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This paper investigates the flexural bearing behavior of reinforced concrete beams through experimental analysis and advanced machine learning predictive models. The primary problem centers around understanding how varying compositions of construction materials, particularly the inclusion of recycled aggregates and carbon fiber-reinforced polymer (CFRP), affect the structural performance of concrete beams. Eight beams, including those with natural aggregates, recycled aggregates, fly ash, and CFRP, were tested. The study employs state-of-the-art machine learning frameworks, including Random Forest Regressor (RFR), XGBoost (XGB), and LightGBM (LGBM). The formation of these models involved data acquisition from experiments, preprocessing of key input features (such as rebars area, cement portion, recycled and natural aggregate masses, silica fume, fly ash, compressive strength, and CFRP presence), model selection, and hyperparameter tuning using Pareto optimization. The models were then evaluated using performance metrics like Mean Squared Error (MSE), Mean Absolute Error (MAE), and coefficient of determination (R 2 ). Outputs focus on load-induced deflection and mid-span displacement. With a dataset of 4851 samples, the optimized models demonstrated excellent performance. The experimental results revealed substantial enhancements in both compressive strength and load-bearing capacity, notably observed in beams incorporating 70% recycled aggregate and 10% silica fume. These beams exhibited a remarkable increase in compressive strength of up to 53.03% and a 7% boost in load-bearing capacity compared to those without recycled aggregate. By integrating experimental analysis with advanced computational techniques, this study advances the understanding of eco-friendly construction materials and their performance, shedding light on the intricate interactions between sustainable construction materials and the flexural bearing behavior of beams., Competing Interests: Declarations Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

AI-based methods to generate images have seen unprecedented advances in recent years challenging both image forensic and human perceptual capabilities. Accordingly, these methods are expected to play an increasingly important role in the fraudulent fabrication of data. This includes images with complicated intrinsic structures such as histological tissue samples, which are harder to forge manually. Here, we use stable diffusion, one of the most recent generative algorithms, to create such a set of artificial histological samples. In a large study with over 800 participants, we study the ability of human subjects to discriminate between these artificial and genuine histological images. Although they perform better than naive participants, we find that even experts fail to reliably identify fabricated data. While participant performance depends on the amount of training data used, even low quantities are sufficient to create convincing images, necessitating methods and policies to detect fabricated data in scientific publications., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Although balance training can improve balance across various populations, the underlying mechanisms, such as how balance training may alter sensory integration, remain unclear. This study examined the effects of balance training with visual input manipulations provided by virtual reality versus conventional balance training on measures of postural sway and sensory integration during balance control. Twenty-two healthy young adults were randomly allocated into a balance training group (BT) or a balance training with virtual reality group (BT + VR). The BT received traditional balance training, while the BT + VR additionally received visual manipulations during the 4-week balance training to elicit sensory conflicts. Static balance was measured in the form of center of pressure (COP) sway speed in trained (eyes open) and untrained (eyes closed) balance conditions. A model-based analysis quantified the sensory integration and feedback characteristics of the balance control mechanism. Herein, the visual weight quantifies the contribution of visual orientation information to balance while the proportional and derivative feedback loop-gains correct for deviations from the desired angular position and angular velocity, respectively. Significant main time effects were observed for the visual sensory contribution to balance (p = 0.002, [Formula: see text] = 0.41) and for the derivative feedback loop-gain (p = 0.011, [Formula: see text] = 0.29). Significant group-by-time interactions were observed for COP sway speed in the untrained task (p = 0.023, [Formula: see text] = 0.23) in favor of BT + VR and in the proportional feedback loop-gain, with reductions only in the BT + VR group (p = 0.043, [Formula: see text] = 0.2). BT + VR resulted in larger performance improvements compared with traditional BT in untrained tasks, most likely due to reduced reliance on visual information. This suggests that the systematic modulation of sensory inputs leads to enhanced capacity for motor adaptation in balance training., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The utilization of biochar as a relatively