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Providing appropriate home health care is one of the increasing concerns in the health care organizations. Home health care provides various services for disabled or elderly individuals at their homes. Also, dealing with the current critical situation of the coronavirus disease (COVID-19) due to the limited capacity of hospitals and the feeling of insecurity in crowded places, home health care is more recommended. This paper addresses a Home Health Care Routing and Scheduling Problem (HHCRSP) with two modes of transportations including public and private modes. Also, multi-depot version of the problem is studied to enhance the service delivery in scattered points. In this study, a mathematical model is presented based on a Mixed Integer Linear Programming (MILP) whose objective function is minimization of the sum of the travel distance and overtime costs. Furthermore, three meta-heuristic algorithms including Invasive Weed Optimization (IWO), Grasshopper Optimization Algorithm (GOA), and Simulated Annealing (SA) are presented for solving large-sized problems. Since the performance of meta-heuristic algorithms depends on setting the parameters, the Taguchi method is used to statistically set parameters of the developed algorithms. The computational results have shown that the proposed IWO has worked better than the other two proposed algorithms statistically. [ABSTRACT FROM AUTHOR]

Bug Algorithms in robotics field play an important role in path planning. The main challenge in conventional bug algorithms is searching the cluttered environment. To solve this problem a method is introduced which uses the concept of swarm robotics that helps in finding path using coordination between robots in swarm. The challenge in this research article is to find a path which is heuristically optimal. A type of bug algorithm is introduced in which parent bug sends two of its child bugs. Each of them has capability of searching in different directions. After searching the path from both sides, parent bug follows the path which is heuristically optimal. Parent and child bugs are equipped with tactile sensors to follow the perimeter of an obstacle. Illustrative simulation results show two test cases in which different scenarios are presented. Results are compared with of bug0 algorithm that is visualized in configuration space as well as in workspace to find the heuristically optimal path.

Dust particles and their associated compounds can adversely affect human health and ecosystems. The aim of this study was to investigate the concentration, health, and ecological risks of selected potentially toxic elements (e.g. Pb, Cd, Cr, Co, Cu, Zn, V, Ni, and As) bound to air particles generated by dust storms in the Sejzi plain desert area within the industrial district of Isfahan metropolitan, Iran. The enrichment factor revealed the highest values for Zn, Pb, and Cd which among them Zn showed the highest value (8.1) with the potential source of industrial activities confirmed by the integrated pollution index, accumulation coefficient, and ecological risk index. Regarding health risk analysis (non-cancer and cancer risks) the elements including Co, As, and Cr showed a significant risk for adults and children across all seasons. It's concluded that mitigation of air particles originated from both natural and industrial activities is necessary to reduce their relevant risks to human being and ecosystems in the region., (© 2024. The Author(s).)

Introduction: To the best of our knowledge, clinically significant endogenous ethylene glycol production has never been reported in humans, very seldom reported in other animals or microorganisms, and then only under rare and specific conditions. We describe the detailed investigations we undertook in two adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol., Methods: Two previously healthy monozygotic adult twin sisters presented with recurrent episodes of apparent ethylene glycol poisoning beginning at age 35, requiring chronic hemodialysis to remove ethylene glycol and its metabolites as well as to restore metabolic homeostasis. The sisters denied ingestion or exposure to ethylene glycol. At their request, they were admitted to hospital under strict supervision to exclude surreptitious ingestion of ethylene glycol and to evaluate the need for treatment. Hemodialysis was withheld during this prospective study. Twin A was admitted for 14 days and twin B for 11 days. Serial biochemical analyses were performed in blood and urine. Clinical exome sequencing and mitochondrial deoxyribonucleic acid sequencing were also completed., Results: In both twins, ethylene glycol was detected in urine, along with intermittent increases in concentrations of lactate, glycolate, and glycine in blood and/or urine. Blood ethylene glycol concentrations, however, remained <62 mg/L (<1 mmol/L) but became positive soon after discharge. The oxalate concentration remained normal in blood and urine. Plasma and urine amino acid profiles showed intermittent small increases in glycine, serine, taurine, proline, and/or alanine concentrations. Exome sequencing and mitochondrial deoxyribonucleic acid sequencing were non-diagnostic. Neither twin has been admitted with metabolic acidosis nor ethylene glycol poisoning since chronic hemodialysis was started. Twin A developed a calcium oxalate dihydrate lithiasis., Discussion: Mitochondrial disease, methylmalonic/propionic/isovaleric aciduria, primary hyperoxaluria, and analyte error were all excluded in these twins, as were obvious common environmental exposures., Conclusion: Detailed investigations were performed in adult monozygotic twin sisters to ascertain whether they were producing endogenous ethylene glycol. Alternative explanations were excluded to the very best of our efforts and knowledge. Global metabolomics, gut microbiome analyses, and whole genome sequencing are pending.

