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Abstract In kidney transplant recipients, urine CXCL9 and CXCL10 (uCXCL9/10) chemokines have reached a sufficiently high level of evidence to be recommended by the European Society of Organ Transplantation for the monitoring of immune quiescence. To assess the risk of acute rejection (AR), the advantage of uCXCL9/10 is their cost-effectiveness and their high diagnostic performance. Here, we evaluated the feasibility of a next-generation immunoassay for quantifying uCXCL9/10 levels. It demonstrated high efficiency with minimal workflow and a 90-min time to result. Preanalytical studies indicated stability of uCXCL9/10 levels and analytical studies confirmed excellent linearity and precision. In a cohort of 1048 samples collected at biopsy, the results correlated significantly with ELISA quantification and were integrated into a previously validated 8-parameter urine chemokine model. The next generation immunoassay achieved an accuracy of 0.84 for AR diagnosis. This study validates this technology as a robust, locally available and unexpensive platform and marks a significant step towards the widespread implementation of uCXCL9/10, for immune quiescence monitoring. Therefore, we developed an open-access web application using uCXCL9/10 to calculate AR risk and improve clinical decision-making to perform biopsy, ushering in a new era in kidney transplantation, where personalized, data-driven care becomes the norm.

The article “Motivation in Foreign Language Learning: Gamification, Personal Learning Environments and Higher Education” presents an innovative pedagogical proposal integrating gamification and Personal Learning Environments (PLEs) to improve students' motivation and academic performance in higher education. The paper details how gamification, by incorporating elements and techniques of video games in the educational environment, encourages active participation and increases student motivation. In parallel, PLEs allow students to personalize their educational process, adapting it to their interests and capabilities, which promotes autonomy and responsibility. The proposal is structured in several stages, from skills diagnosis to implementing and evaluating the pedagogical strategy, using practical tools such as the gamification platform Gimkit and motivation surveys such as “The Instructional Materials Motivation Survey” (IMMS). The expected results include increased motivation, academic performance, and the development of self-directed and personal learning management skills. This practical approach ensures that the proposed strategy can be easily implemented and its effectiveness can be measured. This approach seeks to respond to the need for innovation in teaching methods and aligns with the demands of an increasingly digitized and student-centered educational environment. Combining gamification and PLEs is a powerful strategy to enhance the learning process, making it more engaging, interactive, and tailored to each learner's needs.

All the factors potentially influencing tacrolimus dose requirement and combinations thereof have never been thoroughly investigated, precluding accurate prediction of tacrolimus starting dose. This prospective, non-interventional, multicenter study in de novo adult kidney transplant recipients over the first year after transplantation aimed to investigate the factors influencing tacrolimus dose-standardized trough blood concentration (C0/D) over the first week post-transplant (D4-D7, primary objective), D8-M3 and M3-M12 (secondary objectives). Statistical analysis employed mixed linear models with repeated measures. Eighteen sites enrolled 440 patients and followed them up for 9.5 ± 4.1 months. Age at baseline (p = 0.0144), end-stage renal disease (p = 0.0092), CYP3A phenotype (p < 0.0001), dyslipidemia at baseline (p = 0.0031), hematocrit (p = 0.0026), total bilirubin (p = 0.0261) and plasma creatinine (p = 0.0484) independently increased with log(C0/D) over D4-D7, explaining together 72.3% of the interindividual variability, and representing a robust model to estimate tacrolimus initial dose. Donor age and CYP3A phenotype were also influential over D8-M3 and M3-12, in addition to recipient age. Corticosteroids, diabetes at baseline, and ASAT yielded inconstant results between D8-M3 and M3-M12. We found no ethnicity effect when CYP3A phenotype was accounted for, and no food effect. Intra-individual variability over M3-M12 was moderate, and significantly lower in patients with chronic hepatic disorder (p = 0.0196) or cancer (p = 0.0132).

The food industry is always looking for ways to innovate in elaborating and packaging food products to ensure the consumer receives the highest quality. The new proposals include the use of polycaprolactone (PCL), a commonly used biopolymer that is soluble in many organic solvents. The PCL features can be modified by forming blends with other polymers and bioactive molecules to expand their applications in the food industry. For instance, there have been developments in packages and active substances that incorporate microcapsules based on PCL. This review explores the applications of PCL in the food industry, encompassing its role as a biodegradable active package and as an encapsulating agent. The review underscores the potential of this polymer in the context of the food industry.

Carao (Cassia grandis) contains numerous bioactive substances that contribute to gastrointestinal well-being. The present study assessed the potential impacts of carao on the viability and performance of Streptococcus thermophilus and Lactobacillus bulgaricus under various adverse conditions. These conditions included bile, acid, gastric juice, and lysozyme exposure, simulating the digestive process from the mouth to the intestines. The activity of proteases from cultures was monitored to examine their proteolytic capabilities. To achieve this, the cultures were cultivated in a solution containing plant material, and the results were compared against a control sample after an incubation period. Subsequently, the total phenolic content, total carotenoid content, antioxidant activity, sugar profile, and acid profile of the plant materials were analyzed. These analyses were conducted to explore these compounds’ influence on cultures’ survival. Seeds contained the highest total phenols (766.87 ± 11.56 µg GAE/mL), total carotenoid content (7.43 ± 0.31 mg Q/mL), and antioxidant activity (40.76 ± 1.87%). Pulp contained the highest moisture (12.55 ± 0.44%), ash (6.45 ± 0.15%), lipid (0.66 ± 0.07%), protein (16.56 ± 0.21%), sucrose (9.07 ± 0.78 g/100 g), and fructose (3.76 ± 0.06 g/ 100 g). The crust had the highest content of ash (85.14 ± 0.27%) and succinic acid (2.01 ± 0.06 g/100 g). Results indicated that seeds negatively affected cultures’ survival in the bile tolerance test and had positive effects on Lactobacillus bulgaricus in the protease activity test. Otherwise, the other carao tissues could not change the results significantly (p > 0.05) compared to the control in different tests. The carao crust positively affected cultures’ against protease activity, especially in Lactobacillus bulgaricus, and had a negative effect on the growth of S. thermophilus in the lysozyme and gastric acid resistance test.