efficient sorbent or stationary phase for the separation and preconcentration of a wide range of analytes represents an innovative approach in current sample pretreatment methods. Appropriate pre- and post-pyrolysis modification of the input precursor and pyrolysis product, respectively, allows targeted design of the physicochemical properties and sorption characteristics of the resulting sorbent. The present work deals with the preparation of pyrolysis materials based on unmodified cattail leaf biomass (BC) and its Mg-modified analogue (MgBC) by a slow pyrolysis process at 500 °C and a residence time of 1 h in a pyrolysis reactor. Physicochemical characterization of BC and MgBC carried out by pH, total C, N, surface size analysis (SSA), 13 C NMR, SEM-EDX and XRD confirmed significant morphological and mineralogical differences between the prepared sorbents. By performing sorption experiments using a model anionic analyte (As) and application of Langmuir isotherm, we found that the predicted maximum sorption capacity of MgBC for As is 13.5-fold higher than that of BC. The sorption process of As by both sorbents is best described by the Sips adsorption isotherm (R 2  ≥ 0.995) and a pseudo-n th order kinetic model (R 2  ≥ 0.997). The optimum pH for As sorption by BC and MgBC sorbents is in the interval 5-6. The presence of competitive phosphate anions (equimolar concentration of 1:1) in the solution significantly reduces the sorption capacity of MgBC for As by 40% for BC by 70%. The presence of Cl- ions showed no significant effect on the sorption capacity of Bc and MgBC for As. Both sorbents were best recovered using 0.1 mol/L NaOH solution when the desorption efficiency for both sorbents was more than 95%. The MgBC sorbent showed 35% retention of As from the real sample in the model SPE column at a flow rate of 0.12 mL/s. Based on the obtained knowledge, it is evident that biochar-based sorbent prepared from Mg-modified precursor represents an effective sorbent for anionic forms of analytes and opens the possibility of its use also in preconcentration and separation techniques., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Bone health screening is crucial before and during androgen deprivation therapy (ADT) for prostate cancer, yet changes in bone mineral density during ADT are often overlooked. To improve surveillance rates, we developed an auto-recruit path integrated into the outpatient system, where a pop-up reminder prompts physicians to arrange bone health screenings when ADT is prescribed without a dual-energy x-ray absorptiometry (DXA) screening in the past year. If selected, the system orders DXA and related examinations automatically. We retrospectively reviewed DXA screening rates from 2000 to 2018. During that period, only 286 out of 3,019 patients (9.5%) received DXA screenings. After implementing the auto-recruit system, 251 out of 747 eligible patients (33.6%) were screened from March 2021 to February 2022. Participants using ADT for over a year had worse T-scores and higher osteoporosis rates (34.5% vs. 23.2%) compared to those using ADT for less than a year. Post-screening, there was a significant increase in calcium supplement and bone protective agent use, highlighting improved patient awareness and proactive bone health management. In conclusion, bone health screening for prostate cancer patients on ADT remains an unmet need. The auto-recruit path in the outpatient system effectively increases screening rates and enhances bone health management., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Despite remarkable improvements in the survival of pediatric acute lymphoblastic leukemia (ALL), sensitive detection and clinical management of central nervous system leukemia (CNSL) are still immensely challenging. Blast cells residing in the CNS but not circulating in the cerebrospinal fluid (CSF) remain undetected by current diagnostic methods, preventing a truly risk-adapted anti-leukemic treatment in this compartment. We examined the clinical applicability of the molecular marker microRNA (miR)-181a quantified in the cell-free CSF to evaluate the level of CNS involvement and to optimize patient stratification based on CNS status. Normalized copy number of miR-181a was longitudinally profiled using droplet digital PCR, and the results were compared with the degree of leukemic involvement of the CNS. After combining cytospin- and flow cytometry (FCM) data with miR-181a expression, we could stratify previously ambiguous cases and reclassify patients into a CNS-positive/miR-significant group (mean ± SE for miR-181a copies: 3300.70 ± 809.69) bearing remarkable infiltration as well as into CNS-minimal/miR-significant and CNS-minimal/miR-minimal groups differentiating putative, clinically significant occult CNSL cases (2503.50 ± 275.89 and 744.02 ± 86.81 copies, respectively, p = 1.13 × 10 -6 ). In summary, miR-181a expression is a promising biomarker for CNSL detection, facilitating the robust identification of patients who could benefit from intensified CNS-directed therapy., Competing Interests: Ethics approval and consent to participate All procedures performed in this study, involving human participants were in accordance with the ethical standards of the Medical Research Council of Hungary, and with the 1964 Helsinki declaration and its later amendments. The study was approved by the central ethical committee (institute: National Scientific and Ethical Committee of the Medical Research Council of Hungary (ETT-TUKEB), approval numbers: 60106–1/2015/EKU and 6886/2019/EKU). The study is compliant with all relevant ethical regulations for human research participants, and informed consent was obtained from all patients or legal guardians. Consent for publication The study is compliant with all relevant ethical regulations for human research participants, and informed consent was obtained from all patients or legal guardians. Data availability The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding author. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Prior research on e-cigarettes' health impacts is inconclusive due to confounding by previous tobacco smoking. Studies of e-cigarette use among people without an established smoking history are informative for this question. A cross-sectional survey was administered across six geopolitical world regions to adults aged 18+ without a history of established cigarette smoking or regular use of other nicotine/tobacco products. Two cohorts were defined based on e-cigarette use: "Vapers Cohort" (N = 491) who used e-cigarettes in the past 7 days and "Control Cohort" (N = 247) who never regularly used e-cigarettes. Frequency of respiratory symptoms (Respiratory Symptom Evaluation Score (RSES)) were compared between cohorts, adjusting for sociodemographics. Tobacco use history and patterns of e-cigarette use was also examined. Respiratory symptoms were rare among both the Vapers and Control Cohorts: 83.3% and 88.4%, respectively, reported "rarely" or "never" experiencing all five RSES items (p = 0.125). The Vapers (vs. Control) Cohort reported modestly more frequent respiratory symptoms (adjusted mean RSES 1.61 vs. 1.43, respectively, p < 0.001); however, this difference (0.18) did not reach the threshold of clinical relevance (0.57). The Vapers (vs. Control) Cohort more often reported former cigarette experimentation (30.8% vs. 12.1%) and former infrequent use of other nicotine/tobacco products (18.1% vs. 5.8%). The Vapers Cohort most often used disposable devices (63.7%) and multiple flavors (approximately 70-80% across primary device type). In this cohort of adults without a history of established combustible tobacco use, e-cigarette use was statistically linked to more frequent respiratory symptoms, though not in a clinically meaningful way. The cross-sectional design of this study cannot establish causality between e-cigarette use and respiratory symptoms., Competing Interests: Declarations Competing interests JZG is the President of Asovape Costa Rica, a Pro-Harm Reduction consumer organization; President of ARDT Iberoamerica, an alliance of Pro-Harm Reduction consumer organizations in Latin America, Spain, and Portugal; Director of Social Media and Audiovisual Producer of INNCO , a global coalition of Pro-Harm Reduction consumer organizations, which received funding from the Foundation for a Smokefree World (FSFW); and a recipient of a scholarship from Knowledge-Action-Change, which received funding from the Foundation for a Smokefree World (FSFW). None of these organizations had any role in, or oversight, of this study. AB is serving Pro Bono as Vice President, American Vapor Manufacturers —Prescott, AZ. Serving Pro Bono as Ambassador, World Vapers Alliance Serving Pro Bono as President, South Carolina Vapor Association, Charleston, SC JJCL is the President of the board of Mexico y el Mundo Vapeando O.N.G. and a scholarship recipient from Knowledge-Action-Change, which received funding from the Foundation for a Smokefree World (FSFW). None of these organizations had any role in, or oversight, of this study. Court Lawyer for vaping industries AM is a recipient of two scholarships from Knowledge-Action-Change, which receives funding from the Foundation for a Smokefree World (FSFW). This organisation has not had any role in, or oversight, of this study. KY is the Co-Founder of the Consumer Advocacy movement Vaping Saved My Life (VSML) Act as a consultant for the Vapour Products Association of South Africa (VPASA), an industry association for vapor product manufacturers and retailers. A member of the Advisory Board for the World Vapers Alliance (W.V.A.), a global consumer advocacy group. Recipient of the Tobacco Harm Reduction Scholarship Programme and Advanced Scholarship Programme from Knowledge Action Change(K.A.C.). K.A.C. receives funding from the Foundation for a Smoke-Free World. MS is a co-founder of Smoke-Free Baltic tobacco harm reduction initiative and a recipient of a scholarship from Knowledge—Action—Change, which received funding from the Foundation for a Smokefree World (FSFW). None of these organizations had any role in, or oversight, of this study. CR is Director of Russell Burnett Research and Consultancy Ltd, which has received research funding and/or consultancy fees from manufacturers of e-cigarettes/vaping products to conduct or consult on studies of individuals’ perceptions and use of tobacco and nicotine products, including e-cigarettes/vaping products. Michael Coughlan is a recipient of a scholarship from Knowledge-Action-Change, which received funding from the Foundation for a Smokefree