The objective of this study was to screen air pollution-induced stress in some plant species in the Sejzi industrial region (Isfahan, Iran). An assessment of APTI and other physiological and biochemical features of significant species in the area was conducted across three seasons: spring, summer, and autumn. The physiological and biochemical factors of the following species were evaluated: Limonium persicum, Atriplex lentiformis, Nitraria schoberi, Haloxylon persicum, Tamarix hispida, Zygophyllum atriplicoides, Karelinia caspica, and Prosopis farcta. The physiological factors assessed included acidity and relative humidity content, while the biochemical factors assessed included proline, sugar, ascorbic acid, and total chlorophyll. Subsequently, a thorough evaluation was carried out on the species under investigation to ascertain their biomonitors' capabilities and APTI. The study findings indicated that the species P. farcta, N. schoberi, and K. caspica consistently had high APTI values during the spring, autumn, and summer seasons, classifying them as tolerant plant species. Conversely, the observed traits showed significant fluctuations across the seasons. The investigation's findings indicate that the species L. persicum, N. schoberi, and K. caspica exhibit higher annual averages of chlorophyll a, chlorophyll b, total chlorophyll, and carotenoid compared to other species. The examination of the annual variation in the tolerance levels of plant species to pollution ranked from highest to lowest was as follows: N. schoberi, P. farcta, K. caspica, Z. atriplicoides, H. persicum, T. hispida, L. persicum, and A. lentiformis. Moreover, based on the annual average, the primary determinants that impact the APTI in the species being studied include ascorbic acid (35%), leaf acidity (19%), total chlorophyll content (35%), and relative humidity content (69%). Furthermore, a distinct and significant correlation was found between proline and sugar levels and the annual APTI values. Additionally, the species P. farcta had the highest API compared to other species. The study revealed the high potential of some plant species against air pollution induced stress which can be used in air and dust pollution management in the region., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown., Methods: All patients with pathogenic/likely pathogenic (P/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine-Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes., Results: Eight hundred patients [40.3 ± 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 ± 13.9%] were included. Over 3.7 [1.4-7.1] years, 139 (17.4%, 3.9%/year) and 72 (9.0%, 1.8%/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF ≤ 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF ≤ 50% (aHR 3.879; P < .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P < .001, and HR 5.064, P < .001, respectively)., Conclusions: Patients with P/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF ≤ 50%, and myocardial injury events., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Pathogenic desmoplakin (DSP) gene variants are associated with the development of a distinct form of arrhythmogenic cardiomyopathy known as DSP cardiomyopathy. Patients harbouring these variants are at high risk for sustained ventricular arrhythmia (VA), but existing tools for individualized arrhythmic risk assessment have proven unreliable in this population., Methods: Patients from the multi-national DSP-ERADOS (Desmoplakin SPecific Effort for a RAre Disease Outcome Study) Network patient registry who had pathogenic or likely pathogenic DSP variants and no sustained VA prior to enrolment were followed longitudinally for the development of first sustained VA event. Clinically guided, step-wise Cox regression analysis was used to develop a novel clinical tool predicting the development of incident VA. Model performance was assessed by c-statistic in both the model development cohort (n = 385) and in an external validation cohort (n = 86)., Results: In total, 471 DSP patients [mean age 37.8 years, 65.6% women, 38.6% probands, 26% with left ventricular ejection fraction (LVEF) < 50%] were followed for a median of 4.0 (interquartile range: 1.6-7.3) years; 71 experienced first sustained VA events {2.6% [95% confidence interval (CI): 2.0, 3.5] events/year}. Within the development cohort, five readily available clinical parameters were identified as independent predictors of VA and included in a novel DSP risk score: female sex [hazard ratio (HR) 1.9 (95% CI: 1.1-3.4)], history of non-sustained ventricular tachycardia [HR 1.7 (95% CI: 1.1-2.8)], natural logarithm of 24-h premature ventricular contraction burden [HR 1.3 (95% CI: 1.1-1.4)], LVEF < 50% [HR 1.5 (95% CI: .95-2.5)], and presence of moderate to severe right ventricular systolic dysfunction [HR 6.0 (95% CI: 2.9-12.5)]. The model demonstrated good risk discrimination within both the development [c-statistic .782 (95% CI: .77-.80)] and external validation [c-statistic .791 (95% CI: .75-.83)] cohorts. The negative predictive value for DSP patients in the external validation cohort deemed to be at low risk for VA (<5% at 5 years; n = 26) was 100%., Conclusions: The DSP risk score is a novel model that leverages readily available clinical parameters to provide individualized VA risk assessment for DSP patients. This tool may help guide decision-making for primary prevention implantable cardioverter-defibrillator placement in this high-risk population and supports a gene-first risk stratification approach., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Restoring motor function after stroke necessitates involvement of numerous cognitive systems. However, the impact of damage to motor and cognitive network organization on recovery is not well understood. To discover correlates of successful recovery, we explored imaging characteristics in chronic stroke subjects by combining noninvasive brain stimulation and fMRI. Twenty stroke survivors (6 months or more after stroke) were randomly assigned to a single session of transcranial direct current stimulation (tDCS) or sham during image acquisition. Twenty healthy subjects were included as controls. tDCS was limited to 10 min at 2 mA to serve as a mode of network modulation rather than therapeutic delivery. Fugl-Meyer Assessments (FMA) revealed significant motor improvement in the chronic stroke group receiving active stimulation (p = 0.0005). Motor changes in this group were correlated in a data-driven fashion with imaging features, including functional connectivity (FC), surface-based morphometry, electric field modeling and network topology, focusing on relevant regions of interest. We observed stimulation-related changes in FC in supplementary motor (p = 0.0029), inferior frontal gyrus (p = 0.0058), and temporo-occipital (p = 0.0095) areas, though these were not directly related to motor improvement. The feature most strongly associated with FMA improvement in the chronic stroke cohort was graph topology of the dorsal attention network (DAN), one of the regions surveyed and one with direct connections to each of the areas with FC changes. Chronic stroke subjects with a greater degree of motor improvement had lower signal transmission cost through the DAN (p = 0.029). While the study was limited by a small stroke cohort with moderate severity and variable lesion location, these results nevertheless suggest a top-down role for higher order areas such as attention in helping to orchestrate the stroke recovery process., (© 2024. The Author(s).)

