe(111). The fact that the measured spin-polarization vector does not change with light polarization can be explained by the absence of a mixing of states with a different total angular momentum J.

We investigate the electronic band structure and the proximity exchange effect in bilayer graphene (BLG) on a family of ferromagnetic multilayers Cr _2 X _2 Te _6 , X = Ge, Si, and Sn, with first principles methods. In each case the intrinsic electric field of the heterostructure induces an orbital gap on the order of 10 meV in the graphene bilayer. The proximity exchange is strongly band-dependent. For example, in the case of Cr _2 Ge _2 Te _6 , the low energy valence band of BLG has exchange splitting of 8 meV, while the low energy conduction band’s splitting is 30 times less (0.3 meV). This striking discrepancy stems from the layer-dependent hybridization with the ferromagnetic substrate. Remarkably, applying a vertical electric field of a few V nm ^–1 reverses the exchange, allowing us to effectively turn ON and OFF proximity magnetism in BLG. Such a field-effect should be generic for van der Waals bilayers on ferromagnetic insulators, opening new possibilities for spin-based devices.

Background: Werner's syndrome is a progeroid syndrome caused by mutations at the WRN helicase locus. Some features of this disorder are also present in laminopathies caused by mutant LMNA encoding nuclear lamin A/C. Because of this similarity, we sequenced LMNA in individuals with atypical Werner's syndrome (wild-type WRN). Methods: Of 129 index patients referred to our international registry for molecular diagnosis of Werner's syndrome, 26 (20%) had wildtype WRN coding regions and were categorised as having atypical Werner's syndrome on the basis of molecular criteria. We sequenced all exons of LMNA in these individuals. Mutations were confirmed at the mRNA level by RT-PCR sequencing. In one patient in whom an LMNA mutation was detected and fibroblasts were available, we established nuclear morphology and subnuclear localisation. Findings: In four (15%) of 26 patients with atypical Werner's syndrome, we noted heterozygosity for novel missense mutations in LMNA, specifically A57P, R133L (in two people), and L140R. The mutations altered relatively conserved residues within lamin A/C. Fibroblasts from the patient with the L140R mutation had a substantially enhanced proportion of nuclei with altered morphology and mislocalised lamins. Individuals with atypical Werner's syndrome with mutations in LMNA had a more severe phenotype than did those with the disorder due to mutant WRN. Interpretation: Our findings indicate that Werner's syndrome is molecularly heterogeneous, and a subset of the disorder can be judged a laminopathy. [ABSTRACT FROM AUTHOR]

Background: Previous research among diverse patient populations suggests that healthcare staff routinely do not talk about sexuality with their patients even when such talks are highly indicated and relevant., Aim: In this study we sought to investigate how patients at outpatient anxiety clinics in Denmark experience sexual communication with healthcare staff and what barriers they encounter in this connection., Methods: We employed a survey design from January 1, 2018, to June 30, 2019. In collaboration with 11 outpatient anxiety clinics in Denmark, patients with a primary diagnosis of panic disorder, social phobia, generalized anxiety, or obsessive-compulsive disorder were invited to participate in the study. The final sample included 272 patients. Survey questions were related to sociodemographic characteristics, sexual activity and dysfunctions, pharmacological treatment adherence, anxiety and depression symptoms, and experience with and barriers to sexual communication. For each participant, clinicians at the clinics provided the International Classification of Diseases, 10th revision, diagnostic codes, medications, and dosage. Study inclusion criteria were not having an organic disorder that may cause anxiety, not having a previous diagnosis of bipolar affective disorder or schizophrenia, and the ability to speak and read Danish., Outcomes: Outcomes included patients' experiences with and barriers to sexual communication with healthcare staff., Results: In total, 61% of the patients in this sample group found it relevant to talk to healthcare staff about sexuality but only 28% of the study patients had done so, of whom 83% reported this communication to be a positive experience. The most frequently reported patient barriers to communication with healthcare professionals regarding sexual concerns were a belief that if sexual matters were relevant, the healthcare staff would bring it up (94%), fear of transgressing their own boundaries (94%), embarrassment (92%), and lack of knowledge as to how to start a conversation about sex (91%)., Clinical Implications: The study results indicated a need for healthcare staff to routinely map out and address sexual matters in their clinical work with anxiety patients while bearing in mind the common patient barriers for this topic., Strengths and Limitations: This study included a large clinical outpatient sample of anxiety patients and an extensive survey. However, the results may not be generalizable across all anxiety patients or patients in general., Conclusion: The results of this study strongly indicate that a majority of anxiety patients find it both relevant and beneficial to discuss sexual matters with healthcare staff in connection with their anxiety treatment, and therefore healthcare staff should be educated and equipped to routinely address these matters while bearing in mind the most common patient barriers for conversations about sexuality., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The current study investigated the phenomenon of faking orgasms, including the reasons why people stop faking orgasms, sociodemographic predictors of faking orgasms, its association with sex toy use, and its association with sexual, relationship, and life satisfaction. A cross-country convenience sample of 11,541 respondents from six European countries (Denmark, Finland, France, Norway, Sweden, and the UK) was collected in May and June 2022 through respondent panels by Cint, a market research software platform. Participants completed an online self-report survey. The study's main findings showed that around 51% of men and women in the study had never faked orgasms, around 28% had faked orgasms but stopped faking and around 13% currently faked orgasms. Further, the reasons for men and women to stop faking orgasms included becoming more comfortable with not having an orgasm, improving sexual communication with their sexual partner, and the partner paying more attention to the respondents' desires and preferences. Finally, it was shown that faking orgasms was associated with lower sexual, relationship, and life satisfaction. The current study represents one of the few research projects focusing on the phenomenon of stopping faking orgasms and reasons for it, with the added strength of including a large male sample.

