Nectin-4-directed antibody-drug conjugates (ADCs): Spotlight on preclinical and clinical evidence.

Nectin-4 (Nectin cell adhesion molecule 4), a type I transmembrane cell adhesion protein, was demonstrated to be overexpressed in a variety of tumors, making it an attractive antigen for targeted therapies such as antibody-drug conjugates (ADCs). Of great note, the US Food and Drug Administration (FDA)-approval of the first Nectin-4-directed ADC, enfortumab vedotin (EV), in urothelial cancer (UC) not only introduced Nectin-4 as a clinically validated and reliable target antigen but also confirmed the evolving role of Nectin-4-directed ADCs as novel and promising cancer therapeutics. In addition to EV, there have been or are currently being seven and eleven Nectin-4-directed ADCs, respectively, in various stages of clinical trials and preclinical development, offering a promising future for the treatment of Nectin-4-positive cancer patients. This study reviewed clinical- and preclinical-stage Nectin-4-directed ADCs.

Developing a label-free full-range highly selective pH nanobiosensor using a novel high quantum yield pH-responsive activated-protein-protected gold nanocluster prepared by a novel ultrasonication-protein-assisted procedure.

A novel, label-free, ultra-selective, reproducible, and reversible pH nanobiosensor was developed for analyzing biofluids, food samples, and real water media utilizing a novel activated-protein-protected gold nanocluster with an ultra-narrow emission band, termed as ABSA-AuNCs. The ABSA-AuNCs were synthesized via a novel ultrasonication-protein-assisted procedure, for the first time, using activated bovine serum albumin as both capping and reducing agents. The ABSA-AuNCs revealed a highly narrow symmetric emission spectrum (λmax = 330.0 nm upon excitation at 312-317 nm), and a highly narrow size distribution of 2.9-3.7 nm along with an enhanced quantum yield of 28.3 %. At present, with a full width at half maximum (FWHM) of 14.0 nm, ABSA-AuNCs have the narrowest bandwidth of fluorescent nanomaterials reported to date. The ABSA-AuNCs were characterized for their stability, size, morphology, crystallinity, structural, and optical properties. The ABSA-AuNCs were found to be appropriate for constructing a label-free ultraselective pH nanobiosensor. A linear range over 2.0-11.0, fast response time of less than 5 s, and long-term stability of 99.7 % after 500 min were achieved. The %RSD for repeatability, intra-day reproducibility, and inter-day reproducibility was found to be 1.4 %, 1.7 %, and 2.3 %, in order, to reveal high repeatable and reproducible results. The selectivity of the pH biosensor was evaluated upon the addition of different interferents, indicating an excellent pH selectivity for the ABSA-AuNCs. Real sample analysis proved the feasibility of the ABSA-AuNCs for accurate, precise, and reliable pH sensing in biofluids (undiluted blood and urine), a variety of food samples, and several real water samples.

A novel biomechanical index for quality assessment of the upper-extremity movements in post-stroke patients.

BACKGROUND: While motor recovery is preferred to compensatory movements for stroke patients with mild to moderate motion impairment, current movement quality assessments rarely reflect the differences between a patient's pre- and post-stroke movement patterns. Such comparison can help therapists to identify the rate of the restoration of premorbid motion patterns and prescribe the most effective treatment. METHODS: This paper attempted to present a new biomechanical metric for the quality of upper-limb movements which uses the subject's optimal movements as a reference to evaluate his/her UL movement quality. To this end, an inverse optimal control algorithm was applied to find an estimation of the patient's premorbid motion patterns. The new biomechanical index was then calculated as a measure of similarity between the optimal and actual movement trajectories. In the next part, various simulation and clinimetric investigations were performed to evaluate the responses of the new index to variations of the movement quality as well as its test-retest reliability and concurrent validity. RESULTS: Simulation-based analyses demonstrated that the proposed index, in contrast to the previous popular biomechanical indices, can successfully detect a wide range of abnormalities in motion signals. In addition, it showed good test-retest reliability (ICC = 0.89) and moderate correlation with clinical indices, Fugl-Meyer Assessment (r = 0.66), Action Research Arm Test (r = 0.47), and ABILHAND (r = 0.27). CONCLUSIONS: Although the proposed index has the same degree of clinimetric properties as the previous metrics, the ability to identify the level of movement restoration and also various types and severities of motor disabilities may lead to better design and management of motor rehabilitation.