The over-activation of tryptophan (Trp) metabolism to kynurenine (Kyn) catalyzed by Indoleamine 2,3-dioxygenase-1 (IDO1) enzyme, is one of the main metabolic pathways involved in tumor microenvironment (TME) immune escape and cancer treatment failure. The most efficient of IDO1 inhibitors is Epacadostat (EPA). Since monotherapy with single-agent IDO1 inhibitor regimen has led to an insufficient anti-tumor activity, we examined the efficacy of simultaneous treatment by Liposomal epacadostat (Lip-EPA) as a potent IDO inhibitor, in combination with docetaxel (DTX) as a complement immunogenic cell death (ICD) agent against B16F10 model. First, the in vitro combination index (CI) of epacadostat (EPA) and DTX was investigated by using the unified theory. Then, the in vivo efficacy of the combination therapy was assessed. Results indicated the synergestic cytotoxic effect of the combination on B16F10 compared to normal fibroblast cells (NIH). The immune profiling demonstrated a significant increase in the percentage of infiltrated T lymphocytes and IFN-γ release, a significant decrease in the percentage of regulatory T cells (Treg) population and the subsequent low levels of IL-10 generation in mice treated with Lip-EPA + DTX. Further, a significant tumor growth delay (TGD = 69.15 %) and an increased life span (ILS > 47.83 %) was observed with the combination strategy. Histopathology analysis revealed a remarkable increase in the Trp concentration following combination treatment, while Kyn levels significantly decreased. Results showed that the nano-liposomal form of IDO1 inhibitor in combination with chemotherapy could significantly improve the imunity response and dominate the tumor immuno-suppressive micro-environment, which merits further investigations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Accurate assessment of the bone supporting the implant is crucial. Early detection of bone defects around the implant can prevent the loss of bone support that ultimately leads to the loss of the implant. Therefore, the purpose of this study is to check the accuracy of CBCT in detecting peri-implant fenestrations around the implant., Materials & Methods: In this laboratory study, healthy beef ribs were used. The ribs were divided into three groups of 12 (control group, 1-2 mm fenestration group, and 2-3 mm fenestration group). The blocks were cut to a length of 20 mm and 36 osteotomies with dimensions of 4 × 12 mm were made by the periodontist in order to place the implant in these bone blocks. Then the titanium implant was placed in the holes and the initial scan was performed with CBCT. In the second group, fenestration-like lesions were created on the same buccal side at a distance of 10 mm from the crest with a diameter of 1-2 mm and in the third group with a diameter of 2-3 mm, and the CBCT scan was performed again with the same parameters. Two radiologists evaluated the images twice for the presence and absence of fenestration., Results: There was no statistically significant difference between direct measurements and CBCT in the fenestration group of 1-2 mm (p < 0.05), but there was a significant difference between direct measurements and CBCT in the fenestration group of 2-3 mm and underestimation was observed in CBCT measurements., Conclusion: The findings of this study showed that CBCT radiography has a higher accuracy in measuring the fenestration around the implant with a smaller diameter and has an acceptable diagnostic value in detecting bone loss around the implant., (© 2024. The Author(s).)

Background and Purpose: The first-generation photon-counting detector CT was recently introduced into clinical practice and represents a promising innovation in high-resolution CT imaging. The purpose of this study was to assess the image quality of ultra-high-resolution photon-counting detector CT compared with energy-integrating detector CT and to explore different reconstruction kernel sharpness levels for the evaluation of intracranial aneurysms., Materials and Methods: Ten patients with intracranial saccular aneurysms who had previously undergone conventional energy-integrating detector CT were prospectively enrolled. CT angiograms were acquired on a clinical dual-source photon-counting detector CT in ultra-high-resolution mode and reconstructed with 4 vascular kernels (Bv36, Bv40, Bv44, Bv48). Quantitative and qualitative image-quality parameters of the intracranial arteries were evaluated. For the quantitative analysis (image noise, SNR, contrast-to-noise ratio), ROIs were manually placed at standard anatomic intracranial and extracranial locations by 1 author. In addition, vessel border sharpness was evaluated quantitatively. For the qualitative analysis, 3 blinded neuroradiologists rated photon-counting detector CT and energy-integrating detector CT image quality for the evaluation of the intracranial vessels (ie, the aneurysms and 9 standard vascular branching locations) on a 5-point Likert-type scale. Additionally, readers independently selected their preferred kernel among the 4 kernels evaluated on photon-counting detector CT., Results: In terms of quantitative image quality, Bv48, the sharpest kernel, yielded increased image noise and decreased SNR and contrast-to-noise ratio parameters compared with Bv36, the smoothest kernel. Compared with energy-integrating detector CT, the Bv48 kernel offered better quantitative image quality for the evaluation of small intracranial vessels ( P  < .001). Image-quality ratings of the Bv48 were superior to those of the energy-integrating detector CT and not significantly different from ratings of the B44 reconstruction kernel. When comparing side by side all 4 photon-counting detector reconstruction kernels, readers selected the B48 kernel as the best to visualize the aneurysms in 80% of cases., Conclusions: Ultra-high-resolution photon-counting detector CT provides improved image quality for neurovascular imaging. Although the less sharp kernels provided superior SNR and contrast-to-noise ratio, the sharpest kernels delivered the best subjective image quality on photon-counting detector CT for the evaluation of intracranial aneurysms., (© 2024 by American Journal of Neuroradiology.)

Kearns-Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder. It is caused by mitochondrial DNA (mtDNA) rearrangements, mostly large-scale deletions of 1.1-10 kb. These deletions primarily affect energy supply through impaired oxidative phosphorylation and reduced ATP production. This impairment gives rise to dysfunction of several tissues, in particular those with high energy demand like brain and muscles. Over the past decades, changes in respiratory chain complexes and energy metabolism have been emphasized, whereas little attention has been paid to other reports on ROS overproduction, protein synthesis inhibition, myelin vacuolation, demyelination, autophagy, apoptosis, and involvement of lipid raft and oligodendrocytes in KSS. Therefore, this paper draws attention towards these relatively underemphasized findings that might further clarify the pathologic cascades following deletions in the mtDNA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multiple Epiphyas species inhabit southwestern Western Australia, including Light Brown Apple Moth (LBAM) Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), a globally significant, polyphagous pest. This study evaluated the efficacy and specificity of lures designed for 3 Epiphyas species: E. postvittana, Epiphyas pulla (Turner), and the undescribed Epiphyas sp. (1) (Common). Additionally, the study sought to determine the presence and distribution of Epiphyas species in 3 significant apple-growing localities. Trapping, together with partial sequencing of the mitochondrial COI gene, found LBAM to be restricted to the Perth Hills and E. pulla, to apple orchards near Manjimup and Pemberton. This geographic disjunction remains unexplained. Epiphyas sp. (1) was not recorded despite using a specifically designed lure. The E. pulla and LBAM traps demonstrated superior efficacy in capturing their target species, while the catch in Epiphyas sp. (1) traps did not significantly differ between the 2. Both E. pulla and LBAM exhibited peak abundance from late spring to the end of summer (October-February), with variations in timing and peak catch of male moths across species, locations, and years. Surveys conducted in April during the harvest period (February-May), when moth traps caught an average of 1-1.8 moths/trap/week, found no Epiphyas larvae or damage on 140,400 mature apples or on 26,000 leaves. While E. pulla and LBAM traps effectively monitor their target moths, genetic identification of trap catch would be necessary if they co-occurred. Encouragingly, the results indicate that both species become relatively rare as harvest season approaches, and neither inflicts significant damage to mature apples under existing management., (© The Author(s) 2024. Published by Oxford University Press on behalf of Entomological Society of America.)

