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Mucosal leishmaniasis is associated with the Leishmania RNA virus and inappropriate cutaneous leishmaniasis treatment

Background Mucosal leishmaniasis (ML) is a severe clinical form of leishmaniasis that is characterized by the destruction of the nasal and/or the oral mucosae and appears as a late complication in 5% to 10% of cutaneous leishmaniasis (CL) cases produced by species belonging to Leishmania (Viannia) subgenus. Some strains of Leishmania spp. carry an RNA virus known as Leishmania RNA virus (LRV) that may contribute to the appearance of ML. Methods To examine the role of LRV type 1 (LRV1) as a risk factor associated with ML, a retrospective case-control study involving 103 patients was conducted. Cases were defined as patients with ML (n = 33), and controls corresponded to patients with CL and without mucosal lesions (n = 70). Clinical data were recorded from the patient’s medical records. Cryopreserved biopsies were used to detect LRV1 and identify Leishmania species. Results The frequency of LRV1 in the 103 patients was 16.5% (95% CI,10.4–25.12) being higher in samples from cases [33.33% (95% CI,18.89–51.76) than from controls [8.57% (95% CI, 3.82–18.10)]. L. (V.) braziliensis was identified in 63.6% of cases and 55.7% of the controls. Multivariate logistic regression indicated that infection with Leishmania spp. carrying LRV1 (OR = 6.30; 95% CI,1.52–26.10, p = 0.011) acts as risk factors for ML occurrence, while the completed treatment for the cutaneous event decreases the risk of ML (OR = 0.039; 95% CI, 0.01–0.12, p < 0.0001). Conclusions Our data support the association between LRV1 and ML occurrence and emphasize the effect of completed treatment for CL in preventing ML.

Activation of S1PR2 on macrophages and the hepatocyte S1PR2/RhoA/ROCK1/MLC2 pathway in vanishing bile duct syndrome

Immunologic bile duct destruction is a pathogenic condition associated with vanishing bile duct syndrome (VBDS) after liver transplantation and hematopoietic stem-cell transplantation. As the bile acid receptor sphingosine 1-phosphate receptor 2 (S1PR2) plays a critical role in recruitment of bone marrow-derived monocytes/macrophages to sites of cholestatic liver injury, S1PR2 expression was examined using cultured macrophages and patient tissues. Bile canaliculi destruction precedes intrahepatic ductopenia; therefore, we focused on hepatocyte S1PR2 and the downstream RhoA/Rho kinase 1 (ROCK1) signaling pathway and bile canaliculi alterations using three-dimensional hepatocyte culture models that form obvious bile canaliculus-like networks. Multiplex immunohistochemistry revealed increased numbers of S1PR2+CD45+CD68+FCN1+ inflammatory macrophages and S1PR2+CD45+CD68+MARCO+ Kupffer cells in liver tissues showing ductopenia due to graft-versus-host disease and rejection post-liver transplant compared with normal liver. Macrophage expression of proinflammatory cytokines, including MCP1, was reduced following S1PR2 inhibition. Taurocholic acid and S1P2 agonist induced hepatocyte S1PR2 and reduced RhoA/ROCK1 expression, resulting in bile canaliculi dilatation. S1PR2 inhibition reversed the effect on RhoA/ROCK1 expression, resulting in maintenance of bile canaliculi through myosin light chain 2 (MLC2) phosphorylation. Activation of S1PR2 on macrophages and S1PR2 on hepatocytes may disrupt bile canaliculi dynamics in VBDS under regulation by RhoA/ROCK1 through MLC2 phosphorylation.

Comparative study of bovine and synthetic hydroxyapatite in micro- and nanosized on osteoblasts action and bone growth

Hydroxyapatite (HA) is widely used as a bone graft. However, information on the head-to-head osteoinductivity and in vivo performance of micro- and nanosized natural and synthetic HA is still lacking. Here, we fabricated nanosized bovine HA (nanoBHA) by using a wet ball milling method and compared its in vitro and in vivo performance with microsized BHA, nanosized synthetic HA (nanoHA), and microsized synthetic HA (HA). The results showed that the wet ball milling method successfully reduced the particle size of BHA to 40 nm without changing its natural characteristics. NanoBHA was able to maintain cell viability and induce cell proliferation and calcium deposits. NanoBHA promoted osteogenic differentiation via OPN as a specific regulator, with a 13-fold greater expression level. NanoBHA and HA also activated ERK1/2 indicated corresponding to the proliferation-differentiation and death of cells, respectively. The calvarial bone defect model showed that nanoBHA induced bone growth based on CT images, which is in line with the histological results showing the presence of bone cells and connective tissue at the nanoBHA implantation site. In conclusion, natural HA outperformed synthetic HA. Our findings will attract interest in further research into nanomaterials and their mechanism of action in bone remodeling.

Enhancing trauma cardiopulmonary resuscitation simulation training with the use of virtual reality (Trauma SimVR): Protocol for a randomized controlled trial

Background With the increasing availability and use of digital tools such as virtual reality in medical education, there is a need to evaluate their impact on clinical performance and decision-making among healthcare professionals. The Trauma SimVR study is investigating the efficacy of virtual reality training in the context of traumatic in-hospital cardiac arrest. Methods and analysis This study protocol (clinicaltrials.gov identifier: NCT06445764) for a single-center, prospective, randomized, controlled trial focuses on first-year residents in anesthesiology/intensive care, traumatology, and emergency medicine. The study will compare the clinical performance in a simulated scenario between participants who received virtual reality training and those who received traditional e-learning courses for preparation. The primary endpoint is the time to a predefined intervention to treat the underlying cause of the simulated traumatic cardiac arrest. Secondary endpoints include protocol deviations, cognitive load during simulated scenarios, and the influence of gender and personality characteristics on learning outcomes. The e-learning and the virtual reality training content will be developed in collaboration with experts from various medical specialties and nursing, focusing on procedural processes, guideline adherence specific to trauma patient care, and traumatic in-hospital cardiac arrest. Results The results of this study will provide valuable insights into the efficacy of virtual reality training, contributing to the advancement of medical education, and serve as a foundation for future research in this rapidly evolving field.

Factors associated with vitamin D levels in Mongolian patients with multiple sclerosis

Background Multiple sclerosis (MS) onset is caused by genetic and environmental factors. Vitamin D has been identified as contributing environmental risk factor, with higher prevalence at latitudes further from the equator. Mongolia, at 45°N, has limited sunlight exposure, increasing the population’s risk for vitamin D deficiency. Objectives To compare vitamin D levels between persons with MS (pwMS) and persons without MS and to identify factors associated with low vitamin D. Methods We investigated associations with vitamin D levels using data from MS cases and controls from Mongolia. We used linear mixed-effects regression with fixed effects (case status, sociodemographics, and predefined variables) and participant-specific random intercepts. Results Of 62 participants (31 pwMS, 31 controls), pwMS had lower summer [median 23.00 ng/ml (interquartile range 11.30–31.50) vs. 25.00 ng/ml (19.25–32.00)] and winter vitamin D levels [21.00 ng/ml (10.60–27.60) vs. 23.50 ng/ml (15.55–28.60)], with a smaller seasonal decline. Vitamin D deficiency was more prevalent in pwMS. None of these findings reached statistical significance. Winter season and being breastfed as a child were associated with significantly lower vitamin D levels. Conclusion Vitamin D deficiency was common among pwMS, which could be influenced by behavioural factors. These findings may inform more targeted recommendations for pwMS to maintain sufficient vitamin D levels.

Changes in urinary concentrations of contemporary and emerging chemicals in commerce during the COVID-19 pandemic: Insights from the Environmental influences on Child Health Outcomes (ECHO) program

Previous research indicates that the COVID-19 pandemic catalyzed alterations in behaviors that may impact exposures to environmental endocrine-disrupting chemicals. This includes changes in the use of chemicals found in consumer products, food packaging, and exposure to air pollutants. Within the Environmental influences on Child Health Outcomes (ECHO) program, a national consortium initiated to understand the effects of environmental exposures on child health and development, our objective was to assess whether urinary concentrations of a wide range of potential endocrine-disrupting chemicals varied before and during the pandemic. Drawing from three racially, ethnically, and socioeconomically diverse ECHO cohorts, we assessed key differences in urinary chemical concentrations related to environmental exposures through food packaging, use of disinfectants, personal care products and air pollutants using repeated urine samples in a subset of 47 participants, who contributed a urine sample prior to the pandemic (between October 2018 and February 2020) and a subsequent urine sample after the pandemic began (between March 2020 and April 2021). We measured urinary concentrations of analytes across several chemical groups, including polycyclic aromatic hydrocarbons (PAHs), phthalates/alternative plasticizers, synthetic phenols (parabens, bisphenols, triclosan, benzophenones), organophosphate esters (OPEs), insecticides and fungicides. Multivariable linear mixed models accounting for key covariates and clustering within cohort and across repeated samples were used to estimate the change in urinary analyte concentrations across time points. We observed decreases in urinary concentrations of some PAHs, bisphenols, benzophenones, and triclosan, and increases in specific OPEs. These biomarker data mirror some of the behavior changes reported in our prior work and support the observation that the pandemic-related behavior changes lead to alterations in chemical exposures that have been linked to adverse health outcomes.