Self-assembled materials capable of modulating their assembly properties in response to specific enzymes play a pivotal role in advancing 'intelligent' encapsulation platforms for biotechnological applications. Here, we introduce a previously unreported class of synthetic nanomaterials that programmatically interact with histone deacetylase (HDAC) as the triggering stimulus for disassembly. These nanomaterials consist of co-polypeptides comprising poly(acetyl L-lysine) and poly(ethylene glycol) blocks. Under neutral pH conditions, they self-assemble into particles. The hydrodynamic diameters of particles were typically withing the range of 108-190 nm, depending on degree of acetylation of the hydrophobic block. However, their stability is compromised upon exposure to HDACs, depending on enzyme concentration and exposure time. Our investigation, utilizing HDAC8 as the model enzyme, revealed that the primary mechanism behind disassembly involves a decrease in amphiphilicity within the block copolymer due to the deacetylation of lysine residues within the particles' hydrophobic domains. To elucidate the response mechanism, we encapsulated a fluorescent dye within these nanoparticles. Upon incubation with HDAC, the nanoparticle structure collapsed, leading to controlled release of the dye over time. Notably, this release was not triggered by denatured HDAC8, other proteolytic enzymes like trypsin, or the co-presence of HDAC8 and its inhibitor. We also demonstrated the biocompatibility and cellular effects of these materials in the context of drug delivery in different types of anticancer cell lines, such as MIA PaCa-2, PANC-1, cancer like stem cells (CSCs), and non-cancerous HPNE cells. We observed that the release of a model drug (such as a STAT3 pathway inhibitor, Napabucasin) can be loaded into these nanoparticles, with >90% of the dosage can be released over 3 h under the influence of HDAC8 enzyme in a controlled fashion. Further, we conducted a comprehensive computational study to unveil the possible interaction mechanism between enzymes and particles. By drawing parallels to the mechanism of naturally occurring histone proteins, this research represents a pioneering step toward developing functional materials capable of harnessing the activity of epigenetic enzymes such as HDACs.

Glass transition temperature of polymers, Tg, is an important thermophysical property, which sometimes can be difficult to measure experimentally. In this regard, data-driven machine learning approaches are important alternatives to assess Tg values, in a high-throughput way. In this study, a large dataset of more than 900 polymers with reported glass transition temperature (T g ) was assembled from various public sources in order to develop a predictive model depicting the structure-property relationships. The collected dataset was curated, explored via cluster analysis, and then split into training and test sets for validation purposes and then polymer structures characterized by molecular descriptors. To find the models, several machine learning techniques, including multiple linear regression (MLR), k-nearest neighbor (k-NN), support vector machine (SVM), random forest (RF), gaussian processes for regression (GPR), and multi-layer perceptron (MLP) were explored. As result, a model with the subset of 15 descriptors accurately predicting the glass transition temperatures was developed. The electronic effect indices were determined to be important properties that positively contribute to the T g values. The SVM-based model showed the best performance with determination coefficients (R 2 ) of 0.813 and 0.770, for training and test sets, respectively. Also, the SVM model showed the lowest estimation error, RMSE = 0.062. In addition, the developed structure-property model was implemented as a web app to be used as an online computational tool to design and evaluate new homopolymers with desired glass transition profiles., (© 2024. The Author(s).)

