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Abstract: The use of Concrete beams reinforced with a combination of fiber reinforced polymer (FRP) and steel bars has increased dramatically in recent years, due to improvement in strength and flexural ductility simultaneously. In this paper, we proposed a new equation for estimating the effective moment of inertia of hybrid FRP-steel reinforced concrete (RC) beams on the basis of the genetic algorithm and experimental results.The genetic algorithm is used to optimize the percent error between experimental and analytical responses. In the proposed equation, additional coefficients are considered in order to take into account the specific properties of FRP bars. The effects of the elastic modulus of FRP and steel bars, the hybrid reinforcement ratio, Af /As, and the different level of loading on the effective moment of inertia has been considered.These coefficients are used to modify Branson’s equation to compute the effective moment of inertia of concrete beams reinforced by FRP and steel bars. Comparison between the experimental and predicted results showed the adequacy of the model used in predicting the effective moment of inertia, and deflection of hybrid – RC beams.

Cabbage moth, Plutella xylostella L., is the most important pest in cabbage and canola cultures in Iran. Nuclear polyhedrosis viruses are known as important natural enemies of this pest. Because of economic importance of cabbage moth and the necessity of its control, MbNPV (Baculoviridae) was chosen to evaluate its effect on cabbage moth. Experimental data showed that the virus had high virulence and could be considered as the important agent for the control of this insect. In infestation of egg surfaces with 1 Ã 105 PIB/ml of MbNPV, all of larvae died three days after hatching. The LC50 value for the second instar larvae of cabbage moth was calculated 11.99 PIB/mm2. The LT50 values for the same larvae with 19.5 and 47.86 PIB/mm2 doses of MbNPV were 7.16 and 6.11 days, respectively. Mean percentages of mortality with 47.86 PIB/mm2 for 2nd, 3rd and 4th instar larvae were 74.44, 42.78 and 11.11, respectively.

Neurodegenerative and neuroinflammatory diseases, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, affect millions of people globally. As aging is a major risk factor for neurodegenerative diseases, the continuous increase in the elderly population across Western societies is also associated with a rising prevalence of these debilitating conditions. The complement system, a crucial component of the innate immune response, has gained increasing attention for its multifaceted involvement in the normal development of the central nervous system (CNS) and the brain but also as a pathogenic driver in several neuroinflammatory disease states. Although complement is generally understood as a liver-derived and blood or interstitial fluid operative system protecting against bloodborne pathogens or threats, recent research, particularly on the role of complement in the healthy and diseased CNS, has demonstrated the importance of locally produced and activated complement components. Here, we provide a succinct overview over the known beneficial and pathological roles of complement in the CNS with focus on local sources of complement, including a discussion on the potential importance of the recently discovered intracellularly active complement system for CNS biology and on infection-triggered neurodegeneration.

Clinical trypanosomiasis in sheep is described for the first time in Iran after history taking, complete physical examination and blood samples collected for laboratory investigations. The client empha-sised on animal weight loss dating back to one week ago. The clinical examination revealed enlarge-ments of the pre-scapular and pre-femoral lymph nodes and pale mucous membranes. Laboratory investigation showed that the sheep had anaemia with hyperproteinaemia. Thin blood smear examina-tion revealed the presence of Trypanosoma. Treatment included diminazene aceturate (3.5 mg/kg, IM) for three consecutive days, flunixin meglumine (1.1 mg/kg, IM), and oxytetracycline (10 mg/kg, IM). The examination of the blood film after treatment showed no parasite. Trypanosomiasis may occur in our climatic condition in sheep. In two cases studied here, two consecutive doses of di-minazene aceturate administration led to clinical cure. The control of trypanosomiasis in farms may be possible through methods for the control of vectors, such as prophylactic treatment and observing of hygiene in husbandry systems for animals at risk.

Toxoplasma gondii and Neospora caninum, two obligatory intracellular protozoan parasites, are im-portant causes of neonatal mortality and abortion in farmed ruminants worldwide. Previously, proto-zoan abortions in small ruminants were attributed to T. gondii, but the role of N. caninum in these abortions was uncertain. The aim of this study was to investigate the role of T. gondii and N. caninum in ovine abortion in Urmia, northwest of Iran using a molecular method. Overall, 130 placenta and brain samples of aborted ovine foetuses were collected. Extracted DNA from placenta and CNS tis-sues of the aborted foetuses were analysed using PCR with primers specific for T. gondii and N. cani¬num. The association of the frequency of T. gondii and N. caninum infection of aborted foetuses with age and breed in flocks was also studied. The results showed that out of the 130 examined ovine foe-tuses, 5.3 and 2.3 % were PCR-positive for T. gondii and N. caninum DNA, respectively. In this study, no significant differences were recorded relating to Toxoplasma and Neospora infection in different age groups in flocks and among sheep breeds included in the present study (P>0.05). The results of this study proved the importance of T. gondii and N. caninum as reasons of abortion in the studied area.

Background and Objective: Hydatidosis is a chronic, zoonotic worldwide infection which induced by larval stage of Echinococcus worm. This study was done to assessment the pure and B hydatid cyst fluid antigens for the serological diagnosis of human hydatidosis. Methods: In this descriptive laboratory study, infected liver with Hydatid cyst were obtained from Tehran's slaughterhouses to prepare cyst fluid in different stages. After draining and purifying the cyst fluid, it was centrifuged and subsequently concentrated. Specificity and sensitivity of sera samples including hydatidosis (n=60), worm parasites (n=55), fascioliasis (n=35), toxocariasissera (n=20) and negative control (n=35) were tested by Counter Immunoelectrophoresis (CIEP), ELISA and Dot ELISA methods. Results: Specificity and sensitivity of pure antigen of hydatid cyst using CIEP method was 68.9% and 86.7%, respectively. Specificity and sensitivity of B-antigen using CIEP method was 87.8% and 83.3%, respectively. Specificity and sensitivity of pure antigen of hydatid cyst using ELISA method was 76.7%, and 93.3%, respectively. Specificity and sensitivity of B-antigen using ELISA method was 96.7% and 88.3%, respectively. Specificity and sensitivity of pure antigen of hydatid cyst using Dot ELISA method was 83.3% and 100%, respectively. Specificity and sensitivity of B-antigen using Dot ELISA method was 100% and 98.3%, respectively. Conclusion: B-antigen using Dot ELISA method is the most suitable serological test for the diagnoses of hydatid test. [ABSTRACT FROM AUTHOR]

This study was carried out to determine Haemoproteus spp. infection in pigeons in Iran. Blood sam-ples collected from pigeons were examined for Haemoproteus spp. using stained blood smears and polymerase chain reaction (PCR). For PCR, DNA was extracted from blood samples and a fragment of 617 bp in size subjected to PCR using HAEMF and HAEMR2 derived from cytochrome b gene of the parasite mitochondrial genome. A total number of 93 blood samples from pigeons were examined for Haemoproteus spp. of which 13 (13.97%) samples were positive in stained blood smears for Haemoproteus spp. and 27 (24.73%) were positive in PCR. Digestion of PCR product with AluI re-striction endonuclease generated only one distinct pattern for all positive samples, which is indicative of identical Haemoproteus spp. presence in infected pigeons. The results also revealed that PCR had higher sensitivity in detecting Haemoproteus spp. in pigeons.

BACKGROUND AND OBJECTIVE: Pseudomonas aeruginosa is one of the main causes of hospital infections. Pathogenic factors in this bacterium may play a role in the resistance to carbapenem and beta-lactam. The purpose of this study was to evaluate the role and function of KPC and MBL enzymes in increasing the pathogenicity of Pseudomonas aeruginosa isolated from burn wounds. METHODS: In this cross-sectional study, 63 isolates of Pseudomonas aeruginosa from burn wounds of different patients were isolated using biochemical tests such as fermentation of sugars in the OF medium, oxidase test, and so on. Determination of resistance pattern and strains with metallobetalactamase and carbapenema was done by disc diffusion method. The oprD gene was used for molecular confirmation of isolates. PCR method was used to detect pathogenicity genes. FINDINGS: Out of 63 isolates of Pseudomonas aeruginosa isolated from burn patients, 10 isolates (15.83%) had KPC enzyme and 13 isolates (20.63%) had MBL enzymes. Doripenem, Ertapenem and meropenem were the most frequent. Also, the lasB gene was observed in 43 isolates (68.25%), plcN gene in 41 isolates (65.07%), lasA gene in 20 isolates (31.74%), apr in 60 isolates (95.23%), phzI gene in 53 isolates (84.12%), the phzII gene in 38 isolates (60.31%), phzH gene in 30 isolates (47.61%) and plcH gene in 56 isolates (88.88%). CONCLUSION: The results of this study showed that the production of Carbapnemase and MBL enzymes increased the pathogenicity of Pseudomonas aeruginosa isolated from burn wounds.

