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Objective: Extended-spectrum beta-lactamase-producing bacteria pose a significant threat to public health due to their resistance to commonly used antibiotics. This meta-analysis aims to determine the prevalence and distribution of extended-spectrum beta-lactamase-producing bacteria in Indonesia., Methods: This systematic review and meta-analysis adhere to PRISMA guidelines to estimate the prevalence of extended-spectrum beta-lactamase-producing bacteria in Indonesia from 2008 to 2024. Systematic searches were conducted by PubMed, ScienceDirect, Google Scholar, and Index Medicus, and data were analyzed using a random-effects model to address heterogeneity., Results: A systematic search yielded 1160 records. After duplicate removal and eligibility screening, 64 studies were included in the qualitative synthesis, and 48 were suitable for quantitative analysis. The pooled prevalence of extended-spectrum beta-lactamase-producing-producing bacteria in Indonesia was 46.38% (95% CI: 39.55%-53.21%) with significant heterogeneity (I 2  = 99.05%), reflecting substantial variability in methodologies, populations, and regional contexts. While Sumatra shows the highest prevalence at 63.99% (95% CI: 62.09%-65.89%) and Kalimantan the lowest at 15.24% (95% CI: 9.45%-21.02%), these findings must be interpreted with caution due to the significant heterogeneity. In hospitals, the prevalence was 47.13% (95% CI: 39.71%-54.54%), and in community was 47.26% (95% CI: 26.47%-59.95%). Adults had a higher prevalence (44.56%, 95% CI: 35.48%-53.64%) than children (32.38%, 95% CI: 20.85%-43.91%). The prevalence of extended-spectrum beta-lactamase-producing Escherichia coli was 57.84% (95% CI: 45.97%-69.72%), and Klebsiella pneumoniae was 51.03% (95% CI: 41.19%-60.86%)., Conclusion: These findings highlight the urgent need for stringent infection control measures, tailored surveillance programmes, and effective antibiotic stewardship in Indonesia to mitigate the impact of extended-spectrum beta-lactamase-producing bacteria on public health. The substantial heterogeneity underscores the complexity of antimicrobial resistance epidemiology in Indonesia, necessitating cautious interpretation of pooled prevalence and standardised methodologies for future research to ensure accurate prevalence estimates., (© 2025 John Wiley & Sons Ltd.)

The steady state of a water distribution system abides by the laws of mass and energy conservation. Hydraulic solvers, such as the one used by EPANET approach the simulation for a given topology with a Newton-Raphson algorithm. However, iterative approximation involves a matrix inversion which acts as a computational bottleneck and may significantly slow down the process. In this work, we propose to rethink the current approach for steady state estimation to leverage the recent advancements in Graphics Processing Unit (GPU) hardware. Modern GPUs enhance matrix multiplication and enable memory-efficient sparse matrix operations, allowing for massive parallelization. Such features are particularly beneficial for state estimation in infrastructure networks, which are characterized by sparse connectivity between system elements. To realize this approach and tap into the potential of GPU-enhanced parallelization, we reformulate the problem as a diffusion process on the edges of a graph. Edge-based diffusion is inherently related to conservation laws governing a water distribution system. Using a numerical approximation scheme, the diffusion leads to a state of the system that satisfies mass and energy conservation principles. Using existing benchmark water distribution systems, we show that the proposed method allows parallelizing thousands of hydraulic simulations simultaneously with very high accuracy., 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 Ltd.)

The Northern Antarctic Peninsula (NAP) and the West Antarctic Ice Sheet (WAIS) are likely to respond rapidly to climate changes by increasing the collapse of peripheral ice shelves and the number of days above 0 °C. These facts make this region a representative hotspot of the global sea level rise and the location of one of the global climate tipping points (thresholds in the Earth system whose changes may become irreversible, if exceeded). Understanding the climate evolution of the NAP, based on past evidences, may help infer its future scenario. Herein, from a comprehensive survey of lacustrine sedimentation in proglacial and periglacial lakes/ponds, we investigated the impact of climate changes on the terrestrial environment in two complementary time scales (Late Holocene and contemporary age). For the longer time scale, regional climate database and biogeochemical properties of Lake Long/NAP sediment core, suggest warming between 4.0 and 2.0 kyr BP following a cooling phase towards the present, that endorse previously suggested Late Holocene Neoglacial (LHN). We attribute the LHN phase to a combined action of long-term decline in total solar irradiance, the Andean volcanism and the El Niño Southern Oscillation. For the contemporary age, we found a rapid coupled response of atmosphere/cryosphere/lithosphere to present warming levels., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Compared to conventional energy integrating detector CT, Photon-Counting CT (PCCT) has the advantage of increased spatial resolution. The pancreas is a highly complex organ anatomically. The increased spatial resolution of PCCT challenges radiologists' knowledge of pancreatic anatomy. The purpose of this review was to review detailed macroscopic and microscopic anatomy of the pancreas in the context of current and future PCCT., Method: This review is based on a literature review of all parts of pancreatic anatomy and a retrospective imaging review of PCCT scans from 20 consecutively included patients without pancreatic pathology (mean age 61.8 years, 11 female), scanned in the workup of pancreatic cancer with a contrast enhanced multiphase protocol. Two radiologists assessed the visibility of the main and accessory pancreatic ducts, side ducts, ampulla, major papilla, minor papilla, pancreatic arteries and veins, regional lymph nodes, coeliac ganglia, and coeliac plexus., Results: The macroscopic anatomy of the pancreas was consistently visualized with PCCT. Visualization of detailed anatomy of the ductal system (including side ducts), papillae, arteries, vein, lymph nodes, and innervation was possible in 90% or more of patients with moderate to good interreader agreement., Conclusion: PCCT scans of the pancreas visualizes previously unseen or inconsistently seen small anatomical structures consistently. Increased knowledge of pancreatic anatomy could have importance in imaging of pancreatic cancer and other pancreatic diseases., 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.)

Background: Opioid use disorder (OUD) care engagement rates in primary care (PC) settings are often low. Little is known about PC team experiences when delivering OUD treatment and potential factors that influence their capacity to engage patients in treatment. Exploring PC team experiences may inform needed supports that can optimize OUD care delivery and improve outcomes for patients with OUD., Objective: We explored multidisciplinary PC team perspectives on barriers and facilitators to engaging patients in OUD treatment., Design: Qualitative study using in-depth interviews., Participants: Primary care clinical teams., Approach: We conducted semi-structured interviews (n = 35) with PC team members involved in OUD care delivery, recruited using a combination of criterion and maximal variation sampling. Data collection and analysis were informed by existing theoretical literature about patient engagement, specifically that patient engagement is influenced by factors across individual (patient, provider), interpersonal (patient-provider), and health system domains. Interviews were professionally transcribed and doubled-coded using a coding schema based on the interview guide while allowing for emergent codes. Coding was iteratively reviewed using a constant comparison approach to identify themes and verified with participants and the full study team., Key Results: Analysis identified five themes that impact PC team ability to engage patients effectively, including limited patient contact (e.g., phone, text) in between visits, varying levels of provider confidence to navigate OUD treatment discussions, structural factors (e.g., schedules, productivity goals) that limited provider time, the role of team-based approaches in lessening discouragement and feelings of burnout, and lack of shared organizational vision for reducing harms from OUD., Conclusions: While the capacity of PC teams to engage patients in OUD care is influenced across multiple levels, some of the most promising opportunities may involve addressing system-level factors that limit PC team time and collaboration and promoting organizational alignment on goals for OUD treatment., Competing Interests: Declarations:. Conflict of Interest:: The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work. The authors did not work with or were otherwise influenced by any external sponsors for this work. Dr. Saxon has received travel support from Alkermes, Inc., consulting fees from Indivior, Inc., and royalties from UpToDate, Inc. Anna Ratzliff, MD, PhD, receives royalties from Wiley for her book on integrated care., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

The ability to recognize anatomical landmarks, microsurgical instruments, and complex scenes and events in a surgical wound using computer vision presents new opportunities for studying microsurgery effectiveness. In this study, we aimed to develop an artificial intelligence-based solution for detecting, segmenting, and tracking microinstruments using a neurosurgical microscope. We have developed a technique to process videos from microscope camera, which involves creating a segmentation mask for the instrument and subsequently tracking it. We compared two segmentation approaches: (1) semantic segmentation using Visual Transformers (pre-trained domain-specific EndoViT model), enhanced with tracking as described by Cheng Y. et al. (our proposed approach), and (2) instance segmentation with tracking based on the YOLOv8l-seg architecture. We conducted experiments using the CholecSeg8k dataset and our proprietary set of neurosurgical videos (PSNV) from microscope. Our approach with tracking outperformed YOLOv8l-seg-based solutions and EndoViT model with no tracking on both CholecSeg8k (mean IoT = 0.8158, mean Dice = 0.8657) and PSNV (mean IoT = 0.7196, mean Dice = 0.8202) datasets. Our experiments with identifying neurosurgical instruments in a microscope's field of view showcase the high quality of these technologies and their potential for valuable applications.

Background: Studying illicit drug circulation and its effects on population health is complicated due to the criminalization of trade and consumption. Illicit drug markets have evolved with IT, moving digital to the "darknet." Previous research has analyzed darknet market listings and customer reviews. Research tools include public health surveys and medical reports but lack neutral data on drugs' spread and impact. This study fills this gap with an analysis of the volume of drugs traded on the darknet market., Objective: We aimed to use the dark web data and officially published indicators to identify the most vulnerable regions of Russia and the correlations between the pairs of variables to measure how illicit drug trade can affect population well-being., Methods: We web-parsed the Hydra darknet drug marketplace using Python code. The dataset encompassed 3045 individual sellers marketing 6721 unique products via 58,563 distinct postings, each representing specific quantities sold in different Russian regions during 2019. In the second stage, we collected 31 variables from official sources to compare officially collected data with darknet data about amounts and types of selling drugs in every 85 regions of Russia. The health-related data were obtained from official published sources-statistical yearbooks. Maps, diagrams, correlation matrixes, and applied observational statistical methods were used., Results: In 2019, a minimum of 124 kilograms of drugs circulated daily in small batches on the Russian darknet. Cannabis dominated the market, being 10 times more prevalent than opiates, and cannabis products' higher availability in the region is correlated with a lower incidence of opiate overdoses. The "grams of opiates in the region" variable is significantly correlated with drug overdose deaths (r=.41; P=.003), HIV-positive cases due to drug use (r=.51; P=.002), and drug court convictions in Russia (r=.39; P=.004). The study identified significant correlations between opiate sales on the darknet and higher rates of HIV among injection drug users (r=.47; P=.003). Conversely, regions with higher cannabis sales exhibited significant negative correlations with indicators of harmful drug use (r=-.52; P=.002) and its prevalence (r=-.49; P=.001). These findings suggest regional variations in drug sales on the darknet may be associated with differing public health outcomes. These indicators accurately reflect regional drug issues, though some official statistics may be incomplete or biased., Conclusions: Our findings point to varying levels of risk associated with different types of drugs sold on the darknet, but further research is needed to explore these relationships in greater depth. The study's findings highlight the importance of considering regional variations in darknet drug sales when developing public health strategies. The significant correlations between drug sales data and public health indicators suggest that region-specific interventions could be more effective in addressing the diverse challenges posed by illicit drug use., (©Sergey Soshnikov, Svetlana Bekker, Bulat Idrisov, Vasiliy Vlassov. Originally published in JMIR Formative Research (https://formative.jmir.org), 15.11.2024.)

The interaction of molecules, in particular, water, with solid interfaces has been studied by a multitude of methods, among them nuclear magnetic resonance spin relaxation. The frequency dependence of the relaxation times follows patterns that have been interpreted in terms of the molecular orientation and dynamics. Several different model approaches could successfully explain limiting cases of 1 H relaxation dispersion in systems with rigid surfaces such as silica gel or glass, but none of them can reproduce the relaxation of both 1 H and 2 H nuclei, which differ in their respective relaxation mechanisms, dipolar vs quadrupolar. From detailed studies of the dynamics of hydration of water in biological materials, the importance of hydrogen and molecular exchange to the longitudinal relaxation time of T 1 was demonstrated. In this work, exchange times of both H 2 O and D 2 O in hydrophilic silica gel are varied in a controlled fashion in a wide range using disodium hydrogen phosphate, and the effect of physical exchange on spin relaxation is quantified for the first time in such systems using the exchange-mediated reorientation model.

Purpose: Pancreatic ductal adenocarcinoma is forecast to become the second most significant cause of cancer mortality as the number of patients with cancer in the main duct of the pancreas grows, and measurement of the pancreatic duct diameter from medical images has been identified as relevant for its early diagnosis., Approach: We propose an automated pancreatic duct centerline tracing method from computed tomography (CT) images that is based on deep reinforcement learning, which employs an artificial agent to interact with the environment and calculates rewards by combining the distances from the target and the centerline. A deep neural network is implemented to forecast step-wise values for each potential action. With the help of this mechanism, the agent can probe along the pancreatic duct centerline using the best possible navigational path. To enhance the tracing accuracy, we employ landmark-based registration, which enables the generation of a probability map of the pancreatic duct. Subsequently, we utilize a gradient-based method on the registered data to extract a probability map specifically indicating the centerline of the pancreatic duct., Results: Three datasets with a total of 115 CT images were used to evaluate the proposed method. Using image hold-out from the first two datasets, the method performance was 2.0, 4.0, and 2.1 mm measured in terms of the mean detection error, Hausdorff distance (HD), and root mean squared error (RMSE), respectively. Using the first two datasets for training and the third one for testing, the method accuracy was 2.2, 4.9, and 2.6 mm measured in terms of the mean detection error, HD, and RMSE, respectively., Conclusions: We present an algorithm for automated pancreatic duct centerline tracing using deep reinforcement learning. We observe that validation on an external dataset confirms the potential for practical utilization of the presented method., (© 2024 Society of Photo-Optical Instrumentation Engineers (SPIE).)

Copper sulfide is a multifunctional material. Copper sulfides are known to be used in photo-electric converters, in plasmonics, in active electrodes of batteries and supercapacitors, etc. The excellent thermoelectric properties of copper sulfide are well-known too. The purpose of this study is to investigate the thermoelectric performance of nanocomposite copper sulfide contained monoclinic Cu 2 S and tetragonal Cu 1.96 S phase. According to scanning electron microscopy, the average particle size of the synthesized powder was about 373 nm. The Li 0.11 Cu 1.89 S sample showed an electronic conductivity of 50-180 S/cm, a Seebeck coefficient of 0.04-0.31 mV/K in the range of 300-700 K, and high power factor 5.8 μW K -2 cm -1 at 672 K. Total thermal conductivity decreases with increasing temperature from 0.61 to 0.22 W∙K -1 m -1 in the range of 300-700 K. Such low thermal conductivity and high power factor made it possible to achieve an extremely high dimensionless thermoelectric figure of merit ZT = 1.76 at 672 K, which allows to consider the Li 0.11 Cu 1.89 S alloy as a promising thermoelectric material., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kubenova Marzhan reports financial support was provided by L N Gumilyov Eurasian National University. Kubenova Marzhan reports a relationship with L N Gumilyov Eurasian 10.13039/100018366National University that includes: employment and funding grants. Kubenova Marzhan has patent No pending to No. The authors declare that there are no competing interests or financial conflicts related to this research. All funding sources have been acknowledged in the manuscript. 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. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Diffuse large B-cell Lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL). The disease generally occurs in older patients. Although at a lower prevalence, the disease also occurs in the adolescent and young adult group (AYA). There is paucity of data in the literature on racial and ethnic disparities in the incidence and survival outcomes of DLBCL in the AYA group. The objective of our study is to demonstrate the disparities in these outcomes. Utilizing SEER, we obtained data on patient demographics, incidence, and survival from 2000 to 2020. We observed statistically significant reduced incidence of DLBCL in all racial groups, except the non-Hispanic Asian and Pacific Islander group (NHAPI). The non-Hispanic Black group (NHB) had one of the lowest survival despite showing the largest decrease in incidence in DLBCL. The differences in the survival could be secondary to socioeconomic factors, however other reasons need to be explored. The increased incidence among the NHAPI group mirrors that of large population-based studies in East Asian countries, however, underlying reasons have not been elucidated., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The pancreas is a complex abdominal organ with many anatomical variations, and therefore automated pancreas segmentation from medical images is a challenging application., Purpose: In this paper, we present a framework for segmenting individual pancreatic subregions and the pancreatic duct from three-dimensional (3D) computed tomography (CT) images., Methods: A multiagent reinforcement learning (RL) network was used to detect landmarks of the head, neck, body, and tail of the pancreas, and landmarks along the pancreatic duct in a selected target CT image. Using the landmark detection results, an atlas of pancreases was nonrigidly registered to the target image, resulting in anatomical probability maps for the pancreatic subregions and duct. The probability maps were augmented with multilabel 3D U-Net architectures to obtain the final segmentation results., Results: To evaluate the performance of our proposed framework, we computed the Dice similarity coefficient (DSC) between the predicted and ground truth manual segmentations on a database of 82 CT images with manually segmented pancreatic subregions and 37 CT images with manually segmented pancreatic ducts. For the four pancreatic subregions, the mean DSC improved from 0.38, 0.44, and 0.39 with standard 3D U-Net, Attention U-Net, and shifted windowing (Swin) U-Net architectures, to 0.51, 0.47, and 0.49, respectively, when utilizing the proposed RL-based framework. For the pancreatic duct, the RL-based framework achieved a mean DSC of 0.70, significantly outperforming the standard approaches and existing methods on different datasets., Conclusions: The resulting accuracy of the proposed RL-based segmentation framework demonstrates an improvement against segmentation with standard U-Net architectures., (© 2024 The Author(s). Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Introduction: The identification of significant DNA markers of primary osteoporosis may gain new insights by studying genome regions involved in mechanisms of epigenetic regulation through interactions with microRNAs., Methods: The authors searched for associations of polymorphic variants of microRNA binding sites of mRNA target genes and polymorphic loci of microRNA genes with primary osteoporosis in a cohort of women and men from the Volga-Ural region of Russia (N = 1.177)., Results: Using case-control association analysis, the authors found that rs1061947 ( COL1A1 ), rs10793442 ( ZNF239 ), rs6854081 ( FGF2 ), and rs11614913 ( miR-196a ) were associated with osteoporotic fractures; rs5854 ( MMP1 ) and rs2910164 ( miR-146a ) were associated with low bone mineral density; and rs10098470 ( TPD52 ), rs11540149 ( VDR ), rs1042673 ( SOX9 ), rs1054204 ( SPARC ), and rs1712 ( FBXO5 ) were markers of both fractures and low bone mineral density. Among the identified associations, ethno specific trends were found, as well as sex-specific associations. Prognostic models were developed, among which the model for predicting osteoporosis in general in women (Area Under Curve = 0.909) achieved the highest level of predictive value. Thus, the potential role of polymorphic variants of microRNA binding sites in the development of primary osteoporosis in men and women from the Volga-Ural region of Russia was demonstrated., 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 Yalaev, Deev, Tyurin, Salakhov, Smirnov, Eremkina, Mokrysheva, Minniakhmetov and Khusainova.)