Iron (Fe) is fundamental to life on earth. In the human body, it is both essential and harmful if above threshold. A similar balance applies to other elements: calcium (Ca), magnesium (Mg), and trace elements including copper (Cu), zinc (Zn), lead (Pb), cadmium (Cd), mercury (Hg), and nickel (Ni). These elements share some proteins involved in the absorption and transport of Fe. Cu and Cd can inhibit Fe absorption, while excess of Fe may antagonize Cu metabolism and reduce ceruloplasmin (Cp). Excessive Fe can hinder Zn absorption and transferrin (Trf) can bind to both Zn and Ni. Ca is able to inhibit the divalent metal transporter 1 (DMT1) in a dose-dependent manner to reduce Fe absorption and low Mg concentrations can exacerbate Fe deficiency. Pb competitively inhibits Fe distribution and elevated Cd absorption reduces Fe uptake. Exposure to Hg is associated with higher ferritin concentrations and Ni alters intracellular Fe metabolism. Fe removal by phlebotomy in hemochromatosis patients has shown to increase the levels of Cd and Pb and alter the concentrations of trace elements in some types of anemia. Yet, the effects of chronic exposure of most trace elements remain poorly understood., (© 2024. The Author(s).)

This study used an integrated approach to mainly assess the water quality of paddy field during cultivation and quantify its equivalent ecological damages. Accordingly, an isolated pilot area with 0.6 ha and subsurface drainage pipes was prepared for flow measurement and multiple pollutant examination (DO, EC, pH, COD, TKN, TN, TP, NO 3 , butachlor) under controlled condition during 94 days of rice cultivation. Based on life cycle impact assessment (LCIA) database, the indices of ReCiPe (2016) were used to convert the examined nutrient and herbicide pollution. Results showed that TKN and TP were significant pollutants and reached the maximum concentrations of 7.2 and 4.9 mg/L in pilot outflow, respectively. Here, their average discharged loads were 56.2 gN/day and 45.3 gP/day. These loads equal leaching 8.5% and 9.4% of applied urea and phosphate fertilizers, respectively. The nutrient export coefficients were 8.4 kgN/ha and 6.8 kgP/ha. Nevertheless, the majority of this pollution was transferred by inflow. The net export coefficients were 0.3 kgN/ha and 2.6 kgP/ha while net leaching rates were 0.3%TN and 3.3%TP. The trend of combined ecological damages also showed that the 11-17th day of cultivation imposed the highest ecological risks. The state-of-the-art index of ecological footprint per food production estimates the equivalent ratio of lost lives by impaired ecosystem against lives saved from starvation. This index showed that 7% of the potential of produced paddy rice in this area for saving lives would be spoiled by releasing pollution to the terrestrial ecosystem in the long term. Yet, it can be enhanced as a matter of direct discharge to the freshwater. Therefore, using suitable agricultural operations or improving farm management practices for pollution abatement or assimilation potential is highly recommended., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: The aim of this article was to investigate whether Schirmer strips gathered during clinical dry eye examinations can be prepared for omics analyses in a standardized way, to adjust for variations in tear volume and enable two separate omics analyses from the same sample. In addition, the intention was to investigate whether fluorescein dye instillation in the eyes gave bias effects on metabolomic analysis., Methods: Twelve samples from six individuals, with normal or reduced tear production, were collected. Half of the samples were harvested after instillation of fluorescein in the eye. Each strip was divided in half along the length and prepared with a new method for extracting tear content from the Schirmer strip. The new method was established to compensate for different dilutions of metabolites in varying Schirmer strip wetting levels when using identical extraction volume for all samples. Metabolomic data were compared in samples with and without fluorescein dye and Schirmer strips ranging from 1 to 35 mm wetting levels using a global LC-MS method., Results: All samples were successfully analyzed with an average of ∼350 relevant features detected per sample after using both positive and negative electrospray ionization mode, despite low tear volumes in some samples and that only one half of the Schirmer strips were used. Principal component analysis plots and heatmaps revealed no bias effects of fluorescein dye presence or different Schirmer strip values when using the proposed method., Conclusion: A high number of relevant metabolomic features can be extracted from longitudinally cut halves of Schirmer strips, which may enable analyses with more than one omics modality from the same sample. With the pre-analytical method described, Schirmer strips can be used for metabolomic analyses even in cases of very low or high tear volume with or without fluorescence.

