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Background: Somatostatin receptor (SSR) targeting radiotracer 68Ga-DOTATATE is used for Positron Emission Tomography (PET)/Computed Tomography (CT) imaging to assess patients with Pheochromocytoma and paraganglioma (PPGL), rare types of Neuroendocrine tumor (NET) which can metastasize thereby becoming difficult to quantify. The goal of this study is to develop an artificial intelligence (AI) model for automated lesion segmentation on whole-body 3D DOTATATE-PET/CT and to automate the tumor burden calculation. 132 68Ga-DOTATATE PET/CT scans from 38 patients with metastatic and inoperable PPGL, were split into 70, and 62 scans, from 20, and 18 patients for training, and test sets, respectively. The training set was further divided into patient-stratified 5 folds for cross-validation. 3D-full resolution nnUNet configuration was trained with 5-fold cross-validation. The model's detection performance was evaluated at both scan and lesion levels for the PPGL test set and two other clinical cohorts with NET (n = 9) and olfactory neuroblastoma (ONB, n = 5). Additionally, quantitative statistical analysis of PET parameters including SUVmax, total lesion uptake (TLU), and total tumor volume (TTV), was conducted. Results: The nnUNet AI model achieved an average 5-fold validation dice similarity coefficient of 0.84 at the scan level. The model achieved dice similarity coefficients (DSC) of 0.88, 0.6, and 0.67 at the scan level, the sensitivity of 86%, 61.13%, and 61.64%, and a positive predictive value of 89%, 74%, and 86.54% at the lesion level for the PPGL test, NET and ONB cohorts, respectively. For PPGL cohorts, smaller lesions with low uptake were missed by the AI model (p < 0.001). Anatomical region-based failure analysis showed most of the false negative and false positive lesions within the liver for all the cohorts, mainly due to the high physiologic liver background activity and image noise on 68Ga- DOTATATE PET scans. Conclusions: The developed deep learning-based AI model showed reliable performance for automated segmentation of metastatic PPGL lesions on whole-body 68Ga-DOTATATE-PET/CT images, which may be beneficial for tumor burden estimation for objective evaluation during therapy follow-up. https://www.clinicaltrials.gov/study/NCT03206060, https://www.clinicaltrials.gov/study/NCT04086485, https://www.clinicaltrials.gov/study/NCT05012098. [ABSTRACT FROM AUTHOR]

This study investigates the effect of adding boron as a ternary addition to binary FeCo alloys. Fe–Co–B ternary alloys with varying boron concentrations between 0 and 2 wt% were synthesized through mechanical alloying. The study aims to analyze the structural, morphological, and magnetic properties of the Fe–Co alloy matrix with the inclusion of boron. The XRD results showed a single solid solution phase of Fe–bcc structure for all alloys, regardless of the boron concentration. It was seen that the low solubility of boron in Fe–Co caused the formation of hard structures at the grain boundaries, resulting in an increase in hardness with an increase in boron concentration. On the other hand, a decreasing trend was observed in coercivity, which is ascribed to the formation of FeB at the grain boundaries, as proved from XRD analysis. An increase in boron concentration did not seem to significantly affect the saturation magnetization, which remained in the range of 190 ± 10 emu/g for all Fe–Co–B alloys. The experimental data was cross checked and further insights were gained; DFT calculations were performed using Vienna Ab Initio Simulation Package. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this consensus was to develop evidence‐ and expert‐based patient‐focused recommendations on the appropriateness of intra‐articular platelet‐rich plasma (PRP) injections in different clinical scenarios of patients with knee osteoarthritis (OA). Methods: The RAND/UCLA Appropriateness Method was used by the European Society of Sports Traumatology, Knee Surgery, and Arthroscopy (ESSKA), as well as the International Cartilage Regeneration and Joint Preservation Society (ICRS) to reach a consensus and produce recommendations for specific patient categories combining best available scientific evidence with the collective judgement of a panel of experts. Results: Scenarios were defined based on first treatment vs first injective treatment vs second injective treatment, age (<50/50–65/66–80/>80), tibiofemoral vs patellofemoral involvement, OA level (Kellgren–Lawrence/KL 0–I/II–III/IV), and joint effusion (dry knee, minor‐mild or major effusion). Out of 216 scenarios, in 84 (38.9%) the indication was considered appropriate, in 9 (4.2%) inappropriate and in 123 (56.9%) uncertain. The parameters associated with the highest consensus were PRP use after failed injective treatments (62.5%), followed by PRP after failed conservative treatments and KL 0–III scenarios (58.3%), while the highest uncertainty was found for PRP use as first treatment and KL IV OA (91.7% and 87.5% of uncertain scenarios, respectively). Conclusion: This ESSKA‐ICRS consensus established recommendations on the appropriateness or inappropriateness of PRP injections for the treatment of knee OA, providing a useful reference for clinical practice. PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0–III OA grade after failed conservative non‐injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. Level of Evidence: Level I. [ABSTRACT FROM AUTHOR]

In this study, dibenzosuberenone (DBS)-based non-enzymatic electrochemical sensors are fabricated and investigated against four different analytes. In the sensor test measurements, it is concluded that the fructose detection performance of the DBS-based sensor is higher than the glucose, maltose, and lactose detection performances. It is observed that this non-enzymatic electrochemical sensor against fructose for all concentration responses indicating reduction and oxidation redox reactions, increases steadily as the concentration increases. The fructose detection limit of the sensor is 8.33 μM in 1 min voltammetric cycle. The sensor detected fructose with 25.92 μAmM−1 sensitivity. Since prepared DBS-based non-enzymatic electrochemical sensors exhibit significant sensitivity, they have potential to be successfully applied in the detection of fructose in a food. This study provides a simple sensor platform for sensitive detection of fructose in foods. In addition, the conductivity and impedance results of all DBS-based sensors are related to each other and are an effective parameter in the current density and sensitivity of the sensors. The high sensitivity of the sensors is associated with their impedance and conductivity. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to characterize bacterial species, aetiology and antibiotic susceptibility connected to bacterial keratitis infections in Östergötland, Sweden. Methods: Retrospective cross-sectional study based on electronic health records for the period 2010–2019. Records of patients diagnosed with infectious keratitis were screened for microbiology confirmed infectious bacterial keratitis. Bacterial species and their susceptibility to antibiotics were determined from microbiology test results. Results: One-hundred and ninety patients with lab culture-confirmed infectious bacterial keratitis were included in the analysis. The most frequently found bacterial species were coagulase-negative staphylococci (39%), Staphylococcus aureus (17%) and Cutibacterium acnes (10%). Pseudomonas spp. was the most frequently found Gram-negative bacterial species (7%). Contact lens wear and severely ill/blind eye were the top two aetiologies associated with bacterial keratitis, 22% of the patients with bacterial keratitis were also diagnosed with glaucoma. Most isolates, 157 out of 173, were susceptible to fluoroquinolones, and 145 out of 155 isolates were susceptible to chloramphenicol. Conclusion: Our results revealed a positive rate of bacterial keratitis of 59% for the samples sent to the laboratory. There was a high susceptibility of the bacterial species to the recommended antibiotics. Our results indicate that it is likely that patients are receiving the correct treatment. Future studies are necessary to monitor changes in antibiotic susceptibility. [ABSTRACT FROM AUTHOR]

Kidney transplantation is the most effective treatment option for most patients with end-stage kidney disease due to reduced mortality, decreased cardiovascular events and increased quality of life compared to patients treated with dialysis. However, kidney transplantation is not devoid of both acute and chronic complications including mineral bone disorders (MBD) which are already present in patients with chronic kidney disease (CKD) before kidney transplantation. The natural history of MBD after kidney transplantation is variable and new markers are needed to define MBD after kidney transplantation. One of these promising molecules is sclerostin. The main action of sclerostin is to inhibit bone formation and mineralization by blocking osteoblast differentiation and function. In kidney transplant recipients (KTRs), various studies have shown that sclerostin is associated with graft function, bone parameters, vascular calcification, and arterial stiffness although non-uniformly. Furthermore, data for inhibition of sclerostin with monoclonal antibody romosozumab for treatment of osteoporosis is available for general population but not in KTRs which osteoporosis is highly prevalent. In this narrative review, we have summarized the studies investigating the change of sclerostin before and after kidney transplantation, the relationship between sclerostin and laboratory parameters, bone metabolism and vascular calcification in the context of kidney transplantation. We also pointed out the uncertainties, explained the causes of divergent findings and suggest further potential study topics regarding sclerostin in kidney transplantation. [ABSTRACT FROM AUTHOR]