Therapeutic monoclonal antibodies have been successful in protecting vulnerable populations against SARS-CoV-2. However, their effectiveness has been hampered by the emergence of new variants. To adapt the therapeutic landscape, health authorities have based their recommendations mostly on in vitro neutralization tests. However, these do not provide a reliable understanding of the changes in the dose-effect relationship and how they may translate into clinical efficacy. Taking the example of EvusheldTM (AZD7442), we aimed to investigate how in vivo data can provide critical quantitative results and project clinical effectiveness. We used the Golden Syrian hamster model to estimate 90 % effective concentrations (EC90) of AZD7442 in vivo against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5 variants. While our in vivo results confirmed the partial loss of AZD7442 activity for BA.1 and BA.2, they showed a much greater loss of efficacy against BA.5 than that obtained in vitro. We analyzed in vivo EC90s in perspective with antibody levels measured in a cohort of immunocompromised patients who received 300 mg of AZD7442. We found that a substantial proportion of patients had serum levels of anti-SARS-CoV-2 spike protein IgG above the estimated in vivo EC90 for BA.1 and BA.2 (21 % and 92 % after 1 month, respectively), but not for BA.5. These findings suggest that AZD7442 is likely to retain clinical efficacy against BA.2 and BA.1, but not against BA.5. Overall, the present study illustrates the importance of complementing in vitro investigations by preclinical studies in animal models to help predict the efficacy of monoclonal antibodies in humans.

Recently, interest in transcriptomic assessment of kidney biopsies has been growing. This study investigates the use of NGS to identify gene expression changes and analyse the pathways involved in rejection. An Illumina bulk RNA sequencing on the polyadenylated RNA of 770 kidney biopsies was conducted. Differentially-expressed genes (DEGs) were determined for AMR and TCMR using DESeq2. Genes were segregated according to their previous descriptions in known panels (microarray or the Banff Human Organ Transplant (B-HOT) panel) to obtain NGS-specific genes. Pathway enrichment analysis was performed using the Reactome and Kyoto Encyclopaedia of Genes and Genomes (KEGG) public repositories. The differential gene expression using NGS analysis identified 6,141 and 8,478 transcripts associated with AMR and TCMR. While most of the genes identified were included in the microarray and the B-HOT panels, NGS analysis identified 603 (9.8%) and 1,186 (14%) new specific genes. Pathways analysis showed that the B-HOT panel was associated with the main immunological processes involved during AMR and TCMR. The microarrays specifically integrated metabolic functions and cell cycle progression processes. Novel NGS-specific based transcripts associated with AMR and TCMR were discovered, which might represent a novel source of targets for drug designing and repurposing.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Abstract Background Genetic literacy among primary healthcare providers is crucial for appropriate patient care with the advances in genetic and genomic medicine. Studies from high-income countries highlight the lack of knowledge in genetics and the need to develop curricula for continuing professional development of non-geneticists. Scarce data is available from resource-constrained countries in Middle East and North Africa. Lebanon is a small country in this region characterized by high rates of consanguinity and genetic disorders like several surrounding countries, such as Jordan, Syria, and Turkey. Methods The primary aim of this study assessed the genetic literacy, self-perceived and actual knowledge as well as practices among primary care providers in Lebanon. The secondary aim identified their educational needs and proposed evidence-based continuing education programs. A cross-sectional survey-based study, using a self-administered questionnaire, was conducted targeting physicians from Family Medicine, Obstetrics and Gynecology, and Pediatrics. The questionnaire was divided into five sections: demographics, familiarity with genetic tests, self-reported and actual knowledge, genetic practices, and educational needs. Statistics were performed using SPSS v24. The Chi-square test was used for independent variables. Differences between mean scores were measured using paired sample t-tests for groups of two levels and one-way ANOVA for more than two. Multiple linear regression was used to study the variables associated with the knowledge score while controlling for other variables. Results The survey included 123 physicians. They were mostly familiar with karyotype as first-tier genetic test. Although 38% perceived their knowledge as good, only 6% scored as such in knowledge assessment. A better knowledge score was observed in academic institutions as well as in urban settings (p

Abstract Chronic kidney disease (CKD) is a public health problem driven by myofibroblast accumulation, leading to interstitial fibrosis. Heterogeneity is a recently recognized characteristic in kidney fibroblasts in CKD, but the role of different populations is still unclear. Here, we characterize a proinflammatory fibroblast population (named CXCL-iFibro), which corresponds to an early state of myofibroblast differentiation in CKD. We demonstrate that CXCL-iFibro co-localize with macrophages in the kidney and participate in their attraction, accumulation, and switch into FOLR2+ macrophages from early CKD stages on. In vitro, macrophages promote the switch of CXCL-iFibro into ECM-secreting myofibroblasts through a WNT/β-catenin-dependent pathway, thereby suggesting a reciprocal crosstalk between these populations of fibroblasts and macrophages. Finally, the detection of CXCL-iFibro at early stages of CKD is predictive of poor patient prognosis, which shows that the CXCL-iFibro population is an early player in CKD progression and demonstrates the clinical relevance of our findings.