Background & Objectives: To adopt appropriate policies and strategies to maintain, preserve, and promote health, accurate information and indicators are required. In this study, the years of life lost due to premature death, which is considered one of the indicators of prioritization of health problems, was calculated and compared with other countries. Methods: This study was an applied cross-sectional investigation. We use death registry data of the Province of Qazvin and population estimation from the Statistical Center of Iran from 2004- 2008 and a standard life table. We calculated YLL and YLL rates by age, sex and cause of death. Results: The leading cause of YLL (premature death) in different age groups in the years 2004-2008 (based on ICD10) showed that the most common causes of death in the neonatal period were perinatal disorders, congenital anomalies, and chromosomal disorders. The leading causes of death in the age group 5-14 years were unintentional injuries and in the age group 15-49 years were unintentional injuries and cardiovascular diseases. The main causes of death in the age group 50-64 years were cardiovascular diseases, cancer, and unintentional injuries. Conclusion: The leading causes of premature death in the Province of Ghazvin were unintentional injuries, cardiovascular diseases, perinatal disorders, and cancers. Several causes are preventable by lifestyle modifications such as reducing the tobacco use, increasing physical activity, and reducing stress.

Background: Tennis elbow is a common orthopedic disease affecting elbow in middle aged people. Ninety percent of patients are cured using conservative treatments. In the past, emphasis was placed on the use of long arm splints for its treatment; however, recent studies put doubt on the use of this method of treatment for the complications arising from the application of splints. The results of using long arm splints for the treatment of Methods: This was a case series non randomized clinical trial involving 25 patients treated with long arm castsplints, and 25 patients treated without the use of splint. Local corticosteroid injections and oral NSAIDs were administered for all patients. The two groups were compared in the third week, third month and sixth month of their treatment for the presence of local tenderness and pain in passive flexion test of wrist and fingers against resistance. Using SPSS 9.0, data were analyzed via repeated measurements test of ANOVA Results: Patients in case and control groups had mean ages 43.6 ± 7.2 and 43.6 ± 6 years, respectively. Prior to any treatments, all patients in this study suffered from pain and tenderness in the origin of forearm extensor muscles. Their pain exacerbated upon passive flexion of wrist and fingers against resistance. No significant difference was seen in third week, third month and sixth month (P value =0.32), and no significant difference was seen in the results of our tests regarding the presence of local tenderness and pain in passive flexion of wrist and fingers against resistance between the two groups Conclusions: After a follow-up period of six months, this study demonstrated no statistically significant difference between the two groups treated with and without long arm splints. Keywords: Tennis elbow, Conservative treatment, Laterals epicondylitis, Cast splint

Aims: In people living with human immune deficiency (PLHIV), the rates of human papillomavirus (HPV) infection, mixed types, and high-risk (HR) strains increase, while the virus clearance is prevented. Here, we report HPV genotyping in PLHIVs from Iran and the Middle East region for the first time., Methods: HPV genotyping in referring individuals from different provinces to our laboratory was evaluated over 2023-2024. For this, the HPV types in specimens were detected through the INNO- LiPA HPV genotyping kit. Statistical analysis was conducted with a 95% confidence interval (95%CI) and P < 0.05. Accordingly, 481 subjects from various provinces participated in this study., Results: The rate of HPV infection was 45.7%, of which 14% were HIV-infected women referred from all provinces. The most prevalent types included 6, 51, and 18, but not 16 HR types. Mixed infections in dually infected women were significantly more than in HPV-infected ones. The HPV+/HIV+ subgroup had the lowest median age. The prevalence of HPV types and mixed infection in PLHIVs was congruent with the previous reports, except for the low rate of type 16 infection, perhaps due to the healthy nature of our subjects. Only HIV+/HPV+ cases' age was similar to the previous reports, perhaps because of sample collection and study designs. Among all factors, age and gender affected the HPV type distribution notably., Conclusion: The current study corroborated the results of many prior reports, demonstrating the considerable impact of HIV status on HPV distribution. The authors recommend implementing a national HPV vaccination and more comprehensive reports of HPV genotyping in PLHIVs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The aim of the current study was to systematically review and quantify the findings of randomized controlled trials (RCTs) assessing the effect of fermented soy products on anthropometric indices, body composition, and metabolic outcomes. PubMed, Scopus, and Web of Science were searched to identify the relevant articles from inception until March 2024. The weighted mean differences (WMD) and corresponding 95% confidence intervals (CI) were calculated as effect sizes and analyzed using the random-effects method. A total of 2205 records were found, of which 15 RCTs were eligible. Results demonstrated significant beneficial effects of fermented soy on body mass index (WMD = -0.14 kg m -2 , 95% CI: -0.28, -0.01, P = 0.039), waist circumference (WMD = -1.50 cm, 95% CI: -2.94, -0.07, P = 0.04), visceral fat (WMD = -692.17 mm 2 , 95% CI: -1011.58, -372.77, P < 0.001), fasting plasma glucose (WMD = -6.39 mg dL -1 , 95% CI: -10.38, -2.40, P = 0.002), and total cholesterol (WMD = -5.0 mg dL -1 , 95% CI: -6.60, -3.39, P < 0.001) compared with controls. However, the responses of other parameters to fermented soy were not significant. Overall, fermented soy may confer health benefits on certain metabolic outcomes, anthropometric indices, and body composition.

Background: To investigate the impact of Melatonin on follicular oxidative stress and assisted reproductive technology (ART) outcomes in women with diminished ovarian reserve (DOR)., Method: We put 68 women with DOR who were going through ART into a randomized controlled trial. Starting on the fifth day of their menstrual cycle, we gave them either 3 mg of Melatonin or a placebo every day before stimulating their ovaries. We obtained follicular fluid during oocyte retrieval, assessed it for oxidative stress indicators, and documented ART outcomes., Results: Melatonin administration markedly enhanced the quantity of oocytes retrieved, fertilization rates, and embryo quality. In addition, Melatonin changed markers of oxidative stress, specifically the levels of reduced glutathione (rGSH) and total antioxidant capacity (TAC). The Melatonin group exhibited significantly elevated biochemical pregnancy rates., Conclusion: Melatonin may improve the quality of oocytes and help with reproductive technology in women with low ovarian reserves, possibly by lowering oxidative stress in the follicles., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Ethics Committees of Urmia University of Medical Sciences (IR.UMSU.REC.1401.262 and IRCT20170529034209N2). Before the study, all subjects signed informed consent. This was a prospective study of patients undergoing fertility treatment at our IVF center. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Breast cancer is the most common type of cancer in women worldwide. A common approach to cancer treatment in clinical practice is to use a combination of drugs to enhance the anticancer activity of drugs while reducing their side effects. In this regard, we evaluated the effectiveness of combined treatment with gemcitabine (GCB) and arsenic (ATO) and how they affect the cell death pathway in cancer cells. Cytotoxic activity of drugs individually or combined against MDA-MB-231 and MCF-7 was performed by MTT method and isobolographic analysis was used to determine the interaction between these factors. The combination of ATO and GCB showed synergistic anti-cancer activity (CI < 1) in both cancer cell lines. The combination of ATO and GCB induced sub-G1 phase arrest, apoptosis and death rates in MCF-7 and MDA-MB-231 cells. The apoptotic response induced by the combination of GCB and ATO was dependent on caspase 3/7. Combined treatment with mitochondrial membrane potential (MMP) reduction and increased reactive oxygen species (ROS) production caused mitochondrial dysfunction. Co-treatment significantly reduced catalase (CAT) activity in both cancer cells compared to the control group and cells treated with each monotherapy. A significant decrease in cellular GSH was observed in cancer cells treated with ATO and GCB. In addition, migration and invasion were significantly reduced in breast cancer cells treated with the combination of ATO and GCB compared to cells treated with ATO and GCB. In conclusion, the combined treatment of ATO and GCB synergistically increased the anti-cancer activity, and these findings provide an effective approach for the treatment of breast cancer. To the best of our knowledge, this is the first study showing promising results for combination therapy with ATO and GCB in breast cancer., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Maleki et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to evaluate the range of clinical and laboratory findings of multisystem inflammatory syndrome in children (MIS-C) with COVID-19 in a tertiary children's hospital in Northwest Iran during 2020-2022. According to the CDC guidelines, this cross-sectional study included 300 pediatric patients diagnosed with MIS-C. Data were collected retrospectively from medical records, focusing on symptoms, organ involvement, laboratory findings, and outcomes. Statistical analysis was performed using SPSS software, with significance set at p-values <0.05. The study population had a median age of 3 years, with a slight male predominance (57.3%). The most affected systems in MIS-C disease were hematological (87%), gastrointestinal (85%), and respiratory (67%). Laboratory analysis highlighted elevated inflammatory markers such as D-dimer (83.3%), ferritin (71.4%), and CRP (49.7%). Abnormal urinalysis was observed in 151 patients (50.3%), with glucosuria in 83 cases (27.7%) and proteinuria in 29 cases (9.7%). The study found a significant correlation between cardiovascular issues and elevated blood platelets, ESR, CRP, and troponin levels (P ≤ 0.01) but not with ferritin, albumin, or D-dimer levels. Also, the examination of disease outcomes in this study revealed that 81.7% of MIS-C patients were isolated during their hospital stay, 18.3% needed ICU care, and 1% died in hospital. We have presented an experience with distinct clinical and laboratory manifestations in MIS-C. Given the lower median age in this study compared to previous studies, reporting clinical and laboratory manifestations of MIS-C in pediatrics with a younger age is valuable for the diagnosis and treatment course. Some laboratory factors were risk factors for cardiovascular involvement, and consequently, echocardiography is recommended in MIS-C patients with these laboratory indications. Given the lack of a specific diagnostic test for this emerging disease, studies focusing on investigating clinical symptoms and findings are valuable., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Farshidgohar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Deep learning techniques hold immense promise for advancing medical image analysis, particularly in tasks like image segmentation, where precise annotation of regions or volumes of interest within medical images is crucial but manually laborious and prone to interobserver and intraobserver biases. As such, deep learning approaches could provide automated solutions for such applications. However, the potential of these techniques is often undermined by challenges in reproducibility and generalizability, which are key barriers to their clinical adoption. This paper introduces the RIDGE checklist, a comprehensive framework designed to assess the Reproducibility, Integrity, Dependability, Generalizability, and Efficiency of deep learning-based medical image segmentation models. The RIDGE checklist is not just a tool for evaluation but also a guideline for researchers striving to improve the quality and transparency of their work. By adhering to the principles outlined in the RIDGE checklist, researchers can ensure that their developed segmentation models are robust, scientifically valid, and applicable in a clinical setting., Competing Interests: Declarations Ethics Approval This research does not involve human participants, their data or biological material. Consent to Participate Not applicable as this research does not involve human subjects. Consent for Publication The manuscript does not contain any individual person’s data in any form (including individual details, images, or videos). All visualization content is anonymized and derived from public resources, ensuring that all data used is publicly available. Competing Interests FM, LM, PR, BK, AG, DW, RD, MM, AHA, SS, NT, and TK are members of the Machine Learning Education Subcommittee of Society for Imaging Informatics in Medicine (SIIM). LM is the Editor of Radiology with salary support from RSNA and serves on the Editorial Board of JMRI. LM has received grant support from the Siemens Research Grant, the Gordon and Betty Moore Foundation, the Mary Kay Foundation, Google, and NCI/NIH. LM has received personal fees from Lunit Insight, ICAD, Guerbet, and Medscape and is on the Advisory Board for ICAD, Lunit, and Guerbet. LM holds stock options in Lunit and has been reimbursed for meeting and travel expenses by the British Society of Breast Radiology, the European Society of Breast Imaging, and the Korean Society of Radiology. LM is also a member of the ISMRM Board of Trustees and serves on the ACR Data Safety Monitoring Board. RF has had a research collaboration/grant and has acted as a consultant and/or speaker for Nuance Communications Inc., Canon Medical Systems Inc., and GE Healthcare. RF is also a co-investigator on a National Institutes of Health STTR grant subaward and a co-principal investigator on a National Science Foundation grant. FK is the Vice-chair of the SIIM Machine Learning Committee, a member of the RIC at RSNA, a member of the AI committee at RSNA, an Early Career Consultant to the Editor of Radiology, and an Associate Editor for Radiology: Artificial Intelligence. FK is also a consultant for MD.ai, a consultant for GE Healthcare, and a speaker for Sharing Progress in Cancer Care. The rest of the authors declare no competing interests., (© 2024. The Author(s).)

With recent advances in the field of tissue engineering, composite films with biocompatibility, antimicrobial properties, and wound healing properties have gained potential applications in the field of wound dressings. In this research work, composite films of soy protein (S)/oxidized tragacanth gum (G) were successfully made using the solution casting process. The metal-organic framework containing curcumin (MOF) with concentrations of 5 and 10 wt% and tannic acid (TA) with concentrations of 6 and 12 wt% were entered into the polymer film. Surface morphology with scanning electron microscope (FE-SEM), thermal stability, mechanical properties, chemical structure, antioxidant, water absorption, cell viability, antibacterial activity, and biodegradability of the prepared films were investigated in laboratory conditions. In addition, the toxicity of the films in the cell environment was investigated, and the results showed that cell growth and proliferation improved in the presence of the prepared films, especially films SG/MOF10/TA6 and SG/MOF10/TA12 due to the presence of TA and MOF containing curcumin. Also, the antibacterial activity of the films showed that the presence of tannic acid and curcumin in the structure of the films increases their ability against pathogens. According to the obtained results, the newly produced nanocomposite film (SG/MOF10/TA12) has a high potential to be used for wound dressing due to its favorable characteristics and was considered the optimal film., 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: The aim of this study was to develop an animal model to investigate whether prolonged intensive endurance exercise induces RV remodeling, taking into account the involvement of Wnt/β-catenin signaling., Methods: Four-week-old male Wistar rats (100 to 125 g) were assigned to four groups (n = 8/group): 1) sixteen weeks of intensive (36 m/min) exercise (INT), 2) twelve weeks of the intensive exercise followed by four weeks of moderate intensity (18 m/min) exercise (INT + MOD), 3) twelve weeks of the intensive exercise followed by four weeks of detraining (INT + DT), and 4) sedentary rats (SED). The exercise protocols were performed five days a week for one h/day. Echocardiography, real-time PCR, western blotting, and histological staining were performed at the end of week sixteen., Results: INT rats developed concentric hypertrophy without diastolic dysfunction compared to SED (p = 0.006) and INT + DT (p = 0.035). Wnt1, β-catenin and CyclinD1 proteins in the training groups were significantly higher than SED rats (p < 0.001). Interestingly, INT rats had higher protein levels than INT + DT and INT + MOD (p < 0.001), with higher gene expression compared to SED rats (p < 0.05). There was also a significant increase in collagen deposition in INT rats compared to SED (p = 0.046) and INT + DT (p = 0.034). Furthermore, INT + MOD and INT + DT rats did not show any adverse structural, functional, or histological changes., Conclusions: Long-term intensive endurance training seems to be associated with increased collagen deposition and wall thickness in the RV through Wnt/β-catenin signaling (which is concentration dependent), without changes in diastolic function., Clinical Perspective: Over the past decades, there has been an ongoing debate about whether the structural and functional adaptations of the cardiovascular system in trained endurance athletes are benign physiological responses to training or potentially pathological changes related to disease. While the adaptations of the left heart are well-documented, the remodeling of the right heart remains a subject of discussion. To gain insights into the ability of sustained high-intensity exercise to cause adverse right ventricular (RV) remodeling, we conducted an experimental study in which male rats were trained to run vigorously for 1 h daily over a 16-week period and compared them to a parallel group of sedentary control rats. Our findings revealed that intense long-term exercise induced morphological changes along with fibrosis affecting the RV. These fibrotic changes were a result of the 16-week vigorous exercise training regimen. If these results are confirmed in humans, they suggest that prolonged high-intensity endurance exercise training may lead to adverse cardiac remodeling. Our findings have important potential implications for the assessment of cardiac remodeling in individuals engaged in high-level exercise training., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to investigate the clinical and molecular characteristics of Giardia duodenalis ( G. duodenalis ) infection and identify potential risk factors in children and teenagers with malignancies in Shiraz, southwestern Iran. A total of 200 fresh fecal samples were collected from children and adolescents suffering from 32 different cancer types at Amir, Nemazee, and Saadi hospitals affiliated with Shiraz University of Medical Sciences between October 2021 and May 2022. Direct microscopy using saline and iodine wet mount was conducted, and all fecal samples were rechecked by SSU -PCR. Subsequently, a specific fragment of the tpi gene was amplified on all samples for prevalence, sequencing, and assemblage identification. Our study found a 4% (8/200) prevalence of G. duodenalis using microscopy and PCR. The molecular findings were consistent with the microscopic results. All eight positive samples with SSU-rRNA gene were also detected as positive with tpi gene and were correctly sequenced. Among the examined cancer patients, two assemblages were identified: A [sub-assemblage AI (2/8, 25%) and sub-assemblage AII (3/8, 37.5%)] and B [sub-assemblage BIV (3/8, 37.5%)]. Notably, patients were more vulnerable to G. duodenalis infection after receiving at least 8 treatment episodes ( p < 0.05) and displaying gastrointestinal symptoms ( p > 0.05). The demographic characteristics of cancer patients with G. duodenalis infection and the statistical conclusions were separately detailed. The small sample size and low prevalence rate in this study hindered precise epidemiological conclusions. Nonetheless, the results suggest that G. duodenalis infection among cancer patients in Shiraz city originates from humans, without any specific animal groups (C-H) involved.

Contaminated water sources can result in outbreaks of parasitic infections such as Blastocystis sp. in communities, creating a substantial strain on healthcare systems and affecting the general health of the population. To ascertain the prevalence and subtype distribution of Blastocystis sp. in water sources globally, a systematic review and meta-analysis of published papers up to May 19, 2024 were carried out. A thorough search of multiple electronic databases (PubMed, Scopus, Google Scholar, and Web of Science) identified 24 studies/28 datasets meeting the inclusion criteria, encompassing 2,451 water samples from 15 countries worldwide. Water samples comprised wastewater (six datasets, 285 samples), tap/drinking water (10 datasets, 253 samples), surface water (eight datasets, 1013 samples), and uncategorized water (four datasets, 900 samples). Total estimates and 95% confidence intervals (CIs) were computed using a random-effects model. This review found that 18.8% (95% CI: 12.8-26.9%) of examined water samples contained Blastocystis sp. Wastewater showed the highest Blastocystis sp. infection rate at 35.5% (95% CI: 13.5-66.1%), followed by tap/drinking water at 19.1% (95% CI: 9.5-34.5%), surface water at 17.6% (95% CI: 7.2-36.8%), and uncategorized water at 9.9% (95% CI: 4.1-21.8%). Sensitivity analysis assessed weighted prevalence variations following the exclusion of individual studies. Subgroup analysis of Blastocystis sp. prevalence was performed based on publication years, countries, continents, WHO regions, sample sizes, and diagnostic methods. Water samples can be the source of infection for nine Blastocystis sp. subtypes (STs) (ST1-ST4, ST6, ST8, ST10, ST21, and ST24), with seven STs (ST1-ST4, ST6, ST8, and ST10) capable of infecting humans. It is important to take preventative and control measures, improve the cleanliness and quality of water sources, and promote public health awareness due to the presence of different parasites such as Blastocystis sp. in water sources.

Background: This study aimed to estimate the prevalence of obesity, overweight, and underweight in celiac disease (CD) at diagnosis before starting the Gluten-free diet (GFD)., Methods: A comprehensive search was conducted in PubMed, Embase, Scopus, and Web of Science until July 2024 to find the cross-sectional and longitudinal studies that measured the body mass index (BMI) in CD patients at diagnosis. The risk of bias assessment was conducted using the Newcastle-Ottawa Quality Assessment scale. Meta-regression analyses were applied to understand whether weight status is associated with CD., Results: A total of 23 studies involving 15,299 CD patients and 815,167 healthy individuals were included in this study. In newly diagnosed CD patients, pooled estimates of the prevalence of obesity, overweight, and underweight before GFD were 11.78%, 18.42%, and 11.04%, respectively. The prevalence of overweight and obesity in newly diagnosed CD patients increased from 22.15% in 2003-2009 to 32.51% in 2016-2021. Meta-regression analyses indicated that the CD patients with higher BMI had a higher mean age (p = 0.001), and female gender had a marginally significant (p = 0.055) association with higher BMI. Only a few CD patients were underweight at the time of diagnosis, and more patients were overweight/obese., Conclusions: our meta-analysis demonstrated that only a few CD patients were underweight at the time of diagnosis, and almost 37% were overweight or obese. Meta-regression showed a significant association between higher BMI and higher mean age and female gender. A delay or failure for diagnosis of CD is more common in overweight/obese patients, resulting in more progression of the disease and counteracting any advantages of diagnosis., (© 2024. The Author(s).)

Introduction: Cervical cancer is among the most common types of cancer in women and is associated with human papillomavirus (HPV) infection. The association between cervical cancer and high-risk HPV infection has been well documented. However, the effect of simultaneous infection with high- and low-risk HPV or low-risk HPV alone on the risk of developing cervical malignancy remains unanswered in guidelines., Method: We investigated the association of high and low-risk HPVs (HR or LR) genotypes with cervical carcinoma risk and pathological and cytological information in cases recruited from a population-based cohort study of 790 patients. Correlation matrix and t-test were used for analysis., Results: The percentage of HR+LR and HR-HPV16/18 were 9.30% and 11.20% in class II, 7.15% and 7.10% in class IV, and 7.15% and 5.80% in As-CUS smears. Interestingly, concurrent infection with HR-HPV and LR-HPV types led to a significant reduction in the risk of developing malignancy compared to the high-risk group (OR=0.3 (0.098-0.925), pvalue=0.04). The percentage of individuals with cervical malignancy was 10.2% and 28.2% within the co-infected and the HR-HPV participants., Conclusion: Our findings suggest that simultaneous infection with high- and low-risk HPV may reduce the risk of cervical malignancy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This research presents a selective and sensitive electrochemical biosensor for the detection of the mesenchymal-epithelial transition factor (c-MET). The biosensing is based on a modification of the SPCE (screen-printed carbon electrode) with the electrospun nanofiber containing eudragit (EU), hydroxypropyl methylcellulose (HPMC), and Zeolite imidazolate frameworks (ZIF-8) nanoparticles. EU/HPMC/ZIF-8 nanofibers have presented a high capability of electron transfer, and more active surface area than bare SPCE due to synergistic effects between EU, HPMC, and ZIF-8. On the other hand, EU/HPMC nanofibers provided high porosity, flexible structures, high specific surface area, and good mechanical strength. The presence of ZIF-8 nanoparticles improved the immobilization of anti-c-MET on the modified SPCE and also resulted in increasing the conductivity. By c-MET incubation on the modified SPCE, c-MET was connected to anti-c-MET, and consequently the electrochemical signal of [Fe(CN) 6 ] 3-/4- as the anion redox probe was reduced. In order to investigate the structural and morphological characteristics and elemental composition of electrospun nanofibers, various characterization methods including FE-SEM, XRD, FTIR, and EDS were used. Under optimum conditions with a working potential range -0.3-0.6 V (vs. Ag/AgCl), linear range (LR), correlation coefficient (R 2 ), sensitivity, and limit of detection (LOD) were acquired at 100 fg/mL-100 ng/mL, 0.9985, 53.28 μA/cm 2 .dec, and 1.28 fg/mL, respectively. Moreover, the mentioned biosensor was investigated in a human plasma sample to determine c-MET and showed ideal results including reproducibility, stability, and good selectivity against other proteins., 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.)

Introduction: The treatment of endocrine problems like thyroid disease, diabetes mellitus (DM), and polycystic ovary syndrome (PCOS) faces significant challenges so that medical professionals worldwide try to find a new therapeutic approach. However, along with common treatments which include medications, hormone replacement therapy, and surgery; there is a growing interest in alternative therapies like laser therapy, which offers a non-invasive and unique technique for treating endocrine disorders alone or in combination with traditional methods. The main goal of this review was to do a systematic review on the role of the laser and Microwave in the treatment endocrine disorders. Methods: In the present systematic review, the most important databases, including PubMed, Scopus and Google Scholar, were searched for the studies examining the effect of lasers on the treatment of endocrine problems by using appropriate keywords and specific strategies from 1995 to 2023. All the studies that were not about lasers and endocrine were excluded. Results: Based on 51 reviewed studies, lasers and radiofrequency ablation such as RFA are effective in the treatment of thyroid diseases, hyperparathyroidism, pancreatic disorders, and sexual dysfunctions. Laser-induced interstitial thermal therapy (LITT) and microwave ablation (MWA) are genuine minimally invasive methods for the treatment of benign nodules, adenomas, and tumor ablation including pancreatic carcinomas and adrenal tumors. Intravenous laser blood irradiation (ILBI) which uses red, UV, and blue light could be effective in treating various metabolic disorders, such as DM. Conclusion: Laser as a cutting-edge and minimally invasive approach could treat various endocrine disorders. It has a great potential to treat and regulate hormonal imbalances, decrease inflammation, and relieve symptoms of various ailments, such as endocrine disorders., Competing Interests: There are no competing interests., (Copyright © 2024 J Lasers Med Sci.)

This review analyzed reported data of Cryptosporidium prevalence in camels and the species/genotype distribution. Four databases (PubMed, Web of Science, Scopus, Google Scholar) were screened, and studies published by April 1, 2024, were included. Total estimates and 95% CIs were calculated using a random-effects model. The weighted prevalence of Cryptosporidium spp. in 7372 camels examined from 12 different countries was estimated at 13.8% with a 95% CI of 10.3-18.4%. The sensitivity analysis based on excluding the individual studies did not result in significant statistical changes in the final weighted prevalence. Subgroup prevalence of Cryptosporidium spp. in camels was analyzed by publication year, continent, WHO region, country, camel type, sample size, diagnostic method, age, and gender. A significant publication bias ( P  < 0.05) was reported in the present study. Limitations encountered in this study encompassed: insufficient study diversity, reliance on single study results, inadequate molecular and serological studies in comparison to microscopic studies, etc., all of which could impact the findings. The study identified eight Cryptosporidium spp. in camels: C. parvum , C. andersoni , C. bovis , C. muris , C. ratti , C. occultus , C. ubiquitum , and C. hominis . The first three species had pooled prevalence rates of 65.5%, 66%, and 19.2%, respectively. Each of the remaining five species was documented using a single dataset/study. Moreover, genotypes IIdA19G1, IIaA15G1R1, If-like-A15G2, IIdA15G1, IIaA15G2R1, IIaA17G2R1, and IIaA18G2R1 ( C. parvum ), genotype IV ( C. ratti ), genotype XIIa ( C. ubiquitum ), and genotype IkA19G1 ( C. hominis ) have been identified in camels globally. The findings suggest that camels can act as a source of infection for a variety of Cryptosporidium species/genotypes, and can therefore play a key role in disseminating this protozoan to humans and animals., Competing Interests: The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2024 The Author(s).)

Context.—: Changes in Paneth cell numbers can be associated with chronic inflammatory diseases of the gastrointestinal tract. So far, no consensus has been achieved on the number of Paneth cells and their relevance to celiac disease (CD)., Objectives.—: To compare crypt and Paneth cell granule areas between patients with CD and those without CD (non-CD) using an artificial intelligence-based solution., Design.—: Hematoxylin-eosin-stained sections of duodenal biopsies from 349 patients at the McGill University Health Centre were analyzed. Of these, 185 had a history of CD and 164 were controls. Slides were digitized, and NoCodeSeg, a code-free workflow using open-source software (QuPath, DeepMIB), was implemented to train deep learning models to segment crypts and Paneth cell granules. The total area of the entire analyzed tissue, epithelium, crypts, and Paneth cell granules was documented for all slides, and comparisons were performed., Results.—: A mean intersection-over-union score of 88.76% and 91.30% was achieved for crypt areas and Paneth cell granule segmentations, respectively. On normalization to total tissue area, the crypt to total tissue area in CD was increased and the Paneth cell granule area to total tissue area decreased when compared to non-CD controls., Conclusions.—: Crypt hyperplasia was confirmed in CD compared to non-CD controls. The area of Paneth cell granules, an indirect measure of Paneth cell function, decreased with increasing severity of CD. More importantly, our study analyzed complete hematoxylin-eosin slide sections using an efficient and easy to use coding-free artificial intelligence workflow., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article., (© 2024 College of American Pathologists.)

Non-alcoholic fatty liver disease (NAFLD), which is a prevalent hepatic condition worldwide, is expected to develop into the leading reason for end-stage fatty liver in the forthcoming decades. Incorporating rapeseed oil into a balanced diet may be beneficial in improving NAFLD. The goal of this trial was to evaluate the impact of substituting ghee with rapeseed oil on primary outcomes such as fatty liver and liver enzymes, as well as on secondary outcomes including glycaemic variables, lipid profile and anthropometric measurements in individuals with NAFLD. Over 12 weeks, 110 patients (seventy men and forty women; BMI (mean) 28·2 (sd 1·6 kg/m 2 ); mean age 42 (sd 9·6) years), who daily consumed ghee, were assigned to the intervention or control group through random allocation. The intervention group was advised to substitute ghee with rapeseed oil in the same amount. The control group continued the consumption of ghee and was instructed to adhere to a healthy diet. Results showed a significant reduction in the steatosis in the intervention group in comparison with the control group ( P < 0·001). However, a significant change in the levels of alanine aminotransferase (–14·4 μg/l), γ-glutamyl transferase (–1·8 μg/l), TAG (–39·7 mg/dl), total cholesterol (–17·2 mg/dl), LDL (–7·5 mg/dl), fasting blood glucose (–7·5 mg/dl), insulin (–3·05 mU/l), Homeostatic Model Assessment for Insulin Resistance (–0·9), Quantitative Insulin-Sensitivity Check Index (+0·01), weight (–4·3 kg), BMI (–0·04 kg/m 2 ), waist (–5·6 cm) and waist:height ratio (–0·04) was seen in the intervention group. The consumption of rapeseed oil instead of ghee caused improvements in liver steatosis and enzymes, glycaemic variables and anthropometric measurements among individuals with NAFLD.

Deep learning models have been used for a variety of image processing tasks. However, most of these models are developed through supervised learning approaches, which rely heavily on the availability of large-scale annotated datasets. Developing such datasets is tedious and expensive. In the absence of an annotated dataset, synthetic data can be used for model development; however, due to the substantial differences between simulated and real data, a phenomenon referred to as domain gap, the resulting models often underperform when applied to real data. In this research, we aim to address this challenge by first computationally simulating a large-scale annotated dataset and then using a generative adversarial network (GAN) to fill the gap between simulated and real images. This approach results in a synthetic dataset that can be effectively utilized to train a deep-learning model. Using this approach, we developed a realistic annotated synthetic dataset for wheat head segmentation. This dataset was then used to develop a deep-learning model for semantic segmentation. The resulting model achieved a Dice score of 83.4% on an internal dataset and Dice scores of 79.6% and 83.6% on two external datasets from the Global Wheat Head Detection datasets. While we proposed this approach in the context of wheat head segmentation, it can be generalized to other crop types or, more broadly, to images with dense, repeated patterns such as those found in cellular imagery.

Objective. Treatment plan optimization in high dose rate brachytherapy often requires manual fine-tuning of penalty weights for each objective, which can be time-consuming and dependent on the planner's experience. To automate this process, this study used a multi-criteria approach called multi-objective Bayesian optimization with q-noisy expected hypervolume improvement as its acquisition function (MOBO-qNEHVI). Approach. The treatment plans of 13 prostate cancer patients were retrospectively imported to a research treatment planning system, RapidBrachyMTPS, where fast mixed integer optimization (FMIO) performs dwell time optimization given a set of penalty weights to deliver 15 Gy to the target volume. MOBO-qNEHVI was used to find patient-specific Pareto optimal penalty weight vectors that yield clinically acceptable dose volume histogram metrics. The relationship between the number of MOBO-qNEHVI iterations and the number of clinically acceptable plans per patient (acceptance rate) was investigated. The performance time was obtained for various parameter configurations. Main results. MOBO-qNEHVI found clinically acceptable treatment plans for all patients. With increasing the number of MOBO-qNEHVI iterations, the acceptance rate grew logarithmically while the performance time grew exponentially. Fixing the penalty weight of the tumour volume to maximum value, adding the target dose as a parameter, initiating MOBO-qNEHVI with 25 parallel sampling of FMIO, and running 6 MOBO-qNEHVI iterations found solutions that delivered 15 Gy to the hottest 95% of the clinical target volume while respecting the dose constraints to the organs at risk. The average acceptance rate for each patient was 89.74% ± 8.11%, and performance time was 66.6 ± 12.6 s. The initiation took 22.47 ± 7.57 s, and each iteration took 7.35 ± 2.45 s to find one Pareto solution. Significance. MOBO-qNEHVI combined with FMIO can automatically explore the trade-offs between treatment plan objectives in a patient specific manner within a minute. This approach can reduce the dependency of plan quality on planner's experience and reduce dose to the organs at risk., (Creative Commons Attribution license.)

The surfaces of nanomaterials with applications in optoelectronics and catalysis control their physicochemical properties. NMR spectroscopy, enhanced by dynamic nuclear polarization (DNP), is a powerful approach to probe the local environment of spin-1/2 nuclei near surfaces. However, this technique often lacks robustness and resolution for half-integer quadrupolar nuclei, which represent more than 66% of the NMR-active isotopes. A novel pulse sequence is introduced here to circumvent these issues. This method is applied to observe with high-resolution 27 Al and 17 O spin-5/2 nuclei on the surface of γ-alumina. Moreover, we report high-resolution 17 O spectra of ZnO nanoparticles used in optoelectronics. Their assignment using DFT calculations allows the first NMR observation of vacancies near the surfaces. Finally, we employ the introduced NMR technique to observe 11 B spin-3/2 nuclei on the surface of partially oxidized boron nitride supported on silica and to distinguish its different BO 2 OH active sites.

Background: Blastocystis sp. is a zoonotic protozoan parasite, and there is limited information about its molecular prevalence and subtypes (STs) distribution in camels globally, especially in Iran., Objectives: This study aimed to examine the prevalence, STs distribution, and zoonotic potential of Blastocystis sp. in one-humped and two-humped camels in Ardabil province, northwestern Iran., Methods: A PCR-sequencing tool using the SSU rRNA gene was employed to examine the occurrence and genetic variation of Blastocystis sp. in 150 faecal samples from Bactrian (Camelus bactrianus, 50 samples) and Dromedary (Camelus dromedarius, 100 samples) camels in Ardabil province., Results: The overall prevalence of Blastocystis sp. in camels was determined to be 12% (18/150) through microscopy and PCR analyses. Phylogenetically, this study identified three distinct zoonotic STs: ST7, ST10, and ST14. ST10 was the most prevalent, comprising 50% (9/18) of the isolated STs from camels. ST14 closely followed with 38.9% (7/18), while ST7 made up 11.1% (2/18) of the total STs. In brief, ST10, ST14, and ST7 represented 50% (7/14), 35.7% (5/14), and 14.3% (2/14) of the Blastocystis-positive cases in one-humped camels, respectively. Further, each of the ST10 and ST14 accounted for 50% (2/4) of the Blastocystis-positive samples in two-humped camels. An analysis of the available data reveals that out of the 37-44 identified Blastocystis STs, 15 (ST1-ST7, ST10, ST14, ST15, ST21, ST24, ST25, ST26, and ST30) have been reported in camels. The predominant STs observed are ST10 and ST14. Furthermore, among the 15 zoonotic STs (ST1-ST10, ST12-ST14, ST16, and ST23) of Blastocystis reported thus far, nine zoonotic STs (ST1-ST7, ST10, and ST14) have been found in camels., Conclusions: These findings indicate that camels serve as a proper reservoir for a diverse array of Blastocystis STs and thereby can play a significant role in the transmission of this protozoan infection to humans, animals, and water reservoirs., (© 2024 The Authors. Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objective. Monte Carlo (MC) simulations are the benchmark for accurate radiotherapy dose calculations, notably in patient-specific high dose rate brachytherapy (HDR BT), in cases where considering tissue heterogeneities is critical. However, the lengthy computational time limits the practical application of MC simulations. Prior research used deep learning (DL) for dose prediction as an alternative to MC simulations. While accurate dose predictions akin to MC were attained, graphics processing unit limitations constrained these predictions to large voxels of 3 mm × 3 mm × 3 mm. This study aimed to enable dose predictions as accurate as MC simulations in 1 mm × 1 mm × 1 mm voxels within a clinically acceptable timeframe. Approach. Computed tomography scans of 98 breast cancer patients treated with Iridium-192-based HDR BT were used: 70 for training, 14 for validation, and 14 for testing. A new cropping strategy based on the distance to the seed was devised to reduce the volume size, enabling efficient training of 3D DL models using 1 mm × 1 mm × 1 mm dose grids. Additionally, novel DL architecture with layer-level fusion were proposed to predict MC simulated dose to medium-in-medium ( D m , m ). These architectures fuse information from TG-43 dose to water-in-water ( D w , w ) with patient tissue composition at the layer-level. Different inputs describing patient body composition were investigated. Main results. The proposed approach demonstrated state-of-the-art performance, on par with the MC D m , m maps, but 300 times faster. The mean absolute percent error for dosimetric indices between the MC and DL-predicted complete treatment plans was 0.17% ± 0.15% for the planning target volume V 100 , 0.30% ± 0.32% for the skin D 2 cc , 0.82% ± 0.79% for the lung D 2 cc , 0.34% ± 0.29% for the chest wall D 2 cc and 1.08% ± 0.98% for the heart D 2 cc . Significance. Unlike the time-consuming MC simulations, the proposed novel strategy efficiently converts TG-43 D w , w maps into precise D m , m maps at high resolution, enabling clinical integration., (Creative Commons Attribution license.)

The objective of this population pharmacokinetic (PK) analysis was to characterize the concentration-time profile of brepocitinib plasma concentration after single- and multiple-oral administration in healthy volunteers (HVs) and patients with immuno-inflammatory diseases. Blood samples from phase I HV and phase II clinical studies of patients with alopecia areata, psoriasis, psoriatic arthritis, ulcerative colitis (UC), vitiligo, and hidradenitis suppurativa were analyzed using a nonlinear mixed-effects modeling approach. Effects of patients' characteristics on brepocitinib exposure were investigated. Overall, 8552 brepocitinib plasma concentrations from 775 individuals were included in the analysis. The PKs of brepocitinib were adequately described by a two-compartment model with first-order absorption and a lag time for tablet formulation, dose-dependent bioavailability, and Box-Cox transformed interindividual variabilities on apparent clearance (CL/F) and apparent central volume of distribution (Vc/F). For a typical 70-kg non-Asian female patient with baseline aspartate aminotransferase of 22 unit/liter, CL/F and Vc/F estimates were 17.5 L/h and 88.5 L, respectively. Asians had a higher exposure (independent of body weight), caused by a 10% lower CL/F when compared to other individuals. Independent of baseline body weight, the male population showed 13% higher Vc/F compared to the female population. Patients with UC were predicted to have 46% slower absorption rate compared to other individuals. The PKs of brepocitinib were well-characterized by a two-compartment model with first-order absorption and dose-dependent bioavailability. Several covariates, such as race and sex, were identified to have statistically significant, but not clinically meaningful, effects on the estimated PK parameters., (© 2024 Pfizer Inc and The Authors. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Introduction: Topical brepocitinib, a tyrosine kinase (TYK)2/Janus kinase (JAK)1 inhibitor, is in development for psoriasis (PsO) and atopic dermatitis (AD). Quantitative analyses of prior clinical trial data were used to inform future clinical trial designs., Methods: Two phase 2b studies in patients with AD and PsO were used to characterize the amount of topical brepocitinib and the resultant systemic trough concentration (C Trough ) using a linear mixed-effects regression (LMER). This model was used to predict brepocitinib systemic C Trough for higher treated body surface areas (BSAs) in adults and children. Information from non-clinical and clinical trials with oral brepocitinib was leveraged to set safety thresholds. This combined approach was used to inform future dose-strength selection and treated BSA limits., Results: Data from 256 patients were analyzed. Patient type, dose strength, and frequency had significant impacts on the dose-exposure relationship. Systemic concentration in patients with PsO was predicted to be 45% lower than in patients with AD from the same dose. When topically applied to the same percentage BSA, brepocitinib systemic exposures are expected to be comparable between adults and children. The systemic steady-state exposure after 3% once daily and twice daily (2 mg/cm 2 ) cream applied to less than 50% BSA in patients with AD and PsO, respectively, maintains at least a threefold margin to non-clinical safety findings and clinical hematologic markers., Conclusion: The relationship between the amount of active drug applied and brepocitinib systemic C Trough , described by LMER, may inform the development strategy for dose optimization in the brepocitinib topical program., (© 2024. The Author(s).)

Introduction: Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are two cutaneous conditions with morphological resemblance, which can complicate the diagnosis in some cases. Using immunohistochemistry staining of biomarkers could be beneficial in resolving this obstacle., Objectives: We investigated a variety of biomarkers assessed in different studies in order to find the most important and helpful biomarkers for differentiation between SCC and lesions capable of spontaneous regression., Methods: MEDLINE via PubMed and Google Scholar database were used to identify relevant literature up to 15 June 2022. The aim of our analyses was to determine the capability of biomarkers to distinguish between SCC and lesions capable of spontaneous regression using calculated individual and pooled odds ratios (OR) and 95% confidence intervals (CI) and I 2 tests., Results: Six potential biomarkers were CD10 with pooled OR= 0.006 (95% CI: 0.001-0.057) and I 2 =0%; COX-2 with pooled OR=0.089 (95% CI: 0.029-0.269) and I 2 =17.1%; elastic fibers with pooled OR= 6.69 (95% CI: 2.928-15.281) and I 2 =0%; IMP-3 with pooled OR=0.145 (95% CI: 0.021-1.001) and I 2 =44.5%; P53 with pooled OR=0.371 (95% CI: 0.188-0.733) and I 2 =55.9%; AT1R with OR=0.026 (95% CI: 0.006-0.107)., Conclusions: We suggest the utilization of the following IHC biomarkers for discrimination between lesions with spontaneous regression such as KA and SCC: CD10, COX-2, and elastic fibers.

Singlet fission (SF) is the process of converting an excited singlet to a pair of excited triplets. Harvesting two charges from a single photon has the potential to increase photovoltaic device efficiencies. Acenes, such as tetracene and pentacene, are model molecules for studying SF. Despite SF being an endoergic process for tetracene and exoergic for pentacene, both acenes exhibit near unity SF quantum efficiencies, raising questions about how tetracene can overcome the energy barrier. Here, we use recently developed instrumentation to measure inelastic neutron scattering (INS) while optically exciting the model molecules using two different excitation energies. The spectroscopic results reveal intermolecular structural relaxation due to the presence of a triplet excited state. The structural dynamics of the combined excited state molecule and surrounding tetracene molecules are further studied using time-dependent density functional theory (TD-DFT), which shows that the singlet and triplet levels shift due to the excited state geometry, reducing the uphill energy barrier for SF to within kT.

Background: Malaria is still the deadliest parasitic disease caused by Plasmodium spp. Due to drug resistance and their unpleasant side effects, of conventional researchers are enormously seeking to achieve antimalarial drugs with more curative effective, less toxic and cost-affordable drugs using more advanced technology such as nanodrugs., Purpose: The present study aimed to examine the antimalarial effects of a novel synthesized nonochloroquine-loaded curcumin relying on dendrimer G2 in susceptible mice., Methods: Antimalarial activity and toxicity of the nanocomposite were examined on BALB/C mice with microscopy, checking RBCs morphology and related enzymatic activity rate., Results: The maximum inhibitory effect of the nanocomposite was seen at 10 mg/kg, killing 98% of P. berghei compared to sole chloroquine, whereas ED50 was reported at 5.5 mg/kg. The safety of the synthesized nanocomposite was confirmed with biochemical tests with no detrimental effects on mice. The sustainability and longevity of the nanodrug increased significantly with the NDC-CQ assay compared to the control groups., Conclusion: The study showed that nonochloroquine-loaded curcumin had a promising inhibitory effect on P. berghei growth in infected mice compared to standard drugs. However, further studies and clinical trials with large samples are recommended to study different aspects of using nanodrug., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This study aims to describe the healthcare resource utilization (HCRU) and direct medical cost of influenza-related hospitalizations to illustrate the persistent economic burden of influenza among adults in the US., Methods: A retrospective cohort study was conducted using the PINC AI Healthcare Database. Adults hospitalized with a diagnosis of influenza between August 1-May 31 from 2016-2023 were identified and stratified by age (18-49, 50-64 and ≥65 years). The index hospitalization was defined as the individual's first influenza-related hospitalization during each season. Patient demographics, comorbidities, and hospitalization characteristics were assessed during the index hospitalization. Index hospitalization length of stay (LOS), in-hospital mortality, intensive care unit (ICU) admissions, mechanical ventilation (MV) usage, and costs were evaluated overall and by MV usage, ICU admission, and secondary complication status. Pre-index influenza-related outpatient and emergency department (ED) visits (7 days prior) were also evaluated., Results: Primarily initiated in the ED, the median LOS for influenza-related hospitalizations was 3-4 days. Inpatient mortality increased with age (2.2-4.4%). Combined mean hospitalization and initial ED visit costs were $12,556-$14,494 (2017/18; high severity season) and $11,384-$12,896 (2022/23; most recent season). Compared to other age groups, adults ≥65 years had higher proportions of hospitalization with no MV or ICU usage. Adults 18-49 years had the highest proportion of ICU admission only, whereas adults 50-64 years had the highest MV usage only and both MV and ICU admission. MV and/or ICU usage was associated with higher hospitalization costs. Increasing proportionally with age, the majority of influenza-related hospitalizations had a secondary complication diagnosis, which were associated with elevated costs., Limitations: Analysis of this hospital-based administrative database relied on coding accuracy. Only hospital system-associated outpatient/ED visits were captured; the full scope of HCRU was under-ascertained., Conclusions: The economic burden of influenza-related hospitalizations remains substantial, driven by underlying conditions, MV/ICU usage and secondary complications.

The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle to cancer treatment and can ultimately result in patient mortality. Epithelial-mesenchymal transition (EMT) is one of the many factors and processes responsible for chemo-resistance. Studies have shown that targeting EMT can help overcome chemo-resistance, and nanotechnology and nanomedicine have emerged as promising approaches to achieve this goal. This article discusses the potential of nanotechnology in inhibiting EMT and proposes a viable strategy to combat chemo-resistance in various solid tumors, including breast cancer, lung cancer, pancreatic cancer, glioblastoma, ovarian cancer, gastric cancer, and hepatocellular carcinoma. While nanotechnology has shown promising results in targeting EMT, further research is necessary to explore its full potential in overcoming chemo-resistance and discovering more effective methods in the future., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Surgical or medical treatment for type B or descending aortic dissections with difficult presentation or stable hemodynamics is debatable. This study aimed to review the type B aortic dissection therapy to assess safety and effectiveness., Materials and Methods: Online databases of PubMed, Science Direct, Web of Science, Cochrane, and Scopus were searched for relevant systematic reviews, guidelines, and meta-analysis studies on the management of type B aortic dissection, up to July 2023. The conclusions were qualitatively synthesized., Results: Best medical therapy (BMT], thoracic aortic endovascular repair (TEVAR), and open surgeries (OS) were management approaches. Hemodynamics classify type B aortic dissection as complex or simple. Both examples reveal decreased in-hospital all-cause mortality with TAVR than OS. Guidelines recommend TEVAR for difficult situations and OS if it fails. Complication analyses favour TEVAR, however left subclavian artery coverage without revascularization increases stroke risk. Studies show Type B aortic dissection is simpler than TEVAR and BMT. Acute or subacute presentation did not affect reintervention rates between treatments. TEVAR had a greater early stroke risk than BMT but a decreased long-term aortic-related and all-cause mortality. The best data showed no differences in in-hospital mortality or early re-intervention between regimens. BMT reduced early stroke but increased late all-cause death., Conclusion: In conclusion, addressing Type B aortic dissection is complicated, depending on presentation and hemodynamics. TEVAR is best for difficult patients, however BMT and OS also work. TEVAR may reduce in-hospital mortality but increase early stroke risk., Competing Interests: None., (Copyright© 2023, Galen Medical Journal.)

A novel electrochemical immunosensor was developed for ultrasensitive determination of the hormone insulin-like growth factor 1 (IGF-1) based on immobilization of a specific monoclonal antibody on the electrospun nanofibers of Polyacrylonitrile (PAN)/Zein-reduced graphene oxide (rGO) nanoparticle. The nanofibers deposited on glassy carbon electrode (GCE) showed good electrochemical behaviors with synergistic effects between PAN, Zein, and rGO. PAN/Zein nanofibers were used due to flexibility, high porosity, good mechanical strength, high specific surface area, and flexible structures, while rGO nanoparticles were used to improve the detection sensitivity and anti-IGF-1 immobilizing. Different characterization techniques were applied consisting of FE-SEM, FT-IR, and EDS for the investigation of morphological features and nanofiber size. The redox reactions of [Fe(CN) 6 ] 4-/3- on the modified electrode surface were probed for studying the immobilization and determination processes, using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Under optimal conditions, LOD (limit of detection) and LOQ (limit of quantification) were obtained as 55.72 fg/mL and 185.73 fg/mL respectively, and sensitivity was acquired 136.29 μA/cm 2 .dec. Moreover, a wide linear range was obtained ranging from 1 pg/mL to 10 ng/mL for IGF-1. Furthermore, the proposed method was applied for the analysis of IGF-1 in several human plasma samples with acceptable results, and it also exhibited high selectivity, stability, and reproducibility., 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.)

As it is now established that global warming and climate change are a reality, international investments are pouring in and rightfully so for climate change mitigation. Carbon capture and separation (CCS) is therefore gaining paramount importance as it is considered one of the powerful solutions for global warming. Sorption on porous materials is a promising alternative to traditional carbon dioxide (CO 2 ) capture technologies. Owing to their sustainable availability, economic viability, and important recyclability, natural products-derived porous carbons have emerged as favorable and competitive materials for CO 2 sorption. Furthermore, the fabrication of high-quality value-added functional porous carbon-based materials using renewable precursors and waste materials is an environmentally friendly approach. This review provides crucial insights and analyses to enhance the understanding of the application of porous carbons in CO 2 capture. Various methods for the synthesis of porous carbon, their structural characterization, and parameters that influence their sorption properties are discussed. The review also delves into the utilization of molecular dynamics (MD), Monte Carlo (MC), density functional theory (DFT), and machine learning techniques for simulating adsorption and validating experimental results. Lastly, the review provides future outlook and research directions for progressing the use of natural products-derived porous carbons for CO 2 capture., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Damage to the mitochondria may lead to serious conditions that are difficult to treat. Doxorubicin is one of the most widely used chemotherapeutic drugs for the treatment of malignancies in children and adults, and reportedly causes damage to the mitochondria. Unfortunately, the dangerous cardiac side effects of doxorubicin appear when the patient is in the midst of a vigorous fight against the disease, either by taking doxorubicin alone or in combination with other drugs. This study aimed to determine whether exogenous healthy and functional mitochondria are internalized by cells, can it help the survival of these cells, and can reduce cardiotoxicity. For this purpose, isolated, pure, and functional exogenous mitochondria were injected into the tail vein of a rat model of doxorubicin-induced cardiotoxicity. After that, the heart function of the rats and their antioxidant status, inflammatory markers, and histopathological examination were investigated. Our findings show that intravenous mitochondrial transplantation provided efficient mitochondrial uptake and reduced cardiotoxicity by reducing ROS production, lipid peroxidation, and inflammation. In addition, the levels of ATP and antioxidant enzymes increased after mitochondrial transplantation; therefore all of these complex processes resulted in the reduction of apoptosis and necrosis in rat heart tissue. These promising results open the way to more effective cancer treatment without the side effects of related drugs. Transplanting exogenous mitochondria probably enhances the cell's mitochondrial network, potentially treating mitochondria-related disorders such as cardiovascular and neurodegenerative diseases, although the exact relationship between mitochondrial damage and these conditions remains unclear., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The physics of micron-scale biological colonies usually benefits from different out-of-equilibrium sources. In bacterial colonies and cellular tissues, the growth process is among the important active sources that determine the dynamics. In this article, we study the generic dynamical instabilities associated with the growth phenomena that may arise in both scalar and vectorial systems. In vectorial systems, where the rotational degrees of particles play a role, a phenomenological growth-mediated torque can affect the rotational dynamics of individual particles. We show that such a growth-mediated torque can result in active traveling waves in the bulk of a growing system. In addition to the bulk properties, we analyze the instabilities in the shape of growing interfaces in both scalar and vectorial systems.

Background: While new studies are being published on the prehospital continuous positive airway pressure (CPAP) application in patients with respiratory failure with conflicting results, previous meta-analyses are showing the benefits of CPAP in the prehospital transfer of patients with respiratory distress. Before the clinical application of high-level evidence, updated pooled estimates are needed based on the growing literature. This study aimed to compare prehospital CPAP with the usual standard oxygen therapy of respiratory failure patients., Materials and Methods: PRISMA guidelines served as the framework for this updated review study. It is an extension of a prior systematic review. We conducted comprehensive searches across several databases, including PubMed, Web of Science, Embase, and Scopus, focusing on randomized trials that juxtaposed pre-hospital CPAP application against standard care. Our primary interest was to assess the in-hospital mortality risks, and we employed random effect models to aggregate risk ratios from the selected studies., Results: Four articles were gathered based on the review of the updated literature (2013 to November 2022) in conjunction with the research incorporated in the preceding meta-analysis with a total number of 747 patients receiving prehospital CPAP with 101 events of in-hospital mortality. In the standard treatment control groups, there were 713 patients and 115 deaths occurred. Pooled mortality risk comparison between the group of prehospital CPAP and standard care patients had no statistically significant difference (P=0.16). There was no heterogenicity. A regression between the year of the studies and the effect size showed increased RR in new studies (P=0.017)., Conclusion: Still more randomized trials are needed with higher sample sizes to conclude the lifesaving efficacy of the out-of-hospital CPAP., Competing Interests: None., (Copyright© 2023, Galen Medical Journal.)

Introduction: Adults aged 18-64 years comprise most of the working population, meaning that influenza infection can be disruptive, causing prolonged absence from the workplace, and reduced productivity and the ability to care for dependents. Influenza vaccine uptake is relatively low, even among the older adults in this population (i.e., aged 50-64 years), reflecting a lack of perceived need for vaccination. This systematic literature review (SLR) aimed to characterize the global burden of influenza in the 18-64 years population., Methods: An electronic database search was conducted and supplemented with conference and gray literature searches. Eligible studies described at least one of clinical, humanistic, or economic outcomes in adults aged 18-64 years and conducted across several global regions. Included studies were published in English, between January 1, 2012, and September 20, 2022., Results: A total of 40 publications were included, with clinical, humanistic, and economic outcomes reported in 39, 5, and 15, respectively. Risk of influenza-associated clinical outcomes were reported to increase with age among the 18-64 years population, including hospitalizations (Yamana et al. in Intern Med 60:3401-3408, 2021; Derqui et al. in Influenza Other Respir Viruses 16:862-872, 2022; Fuller et al. in Influenza Other Respir Viruses 16:265-275, 2022; Ortiz et al. in Crit Care Med 42:2325-2332, 2014; Yandrapalli et al. in Ann Transl Med 6:318, 2018; Zimmerman et al. in Influenza Other Respir Viruses 16:1133-1140, 2022). ICU admissions, mortality, ER/outpatient visits, and use of mechanical ventilation were recorded. Adults aged 18-64 years with underlying comorbidities were at higher risk of influenza-related hospitalizations, ICU admission, and mortality than otherwise healthy individuals. Length of hospital stay increased with age, although a lack of stratification across other economic outcomes prevented identification of further trends across age groups., Conclusions: High levels of hospitalization and outpatient visits demonstrated a clinical influenza-associated burden on patients and healthcare systems, which is exacerbated by comorbidities. Considering the size and breadth of the general population aged 18-64 years, the limited humanistic and economic findings of this SLR likely reflect an underreported burden. Greater investigation into indirect costs and prolonged absenteeism associated with influenza infection is required to fully understand the economic burden in this population., (© 2023. The Author(s).)

An electrochemical immunosensing platform was developed for the detection of receptor tyrosine kinase-orphan receptor-2 (ROR2) at a glassy carbon electrode (GCE) modified with the electrospun nanofiber containing polyvinylpyrrolidone (PVP), soy, and Au nanoparticles (AuNPs). The PVP/soy/AuNP nanofiber exhibited good electrochemical behavior due to synergistic effects between PVP, soy, and AuNPs. The PVP/soy in the modified film provided good mechanical strength, high porosity, flexible structures, and high specific surface area. On the other hand, the presence of AuNPs effectively improved conductivity, as well as the immobilization of anti-ROR2 on the modified GCE, leading to enhanced sensitivity. Various characterization approaches such as FE-SEM, FTIR, and EDS were used for investigating the morphological and structural features, and the elemental composition. The designed immunosensor performance was investigated using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), and differential pulse voltammetry (DPV). Under optimum conditions with a working potential range from -0.2 to 0.6 V (vs. SCE), sensitivity, linear range (LR), limit of detection (LOD), and correlation coefficient (R 2 ) were acquired at 122.26 μA/cm 2 dec, 0.01-1000 pg/mL, 3.39 fg/mL, and 0.9974, respectively. Furthermore, the determination of ROR2 in human plasma samples using the designed immunosensing platform was examined and exhibited satisfactory results including good selectivity against other proteins, reproducibility, and cyclic stability., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Acute myeloid leukemia (AML) comprises a multifarious and heterogeneous array of illnesses characterized by the anomalous proliferation of myeloid cells in the bone marrow microenvironment (BMM). The BMM plays a pivotal role in promoting AML progression, angiogenesis, and metastasis. The immune checkpoints (ICs) and metabolic processes are the key players in this process. In this review, we delineate the metabolic and immune checkpoint characteristics of the AML BMM, with a focus on the roles of BMM cells e.g. tumor-associated macrophages, natural killer cells, dendritic cells, metabolic profiles and related signaling pathways. We also discuss the signaling pathways stimulated in AML cells by BMM factors that lead to AML progression. We then delve into the roles of immune checkpoints in AML angiogenesis, metastasis, and cell proliferation, including co-stimulatory and inhibitory ICs. Lastly, we discuss the potential therapeutic approaches and future directions for AML treatment, emphasizing the potential of targeting metabolic and immune checkpoints in AML BMM as prognostic and therapeutic targets. In conclusion, the modulation of these processes through the use of directed drugs opens up new promising avenues in combating AML. Thereby, a comprehensive elucidation of the significance of these AML BMM cells' metabolic and immune checkpoints and signaling pathways on leukemic cells can be undertaken in the future investigations. Additionally, these checkpoints and cells should be considered plausible multi-targeted therapies for AML in combination with other conventional treatments in AML. Video Abstract., (© 2023. BioMed Central Ltd., part of Springer Nature.)