Linear Quadratic Regulator (LQR) is one of the most prevalent methods used in the control of unmanned aerial vehicles. LQR controllers are commonly employed in the control of both linear and non-linear systems due to their advantages such as easy-to-apply and high-performance structure. However, there is one main difficulty that plays a significant role in the manner of determining the gain for the control signal: choosing appropriate weighting matrices. The selection of these matrices that directly affect the controller performance is generally performed by trial and error, which is laborious and time-consuming. Accordingly, various optimization algorithms have been utilized to determine the weighting matrices of the LQR controller. In this paper, the weighting matrices of the designed LQR controller were obtained using Standard Genetic Algorithm, Differential Evolution, Particle Swarm Optimization, and Grey Wolf Optimization algorithms. The obtained weighting matrices of the LQR controller were tested on an unmanned aerial vehicle simulation, and the performance of optimization algorithms were presented comparatively. [ABSTRACT FROM AUTHOR]

Heavy metal concentrations, which have increased continuously in the environment this century due to anthropogenic factors, severely threaten human and environmental health. Antimony (Sb) is one of the most toxic and harmful heavy metals in terms of human and environmental health. Therefore, the priority research subjects are monitoring the alteration of Sb pollution in the airborne and reducing pollution. This study was conducted to conclude the proper species to monitor and drop airborne Sb contamination on trees grown in Düzce, the 5th most polluted European city. This study examined samples taken from Pseudotsuga menziesii, Cupressus arizonica, Pinus pinaster, Picea orientalis, and Cedrus atlantica, and the Sb concentration changes based on tree species, route, tissue, and age range in the last 40 years were evaluated. The study hypothesizes that Sb concentration varies depending on (1) tree species, (2) direction, (3) plant tissue, and (4) age range, all confirmed in this study. In conclusion, the maximum concentrations were achieved in the outer bark and east (5.45 µg g−1) and north directions (6.72 µg g−1), with high traffic density. In addition, the mining and industrial places (sources of metal pollution) are not close to the study area. Therefore, it was concluded that traffic pollution was the primary source of Sb pollution in the study area. The study revealed that C. arizonica is the most suitable species for monitoring and reducing the change in Sb pollution because the highest Sb concentration (4.47 µg g−1) in wood (the largest organ) was obtained in C. arizonica. [ABSTRACT FROM AUTHOR]

We investigated interactions between Ti6Al4V alloys and strontium zirconate (SrZrO3) ceramic to assess its potential as a refractory mold material in investment casting. We developed a robust yet simple procedure to examine both the liquid–solid and solid–solid interactions using pellets in drop casting and diffusion couple methods. Reaction layers were characterized using optical microscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and x-ray diffraction (XRD). The results were compared to alumina (Al2O3) which is still a common refractory ceramic for molds in investment casting. Our findings indicate that Ti6Al4V surfaces in contact with SrZrO3 had no apparent changes in surface chemistry nor microstructure. On the other hand, Ti6Al4V surfaces in contact with Al2O3 developed γ-TiAl and α2-Ti3Al intermetallics with thicknesses of ~ 100 μm in diffusion couples and ~ 10 μm in drop-casting experiments. Nanoindentation results showed that the surface of Ti6Al4V in contact with Al2O3 was significantly harder compared to SrZrO3, confirming our conclusion. Given the time and costs associated with mechanical and chemical removal of reaction layers on Ti6Al4V castings, SrZrO3 can be a better choice for a mold material in the investment casting of titanium alloys. [ABSTRACT FROM AUTHOR]

The Druze are a distinct group known for their close community, traditions, and consanguineous marriages, dating back to the eleventh century. This practice has led to unique genetic variations, impacting both pathology and gene-associated phenotypes. Some Druze clans, particularly those with exceptional long-lived family heads (ELLI), attracted attention. Given that the bulk of these ELLI were men, the d3GHR polymorphism was the first obvious possibility. Among the 73 clan members, 8.2% carried the d3GHR isoform, with nearly 11% being males. There was a significant age-related increase (p = 0.04) in this isoform among males, leading to examination of potential environmental mediators affecting gene regulation among these carriers during life (namely epigenetic). We focused on DNA methylation due to its crucial role in gene regulation, development, and disease progression. We analyzed DNA samples from 14 clan members with different GHR genotypes, finding a significant (p < 0.05) negative correlation between DNA methylation levels and age. Employing a biological age clock, we observed a significant + 4.229 years favoring the d3GHR group over the WT and heterozygous groups. In conclusion, this study highlights the advantage of d3GHR carriers among this unique Druze clan and underscores the importance of genotype-environment interaction in epigenetic regulation and its impact on health. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, a condition marked by progressive muscle mass and function decline, presents significant challenges in aging populations and those with chronic illnesses. Current standard treatments such as dietary interventions and exercise programs are often unsustainable. There is increasing interest in pharmacological interventions like bimagrumab, a monoclonal antibody that promotes muscle hypertrophy by inhibiting muscle atrophy ligands. Bimagrumab has shown effectiveness in various conditions, including sarcopenia. Aim: The primary objective of this meta-analysis is to evaluate the impact of bimagrumab treatment on both physical performance and body composition among patients diagnosed with sarcopenia. Materials and methods: This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched PubMed, Ovid/Medline, Web of Science, and the Cochrane Library databases up to June 2024 using appropriate Medical Subject Headings (MeSH) terms and keywords related to bimagrumab and sarcopenia. Eligible studies were randomized controlled trials (RCTs) that assessed the effects of bimagrumab on physical performance (e.g., muscle strength, gait speed, six-minute walk distance) and body composition (e.g., muscle volume, fat-free body mass, fat body mass) in patients with sarcopenia. Data extraction was independently performed by two reviewers using a standardized form, with discrepancies resolved through discussion or consultation with a third reviewer. Results: From an initial search yielding 46 records, we screened titles, abstracts, and full texts to include seven RCTs in our meta-analysis. Bimagrumab treatment significantly increased thigh muscle volume (mean difference [MD] 5.29%, 95% confidence interval [CI] 4.08% to 6.50%, P < 0.001; moderate heterogeneity χ2 = 6.41, I2 = 38%, P = 0.17) and fat-free body mass (MD 1.90 kg, 95% CI 1.57 kg to 2.23 kg, P < 0.001; moderate heterogeneity χ2 = 8.60, I2 = 30%, P = 0.20), while decreasing fat body mass compared to placebo (MD − 4.55 kg, 95% CI − 5.08 kg to − 4.01 kg, P < 0.001; substantial heterogeneity χ2 = 27.44, I2 = 89%, P < 0.001). However, no significant improvement was observed in muscle strength or physical performance measures such as gait speed and six-minute walk distance with bimagrumab treatment, except among participants with slower baseline walking speeds or distances. Discussion and conclusion: This meta-analysis provides valuable insights into the effects of bimagrumab on sarcopenic patients, highlighting its significant improvements in body composition parameters but limited impact on functional outcomes. The observed heterogeneity in outcomes across studies underscores the need for cautious interpretation, considering variations in study populations, treatment durations, and outcome assessments. While bimagrumab shows promise as a safe pharmacological intervention for enhancing muscle mass and reducing fat mass in sarcopenia, its minimal effects on muscle strength and broader physical performance suggest potential limitations in translating body composition improvements into functional gains. Further research is needed to clarify its long-term efficacy, optimal dosing regimens, and potential benefits for specific subgroups of sarcopenic patients. [ABSTRACT FROM AUTHOR]