World (FSFW). None of these organizations had any role in, or oversight, of this study. AS provides consulting services on tobacco harm reduction to Juul Labs, Inc. (JLI) through PinneyAssociates. She also individually provides consulting services on behavioral science to the Center of Excellence for the Acceleration of Harm Reduction (CoEHAR) through ECLAT Srl., which received funding from the Foundation for a Smokefree World (FSFW). None of these funders had any role in, or oversight, of this study. GC declares no conflict. PC declares no conflict. VT declares no conflict. RP is full tenured professor of Internal Medicine at the University of Catania (Italy) and Medical Director of the Institute for Internal Medicine and Clinical Immunology at the same University. He has received grants from U-BIOPRED and AIR-PROM, Integral Rheumatology & Immunology Specialists Network (IRIS), Foundation for a Smoke Free World, Pfizer, GlaxoSmithKline, CV Therapeutics, NeuroSearch A/S, Sandoz, Merk Sharp & Dohme, Boehringer Ingelheim, Novartis, Arbi Group Srl., Duska Therapeutics, Forest Laboratories, Ministero dell Universita’ e della Ricerca (MUR) Bando PNRR 3277/2021 (CUP E63C22000900006) and 341/2022 (CUP E63C22002080006), funded by NextGenerationEU of the European Union (EU), and the ministerial grant PON REACT-EU 2021 GREEN- Bando 3411/2021 by Ministero dell Universita’ e (MUR) – PNRR EU Community. He is founder of the Center for Tobacco Prevention and Treatment (CPCT) at the University of Catania and of the Center of Excellence for the Acceleration of Harm Reduction at the same university. He receives consultancy fees from Pfizer, Boehringer Ingelheim, Duska Therapeutics, Forest Laboratories, CV Therapeutics, Sermo Inc., GRG Health, Clarivate Analytics, Guidepoint Expert Network, and GLG Group. He receives textbooks royalties from Elsevier. He is also involved in a patent application for ECLAT Srl. He is a pro bono scientific advisor for Lega Italiana Anti Fumo (LIAF) and the International Network of Nicotine Consumers Organizations (INNCO); and he is Chair of the European Technical Committee for Standardization on “Requirements and test methods for emissions of electronic cigarettes” (CEN/TC 437; WG4). Ethical approval The study protocol received approval from the Ethics Review Board of the Dipartimento di Scienze della Formazione Sezione di Psicologia at the University of Catania (approval date, 25 November 2020). All participants provided written informed consent., (© 2024. The Author(s).)

Breast cancer is one of the deadliest malignancies in women worldwide. Zinc finger protein 32 (ZNF32) has been reported to be involved in autophagy and stem cell like properties of breast cancer cells. However, the effects, mechanisms, target genes and pathways of ZNF32 in breast cancer development have not been fully explored. In this study, stable ZNF32 overexpression breast cancer cell line was generated, and we used RNA-seq and RT-qPCR to quantify and verify the changes in transcription levels in breast cancer cells under ZNF32 overexpression. Transcriptome analysis showed that high expression of ZNF32 is accompanied by changes in downstream focal adhesion, ECM-receptor interaction, PI3K-AKT, HIPPO and TNF signaling pathways, which are critical for the occurrence and development of cancer. Multiple differentially expressed genes (DEGs) were significantly involved in cell proliferation, adhesion and migration, including 11 DEGs such as CA9, CRLF1 and ENPP2P with fundamental change of regulation modes. All the 11 DEGs were validated by RT-qPCR, and 9 of them contained potential transcriptional binding sequences of ZNF32 in their promoter region. This study provides a holistic perspective on the role and molecular mechanism of ZNF32 in breast cancer progression., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

One of the key factors in manufacturing products by fused deposition molding (FDM) or layer-by-layer printing technology is the material intensity of the product. The task of reducing the amount of material required to manufacture a product without significant loss of mechanical properties is one of the most practically important technological tasks. Material saving in FDM printing of products allows to reduce financial costs and increase the speed of manufacturing of the final product without reducing (or not significantly reducing) the quality properties of the product. In our work it is demonstrated that using Combs filling type and materials of poly lactic acid (PLA) and polyethylene terephthalate glycol (PETG) it is possible to achieve material savings of up to 23% at 50% filling for PLA and 17% at 75% filling for PETG without significant reduction of product strength in comparison with other filling types. Exceptions are PLA samples with 100% fill and Lateral fill. Application of Kruskal-Wallis criterion and Dunn's criterion with Bonferroni multiple comparison correction showed that there were no statistically significant differences within the strength limits of samples made by FDM printing technology from PLA and PETG plastics (p-value = 0.0514), as well as samples with Triangle and Grid filling type (p-value = 1). Based on this result, three groups of samples statistically significantly differing in ultimate strength were identified by