Mortality in Recipients of Durable Left Ventricular Assist Devices Undergoing Ventricular Tachycardia Ablation.

BACKGROUND: Left ventricular assist device (LVAD) recipients have a higher incidence of ventricular tachycardia (VT). However, the role of VT ablation in this population is not well-established. OBJECTIVES: This single-center retrospective cohort study sought to examine the impact of post-LVAD implant VT ablation on survival. METHODS: This retrospective study examined a cohort of patients that underwent LVAD implantation at Baylor St. Luke's Medical Center and Texas Heart Institute between January 2011 and January 2021. All-cause estimated mortality was compared across LVAD recipients based on the incidence of VT, timing of VT onset, and the occurrence and timing of VT ablation utilizing Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Post-implant VT occurred in 53% of 575 LVAD recipients. Higher mortality was seen among patients with post-implant VT within a year of implantation (HR: 1.62 [95% CI: 1.15-2.27]). Among this cohort, patients who were treated with a catheter ablation had superior survival compared with patients treated with medical therapy alone for the 45 months following VT onset (HR: 0.48 [95% CI: 0.26-0.89]). Moreover, performance of an ablation in this population aligned mortality rates with those who did not experience post-implant VT (HR: 1.18 [95% CI: 0.71-1.98]). CONCLUSIONS: VT occurrence within 1 year of LVAD implantation was associated with worse survival. However, performance of VT ablation in this population was correlated with improved survival compared with medical management alone. Among patients with refractory VT, catheter ablation aligned survival with other LVAD participants without post-implant VT. Catheter ablation of VT is associated with improved survival in LVAD recipients, but further prospective randomized studies are needed to compare VT ablation to medical management in LVAD recipients.

Efficacy of liver free and Chitosan against Eimeria tenella in chickens.

Eimeria spp. are the pathogen that causes coccidiosis, a significant disease that affects intensively reared livestock, especially poultry. Anticoccidial feed additives, chemicals, and ionophores have routinely been employed to reduce Eimeria infections in broiler production. Therefore, the shift to antibiotic-free and organic farming necessitates novel coccidiosis preventive strategies. The present study evaluated the effects of potential feed additives, liver free and chitosan, against Eimeria tenella infection in White Leghorn broiler female chickens. One hundred sixty-five 1-day-old White Leghorn broiler female chicks were divided into 11 groups (15 female chicks per group), including the positive control group (G1), the negative control group (G2), a chitosan-treated group (G3), a chitosan-treated-infected group (G4), the liver free-treated group (G5), the liver free-treated-infected group (G6), the liver free-and-chitosan-treated group (G7), the liver free-and-chitosan-infected group (G8), the therapeutic liver free-and-chitosan-treated-infected group (G9), the sulfaquinoxaline-treated group (G10), and the sulfaquinoxaline-treated-infected group (G11). Chitosan was fed to the chicks in G3 and G4 as a preventative measure at a dose of 250 mg/kg. The G5 and G6 groups received 1.5 mg/kg of Liverfree. The G7 and G8 groups received chitosan and Liverfree. The G10 and G11 groups were administered 2 g/L of sulfaquinoxaline. From the moment the chicks arrived at Foshan University (one-day-old chicks) until the completion of the experiment, all medications were given to them as a preventative measure. G8 did; however, receive chitosan and liver free as therapeutic supplements at 7 dpi. The current study showed that the combination of liver free and chitosan can achieve better prophylactic and therapeutic effects than either alone. In E. tenella challenged chickens, G8 and G9 chickens showed reduced oocyst shedding and lesion score, improved growth performance (body weight, body weight gain, feed intake, feed conversion ratio, and mortality rate), and cecal histology. The current study demonstrates that combining liver free and chitosan has superior preventive and therapeutic benefits than either alone, and they could also be used as alternative anticoccidial agents.

Intramuscular Hemangioma of Lateral Rectus Muscle with Rare Presentation as an Epibulbar Mass: A Case Report and Review of Literature.