Introduction: Ileostomy, frequently created after colorectal resections, hinders the physiologic function of the colon and can lead to dehydration and acute kidney injury due to high stoma outputs. This study aimed to evaluate the effectiveness of preventive measures on ileostomy-induced dehydration and related readmissions in a high-volume unit. Methods: In this prospective cohort study at a high-volume colorectal surgery department in Turkiye, the Prospective Ileostomy-induced Dehydration Prevention Bundle Project (PIDBP) was assessed from March 2021 to March 2022. The study enrolled patients undergoing colorectal surgery with ileostomy and involved comprehensive inpatient stoma care, education, and a structured post-discharge follow-up. The follow-up included the "Hydration follow-up scale" to monitor ileostomy output and related complications. The primary outcome was the readmission rate due to dehydration-related complications. The patients receiving the bundle intervention were compared with patients treated in the preceding year, focusing on the effectiveness of interventions such as dietary adjustments, fluid therapy, and pharmacological management. Results: In the study, 104 patients were analyzed, divided into 54 pre-bundle and 50 bundle group patients, with no significant differences in patient characteristics. While the overall readmission rate due to dehydration was 12.5%, a significant reduction in dehydration-related readmissions was observed in the bundle group compared to the pre-bundle group (2% vs. 22%, p = 0.002). Univariate analysis identified high stoma output (> 800 ml/24 h) (p < 0.001), chronic renal failure (CRF) (p = 0.01), postoperative ileus (p = 0.03), higher ASA status (p = 0.04), extended hospital stays (p = 0.03), and small bowel resections (especially in J-pouch patients) (p < 0.001) as significant predictors of readmission. Multivariate analysis revealed that the mean ileostomy output before discharge was the sole significant predictor of dehydration-related readmission (OR 1.01), with an optimal cutoff of 877.5 ml/day identified with an area under the curve (AUC) of 0.947, demonstrating high sensitivity (92.3%) and specificity (86.8%) in predicting readmission risk. Conclusion: The Prospective Ileostomy-induced Dehydration Prevention Bundle Project significantly reduced readmission rates after colorectal surgery. [ABSTRACT FROM AUTHOR]

Purpose: The triticeal cartilage, situated within the lateral thyrohyoid membrane, remains elusive in function yet crucial in clinical contexts. Composed of hyaline cartilage, it is prone to ossification, potentially leading to diagnostic challenges such as misidentification with atherosclerosis or fractures. Methods: This study, aiming to establish its prevalence and highlight clinical relevance, conducted a systematic review across several electronic databases such as Medline, PUBMED, Scopus, Google Scholar, Web of Science, SpringerLink and Sciencedirect using keywords "triticeal cartilage", "triticeous cartilage" or "cartilago triticea". An assurance tool for anatomical investigations was used to assess the quality of the methodology (AQUA). A random effects model was utilized to determine the pooled prevalence. Results: The true prevalence of triticeal cartilage was found to be variable, with an overall pooled proportion of 43% while crude prevalence were 50.6%. Its crude prevalence was notably higher in women compared to men, in contrary true prevalence was higher in men, posing sex-related disparities. It was mostly seen bilaterally. When the morphologic characteristics of the cartilage were evaluated, classification differences were observed in terms of shape, with a mean length of 5.48 mm, a mean width of 3.04 mm and a mean weight of 62.32 mg. The vertebral level at which the TC was located was mostly C4. The degree of calcification of the cartilage was most commonly mild. Conclusion: In conclusion, triticeal cartilage holds significant clinical importance, necessitating vigilance during diagnostic evaluations and surgical approaches. Further studies are imperative to elucidate its function comprehensively and refine diagnostic strategies, ensuring optimal patient care in neck-related pathologies. [ABSTRACT FROM AUTHOR]

Purpose: Carbapenem resistant Pseudomonas aeruginosa (CR-PA) is escalating worldwide and leaves clinicians few therapeutic options in recent years, β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of P. aeruginosa infection and have shown potent activity against isolates defined as carbapenem resistant. The aim of this study was to determine the phenotypic profile of these agents against CR-PA in the emerging setting of carbapenemases. Methods: CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods. Results: 244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC50/90(S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1 mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%). Conslusion: While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered. [ABSTRACT FROM AUTHOR]

Objectives: Head and neck cancers (HNCs) represent a significant global health concern due to high morbidity and mortality rates. Despite therapeutic advances, the prognosis for advanced or recurrent cases remains challenging. Nivolumab obtained approval for recurrent or metastatic HNC based on the Phase III CheckMate 141 trial. This study aimed to evaluate the real-world outcomes of nivolumab in patients with non-nasopharyngeal HNC. Design: In this multicenter retrospective study, we analyzed 124 patients with recurrent or metastatic non-nasopharyngeal HNC who received nivolumab in the second-line setting and beyond. Data were collected from 20 different cancer centers across Turkey. The effectiveness and safety of the treatment and survival outcomes were evaluated. Results: Nivolumab exhibited favorable clinical responses, yielding an objective response rate of 29.9% and a disease control rate of 55.7%. Safety assessments revealed a generally well-tolerated profile, with no instances of treatment discontinuation or mortality due to side effects. Survival analysis disclosed a median overall survival (OS) of 11.8 (95% CI 8.4–15.2) months. Multivariate analysis revealed that ECOG-PS ≥ 1 (HR: 1.64, p = 0.045), laryngeal location (HR: 0.531, p = 0.024), and neutrophil-to-lymphocyte ratio > 3.5 (HR: 1.97, p = 0.007) were independent predictors of OS. Conclusions: Nivolumab is an effective and safe treatment option for patients with recurrent or metastatic non-nasopharyngeal HNC in real-world settings. Further studies are needed on factors affecting response to treatment and survival outcomes. [ABSTRACT FROM AUTHOR]

Motivated by applications in queueing theory, we consider a class of singular stochastic control problems whose state space is the d-dimensional positive orthant. The original problem is approximated by a drift control problem, to which we apply a recently developed computational method that is feasible for dimensions up to d = 30 or more. To show that nearly optimal solutions are obtainable using this method, we present computational results for a variety of examples, including queueing network examples that have appeared previously in the literature. [ABSTRACT FROM AUTHOR]

This paper studies a diffusion control problem motivated by challenges faced by public health agencies who run clinics to serve the public. A key challenge for these agencies is to motivate individuals to participate in the services provided. They must manage the flow of (voluntary) participants so that the clinic capacity is highly utilized, but not overwhelmed. The organization can deploy costly promotion activities to increase the inflow of participants. Ideally, the system manager would like to have enough participants waiting in a queue to serve as many individuals as possible and efficiently use clinic capacity. However, if too many participants sign up, resulting in a long wait, participants may become irritated and hesitate to participate again in future. We develop a diffusion model of managing participant inflow mechanisms. Each mechanism corresponds to choosing a particular drift rate parameter for the diffusion model. The system manager seeks to balance three different costs optimally: (i) a linear holding cost that captures the congestion concerns, (ii) an idleness penalty corresponding to wasted clinic capacity and negative impact on public health, and (iii) costs of promotion activities. We show that a nested-threshold policy for deployment of participant inflow mechanisms is optimal under the long-run average cost criterion. In this policy, the system manager progressively deploys mechanisms in increasing order of cost, as the number of participants in the queue decreases. We derive explicit formulas for the queue length thresholds that trigger each promotion activity, providing the system manager with guidance on when to use each mechanism. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin G replacement therapy (IgRT), intravenous (IV) and subcutaneous (SC) routes, is pivotal in treatment of primary immunodeficiencies (PID). In recent years, facilitated subcutaneous immunoglobulin (fSCIG), a combination of rHuPH20 and 10% IgG has emerged as a delivery method to combine advantages of both IV and SC. Method: In an observational prospective cohort, we investigated patient experience with fSCIG in PID patients from 5 PID centers for up to 12 months. We assessed the efficacy and safety of this treatment with patient/caregiver- and physician-reported indicators. Additionally, we analyzed patient treatment satisfaction (TSQM-9) and quality of life (QoL). Results: We enrolled 29 patients (22 pediatric and 7 adults; 14 females and 15 males; (median: 15, min–max: 2–40.9 years) who initiated fSCIG as IgRT-naive (n = 1), switched from conventional rapid-push 10% SCIG (n = 6) or IVIG (n = 22). Among the participants, 19 (65%) exhibited antibody deficiencies, 8 (27%) combined immunodeficiencies, and 2 (7%) immune dysregulations. Remarkably, targeted trough immunoglobulin G levels were achieved under all previous IgRTs as well as fSCIG. No severe systemic adverse drug reactions were documented, despite prevalent local (%86.45) and mild systemic (%26.45) adverse reactions were noted with fSCIG. Due to mild systemic symptoms, 2 patients switched from fSCIG to 10% SCIG. The patient satisfaction survey revealed a notable increase at 2-4th (p = 0.102); 5-8th (p = 0.006) and 9-12th (p < 0.001) months compared to the baseline. No significant trends were observed in QoL surveys. Conclusion: fSCIG demonstrates admissable tolerability and efficacy in managing PIDs in addition to notable increase of patients' drug satisfaction with IgRT. The identified benefits support the continuation of this therapy despite the local reactions. [ABSTRACT FROM AUTHOR]