The impact of The Quality and Safety Education (QSEN) program on the knowledge, skills, and attitudes of junior nurses

Background The quality and safety education for nurses (QSEN) competency program represents a valuable initiative in nursing practice and education, equipping nurses with the essential knowledge, attitude, and skills (KAS) required to deliver safe, efficient, and patient-centered care. Purpose This study aims to determine the impact of QSEN competency on the KAS of nurses in Palestine. Method A quasi-experimental pre-test and post-test design with two groups was used utilizing a questionnaire to collect data from 164 Junior nurses in two governmental hospitals within the period of 25th, January to the 10th February 2024. Patricia Benner’s theory suggests that a strong educational foundation and diverse experiences enable nurses to enhance their patient care knowledge and abilities over time. Results The findings indicate that nurses in Palestine can benefit from targeted interventions and QSEN educational programs aimed at improving their patient-centered care competence, as post-test scores show a significant rise over pre-test scores. Junior nurses who participated in the QSEN program experienced a 57% increase in knowledge, a 57% increase in skills, and a 64% increase in attitudes. The intervention significantly improved knowledge (77.02 vs. 49.19, p < 0.001), quality and safety skills (70.16 vs. 44.61, p < 0.001), and attitudes (75.47 vs. 46.16, p < 0.001) among participants post-procedure, indicating a substantial positive impact on these areas, demonstrating the effectiveness of the educational intervention. Conclusion The study demonstrates that an educational intervention improves junior nurses’ KSAs for six QSEN competencies, leading to higher average scores in quality and safety competence subscales, thereby enhancing staff satisfaction, and reducing medical errors, and patient safety.

Gender biases and hate speech: Promoters and targets in the Argentinean political context

Hate speech found in social media a place to flourish. In the Argentinean context, new right-wing parties have disrupted the political arena, winning the elections of 2023. Many of these new right-wing figures grew in popularity due to their use of social media, on a background of increasing political violence. In this article, we use quantitative and qualitative tools to investigate the prevalence of hate speech targeting women politicians and analyze the role of different political affiliations in promoting such discourse. Furthermore, we propose a model that predicts users’ political alignments based on their profile descriptions, allowing us to explore the distribution of hate speech among different political orientations. Our results provide a descriptive account of the relationship between hate speech by politicians and other users and shows that right-wing political figures and supporters are strong emissors of hate speech, while women, especially those from the left-wing are more prone to receive violent content.

The ionic liquid-assisted sample preparation method pTRUST allows sensitive proteome characterization of a variety of bacterial endospores to aid in the search for protein biomarkers

Bacterial endospores are ubiquitous and are responsible for various human infections. Recently, we reported that an ionic liquid (IL)-based sample preparation method (named pTRUST) facilitated highly efficient shotgun analysis of the Bacillus subtilis spore proteome in trace samples. In this study, we evaluated the efficiency and applicability of the pTRUST technology using three different spore preparations: one purified from the closely related subspecies B. subtilis natto and two from B. licheniformis and B. cereus. We showed that the pTRUST method allowed rapid solubilization and processing of all tested spore samples prepared for highly sensitive mass spectrometry (MS) analysis. Bioinformatics analysis using the BLAST program suggested that a set of 25 proteins commonly identified between the above three species and B. subtilis spores may be universal biomarkers among various bacterial species, including 43 spore-producing bacteria associated with industrial dairy processing environments and product spoilage. In contrast, the two identified proteins, D4FV94 in B. subtilis natto and Q737A2 in B. cereus, are likely species-specific biomarkers, because their orthologs are absent or rare in all organisms. The sensitivity and applicability of pTRUST, along with the putative protein biomarkers identified in this study, will facilitate a wide spectrum of spore research for biological and clinical applications.

Precise phenotyping method using image data for carcass marbling score in Hanwoo cattle

With the development of the Korean economy, demand for high-quality beef, specifically Hanwoo beef, is escalating, with marbling traits—measured by the widely used marbling score—being a key contributor to meat palatability. The differences between the high-quality and the lower-quality meat, according to the satisfaction of the customers, are not the result from only the degree of marbling but also from the delicacy of the marbling flecks distribution. Using the computer marbling analysis technique, an index for quantifying marbling fineness of 256 sirloin cuts at 12th– 13th thoracic vertebra named F7 index was developed in this study. F7 index is defined as the standard deviation of the ratios of marbling particles area to the tile area, was developed in this study. At the optimal step size of 70 tiles per axis, F7 index discriminated dramatically the finely marbled and coarsely marbled sirloin with Beef Marbling Score from 6 to 9, with P value = 1.340 × 10−27 < 0.05 of. Although the efficiency of computer image analysis procedure with the F7 index is still being optimized, the F7 index shows great potential to enhance the accuracy of Hanwoo beef quality grading alongside marbling score and support the development of improved breeding strategies for the Hanwoo cattle population in Korea.

Correction: Knowledge, attitude, and perceptions about polycystic ovarian syndrome, and its determinants among Pakistani undergraduate students

Generative adversarial local density-based unsupervised anomaly detection

Anomaly detection is crucial in areas such as financial fraud identification, cybersecurity defense, and health monitoring, as it directly affects the accuracy and security of decision-making. Existing generative adversarial nets (GANs)-based anomaly detection methods overlook the importance of local density, limiting their effectiveness in detecting anomaly objects in complex data distributions. To address this challenge, we introduce a generative adversarial local density-based anomaly detection (GALD) method, which combines the data distribution modeling capabilities of GANs with local synthetic density analysis. This approach not only considers different data distributions but also incorporates neighborhood relationships, enhancing anomaly detection accuracy. First, by utilizing the adversarial process of GANs, including the loss function and the rarity of anomaly objects, we constrain the generator to primarily fit the probability distribution of normal objects during the unsupervised training process; Subsequently, a synthetic dataset is sampled from the generator, and the local synthetic density, which is defined by measuring the inverse of the sum of distances between a data point and all objects in its synthetic neighborhood, is calculated; Finally, the objects that show substantial density deviations from the synthetic data are classified as anomaly objects. Extensive experiments on seven real-world datasets from various domains, including medical diagnostics, industrial monitoring, and material analysis, were conducted using seven state-of-the-art anomaly detection methods as benchmarks. The GALD method achieved an average AUC of 0.874 and an accuracy of 94.34%, outperforming the second-best method by 7.2% and 6%, respectively.

Unveiling diabetes onset: Optimized XGBoost with Bayesian optimization for enhanced prediction

Diabetes, a chronic condition affecting millions worldwide, necessitates early intervention to prevent severe complications. While accurately predicting diabetes onset or progression remains challenging due to complex and imbalanced datasets, recent advancements in machine learning offer potential solutions. Traditional prediction models, often limited by default parameters, have been superseded by more sophisticated approaches. Leveraging Bayesian optimization to fine-tune XGBoost, researchers can harness the power of complex data analysis to improve predictive accuracy. By identifying key factors influencing diabetes risk, personalized prevention strategies can be developed, ultimately enhancing patient outcomes. Successful implementation requires meticulous data management, stringent ethical considerations, and seamless integration into healthcare systems. This study focused on optimizing the hyperparameters of an XGBoost ensemble machine learning model using Bayesian optimization. Compared to grid search XGBoost (accuracy: 97.24%, F1-score: 95.72%, MCC: 81.02%), the XGBoost with Bayesian optimization achieved slightly improved performance (accuracy: 97.26%, F1-score: 95.72%, MCC:81.18%). Although the improvements observed in this study are modest, the optimized XGBoost model with Bayesian optimization represents a promising step towards revolutionizing diabetes prevention and treatment. This approach holds significant potential to improve outcomes for individuals at risk of developing diabetes.

Trump tariffs and the U.S. defense industry

In March 2018, U.S. President Trump announced that the U.S. would start imposing tariffs on steel and aluminum imports from most exporting countries around the world. This study explores the impact of introducing these tariffs on the equity return of U.S. defense companies. As the defense industry stands among the largest metal consumers in the U.S., it is expected that these import restrictions have deteriorated the business performance of the U.S. defense industry. For this study, a novel trade uncertainty indicator has been constructed that is based on the key events related to the invocation of Section 232 of the Trade Expansion Act. This section empowers the President to impose trade restrictions when the quantity of imports threatens to impair national security. My empirical analysis reveals that investors perceived the introduction of the steel and aluminum tariffs as detrimental to U.S. defense companies. The negative abnormal stock returns in the days around several key tariff-related events evidence this. Already in the period before the Department of Commerce released the findings of its investigation, investors were speculating on the possible introduction of trade barriers. However, the height of the imposed tariff exceeded their expectations since the negative sentiment was further reinforced after the official announcement of the tariff by President Trump.

Differential GTP-dependent in-vitro polymerization of recombinant Physcomitrella FtsZ proteins

Abstract Bacterial cell division and plant chloroplast division require selfassembling Filamentous temperature-sensitive Z (FtsZ) proteins. FtsZ proteins are GTPases sharing structural and biochemical similarities with eukaryotic tubulin. In the moss Physcomitrella, the morphology of the FtsZ polymer networks varies between the different FtsZ isoforms. The underlying mechanism and foundation of the distinct networks is unknown. Here, we investigated the interaction of Physcomitrella FtsZ2-1 with FtsZ1 isoforms via co-immunoprecipitation and mass spectrometry, and found protein-protein interaction in vivo. We tagged FtsZ1-2 and FtsZ2-1 with different fluorophores and expressed both in E. coli , which led to the formation of defined structures within the cells and to an influence on bacterial cell division and morphology. Furthermore, we have optimized the purification protocols for FtsZ1-2 and FtsZ2-1 expressed in E. coli and characterized their GTPase activity and polymerization in vitro. Both FtsZ isoforms showed GTPase activity. Stoichiometric mixing of both proteins led to a significantly increased GTPase activity, indicating a synergistic interaction between them. In light scattering assays, we observed GTP-dependent assembly of FtsZ1-2 and of FtsZ2-1 in a protein concentration dependent manner. Stoichiometric mixing of both proteins resulted in significantly faster polymerization, again indicating a synergistic interaction between them. Under the same conditions used for GTPase and light scattering assays both FtsZ isoforms formed filaments in a GTP-dependent manner as visualized by transmission electron microscopy (TEM). Taken together, our results reveal that Physcomitrella FtsZ1-2 and FtsZ2-1 are functionally different, can synergistically interact in vivo and in vitro, and differ in their properties from FtsZ proteins from bacteria, archaea and vascular plants.

Islet NO-Synthases, extracellular NO and glucose-stimulated insulin secretion: Possible impact of neuronal NO-Synthase on the pentose phosphate pathway

The impact of islet neuronal nitric oxide synthase (nNOS) on glucose-stimulated insulin secretion (GSIS) is less understood. We investigated this issue by performing simultaneous measurements of the activity of nNOS versus inducible NOS (iNOS) in GSIS using isolated murine islets. Additionally, the significance of extracellular NO on GSIS was studied. Islets incubated at basal glucose showed modest nNOS but no iNOS activity. Glucose-induced concentration-response studies revealed an increase in both NOS activities in relation to secreted insulin. Culturing at high glucose increased both nNOS and iNOS activities inducing a marked decrease in GSIS in a following short-term incubation at high glucose. Culturing at half-maximal glucose showed strong iNOS expression revealed by fluorescence microscopy also in human islets. Experiments with nNOS-inhibitors revealed that GSIS was inversely related to nNOS activity, the effect of iNOS activity being negligible. The increased GSIS after blockade of nNOS was reversed by the intracellular NO-donor hydroxylamine. The enhancing effect on GSIS by nNOS inhibition was independent of membrane depolarization and most likely exerted in the pentose phosphate pathway (PPP). GSIS was markedly reduced, 50%, by glucose-6-phosphate dehydrogenase (G-6-PD) inhibition both in the absence and presence of nNOS inhibition. NO gas stimulated GSIS at low and inhibited at high NO concentrations. The stimulatory action was dependent on membrane thiol groups. In comparison, carbon monoxide (CO) exclusively potentiated GSIS. CO rather than NO stimulated islet cyclic GMP during GSIS. It is suggested that increased nNOS activity restrains GSIS, and that the alternative pathway along the PPP initially might involve as much as 50% of total GSIS. In the PPP, the acute insulin response is downregulated by a negative feedback effect executed by a marked upregulation of nNOS activity elicited from secreted insulin exciting insulin receptors at exocytotic sites of an nNOS-associated population of secretory granules.