BackgroundAbout 10–20% of pancreas allografts are still lost in the early postoperative period despite the identification of numerous detrimental risk factors that correlate with graft thrombosis.MethodsWe conducted a multicenter study including 899 pancreas transplant recipients between 2000 and 2018. Early pancreas failure due to complete thrombosis, long-term pancreas, kidney and patient survivals were analyzed and adjusted to donor, recipient and perioperative variables using a multivariate cause-specific Cox model stratified to transplant centers.ResultsPancreas from donors with history of hypertension (6.7%), as well as with high body mass index (BMI), were independently associated with an increased risk of pancreas failure within the first 30 post-operative days (respectively, HR= 2.57, 95% CI from 1.35 to 4.89 and HR= 1.11, 95% CI from 1.04 to 1.19). Interaction term between hypertension and BMI was negative. Donor hypertension also impacted long-term pancreas survival (HR= 1.88, 95% CI from 1.13 to 3.12). However, when pancreas survival was calculated after the postoperative day 30, donor hypertension was no longer a significant risk factor (HR= 1.22, 95% CI from 0.47 to 3.15). A lower pancreas survival was observed in patients receiving a pancreas from a hypertensive donor without RAAS (Renin Angiotensin Aldosterone System) blockers compared to others (50% vs 14%, p < 0.001). Pancreas survival was similar among non-hypertensive donors and hypertensive ones under RAAS blockers.ConclusionDonor hypertension was a significant and independent risk factor of pancreas failure. The well-known pathogenic role of renin-angiotensin-aldosterone system seems to be involved in the genesis of this immediate graft failure.

The earliest representatives of Chalcidoidea are described from Barremian age Early Cretaceous Lebanese amber and classified in Protoitidae Ulmer & Krogmann, fam. nov. (Hymenoptera: Chalcidoidea). Protoitidae exhibits a high morphological diversity of the terminal metasomal tergum which may indicate a broad spectrum of oviposition capabilities and the ability to occupy a diverse range of ecological niches. Protoitidae comprises two genera, Protoita Ulmer & Krogmann, gen. nov., and Cretaxenomerus Nel & Azar, 2005 based on C. jankotejai Nel & Azar, 2005, which is transferred from Scelionidae (Hymenoptera: Platygastroidea) to Protoitidae. Together, 10 new species, all by Ulmer and Krogmann, are described in the two included genera–Protoita bidentata, P. istvani, P. noyesi, P. petersi, Cretaxenomerus brevis, C. curvus, C. deangelis, C. mirari, C. tenuipenna, and C. vitreus. Keys to the genera and species of Protoitidae are provided. In addition, we examine the postulated plesiomorphies and apomorphies within Chalcidoidea with respect to the fossil record, and provide additional hypotheses on their biogeographic origins.

Abstract The combination of wind energy as a source of production and hydrogen as a carrier and reservoir of energy has been a successful partnership. The unstable nature of wind and the long-term storage capability of hydrogen make them a prosperous pair. Many researches have been done in this field. In most of these researches, the focus has been on the production at the scale of wind farms or on the wind potential of the region. But in this project, the goal was to answer this question: is it possible to meet the energy needs of a household using the combination of wind energy and hydrogen? This project has created a step-by-step algorithm to answer this question. This algorithm starts by modeling the wind speed and finally ends by determining the overall dimensions of the system, including the active surface of the electrolyzer and the surface covered by the turbine. In this way, various components of the mini-Factory, such as electrolyzer, wind turbine, generator, and converter, have been investigated. Finally, an effort was made to select the most optimal operating conditions as well as the appropriate type for each of these components to achieve the expected output.

Abstract Rejection remains the main cause of premature graft loss after kidney transplantation, despite the use of potent immunosuppression. This highlights the need to better understand the composition and the cell-to-cell interactions of the alloreactive inflammatory infiltrate. Here, we performed droplet-based single-cell RNA sequencing of 35,152 transcriptomes from 16 kidney transplant biopsies with varying phenotypes and severities of rejection and without rejection, and identified cell-type specific gene expression signatures for deconvolution of bulk tissue. A specific association was identified between recipient-derived FCGR3A+ monocytes, FCGR3A + NK cells and the severity of intragraft inflammation. Activated FCGR3A+ monocytes overexpressed CD47 and LILR genes and increased paracrine signaling pathways promoting T cell infiltration. FCGR3A + NK cells overexpressed FCRL3, suggesting that antibody-dependent cytotoxicity is a central mechanism of NK-cell mediated graft injury. Multiplexed immunofluorescence using 38 markers on 18 independent biopsy slides confirmed this role of FcγRIII+ NK and FcγRIII+ nonclassical monocytes in antibody-mediated rejection, with specificity to the glomerular area. These results highlight the central involvement of innate immune cells in the pathogenesis of allograft rejection and identify several potential therapeutic targets that might improve allograft longevity.

To address the need for improved biomarkers for kidney transplant rejection, European Society of Organ Transplantation (ESOT) convened a dedicated working group comprised of experts in kidney transplant biomarkers to review literature pertaining to clinical and subclinical acute rejection to develop guidelines in the screening and diagnosis of acute rejection that were subsequently discussed and voted on during the Consensus Conference that took place in person in Prague. The findings and recommendations of the Working Group on Molecular Biomarkers of Kidney Transplant Rejection are presented in this article.

In exclusively breastfed newborns, hypernatremic dehydration is associated with a free water deficit secondary to insufficient fluid intake. Failure of newborns to regain their birth weight by the 10th day of life should be investigated urgently. In this report, we present a case of a 2 -week-old girl who presented to our institution for 30% weight loss and was found to have severe hypernatremic dehydration associated with acute renal failure (creatinine 4 mg/dL). Upon further investigation, the breast milk sodium content was found to be extremely elevated (90 mEq/L). To our knowledge, the following reported case of severe neonatal hypernatremic dehydration associated with acute renal failure has the most elevated breast milk sodium content, serum sodium, and serum creatinine levels described in the literature. Thus, hypernatremic dehydration secondary to elevated breast milk content should always be borne in mind and investigated whenever suspected.