Unfolded protein accumulation in the endoplasmic reticulum (ER) triggers ER stress, leading to a unique transcriptomic response called unfolded protein response (UPR). While ER stress is linked to various environmental stresses, its role in plant responses to heavy metal toxicity remains unclear. This study aimed to elucidate if heavy metals Fe, Zn, Cu, and As induce ER stress in plants. For this purpose, Arabidopsis thaliana seedlings were treated with Fe (200, 400 µM), Zn (500, 700 µM), Cu (25, 50 µM), and As (250, 500 µM) for 7 days, which resulted in 50–70% decrease in plant growth. All treatments increased insoluble protein levels, indicating unfolded protein accumulation, with the highest induction observed for 50 µM Cu treatment (fivefold). Expressions of genes involved in the perception and signaling of ER stress (IRE1, bZIP28, bZIP60, bZIP17) indicate that Zn toxicity specifically induces bZIP28 but not the IRE1 branch of UPR. All metals except Fe also induced genes associated with protein folding in the ER (BIP1, BIP3, and CNX) and ER-associated protein degradation (ERAD) (HRD1). This finding indicates Zn, Cu, and As but not Fe cause ER stress in plants. Furthermore, increased expression of ER oxidoreductase 1 (ERO1) suggests that metal toxicity also disrupts oxidative protein folding in the ER lumen. This study enhances our understanding of the intricate interplay between essential nutrients, metal toxicity, protein folding machinery, and ER stress, demonstrating that heavy metal toxicity has an ER stress component in plants alongside its established effects on energy metabolism, membrane integrity, and oxidative stress. [ABSTRACT FROM AUTHOR]

Objective: To assess impact of image quality on prostate cancer extraprostatic extension (EPE) detection on MRI using a deep learning-based AI algorithm. Materials and methods: This retrospective, single institution study included patients who were imaged with mpMRI and subsequently underwent radical prostatectomy from June 2007 to August 2022. One genitourinary radiologist prospectively evaluated each patient using the NCI EPE grading system. Each T2WI was classified as low- or high-quality by a previously developed AI algorithm. Fisher's exact tests were performed to compare EPE detection metrics between low- and high-quality images. Univariable and multivariable analyses were conducted to assess the predictive value of image quality for pathological EPE. Results: A total of 773 consecutive patients (median age 61 [IQR 56–67] years) were evaluated. At radical prostatectomy, 23% (180/773) of patients had EPE at pathology, and 41% (131/318) of positive EPE calls on mpMRI were confirmed to have EPE. The AI algorithm classified 36% (280/773) of T2WIs as low-quality and 64% (493/773) as high-quality. For EPE grade ≥ 1, high-quality T2WI significantly improved specificity for EPE detection (72% [95% CI 67–76%] vs. 63% [95% CI 56–69%], P = 0.03), but did not significantly affect sensitivity (72% [95% CI 62–80%] vs. 75% [95% CI 63–85%]), positive predictive value (44% [95% CI 39–49%] vs. 38% [95% CI 32–43%]), or negative predictive value (89% [95% CI 86–92%] vs. 89% [95% CI 85–93%]). Sensitivity, specificity, PPV, and NPV for EPE grades ≥ 2 and ≥ 3 did not show significant differences attributable to imaging quality. For NCI EPE grade 1, high-quality images (OR 3.05, 95% CI 1.54–5.86; P < 0.001) demonstrated a stronger association with pathologic EPE than low-quality images (OR 1.76, 95% CI 0.63–4.24; P = 0.24). Conclusion: Our study successfully employed a deep learning-based AI algorithm to classify image quality of prostate MRI and demonstrated that better quality T2WI was associated with more accurate prediction of EPE at final pathology. [ABSTRACT FROM AUTHOR]

Over the past decade, the increasing emphasis on sustainable material production has brought aerogel technology to the forefront of scientific and industrial research. Aerogels are known for their extraordinary properties, such as high porosity and low density, which make them suitable for a wide range of applications from thermal insulation in buildings to drug delivery systems. This review systematically investigates the sustainability of aerogel production by analyzing the environmental impacts identified in recent life cycle assessments (LCAs). It examines studies on aerogel production using different precursors, solvents, and energy-intensive production methods, especially drying techniques, providing a comprehensive analysis of the environmental footprints and highlighting several hotspots. The review particularly focuses on identifying the disparities in LCA methodologies and the results obtained, which are crucial for crafting a roadmap toward more sustainable aerogel production. The findings emphasize the need for standardized functional units and lifecycle phases that reflect the specific applications of aerogels, thus enabling more accurate comparisons and assessments. The review concludes with a discussion of the critical gaps in current LCA studies of aerogels. It also offers sustainability recommendations based on identified hotspots, advocating for improvements in aerogel production techniques that minimize environmental impacts, enhance material efficiency, and reduce waste. By addressing these gaps, this paper aims to foster a deeper understanding of aerogel sustainability and encourage the development of more environmentally friendly practices in aerogel production and application. [ABSTRACT FROM AUTHOR]

Background: In contemporary surgically treated patients with localized high-grade (G3 or G4) clear-cell renal cell carcinoma (ccRCC), it is not known whether presence of sarcomatoid dedifferentiation is an independent predictor and/or an effect modifier, when cancer-specific mortality (CSM) represents an endpoint. Methods: Within the Surveillance, Epidemiology, and End Results database, all surgically treated localized high-grade ccRCC patients treated between 2010 and 2020 were identified. Univariable and multivariable Cox-regression models were used. Results: In 18,853 surgically treated localized high-grade (G3 or G4) ccRCC patients, 5-year CSM-free survival was 87% (62% vs. 88% with vs. without sarcomatoid dedifferentiation, p < 0.001). Presence of sarcomatoid dedifferentiation was an independent predictor of higher CSM (hazard ratio [HR] 1.8, p < 0.001). In univariable survival analyses predicting CSM, presence versus absence of sarcomatoid dedifferentiation in G3 versus G4 yielded the following hazard ratios: HR 1.0 in absent sarcomatoid dedifferentiation in G3; HR 2.7 (p < 0.001) in absent sarcomatoid dedifferentiation in G4; HR 3.9 (p < 0.001) in present sarcomatoid dedifferentiation in G3; HR 5.1 (p < 0.001) in present sarcomatoid dedifferentiation in G4. Finally, in multivariable Cox-regression analyses, the interaction terms defining present versus absent sarcomatoid dedifferentiation in G3 versus G4 represented independent predictors of higher CSM. Conclusions: In contemporary surgically treated patients with localized high-grade ccRCC, sarcomatoid dedifferentiation is not only an independent multivariable predictor of higher CSM, but also interacts with tumor grade and results in even better ability to predict CSM. [ABSTRACT FROM AUTHOR]

Background: The advancements in wearable technology have made the detection of arrhythmias more accessible. While smartwatches are commonly used to detect patients with atrial fibrillation, their effectiveness in the differential diagnosis of supraventricular tachycardias (SVT) lacks consensus. Methods: A study was conducted on 47 patients with documented SVTs on a 12-lead ECG. All patients in the cohort underwent electrophysiology study with induction of SVT. A 6th generation Apple Watch was used to record ECG tracings during baseline sinus rhythm and during induced SVT. Cardiology residents and attending cardiologists evaluated these recordings to diagnose the differential diagnosis of SVT. Results: The evaluation revealed 27 cases of typical atrioventricular nodal reentrant tachycardia (AVNRT), 11 cases of atrioventricular reentrant tachycardia (AVRT), and 9 cases of atrial tachycardia/atrial flutter (AT/AFL) among the induced tachycardias. Attending physicians achieved an accuracy of 66.0 to 76.6%, and residents demonstrated accuracy rates between 68.1 and 74.5%. Interrater reliability was assessed using Fleiss's Kappa method, resulting in a moderate level of agreement between residents (Kappa = 0.465, p < 0.001, 95% CI 0.30–0.63) and attendings (Kappa = 0.519, p < 0.001, 95% CI 0.35–0.68). The overall Kappa value was 0.417 (p < 0.001, 95% CI 0.34–0.49). Conclusions: Smartwatch recordings demonstrate moderate feasibility in diagnosing SVT when following a pre-specified algorithm. However, this diagnostic performance was lower than the accuracy obtained from 12-lead ECG tracings when blinded to procedure outcomes. [ABSTRACT FROM AUTHOR]