methods of hierarchical cluster analysis; in each group (except for group 1, which included samples made of PLA plastic with Lateral filling type and 100% filling), correlation analysis was performed (Spearman correlation was used). The results of the correlation analysis showed a stable average correlation between the percentage of filling, modulus along the secant 0.05-0.2% strain, ultimate strength and strain corresponding to the yield stress. Analysis of the correlation graph showed that the main parameter correlating with all mechanical properties of the specimen is the 0.05-0.2% strain modulus. Based on this conclusion, robust regression equations predicting the 0.05-0.2% strain modulus as a function of the percentage of specimen filling were constructed for the two selected groups. Analysis of the equations showed that in the third group of specimens, the average modulus of 0.05-0.2% strain is more than twice the modulus of 0.05-0.2% strain in the second group. The detected statistical regularities can be explained by the mechanism of strain hardening, the actual value of which depends on the structure of the macrodefect (type of filling), properties and volume of the material (percentage of filling) used in the fabrication of samples using FDM printing technology., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Skin ageing results in wrinkling. In this study, we discuss four types of facial wrinkles: Crow's Feet wrinkles, forehead wrinkles, glabellar frown wrinkles, and nasolabial folds. These four phenotypes can be assessed either with a photo-numeric scale developed and validated on Caucasian skin (i.e., Caucasian scale) or with a photo-numeric scale developed and validated on Chinese skin (i.e., Chinese scale). As Caucasian and Chinese skin have inherent differences, the main objective of this study is to determine whether these inherent differences affect the suitability of evaluating facial wrinkles on ethnic Chinese skin with a Caucasian scale. Three trained assessors studied four types of wrinkles on the faces of 1,081 ethnic Chinese young adults from the Singapore/Malaysia Cross-sectional Genetics Epidemiology Study (SMCGES). We found that Caucasian scales and Chinese scales are concordant (Spearman's Rank Correlation (ρ) values: 0.53-0.80) and the level of agreement between the Caucasian scales and Chinese scales is moderately high (Cohen's Kappa (κ) values: 0.40-0.49). When tested on ethnic Chinese skin, both the Caucasian scale and the Chinese scale are largely consistent in showing presence or absence of a given facial wrinkle (Area under curve (AUC) values: 0.79-0.90). All assessors are highly internally consistent (Weighted Kappa (κ w ) values: 0.686-0.992). Our results build confidence that four types of facial wrinkles on ethnic Chinese faces can be assessed with Caucasian scales. To the best of our knowledge, Chinese scales for facial wrinkles beyond the four types discussed here have yet to be developed. Caucasian scales for these other facial wrinkles will also need to be tested for their suitability to be used on ethnic Chinese skin as and when more Chinese scales are developed., Competing Interests: Declarations Ethics approval and consent This study was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practices, and in compliance with local regulatory requirements. The cross-sectional studies in Singapore were conducted on the National University of Singapore (NUS) campus annually between 2005 and 2023 with the approval of the Institutional Review Board (Reference Code: NUS-07-023, NUS-09-256, NUS-10-445, NUS-13-075, NUS-14-150, and NUS-18-036) and by the Helsinki declaration, of which, participants between 2011 and 2022 participated in the current skin ageing study (Reference Code: NUS-2020-495). The cross-sectional studies in Malaysia were held in Universiti Tunku Abdul Rahman (UTAR) Campus and Sunway University. Ethical approval was granted from the Scientific and Ethical Review Committee of UTAR (Reference Code: U/SERC/03/2016) and the Sunway University Research Ethics Committee (Reference Code: SUREC 2019/029 and SUREC 2022/049). Before the data collection, all participants involved signed an informed consent form. Consent for publication All authors have read and consented to the publication of this manuscript. Competing interests F.T.C reports grants from the National University of Singapore, Singapore Ministry of Education Academic Research Fund, Singapore Immunology Network, National Medical Research Council (NMRC) (Singapore), Biomedical Research Council (BMRC) (Singapore), National Research Foundation (NRF) (Singapore), Singapore Food Agency (SFA), Singapore’s Economic Development Board (EDB), and the Agency for Science Technology and Research (A*STAR) (Singapore), during the conduct of the study; and consulting fees from Sime Darby Technology Centre; First Resources Ltd; Genting Plantation, Olam International, Musim Mas, and Syngenta Crop Protection, outside the submitted work. The other authors declare no other competing interests. This research is supported by the National Research Foundation Singapore under its Open Fund-Large Collaborative Grant (MOH-001636) (A-8002641-00-00) and administered by the Singapore Ministry of Health’s National Medical Research Council., (© 2024. The Author(s).)