Morphological databases play an important role in linguistic research today. While several exist for the study of inflectional morphology in French, there is still a lack of resources for derivational morphology. This article presents Démonette-2, a new release of the French derivational morphology database Démonette. Developed in the context of the Démonext project, this database provides a framework in which it is possible to integrate various existing derivational resources. Démonette is characterized by its relational nature, which makes it possible to describe an extensive set of word formation patterns, including suffixation, prefixation, and a variety of non-canonical derivational processes such as conversion and parasynthetic formations. It reconciles broad coverage and fine-grained descriptions and is suitable for different audiences: morphologists working in different theoretical frameworks, teachers, speech therapists, NLP specialists, etc. The article presents in detail the structure and content of Démonette, its evolution since the first version, and its query interface.

AbstractThe purpose of this study is to examine the role of budgetary participation of employees in boosting their performance and through mental model and individual creativity. To address this research question, the study conducts a survey among 78 municipal officers from Lampung regional province using smartPLS method. The study shows that budgetary participation could improve individual performance through mental model building and individual creativity. The direct correlation between budgetary participation and individual performance could be proved statistically. The study reveals that budgetary participation could improve mental model building which in turn will boost individual creativity and performance. This research is the first to empirically examine the positive effect of mental model and creativity for the positive correlation between participation in decision making and individual performance in municipal government.

A new fossil ceratopogonid genus and species from Lower Cretaceous Lebanese amber, Baskintoconops maaloufi Pielowska-Ceranowska gen. et sp. nov., is described and illustrated. The studied material originates from a newly discovered amber site in the Lebanese village Baskinta at a locality dubbed Qanat Bakish. The described genus is typified by its wing venation pattern combining characters of genera Fossileptoconops and Jordanoconops belonging to the subfamily Leptoconopinae.

In judo combat, the approach and gripping phases play a crucial role in determining victory, and it is believed that they can be influenced by the current rules. The objective of this study was to compare the technical-tactical actions executed by female judokas in the approach and gripping subphases during international competitions held in the 2016 and 2020 Olympic cycles, which featured different rules. We analyzed 1332 combat videos from the top 20 female judo athletes in the world rankings. These videos were equally distributed across weight divisions in the 2016 and 2020 Olympic cycles (48 kg = 132; 52 kg = 72; 57 kg = 109; 63 kg = 96; 70 kg = 69; 78 kg = 106; >78 kg = 82; total = 666 combats per cycle). The athletes in the 2020 cycle spent more time executing approach actions without contact with the judogi (formless: 2020 = 26.9; 2016 = 21.3 s; p 78 kg; p 78 kg; right dorsal = 63 kg; left dorsal = 63 kg, 78 kg; right collar left sleeve = 48 kg, 52 kg; right dorsal left sleeve = 78 kg; right dorsal left collar = 48 kg, 70 kg; right dorsal left dorsal = 48 kg, 63 kg; p

Abstract Background Advanced chronic kidney disease is associated with muscle wasting, but how glomerular filtration rate (GFR) recovery after kidney transplantation is associated with muscle mass is unknown. Methods We took advantage of the simultaneous measurement of GFR (using iohexol plasma clearance; ioGFR) and creatinine excretion rate (a surrogate marker of muscle mass; CER) performed 3 months after transplantation and at a later time point at our institution to investigate the interplay between allograft function, muscle mass, and outcome in kidney transplant recipients. Results Between June 2005 and October 2019, 1319 successive kidney transplant recipients (mean age 50.4 ± 14.6; 38.7% female) underwent GFR measurement at our institution 3 months after kidney transplantation. CER (CER3) and ioGFR (ioGFR3) were 7.7 ± 2.6 μmol/min and 53 ± 17.1 mL/min/1.73 m2, respectively. Multivariable analysis identified female gender, older donor and recipient age, reduced body mass index, coronary disease, dialysis history, proteinuria, and reduced ioGFR3 as independent predictors of low CER3 (ioGFR3: β coefficient 0.19 [95% confidence interval 0.14 to 0.24]). A total of 1165 patients had a subsequent CER measurement after a median follow‐up of 9.5 months. Of them, 373 (32%) experienced an increase in CER > 10%, while 222 (19%) showed a CER decrease of more than 10%. Multivariable analysis adjusted for CER3 and other confounders identified ioGFR3 as an independent predictor of CER at follow‐up (β coefficient 0.11 [95% confidence interval 0.07 to 0.16]). In multivariable Cox analysis, reduced CER at 3 months or at follow‐up were consistently associated with mortality (hazard ratio [95% confidence interval] at 3 months: 0.82 [0.74 to 0.91]; at follow‐up: 0.79 [0.69 to 0.99]) but not with graft loss. Conclusions Glomerular filtration rate recovery is a determinant of muscle mass variation after kidney transplantation. Early interventions targeting muscle mass gain may be beneficial for kidney transplant recipients.

Fractures of the distal femur in young populations are usually due to a high-energy trauma mechanism. They often present with various associated osseous and soft tissue injuries. A case of bilateral open distal femur fractures with associated bilateral quadriceps tendon rupture is presented. This injury has not been previously reported in the literature. A 45-year-old male patient who sustained an axial injury to both his lower limbs after jumping from his house balcony while escaping a fire is presented. He was found to have bilateral open fractures of the distal femurs, associated with bilateral rupture of the quadriceps tendons. Both fractures were repaired via open reduction internal fixation using plate osteosynthesis. The quadriceps tendons were also repaired. Two years later, a persistent right femur nonunion was managed surgically with a re-do plate osteosynthesis and mesenchymal cell injection. The patient is in a good clinical condition after a follow-up of 5 years postoperatively. Rupture of the quadriceps tendon in association with distal femur fractures is a rare finding. However, understanding the mechanics and deforming forces of the fracture is crucial to explain the tendon injury. Open reduction internal fixation with primary repair of the quadriceps has led to successful outcomes in both lower limbs, with restoration of the patient’s baseline of motion and daily living.

Petra is one of the ritual dolls used by the Tenggerese people. Petra is generally used in funeral ceremonies as a symbol of ancestral spirits or people who have died, so petra is a doll that is respected by the local community. This study focuses on examining the plant lexicon that composes Petra dolls. This research was conducted to increase the understanding of the local community about the dolls commonly used in rituals as a symbol of the ancestors and to examine the possibility of inter-language contact. This research was conducted in Tengger Village using a qualitative descriptive approach with observation and interview data collection methods. Sources of data were obtained from traditional healers and Pak Sepuh. Data analysis used lexical semantic analysis. The results of this study show the lexicon of the plants that make up the petra doll; the meaning indicated; and petra as a marker of ancestral identity. Petra is made from selected plants that grow in the Tengger region and become a medium for ancestral spirits in funeral ceremonies. Therefore, Petra is a form of respect for the local community towards their ancestors until now. Keywords: Petra Doll, Lexicon, Tengger, Antropolinguistic, Lexicon Semantics

Abstract Background This study aimed to report the prevalence of HER2-neu in newly diagnosed early or metastatic gastric cancer (GC) patients, to determine the percentage of patients achieving various IHC scores correlating with the ISH results and to establish a database for GC patients in Lebanon. Methods This was a national, multicenter, descriptive and cross-sectional study in patients with histologically confirmed early or metastatic GC newly diagnosed. All eligible patients underwent the IHC and ISH tests in a central laboratory. Demographics, medical history and histopathology data were collected. Results One hundred fifty-seven patients were included (mean age at diagnosis: 63 ± 14.1 years) during a 3.5 year period. The prevalence of HER2-neu over expression was 21% (95% CI: 15.3–27.4) using ICH and ISH. Agreement between IHC and ISH results was significantly substantial (kappa = 0.681; p-value

We explore three-body binary formation (3BBF), the formation of a bound system via gravitational scattering of three initially unbound bodies (3UB), using direct numerical integrations. For the first time, we consider systems with unequal masses, as well as finite-size and post-Newtonian effects. Our analytically derived encounter rates and numerical scattering results reproduce the 3BBF rate predicted by Goodman & Hut for hard binaries in dense star clusters. We find that 3BBF occurs overwhelmingly through nonresonant encounters and that the two most-massive bodies are never the most likely to bind. Instead, 3BBF favors pairing the two least-massive bodies (for wide binaries) or the most- plus least-massive bodies (for hard binaries). 3BBF overwhelmingly favors wide-binary formation with superthermal eccentricities, perhaps helping to explain the eccentric wide binaries observed by Gaia. Hard-binary formation is far rarer, but with a thermal eccentricity distribution. The semimajor axis distribution scales cumulatively as a ^3 for hard and slightly wider binaries. Although mergers are rare between black holes when including relativistic effects, direct collisions occur frequently between main-sequence stars—more often than hard 3BBF. Yet, these collisions do not significantly suppress hard 3BBF at the low-velocity dispersions typical of open or globular clusters. Energy dissipation through gravitational radiation leads to a small probability of a bound, hierarchical triple system forming directly from 3UB.

This study aims to use advanced machine learning techniques supported by Principal Component Analysis (PCA) to estimate body weight (BW) in buffalos raised in southeastern Mexico and compare their performance. The first stage of the current study consists of body measurements and the process of determining the most informative variables using PCA, a dimension reduction method. This process reduces the data size by eliminating the complex structure of the model and provides a faster and more effective learning process. As a second stage, two separate prediction models were developed with Gradient Boosting and Random Forest algorithms, using the principal components obtained from the data set reduced by PCA. The performances of both models were compared using R2, RMSE and MAE metrics, and showed that the Gradient Boosting model achieved a better prediction performance with a higher R2 value and lower error rates than the Random Forest model. In conclusion, PCA-supported modeling applications can provide more reliable results, and the Gradient Boosting algorithm is superior to Random Forest in this context. The current study demonstrates the potential use of machine learning approaches in estimating body weight in water buffalos, and will support sustainable animal husbandry by contributing to decision making processes in the field of animal science.

Acute kidney injury is one of the most important complications in patients with COVID-19 and is considered a negative prognostic factor with respect to patient survival. The occurrence of direct infection of the kidney by SARS-CoV-2, and its contribution to the renal deterioration process, remain controversial issues. By studying 32 renal biopsies from patients with COVID-19, we verified that the major pathological feature of COVID-19 is acute tubular injury (ATI). Using single-molecule fluorescence in situ hybridization, we showed that SARS-CoV-2 infected living renal cells and that infection, which paralleled renal angiotensin-converting enzyme 2 expression levels, was associated with increased death. Mechanistically, a transcriptomic analysis uncovered specific molecular signatures in SARS-CoV-2–infected kidneys as compared with healthy kidneys and non–COVID-19 ATI kidneys. On the other hand, we demonstrated that SARS-CoV-2 and hantavirus, 2 RNA viruses, activated different genetic networks despite triggering the same pathological lesions. Finally, we identified X-linked inhibitor of apoptosis-associated factor 1 as a critical target of SARS-CoV-2 infection. In conclusion, this study demonstrated that SARS-CoV-2 can directly infect living renal cells and identified specific druggable molecular targets that can potentially aid in the design of novel therapeutic strategies to preserve renal function in patients with COVID-19.