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Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. It is mostly sporadic, with the C9orf72 repeat expansion being the most common genetic cause. While the prevalence of C9orf72-ALS in patients from different populations has been studied, data regarding the yield of C9orf72 compared to an ALS gene panel testing is limited. We aimed to explore the application of C9orf72 versus a gene panel in the general Israeli population. A total of 140 ALS patients attended our Neurogenetics Clinic throughout 2018–2023. Disease onset was between ages 60 and 69 years for most patients (34%); however, a quarter had an early-onset disease (< 50 years). Overall, 119 patients (85%) were genetically evaluated: 116 (97%) were tested for the C9orf72 repeat expansion and 64 (54%) underwent gene panel testing. The C9orf72 repeat expansion had a prevalence of 21% among Ashkenazi Jewish patients compared to 5.7% in non-Ashkenazi patients, while the gene panel had a higher yield in non-Ashkenazi patients with 14% disease-causing variants compared to 5.7% in Ashkenazi Jews. Among early-onset ALS patients, panel testing was positive in 12% compared to 2.9% for C9orf72. We suggest a testing strategy for the Israeli ALS patients: C9orf72 should be the first-tier test in Ashkenazi Jewish patients, while a gene panel should be considered as the first step in non-Ashkenazi and early-onset patients. Tiered testing has important implications for patient management, including prognosis, ongoing clinical trials, and prevention in future generations. Similar studies should be implemented worldwide to uncover the diverse ALS genetic architecture and facilitate tailored care. [ABSTRACT FROM AUTHOR]

Assessment of existing reinforced concrete (RC) structures after an earthquake is a challenging task that must somehow relate qualitative and quantitative observations in the plastic hinge regions and the associated residual deformation capacity of damaged structures. Having an estimate available for the remaining drift capacity will result in more economical and informed decisions regarding demolition or strengthening options. This study aims to develop a practical methodology to estimate the maximum drift demand of an RC column based on the residual crack width. For this purpose, fiber-based frame elements are used to model the RC column considering appropriately concrete behavior in compression and tension stiffening effects. Afterwards, the accuracy and reliability of the proposed methodology are demonstrated by validating the computational approach with two cyclic experimental results from literature and new test data for a one-bay one-story RC frame conducted within the course of this study. A comprehensive parametric study is performed for RC columns with different axial loads, longitudinal and transverse reinforcement ratios, and ground motions to exhibit the stochastic behavior. The study identifies the axial load ratio as the predominant parameter. Key findings include strong correlations between maximum drift ratios and total residual crack widths, as well as maximum compressive strains, with regression analysis yielding equations for accurate drift ratio estimation. Simple predictive models are proposed to estimate the maximum deformation demands based on observed residual crack widths. Residual cracking exceeding 5 mm poses significant risk for the columns with axial load ratios above 0.4, with 90% probability of exceedance 2% drift ratio. [ABSTRACT FROM AUTHOR]

A fuzzy logic control strategy for temperature and relative humidity control of air-handling unit in heating, ventilating, and air-conditioning systems is proposed. Those systems operating in the cooling process are multi-variable and nonlinear systems and their control is very difficult. The dynamics of all elements of the system are presented and the case of an unknown external disturbance is also considered. The zone temperature is regulated by controlling the flow rate of cold water passing through the cooling coil. The numerical results for the uncontrolled, On–Off controlled, and Proportional-Integral-Derivative (PID) controlled systems are compared with the proposed fuzzy logic controlled system under the weather conditions of Istanbul, Turkey in summer season. From the numerical results, it was observed that for the zone temperature the 78 min settling time of the uncontrolled case was reduced to the 26 min by the proposed fuzzy logic controller, which yielded the best result among the other controllers. The PID and fuzzy logic controllers provided smoother control signals when compared to the fluctuating control signal of the On–Off controller for the flow rate of cold water. The energy consumptions of the controllers, normalized with respect to the uncontrolled case, were also compared to show the expense of achieving fast time response. The increase is only between 2.5–7.4% and the proposed fuzzy logic controller used less energy than the PID controller. [ABSTRACT FROM AUTHOR]

Navigation and planning for unmanned aerial vehicles (UAVs) based on visual-inertial sensors has been a popular research area in recent years. However, most visual sensors are prone to high error rates when exposed to disturbances such as excessive brightness and blur, which can lead to catastrophic performance drops in perception and motion planning systems. This study proposes a novel framework to address the coupled perception-planning problem in high-risk environments. This achieved by developing algorithms that can automatically adjust the agility of the UAV maneuvers based on the predicted error rate of the pose estimation system. The fundamental idea behind our work is to demonstrate that highly agile maneuvers become infeasible to execute when visual measurements are noisy. Thus, agility should be traded-off with safety to enable efficient risk management. Our study focuses on navigating a quadcopter through a sequence of gates on an unknown map, and we rely on existing deep learning methods for visual gate-pose estimation. In addition, we develop an architecture for estimating the pose error under high disturbance visual inputs. We use the estimated pose errors to train a reinforcement learning agent to tune the parameters of the motion planning algorithm to safely navigate the environment while minimizing the track completion time. Simulation results demonstrate that our proposed approach yields significantly fewer crashes and higher track completion rates compared to approaches that do not utilize reinforcement learning. [ABSTRACT FROM AUTHOR]

High-throughput transcriptomics is of increasing fundamental biological and clinical interest. The generation of molecular data from large collections of samples, such as biobanks and drug libraries, is boosting the development of new biomarkers and treatments. Focusing on gene expression, the transcriptomic market exploits the benefits of next-generation sequencing (NGS), leveraging RNA sequencing (RNA-seq) as standard for measuring genome-wide gene expression in biological samples. The cumbersome sample preparation, including RNA extraction, conversion to cDNA and amplification, prevents high-throughput translation of RNA-seq technologies. Bulk RNA barcoding and sequencing (BRB-seq) addresses this limitation by enabling sample preparation in multi-well plate format. Sample multiplexing combined with early pooling into a single tube reduces reagents consumption and manual steps. Enabling simultaneous pooling of all samples from the multi-well plate into one tube, our technology relies on smart labware: a pooling lid comprising fluidic features and small pins to transport the liquid, adapted to standard 96-well plates. Operated with standard fluidic tubes and pump, the system enables over 90% recovery of liquid in a single step in less than a minute. Large scale manufacturing of the lid is demonstrated with the transition from a milled polycarbonate/steel prototype into an injection molded polystyrene lid. The pooling lid demonstrated its value in supporting high-throughput barcode-based sequencing by pooling 96 different DNA barcodes directly from a standard 96-well plate, followed by processing within the single sample pool. This new pooling technology shows great potential to address medium throughput needs in the BRB-seq workflow, thereby addressing the challenge of large-scale and cost-efficient sample preparation for RNA-seq. [ABSTRACT FROM AUTHOR]