Competing Interests: NC-C declares grants from UCB and Roche. JES reports grants and consultancy fees from UCB. GMdF declares no competing interests.

Background: The risk for recurrence in patients with distal gastric cancer can be reduced by surgical radicality. However, dispute exists about the value of the proposed minimum proximal margin distance (PMD). Here, we assess the prognostic value of the safety distance between the proximal resection margin and the tumor., Patients and Methods: This is a single-center cohort study of patients undergoing distal gastrectomy for gastric adenocarcinoma (2001-2021). Cohorts were defined by adequacy of the PMD according to the European Society for Medical Oncology (ESMO) guidelines (≥ 5 cm for intestinal and ≥ 8 cm for diffuse Laurén's subtypes). Overall survival (OS) and time to progression (TTP) were assessed by log-rank and multivariable Cox-regression analyses., Results: Of 176 patients, 70 (39.8%) had a sufficient PMD. An adequate PMD was associated with cancer of the intestinal subtype (67% vs. 45%, p = 0.010). Estimated 5-year survival was 63% [95% confidence interval (CI) 51-78] and 62% (95% CI 53-73) for adequate and inadequate PMD, respectively. Overall, an adequate PMD was not prognostic for OS (HR 0.81, 95% CI 0.48-1.38) in the multivariable analysis. However, in patients with diffuse subtype, an adequate PMD was associated with improved oncological outcomes (median OS not reached versus 131 months, p = 0.038, median TTP not reached versus 88.0 months, p = 0.003)., Conclusion: Patients with diffuse gastric cancer are at greater risk to undergo resection with an inadequate PMD, which in those patients is associated with worse oncological outcomes. For the intestinal subtype, there was no prognostic association with PMD, indicating that a distal gastrectomy with partial preservation of the gastric function may also be feasible in the setting where an extensive PMD is not achievable., (© 2024. The Author(s).)

This work is devoted to the investigation of dielectric permittivity which is influenced by electronic, ionic, and dipolar polarization mechanisms, contributing to the material's capacity to store electrical energy. In this study, an extended dataset of 86 polymers was analyzed, and two quantitative structure-property relationship (QSPR) models were developed to predict dielectric permittivity. From an initial set of 1273 descriptors, the most relevant ones were selected using a genetic algorithm, and machine learning models were built using the Gradient Boosting Regressor (GBR). In contrast to Multiple Linear Regression (MLR)- and Partial Least Squares (PLS)-based models, the gradient boosting models excel in handling nonlinear relationships and multicollinearity, iteratively optimizing decision trees to improve accuracy without overfitting. The developed GBR models showed high R 2 coefficients of 0.938 and 0.822, for the training and test sets, respectively. An Accumulated Local Effect (ALE) technique was applied to assess the relationship between the selected descriptors-eight for the GB_A model and six for the GB_B model, and their impact on target property. ALE analysis revealed that descriptors such as TDB09m had a strong positive effect on permittivity, while MLOGP2 showed a negative effect. These results highlight the effectiveness of the GBR approach in predicting the dielectric properties of polymers, offering improved accuracy and interpretability.