Belatacept, a CTLA4-Ig, was designed to prevent rejection and graft loss in kidney transplant recipients. This immunotherapy showed a long-term clinical benefit mainly on renal function and better glycemic control but was also associated with a higher number of severe infectious diseases, particularly CMV disease, and lymphoproliferative disease. Therapeutic drug monitoring usually guides the benefit–risk assessment of long-term immunosuppression. In this study, an analytical method by LC-MS/MS was developed in 20 microL of plasma for the belatacept quantification. Intra- and inter-assay precision and accuracy were lower than 20% for the limit of quantification, and 15% for higher concentrations. The method was implemented in our lab and provided data about the inter-variability (N = 108) and intra-variability (N = 33) of belatacept concentrations in kidney transplant recipients with a stable renal function, after conversion from a CNI- to a belatacept-based regimen.

Weevil (Rhynchophorus palmarum) powder, teosinte (Dioon mejiae) and Caesar’s mushroom (Amanita caesarea) flour have bioactive compounds with significant nutritional applications. This paper aimed to examine the influence of weevil, teosinte, and mushroom powders on the protease activity, acid tolerance, bile tolerance, lysozyme tolerance, and gastric juice resistance ability of Lactobacillus acidophilus LA-K. Acid tolerance was determined by adjusting the pH of MRS broth to 2.0 for L. acidophilus incubated under aerobic conditions at 37 °C. Bile tolerance was determined by incorporating 0.3% of oxgall. Protease activity was determined spectrophotometrically at 340 nm. Resistance to 100 mg/L of lysozyme in an electrolyte solution was also determined. All ingredients were incorporated at 2% (w/v), while the control had no added ingredients. Acid and lysozyme tolerance were examined at 0, 30, 60, 90, and 120 min of incubation, whereas bile tolerance was analyzed at 0, 4, and 8 h. Gastric juice tolerance was determined at pH 2, 3, 4, 5, and 7 during 0 and 30 min of incubation, while protease activity was evaluated at 0, 12, and 24 h. Use of weevil flour, and Caesar’s mushroom powder resulted in significantly (p < 0.05) lower counts for bile tolerance, acid tolerance, lysozyme resistance and simulated gastric juice tolerance characteristics. Protease activity increased with the use of teosinte flour. As such, this probiotic bacterium can be used alongside certain novel food sources at 2% concentration in the manufacture of fermented products such as yogurt.

Abstract Background Due to increased risk of pyelonephritis, patients with intestinal reconstruction of the lower urinary tract (IRLUT) have long been advised against kidney transplantation. The aim of this study was to compare the outcomes of transplantation between patients with IRLUT and patients with normal LUT (NLUT) using propensity score matching method. Methods The study included 23 kidney recipients with IRLUT matched to 46 kidney recipients with NLUT using known allograft survival and pyelonephritis risk factors as covariates. One‐, 5‐, and 10‐year graft survival, pyelonephritis, and surgical complications occurrence and graft function were compared. Results One‐, 5‐, and 10‐year graft survival were 96%, 91%, and 63% in the IRLUT group and 96%, 88%, and 70% in the NLUT group, respectively (p = 0.72). Patients with IRLUT had increased cumulative risk of pyelonephritis at 10 years (70% vs. 19%; log‐rank

O presente estudo relacionou a resistência mental e o desempenho da aptidão física de atletas de boxe com os cinco grandes fatores. Para isso, compuseram o presente estudo onze boxeadores recreativos que competiram em nível estadual e estavam treinando regularmente (técnico e tático) 4 vezes por semana durante o período de avaliação. O Big Five Inventory (BFI) de 44 itens mede as dimensões de Conscienciosidade, Amabilidade, Neuroticismo, Abertura e Extroversão e o Questionário de Resistência Mental Esportiva (SMTQ) de 14 itens foram aplicados com Testes de Força, Potência e Resistência, Pearson e as correlações de Spearman foram utilizadas para verificar a associação entre IMC, testes físicos e mentais, respectivamente, p≤0.05. Nossos resultados demonstraram correlação significativa e forte entre o fator de amabilidade e o teste de abdominais, com 40,9±12,4 freq./min (r=0,72, p=0,02) e, no SMTQ, uma forte correlação entre Neuroticismo e Controle [10 (9;12) pontuação, r=0.76, p≤0,01], Constância [10(9;12) pontuação, r=0.84, p≤0,001] e total SMQT [37(34;37) pontuação, r= 0.84, p≤0,001]. Em conclusão, esses resultados sugerem que os fatores de neuroticismo estão associados à resistência mental, enquanto o fator de amabilidade está associado à capacidade de resistência muscular. Os resultados de resistência mental e resistência estão associados à personalidade dos boxeadores, cuja motivação os motiva implacavelmente para o sucesso e promove o sucesso em ambientes de treinamento de boxe ou durante campeonatos.

Coaches and psychologists can use time-motion analysis to elaborate specific interventions for female BJJ athletes, increasing specific training context and reducing unnecessary psychological and physical demands and injuries. Therefore, the present study aimed to analyze high-level BJJ female athletes in the 2020 Pan-American Games by comparing the weight categories on the time-motion analysis. The time-motion analysis (i.e., approach, gripping, attack, defensive actions, transition, mounting, guard, side control, and submissions) of 422 high-level female BJJ combats was divided and compared by weight category as follows: Rooster (n = 8), Light Feather (n = 18), Feather (n = 122), Light (n = 84), Middle (n = 74), Medium Heavy (n = 44), Heavy (n = 36), Super Heavy (n = 36), using p ≤ 0.05. The main results indicated that the Super heavyweight category [3.1 (5.8;119.9) s] had a shorter gripping time than other weight categories, p ≤ 0.05. In contrast, roosters [7.2 (3.5;64.6) s] had longer gripping, transition [14.0 (4.8;29.6) s], and attack time [76.2 (27.7, 93.2)] than the light feather, middlers, and heavier weight categories, p ≤ 0.05. These findings should be considered for the psychological interventions and training prescription.