This study focuses on synthesizing and characterizing mechanically alloyed refractory high entropy alloys (RHEA) containing TiMoNb, Cr, W, and Cr + W. Analytical techniques including XRD, SEM, EDX, DTA, and TGA were employed to explore the influence of Cr and W on the alloys' structure, morphology, and thermal stability towards oxidation. XRD analysis confirmed the formation of a single-phase bcc solid solution in TiMoNbCr, TiMoNbW, and TiMoNbCrW alloys. Crystallite size decreased as milling progressed, yielding average sizes of approximately 7.2 nm, 7.4 nm, and 9.7 nm, with lattice strains of 1.143%, 1.148%, and 1.15%, respectively. Both experimental and calculated values of lattice parameters converged to around 3.1685 ± 0.002 and 3.1791 ± 0.010 Å for all three alloys. The synergy of Cr and W in TiMoNb was observed for the first time, impacting dislocation density, hardness, and oxidation stability. TiMoNbCrW exhibited reduced dislocation density and the highest hardness (502 HV). TGA indicated enhanced oxidation resistance up to 400 °C for TiMoNbCrW compared to the most vulnerable TiMoNbCr alloy. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Marriage: An institution you cannot disparage? Evidence on the marriage norms of entrepreneurs" published in the journal Small Business Economics. The correction addresses a mistake in the layout of Table 1 in the original article. The corrected version of the table includes summary statistics and pairwise correlations related to variables such as companion marriage, entrepreneurship, family entrepreneurship, co-working spouse, gender, age, and education. The document provides a link to the original article for further reference. [Extracted from the article]

Entrepreneurship research increasingly acknowledges marriage as an important resource for long-term commitment to entrepreneurial ventures. At the same time, family scholars emphasize the deinstitutionalization of marriage in many countries, meaning that marriage as formalized and long-term companionship has lost importance. We contend that outdated ideological positions in entrepreneurship studies on marriage potentially obscure the more complex reality of the marriage norms of entrepreneurs. Using representative panel data from Germany, our study demonstrates that there is substantial heterogeneity among marriage norms internalized by entrepreneurs in various contexts. While entrepreneurs, on average, are less likely to internalize companion marriage norms than the general population, family entrepreneurs are significantly more likely to internalize companion marriage norms. We provide new insight into the link between marriage norms and entrepreneurship and open promising new areas of inquiry with regard to social norms and entrepreneurial activity. Plain English Summary: Entrepreneurs and family entrepreneurs embrace different marriage norms. Entrepreneurs are less inclined to embrace traditional companion marriage norms compared to the general population, while family entrepreneurs tend to be more traditional. Previous research on entrepreneurship suggests that marriage can be beneficial for business development, providing a long-term perspective. However, marriage norms have changed significantly in Western countries and now challenge traditional views. This study examines marriage norms among entrepreneurs using representative panel data from Germany. The results highlight the need to update assumptions about marriage in entrepreneurship research. Scholars should view marriage not as a binary status but as dynamic sets of norms that vary among entrepreneurs and family entrepreneurs. Future entrepreneurial theory should consider social norms at the crossroads of institutional changes, entrepreneurial contexts, and internalized norms. [ABSTRACT FROM AUTHOR]

Background: To investigate the predictable parameters associated with downgrading in patients with a Gleason score (GS) 8 (4+4) in prostate biopsy after radical prostatectomy. Methods: We retrospectively analyzed 62 patients with a GS of 4+4 on prostate biopsy who underwent robotic radical prostatectomy between 2017 and 2022. Results: 38 of 62 (61.2%) were downgraded. In multivariable logistic regression model, Ga-68 prostate-specific membrane antigen (PSMA) positron-emission tomography (PET)/computed tomography (CT) SUV max was independent predictor of downgrading (OR 0.904; p = 0.011) and a Logistic Regression model was constructed using the following formula: Y = 1.465–0.95 (PSMA PET/CT SUV max). The model using this variable correctly predicted the downgrading in 72.6% of patients. The AUC for PSMA PET/CT SUV max was 0.709 the cut off being 8.8. A subgroup analysis was performed in 37 patients who had no other European Association of Urology (EAU) high risk features. 25 out of 37 (67.5%) were downgraded, and 21 of these 25 had organ confined disease. Low PSMA SUV max (<8.1) and percentage of GS 4+4 biopsy cores to cancer bearing cores (45.0%) were independently associated with downgrading to GS 7. Conclusion: PSMA PET/CT can be used to predict downgrading in patients with GS 4+4 PCa. Patients with GS 4+4 disease, but no other EAU high risk features, low percentage of GS 4+4 biopsy cores to cancer bearing cores, and a low PSMA PET/CT SUV max are associated with a high likelihood of the cancer reclassification to intermediate risk group. [ABSTRACT FROM AUTHOR]

Studies consistently showed that sodium-glucose cotransporter inhibitors (SGLTi) have cardiovascular and renal benefits, independent of their glucose lowering effects. Recent studies showed that SGLTi might influence gut microbiota. We performed a narrative review of publications focusing on use of SGLTi and changes in gut microbiota. Most studies showed that use of SGLTi re-shapes gut microbiota. These studies are heterogeneous regarding in study designs, doses and types of drugs used (SGLT1i vs. SGLT2i, or SGLT1/2i in combination) and the methods used to determine gut microbiota. However, existing data showed that SGLTi might alter food fermentation and gut permeability, which might translate into clinical outcomes. Thus the objective of this review is to summarize and discuss the updated data regarding SGLTi and changes in gut microbiota for the first time and suggest further study points that needs to be discovered. [ABSTRACT FROM AUTHOR]

Introduction: Accurate diagnosis and treatment of kidney tumors greatly benefit from automated solutions for detection and classification on MRI. In this study, we explore the application of a deep learning algorithm, YOLOv7, for detecting kidney tumors on contrast-enhanced MRI. Material and methods: We assessed the performance of YOLOv7 tumor detection on excretory phase MRIs in a large institutional cohort of patients with RCC. Tumors were segmented on MRI using ITK-SNAP and converted to bounding boxes. The cohort was randomly divided into ten benchmarks for training and testing the YOLOv7 algorithm. The model was evaluated using both 2-dimensional and a novel in-house developed 2.5-dimensional approach. Performance measures included F1, Positive Predictive Value (PPV), Sensitivity, F1 curve, PPV-Sensitivity curve, Intersection over Union (IoU), and mean average PPV (mAP). Results: A total of 326 patients with 1034 tumors with 7 different pathologies were analyzed across ten benchmarks. The average 2D evaluation results were as follows: Positive Predictive Value (PPV) of 0.69 ± 0.05, sensitivity of 0.39 ± 0.02, and F1 score of 0.43 ± 0.03. For the 2.5D evaluation, the average results included a PPV of 0.72 ± 0.06, sensitivity of 0.61 ± 0.06, and F1 score of 0.66 ± 0.04. The best model performance demonstrated a 2.5D PPV of 0.75, sensitivity of 0.69, and F1 score of 0.72. Conclusion: Using computer vision for tumor identification is a cutting-edge and rapidly expanding subject. In this work, we showed that YOLOv7 can be utilized in the detection of kidney cancers. [ABSTRACT FROM AUTHOR]

Introduction: Classification of clear cell renal cell carcinoma (ccRCC) growth rates in patients with Von Hippel–Lindau (VHL) syndrome has several ramifications for tumor monitoring and surgical planning. Using two separate machine-learning algorithms, we sought to produce models to predict ccRCC growth rate classes based on qualitative MRI-derived characteristics. Material and Methods: We used a prospectively maintained database of patients with VHL who underwent surgical resection for ccRCC between January 2015 and June 2022. We employed a threshold growth rate of 0.5 cm per year to categorize ccRCC tumors into two distinct groups—'slow-growing' and 'fast-growing'. Utilizing a questionnaire of qualitative imaging features, two radiologists assessed each lesion on different MRI sequences. Two machine-learning models, a stacked ensemble technique and a decision tree algorithm, were used to predict the tumor growth rate classes. Positive predictive value (PPV), sensitivity, and F1-score were used to evaluate the performance of the models. Results: This study comprises 55 patients with VHL with 128 ccRCC tumors. Patients' median age was 48 years, and 28 patients were males. Each patient had an average of two tumors, with a median size of 2.1 cm and a median growth rate of 0.35 cm/year. The overall performance of the stacked and DT model had 0.77 ± 0.05 and 0.71 ± 0.06 accuracies, respectively. The best stacked model achieved a PPV of 0.92, a sensitivity of 0.91, and an F1-score of 0.90. Conclusion: This study provides valuable insight into the potential of machine-learning analysis for the determination of renal tumor growth rate in patients with VHL. This finding could be utilized as an assistive tool for the individualized screening and follow-up of this population. [ABSTRACT FROM AUTHOR]