Additive manufacturing of metallic parts by Selective Laser Melting (SLM) implies high temperature gradients and small volume of the melt bath. These conditions make the process scales close to those available for state-of-the-art massively parallel atomistic simulations. In the paper, the microscopic mechanisms responsible for the formation of primary microstructure during molten metal solidification are investigated using classical molecular dynamics (CMD). The 316L austenitic stainless steel with face centred cubic lattice, which is widely used in industry including SLM applications was chosen as a material for the CMD simulations. It was shown that solidified material inherits substrate defects and catches new ones, which interact with the solidification front thus producing the primary microstructure. Peculiarities of solidification in different crystallographic directions and solidification front interaction with grain boundaries and newly produced defects (mostly twin boundaries) as well as their formation are under study. Resulting microstructures of virtual samples are compared with those of real samples produced by SLM and analysed by the electron backscatter diffraction (EBSD) method. The comparison shows similarities of EBSD and CMD sample patterns and evidences for the capability of the large-scale atomistic simulations to reproduce main features of the microstructures formed in the metallic SLM additive production., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Orofacial clefts are among the most prevalent birth defects, with severe medical and psychosocial consequences. Cleft lip with or without cleft palate (CL ± P) and cleft palate only (CPO) affect on average nearly 1/700 births worldwide. The cause of most non-syndromic cases is unknown. Maternal factors and disorders are assumed to modify the risk of orofacial clefting. In the present study, we performed a systematic review and meta-analysis to analyze the effects of maternal underweight, obesity, hypertension, diabetes, as well as smoking, and alcohol consumption on the development of orofacial clefts. As CL ± CP and CPO have distinct pathogenetic backgrounds, these cleft subtypes were assessed separately. Altogether, 5,830 studies were identified and 64 of them met the inclusion and exclusion criteria. Obesity significantly elevated the odds of clefting (OR = 1.28, CI:1.08-1.51) (OR CL±CP  = 1.23, CI:1.01-1.50; OR CPO  = 1.31, CI:0.97-1.77). Maternal underweight also significantly increased the odds of clefting (OR = 1.21 CI:1.06-1.38). In mothers with type 1 diabetes, the odds of cleft development were significantly elevated (OR = 1,75, CI:1.45-2.12). Essential hypertension was also associated with higher odds of developing cleft (OR = 1.55, CI:1.18-2.03). Smoking during pregnancy significantly elevated the odds of cleft development (OR = 1.55, CI:1.34-1.79) (OR CL±CP  = 1.58, CI:1.36-1.83; OR CPO  = 1.50, CI:1.15-1.96). Passive smoking was even more damaging than active tobacco use, but alcohol consumption had no effect. In conclusion, this study clearly showed the importance of maintaining normal maternal body weight and emphasized the importance of hypertension and type 1 diabetes care in the first months of pregnancy. It also highlighted similarnegative effects of passive and active smoking, while alcohol consumption did not seem to be a significant risk factor for cleft development. However, there is a complete lack of available studies on the interactions of these factors, which is an essential direction for improving prevention., Competing Interests: Declarations Conflict of interest There is nothing to declare., (© 2024. The Author(s).)

p-NiO/n-Ga 2 O 3 heterojunction (HJ) diodes exhibit much larger changes in their properties upon 1.1 MeV proton irradiation than Schottky diodes (SDs) prepared on the same material. In p-NiO/Ga 2 O 3 HJ diodes, the narrow region adjacent to the HJ boundary is found to contain a high density of relatively deep centers with levels near E C -0.17 eV and a depleted region in the immediate vicinity of the HJ boundary. The series resistance of the HJ diodes is slightly higher than for the Schottky diodes and shows a temperature dependence with activation energy ~ 0.12 eV, like the temperature dependence of the NiO film resistivity. Irradiation with 1.1 MeV protons leads to a decrease of the hole concentration in the NiO, with a high carrier removal rate of ~ 1.3 × 10 5  cm -1 and a strong compensation of the interfacial region where the concentration of the E C -0.17 eV centers decreases with a high rate of ~ 7 × 10 3  cm -1 . The combined action of these two effects gives rise to the much stronger increase of the series resistance of the HJ diodes compared to Schottky diodes. The observed differences between the radiation response of the HJs and SDs cannot be credibly attributed to the changes of the density of any of the deep electron and hole traps detected in our experiments., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Astaxanthin due to its strong antioxidant activity is believed to reduce oxidative stress and therefore is considered as feed additive in pathological conditions and also for the athletes. It is promoted by several equine web portals, however, data supporting that concept in horses is limited. Thus, the aim of this study was to evaluate the effect of astaxanthin supplementation on the parameters of oxidative status in 3 years old, racing Arabian horses during long term observation and the changes related to a single training session of high intensity. Six horses were supplemented with astaxanthin at a dose of 0.52-0.58 mg/kg BW and 7 received no supplementation. Astaxanthin supplementation resulted in the increase in total antioxidant status by 31.5%, accompanied by decreases in the amount of total thiobarbituric acid-reactive substances -TBARS and glutathione reductases - GR values by 34.5% and 45.4%, respectively, after 1 month and this effect persisted until the end of the observation. After individual training session the activities of glutathione peroxidases and GR were lower by 69% and 46%, respectively, and TBARS lower by 38% in supplemented horses. These results directly confirmed the beneficial effects of astaxanthin supplementation on the antioxidant status of race horses. Astaxanthin partially counterbalance the training-related oxidative stress, save the horse natural antioxidant defense, and shift the redox status towards a more reducing environment. At the same time, exercise-induced reactive oxygen species production at certain level was maintained and so that contributed to training progress., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval and consent to participate All the procedures of blood sampling were performed as part of routine health examination and exercise test and thus, according to the European directive EU/2010/63 and Polish regulations regarding experiments in animal there was no need for the approval of Ethics Committee for the described procedures, qualified as non-experimental clinical veterinary practices, excluded from the directive. The trainer granted a written informed consent for the use of blood for scientific analyses. The authors complied with the ARRIVE guidelines (https://arriveguidelines.org)., (© 2024. The Author(s).)

Early and accurate diagnosis is crucial to prevent disease development and define therapeutic strategies. Due to predominantly unspecific symptoms, diagnosis of autoimmune diseases (AID) is notoriously challenging. Clinical decision support systems (CDSS) are a promising method with the potential to enhance and expedite precise diagnostics by physicians. However, due to the difficulties of integrating and encoding multi-omics data with clinical values, as well as a lack of standardization, such systems are often limited to certain data types. Accordingly, even sophisticated data models fall short when making accurate disease diagnoses and presenting data analyses in a user-friendly form. Therefore, the integration of various data types is not only an opportunity but also a competitive advantage for research and industry. We have developed an integration pipeline to enable the use of machine learning for patient classification based on multi-omics data in combination with clinical values and laboratory results. The application of our framework resulted in up to 96% prediction accuracy of autoimmune diseases with machine learning models. Our results deliver insights into autoimmune disease research and have the potential to be adapted for applications across disease conditions., Competing Interests: D eclarations Conflict of interest Jan Kruta, Raphael Carapito, Marten Trendelenburg, Thierry Martin, Marta Rizzi, Reinhard E. Voll, Andrea Cavalli, Eriberto Natali, Patrick Meier, Marc Stawiski, Johannes Mosbacher, Annette Mollet, Miriam Capri, Enrico Giampieri, Aurelia Santoro and Erik Schkommodau declare that they have no conflict of interest. Enkelejda Miho owns shares in aiNET GmbH. Ethics approval This study, involving human participants, complies with the Declaration of Helsinki and has received approvals from the appropriate medical ethical committees. The study has been approved by the CHU Strasbourg Medical Ethical Committee under the approval number CPP- IV- Est- 08/02/2011. Participants gave their informed consent prior to their involvement in the study., (© 2024. The Author(s).)

This study aimed to describe a novel sandwich technique of minimally invasive surgical implantation by using corneal stromal lenticules for corneal perforation. This prospective observational study included nine patients aged 23-79 years (mean, 54 ± 9) from Tianjin Eye Hospital. Corneal stromal lenticules with a central thickness of 120 μm were obtained from small incision lenticule extraction(SMILE). With the corneal perforation as the central point, an iris-repositor was used to manually create a mid-stromal pocket; the stromal lenticular button was gently inserted into the intrastromal pocket and flattened. The graft was sandwiched between the anterior and posterior corneal stromal pockets; the incision was closed using two sutures. The primary health outcome measured in this study was the logMAR best spectacle-visual acuity at 6 months postoperatively. Corneal perforation closure and anterior chamber formation occurred immediately after surgery. No epithelial implantation, infection, or allogeneic rejection was observed during the follow-up. No patients required a penetrating keratoplasty. Anterior segment optical coherence tomography revealed a mean thickness of the grafted tissue of 122 ± 21 μm, with a clear interface in all cases. Comparing the baseline and postoperative 6-month values, the mean logMAR best spectacle-corrected visual acuity was improved from 0.18 ± 0.12 to 0.52 ± 0.31 (P < 0.001). There was significant reduction in the mean manifest spherical equivalent, refractive cylinder, and mean keratometry readings. The novel minimally invasive surgical method for corneal implantation. It was an effective alternative treatment that could restore corneal integrity and improve vision in patients with corneal perforations. This method appears safe, easy, cost- and time-effective, and reliable., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The implementation of home-care robots is sometimes unsuccessful. This study aimed to explore factors explaining people's willingness to use home-care robots, particularly among care recipients and caregivers. Surveys were conducted in Japan, Ireland, and Finland. The survey questionnaire comprised four categories (familiarity with robots, important points about home-care robots, functions expected from home-care robots, and ethically acceptable uses), with 48 items assessing users' willingness to use home-care robots. The responses from 525 Japanese, 163 Irish, and 170 Finnish respondents were analyzed to identify common and distinct factors influencing their willingness to use these robots. Common factors across the countries included "willingness to participate in research and development," "interest in robot-related news," and "having a positive impression of robots". The distinct factors for each country were: "convenience" in Japan; "notifying family members and support personnel when an unexpected change occurs in an older person" in Ireland; and "design" in Finland. Therefore, developers should determine potential users' willingness to participate in the research and development of home-care robots and consider a system that involves them in the development process., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Due