Utility of complexity analysis in electroencephalography and electromyography for automated classification of sleep-wake states in mice

Structural design and safety performance of a novel high-strength steel lightweight guardrail

Highway guardrails are critical safety infrastructure along roadways, designed to redirect vehicles back into their lanes and facilitate a gradual deceleration to a complete stop. Traditional highway steel guardrails exhibit significant limitations, including inadequate energy absorption, susceptibility to corrosion, and an increased risk of vehicles leaving the roadway during severe collisions. Furthermore, the production and transportation of these guardrails contribute to substantial carbon emissions and environmental pollution. This study presents an optimization of the cross-sectional shape of the conventional corrugated beam guardrail, proposing a lightweight structure that incorporates high yield strength steel plate HR700F to enhance energy absorption capacity. The safety performance of the proposed guardrail is rigorously assessed through finite element numerical simulations and full-scale collision tests with real vehicles. Key performance indicators—such as the maximum dynamic lateral deflection of the guardrail, occupant impact velocity, and acceleration—are utilized to evaluate the energy absorption and protective efficacy of the structure. Results indicate that the optimized guardrail not only meets SB-level safety standards but also demonstrates superior anti-collision performance and effective energy absorption and buffering characteristics. The proposed design achieves a reduction in beam plate thickness by 1.3 mm, resulting in a lightweight structure with a weight reduction of up to 44%, thereby supporting the advancement of low-carbon, environmentally sustainable transportation solutions.

Impact of frequent ARID1A mutations on protein stability provides insights into cancer pathogenesis

Low regulatory T-cells frequency is associated with graft rejection after small bowel transplantation: Clinical and experimental evidence

Background Intestinal transplantation (ITx) represents the only curative option for patients with irreversible intestinal failure. Nevertheless, its rejection rate surpasses that of other solid organ transplants due to the heightened immunological load of the gut. Regulatory T-cells (Tregs) are key players in the induction and maintenance of peripheral tolerance, suggesting their potential involvement in modulating host vs. graft responses after ITx. Thus, we investigated the association of Tregs with allograft outcomes in pediatric patients and in an experimental model of small bowel transplantation. Methods Treg frequency in human samples was analyzed by Flow cytometry (CD4+CD25highCD127-, blood samples) and immunohistochemistry (FoxP3, graft samples). Experimental allogenic-heterotopic small bowel transplantation was performed in rats and animals divided into 3 groups: non-immunosuppressant treatment, rapamycin (2 mg/kg), and tacrolimus (0.6 mg/kg) treatment. Acute cellular rejection (ACR) was diagnosed based on clinical and histological findings, graft gene expression of pro- and anti-inflammatory mediators assessed by RT-qPCR, serum IL-6 and IL-10 levels by Luminex, and Treg frequency analyzed by flow cytometry (CD4+CD25highFoxP3+). Results Blood samples from patients undergoing ACR exhibited a significant reduction in the Treg number compared to those with normo-functional grafts. Similarly, a diminished number of FoxP3+ cells was observed in mucosa samples with ACR. In the experimental model, rapamycin-treated animals displayed clinical and histological findings resembling those not receiving immunosuppression treatment. Notably, ACR correlated with a high CD8/CD4 ratio, loss of T-cell chimerism, mRNA upregulation of pro-inflammatory genes and diminished graft Treg frequency. In contrast, tacrolimus treatment prevented ACR and facilitate blood and graft Treg expansion. Remarkably, recipients who achieved Treg expansion within the graft remained free of ACR even after discontinuation of the immunosuppressant treatment and this phenomenon was associated with increased levels of serum IL-10. Conclusion Our clinical and experimental findings underscore the association between Treg frequency and graft rejection after ITx, advocating for strategies that promote their expansion within the gut mucosa to enhance long-term outcomes.