Transmission of fungi in the air and its impact on health are regarded as important public health issues. Bioaerosols play an important role in causing or exacerbating infectious diseases, acute toxic effects, allergies, and cardiopulmonary symptoms. As many people use the public transportation system daily, it is necessary to determine the type and manner of dispersal and abundance of airborne fungi in public transport places. Three public transportation systems including a bus station, a train station, and an airport in Ahvaz city (Iran) were examined. At each of these stations, the air samples were taken from inside and outside the hall stations, and in-vehicle. A bio-stage Anderson sampler was used by suctioning air and passing it over a Petri dish containing culture medium Sabouraud Dextrose Agar (SDA). Relative humidity (RH, %), temperature (T, ◦ C), and mass concentration of particulate matter (PM 1 , PM 2.5 , and PM 10, μg/m 3 ) at the sampling points were measured. The highest concentration of airborne fungi was observed in the airport. The concentration of fungi in the ambient air was higher than that in the indoor air of halls and in-vehicle. In all sampling points, the ambient predominant airborne fungi were Cladosporium and Alternaria, while the indoor predominant airborne fungi were Cladosporium, Aspergillus, and Penicillium. The indoor to outdoor ratio showed that the fungi were of an external origin. Due to the influence of the ambient air on indoor air, it is recommended to use proper ventilation and enhance the hygiene level of vehicles in public transportation systems to reduce exposure to environmentally pathogenic bioaerosols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to evaluate the association between Quality of Life (QOL) and independent factors, emphasizing Socio Economic Status (SES) in northwestern Iran. A population-based cross-sectional study was performed within the Persian Traffic safety and health Cohort in 2020. Participants were chosen using stratified random sampling method. The majority of participants (69%) were aged between 30 and 65. Around half of the participants were males (54.44%). Most of the female respondents were categorized as very low and medium levels of SES Based on multiple linear regression analysis, the QOL among females was lower compared to males (β: - 0.92, 95% CI - 1.82 to - 0.22). There was a negative association between SES and QOL; individuals with low and very low levels of SES had a lower QOL than those with a medium level of SES (β: - 4.38, 95% CI - 5.9 to - 2.86) (β: - 2.65, 95% CI - 4.08 to - 1.22). The current study highlights that higher SES and educational levels are positively associated with higher QOL. Conversely, older age, females, and widowed individuals are linked with lower QOL., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this study in silico a candidate diagnostic peptide-based tool was designed in four stages including diagnosis of coronavirus diseases, simultaneously identifying of COVID-19 and SARS from other members of this family, specific identification of SARS-CoV2, and diagnosis of COVID-19 Omicron. Designed candidate peptides consist of four immunodominant peptides from the proteins of the SARS-CoV-2 spike (S) and membrane (M). The tertiary structure of each peptide was predicted. The stimulation ability of the humoral immunity for each peptide was evaluated. Finally, in silico cloning was performed to develop an expression strategy for each peptide. These four peptides have suitable immunogenicity, appropriate construct, and the ability to be expressed in E.coli . These results must be experimentally validated in vitro and in vivo to ensure the immunogenicity of the kit.Communicated by Ramaswamy H. Sarma.

Background: Distraction is one of the main driver's behavioral factors that reduces the performance of the drivers and might increase the accident risk. Distraction while driving holds significant importance, especially among professional drivers, and failure to address this matter may result in adverse implications for traffic safety. The present study was conducted to investigate distraction and related risk factors between two groups of private vehicle drivers and taxi drivers., Methods: This analytical cross-sectional study was carried out in Tabriz, Iran in 2022. The total sample size in this study was 701 taxi drivers, professional drivers, and private vehicle drivers. The independent samples t-test was used to determine the statistically significant difference between groups and its sub-scales between the two studied groups. Moreover, the multivariable linear regression analysis was used to determine the predictors that affect distraction score. The test's level of significance was considered at 0.05., Results: The mean distraction score among taxi drivers surpasses that of private vehicle drivers (2.82 vs. 2.32, p-value<0.05). The drivers with negative scores, over the past year, among private vehicle drivers and taxi drivers were 2.5 % and 5.2 %, respectively (p-value<0.05). A group of taxi drivers exhibits a higher level of distraction while driving and the mean distraction score for private vehicle drivers is lower than that of taxi drivers (β = -0.11, CI 95 %: 0.17, -0.05). Also, a history of damage or injury accidents has a significant impact on distraction while driving (β = 0.12, CI 95 %; 0.06-0.17)., Conclusions: The results indicate that distraction while driving is high amongst taxi drivers rather than private vehicle drivers. To have effective driver safety promotion interventions, it is recommended to consider driver distraction based on professional and non-professional drivers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objectives : The aim of this study was to evaluate Cu-64 PET phantom image quality using Bayesian Penalized Likelihood (BPL) and Ordered Subset Expectation Maximum with point-spread function modeling (OSEM-PSF) reconstruction algorithms. In the BPL, the regularization parameterβwas varied to identify the optimum value for image quality. In the OSEM-PSF, the effect of acquisition time was evaluated to assess the feasibility of shortened scan duration. Methods : A NEMA IEC PET body phantom was filled with known activities of water soluble Cu-64. The phantom was imaged on a PET/CT scanner and was reconstructed using BPL and OSEM-PSF algorithms. For the BPL reconstruction, variousβvalues (150, 250, 350, 450, and 550) were evaluated. For the OSEM-PSF algorithm, reconstructions were performed using list-mode data intervals ranging from 7.5 to 240 s. Image quality was assessed by evaluating the signal to noise ratio (SNR), contrast to noise ratio (CNR), and background variability (BV). Results : The SNR and CNR were higher in images reconstructed with BPL compared to OSEM-PSF. Both the SNR and CNR increased with increasing β , peaking atβ= 550. The CNR for all β , sphere sizes and tumor-to-background ratios (TBRs) satisfied the Rose criterion for image detectability (CNR > 5). BPL reconstructed images with β = 550 demonstrated the highest improvement in image quality. For OSEM-PSF reconstructed images with list-mode data duration ≥ 120 s, the noise level and CNR were not significantly different from the baseline 240 s list-mode data duration. Conclusions : BPL reconstruction improved Cu-64 PET phantom image quality by increasing SNR and CNR relative to OSEM-PSF reconstruction. Additionally, this study demonstrated scan time can be reduced from 240 to 120 s when using OSEM-PSF reconstruction while maintaining similar image quality. This study provides baseline data that may guide future studies aimed to improve clinical Cu-64 imaging., (© 2024 IOP Publishing Ltd.)