to their small size, flexibility, and adhesive properties, extracellular vesicles (EVs) hold promises as effective drug delivery systems. However, challenges such as the variability in vesicle types and the need to maintain their integrity for medical applications exist. Curcumin, a compound found in turmeric and known for its diverse health benefits, including anti-cancer and anti-inflammatory properties, faces obstacles in clinical use due to issues like low solubility, limited absorption, and rapid breakdown in the body. This study aimed to incorporate large-sized curcumin-loaded extracellular vesicles (lEVs) into fast-dissolving nanofibers made of poly(vinyl alcohol) (PVA) by electrospinning. By using aqueous PVA-based solutions for electrospinning, the presence of curcumin-loaded lEVs in the nanofibers was confirmed by confocal laser scanning microscopy. Furthermore, the release study demonstrated high concentrations of the drug in nanofibers containing lEVs. These findings are significant for advancing the development and utilization of active ingredient-loaded EV systems within nanofibrous formulations, potentially leading to improved patient outcomes., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Fluid overload predicts morbidity and mortality in dialysis patients. Diuretics can reduce fluid overload, but their effects on morbi-mortality following inception remain ill-defined. To determine whether diuretics reduce mortality and hospitalization rates in incident dialysis patients in the first 2 years after inception. Adult patients starting dialysis between 2009 and 2015 in the REIN registry were matched with the SNDS database and divided into four subgroups according to loop diuretics exposure: < 5%, 5-50%, 50-80% or > 80% over the observation period of each patient. The incidence of hospitalization was described based on the primary diagnoses of the discharge summaries and codes. In this study, which included 67,736 patients, 53,829 (79.5%) who had varying degrees of diuretic exposure exhibited a significantly lower mortality rate at 2 years compared to those without diuretic exposure (24.8% [95% CI 24.4-25.2], vs 37.5% [95% CI 36.7-38.3] respectively). However, the duration of diuretic exposure significantly impacted outcomes. The all-cause mortality rate at two years was highest in the group with ≥ 80% exposure (68.2% [95% CI 67.3-69.1]), followed by those with 50-80% exposure (15.7% [95% CI 15.0-16.4]), and those with 5-50% exposure (6.6% [95% CI 6.3-7.0]). An inverse probability weighting (IPW) propensity score analysis supported these findings. Stratified analyses showed consistent results regardless of a history of congestive heart failure and were similar for both hemodialysis and peritoneal dialysis patients. Additionally, the number of hospitalizations and length of stay were generally higher in the group with the longest exposure to loop diuretics. Diuretic exposure was generally associated with a lower mortality rate in dialysis patients. However, prolonged exposure (≥ 80%) was linked to an increased risk of mortality and hospitalization. This prolonged exposure may indicate residual diuresis at the cost of chronic fluid overload., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Biological drivers of empathy have been explored in an interdisciplinary manner for decades. Research that merges the psychological and genetic perspectives of empathy has recently gained interest, and more complex designs and analyses are needed. Empathy is a multidimensional construct that might be regarded both dispositionally (as a personality trait) and contextually (experienced and/or expressed in a particular relationship/situation). This study analyzed genetic variations associated with genes encoding oxytocin, arginine vasopressin, and receptors that regulate their secretion as predictors of the empathic dimensions of emotional (empathic concern and personal distress) and cognitive (perspective taking) dyadic factors of partners in heterosexual intimate relationships. Machine learning methods to capture both linear and nonlinear relationships between SNPs, RS1 and RS2 repeat polymorphisms and dimensions of empathy in couples were employed. A total of 442 individuals (221 couples) participated in this study. Empathy was measured by the Polish version of the Interpersonal Reactivity Index and the Interpersonal Reactivity Index for Couples. The MassARRAY® 4 instrument, which combines mass spectrometry with endpoint PCR, was used for genotyping all 14 genetic variations. Microsatellite fragment analysis was performed by denaturing polyacrylamide gel electrophoresis. The results confirmed the significance of certain genetic alterations linked to oxytocin, vasopressin, serotonin and estrogen for dispositional and dyadic empathy (mainly rs1884051, rs6311, RS1, rs4686302, and rs1042778) in couples. The effects were stronger for the prediction of emotional and dyadic empathy than for perspective taking. Separate analyses for women and men indicated different predictive effects of genes for empathy (for example, effects of rs53576 were indicated only in women), which are also experienced and expressed in couples. Different dimensions of empathy should be included when the genetic predictors of empathy are examined., (© 2024. The Author(s).)