Introduction: Intramuscular hemangiomas of extraocular muscles are extremely rare tumors that usually present as retro-orbital masses causing proptosis. We describe a previously unreported presentation, in the form of an epibulbar mass; this easily accessible location allows direct imaging, complete surgical resection, and histopathological confirmation, providing a unique perspective. Case Presentation: A 69-year-old woman presented with a painless dark red mass in the lateral part of the right eye, which had been slowly enlarging over the last 18 months. Clinical features and imaging were suggestive of a benign vascular tumor of the conjunctiva. During surgical resection, the mass was observed to be enmeshed within the fibers of the lateral rectus muscle. Careful dissection from muscle fibers was needed for complete excision. Histopathology revealed the diagnosis of an intramuscular hemangioma of extraocular muscle. Conclusion: In this report, we describe the atypical anterior epibulbar presentation of intramuscular hemangioma of the lateral rectus muscle. We discuss the differential diagnoses and management of this rare tumor along with a review of existing literature. Careful surgical resection achieved complete resolution in this case without recurrence.

Effects of Whole-Body Vibration Therapy in Weight-Bearing and Non-Weight Bearing Positions for Upper and Lower Extremities on Balance and Cervical Joint Position Sense in Children With Cerebral Palsy.

INTRODUCTION: Cerebral palsy (CP) is a complex pathological entity that affects muscular control, coordination, proprioception, fine and gross motor abilities, position, stability, and, in some cases, cognition. This study aimed to compare the effects of whole-body vibration therapy (WBVT) in weight bearing and non-weight bearing positions for the upper and lower extremities on balance and cervical joint position sense in children with spastic CP. METHODS: A randomized controlled trial was carried out on 60 hemiplegic children with spastic CP aged 5-15 years. Following randomization, all participants were allocated into six equal-sized groups based on the application of WBVT for upper extremities, lower extremities, or both simultaneously in either weight-bearing or non-weight-bearing positions. Pediatric balance scale (PBS) and laser tracker system were used to assess functional balance and cervical joint position sense. RESULTS: One-way analysis of variance for Inter-group analysis showed a statistically significant difference among all groups in PBS and cervical joint position sense (p<0.05). CONCLUSION: WBVT was found to be beneficial in improving balance and cervical joint position sense in both weight-bearing and non-weight-bearing positions for the upper and lower extremities in children with cerebral palsy. However, the simultaneous application of WBVT in weight-bearing positions for both upper and lower extremities showed the most significant improvements in improving both balance and cervical joint position sense, indicating the most efficacious position of this treatment approach in children with cerebral palsy.

Ameliorative effects of umbelliferone against acetaminophen-induced hepatic oxidative stress and inflammation in mice.

Background and purpose: Acetaminophen (APAP) is a commonly used antipyretic and pain reliever that its overdose causes acute liver toxicity. Umbelliferone (UMB) has many pharmacological effects. In this study, the hepatoprotective effect of UMB on acute hepatotoxicity induced by APAP was investigated. Experimental approach: Forty-nine male mice were separated into seven groups. The control received vehicle (i.p.), UMB group received UMB (120 mg/kg, i.p.), APAP group was treated with a single dose of APAP (350 mg/kg, i.p.), and pretreated groups received N-acetylcysteine (NAC, 200 mg/kg, i.p.) or different doses of UMB (30, 60, and 120 mg/kg, i.p.), respectively before APAP. Twenty-four hours after APAP injection, mice were sacrificed and blood and liver samples were collected. Then, serum and tissue samples were investigated for biochemical and histological studies. Findings/Results: A single dose of APAP caused elevation in the serum liver enzymes, including alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. The amounts of thiobarbituric acid reactive substances, tumor necrosis factor-alpha, and nitric oxide increased in the mice's liver tissue. Moreover, the amount of total thiol and the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) significantly diminished in the APAP group. Histological results confirmed the hepatotoxicity induced by APAP. However, UMB (more effective at 60 and 120 mg/kg) lessened APAP-induced hepatic injuries, which is comparable with NAC effects. Conclusion and implications: The findings of this study provided evidence that UMB ameliorates liver injury induced by APAP through its antioxidant and anti-inflammatory effects.