Objective: The American Academy of Pediatrics recommends that pediatric providers screen families for food insecurity and connect them to appropriate resources. However, it is unclear how clinics can best provide families with resources consistent with their needs and preferences. In this study, we elicited caregiver preferences for clinic-based food assistance., Methods: We conducted a cross-sectional discrete choice experiment in which caregivers at 2 pediatric primary care clinics were asked to choose between hypothetical food programs. Programs varied across 4 categories: 1) resources provided (eg, food delivery, food in clinic, assistance enrolling in benefits); 2) support staff providing resources (eg, social worker, community health worker, physician, or nurse); 3) outreach modality (eg, phone, email, text); and 4) outreach frequency. Multinomial logistic regression was used to assess caregiver preferences within each category and the relative importance of each category to caregiver decisions., Results: We surveyed 142 caregivers who were predominantly Black (87%) and Medicaid-insured (90%). Caregiver preferences for food programs were most strongly influenced by the food resources provided. Caregivers preferred food delivery over other forms of food supports, such as food provided in clinic. They preferred assistance from a benefits enrollment specialist, community health worker, or social worker to assistance from a physician or nurse., Conclusions: Pediatric clinics serving families at risk of food insecurity should use caregiver preferences to inform the design of family-centered interventions. Clinics should consider connecting caregivers with food delivery programs, and pediatric payors should adopt reimbursement models that support multidisciplinary team-based care to address food insecurity., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Background and Objective: In 2019, Pennsylvania launched a Children's Development Account (CDA) program that invests $100 in an education savings account for every child born in the state. However, as of 2021, only 10.6% of families claimed the investment. Low-income communities may stand to benefit most from educational investments, but few studies have assessed barriers and facilitators of uptake in these communities. We sought to examine low-income caregivers' perceptions of and barriers and facilitators to participation in a statewide CDA program and their receptivity to clinic-based financial counseling through a medical financial partnership., Methods: We surveyed 100 caregivers of Medicaid-insured children from 2 primary care practices serving a predominantly low-income community. From these 100, we purposively sampled 30 caregivers for follow-up interviews., Results: The 100 survey participants were predominantly female (83%), Black or African American (92%), and non-Hispanic or Latino (93%). Twenty-nine percent of survey participants were aware of the CDA program, 4% had enrolled, and 64% were interested in clinic-based financial counseling. In interviews, caregivers identified several barriers to and facilitators of engagement in the CDA program. They also identified several strategies to boost engagement, including simplifying registration, providing additional and personalized program information, expanding the investment amount, and providing clinic- and community-based outreach., Conclusions: Low-income caregivers identified several barriers to enrollment in a statewide CDA program and strategies to boost enrollment, including clinic-based financial counseling. Future research should examine the effectiveness, cost-effectiveness, and long-term financial and health consequences of clinic-based financial services for low-income families., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2023 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Objective: Parents of pediatric patients are key stakeholders in the design and implementation of health-related social needs (HRSN) screening programs. Yet, there is little research exploring their perspectives on the documentation and sharing of HRSN data. We aimed to examine parents' preferences regarding how HRSN data are documented and shared., Methods: We conducted semi-structured interviews with parents of hospitalized children participating in an HRSN screening program at a quaternary care children's hospital. Interviews were coded using an inductive and deductive approach to identify emergent themes., Results: The 20 interviewed parents were uniformly female with 55% identifying as Black or African American and 20% identifying as Hispanic or Latino. Parents expressed comfort with electronic health record documentation of HRSN data and the use of International Classification of Diseases, 10th Revision Z codes as long as this information was used to provide families with meaningful support. Most parents viewed social workers and medical teams as the most appropriate recipients of HRSN data. Few parents felt comfortable with HRSN data being shared with payors. Parents desired transparency around HRSN data sharing. Many expressed concerns that documentation and sharing of HRSN data could lead to unwanted or unsafe disclosures or result in child welfare referrals., Conclusions: Parents expressed comfort with HRSN documentation and sharing with health care providers, but requested that providers be transparent and respect parental preferences regarding data sharing to mitigate potential harms. When implementing HRSN support programs, health systems and payors should prioritize transparency around documentation and data sharing with families., (Copyright © 2024 by the American Academy of Pediatrics.)

Aims: To compare the association between measures of left atrial (LA) structure and function, derived from cardiovascular magnetic resonance (CMR), with cardiovascular (CV) death or non-fatal heart failure (HF) events in patients with non-ischaemic dilated cardiomyopathy (DCM)., Methods and Results: CMR studies of 580 prospectively recruited patients with DCM in sinus rhythm (median age 54 [interquartile range 44-64] years, 61% men, median LVEF 42% [30-51%]) were analysed for measures of LA structure (left atrial maximum volume index [LAVImax], left atrial minimum volume index [LAVImin]) and function (left atrial emptying fraction [LAEF], left atrial reservoir strain [LARS], left atrial conduit strain [LACS] and left atrial booster strain [LABS]). Over median follow-up of 7.4 years, 103 patients (18%) met the primary endpoint. Apart from LACS, each measure of LA structure and function was associated with the primary endpoint after adjusting for other important prognostic variables. The addition of each LA metric to a baseline model containing the same important prognostic covariates improved model discrimination, with LAVImin providing the greatest improvement (C-statistic improvement: 0.702 to 0.738; χ2 test comparing likelihood ratio p < 0.0001; categorical net reclassification index: 0.210 (95% CI 0.023-0.392)). Patients in the highest tercile of LAVImin had similar event rates to those with persistent atrial fibrillation. Measures of LA strain did not enhance model discrimination above LA volumetric measures., Conclusion: Measure of left atrial structure and function offer important prognostic information in patients with DCM and enhance prediction of adverse outcomes. LA strain was not incremental to volumetric analysis for risk prediction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Quorum sensing enables cell-cell communication in bacteria and regulates biofilm formation. Biofilm production promotes pathogenicity of Escherichia coli and causes infections. However, antibiotic resistance limits conventional treatment efficacy against biofilm infections. Quorum quenching offers an alternative by disrupting quorum sensing signals. Allicin, extracted from garlic, possesses antimicrobial and anti-quorum sensing properties. This study employed molecular docking and dynamics simulations to investigate allicin's interaction with the E. coli quorum sensing system, specifically targeting the cytoplasmic SidA receptor protein. SidA binds to N-acyl-homoserine lactone ligands and regulates quorum sensing in E. coli . The crystal structure of SidA was obtained from the PDB. Molecular docking revealed that allicin competitively binds to the ligand-binding pocket of SidA. Simulations analyzed the effects of allicin binding on SidA stability and affinity for N-acyl-homoserine lactones over 200 ns. Parameters like RMSD, RMSF, and hydrogen bonding indicated SidA was more stable when bound to allicin compared to unbound. Binding free energies suggested allicin reduced SidA's affinity for native ligands. Therefore, allicin binding to SidA alters its conformation and inhibits interaction with N-acyl-homoserine lactones, disrupting quorum sensing signaling and biofilm production in E. coli .Communicated by Ramaswamy H. Sarma.

5-Fluorouracil (5FU) is a chemotherapy drug used to treat various cancers, such as colorectal, prostate, skin, pancreas, and stomach, as an ointment or solution. However, its consumption has several side effects. Therefore, a new derivative of fluorouracil containing 5-Amino-1H-tetrazole was designed and synthesized through multi-step synthesis to reduce urea excretion and toxicity. The effectiveness of the synthesized drug on the Adenocarcinoma gastric cell line (AGS) gastric cancer cell line was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test, which showed that the new 5-fluorouracil (5FU) analog, with an IC 50 of 15.67 µg/mL, is more effective in inhibiting the proliferation of AGS cells after 24 h compared to both synthesized and reported 5FU. In addition, In-silico studies showed that the new 5FU derivative based on amino tetrazole, with a binding energy of -7.2 kcal/mol, exhibits greater anti-cancer activity against the BCL2 enzyme than 5FU, with a binding energy of - 4.8 kcal/mol. It is predicted that the new 5FU derivative will be effective in treating gastric and colorectal cancers. The new derivative of the 5-fluorouracil drug was characterized and identified using FTIR and NMR spectroscopy.Communicated by Ramaswamy H. Sarma.

Background: Patients with likely pathogenic/pathogenic desmoplakin ( DSP ) variants are poorly characterized. Some of them meet diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC), but it is unclear how risk stratification strategies for ARVC perform in this setting., Objectives: The purpose of this study was to characterize arrhythmic outcomes and to test the performance of the recently validated ARVC risk calculator in patients with DSP likely pathogenic/pathogenic variants fulfilling definite 2010 ARVC Task Force Criteria ( DSP -TFC+)., Methods: DSP -TFC+ patients were enrolled from 20 institutions across 3 continents. Ventricular arrhythmias (VA), defined as a composite of sustained ventricular tachycardia (VT), appropriate implantable cardioverter defibrillator therapies, and ventricular fibrillation/sudden cardiac death events in follow-up, were reported as the primary outcome. We tested the performance of the ARVC risk calculator for VA prediction, reporting c-statistics., Results: Among 252 DSP -TFC+ patients (age 39.6 ± 16.9 years, 35.3% male), 94 (37.3%) experienced VA over 44.5 [IQR: 19.6-78.3] months. Patients with left ventricle involvement (n = 194) were at higher VA risk (log-rank P  = 0.0239). History of nonsustained VT (aHR 2.097; P  = 0.004) showed the strongest association with VA occurrence during the first 5-year follow-up. Neither age ( P  = 0.723) nor male sex ( P  = 0.200) was associated with VAs at follow-up. In 204 patients without VA at diagnosis, incident VA rate was high (32.8%; 7.37%/y). The ARVC risk calculator performed poorly overall (c-statistic 0.604 [0.594-0.614]) and very poorly in patients with left ventricular disease (c-statistic 0.558 [0.556-0.560])., Conclusions: DSP -TFC+ patients are at substantial risk for VAs. The ARVC risk calculator performs poorly in DSP -TFC+ patients suggesting need for a gene-specific risk algorithm. Meanwhile, DSP -TFC+ patients with nonsustained VT should be considered as high-risk., Competing Interests: The Johns Hopkins ARVC program (Dr James, Gasperetti, Calkins, Carrick, Murray, and Tondo) is supported by the Leonie-Wild Foundation, the Leyla Erkan Family Fund for ARVD Research, the Hugh Calkins, Marvin H. Weiner, and Jacqueline J. Bernstein Cardiac Arrhythmia Center, the Dr Francis P. Chiramonte Private Foundation, the Dr Satish, Rupal, and Robin Shah ARVD Fund at 10.13039/100007880Johns Hopkins, the Bogle Foundation, the Campanella family, the Patrick J. Harrison family, the 10.13039/501100019817Peter French Memorial Foundation, and the Wilmerding Endowments and 10.13039/100000002NIH/10.13039/100006108NCATS UL1 TR003098. ASJMtR and PVT acknowledge support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Netherlands Heart Foundation, grant nos. CVON2018-30 PREDICT2, CVON2015-12 eDETECT, 2020B005 Double Dose. ASJMtR is supported by the 10.13039/501100001826ZonMW Off-Road Grant 2021. The Zurich ARVC Program is supported by the 10.13039/501100011561Georg und Bertha Schwyzer-Winiker Foundation, 10.13039/501100007252Baugarten Foundation, Wild Foundation, 10.13039/501100001711Swiss National Science Foundation (SNF), and the 10.13039/501100004362Swiss Heart Foundation. The Bologna Cardiomyopathy Registry has received funding support from the 10.13039/501100003196Italian Ministry of Health, RC-2022-2773270 project AAMW received funding from CVON Predict-2. Dr Mestroni is supported by 10.13039/100000002NIH R01HL69071, R01HL116906, R01HL147064, 10.13039/100000002NIH/10.13039/100006108NCATS UL1 TR002535 and UL1 TR001082. Dr Yazdani is supported by 10.13039/501100000274British Heart Foundation FS/CRTF/23/24448 and Alexander Jansons Myocarditis UK. Dr Prasad has received funding from Alexander Jansons Myocarditis UK, 10.13039/501100000833Rosetrees Trust, and 10.13039/501100000274British Heart Foundation. Dr Medo is supported by the 10.13039/100001825Rose Foundation. This work was supported by the 10.13039/501100000265Medical Research Council (UK), 10.13039/501100000274British Heart Foundation [RE/18/4/34215], the 10.13039/501100013342NIHR Imperial College Biomedical Research Centre, the 10.13039/501100000272NIHR Royal Brompton Biomedical Research Centre, and the 10.13039/501100000282Sir Jules Thorn Charitable Trust [21JTA]. Dr Saguner has received educational grants through his institution from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, BMS/Pfizer, and Medtronic; and speaker/advisory board/consulting fees from Abbott, Bayer Healthcare, Daiichi-Sankyo, Medtronic, Novartis, and Pfizer. Dr Lakdawala has received unrestricted research support from Pfizer and the O’Hare and Steggall Family Foundations and consulting fees from BMS, Pfizer, Cytokinetics, Sarepta, and Tenaya. Dr Mestroni received educational grant from Greenstone; and advisory board/consulting fees from Tenaya, StrideBio, and Unicure. Dr Gasperetti received advisory board/consulting fees from Lexeo, and has served as an unpaid consultant for StrideBio. Dr James has received research grants from StrideBio Inc and Lexeo Inc; has received advisory board/consulting fees from Pfizer and Lexeo; and has served as an unpaid consultant for StrideBio and Tenaya. Dr Ware has received research support from Bristol-Myers Squibb; and advisory board/consultancy fees from Bristol-Myers Squibb, Foresite Labs, and Pfizer. Dr Calkins is a consultant for Medtronic Inc, Biosense Webster, Pfizer, StrideBio, Rocket, and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Staphylococcus aureus is a prevalent Gram-positive bacteria leading cause of a wide range of human pathologies. Moreover, antibiotic résistance of pathogenesis bacteria is one of the worldwide health problems. In Gram-positive bacteria, the enzyme of SrtA, is responsible for the anchoring of surface-exposed proteins to the cell wall peptidoglycan. Because of its critical role in Gram-positive bacterial pathogenesis, SrtA is an attractive target for anti-virulence during drug development. To date, some SrtA inhibitors have been discovered most of them being derived from flavonoid compounds, like Myricetin. In order to provide potential hit molecules against SrtA for clinical use, we obtained a total of 293 compounds by performing in silico shape-based screening of compound libraries against Myristin as a reference structure. Employing molecular docking and scoring functions, the top 3 compounds Apigenin, Efloxate, and Compound 8261032 were screened by comparing their docking scores with Myricetin. Furthermore, MD simulations and MM-PBSA binding energy calculation studies revealed that only Compound 8261032 strongly binds to the catalytic core of the SrtA enzyme than Myricetin, and stable behavior was consistently observed in the docking complex. Compound 8261032 showed a good number of hydrogen bonds with SrtA and higher MM-PBSA binding energy when compared to all three molecules. Also, it makes strength interactions with Arg139 and His62, which are critical for SrtA biological activity. This study showed that the development of this inhibitor could be a fundamental strategy against resistant bacteria, but further studies in vitro are needed to confirm this claim.Communicated by Ramaswamy H. Sarma.

Recombinant factor VII, produced in recombinant BHK cell line, is secreted as a single chain zymogen form (rFVII, non-activated) in cell culture supernatant and subsequently converts to its active form during anion exchange chromatography step in the downstream purification process, with the aid of calcium ion. Single chain rFVII impurity (non-activated form) in final drug products should not exceed more than 3.0 % of total rFVIIa content. Therefore, one of the most essential quality control tests in pharmaceutical companies is to precisely quantify and report this impurity. SDS-PAGE, as a traditional method in quality control laboratories to quantify single chain rFVII, is a laborious, time-consuming, low output, and semi-quantitative method for quantification of non-activated form impurity which utilizes a densitometer to scan the gel and calculate the non-activated form band density. In this work, we developed two novel instrumental-based techniques (SE-UPLC and CE-SDS) with superior precision, accuracy, sensitivity, and efficiency that overcome SDS-PAGE shortcomings. The results of both methods were comparable to SDS-PAGE and showed an even higher correlation with expected values. Finally, we concluded that these two methods could be used as a high throughput routine method in quality control laboratories as an alternative choice to manual SDS-PAGE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cervical cancer (CC) is a major global health problem and leading cause of cancer deaths among women worldwide. Early detection through screening programs has reduced mortality; however, screening compliance remains low. Identifying non-invasive biomarkers through proteomics for diagnosis and monitoring response to treatment could improve patient outcomes. Here we review recent proteomics studies which have uncovered biomarkers and potential drug targets for CC. Additionally, we explore into the role of cervical cancer stem cells and their potential implications in driving CC progression and therapy resistance. Although challenges remain, proteomics has the potential to revolutionize the field of cervical cancer research and improve patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jafari, Farahani, Abdollahpour-Alitappeh, Manzari-Tavakoli, Yazdani and Rezaei-Tavirani.)

Transient receptor potential (TRP) channels are a large and diverse family of transmembrane ion channels that are widely expressed, have important physiological roles, and are associated with many human diseases. These proteins are actively pursued as promising drug targets, benefitting greatly from advances in structural and mechanistic studies of TRP channels. At the same time, the complex, polymodal activation and regulation of TRP channels have presented formidable challenges. In this short review, we summarize recent progresses toward understanding the structural basis of TRP channel function, as well as potential ligand binding sites that could be targeted for therapeutics. A particular focus is on the current understanding of the molecular mechanisms of TRP channel activation and regulation, where many fundamental questions remain unanswered. We believe that a deeper understanding of the functional mechanisms of TRP channels will be critical and likely transformative toward developing successful therapeutic strategies targeting these exciting proteins. This endeavor will require concerted efforts from computation, structural biology, medicinal chemistry, electrophysiology, pharmacology, drug safety and clinical studies., Competing Interests: MY was employed by Modeling and Informatics, Merck & Co., Inc., United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Huang, Korsunsky, Yazdani and Chen.)