Background: Mesenchymal stem cells (MSCs) have emerged as novel therapies for supporting arteriovenous fistula (AVF) maturation, and bioresorbable polymeric scaffolds have enabled sustained MSC delivery into maturing AVFs. However, the radiolucency of biopolymeric wraps prevents in vivo monitoring of their integrity and location, hindering long-term preclinical investigations., Methods: We infused bismuth nanoparticles (BiNPs) into polycaprolactone (PCL) to fabricate an electrospun perivascular wrap capable of MSC delivery and conducive to longitudinal monitoring using conventional imaging. We tested the wraps' effects on the attenuation of markers of neointimal hyperplasia (i.e., endothelial dysfunction, hypoxia, and inflammation), the leading cause of AVF failure, in rats with induced chronic kidney disease (n = 3 per time point) for the following groups: control (no wrap), PCL wrap, PCL with MSCs, PCL-Bi (BiNP-infused wrap), and PCL-Bi with MSCs., Results: Physicochemical characterization and in vitro biocompatibility tests revealed that BiNP infusion did not alter the wrap's non-cytotoxicity toward vascular cells, hemocompatibility, and capacity for MSC loading but facilitated long-term monitoring via micro-computed tomography. After 8 weeks, all treatment groups demonstrated significant improvement in wall-to-lumen ratio on ultrasonography (P < 0.001), neointima-to-lumen ratio on histomorphometry (P < 0.001), and attenuation of neointimal hypoxia on immunohistochemistry (P < 0.05). Compared to non-MSC wraps, MSC-loaded wraps not only attenuated endothelial dysfunction and neointimal inflammation but also reduced hypoxia and inflammation across all vascular layers., Conclusion: These results demonstrate that MSC delivery through a radiopaque polymeric wrap could enhance AVF patency outcomes through the inhibition of multiple pathways inducing AVF failure., 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.)

Introduction: Recent studies suggest the existence of a physiologic basis for bone rarefaction and increased risk for fractures. This study aimed to address anthropometric differences between patients with narcolepsy type 1 (NT1) and type 2 (NT2) and discrepancies in bone mineral content (BMC) as a function of hypocretin-1 (Hcrt-1) measured in cerebrospinal fluid (CSF)., Methods: We have evaluated 31 adult patients (aged 18-65 years) with NT1 and 18 patients with NT2, comparing the groups in terms of anthropometric variables - body mass index (BMI) and waist-to-hip ratio (WHR) - and percentage of bone mineral content (%BMC), measured by bioelectrical impedance analysis (BIA). Statistical analysis assessed the effects of Hcrt-1 levels on CSF, dietary intake, and medication use over these variables. Statistical significance was achieved with a confidence interval of 95 % and p < 0.05., Results: Patients with NT1 presented with higher BMI (32.04 ± 6.95 vs. 25.38 ± 4.26 kg/m 2 ; p < 0.01) and WHR (0.89 ± 0.09 vs. 0.83 ± 0.09; p = 0.02) compared to NT2, in detriment of %BMC, which was lower for NT1 (4.1 ± 1.02 vs. 4.89 ± 0.59; p < 0.01). Hcrt-1 in CSF showed a positive correlation with %BMC (r = +0.48, p < 0.01) and a negative correlation with anthropometric features (BMI: r = -0.54, p < 0.01; WHR: r = -0.37, p = 0.01). There was a correlation between WHR and diary caloric intake (r = +0.42, p < 0.01)., Conclusion: The evaluation of patients with narcolepsy presupposes a syndromic approach comprising symptoms that go far beyond excessive daytime sleepiness. The integrated follow-up, including nutritional profile and anthropometric features, should add value in reducing morbidity in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Cervical cancer is a major global health issue, ranking as the fourth most common cancer in women worldwide. Depending on stage, histology, and patient factors, the standard management of cervical cancer is a combination of treatment approaches, including (fertility- or non-fertility-sparing) surgery, radiotherapy, platinum-based chemotherapy, and novel systemic therapies such as bevacizumab, immune checkpoint inhibitors, and antibody-drug conjugates. While ambitious global initiatives seek to eliminate cervical cancer as a public health problem, the management of cervical cancer continues to evolve with major advances in imaging modalities, surgical approaches, identification of histopathological risk factors, radiotherapy techniques, and biomarker-driven personalized therapies. In particular, the introduction of immune checkpoint inhibitors has dramatically altered the treatment of cervical cancer, leading to significant survival benefits in both locally advanced and metastatic/recurrent settings. As the landscape of cervical cancer therapies continues to evolve, the aim of the present review is to provide a comprehensive discussion of the current state and the latest practice-changing updates in cervical cancer., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Primary effusion lymphoma (PEL) is a rare B-cell non-Hodgkin lymphoma associated with Kaposi Sarcoma-associated herpesvirus (KSHV/HHV8) infection. Lymphoma cells are coinfected with Epstein-Barr virus (EBV) in 60-80% of cases. Tools allowing a reliable PEL diagnosis are lacking. This study reports PEL diagnosis in 4 patients using a Flow-Fluorescence in situ hybridization (FlowFISH) technique that allowed detection of differentially expressed EBV and HHV8 transcripts within the same sample, revealing viral heterogeneity of the disease. Moreover, infected cells exhibited variable expressions of CD19, CD38, CD40, and CD138. Therefore, FlowFISH is a promising tool to diagnose and characterize complex viral lymphoproliferations., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

Ubiquitin-proteasome system (UPS) is a highly regulated mechanism of intracellular protein degradation and turnover. The UPS is involved in different biological activities, such as the regulation of gene transcription and cell cycle. Several researchers have applied cheminformatics and artificial intelligence methods to study the inhibition of proteasomes, including the prediction of UPP inhibitors. Following this idea, we applied a new tool for obtaining molecular descriptors (MDs) for modeling proteasome Inhibition in terms of EC 50 (µmol/L), in which a set of new MDs called atomic weighted vectors (AWV) and several prediction algorithms were used in cheminformatics studies. In the manuscript, a set of descriptors based on AWV are presented as datasets for training different machine learning techniques, such as linear regression, multiple linear regression (MLR), random forest (RF), K-nearest neighbors (IBK), multi-layer perceptron, best-first search, and genetic algorithm. The results suggest that these atomic descriptors allow adequate modeling of proteasome inhibitors despite artificial intelligence techniques, as a variant to build efficient models for the prediction of inhibitory activity., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

While there is a considerable body of literature on sexual aggression, we know much less about the violation of sexual boundaries within professional relationships. To address this knowledge gap, the characteristics of cases of sexual misconduct in the province of Quebec were extracted, based on a search of published disciplinary decisions between 1998 and 2020, using the legal databases CANLII and SOQUIJ. The search yielded 296 decisions including 249 male and 47 female members from 22 professional orders, and involving 470 victims. Results indicate that male professionals approaching mid-career accounted for a greater proportion of cases of sexual misconduct. Moreover, physical and mental health professionals were overrepresented in cases, as were female adult victims. Acts of sexual misconduct concerned mostly sexual touching and intercourse and occurred during consultations. Female professionals were more inclined to establish romantic and sexual relationships with clients than their male counterparts. Of the 92.0% of professionals found guilty of at least one count of sexual misconduct, two thirds eventually returned to practice. Following the guilty verdict, few faced rehabilitative measures. Recommendations are provided for the prevention of sexual recidivism and the accompaniment of victims of sexual misconduct throughout the disciplinary process., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Neurodegenerative diseases involve progressive neuronal death. Traditional treatments often struggle due to solubility, bioavailability, and crossing the Blood-Brain Barrier (BBB). Nanoparticles (NPs) in biomedical field are garnering growing attention as neurodegenerative disease drugs (NDDs) carrier to the central nervous system. Here, we introduced computational and experimental analysis. In the computational study, a specific IFPTML technique was used, which combined Information Fusion (IF) + Perturbation Theory (PT) + Machine Learning (ML) to select the most promising Nanoparticle Neuronal Disease Drug Delivery (N2D3) systems. For the application of IFPTML model in the nanoscience, NANO.PTML is used. IF-process was carried out between 4403 NDDs assays and 260 cytotoxicity NP assays conducting a dataset of 500,000 cases. The optimal IFPTML was the Decision Tree (DT) algorithm which shown satisfactory performance with specificity values of 96.4% and 96.2%, and sensitivity values of 79.3% and 75.7% in the training (375k/75%) and validation (125k/25%) set. Moreover, the DT model obtained Area Under Receiver Operating Characteristic (AUROC) scores of 0.97 and 0.96 in the training and validation series, highlighting its effectiveness in classification tasks. In the experimental part, two samples of NPs (Fe 3 O 4 &#95;A and Fe 3 O 4 &#95;B) were synthesized by thermal decomposition of an iron(III) oleate (FeOl) precursor and structurally characterized by different methods. Additionally, in order to make the as-synthesized hydrophobic NPs (Fe 3 O 4 &#95;A and Fe 3 O 4 &#95;B) soluble in water the amphiphilic CTAB (Cetyl Trimethyl Ammonium Bromide) molecule was employed. Therefore, to conduct a study with a wider range of NP system variants, an experimental illustrative simulation experiment was performed using the IFPTML-DT model. For this, a set of 500,000 prediction dataset was created. The outcome of this experiment highlighted certain NANO.PTML systems as promising candidates for further investigation. The NANO.PTML approach holds potential to accelerate experimental investigations and offer initial insights into various NP and NDDs compounds, serving as an efficient alternative to time-consuming trial-and-error procedures., (© 2024. The Author(s).)

Background: For patients receiving immune checkpoint inhibitors, early detection of immune-related adverse events (irAEs) is critical for one's safety. To this end, a smartphone app (SOFIA) was developed that featured the assessment of electronic patient-reported outcomes (ePROs) focusing on irAEs as well as a set of comprehensive supportive information. Its feasibility and preliminary efficacy were evaluated in a randomized controlled trial (RCT)., Methods: Patients who received immune checkpoint inhibition therapy were randomly assigned to an intervention group (IG) or a control group (CG; care as usual). During the 12-week intervention period, IG patients used SOFIA to report twice weekly ePROs and receive cancer- and immunotherapy-relevant contents. Before a patient's next clinical visit, the physician in charge was given the ePRO reports. The primary objective was to test the feasibility of SOFIA. Furthermore, the preliminary efficacy of SOFIA for health-related quality of life (HRQOL), psychosocial outcomes, and medical data was examined. Clinical outcomes were assessed at baseline (T0), post-intervention (T1), and a 3-month follow-up (T2)., Results: Seventy-one patients were randomized to the IG (n = 34) or the CG (n = 37). SOFIA showed high feasibility and acceptance. At T1, patients in the IG reported significantly better HRQOL and role functioning and less depression, distress, and appetite loss. No significant differences were revealed regarding medical data, the utilization of supportive care services, or survival., Conclusions: SOFIA showed high feasibility and acceptance and improved HRQOL and psychosocial outcomes. These results suggest further evaluation of efficacy in a large-scale confirmatory multicenter RCT., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Risk governance is central for the successful and ethical operation of biobanks and the continued social license for being custodians of samples and data. Risks in biobanking are often framed as risks for participants, whereas the biobank's risks are often considered as technical ones. Risk governance relies on identifying, assessing, mitigating and communicating all risks based on technical and standardized procedures. However, within such processes, biobank staff are often involved tangentially. In this study, the aim has been to conduct a risk mapping exercise bringing biobank staff as key actors into the process, making better sense of emerging structure of biobanks. Methods: Based on the qualitative research method of situational analysis as well as the card-based discussion and stakeholder engagement processes, risk mapping was conducted at the biobank setting as an interactive engagement exercise. The analyzed material comprises mainly of moderated group discussions. Results: The findings from the risk mapping activity are framed through an organismic metaphor: the biobank as a growing , living organism in a changing environment , where trust and sustainability are cross-cutting elements in making sense of the risks. Focusing on the situatedness of the dynamics within biobanking activity highlights the importance of prioritizing relations at the core of risk governance and promoting ethicality in the biobanking process by expanding the repertoire of considered risks. Conclusion: With the organismic metaphor, the research brings the diverse group of biobank staff to the central stage for risk governance, highlighting how accounting for such diversity and interdependencies at the biobank setting is a prerequisite for an adaptive risk governance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Akyüz, Goisauf, Martin, Mayrhofer, Antoniou, Charalambidou, Deltas, Malatras, Papagregoriou, Stefanou and Voutounou.)

In recent years, alternative animal testing methods such as computational and machine learning approaches have become increasingly crucial for toxicity testing. However, the complexity and scarcity of available biomedical data challenge the development of predictive models. Combining nonlinear machine learning together with multicondition descriptors offers a solution for using data from various assays to create a robust model. This work applies multicondition descriptors (MCDs) to develop a QSTR (Quantitative Structure-Toxicity Relationship) model based on a large toxicity data set comprising more than 80,000 compounds and 59 different end points (122,572 data points). The prediction capabilities of developed single-task multi-end point machine learning models as well as a novel data analysis approach with the use of Convolutional Neural Networks (CNN) are discussed. The results show that using MCDs significantly improves the model and using them with CNN-1D yields the best result ( R 2 train = 0.93, R 2 ext = 0.70). Several structural features showed a high level of contribution to the toxicity, including van der Waals surface area (VSA), number of nitrogen-containing fragments (nN+), presence of S-P fragments, ionization potential, and presence of C-N fragments. The developed models can be very useful tools to predict the toxicity of various compounds under different conditions, enabling quick toxicity assessment of new compounds.