Masked pre-training of transformers for histology image analysis.

In digital pathology, whole-slide images (WSIs) are widely used for applications such as cancer diagnosis and prognosis prediction. Vision transformer (ViT) models have recently emerged as a promising method for encoding large regions of WSIs while preserving spatial relationships among patches. However, due to the large number of model parameters and limited labeled data, applying transformer models to WSIs remains challenging. In this study, we propose a pretext task to train the transformer model in a self-supervised manner. Our model, MaskHIT, uses the transformer output to reconstruct masked patches, measured by contrastive loss. We pre-trained MaskHIT model using over 7000 WSIs from TCGA and extensively evaluated its performance in multiple experiments, covering survival prediction, cancer subtype classification, and grade prediction tasks. Our experiments demonstrate that the pre-training procedure enables context-aware understanding of WSIs, facilitates the learning of representative histological features based on patch positions and visual patterns, and is essential for the ViT model to achieve optimal results on WSI-level tasks. The pre-trained MaskHIT surpasses various multiple instance learning approaches by 3% and 2% on survival prediction and cancer subtype classification tasks, and also outperforms recent state-of-the-art transformer-based methods. Finally, a comparison between the attention maps generated by the MaskHIT model with pathologist's annotations indicates that the model can accurately identify clinically relevant histological structures on the whole slide for each task.

Adhesion dynamics of Janus nanocarriers to endothelial cells: A dissipative particle dynamics study.

Janus nanocarriers (NCs) provide promising features in interfacial applications such as targeted drug delivery. Herein, we use dissipative particle dynamics simulations to study the adhesion dynamics of NCs with Janus ligand compositions to the endothelial cell as a function of a series of effects, such as the initial orientation, ligand density, shape, and size of Janus NCs. The Janus NCs, with its long axis parallel to the endothelial glycocalyx (EG) layer, has the best penetration depth due to its lower potential energy and the lowest shell entropy loss. Among different shapes of Janus NCs, both the potential energy and the EG entropy loss control the penetration. In fact, at the parallel orientations, Janus shapes with a robust mechanical strength and larger surface area at the EG/water interface can rotate and penetrate more efficiently. An increase in the ligand density of Janus NCs increases entropy losses of both the hydrophilic and the hydrophobic ligands and decreases the potential energy. Thus, for a specific Janus NCs, functionalizing with an appropriate ligand density would help driving forces prevail over barriers of penetration into the EG layer. For a particular ligand density, once the radius of the Janus NCs exceeds the appropriate size, barriers such as hydrophobic ligands and shell entropy losses are also reinforced significantly and surpass driving forces. Our observations reveal that entropy losses for hydrophobic ligands of Janus NCs and for the shell of NCs are decisive for the adhesion and penetration of Janus NCs to endothelial cells.

Impact of Denture Use on Oral Health-Related Quality of Life in Yemeni Patients: A Cross-Sectional Analysis.

BACKGROUND We used the 14-item Oral Health Impact Profile-14 (OHIP-14) questionnaire to evaluate the association between sociodemographic variables and oral health-related quality of life in 241 wearers of removable partial or complete dentures attending a single center in Yemen. MATERIAL AND METHODS A total of 241 partial dentures (PD) and complete dentures (CD) wearers were enrolled from the Department of Prosthodontics at the Faculty of Dentistry, Sana'a University, and the University of Science and Technology. Data were collected before the commencement of denture wearing and after 3-6 months of denture use. The questionnaire consisted of sociodemographic information and denture type, and another for the OHIP to assess oral health-related quality of life (OHRQoL), oral health impact profile scale comprises 7 subscales, each evaluating different aspects of oral health and functionality. Descriptive statistics were calculated for participants. Independent t tests were performed to compare different patient groups, focusing on PD and CD wearers. Paired-sample t tests were used to examine changes within patient groups before and after removable denture use. RESULTS Among all participants, 67.6% were male, wearers of CDs were 74.6% male, PDs were 58.3%, and was consistent for CD (71.0%) and PD (72.8%) wearers. The wearing prostheses significantly impacted the OHRQoL of patients using both PDs and CDs (P<0.01). Among CD wearers, 4 of these subscales (3-6) were statistically significant, but the handicaps subscale showed evident reductions in physical pain after treatment among PD wearers. CONCLUSIONS Wearing dentures positively affects the OHRQoL of patients, influencing various aspects of their health, including functional, physical, psychological, and social well-being.