Purpose: Deficiency of stromal interaction molecule 1 (STIM1) results in combined immunodeficiency accompanied by extra-immunological findings like enamel defects and myopathy. We here studied a patient with a STIM1 loss-of-function mutation who presented with severe lymphoproliferation. We sought to explore the efficacy of the mTOR inhibitor rapamycin in controlling disease manifestations and reversing aberrant T-cell subsets and functions, which has never been used previously in this disorder. Methods: Clinical findings of the patient were collected over time. We performed immunological evaluations before and after initiation of rapamycin treatment, including detailed lymphocyte subset analyses, alterations in frequencies of circulating T follicular helper (cTFH) and regulatory T (Treg) cells and their subtypes as well as T cell activation and proliferation capacities. Results: A novel homozygous exon 2 deletion in STIM1 was detected in a 3-year-old girl with severe lymphoproliferation, recurrent infections, myopathy, iris hypoplasia, and enamel hypoplasia. Lymphoproliferation was associated with severe T-cell infiltrates. The deletion resulted in a complete loss of protein expression, associated with a lack of store-operated calcium entry response, defective T-cell activation, proliferation, and cytokine production. Interestingly, patient blood contained fewer cTFH and increased circulating follicular regulatory (cTFR) cells. Abnormal skewing towards TH2-like responses in certain T-cell subpopulations like cTFH, non-cTFH memory T-helper, and Treg cells was associated with increased eosinophil numbers and serum IgE levels. Treatment with rapamycin controlled lymphoproliferation, improved T-cell activation and proliferation capacities, reversed T-cell responses, and repressed high IgE levels and eosinophilia. Conclusions: This study enhances our understanding of STIM1 deficiency by uncovering additional abnormal T-cell responses, and reveals for the first time the potential therapeutic utility of rapamycin for this disorder. [ABSTRACT FROM AUTHOR]

Purpose: Irreparable rotator cuff tears are disabling and can severely affect daily life activities, especially when young and active patients are involved. The definition is still debated, and they can have several clinical presentations. The treatment depends on the clinical presentation and the patient's age. Methods: The survey was developed by the ESSKA U45 Committee and was uploaded on the ESSKA website. Fifty‐seven questionnaires were returned. Several aspects of the diagnosis and treatment of massive irreparable cuff tears were investigated. Moreover, treatment options for specific clinical scenarios were given for posterior‐superior and anterior‐superior cuff tears in young and old patients. Results: Fatty degeneration of the muscles was the most common criterion to define an irreparable tear (59.7%). In young patients with external rotation with the arm at side lag, partial repair of the cuff was the most common option (41.8%); in case of external rotation with the arm at side + external rotation at 90° of abduction lag without pseudoparalysis, the most common option was partial repair of the cuff + latissimus dorsi or lower trapezius transfer (39.3%), and in case of external rotation with the arm at side + external rotation at 90° of abduction lag with pseudoparalysis, partial repair of the cuff + latissimus dorsi or lower trapezius transfer was still the most common option (25.5%). The same scenarios in old patients yielded the following results: reverse prosthesis (49.1%), reverse prosthesis (44.6%) and reverse prosthesis ± latissimus dorsi or lower trapezius transfer (44.6%), respectively. Conclusions: The present survey clearly confirms that biological options (partial cuff repairs and tendon transfers) are the reference in the case of young patients with deficient cuffs (both posterior and anterior). Reverse shoulder prosthesis is the most common treatment option in old patients in all clinical scenarios. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) consensus is to provide recommendations based on evidence and expert opinion to improve indications, decision‐making and administration‐related aspects when using blood‐derived orthobiologics (for simplicity indicated as PRP—platelet‐rich plasma—with PRP being the most common product) for the management of knee osteoarthritis (OA). Methods: Leading European expert clinicians and scientists were divided into a steering group, a rating group and a peer review group. The steering group prepared 28 question—statement sets divided into three sections: PRP rationale and indications, PRP preparation and characterisation and PRP protocol. The quality of the statements received grades of recommendation ranging from A (high‐level scientific support) to B (scientific presumption), C (low‐level scientific support) or D (expert opinion). The question–statement sets were then evaluated by the rating group, and the statements scored from 1 to 9 based on their degree of agreement with the statements produced by the steering group. Once a general consensus was reached between the steering and rating groups, the document was submitted to the peer review group who evaluated the geographic adaptability and approved the document. A final combined meeting of all the members of the consensus was held to produce the official document. Results: The literature review on the use of blood‐derived products for knee OA revealed that 9 of 28 questions/statements had the support of high‐level scientific literature, while the other 19 were supported by a medium‐low scientific quality. Three of the 28 recommendations were grade A recommendations: (1) There is enough preclinical and clinical evidence to support the use of PRP in knee OA. This recommendation was considered appropriate with a strong agreement (mean: 8). (2) Clinical evidence has shown the effectiveness of PRP in patients for mild to moderate degrees of knee OA (KL ≤ 3). This recommendation was considered appropriate with a strong agreement (mean: 8.1). (3) PRP injections have been shown to provide a longer effect in comparison to the short‐term effect of CS injections. They also seem to provide a safer use profile with less potential related complications. This recommendation was considered appropriate with a very strong agreement (mean: 8.7). Six statements were grade B recommendations, 7 were grade C and 12 were grade D. The mean rating score was 8.2 ± 0.3. Conclusions: The consensus group reached a high level of agreement on all the questions/statements despite the lack of clear evidence for some questions. According to the results from this consensus group, given the large body of existing literature and expert opinions, PRP was regarded as a valid treatment option for knee OA and as a possible first‐line injectable treatment option for nonoperative management of knee OA, mainly for KL grades 1–3. Level of Evidence: Level II. [ABSTRACT FROM AUTHOR]

The spread of health misinformation has the potential to cause serious harm to public health, from leading to vaccine hesitancy to adoption of unproven disease treatments. In addition, it could have other effects on society such as an increase in hate speech towards ethnic groups or medical experts. To counteract the sheer amount of misinformation, there is a need to use automatic detection methods. In this paper we conduct a systematic review of the computer science literature exploring text mining techniques and machine learning methods to detect health misinformation. To organize the reviewed papers, we propose a taxonomy, examine publicly available datasets, and conduct a content-based analysis to investigate analogies and differences among Covid-19 datasets and datasets related to other health domains. Finally, we describe open challenges and conclude with future directions. [ABSTRACT FROM AUTHOR]

Neurons form the basic anatomical and functional structure of the nervous system, and defects in neuronal differentiation or formation of neurites are associated with various psychiatric and neurodevelopmental disorders. Dynamic changes in the cytoskeleton are essential for this process, which is, inter alia, controlled by the dedicator of cytokinesis 4 (DOCK4) through the activation of RAC1. Here, we clinically describe 7 individuals (6 males and one female) with variants in DOCK4 and overlapping phenotype of mild to severe global developmental delay. Additional symptoms include coordination or gait abnormalities, microcephaly, nonspecific brain malformations, hypotonia and seizures. Four individuals carry missense variants (three of them detected de novo) and three individuals carry null variants (two of them maternally inherited). Molecular modeling of the heterozygous missense variants suggests that the majority of them affect the globular structure of DOCK4. In vitro functional expression studies in transfected Neuro-2A cells showed that all missense variants impaired neurite outgrowth. Furthermore, Dock4 knockout Neuro-2A cells also exhibited defects in promoting neurite outgrowth. Our results, including clinical, molecular and functional data, suggest that loss-of-function variants in DOCK4 probable cause a variable spectrum of a novel neurodevelopmental disorder with microcephaly. [ABSTRACT FROM AUTHOR]

The increase in heavy metal concentrations in the air, especially after the Industrial Revolution, is notable for the scientific world because of the adverse effects that threaten environmental and human health. Among the trace elements, nickel (Ni) is carcinogenic, and all barium (Ba) compounds are toxic. Trace elements are critical for human and environmental health. Their threat further increases, especially in the urban areas and surroundings with a high population. In urban areas, the trace element contamination in the airborne can be reduced using plants. However, which plant and plant organs absorb trace elements could not be determined. In the present study, Ni and Ba concentrations in the branch, wood, and leaf samples of 14 species collected from the city center of Mersin province were determined. As a result, broad-leaved species' Ni and Ba concentrations in their leaf sample were generally higher than other species. Almost all species had the lowest Ni and Ba concentrations in their wood samples. Among these 14 species, it was found that Ni concentration was very high, especially in non-washed leaves of Platanus orientalis, Photinia serrulata, and Citrus reticulate, and Ba concentration was very high in Citrus reticulata, Chamaecyparis lawsoniana, Laurus nobilis, and Acer hyrcanum. Using broad-leaved species in urban areas where pollution is at high levels will significantly contribute to reducing Ni and Ba pollution. It is recommended that these points be considered in future urban landscaping projects. [ABSTRACT FROM AUTHOR]