Objectives: To evaluate the risk of liver fibrosis and associated factors with the non-invasive fibrosis score-4 (FIB-4) index in patients with inflammatory arthritis using methotrexate (MTX)., Methods: Patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) who were followed up in the rheumatology outpatient clinic, who were on methotrexate only and for whom FIB-4 index was could be calculated at methotrexate initiation and follow-up were included. The FIB-4 index was calculated according to the following formula: age (years) × AST(IU/L)/(platelet count(10 (9)/L) × √ALT(IU/L)). The patients' demographics, comorbidities, other treatments, cumulative MTX dose, and reasons for MTX cessation were assessed. For the multivariate analysis, possible factors associated with intermediate-high risk FIB-4 index at last visit were determined., Results: A total of 107 patients were enrolled in the study, of whom 82 (76.6%) had RA and 25 (23.4%) had PsA. At the initiation of MTX, 24 (22.4%) patients had intermediate-high risk FIB-4 index. Comorbidities and the rate of ≥3-4 Charlson comorbidity index were more common in patients with intermediate-high risk FIB-4 index. A total of 37 (34.5%) patients had intermediate-high risk FIB-4 index at the last visit after median 3.6 (0.3-22.06) years follow-up. The median cumulative MTX dose was 2550 mg (1050-13.991). Cumulative MTX dose [OR 1.18 (1.01-1.33), p = .03] and diabetes mellitus [OR 4.60 (1.74-12.50), p = .002] were associated factors with intermediate-high risk FIB-4 index. The concomitant use of hydroxychloroquine (HCQ) was found to be a low-risk factor for FIB-4 index [OR 0.28 (0.10-0.78) p = .015]., Conclusion: The FIB-4 index is a non-invasive method that can be used in daily rheumatology practice for the evaluation and follow-up of patients who will use methotrexate. Comorbidities and cumulative MTX dose seem to be related with the risk of liver fibrosis. Concomitant use of HCQ with MTX may reduce the risk of liver fibrosis., (© 2024 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Introduction: Engagement is a critical component of successful treatment for opioid use disorder (OUD). However, rates of patient engagement in OUD treatment, especially in outpatient settings, are variable and often low. Little is known about the specific strategies members of primary care teams use to initiate and encourage ongoing participation in OUD treatment. In a national cohort of primary care clinics in the U.S., we explored the perspectives of primary care team members on the meaning of and approaches to OUD treatment engagement., Methods: We conducted semi-structured interviews with 35 providers from multidisciplinary primary care teams in an existing national cohort of 13 clinics across seven states. Teams were delivering OUD treatment via the Collaborative Care Model, a model that combines primary care providers (PCP), behavioral health care managers (BHCM) and consulting psychiatric providers (CPP) in a structured way to provide patient-centered, team-based, and measurement-based care. Interview participants included 14 PCPs, 13 BHCMs, and 8 CPPs. Interviews asked open-ended questions about provider experiences and practices that aided or hindered patient engagement in OUD treatment. Interview transcripts were double-coded by trained qualitative researchers and analyzed using a combination of deductive and inductive approaches to identify themes., Results: Two themes emerged that describe provider perspectives on the meaning of engagement: 1) qualifying engagement by the volume of contact with patients, and 2) the need for more multidimensional measures of engagement. Six themes emerged that characterized provider engagement practices: 1) creating an environment of disclosure, 2) normalizing OUD treatment, 3) offering gentle but persistent outreach, 4) providing human connection and encouragement, 5) tailoring treatment to patient needs, and 6) avoiding stigmatizing responses. Analysis identified multiple replicable strategies that providers used to support these engagement practices., Conclusions: Providers consistently apply a range of strategies when trying to engage patients in OUD treatment. Specific engagement strategies used embodied compassion and pragmatism, hallmarks of patient-centered care. Further research is needed to understand the impact of scaling engagement approaches across all care settings., Competing Interests: Declaration of competing interest The authors do not have any personal, professional, or financial conflicts of interest to disclose for this work. The authors did not work with or were otherwise influenced by any external sponsors for this work. Dr. Saxon has received travel support from Alkermes, Inc., consulting fees from Indivior, Inc., and royalties from UpToDate, Inc. Anna Ratzliff, MD, PhD receives royalties from Wiley for her book on integrated care., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Radiation therapy plays a crucial role in cancer treatment, necessitating precise delivery of radiation to tumors while sparing healthy tissues over multiple days. Computed tomography (CT) is integral for treatment planning, offering electron density data crucial for accurate dose calculations. However, accurately representing patient anatomy is challenging, especially in adaptive radiotherapy, where CT is not acquired daily. Magnetic resonance imaging (MRI) provides superior soft-tissue contrast. Still, it lacks electron density information, while cone beam CT (CBCT) lacks direct electron density calibration and is mainly used for patient positioning. Adopting MRI-only or CBCT-based adaptive radiotherapy eliminates the need for CT planning but presents challenges. Synthetic CT (sCT) generation techniques aim to address these challenges by using image synthesis to bridge the gap between MRI, CBCT, and CT. The SynthRAD2023 challenge was organized to compare synthetic CT generation methods using multi-center ground truth data from 1080 patients, divided into two tasks: (1) MRI-to-CT and (2) CBCT-to-CT. The evaluation included image similarity and dose-based metrics from proton and photon plans. The challenge attracted significant participation, with 617 registrations and 22/17 valid submissions for tasks 1/2. Top-performing teams achieved high structural similarity indices (≥0.87/0.90) and gamma pass rates for photon (≥98.1%/99.0%) and proton (≥97.3%/97.0%) plans. However, no significant correlation was found between image similarity metrics and dose accuracy, emphasizing the need for dose evaluation when assessing the clinical applicability of sCT. SynthRAD2023 facilitated the investigation and benchmarking of sCT generation techniques, providing insights for developing MRI-only and CBCT-based adaptive radiotherapy. It showcased the growing capacity of deep learning to produce high-quality sCT, reducing reliance on conventional CT for treatment planning., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Maspero reports financial support was provided by EWUU alliance. Manya Afonso, Maureen van Eijnatten reports financial support was provided by EWUU alliance. Runqi Wang, Tao Song, Zhihao Zhang, Long Wang reports a relationship with Subtle Medical that includes: employment. Alexandra Alain-Beaudoin, Silvain Bériault reports a relationship with Elekta Ltd that includes: employment. Alexandra Alain-Beaudoin, Silvain Beriault has patent pending to Elekta Ltd. Pengxin Yu reports a relationship with Infervision Medical Technology Co., Ltd that includes: employment. Gengwan Li, Xueru Zhang reports a relationship with Canon Medical Systems Corporation that includes: employment. Lujia Zhong, Zhiwei Deng reports financial support was provided by University of Southern California. Valentin Boussot reports financial support was provided by French National Research Agency. Valentin Boussot reports financial support was provided by Rennes Métropole. Cédric Hémon reports financial support was provided by Elekta AB. Cédric Hémon reports financial support was provided by CominLabs. Valentin Boussot reports a relationship with University of Rennes that includes: employment. Cédric Hémon reports a relationship with University of Rennes that includes: employment. Cédric Hémon reports a relationship with Centre Eugène Marquis that includes: employment. Lu Bai, Shaobin Wang reports a relationship with MedMind Technology Co. Ltd that includes: employment. Lu Bai and Shaobing Wang had adopted some training ideas from Du Yi who is a staff in Institute of Medical Technology, Peking University Health Science Center, Beijing, China Derk Mus, Bram Kooiman reports a relationship with MRI Guidance BV that includes: employment. Chelsea Sargeant reports a relationship with Elekta AB that includes: funding grants and travel reimbursement. Edward Henderson reports a relationship with Manchester Cancer Research Centre that includes: funding grants and travel reimbursement. Zijie Chen, Enpei Wang reports a relationship with Shenying Medical Technology (Shenzhen) Co., Ltd that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The article examines the concentration of 9 heavy metals (Hg, Pb, Zn, Cr, Co, Ni, Cu, Ba and V) and As in the soil cover of the urban area in one of the largest cities in Russia, Ufa (the Republic of Bashkortostan). It is compared with aggregated data of concentrations on urbanized areas in surface soils throughout the world. For elements exceeding the average background values in soils of the urban area (Cr, Ni, Cu and Co), the average concentrations in the city soils were 346, 101, 51 and 18 ppm, respectively. Using enrichment factor (EF), geoaccumulation index (I geo ), and concentration coefficients (CC), Cr and Ni were identified as elements entering the soil cover as a result of anthropogenic pollution. Although the level of their enrichment and contamination of soils in the most territory of the city corresponds to the moderate class, there are sites with critical threshold values. Spatial analysis of heavy metals distribution was carried out based on the results of pollution load index (PLI) and ecological risk factor (Er) calculations with the use of graphical presentation of results, which allowed specific and detailed description of sites calling for special attention. The use of cluster analysis allowed dividing the sample of chemical elements into groups with probably similar sources of entry into the environment. Monte Carlo modeling of risk calculation showed negligible non-cancer risks for both adult and child populations in most of the city. While children's exposure to Cr was of concern in the more residential part of the city, free of large industrial plants, As posed a threat with respect to cancer risks in the southern part of the city, with elevated concentrations and other HMs in vicinity of the oil refineries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The present work explores the specificity of supramolecular assemblies comprising dialkylaminostyrylhetarene dye molecules incorporated into phosphatidylcholine (PC) or phosphatidylserine (PS) aggregates. In PS-based assemblies, the dyes demonstrate a concentration-dependent fluorescent response, distinguishing anionic proteins such as bovine serum albumin (BSA) and pepsin from lysozyme (LYZ) in aqueous solutions. Conversely, no significant response is observed when the dyes are incorporated into the well-organized bilayers of neutral PC. The fluorescent response arises from the binding of dyes to proteins, leading to the detachment of dye molecules from the assemblies, rather than from the binding of proteins to the assemblies, although the latter process is facilitated by electrostatic attraction. Thus, both the poor ordering of PS molecules and the interfacial arrangement of the dyes are prerequisites for the fluorescent response of dye-PS aggregates. The structure of the dyes significantly impacts the spectral features of dye-PS and dye-protein assemblies. An optimal dye structure has been identified for the recognition of BSA, with a limit of detection (LOD) of 10.8 nM., 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.)

Data-driven metamodels reproduce the input-output mapping of physics-based models while significantly reducing simulation times. Such techniques are widely used in the design, control, and optimization of water distribution systems. Recent research highlights the potential of metamodels based on Graph Neural Networks as they efficiently leverage graph-structured characteristics of water distribution systems. Furthermore, these metamodels possess inductive biases that facilitate generalization to unseen topologies. Transferable metamodels are particularly advantageous for problems that require an efficient evaluation of many alternative layouts or when training data is scarce. However, the transferability of metamodels based on GNNs remains limited, due to the lack of representation of physical processes that occur on edge level, i.e. pipes. To address this limitation, our work introduces Edge-Based Graph Neural Networks, which extend the set of inductive biases and represent link-level processes in more detail than traditional Graph Neural Networks. Such an architecture is theoretically related to the constraints of mass conservation at the junctions. To verify our approach, we test the suitability of the edge-based network to estimate pipe flowrates and nodal pressures emulating steady-state EPANET simulations. We first compare the effectiveness of the metamodels on several benchmark water distribution systems against Graph Neural Networks. Then, we explore transferability by evaluating the performance on unseen systems. For each configuration, we calculate model performance metrics, such as coefficient of determination and speed-up with respect to the original numerical model. Our results show that the proposed method captures the pipe-level physical processes more accurately than node-based models. When tested on unseen water networks with a similar distribution of demands, our model retains a good generalization performance with a coefficient of determination of up to 0.98 for flowrates and up to 0.95 for predicted heads. Further developments could include simultaneous derivation of pressures and flowrates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Purpose: To promote the development of auto-segmentation methods for head and neck (HaN) radiation treatment (RT) planning that exploit the information of computed tomography (CT) and magnetic resonance (MR) imaging modalities, we organized HaN-Seg: The Head and Neck Organ-at-Risk CT and MR Segmentation Challenge., Materials and Methods: The challenge task was to automatically segment 30 organs-at-risk (OARs) of the HaN region in 14 withheld test cases given the availability of 42 publicly available training cases. Each case consisted of one contrast-enhanced CT and one T1-weighted MR image of the HaN region of the same patient, with up to 30 corresponding reference OAR delineation masks. The performance was evaluated in terms of the Dice similarity coefficient (DSC) and 95-percentile Hausdorff distance (HD 95 ), and statistical ranking was applied for each metric by pairwise comparison of the submitted methods using the Wilcoxon signed-rank test., Results: While 23 teams registered for the challenge, only seven submitted their methods for the final phase. The top-performing team achieved a DSC of 76.9 % and a HD 95 of 3.5 mm. All participating teams utilized architectures based on U-Net, with the winning team leveraging rigid MR to CT registration combined with network entry-level concatenation of both modalities., Conclusion: This challenge simulated a real-world clinical scenario by providing non-registered MR and CT images with varying fields-of-view and voxel sizes. Remarkably, the top-performing teams achieved segmentation performance surpassing the inter-observer agreement on the same dataset. These results set a benchmark for future research on this publicly available dataset and on paired multi-modal image segmentation in general., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The impact of social media has been significant on various aspects of life, particularly mental health. Growing concerns about the adverse effects of social media use have prompted the exploration of experimental interventions, defined as digital detox interventions. However, it remains unclear whether digital detox interventions are effective for mental health outcomes. The aim of this study was to provide comprehensive insights into the effects of digital detox interventions on various mental health outcomes, including depression, life satisfaction, stress, and mental well-being. Following the PRISMA guidelines, systematic searches were carried out in online databases, including PubMed and ScienceDirect, within the publication range of 2013 and 2023. A total of 2578 titles and abstracts were screened, and 10 studies were included in the analysis. A risk of bias assessment was conducted using RoB 2.0 and the Newcastle-Ottawa scale, while statistical analysis was conducted using RevMan 5.4.1. Our data indicated a significant effect of digital detox in mitigating depression with the standardized mean difference (SMD: -0.29; 95%CI: -0.51, -0.07, p =0.01). No statistically significant effects were discerned in terms of life satisfaction (SMD: 0.20; 95%CI: -0.12, 0.52, p =0.23), stress (SMD: -0.31; 95%CI: -0.83, 0.21, p =0.24), and overall mental well-being (SMD: 0.04; 95%CI: -0.54, 0.62, p =0.90). These data underscore the nuanced and selective influence of digital detox on distinct facets of mental health. In conclusion, digital detox interventions significantly reduce depressive symptoms, suggesting that intentional reduction or cessation of digital engagement may help alleviate contributing factors. However, no statistically significant effects were observed in mental well-being, life satisfaction, and stress. This discrepancy may be due to the complex nature of these constructs, involving various factors beyond the scope of digital detox interventions., Competing Interests: All the authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Integrating artificial intelligence (AI) into medical and dental applications can be challenging due to clinicians' distrust of computer predictions and the potential risks associated with erroneous outputs. We introduce the idea of using AI to trigger second opinions in cases where there is a disagreement between the clinician and the algorithm. By keeping the AI prediction hidden throughout the diagnostic process, we minimize the risks associated with distrust and erroneous predictions, relying solely on human predictions. The experiment involved 3 experienced dentists, 25 dental students, and 290 patients treated for advanced caries across 6 centers. We developed an AI model to predict pulp status following advanced caries treatment. Clinicians were asked to perform the same prediction without the assistance of the AI model. The second opinion framework was tested in a 1000-trial simulation. The average F1-score of the clinicians increased significantly from 0.586 to 0.645., (© 2024. The Author(s).)

The Ser/Thr protein phosphatase 2 A (PP2A) regulates the dephosphorylation of many phosphoproteins. Substrate recognition are mediated by B regulatory subunits. Here, we report the identification of a substrate conserved motif [RK]-V-x-x-[VI]-R in FAM122A, an inhibitor of B55α/PP2A. This motif is necessary for FAM122A binding to B55α, and computational structure prediction suggests the motif, which is helical, blocks substrate docking to the same site. In this model, FAM122A also spatially constrains substrate access by occluding the catalytic subunit. Consistently, FAM122A functions as a competitive inhibitor as it prevents substrate binding and dephosphorylation of CDK substrates by B55α/PP2A in cell lysates. FAM122A deficiency in human cell lines reduces the proliferation rate, cell cycle progression, and hinders G1/S and intra-S phase cell cycle checkpoints. FAM122A-KO in HEK293 cells attenuates CHK1 and CHK2 activation in response to replication stress. Overall, these data strongly suggest that FAM122A is a short helical motif (SHeM)-dependent, substrate-competitive inhibitor of B55α/PP2A that suppresses multiple functions of B55α in the DNA damage response and in timely progression through the cell cycle interphase., (© 2024. The Author(s).)

The search for the molecular markers of osteoporosis (OP), based on the analysis of differential deoxyribonucleic acid (DNA) methylation in bone cells and peripheral blood cells, is promising for developments in the field of the early diagnosis and targeted therapy of the disease. The Runt-related transcription factor 2 ( RUNX2 ) gene is one of the key genes of bone metabolism, which is of interest in the search for epigenetic signatures and aberrations associated with the risk of developing OP. Based on pyrosequencing, the analysis of the RUNX2 methylation profile from a pool of peripheral blood cells in men and women over 50 years of age of Russian ethnicity from the Volga-Ural region of Russia was carried out. The level of DNA methylation in three CpG sites of the RUNX2 gene was assessed and statistically significant hypomethylation was revealed in all three studied CpG sites in men (U = 746.5, p = 0.004; U = 784, p = 0.01; U = 788.5, p = 0.01, respectively) and in one CpG site in women (U = 537, p = 0.03) with primary OP compared with control. In the general sample, associations were preserved for the first CpG site (U = 2561, p = 0.0001766). The results were obtained for the first time and indicate the existence of potentially new epigenetic signatures of RUNX2 in individuals with OP.

Aim: Pulmonary artery involvement is a severe complication of Behcet's disease (BD). Although venous thrombosis is common in BD, pulmonary embolism is considered to be rare because the inflammatory nature makes the thrombi strongly adherent to the venous walls. This study aimed to define the radiological characteristics of pulmonary artery thrombosis (PAT) on computed tomography (CT) imaging in BD patients., Methods: We retrospectively evaluated 165 BD patients with vascular involvement. Among the patients with venous involvement (n = 146), we identified 65 patients who had undergone thorax CT imaging previously. Fourteen patients who were diagnosed with PAT were included in the study. Expert radiologists re-evaluated the patients' initial and control thorax CT scans, classified the PAT as acute or chronic based on their radiological features., Results: The patients' median age was 35 (min-max: 15-60) years at the time of the initial CT scan, and nine were male. Twelve (85.7%) patients were symptomatic at the time of CT evaluation. Upon re-evaluating the thorax CTs, acute PAT was diagnosed in six (42.8%); chronic PAT was detected in eight (57.1%) patients. Two patients with chronic PAT also had acute PAT. Pulmonary artery aneurysms were present in three (21.4%) patients, and intracardiac thrombus was found in three (21.4%) patients., Conclusion: A significant number of BD patients with venous involvement had radiological findings consistent with acute PAT potentially due to pulmonary emboli in this study. The clinical importance of these lesions has to be defined with future studies., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Lack of access to resources is a "fundamental cause" of poor HIV outcomes across the care cascade globally and may have the greatest impact on groups with co-existing marginalized identities. In a sample of people living with HIV (PWH) who inject drugs and were not on antiretroviral therapy (ART), we explored associations between access to resources and HIV severity. Fundamental Cause Theory (FCT) sees socioeconomic status/access to resources as a root cause of disease and emphasizes that individuals with limited resources have fewer means to mitigate health risks and implement protective behaviors, which ultimately generates disparities in health outcomes. Guided by the FCT, we hypothesized that resource depletion (primary aim) and lower income (secondary aim) were associated with increased HIV severity. Using baseline data from the Linking Infectious and Narcology Care (LINC-II) trial of ART-naive PWH who inject drugs in St. Petersburg, Russia (n = 225), we examined the association between "past year resource runout" (yes vs. no) and "low-income (< 300 USD a month)" and the outcome HIV severity (CD4 count, continuous). We fit two separate linear regression models adjusted for gender, age, time since HIV diagnosis, and prior ART use. Participants had a mean age of 37.5 years and were 60% male. Two thirds (66%) reported resource depletion, and 30% had income below 300 USD a month. Average CD4 count was 416 cells/mm 3  (SD 285). No significant association was identified between either resource depletion or low-income and HIV severity (adjusted mean difference in CD4 count for resource depletion: - 4.16, 95% CI - 82.93, 74.62; adjusted mean difference in CD4 count for low-income: 68.13, 95% CI - 15.78, 152.04). Below-average income and running out of resources were common among PWH who inject drugs and are not on ART in St. Petersburg, Russia. Resource depletion and low-income were not significantly associated with HIV disease severity as captured by CD4 count. The nuanced relationship between socioeconomic status and HIV severity among people with HIV who inject drugs and not on ART merits further examination in a larger sample., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Marfan Syndrome (MFS), a genetic disorder impacting connective tissue, manifests in a wide array of phenotypes which can affect numerous bodily systems, especially the thoracic aorta. The syndrome often presents distinct facial features that potentially allow for diagnostic clinical recognition. Herein, we explore the potential of Artificial Intelligence (AI) in diagnosing Marfan syndrome from ordinary facial images, as assessed by overall accuracy, F1 score, and area under the ROC curve., Methods: This study explores the utilization of Convolutional Neural Networks (CNN) for MFS identification through facial images, offering a novel, non-invasive, automated, and computerized diagnostic approach. The research examines the accuracy of Neural Networks in the diagnosis of Marfan Disease from ordinary on-line facial images. The model was trained on 80 % of 672 facial images (182 Marfan and 490 control). The other 20 % of images were used as the test set., Results: Overall accuracy was 98.5 % (0 % false positive, 2 % false negative). F1 score was 97 % for Marfan facies and 99 % for non-Marfan facies. Area under the ROC curve was 100 %., Conclusion: An Artificial Intelligence (AI) program was able to distinguish Marfan from non-Marfan facial images (from ordinary on-line photographs) with an extremely high degree of accuracy. Clinical usefulness of this program is anticipated. However, due to the limited and preliminary nature of this work, this should be viewed as only a pilot study., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:John A Elefteriades reports a relationship with Coolspine that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Understanding how poly(carboxylate)s of chemical admixtures interact with calcium ions in cement pore solutions in the presence of silica fume is fundamental to developing better chemical admixtures for concrete production. In this work, the intermolecular interactions of calcium ions with a poly(carboxylate) superplasticizer type of chemical admixture was investigated via classical all-atom molecular dynamics (MD) simulations and Density Functional Theory (DFT) calculation methods in the presence of silica fume. The classical all-atom MD simulation and DFT calculation results indicate that calcium ions are interacting with oxygen atoms of the carboxylate group of PCE. The better interaction energy could mean an improved adsorption of the PCE segment with calcium ions. In this regard, it can be noted that the ester-based PCE segment could have a better adsorption onto calcium ions in comparison with the ether-based PCE segment. Moreover, the presence of silicon dioxide could improve the adsorption of the PCE segment onto calcium ions.

Machine learning (ML) has revolutionized medical image-based diagnostics. In this review, we cover a rapidly emerging field that can be potentially significantly impacted by ML - eye tracking in medical imaging. The review investigates the clinical, algorithmic, and hardware properties of the existing studies. In particular, it evaluates 1) the type of eye-tracking equipment used and how the equipment aligns with study aims; 2) the software required to record and process eye-tracking data, which often requires user interface development, and controller command and voice recording; 3) the ML methodology utilized depending on the anatomy of interest, gaze data representation, and target clinical application. The review concludes with a summary of recommendations for future studies, and confirms that the inclusion of gaze data broadens the ML applicability in Radiology from computer-aided diagnosis (CAD) to gaze-based image annotation, physicians' error detection, fatigue recognition, and other areas of potentially high research and clinical impact.

To date, researchers in chase of economic cost-efficiency are faced with the problem of developing effective catalysts for water splitting without the use of platinoids. Herein, catalytic properties of hexanuclear rhenium cluster complexes are investigated in application to the hydrogen evolution reaction (HER). A paste composite electrode containing the cluster complexes was obtained, producing a current density of 10 mA cm -2 at an extraordinarily low overpotential of 90 mV (RHE). The {Re 6 Se 8 }-based complexes have shown very favorable reaction kinetics via 102 mV dec -1 value of the Tafel slope for HER reaction within the composition of the paste electrode. Model calculations of kinetic parameters using density functional theory also support the experimental findings. This work underscores the perspectivity of rhenium cluster compounds in HER and opens a promising avenue toward the practical implementation of hydrogen production through electrochemical water splitting.

Myelination enables electrical impulses to propagate on axons at the highest speed, encoding essential life functions. The Rho family GTPases, RAC1 and CDC42, have been shown to critically regulate Schwann cell myelination. P21-activated kinase 2 (PAK2) is an effector of RAC1/CDC42, but its specific role in myelination remains undetermined. We produced a Schwann cell-specific knockout mouse of Pak2 (scPak2-/-) to evaluate PAK2's role in myelination. Deletion of Pak2, specifically in mouse Schwann cells, resulted in severe hypomyelination, slowed nerve conduction velocity and behaviour dysfunctions in the scPak2-/- peripheral nerve. Many Schwann cells in scPak2-/- sciatic nerves were arrested at the stage of axonal sorting. These abnormalities were rescued by reintroducing Pak2, but not the kinase-dead mutation of Pak2, via lentivirus delivery to scPak2-/- Schwann cells in vivo. Moreover, ablation of Pak2 in Schwann cells blocked the promyelinating effect driven by neuregulin-1, prion protein and inactivated RAC1/CDC42. Conversely, the ablation of Pak2 in neurons exhibited no phenotype. Such PAK2 activity can also be either enhanced or inhibited by different myelin lipids. We have identified a novel promyelinating factor, PAK2, that acts as a critical convergence point for multiple promyelinating signalling pathways. The promyelination by PAK2 is Schwann cell-autonomous. Myelin lipids, identified as inhibitors or activators of PAK2, may be utilized to develop therapies for repairing abnormal myelin in peripheral neuropathies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The global aluminium industry is ever-changing and primarily relies on bauxite as its traditional source. However, due to the finite reserves of processed bauxite, alternative sources need to be found. Nephelines have emerged as potential alumina sources. In addition to alumina, nepheline processing can yield marketable products such as soda, potash, cement, and rare metals. The objective of this study was to identify the ideal conditions for selectively extracting potassium from alkaline leaching solutions while separating it from sodium alkali, aluminium, and silicon during the comprehensive processing of nepheline syenites from the Kubasadyr deposit. This approach involved a two-stage hydrothermal leaching process with an incremental calcium addition. Under optimal conditions, the potassium extraction in the alkaline solution reached 93.91 %. The resulting leaching solution served as a feedstock for potassium sulfate production through the crystallization method. The preliminary selective separation of potassium played a crucial role in mitigating its adverse effects on the extraction of aluminium, which is the primary processed product; thus, the economic viability of production was enhanced., 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).)

Acute cardiac rejection remains a significant challenge in the post-transplant period, necessitating meticulous monitoring and timely intervention to prevent graft failure. Thus, the goal of the present study was to identify novel biomarkers involved in acute cardiac rejection, paving the way for personalized diagnostic, preventive, and treatment strategies. A total of 809 differentially expressed genes were identified in the GSE150059 dataset. We intersected genes selected by analysis of variance, recursive feature elimination, least absolute shrinkage and selection operator, and random forest classifier to identify the most relevant genes involved in acute cardiac rejection. Thus, HCP5, KLRD1, GZMB, PLA1A, GNLY, and KLRB1 were used to train eight machine learning models: random forest, logistic regression, decision trees, support vector machines, gradient boosting machines, K-nearest neighbors, XGBoost, and neural networks. Models were trained, tested, and validated on the GSE150059 dataset (MMDx-based diagnosis of rejection). Eight algorithms achieved great performance in predicting acute cardiac rejection. However, all machine learning models demonstrated poor performance in two external validation sets that had rejection diagnosis based on histology: merged GSE2596 and GSE4470 dataset and GSE9377 dataset, thus highlighting differences between these two methods. According to SHAP and LIME, KLRD1 and HCP5 were the most impactful genes.

Air and water-stable zinc (II) complexes of neutral pincer bis(diphenylphosphino)-2,6-di(amino)pyridine ("PN 3 P") ligands are reported. These compounds, [Zn(κ 2 -2,6-{Ph 2 PNR} 2 (NC 5 H 3 ))Br 2 ] (R=Me, 1; R=H, 2), were shown to be capable of electrocatalytic reduction of CO 2 at -2.3 V vs. Fc +/0 to selectively yield CO in mixed water/acetonitrile solutions. These complexes also electrocatalytically generate H 2 from water in acetonitrile solutions, at the same potential, with Faradaic efficiencies of up to 90 %. DFT computations support a proposed mechanism involving the first reduction of 1 or 2 occurring at the PN 3 P ligand. Furthermore, computational analysis suggested a mechanism involving metal-ligand cooperation of a Lewis acidic Zn(II) and a basic ligand., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Gas inflow control in oil wells is one of the most challenging types of repair and sealing operations, the success rate of which does not exceed, as a rule, 30%. Conventional shutoff methods are often ineffective for this purpose. For instance, cement solutions cannot be injected into wells in the required volumes, while gel screens can only temporarily block the breakthrough zones, as gas easily seeps through the gel, forming new channels for gas inflow. Technology for the two-stage injection of gas-insulating gel systems for gas control in horizontal wells was developed. At the first stage, a self-generating foam gel composition (FGC), consisting of gel-forming and gas-forming compositions, was used. A foam gel structure with enhanced rheological and flow characteristics was formed over a controlled time as a result of the interaction between the gel-forming and gas-forming compounds. A PAM-based hydrogel crosslinked with an organic crosslinker was added to the FGC at the second stage of treatment. The laboratory experiments substantiated the technology of well gas and water shutoff by the sequential injection of self-generating foam gel composition and hydrogel. Field tests confirmed the correctness of the chosen concept. It is very important to clearly identify the sources of gas inflow for the success of this well intervention and take into account the well design, as well as the reservoir geological structure and characteristics. The gas shutoff operation can be properly designed for each well only by comparing all these factors. The validity of the selected technology was tested through a series of laboratory experiments. Successful laboratory tests allowed for the application of the studied technology in a field setting, where the gas shutoff agent was injected into three horizontal wells. As a result of the field application, the gas inflow was successfully isolated in two wells. However, the application of the technology failed in the third well which gave an opportunity to revisit the technology's design and to review the sources of gas inflow. Overall, the achieved success rate of 66% demonstrated the high efficiency of the studied technology and supported its wider application in the field.

The YsxC protein from Staphylococcus aureus is a GTP-binding protein from the TRAFAC superfamily of the TrmE-Era-EngA-EngB-Septin-like GTPase class, EngB family of GTPases. Recent structural and biochemical studies of YsxC function show that it is an integral part of the pathogenic microorganism life cycle, as it is involved in the assembly of the large 50S ribosomal subunit. Structural studies of this protein with its specific functional features make it an attractive target for further development of new selective antimicrobials. In this study, we cloned the ysxC protein gene from S. aureus, overexpressed the protein in E. coli, and subsequently purified and crystallized it. Protein crystals were successfully grown using the vapor diffusion method, yielding diffraction data with a resolution of up to 2 Å. Comparative analysis of the structure of SaYsxC with known three-dimensional structures of homologs from other microorganisms showed the presence of structural differences for the apo form., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Konstantin Usachev reports financial support was provided by Russian Science Foundation. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Omics technologies accumulated an enormous amount of data that advanced knowledge about the molecular pathogenesis of type 1 diabetes mellitus and identified a number of fundamental problems focused on the transition to personalized diabetology in the future. Among them, the most significant are the following: (1) clinical and genetic heterogeneity of type 1 diabetes mellitus; (2) the prognostic significance of DNA markers beyond the HLA genes; (3) assessment of the contribution of a large number of DNA markers to the polygenic risk of disease progress; (4) the existence of ethnic population differences in the distribution of frequencies of risk alleles and genotypes; (5) the infancy of epigenetic research into type 1 diabetes mellitus. Disclosure of these issues is one of the priorities of fundamental diabetology and practical healthcare. The purpose of this review is the systemization of the results of modern molecular genetic, transcriptomic, and epigenetic investigations of type 1 diabetes mellitus in general, as well as its individual forms. The paper summarizes data on the role of risk HLA haplotypes and a number of other candidate genes and loci, identified through genome-wide association studies, in the development of this disease and in alterations in T cell signaling. In addition, this review assesses the contribution of differential DNA methylation and the role of microRNAs in the formation of the molecular pathogenesis of type 1 diabetes mellitus, as well as discusses the most currently central trends in the context of early diagnosis of type 1 diabetes mellitus., Competing Interests: The authors declare no conflicts of interest.

The regulation of cellular processes by ion channels has become central to the study of cancer mechanisms. Designing molecules that can modify ion channels specific to tumor cells is a promising area of targeted drug delivery and therapy. Despite their potential in drug discovery, venom peptides-a group of natural products-have largely remained understudied and under-characterized. In general, venom peptides display high specificity and selectivity for their target ion channels. Therefore, they may represent an effective strategy for selectively targeting the dysregulation of ion channels in tumor cells. This review examines existing venom peptide therapies for different cancer types and focuses on the application of snail venom peptides in hepatocellular carcinoma (HCC), the most common form of primary liver cancer worldwide. We provide insights into the mode of action of venom peptides that have been shown to target tumors. We also explore the benefit of using new computational methods like de novo protein structure prediction to screen venom peptides and identify potential druggable candidates. Finally, we summarize the role of cell culture, animal, and organoid models in developing effective therapies against HCC and highlight the need for creating models that represent the most disproportionately affected ethnicities in HCC., (©2023 The Authors; Published by the American Association for Cancer Research.)

The common genetic underpinnings of thoracic aortic aneurysms and aneurysms and dissections of several other major arterial circuits have been described in the literature. These include thoracic and abdominal aortic aneurysms, thoracic and intracranial aneurysms, thoracic aortic aneurysms, and spontaneous coronary artery dissections. In this study, we provide a unified report of these observations and investigate any genetic commonality between the above four arterial circulations., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

POLE driver mutations in the exonuclease domain (ExoD driver) are prevalent in several cancers, including colorectal cancer and endometrial cancer, leading to dramatically ultra-high tumor mutation burden (TMB). To understand whether POLE mutations that are not classified as drivers (POLE Variant) contribute to mutagenesis, we assessed TMB in 447 POLE-mutated colorectal cancers, endometrial cancers, and ovarian cancers classified as TMB-high ≥10 mutations/Mb (mut/Mb) or TMB-low <10 mut/Mb. TMB was significantly highest in tumors with "POLE ExoD driver plus POLE Variant" (colorectal cancer and endometrial cancer, P < 0.001; ovarian cancer, P < 0.05). TMB increased with additional POLE variants (P < 0.001), but plateaued at 2, suggesting an association between the presence of these variants and TMB. Integrated analysis of AlphaFold2 POLE models and quantitative stability estimates predicted the impact of multiple POLE variants on POLE functionality. The prevalence of immunogenic neoepitopes was notably higher in the "POLE ExoD driver plus POLE Variant" tumors. Overall, this study reveals a novel correlation between POLE variants in POLE ExoD-driven tumors, and ultra-high TMB. Currently, only select pathogenic ExoD mutations with a reliable association with ultra-high TMB inform clinical practice. Thus, these findings are hypothesis-generating, require functional validation, and could potentially inform tumor classification, treatment responses, and clinical outcomes., Significance: Somatic POLE ExoD driver mutations cause proofreading deficiency that induces high TMB. This study suggests a novel modifier role for POLE variants in POLE ExoD-driven tumors, associated with ultra-high TMB. These data, in addition to future functional studies, may inform tumor classification, therapeutic response, and patient outcomes., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Key Message: QPm.NOBAL-3A is an important QTL providing robust adult plant powdery mildew resistance in Nordic and Baltic spring wheat, aiding sustainable crop protection and breeding. Powdery mildew, caused by the biotrophic fungal pathogen Blumeria graminis f. sp. tritici, poses a significant threat to bread wheat (Triticum aestivum L.), one of the world's most crucial cereal crops. Enhancing cultivar resistance against this devastating disease requires a comprehensive understanding of the genetic basis of powdery mildew resistance. In this study, we performed a genome-wide association study (GWAS) using extensive field trial data from multiple environments across Estonia, Latvia, Lithuania, and Norway. The study involved a diverse panel of recent wheat cultivars and breeding lines sourced from the Baltic region and Norway. We identified a major quantitative trait locus (QTL) on chromosome 3A, designated as QPm.NOBAL-3A, which consistently conferred high resistance to powdery mildew across various environments and countries. Furthermore, the consistency of the QTL haplotype effect was validated using an independent Norwegian spring wheat panel. Subsequent greenhouse seedling inoculations with 15 representative powdery mildew isolates on a subset of the GWAS panel indicated that this QTL provides adult plant resistance and is likely of race non-specific nature. Moreover, we developed and validated KASP markers for QPm.NOBAL-3A tailored for use in breeding. These findings provide a critical foundation for marker-assisted selection in breeding programs aimed at pyramiding resistance QTL/genes to achieve durable and broad-spectrum resistance against powdery mildew., (© 2024. The Author(s).)

Ribosome biogenesis is an energy-intense multistep process where even minimal defects can cause severe phenotypes up to cell death. Ribosome assembly is facilitated by biogenesis factors such as ribosome assembly factors. These proteins facilitate the interaction of ribosomal proteins with rRNA and correct rRNA folding. One of these maturation factors is RimP which is required for efficient 16S rRNA processing and 30S ribosomal subunit assembly. Here, we describe the binding mode of Staphylococcus aureus RimP to the small ribosomal subunit and present a 4.2 Å resolution cryo-EM reconstruction of the 30S-RimP complex. Together with the solution structure of RimP solved by NMR spectroscopy and RimP-uS12 complex analysis by EPR, DEER, and SAXS approaches, we show the specificity of RimP binding to the 30S subunit from S. aureus. We believe the results presented in this work will contribute to the understanding of the RimP role in the ribosome assembly mechanism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Stigma that people with HIV who inject drugs experience negatively impacts HIV and substance use care, but stigma's association with sharing injection equipment is not known. This is a cross-sectional analysis of data from two studies of people with HIV reporting drug injection ( N  = 319) in St. Petersburg, Russia (September 2018-December 2020). We used logistic regression to examine associations between HIV stigma and substance use stigma scores (categorised into quartiles) and past 30-day equipment sharing, adjusting for demographic and clinical characteristics. Secondary analyses examined associations of arrest history and social support with sharing equipment. Almost half (48.6%) of participants reported sharing injection equipment. Among groups who did and did not share, mean HIV stigma (2.3 vs 2.2) and substance use stigma (32 vs 31) scores were similar. Adjusted analyses detected no significant associations between HIV stigma quartiles (global p -value = 0.85) or substance use stigma quartiles (global p -value = 0.51) and sharing equipment. Neither arrest history nor social support were significantly associated with sharing equipment. In this cohort, sharing injection equipment was common and did not vary based on stigma, arrest history, or social support. To reduce equipment sharing, investments in sterile injection equipment access in Russia should be prioritised over interventions to address stigma.

The proposed paper is devoted to the analysis of the urbanization effects on soil cover using physico-chemical parameters and stable isotopic signatures on the example of Tyumen. The study methods included analysis of C and N elemental and isotope (δ 13 C and δ 15 N) composition, analysis of soil physico-chemical properties and major oxides content. The results of the survey have shown that soil properties within the city limits vary significantly depending on both anthropogenic activities and geomorphological context. The urban soils of Tyumen differ from very strongly acidic with pH values down to 4.8 to strongly alkaline with pH values reaching 8.9, and from sandy loams to silty loams by texture. The study results have shown that δ 13 C values varied from - 33.86 to - 25.14‰ and δ 15 N values varied in range, especially, from - 1.66 to 13.38‰. The range of these signatures was smaller than those reported for urbanized areas in Europe and USA. The δ 13 C values in our case were more related to the geological and landscape parameters of the study area, rather than with urban disturbances and development of urban ecosystems. At the same time, the δ 15 N values probably indicate zones with increased atmospheric N deposition in the case of Tyumen. The application δ 13 C and δ 15 N is a promising tool for analysis of urban soil disturbances and functions, though the regional context should be taken into account., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: The objective was to examine the effect of giving Artificial Intelligence (AI)-based radiographic information versus standard radiographic and clinical information to dental students on their pulp exposure prediction ability., Methods: 292 preoperative bitewing radiographs from patients previously treated were used. A multi-path neural network was implemented. The first path was a convolutional neural network (CNN) based on ResNet-50 architecture. The second path was a neural network trained on the distance between the pulp and lesion extracted from X-ray segmentations. Both paths merged and were followed by fully connected layers that predicted the probability of pulp exposure. A trial concerning the prediction of pulp exposure based on radiographic input and information on age and pain was conducted, involving 25 dental students. The data displayed was divided into 4 groups (G): G X-ray , G X-ray+clinical data , G X-ray+AI , G X-ray+clinical data+AI ., Results: The results showed that AI surpassed the performance of students in all groups with an F1-score of 0.71 (P < 0.001). The students' F1-score in G X-ray+AI and G X-ray+clinical data+AI with model prediction (0.61 and 0.61 respectively) was slightly higher than the F1-score in G X-ray and G X-ray+clinical data (0.58 and 0.59 respectively) with a borderline statistical significance of P = 0.054., Conclusions: Although the AI model had much better performance than all groups, the participants when given AI prediction, benefited only 'slightly'. AI technology seems promising, but more explainable AI predictions along with a 'learning curve' are warranted., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This project has been selected for UCPH Data+ funding (Strategy 2023 funds) at the University of Copenhagen, Denmark. Also, the current research was funded by the Danish Endodontic Society. The authors had no other conflicting interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Serious concerns about the negative impact of ethylenediaminetetraacetic acid (EDTA) on the environment resulted in severe restrictions imposed on this compound in many countries. One of the main concerns is related to the use of EDTA in agriculture as a chelator in microelement fertilizers: being introduced directly into the sawing fields, it penetrates into groundwater, with no chance to be captured/recycled. Respectively, there is an active search for environmentally friendly, biodegradable alternatives for this chelator. In this study, we proposed a biodegradable chelating agent, 2-((1,2-dicarboxyethyl)amino)pentanedioic acid (IGSA). It was synthesized in accordance with the principles of "green chemistry" from readily available nonhazardous precursors using water as a solvent; in addition, the method yields literally no waste. The synthesized chelator in the form of the crude reaction mixture was further used for preparing a multicomponent micronutrient fertilizer (B, Zn, Fe, Cu, Mn, and Mo). The fertilizer was shown to be highly biodegradable (72% in 28 days), while the EDTA-based product degraded only by 13%. The plant growing efficiency was tested on lettuce in the greenhouse experiments. The results were compared against the known commercial fertilizers based on EDTA and iminodisuccinic acid (IDS). The newly developed IGSA-based fertilizer significantly outperformed the EDTA-based fertilizer in lettuce biomass (1.4 and 1.6 times for root and foliar application, respectively). The total mineral uptake was almost two times higher (1.9 and 1.8 times for root and foliar treatments, respectively) compared to the EDTA-based complex and even slightly higher (1.2 and 1.1 times, respectively) compared to the IDS-based complex. Our work opens the doors for the industrial scale production and application of this fully "green", inexpensive microelement fertilizer that has the potential to replace the EDTA-based products.

Humans have 437 catalytically competent protein kinase domains with the typical kinase fold, similar to the structure of Protein Kinase A (PKA). Only 155 of these kinases are in the Protein Data Bank in their active form. The active form of a kinase must satisfy requirements for binding ATP, magnesium, and substrate. From structural bioinformatics analysis of 40 unique substrate-bound kinases, we derived several criteria for the active form of protein kinases. We include requirements on the DFG motif of the activation loop but also on the positions of the N-terminal and C-terminal segments of the activation loop that must be placed appropriately to bind substrate. Because the active form of catalytic kinases is needed for understanding substrate specificity and the effects of mutations on catalytic activity in cancer and other diseases, we used AlphaFold2 to produce models of all 437 human protein kinases in the active form. This was accomplished with templates in the active form from the PDB and shallow multiple sequence alignments of orthologs and close homologs of the query protein. We selected models for each kinase based on the pLDDT scores of the activation loop residues, demonstrating that the highest scoring models have the lowest or close to the lowest RMSD to 22 non-redundant substrate-bound structures in the PDB. A larger benchmark of all 130 active kinase structures with complete activation loops in the PDB shows that 80% of the highest-scoring AlphaFold2 models have RMSD < 1.0 Å and 90% have RMSD < 2.0 Å over the activation loop backbone atoms. Models for all 437 catalytic kinases are available at http://dunbrack.fccc.edu/kincore/activemodels. We believe they may be useful for interpreting mutations leading to constitutive catalytic activity in cancer as well as for templates for modeling substrate and inhibitor binding for molecules which bind to the active state.

Janus Kinase-1 (JAK1) plays key roles during neurodevelopment and following neuronal injury, while activatory JAK1 mutations are linked to leukemia. In mice, Jak1 genetic deletion results in perinatal lethality, suggesting non-redundant roles and/or regulation of JAK1 for which other JAKs cannot compensate. Proteomic studies reveal that JAK1 is more likely palmitoylated compared to other JAKs, implicating palmitoylation as a possible JAK1-specific regulatory mechanism. However, the importance of palmitoylation for JAK1 signaling has not been addressed. Here, we report that JAK1 is palmitoylated in transfected HEK293T cells and endogenously in cultured Dorsal Root Ganglion (DRG) neurons. We further use comprehensive screening in transfected non-neuronal cells and shRNA-mediated knockdown in DRG neurons to identify the related enzymes ZDHHC3 and ZDHHC7 as dominant protein acyltransferases (PATs) for JAK1. Surprisingly, we found palmitoylation minimally affects JAK1 localization in neurons, but is critical for JAK1's kinase activity in cells and even in vitro. We propose this requirement is likely because palmitoylation facilitates transphosphorylation of key sites in JAK1's activation loop, a possibility consistent with structural models of JAK1. Importantly, we demonstrate a leukemia-associated JAK1 mutation overrides the palmitoylation-dependence of JAK1 activity, potentially explaining why this mutation is oncogenic. Finally, we show that JAK1 palmitoylation is important for neuropoietic cytokine-dependent signaling and neuronal survival and that combined Zdhhc3/7 loss phenocopies loss of palmitoyl-JAK1. These findings provide new insights into the control of JAK signaling in both physiological and pathological contexts., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)