On-demand activatable peroxidase-mimicking enzymatic polymer nanocomposite films.

Nanozymes continue to attract considerable attention to minimise the dependence on expensive enzymes in bioassays, particularly in medical diagnostics. While there has been considerable effort directed towards developing different nanozymes, there has been limited progress in fabricating composite materials based on such nanozymes. One of the biggest gaps in the field is the control, tuneability, and on-demand catalytic response. Herein, a nanocomposite nanozymatic film that enables precise tuning of catalytic activity through stretching is demonstrated. In a systematic study, we developed poly(styrene-stat-n-butyl acrylate)/iron oxide-embedded porous silica nanoparticle (FeSiNP) nanocomposite films with controlled, highly tuneable, and on-demand activatable peroxidase-like activity. The polymer/FeSiNP nanocomposite was designed to undergo film formation at ambient temperature yielding a highly flexible and stretchable film, responsible for enabling precise control over the peroxidase-like activity. The fabricated nanocomposite films exhibited a prolonged FeSiNP dose-dependent catalytic response. Interestingly, the optimised composite films with 10 wt% FeSiNP exhibited a drastic change in the enzymatic activity upon stretching, which provides the nanocomposite films with an on-demand performance activation characteristic. This is the first report showing control over the nanozyme activity using a nanocomposite film, which is expected to pave the way for further research in the field leading to the development of system-embedded activatable sensors for diagnostic, food spoilage, and environmental applications.

The effectiveness of the WHO school mental health package in promoting mental health literacy among secondary school teachers in Qatar: a randomized controlled trial.

Teachers' mental health literacy (MHL) is fundamental for recognizing and assisting students with mental disorders. The aim of this study was to assess the effectiveness of the World Health Organization School Mental Health Program (WHO-SMHP) in promoting MHL among secondary schools' teachers in Qatar. We conducted a two-arm randomized control trial. Teachers working in governmental secondary schools were eligible for selection. A total of 16 schools (8 intervention, 8 control) randomly selected and stratified by gender then randomly assigned (1:1). Participants and study team were aware of group assignment. Assessment of teachers' MHL was at day 0, 3 then 3 months afterward. Bivariat analysis and Generalized Estimating Equations were used in analysis. The primary outcome was teachers MHL. Secondary outcome was the influence of sociodemographic characteristics on the level of MHL. Between October 30, 2018 and March 21, 2019, we randomly assigned 195 teachers from 16 schools to attend training workshop on WHO-SMHP (n = 95) or usual practice (n = 100). Compared with controls, teachers from intervention group demonstrated a significant improvement in the level of MHL at day three (mean difference = 19.1, 95% CI = 17.0-21.2, Cohen's d = 2.63; p < 0.001).) and after three months (mean difference 16.61, 95% CI = 13.96-19.26, Cohen's d = 1.86; p < 001). There were no significant differences related to influence of other variables on MHL. To our knowledge, this is the first trial to prove the effectiveness of the (WHO-SMHP) in promoting teachers MHL, which can be successfully implemented in a wider scale.

Rhodopsin-based light-harvesting system for sustainable synthetic biology.

Rhodopsins, a diverse class of light-sensitive proteins found in various life domains, have attracted considerable interest for their potential applications in sustainable synthetic biology. These proteins exhibit remarkable photochemical properties, undergoing conformational changes upon light absorption that drive a variety of biological processes. Exploiting rhodopsin's natural properties could pave the way for creating sustainable and energy-efficient technologies. Rhodopsin-based light-harvesting systems offer innovative solutions to a few key challenges in sustainable engineering, from bioproduction to renewable energy conversion. In this opinion article, we explore the recent advancements and future possibilities of employing rhodopsins for sustainable engineering, underscoring the transformative potential of these biomolecules.