In this study, the activated carbon (TmAC) with a high surface area and appropriate pore distribution was produced from einkorn (Triticum monococcum L.) husks by using ZnCl2 with chemical activation method. The efficiency of the obtained activated carbon on the adsorption of anionic (metanil yellow) and cationic (methylene blue) dyestuffs from aqueous solutions was investigated in more detail. In addition, the surface characterization of activated carbon was performed using thermogravimetric analysis-differential thermal analysis (TGA-DTA), elemental analysis, scanning electron microscopy (SEM) images, Brunauer–Emmett–Teller (BET) specific surface areas, N2 adsorption–desorption isotherms, pore volumes, pore size distributions, and Fourier-transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) spectra. The highest surface area of activated carbon was measured as 1321 m2 g−1 at the carbonization temperature of 500 °C by using impregnation ratio (w/w = 2.0). Batch method was used in adsorption experiments. The parameters affecting the adsorption studies such as adsorbent concentration, initial dye concentration, adsorption time, temperature, and pH were investigated. The adsorption mechanisms of metanil yellow (MY) and methylene blue (MB) on activated carbon were explained by using isotherms (Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich), kinetic models (pseudo-first-order and pseudo-second-order), and the thermodynamic parameters (Gibbs free energy, enthalpy, and entropy). [ABSTRACT FROM AUTHOR]

Numerous studies have addressed climate change's impact on agriculture, yet the specific effects on wheat production in Turkey remain under-explored. This research aims to bridge this gap by quantifying these impacts in Turkey over 25 years. As the region's principal wheat producer, Turkey offers a unique context, situated in the area where wheat was first domesticated. We analyzed a comprehensive dataset comprising over 20,000 records from 820 political districts, employing a panel data fixed-effect model to mitigate unobserved heterogeneity and reveal dynamic time-related patterns. We focused on critical climate variables: temperature, precipitation, and drought. The results show a significant 9% decrease in wheat yields following a 1.5 °C rise in temperature, affecting nearly 1 million hectares. A notable finding is the 'May effect', highlighting how climatic changes in May disproportionately affect wheat yields. This study provides detailed insights into the temporal and geographic aspects of climate change's impact on wheat production, emphasizing the need for targeted policy actions and strategic agricultural planning, particularly in dry areas. [ABSTRACT FROM AUTHOR]

THOC6 variants are the genetic basis of autosomal recessive THOC6 Intellectual Disability Syndrome (TIDS). THOC6 is critical for mammalian Transcription Export complex (TREX) tetramer formation, which is composed of four six-subunit THO monomers. The TREX tetramer facilitates mammalian RNA processing, in addition to the nuclear mRNA export functions of the TREX dimer conserved through yeast. Human and mouse TIDS model systems revealed novel THOC6-dependent, species-specific TREX tetramer functions. Germline biallelic Thoc6 loss-of-function (LOF) variants result in mouse embryonic lethality. Biallelic THOC6 LOF variants reduce the binding affinity of ALYREF to THOC5 without affecting the protein expression of TREX members, implicating impaired TREX tetramer formation. Defects in RNA nuclear export functions were not detected in biallelic THOC6 LOF human neural cells. Instead, mis-splicing was detected in human and mouse neural tissue, revealing novel THOC6-mediated TREX coordination of mRNA processing. We demonstrate that THOC6 is required for key signaling pathways known to regulate the transition from proliferative to neurogenic divisions during human corticogenesis. Together, these findings implicate altered RNA processing in the developmental biology of TIDS neuropathology. THOC6 is required for TREX tetramer formation. Analysis of pathogenic THOC6 variants differentiate the conserved mRNA export functions of TREX dimers and RNA processing functions of TREX tetramers underlying THOC6 Intellectual Disability Syndrome. [ABSTRACT FROM AUTHOR]

There has recently been an increasing interest in the quantification of success in different fields of human activities. However, most of the research in this field solely focuses on success as a collective phenomenon to be understood in terms of a network structure or overall statistics. Moreover, research in this field rarely attempts to predict success. In this work, we consider real data in the Turkish movie industry, with a focus on individual criteria of success and predict annus mirabilis, also known as the miracle year of the performers, through several machine learning algorithms. We find that this prediction can be achieved best by using a random forest model yielding 92 and 90 percent accuracy for actresses and actors, respectively. Next, we provided a novel q-deformed generalization of the k-Nearest Neighbor (kNN) algorithm, which yields the unnormalized kNN algorithm when the parameter q = 0 , and logarithmic normalized kNN algorithm for q = 1 . This generalization increases the prediction accuracy of the miracle year by one percent for the optimal value q = - 3 of the parameter compared to the random forest algorithm. In addition, we found out that the probability of career length follows an exponential distribution in the intermediate region, hence distinguishing two outlier groups. The former group is formed by those with only one movie credit (almost seventy five percent of the acting guild), and the latter group corresponds to those with a career length exceeding thirty five years (almost one percent). The probability distribution of acting in n movies, on the other hand, is observed to be a power law with an exponent corresponding to Zipf's law if ordered in rank. This behavior seems to be the norm in the film industry and is a signature of the memory-dependent (namely, popularity-dependent) choices of directors and producers. We investigated whether gender plays a role in the Turkish fılm industry, and found out that it does, favoring actors in terms of duration of activity. However, after a certain threshold of career length, namely L = 55 years, it is more likely to find active actresses. [ABSTRACT FROM AUTHOR]

A system manager makes dynamic pricing and dispatch control decisions in a queueing network model motivated by ride hailing applications. A novel feature of the model is that it incorporates travel times. Unfortunately, this renders the exact analysis of the problem intractable. Therefore, we study this problem in the heavy traffic regime. Under the assumptions of complete resource pooling and common travel time and routing distributions, we solve the problem in closed form by analyzing the corresponding Bellman equation. Using this solution, we propose a policy for the queueing system and illustrate its effectiveness in a simulation study. [ABSTRACT FROM AUTHOR]

Various surgical and anatomical classifications have been proposed to date related to ACoA aneurysm projection. Nonetheless, a universally accepted classification system is yet to be established. This study is aimed at establishing a standardized classification system for ACoA aneurysms with utilization 3D technology and defining reference lines for their projections. The goal is to create a simple, understandable, surgically beneficial, and reliable classification system based on neurovascular structures in the region, including safe and hazardous zones. The radiologic data of 96 patients with ACoA aneurysm who were treated in our university hospital between 2012 and 2020 were retrospectively analyzed, and a planned classification scale was developed with the data obtained. The classification aimed to create 9 main projection groups in the sagittal plane: superior, inferior, anterior, and posterior in linear orientation, and anterosuperior, posterosuperior, anteroinferior, posteroinferior, and complex in quadrant orientation. The coronal and axial planes included medial, lateral, and midline classifications, resulting in a 3-dimensional classification system with 25 projections. Among the 96 patients, 32 had linear and 64 had quadrant projections. In the sagittal plane, the linear projection breakdown was as follows: superior (28%), inferior (6.25%), anterior (53%), and posterior (12.5%). For the quadrant projection, the distribution was as follows: anterosuperior (53%), posterosuperior (12.5%), anteroinferior (21.87%), posteroinferior (3.12%), and complex (9.37%). Overall, 35.4% aneurysms were anterosuperior, 17.7% anterior, 14.58% anteroinferior, 9.37% superior, 8.3% posterosuperior, 6.25% complex, 4.16% posterior, 2.08% posteroinferior, and 2.08% inferior projection. Our study proposes a projection classification that utilizes 3D technology for safe surgery based on neurovascular structures in the region and thus better reveals safe and hazardous zones, including three plans, three dimensions, and two orientations. The use of this classification system offers valuable guidance for daily practice in the treatment of ACoA aneurysms. [ABSTRACT FROM AUTHOR]