Intraosseous ganglion cysts (IGC) of the carpal bones are frequently reported in the literature, involving at most two carpal bones of the same wrist. Only one case recently described the presence of multiple intraosseous ganglion lesions in the capitate, lunate, and triquetrum, resulting in chronic wrist pain. The following study reports the first case of multiple IGCs causing a unilateral carpal tunnel syndrome (CTS), in a 56-year-old woman, with no previous history of trauma. Failure of conservative management prompted carpal tunnel release and the surgical excision of the ICGs, followed by autologous bone grafting to fill in the defects. Consequently, IGCs must be considered in the differential diagnosis of unilateral CTS due to the expansile nature of the bone lesions.

Abstract The prevalence of coronary artery anomalies has been increasing due to the increasing usage of coronary angiography. There is a paucity of literature concerning management of viral-induced myocarditis in patients with anomalous coronary artery. We present a very unusual case of a 44-year-old man with anomalous origin of the left circumflex artery from the proximal ostium of the right coronary artery who was admitted for COVID-19-induced myocarditis. He presented with signs of heart failure and coronary angiography revealed the left circumflex artery with a separate ostium originating from the proximal right coronary artery. He was treated medically with Bisoprolol, Perindopril Arginine, Rivaroxaban, and Furosemide. His condition improved rapidly and he resumed regular life within 1 month. Coexistence of cardiac disease such as viral-induced myocarditis with an underlying anomalous origin of the coronary artery is challenging to spot and can lead to worse outcomes in case of misdiagnosis and inaccurate management.

Abstract The mechanisms underlying the development of glomerular lesions during aging are largely unknown. It has been suggested that senescence might play a role, but the pathophysiological link between senescence and lesion development remains unexplained. Here, we uncovered an unexpected role for glomerular endothelial cells during aging. In fact, we discovered a detrimental cross‐talk between senescent endothelial cells and podocytes, through PAI‐1. In vivo, selective inactivation of PAI‐1 in endothelial cells protected glomeruli from lesion development and podocyte loss in aged mice. In vitro, blocking PAI‐1 in supernatants from senescent endothelial cells prevented podocyte apoptosis. Consistently, depletion of senescent cells prevented podocyte loss in old p16 INK‐ATTAC transgenic mice. Importantly, these experimental findings are relevant to humans. We showed that glomerular PAI‐1 expression was predictive of poor outcomes in transplanted kidneys from elderly donors. In addition, we observed that in elderly patients, urinary PAI‐1 was associated with age‐related chronic kidney disease. Altogether, these results uncover a novel mechanism of kidney disease and identify PAI‐1 as a promising biomarker of kidney dysfunction in allografts from elderly donors.

Chimeric antigen receptor engineering in T cells has been shown to be of great potential therapeutic benefit in a range of immune pathologies, although the functionality of such cell therapies can be limited due to tonic signalling and the induction of dysfunction. Here the authors show transient inhibition of mTOR can rescue their 41-BB-CAR-Tregs from tonic signalling-induced dysfunction.

Energy metabolism failure in proximal tubule cells (PTCs) is a hallmark of chronic kidney injury. We combined transcriptomic, metabolomic, and lipidomic approaches in experimental models and patient cohorts to investigate the molecular basis of the progression to chronic kidney allograft injury initiated by ischemia/reperfusion injury (IRI). The urinary metabolome of kidney transplant recipients with chronic allograft injury and who experienced severe IRI was substantially enriched with long chain fatty acids (FAs). We identified a renal FA-related gene signature with low levels of carnitine palmitoyltransferase 2 (Cpt2) and acyl-CoA synthetase medium chain family member 5 (Acsm5) and high levels of acyl-CoA synthetase long chain family member 4 and 5 (Acsl4 and Acsl5) associated with IRI, transition to chronic injury, and established chronic kidney disease in mouse models and kidney transplant recipients. The findings were consistent with the presence of Cpt2–Acsl4+Acsl5+Acsm5– PTCs failing to recover from IRI as identified by single-nucleus RNA-Seq. In vitro experiments indicated that ER stress contributed to CPT2 repression, which, in turn, promoted lipids’ accumulation, drove profibrogenic epithelial phenotypic changes, and activated the unfolded protein response. ER stress through CPT2 inhibition and lipid accumulation engaged an auto-amplification loop leading to lipotoxicity and self-sustained cellular stress. Thus, IRI imprints a persistent FA metabolism disturbance in the proximal tubule, sustaining the progression to chronic kidney allograft injury.

Objetivo. Predecir la composición tisular de canales de corderos “Blackbelly” usando mediciones in vivo y postmortem. Materiales y métodos. Se utilizaron 20 corderos con una edad de siete meses y peso de 29.07±2.88 kg en promedio. Antes del sacrificio, se midió con ultrasonografía la grasa subcutánea, la profundidad, la amplitud y el área del músculo Longissimus dorsi. Posterior al sacrificio, se registró el peso de la canal y de los tejidos: músculo, grasa y hueso. En la canal, también se midió y registró la profundidad torácica, el largo, el perímetro, el largo y ancho de la pierna, así como el índice de compacidad. Para predecir la composición tisular de las canales se usó análisis de correlación y modelos de regresión. Resultados. Los tejidos de la canal se correlacionaron con la profundidad del músculo L. dorsi (p≤0.05; r entre 0.67 y 0.80) y con el índice de compacidad de la canal (p≤0.05; r varió de 0.54 a 0.75). Las ecuaciones de predicción de la composición tisular de la canal tuvieron una r2 que osciló entre 0.71 a 0.78 para el tejido graso (p≤0.001). Conclusiones. El uso de mediciones in vivo y postmortem permitieron predecir la composición tisular de canales de corderos con una precisión de moderada a alta (r2 >0.71≤ y ≤0.78).

Nipple fruit (Solanum mammosum) has been considered to have great pharmaceutical potential because of its high amounts of solamargine and solasonine. This study aimed to examine the effect of nipple fruit at different concentrations (0.5%, 1%, and 2% (w/v)) on the viability, acid, bile, lysozyme, and gastric juice tolerance, and protease activity of Lactobacillus acidophilus LA K. The viability was studied in MRS broth. Acid tolerance was determined by adjusting the pH to 2, whereas bile tolerance was examined with oxgall 0.3% (w/v) in MRS broth. Lysozyme resistance was investigated in an electrolyte solution with lysozyme (100 mg/L), while gastric juice tolerance was analyzed with pepsin and NaCl. Protease activity was determined spectrophotometrically at 340 nm in skim milk with o-phthaldialdehyde reagent. L. acidophilus LA K was incubated anaerobically (37 °C). Microbial growth was determined every 2 h for 10 h of incubation. Acid tolerance was determined at 0, 5, and 15 min, whereas bile tolerance was analyzed at 0, 4, and 8 h of incubation. Lysozyme tolerance was determined at 0, 1, and 2 h of incubation, while gastric juice tolerance was determined at pH 2, 3, 4, 5, and 7. Protease activity was evaluated at 0, 12, and 24 h incubation. Nipple fruit’s chemical and bioactive compounds were also examined to discuss their impact on the survival of L. acidophilus LA K. Nipple fruit did not affect microbial growth, bile, and acid tolerance. Nipple fruit at 2% had higher survivability on the simulated gastric juice and lysozyme resistance and increased protease activity.

Periprosthetic hip infections are a dreaded complication met among most orthopedic surgeons after arthroplasty procedures especially in susceptible patients. We report a case of a patient with periprosthetic infection after a revised total hip arthroplasty. She was treated with deep lavage and debridement, combined with IV anti-biotherapy and vacuum dressings. A 4-year follow-up shows an infection-free patient with an acceptable functional status and quality of life. Suppression of the infection, with salvage of the prosthesis and maintaining an acceptable functional status, is a satisfactory result that can be achieved in selected cases.

Abstract Metamorphosis is a key innovation allowing the same species to inhabit different environments and accomplish different functions, leading to evolutionary success in many animal groups. Astigmata is a megadiverse lineage of mites that expanded into a great number of habitats via associations with invertebrate and vertebrate hosts (human associates include stored food mites, house dust mites, and scabies). The evolutionary success of Astigmata is linked to phoresy-related metamorphosis, namely the origin of the heteromorphic deutonymph, which is highly specialized for phoresy (dispersal on hosts). The origin of this instar is enigmatic since it is morphologically divergent and no intermediate forms are known. Here we describe the heteromorphic deutonymph of Levantoglyphus sidorchukae n. gen. and sp. (Levantoglyphidae fam. n.) from early Cretaceous amber of Lebanon (129 Ma), which displays a transitional morphology. It is similar to extant phoretic deutonymphs in its modifications for phoresy but has the masticatory system and other parts of the gnathosoma well-developed. These aspects point to a gradual evolution of the astigmatid heteromorphic morphology and metamorphosis. The presence of well-developed presumably host-seeking sensory elements on the gnathosoma suggests that the deutonymph was not feeding either during phoretic or pre- or postphoretic periods.

This research study verified the technical–tactical actions during the mixed martial arts (MMA) fights to generate serious enough injury to stop the MMA round, determining technical-tactical potential risk factors for injury in official MMA combats, according to Concussion or Resignation per Submission. A total of 990 rounds with concussions and 627 resignations per submission were considered with severe injury (i.e., a fight ended by a doctor or referee). All injuries were diagnosed and managed by attending ringside physicians during the MMA fights and rounds and had a continuous technical–tactical behavior analysis, p ≤ 0.05. The leading cause of concussion was due to head trauma (~90%), with higher dependence on head strikes scored actions. Comparisons between Concussion and Resignation per Submission combats demonstrated differences between distance head strikes actions [13(6,25) vs. 9(4,18) frequencies], clinch head strikes actions [1(0;4) vs. 1(0;3) frequencies], ground head strikes actions [1(0;8) vs. 2(0;10) frequencies] and takedowns actions [0(0;1) vs. 1(0;2) frequencies]. This information may provide significant evidence regarding the doctor stoppage in concussion combats and when it could be called by officials supervising MMA.

The present study is a descriptive-documental study that evaluates a survey database about Brazilian Jiu-Jitsu (BJJ) practitioners and concussions. We investigate any relationship between lifetime practice and the incidence of concussions in adults. For this, an online survey composed of 17 questions was sent to 42 BJJ coaches. The Survey Monkey platform was used to host the survey. Some demographic data was collected, followed by questions related to the BJJ practice. A total of 791 practitioners had completed or partially answered the survey. The results show that concussions are more frequent at the beginner's white 49.0% and blue belt 33.3% (p≤ 0.01). The symptom "seeing stars" showed a positive and significant correlation (r= 0.169, p≤ 0.002) with a white and blue belt. After a concussion, white and blue belts return faster than the others (χ2= 190.964; p≤ 0.01). White, blue, and purple belts are the least likely to seek medical care after a concussion (χ2= 14.874; p≤ 0.01). Together, our results showed the need for an educational intervention with the BJJ coaches and beginners regarding awareness about concussions and possible post-traumatic issues and creating procedures to deal with concussions in BJJ.