Genotypes, epidemiological variables and fungicides application associated with wheat leaf rust development and grain yield.

The present study was carried out at the Plant Pathology Hafizabad Research Station, the University of Layyah, during the crop seasons 2021-2022 and 2022-2023 to evaluate the response of various wheat genotypes against leaf rust severity (%), environmental conditions favourable for disease development and grain yield. Except for minimum temperature and minimum relative humidity, which had a negative association with disease development, there was a significant correlation between leaf rust severity (%) and all environmental conditions such as maximum temperature, maximum relative humidity, rainfall, and wind speed. All epidemiological variables such as maximum temperature, minimum temperature, minimum relative humidity, rainfall and wind speed significantly affect the disease progression. The disease predictive model accounted for 48-69 % variability in leaf rust severity. The model performance was evaluated using the coefficient of determination (R2 = 0.69) and RMSE, both demonstrated acceptable predictive results for leaf rust severity (%) management. Leaf rust severity (%) increased with an increase in maximum temperature (17.8-30 °C), maximum relative humidity (76.3-85 %), rainfall (2.2-10.85 mm) and wind speed 1.1-2.7 km/h and decreased with the increase of minimum temperature (7.91-16.71 °C) minimum relative humidity (47.15-56.45 %) during both rating seasons 2021-2022 and 2022-2023. The single and two applications of fungicides at the Zadok's scale 3, ZS 4.3, and ZS 5.4 stages led to a significant reduction in grain yield losses caused by leaf rust severity (%) in both the 2021-2022 and 2022-2023 crop seasons. Single and two sprays of prothioconazole, were found to be the first choice among all treatments to reduce the disease severity and increase grain production and maximum gross revenue (513.1-777.8$/ha), as compared to followed by single and two sprays of propiconazole (Progress), tebuconazole + trifloxystrobin, tebuconazole, bixafen + tebuconazole, and propiconazole (Tilt), respectively. These findings recommend the involvement of genotype resistance and weather predictors in wheat leaf rust development, along with fungicide application studies, to improve the predictability of host resistance to disease, future models, and the sustainability of disease control methods.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients.

INTRODUCTION: Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. MATERIAL AND METHOD: MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. RESULT: Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = -.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). CONCLUSION: An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.

Assessment of heavy metal levels in polyculture fish farms and their aquatic ecosystems: an integrative study addressing environmental and human health risks associated with dam water usage.

This study examines the levels of heavy metals in polyculture fish (Labeo rohita, Cyprinus carpio, and Catla catla), water, and sediment in Tanda Dam, Kohat, Pakistan, aiming to understand environmental and health risks. Samples of fish, water, and sediment were collected from 3 fish farms, and heavy metal concentrations were measured using a Flame Atomic Absorption Spectrophotometer (AAS). Results reveal that C. catla exhibited significantly higher (p < 0.05) levels of Zn than other fish species. Conversely, C. carpio showed significantly higher (p < 0.05) concentrations of Pb, Cd, Cr, Mn, Cu, As, and Ni than other species. The heavy metal hierarchy in C. carpio was found to be Zn > Cu > Pb > Cr > Cd > Mn > As > Ni. While heavy metal levels in L. rohita and C. catla generally fell within reference ranges, exceptions were noted for Zn, Pb, and Cd. Conversely, in C. carpio, all metals exceeded reference ranges except for Cu and Ni. Principal Component Analysis (PCA) indicated a close relationship between water and sediment. Additionally, cluster analysis suggested that C. catla formed a distinct cluster from L. rohita and C. carpio, implying different responses to the environment. Despite concerns raised by the Geoaccumulation Index (Igeo) and Contamination Factor (CF), particularly for Cd, which exhibited a high CF. Furthermore, Hazard Index (HI) values for all three fish species were below 1, suggesting low health risks. However, elevated Igeo and CF values for Cd suggest significant pollution originating from anthropogenic sources. This study underscores the importance of monitoring heavy metals in water for both environmental preservation and human health protection. Future research efforts should prioritize pollution control measures to ensure ecosystem and public health safety.

Personalized evaluation of the passive myocardium in ischemic cardiomyopathy via computational modeling using Bayesian optimization.

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure-volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine.