Search

Introduction: Despite recent advancements in the treatment of metastatic uveal melanoma (UM), the availability of further treatment options remains limited and the prognosis continues to be poor in many cases. In addition to tebentafusp, immune checkpoint blockade (ICB, PD-1 (+/-) CTLA-4 antibodies) is commonly used for metastatic UM, in particular in HLA-A 02:01-negative patients. However, ICB comes at the cost of potentially severe immune-related adverse events (irAE). Thus, the selection of patient groups that are more likely to benefit from ICB is desirable., Methods: In this analysis, 194 patients with metastatic UM undergoing ICB were included. Patients were recruited from German skin cancer sites and the ADOReg registry. To investigate the association of irAE occurrence with treatment response, progression-free survival (PFS), and overall survival (OS) two cohorts were compared: patients without irAE or grade 1/2 irAE (n=137) and patients with grade 3/4 irAE (n=57)., Results: In the entire population, the median OS was 16.4 months, and the median PFS was 2.8 months. Patients with grade 3/4 irAE showed more favorable survival than patients without or grade 1/2 irAE (p=0.0071). IrAE occurred in 44.7% (87/194), and severe irAE in 29.4% (57/194) of patients. Interestingly, irColitis and irHepatitis were significantly associated with longer OS (p=0.0031 and p=0.011, respectively)., Conclusions: This data may indicate an association between irAE and favorable survival outcomes in patients with metastatic UM undergoing ICB treatment and suggests that a reduced tolerance to tumor antigens could be linked to reduced tolerance to self-antigens., Competing Interests: AG speaker´s honoraria from Allmirall, Amgen, Bristol-Myers Squibb, Immunocore, MSD Sharp & Dohme and Roche; intermittent advisory board relationships with Amgen, Bristol-Myers Squibb, Novartis, MSD Sharp & Dohme, Pierre Fabre Pharmaceuticals, Pfizer, Roche and Sanofi Genzyme; travel and congress fee support from Bristol-Myers Squibb, MSD Sharp & Dohme, Novartis, Pierre Fabre Pharmaceuticals and Roche. Clinical studies: Amgen, Array, Bristol-Myers Squibb, Delcath Systems Inc, GSK, Novartis, MSD Sharp & Dohme, Pfizer, and Roche. CB declares speaker´s and/or consultancy honoraria from Almirall, Bristol-Myers Squibb, Delcath, Immunocore, Leo Pharma, Miltenyi, MSD Sharp & Dohme, Novartis, Pierre Fabre Pharmaceuticals, Regeneron, and Sanofi-Aventis outside the submitted work. CP received honoraria speaker honoraria or honoraria as a consultant and travel support from Novartis, Bristol-Myers Squibb, Roche, Merck Serono, MSD Sharp & Dohme, Celgene, AbbVie, Sun Pharma, UCB, Allergy Therapeutics, and LEO. FM has received travel support or/and speaker’s fees or/and advisor’s honoraria by Novartis, Roche, Bristol-Myers Squibb, MSD Sharp & Dohme, Pierre Fabre Pharmaceuticals, Sanofi, and Immunocore and research funding from Novartis and Roche. FZ declares speakers and advisory board honoraria and/or travel support from Bristol-Myers Squibb, MSD Sharp & Dohme, Roche, Novartis, Pierre Fabre Pharmaceuticals, and Sanofi-Aventis outside the submitted work. JCH declares research support from Bristol Myers Squibb, Sanofi, and Sunpharma, advisory board honoraria from GSK, Pierre Fabre Pharmaceuticals, Sun Pharma, speaker honoraria from Amgen, Bristol-Myers Squibb, Delcath, GSK, Immuno core, MSD Sharp & Dohme, Novartis, Sanofi and Sun Pharma and travel support from Bristol-Myers Squibb, Iovance and Sun Pharma. SH declares speakers and advisory board honoraria from Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Sanofi, Sun Pharma, and Pierre Fabre Pharmaceuticals. JUl: Speakers and advisory board honoraria from Bristol-Myers Squibb, Kyowa-Kirin, Merck Sharp & Dohme, Novartis, Pierre Fabre Pharmaceuticals and Sanofi, and travel support from Pierre Fabre Pharmaceuticals. JUt is on the advisory board or has received honoraria and travel support from Amgen, Bristol-Myers Squibb, GSK, Immunocore, LeoPharma, Merck Sharp and Dohme, Novartis, Pierre Fabre Pharmaceuticals, Roche, Sanofi outside the submitted work. KCK serves as a consultant to Philogen, Bristol-Myers Squibb, MSD Sharp & Dohme, Sanofi Aventis, and Immunocore and received travel grants and speaker fees from Philogen, Pierre Fabre Pharmaceuticals, Bristol-Myers Squibb, MSD Sharp & Dohme, Sun Pharma, Sanofi Aventis, Novartis, Medac and has received research support by Novartis. K-MT received speaker or consultant honoraria and travel support from Bristol-Myers Squibb, MSD Sharp & Dohme, Roche, Novartis, Pierre Fabre Pharmaceuticals, Sanofi Genzyme, Sun Pharma, Amgen, LEO Pharma, Galderma, Almirall, and Candela. ME declares honoraria and travel support from Bristol-Myers Squibb, Immunocore, Novartis, Pierre Fabre Pharmaceuticals, and Sanofi, outside the submitted work. MVH: Honoraria from MSD Sharp & Dohme, Bristol-Myers Squibb, Roche, Novartis, Sun Pharma, Sanofi, Almirall, Biofrontera, Galderma. PM Research support: Novartis, Bristol-Myers Squibb, MSD Sharp & Dohme. Honoraria for lectures: Roche, Bristol-Myers-Squibb, Novartis, MSD Sharp & Dohme, Almirall, Amgen, Merck-Serono, Pierre Fabre Pharmaceuticals, Sanofi, Sun Pharma, Baiersdorf; Honoraria for advisory boards: Roche Pharma, Bristol-Myers-Squibb, Novartis, MSD Sharp & Dohme, Almirall, Amgen, Pierre Fabre Pharmaceuticals, MSD Sharp & Dohme, Immunocore, Sun Pharma, Sanofi. PT: Bristol-Myers Squibb, Novartis, MSD Sharp & Dohme, Pierre Fabre Pharmaceuticals, CureVac, Roche, Kyowa Kirin, Biofrontera, Invited Speaker, Personal BMS, Novartis, Pierre Fabre Pharmaceuticals, Merck Serono, Sanofi, Roche, Kyowa Kirin, Advisory Board, Personal BMS, Pierre Fabre Pharmaceuticals, Other, Personal, Travel support. RG Research support: Amgen, MSD Sharp & Dohme, Sun Pharma, Sanofi/Regeneron, Almirall, Kyowa Kirin. Honoraria for lectures: Bristol-Myers-Squibb, Novartis, MSD Sharp & Dohme, Almirall, Amgen, MSD Sharp & Dohme, Sun, Pierre Fabre Pharmaceuticals, Sanofi/Regeneron, Sun Pharma Honoraria for advisory boards: Bristol-Myers-Squibb, Novartis, MSD Sharp & Dohme, Almirall, Amgen, Pierre Fabre Pharmaceuticals, MSD Sharp & Dohme, 4SC, Immunocore, Sun Pharma, Sanofi/Regeneron, Delcath. SU declares research support from Bristol-Myers Squibb and MSD Sharp & Dohme; speakers and advisory board honoraria from Bristol-Myers Squibb, MSD Sharp & Dohme, Merck Serono, Novartis, and Roche, and travel support from Bristol-Myers Squibb, and MSD Sharp & Dohme. UL declares research support from MSD Sharp & Dohme; speakers and advisory board honoraria from MSD Sharp & Dohme, Novartis, Sanofi, and Sun Pharma, and travel support from Pierre Fabre Pharmaceuticals and Sun Pharma. BS Speakers honoria and/or travel support from Amgen, Bristol-Myers Squibb, MSD Sharp & Dohme, Jansen, Novartis, Roche, Sun Pharma, abbvie, Sanofi, Pierre Fabre Pharmaceuticals, Boehringer Ingelheim and Pfizer. 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 reviewer AT declared a past co-authorship with the author RG, JH, SH, KCK, CL, FM, MM, PT, K-MT, FZ, and MVH to the handling editor., (Copyright © 2024 Koch, Petzold, Dippel, Erdmann, Gesierich, Gutzmer, Hassel, Haferkamp, Kähler, Kreuzberg, Leiter, Loquai, Meier, Meissner, Mohr, Pföhler, Rahimi, Schell, Terheyden, Thoms, Ugurel, Ulrich, Utikal, Weichenthal, Ziller, Berking and Heppt.)

Fluorescence spectroscopy serves as a vital technique for studying the interaction between light and fluorescent molecules. It encompasses a range of methods, each presenting unique advantages and applications. This technique finds utility in various chemical studies. This review discusses Fluorescence spectroscopy, its branches such as Time-Resolved Fluorescence Spectroscopy (TRFS) and Fluorescence Lifetime Imaging Microscopy (FLIM), and their integration with other spectroscopic methods, including Raman, Infrared (IR), and Circular Dichroism (CD) spectroscopies. By delving into these methods, we aim to provide a comprehensive understanding of the capabilities and significance of fluorescence spectroscopy in scientific research, highlighting its diverse applications and the enhanced understanding it brings when combined with other spectroscopic methods. This review looks at each technique's unique features and applications. It discusses the prospects of their combined use in advancing scientific understanding and applications across various domains., (© 2024 IOP Publishing Ltd.)

Celiac disease (CD) is a chronic autoimmune enteropathy and multifactorial disease caused by inappropriate immune responses to gluten in the small intestine. Weight loss, anemia, osteoporosis, arthritis, and hepatitis are among the extraintestinal manifestations of active CD. Currently, a strict lifelong gluten-free diet (GFD) is the only safe, effective, and available treatment. Despite the social burden, high expenses, and challenges of following a GFD, 2 to 5 percent of patients do not demonstrate clinical or pathophysiological improvement. Therefore, we need novel and alternative therapeutic approaches for patients. Innovative approaches encompass a broad spectrum of strategies, including enzymatic degradation of gluten, inhibition of intestinal permeability, modulation of the immune response, inhibition of the transglutaminase 2 (TG2) enzyme, blocking antigen presentation by HLA-DQ2/8, and induction of tolerance. Hence, this review is focused on comprehensive therapeutic strategies ranging from dietary approaches to novel methods such as antigen-based immunotherapy, cell and gene therapy, and the usage of nanoparticles for CD treatment., 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.)

Objectives: Sleeve gastrectomy (SG) is one of the most commonly performed weight loss (WL) bariatric procedures. The main goal of WL is reducing total body weight (TBW) and fat mass (FM). However, TBW loss is systematically accompanied by a decline in fat-free mass (FFM), predominantly in the first post-surgical month, despite protein supplementation. Branched-chain amino acids (BCAAs) and vitamin D seem to attenuate loss of FFM and, thus, reduce the decline in muscle strength (MS). However, data on the role of an integrated supplementation with whey protein plus BCAAs plus vitamin D (P+BCAAs+Vit.D) vs. protein alone on total weight loss (TWL), fat mass (FM), fat-free mass (FFM), and (MS) in the first month after SG are lacking. Therefore, the present study aims to evaluate the impact of P+BCAAs+Vit.D vs. protein alone supplementation on TWL, FM, FFM, and MS in the first month after SG., Materials and Methods: Before SG and at 1 month afterward, we prospectively measured and compared TBW, FM, FFM, and MS in 57 patients who received either a supplementation with P+BCAAs+Vit.D (n = 31) or protein alone (n = 26). The impact of P+BCAAs+Vit.D and protein alone supplementation on clinical status was also evaluated., Results: Despite non-significant variation in TBW, FM decreased more significantly (18.5% vs. 13.2%, p = 0.023) with the P+BCAA+Vit.D supplementation compared to protein alone. Furthermore, the P+BCAA+Vit.D group showed a significantly lower decrease in FFM (4.1% vs. 11.4%, p < 0.001) and MS (3.8% vs. 18.5%, p < 0.001) compared to the protein alone group. No significant alterations in clinical status were seen in either group., Conclusion: P+BCAA+Vit.D supplementation is more effective than protein alone in determining FM loss and is associated with a lower decrease in FFM and MS, without interfering with clinical status in patients 1 month after SG.

This study addresses research gaps regarding the impact of professional bereavement photography for perinatal loss. Utilizing a mixed-methods research design, 504 parents completed an online survey measuring their attitudes toward bereavement photography and its impact. Thirty-one parents participated in semi-structured interviews. The results indicate a high level of acceptability and satisfaction for professional bereavement photography by parents (including those from more diverse backgrounds). Data triangulation confirmed that photos are valuable in enfranchising grief, validating parental and babies' identities and facilitating connections with others. Significant correlations were found for sharing of photos with both positive attitudes toward photography and for continuing bonds. The expression of continuing bonds in public social media spaces suggests increased social acceptance and validation for grieving perinatal losses. The findings from this study further inform practice guidelines for supporting perinatal loss.

Efficient solar-driven syngas production (CO+H 2 mixture) from CO 2 and H 2 O with a suitable photocatalyst and fundamental understanding of the reaction mechanism are the desired approach towards the carbon recycling process. Herein, we report the design and development of an unique COF-topological quantum material nano-heterostructure, COF@TI with a newly synthesized donor-acceptor based COF and two dimensional (2D) nanosheets of strong topological insulator (TI), PbBi 2 Te 4 . The intrinsic robust metallic surfaces of the TI act as electron reservoir, minimising the fast electron-hole recombination process, and the presence of 6s 2 lone pairs in Pb 2+ and Bi 3+ in the TI helps for efficient CO 2 binding, which are responsible for boosting overall catalytic activity. In variable ratio of acetonitrile-water (MeCN : H 2 O) solvent mixture COF@TI produces syngas with different ratios of CO and H 2 . COF@TI nano-heterostructure enables to produce higher amount of syngas with more controllable ratios of CO and H 2 compared to pristine COF. The electron transfer route from COF to TI was realized from Kelvin probe force microscopy (KPFM) analysis, charge density difference calculation, excited state lifetime and photoelectrochemical measurements. Finally, a probable mechanistic pathway has been established after identifying the catalytic sites and reaction intermediates by in situ DRIFTS study and DFT calculation., (© 2024 Wiley‐VCH GmbH.)

In this study, we conducted an extensive investigation into broadband near-infrared luminescence of Cr 3+ -doped Ca 3 Y 2 Ge 3 O 12 garnet, employing first-principles calculations within the density functional theory framework. Our initial focus involved determining the site occupancy of Cr 3+ activator ions, which revealed a pronounced preference for the Y 3+ sites over the Ca 2+ and Ge 4+ sites, as evidenced by the formation energy calculations. Subsequently, the geometric structures of the excited states 2 E and 4 T 2 , along with their optical transition energies relative to the ground state 4 A 2 in Ca 3 Y 2 Ge 3 O 12 :Cr 3+ , were successfully modeled using the ΔSCF method. Calculation convergence challenges were effectively addressed through the proposed fractional particle occupancy schemes. The constructed host-referred binding energy diagram provided a clear description of the luminescence kinetics process in the garnet, which explained the high quantum efficiency of emission. Furthermore, the accurate prediction of thermal excitation energy yielded insights into the thermal stability of the compound, as illustrated in the calculated configuration coordinate diagram. More importantly, all calculated data were consistently aligned with the experimental results. This research not only advances our understanding of the intricate interplay between geometric and electronic structures, optical properties, and thermal behavior in Cr 3+ -doped garnets but also lays the groundwork for future breakthroughs in the high-throughput design and optimization of luminescent performance and thermal stability in Cr 3+ -doped phosphors.

Purpose: Infection by the intracellular apicomplexan parasite Toxoplasma gondii has serious clinical consequences in humans and veterinarians around the world. Although about a third of the world's population is infected with T. gondii , there is still no effective vaccine against this disease. The aim of this study was to develop and evaluate a multimeric vaccine against T. gondii using the proteins calcium-dependent protein kinase (CDPK)1, CDPK2, CDPK3, and CDPK5., Materials and Methods: Top-ranked major histocompatibility complex (MHC)-I and MHC-II binding as well as shared, immunodominant linear B-cell epitopes were predicted and linked using appropriate linkers. Moreover, the 50S ribosomal protein L7/L12 (adjuvant) was mixed with the construct's N-terminal to increase the immunogenicity. Then, the vaccine's physicochemical characteristics, antigenicity, allergenicity, secondary and tertiary structure were predicted., Results: The finally-engineered chimeric vaccine had a length of 680 amino acids with a molecular weight of 74.66 kDa. Analyses of immunogenicity, allergenicity, and multiple physiochemical parameters indicated that the constructed vaccine candidate was soluble, non-allergenic, and immunogenic, making it compatible with humans and hence, a potentially viable and safe vaccine candidate against T. gondii parasite., Conclusion: In silico , the vaccine construct was able to trigger primary immune responses. However, further laboratory studies are needed to confirm its effectiveness and safety., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Korean Vaccine Society.)

Urban gas pipelines pose significant risks to public safety and infrastructure integrity, necessitating thorough risk assessment methodologies to mitigate potential hazards. This study investigates the dynamics of population distribution, demographic characteristics, and building structures to assess the risk associated with gas pipelines. Using geospatial analysis techniques, we analyze population distribution patterns during both day and night periods. Additionally, we conduct an in-depth vulnerability assessment considering multiple criteria maps, highlighting areas of heightened vulnerability in proximity to gas pipelines and older buildings. This study incorporated the concept of individual risk and the intrinsic parameters of gas pipelines to develop a hazard map. Hazard analysis identifies areas with elevated risks, particularly around main pipeline intersections and high-pressure zones. Integrating hazard and vulnerability assessments, we generate risk maps for both day and night periods, providing valuable insights into spatial risk distribution dynamics. The findings underscore the importance of considering temporal variations in risk assessment and integrating demographic and structural factors into hazard analysis for informed decision-making in pipeline management and safety measures., (© 2024. The Author(s).)

Background and Objective: This study aimed to compare physical and cognitive functions between post-coronavirus disease 2019 (COVID-19) participants and healthy matched controls and investigate associations between physical and cognitive impairments with quality of life., Methods: Twenty-three post-COVID-19 participants and 23 age and sex-matched healthy people without a history of COVID-19 were included. Physical function was assessed using the Medical Research Council Sum Score (MRC-SS), 2 min Step Test, Modified Borg Scale, and Short Physical Performance Battery (SPPB) Test. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), Trail Making Test (TMT), and Stroop test, and the quality of life was evaluated using the Euro Quality of Life-5 Dimensions-3 Levels (EQ-5D-3l) questionnaire. Assessments were performed by a physical therapist in one session., Results: Mann-Whitney U test showed that in the post-COVID-19 group, compared to the control group, the number of steps in the 2 min Step Test ( p  < 0.001, ES = 0.57) and the scores of the SPPB ( p  = 0.03, ES = 0.32), MoCA ( p  = 0.003, ES = 0.44), Stroop test ( p  < 0.001, ES = 0.75), and the EQ-5D-3l visual analog scale ( p  = 0.027, ES = 0.32) were significantly lower. In addition, the Modified Borg Scale score ( p  < 0.001, ES = 0.6), TMT-A ( p  = 0.013, ES = 0.36) and TMT-B ( p  = 0.016, ES = 0.35) times, and the Stroop time ( p  < 0.001, ES = 0.61) were significantly higher in the post-COVID-19 group. There were no significant between-group differences in the MRC-SS score ( p  = 0.055, ES = 0.28). Furthermore, there were significant moderate to high associations between physical and cognitive functions and the quality of life in post-COVID-19 participants., Conclusions: On average 4 months after symptomatic COVID-19, post-COVID-19 participants had significant impairments in physical and cognitive functions compared to healthy matched controls that were significantly correlated with the quality of life. These findings highlight the need for a comprehensive assessment to plan appropriate management strategies., 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., (© 2024 Rahimi, Saadat, Hessam, Ravanbakhsh, Monjezi.)

Those who participate in and contribute to academic publishing are affected by its evolution. Funding bodies, academic institutions, researchers and peer-reviewers, junior scholars, freelance language editors, language-editing services, and journal editors are to enforce and uphold the ethical norms on which academic publishing is founded. Deviating from such norms will challenge and threaten the scholarly reputation, academic careers, and institutional standing; reduce the publishers' true impacts; squander public funding; and erode the public trust to the academic enterprise. Rigorous review is paramount because peer-review norms guarantee that scientific findings are scrutinized before being publicized. Volunteer peer-reviewers and guest journal editors devote an immense amount of unremunerated time to reviewing papers, voluntarily serving the scientific community, and benefiting the publishers. Some mega-journals are motivated to mass-produce publications and attract the funded projects instead of maintaining the scientific rigor. The rapid development of mega-journals may diminish some traditional journals by outcompeting their impacts. Artificial intelligence (AI) tools/algorithms such as ChatGPT may be misused to contribute to the mass-production of publications which may have not been rigorously revised or peer-reviewed. Maintaining norms that guarantee scientific rigor and academic integrity enable the academic community to overcome the new challenges such as mega-journals and AI tools., (© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Systemic lupus erythematosus (SLE) is an autoimmune disease with an unknown etiology that has widespread clinical and immunological manifestations. Despite the increase in knowledge about the pathogenesis process and the increase in treatment options, however, the treatments fail in half of the cases. Therefore, there is still a need for research on new therapies. Mesenchymal stem cells (MSCs) are powerful regulators of the immune system and can reduce the symptoms of systemic lupus erythematosus. This study aimed to review the mechanisms of immune system modulation by MSCs and the role of these cells in the treatment of SLE. MSCs suppress T lymphocytes through various mechanisms, including the production of transforming growth factor-beta (TGF-B), prostaglandin E2 (PGE2), nitric oxide (NO), and indolamine 2 and 3-oxygenase (IDO). In addition, MSCs inhibit the production of their autoantibodies by inhibiting the differentiation of lymphocytes. The production of autoantibodies against nuclear antigens is an important feature of SLE. On the other hand, MSCs inhibit antigen delivery by antigen-presenting cells (APCs) to T lymphocytes. Studies in animal models have shown the effectiveness of these cells in treating SLE. However, few studies have been performed on the effectiveness of this treatment in humans. It can be expected that new treatment strategies for SLE will be introduced in the future, given the promising results of MSCs application.

Background: The prognostic impact of contrast-associated acute kidney injury (CA-AKI) in patients undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) remains underestimated., Methods: We examined 2707 consecutive procedures performed in a referral CTO center between 2015 and 2019. CA-AKI was defined as an increase in serum creatinine ≥ 0.3 mg/dL or ≥ 50% within 48 h post-PCI. Primary endpoints were in-hospital major adverse cardiac and cerebrovascular events (MACCE, composite of all-cause death, myocardial infarction, target vessel revascularization, stroke) and at one year of follow-up., Results: The overall incidence of CA-AKI was 11.5%. Technical success was comparable (87.2% vs. 90.5%, p = 0.056) whereas procedural success was lower in the CA-AKI group (84.3% vs. 89.7%, p = 0.004). Overall in-hospital MACCE was 1.3%, and it was similar in patients with and without CA-AKI (1.6% vs. 1.3%, p = 0.655); however, the rate of pericardial tamponade requiring pericardiocentesis was significantly higher in patients with CA-AKI (2.2% vs. 0.5%, p = 0.001). In multivariate analysis, CA-AKI was not independently associated with higher risk for in-hospital MACCE (adjusted odds ratio [OR] 1.34, 95% confidence intervals [CI] 0.45-3.19, p = 0.563). At a median follow-up time of 14 months (interquartile range [IQR], 11 to 35 months), one-year MACCE was significantly higher in patients with vs. without CA-AKI (20.8% vs. 12.8%, p < 0.001), and CA-AKI increased the risk for one-year MACCE (adjusted hazard ratio [HR] 1.46, 95% CI 1.07-1.95, p = 0.017) following CTO PCI., Conclusions: CA-AKI in patients undergoing CTO PCI occurs in approximately one out of 10 patients. Our study highlights that patients developing CA-AKI are at increased risk for long-term MACCE.

Thyroid and gonadotropin hormones play an essential role in the regulation of regulating various physiological functions. The effects of melatonin and zinc (Zn) on these hormones have already been investigated. The aim of the present study was to investigate the effect of melatonin with and without zinc on the levels of gonadotropin hormones and thyroid hormones (triiodothyronine (T 3 ), thyroxine (T 4 ) and thyroid-stimulating hormone (TSH)) in female rats. In general, 35 sexually mature female rats were randomly divided into five treatment groups, with each group comprising 7 rats, in a completely randomized design (CRD) during the research. The rats were treated daily with Zn and melatonin via gavage as follows T1 (control 1, basal diet), T2 (control 2, treatment with normal saline) and the other experimental groups, including T 3 , T 4 and T 5 , were treated with Zn (40 ppm), melatonin (5 mg/kg) or a combination of Zn and melatonin at the same dose. The administration of the drugs was continued for 20 days (daily) . Plasma samples were then taken for the determination of LH, FFH, LH/FSH, estrogen, progesterone, T 3 , T 4 and TSH levels. The results showed no significant differences in FSH and LH levels between treatments. Estrogen, progesterone and TSH levels were higher in the rats receiving 5 mg melatonin per day than in the other groups, but not statistically significant ( P >0.05). However, T 3 levels decreased significantly in the group receiving 40 mg/kg Zn compared to the other experiments. ( P <0.05). The results showed no significant difference between the treatments in terms of T 4 levels ( P >0.05). In conclusion, no remarkable changes in other variables were observed in female rats receiving melatonin, Zn or a combination of melatonin and Zn, with the exception of T 3 ., Competing Interests: The writers declare to the fact that they have no conflict of interest.

This study aimed to investigate the effect of varying quantities of zinc oxide nanoparticles (ZnO NPs) on growth performance and mucosal enzyme activity in Japanese quails at an early age. Using a completely randomized experimental design, 160 one-day-old quail chicks were randomly assigned to 4 experimental treatments and each treatment contained 4 replicate pens of 10 birds. The experimental treatments included T1: control (a basal diet containing 35.2 mg Zn only ), T2, T3, and T4 containing basal diet plus 20, 40, and 60 mg ZnO NPs, respectively. Performance characteristics were recorded weekly. After 21 days, one quail was selected and slaughtered from each experimental cage with a body weight equal to the average body weight of quails in the same experimental cage. After slaughtering and opening the abdominal cavity, a 5 cm sample was taken from the jejunum of the small intestine. The jejunum sample was stored at -80°C until the measurement of alkaline phosphatase, amylase, and lipase enzymes. The results showed that live weight was higher in the T3 and T4 groups than in the control group ( P <0.05). The feed conversion ratio was also lower in birds fed with basal diets supplemented with 40 and 60 mg ZnO NPs/kg (T3 and T4, respectively), compared to control treatments ( P >0.05). The results showed that amylase and lipase activity increased in the birds fed with 40 and 60 mg ZnO NPs/kg of the basal diet, in comparison to the control treatment; however, they were not significant ( P >0.05). The results of this study indicated that the addition of 40 or 60 mg ZnO NPs/kg to the basal diet could be used as a supplement to improve performance traits and enhance mucosal enzyme activity in Japanese quail in the starter stage., Competing Interests: The authors declare that they have no conflict of interest.

Background: Fibrodysplasia ossificans progressiva (FOP) as a rare and heritable disorder with the infrequent genetic transmission of the condition is a catastrophic disorder of heterotopic ossification (HO) and a cause of extraskeletal bone formation in humans. Given the lack of effective treatment for this disease, the important point is to avoid aggravating factors such as bone biopsy, surgery, and intramuscular injection., Case Presentation: In this report, we present a 52-year-old female patient, Kurdish ethnic, suspected to FOP who had a surgical intervention on the second toe of the right foot, which subsequently, it caused further deterioration of the disease in the person including necrosis and amputation of the distal phalanx of the second toe., Conclusions: Although, based on our investigation and the available scientific evidence, surgery may a cause for faster progression and worsening of the FOP disorder, but its proof requires further studies., (© 2023. The Author(s).)

Objective: Transcranial direct current stimulation (tDCS) has demonstrated its efficacy in alleviating pain among individuals with musculoskeletal disorders. This review focuses on the application of tDCS as a therapeutic intervention for managing knee osteoarthritis (OA), a prevalent musculoskeletal condition. The primary objective is to assess the effectiveness of tDCS(add-on tDCS and /or stand-alone tDCS), whether as an add-on to existing treatments or as a standalone therapy, in reducing pain and enhancing functional capacity in patients with knee OA., Methods: A comprehensive search was conducted across multiple databases, including PubMed, Science Direct, OVID, MEDLINE, CINAHL, EMBASE, ProQuest, and Google Scholar, and Web of Science. The search terms employed were "Transcranial direct current stimulation" or "tDCS" in combination with "Osteoarthritis" or "OA" and "knee." After eliminating duplicates and studies that did not meet the inclusion criteria, a total of 14 relevant articles were identified for review., Results: Among the included studies, twelve reported statistically significant improvements in pain levels when comparing the active tDCS group to the sham tDCS group. Only two studies reported no significant difference in pain intensity between the active tDCS and sham tDCS groups. Findings regarding functional abilities were diverse, with some studies demonstrating a significant enhancement in functional outcomes in the active tDCS group, while others observed no statistically significant differences., Conclusion: The results of this review suggest that tDCS holds promise as a pain management intervention for individuals with knee OA. Notably, anodal tDCS applied over the primary motor cortex (M1) appears to be particularly effective in alleviating pain in patients with knee OA. However, the impact of tDCS on functional performance appears to be limited., Competing Interests: Declaration of Competing Interest No conflicts of interest were reported for this study., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The main challenge of using nanoliposome systems is controlling their size and stability. In order to overcome this challenge, according to the research conducted at the Research Centre for New Technologies of Biological Engineering, University of Tehran, a model for predicting the size and stability of nanoliposome systems based on thermodynamic relations has been presented. In this model, by using the presented equations and without performing many experiments in the laboratory environment, the effect of temperature, ionic power and different pH can be considered simultaneously whereas examining the components of size, stability and any feature were considered before. Synthesis and application of liposomal nanocarriers in different operating conditions can be investigated and predicted, and due to the change in temperature and pH, the smallest size of th system can be obtained. In this study, we were able to model the synthesis and storage conditions of liposomal nanocarriers at different temperatures and acidic, neutral and alkaline pHs, based on the calculation of mathematical equations. This model also indicates that with increasing temperature, the radius increases but with increasing pH, the radius first increases and then decreases. Therefore, this model can be used to predict size and stability in different operating conditions. In fact, with this modelling method, there is no need to study through laboratory methods and analysis to determine the size, stability and surface loads, and in terms of Accuracy, time and cost savings are affordable.

There is evidence that high daily intake of aluminum (Al) is associated with an increased risk of dementia or cognitive decline. We injected L-arginine into the dorsal hippocampus (DH) of an AlCl3-induced Alzheimer's model and studied memory deficit, β-amyloid (βA) accumulation, neurodegeneration, and molecular changes. Male Wistar rats were cannulated unilaterally in the DH under a stereotaxic apparatus and a dose of AlCl3 (1-200 μg/rat) was injected into the CA1. After recovery, L-arginine and L-NAME (0.05-25 μg/rat) were injected into CA1 and animals were tested in novelty seeking task. One group received βA (2 μg/rat, intra CA1) as a reference group. Control groups received saline (1 μL/rat, intra-CA1) and galantamine (25 μg/rat, intra-CA1), respectively. Finally, rats were anesthetized and hippocampal tissues were isolated on ice. Levels of neuronal NO synthase (nNOS), β-secretase and soluble guanylyl cyclase (sGC) were measured by western blotting. βA formation and the number of CA1 neurons were assessed by Congo red and Nissl staining. NOS activation by NADPH-diaphorase (NADPH-d) was investigated. All data were analyzed using analysis of variance (ANOVA) at α = 0.05 level. Like βA, AlCl3 (25 μg/rat) caused accumulation of βA in the DH and increased stopping of the animal on the novel side (indicating a recall deficit). CA1 neurons decreased, and nNOS and β-secretase, but not sGC, showed a change consistent with Alzheimer's. However, prophylactic intervention of L-arginine at 3-9 μg/rat was protective, probably by nNOS stimulation in DH, as shown by NADPH-d assay. L-arginine may protect against Alzheimer's by increasing hippocampal NO levels., Competing Interests: Declaration of competing interest The authors of this article have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: Precocious puberty in girls has been associated with an increased risk of stress and anxiety in their mothers. This study aimed to investigate the effect of cognitive behavioral therapy (CBT) on perceived stress and anxiety of mothers of girls with precocious puberty symptoms., Methods: This randomized controlled trial was conducted on 70 mothers of girls with precocious puberty symptoms in Tabriz-Iran, 2021. The participants were randomly assigned to CBT and control groups through blocked randomization. Group counseling was provided to the intervention group in eight sessions of 45-60 min weekly with 5 to 7 women. A booklet containing explanations about puberty was provided for the both groups. Data were collected using the questionnaires of socio-demographic characteristics, Spielberger State-Trait Anxiety Inventory (STAI), Perceived Stress Scale (PSS) and quality of life (SF-36). Independent t-test, ANCOVA, chi-square, and fisher's exact tests were used to compare the outcomes between the groups., Findings: After the intervention, based on ANCOVA test with adjusting the baseline values, mean scores of stress (mean difference (MD): -10.75; 95% confidence interval (95% CI): -11.77 to -9.72; P < 0.001), state anxiety (MD: -14.36; 95% CI: -15.7 to -12.7; P < 0.001) and trait anxiety (MD: -12.8; 95% CI: -14.4 to -11.1; P < 0.001) were significantly lower in CBT group compared to the control group. Also mean score of quality of life (MD: 9.82; 95% CI: -6.74 to -12.90; P < 0.001) was significantly higher in CBT group compared to the control group., Conclusion: Based on the results, group CBT is effective in reducing stress and anxiety and improving the quality of life of mothers of girls with precocious puberty symptoms. However, more studies are required to make a definite conclusion in this field., Trial Registration: Iranian Registry of Clinical Trials (IRCT): IRCT20110826007418N6. Date of registration: 11/10/2021. URL: https://en.irct.ir/trial/57346 ; Date of first registration: 11/10/2021., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The integrated stress response is a signaling network comprising four branches, each sensing different cellular stressors, converging on the phosphorylation of eIF2α to downregulate global translation and initiate recovery. One of these branches includes GCN2, which senses cellular amino acid insufficiency and participates in maintaining amino acid homeostasis. Previous studies have shown that GCN2 is a viable cancer target when amino acid stress is induced by inhibiting an additional target. In this light, we screened numerous drugs for their potential to synergize with the GCN2 inhibitor TAP20. The drug sensitivity of six cancer cell lines to a panel of 25 compounds was assessed. Each compound was then combined with TAP20 at concentrations below their IC 50 , and the impact on cell growth was evaluated. The strongly synergistic combinations were further characterized using synergy analyses and matrix-dependent invasion assays. Inhibitors of proteostasis and the MEK-ERK pathway, as well as the pan-CDK inhibitors, flavopiridol, and seliciclib, were potently synergistic with TAP20 in two cell lines. Among their common CDK targets was CDK7, which was more selectively targeted by THZ-1 and synergized with TAP20. Moreover, these combinations were partially synergistic when assessed using matrix-dependent invasion assays. However, TAP20 alone was sufficient to restrict invasion at concentrations well below its growth-inhibitory IC 50 . We conclude that GCN2 inhibition can be further explored in vivo as a cancer target.

Background Prenatal glucocorticoids are commonly used in pregnancies before 34 weeks of gestation in women at risk of preterm delivery; however, the effects of these drugs on late preterm infants (those born after the 34th week of pregnancy) are controversial. As a result, we aimed to investigate the effect of a single course of betamethasone (two doses of betamethasone every 24 hours) on the neonatal outcome of late preterm births. Methods We retrospectively assessed all spontaneous late preterm births (34-36+6 weeks of gestation) at a tertiary hospital in Iran over a period of two and a half years. Exclusion criteria included multiple pregnancies, induced labor, and fetal malformations identified in sonograms. Neonatal outcome measures encompassed first and five-minute Apgar scores, respiratory distress syndrome, neonatal death, birth asphyxia, and the need for positive pressure ventilation, continuous positive airway pressure, tracheal intubation, and surfactant. Baseline characteristics, such as maternal age, parity, fetal gender, and high-risk pregnancy, were considered confounding variables. High-risk pregnancies were defined as any cases involving prolonged rupture of membranes or maternal comorbidities such as severe anemia, preeclampsia, diabetes, or COVID-19. Results During the study period, there were 830 spontaneous preterm births at our center. Of these, only 195 (23.5%) received complete doses of betamethasone. Low birth weight was more common in mothers who did not receive betamethasone compared to those who did (63.6% vs. 41.2%). The mean gestational age was lower in mothers who received betamethasone than in those who did not. Respiratory distress syndrome was more common in mothers who received betamethasone (P<0.001, RR 2.11, 95% CI (0.98-4.18)). However, after adjusting for confounding factors, such as gestational age and birth weight, betamethasone did not increase the risk of respiratory distress syndrome. Other adverse neonatal outcomes did not differ significantly. Conclusions There were no differences in neonatal outcomes between those who received betamethasone and those who did not., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rahimi et al.)

Background: Diagnostic imaging decision support (DI-DS) systems could be effective tools for reducing inappropriate diagnostic imaging examinations. Since effective design and evaluation of these systems requires in-depth understanding of their features and functions, the present study aims to map the existing literature on DI-DS systems to identify features and functions of these systems., Methods: The search was performed using Scopus, Embase, PubMed, Web of Science, and Cochrane Central Registry of Controlled Trials (CENTRAL) and was limited to 2000 to 2021. Analytical studies, descriptive studies, reviews and book chapters that explicitly addressed the functions or features of DI-DS systems were included., Results: A total of 6,046 studies were identified. Out of these, 55 studies met the inclusion criteria. From these, 22 functions and 22 features were identified. Some of the identified features were: visibility, content chunking/grouping, deployed as a multidisciplinary program, clinically valid and relevant feedback, embedding current evidence, and targeted recommendations. And, some of the identified functions were: displaying an appropriateness score, recommending alternative or more appropriate imaging examination(s), providing recommendations for next diagnostic steps, and providing safety alerts., Conclusions: The set of features and functions obtained in the present study can provide a basis for developing well-designed DI-DS systems, which could help to improve adherence to diagnostic imaging guidelines, minimize unnecessary costs, and improve the outcome of care through appropriate diagnosis and on-time care delivery., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Metastases of uveal melanoma (UM) spread predominantly to the liver. Due to low response rates to systemic therapies, liver-directed therapies (LDT) are commonly used for tumor control. The impact of LDT on the response to systemic treatment is unknown. A total of 182 patients with metastatic UM treated with immune checkpoint blockade (ICB) were included in this analysis. Patients were recruited from prospective skin cancer centers and the German national skin cancer registry (ADOReg) of the German Dermatologic Cooperative Oncology Group (DeCOG). Two cohorts were compared: patients with LDT (cohort A, n = 78) versus those without LDT (cohort B, n = 104). Data were analyzed for response to treatment, progression-free survival (PFS), and overall survival (OS). The median OS was significantly longer in cohort A than in cohort B (20.1 vs. 13.8 months; P = 0.0016) and a trend towards improved PFS was observed for cohort A (3.0 vs. 2.5 months; P = 0.054). The objective response rate to any ICB (16.7% vs. 3.8%, P = 0.0073) and combined ICB (14.1% vs. 4.5%, P = 0.017) was more favorable in cohort A. Our data suggest that the combination of LDT with ICB may be associated with a survival benefit and higher treatment response to ICB in patients with metastatic UM., (© 2023. The Author(s).)

Introduction: The effect of sub-clinical hypothyroidism (SCH) in pregnancy has been controversial. Furthermore, the impact of levothyroxine replacement on improving outcomes in pregnant women with SCH is unknown. This study aimed to assess the maternal and neonatal outcomes of pregnant women with SCH who were treated with levothyroxine replacement., Methods: This retrospective chart review was conducted at a tertiary hospital in Iran between 2020 and 2022. All pregnant women who had given birth during the study period were recruited. Those who did not have thyroid function test results within 10-12 weeks, as well as those with SCH who did not have levothyroxine replacement, were excluded. The subjects were divided into two groups based on the 2017 American Thyroid Association (ATA) criteria: non-SCH (TSH values 0.27-2.5 mIU/L) and SCH (TSH values more than 4.0 mIU/L). The demographic, obstetric, maternal, and neonatal outcomes of both groups were compared. The Chi-square test was used to compare the categorical variables. Binary logistic regression was used to assess differences in categorical variables., Results: With a frequency of 10.5%, 935 women out of 8888 were diagnosed with SCH. In terms of age, educational level, living residency, medical insurance, access to prenatal care, and smoking status, there were no differences between the two groups. In terms of gestational age, parity, onset of labor, history of infertility, hypertension, cardiovascular disease, anemia, and overt diabetes, there were no differences between the two groups; however, gestational diabetes was more common in those with SCH. Compared with the non-SCH group, the prevalence and risks of gestational diabetes [19.8 vs. 14.2, odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.72-3.95] were significantly higher in the SCH group after controlling for confounding factors. There were no differences in neonatal outcomes between the two groups., Conclusions: Except for gestational diabetes, we found no significant adverse events in terms of maternal and neonatal outcomes among women with SCH who were treated with levothyroxine., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Safavi Ardabili et al.)

Objective: A small percentage of acute pulmonary thromboembolisms (PTE) persist as chronic fibrin clots, potentially leading to chronic thromboembolic pulmonary hypertension (CTEPH). A scoring system for evaluating the burden of acute PTE based on computed tomography pulmonary angiogram (CTPA) findings was tested for its association with CTEPH within one year., Material and Methods: In this retrospective cohort of 475 patients with a definitive diagnosis of acute PTE, the Qanadli score (QS) was calculated on the initial CTPA. Through regular follow-up over 1 year, symptomatic patients underwent extensive evaluation., Results: Of the 475 patients enrolled in the study [age 58.3 ± 16.6, 195 (41.1%) female, QS: 13.01 ± 7.37/40], 321 patients completed the study. A total of 22 (6.8%) patients were definitively diagnosed with CTEPH. In univariate analysis, the initial QS was significantly higher in patients with subsequent CTEPH than in patients without (17 ± 5.6 vs. 13 ± 7.6, P = .009). QS was directly associated with CTEPH (odds ratio: 1.08, 95% confidence interval: 1.0-1.16, P = .042). The evolution of CTEPH in men could be predicted with a sensitivity of 100% and a specificity of 54% when a cut-off point of 14.5 (43.5%) was set for QS. The area under the receiver operating characteristic curve in this setting was 0.74 with a P-value of .032. Qanadli score failed to predict CTEPH in women., Conclusion: Scoring the clot burden in the pulmonary arteries through the Qanadli method can predict the evolution of CTEPH only in men 1 year after acute PTE. Women comprise most of the CTEPH patients. Thus, strict follow-up adherence seems to be even more important in women.

Background: Evidence on the optimal timing of RA is scarce, although increased periprocedural complications for unplanned procedures have been reported., Aims: To compare planned versus unplanned use of rotational atherectomy (RA) for plaque modification in patients with severely calcified coronary lesions., Methods: Procedural and 1-year follow-up data of planned (n = 562 lesions in 448 vessels of 416 patients) and unplanned (n = 490 lesions in 435 vessels of 403 patients) RA between 2008 and 2020 were analyzed using the propensity score methods. The primary composite endpoint was target lesion failure (TLF), defined as cardiovascular death (CVD), target vessel myocardial infarction (TVMI), or target lesion revascularization (TLR)., Results: Angiographic success was > 99% in both groups. Fluoroscopy time and contrast volume were significantly lower in planned RA (p < 0.001). Periprocedural complications including slow-flow, coronary dissection, and MI occurred in 4.8% after planned, and in 5.7% after unplanned RA. TLF occurred in 18.5% after planned, and in 14.7% after unplanned RA. Weighted subdistribution hazard ratios for TLFs revealed an unfavorable 1-year outcome for planned RA (sHR 1.62 [1.07-2.45], p = 0.023), which was driven by TLR (sHR 2.01 [1.18-3.46], p = 0.011), but not by CVD, or TVMI. No differences were observed in all-cause mortality., Conclusions: Unplanned RA was associated with favorable outcome when compared to planned RA. Thus, RA can safely be reserved for lesions that prove untreatable by conventional means. Randomized and prospective trials are needed to evaluate a predominant use of rotational atherectomy as a bailout strategy in the future., (© 2023. The Author(s).)

Adults with obesity have a higher risk of hospitalization and high hospitalization-related healthcare costs. However, a predictive model for the risk of readmission in patients with severe obesity is lacking. We conducted a retrospective cohort study enrolling all patients admitted for severe obesity (BMI ≥ 40 kg/m 2 ) between 2009 and 2018 to the Istituto Auxologico Italiano in Piancavallo. For each patient, all subsequent hospitalizations were identified from the regional database by a deterministic record-linkage procedure. A total of 1136 patients were enrolled and followed up for a median of 5.7 years (IQR: 3.1-8.2). The predictive factors associated with hospital readmission were age (HR = 1.02, 95%CI: 1.01-1.03, p < 0.001), BMI (HR = 1.02, 95%CI: 1.01-1.03, p = 0.001), smoking habit (HR = 1.17, 95%CI: 0.99-1.38, p = 0.060), serum creatinine (HR = 1.22, 95%CI: 1.04-1.44, p = 0.016), diabetes (HR = 1.17, 95%CI: 1.00-1.36, p = 0.045), and number of admissions in the previous two years (HR = 1.15, 95%CI: 1.07-1.23, p < 0.001). BMI lost its predictive role when restricting the analysis to readmissions within 90 days. BMI and diabetes lost their predictive roles when further restricting the analysis to readmissions within 30 days. In conclusion, in this study, we identified predictive variables associated with early and long-term hospital readmission in patients with severe obesity. Whether addressing modifiable risk factors could improve the outcome remains to be established.

Non-equilibrium spin-polarized transport properties of antiferromagnetic stanene nanoribbons are theoretically studied under the combining effect of a normal electric field and linearly polarized irradiation based on the tight-binding model at room temperature. Due to the existence of spin-orbit coupling in stanene lattice, applying normal electric field leads to splitting of band degeneracy of spin-resolved energy levels in conduction and valence bands. Furthermore, unequivalent absorption of the polarized photons at two valleys which is attributed to an antiferromagnetic exchange field results in unequal spin-polarized photocurrent for spin-up and spin-down components. Interestingly, in the presence of band bending which has been induced by edge potentials, an allowable quantum efficiency occurs over a wider wavelength region of the incident light. It is especially important that the variation of an exchange magnetic field generates spin semi-conducting behavior in the bended band structure. Moreover, it is shown that optical spin-filtering effect is obtained under the simultaneous effect of uniaxial strain and narrow edge potential., (© 2023. Springer Nature Limited.)

In this study, a new electrochemical sensor was designed based on a hybrid of polyamide (PA) and chromotropic acid (CA) nanofibers electrospun on a glassy carbon electrode (GCE) configured as PANFs-CANFs/GCE. The electrochemical response of this sensor showed an excellent electrochemical activity for the detection of Hg 2+ ions using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods. The proposed sensor exhibited the prominent electrocatalytic value of (α = 0.60, Log Ks = 3.45 s -1 and Γ = 3.30 × 10 -9 mmol/cm 2 ) as a result of PANFs-CANFs/GCE response to Hg 2+ ions. The recommended sensor also demonstrated a linear portion in the calibration curve over the concentration range of 30 to 450 nM with the limit of detection (LOD) and limit of quantitation (LOQ) of 9.98 nM and 29.97 nM, respectively. The fabricated sensor revealed reproducible and repeatable responses with a high level of stability. Therefore, we highly recommend this new electro-spun based sensor for quantifying Hg 2+ in drinking water and canned fish samples with the accurate and precise results and no side interferences., 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 Ltd. All rights reserved.)

Background: Nitric oxide is a chemical agent produced by endothelial cells in a healthy blood vessel, inhibiting the overgrowth of vascular smooth muscle cells and regulating vessel tone. Liposomes are biocompatible and biodegradable drug carriers with a similar structure to cell bilayer phospholipid membrane that can be used as useful nitric oxide carriers in vascular grafts., Method: Using a custom-designed apparatus, the sheep carotid arteries were decellularized while still maintaining important components of the vascular extracellular matrix (ECM), allowing them to be used as small-diameter vascular grafts. A chemical signal of sodium nitrite was applied to control smooth muscle cells' behavior under static and dynamic cell culture conditions. The thin film hydration approach was used to create nano-liposomes, which were then used as sodium nitrite carriers to control the drug release rate and enhance the amount of drug loaded into the liposomes., Results: The ratio of 80:20:2 for DPPC: Cholesterol: PEG was determined as the optimum formulation of the liposome structure with high drug encapsulation efficiency (98%) and optimum drug release rate (the drug release rate was 40%, 65%, and 83% after 24, 48, and 72 h, respectively). MTT assay results showed an improvement in endothelial cell proliferation in the presence of nano-liposomal sodium nitrite (LNS) at the concentration of 0.5 μg/mL. Using a suitable concentration of liposomal sodium nitrite (0.5 μg/mL) put onto the constructed scaffold resulted in the controllable development of smooth muscle cells in the experiment. The culture of smooth muscle cells in a pulsatile perfusion bioreactor indicated that in the presence of synthesized liposomal sodium nitrite, the overgrowth of smooth muscle cells was inhibited in dynamic cell culture conditions. The mechanical properties of ECM graft were measured, and a multi-scale model with an accuracy of 83% was proposed to predict mechanical properties successfully., Conclusion: The liposomal drug-loaded small-diameter vascular graft can prevent the overgrowth of SMCs and the formation of intimal hyperplasia in the graft. Aside from that, the effect of LNS on endothelial has the potential to stimulate endothelial cell proliferation and re-endothelialization., (© 2023 The Authors. Artificial Organs published by International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Background: Childhood lymphoma is the second leading cause of cancer in children under 15 years of age in Iran. The aim of this study was to investigate the spatial and time variations in lymphoma incidence as well as the children's survival time in Iran., Method: This cross-sectional study was conducted using lymphoma cases (children under 14 years of age) from 2005 to 2015, and the data were obtained from the National Cancer Registry Center. The frequency, age-standardised incidence rate (ASIR), spatial clustering in national level and the survival rate (1 year and 5 years) using Kaplan-Meier method were evaluated. We used Spatial and Temporal Scan statistics software in order to detect statistically significant clusters in spatial analysis., Results: A total number of 746 girls and 1610 boys were diagnosed with lymphoma during a 10-year period. ASIRs (per 100 000 people) for girls ranged from 0 in Ilam to 3.47 in Yasuj, and it ranged from 0.19 in Ilam to 5.91 in Yazd for boys from 2005 to 2015. Spatial analysis result showed a large statistically significant cluster (the most likely cluster) for both boys (relative risk (RR)=2.37) and girls (RR=2.49) located in the northwest of Iran. Fortunately, survival rate for both boys and girls was over 95.5%., Conclusion: Lymphoma incidence rates had heterogeneous geographical distribution, and some significant clusters were identified which strengthens the role of possible aetiological factors, and further studies are needed to clarify this ambiguity. Fortunately, the survival rate of this cancer in Iran was good and it was similar to the high-income countries., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Glioblastoma (GBM) is an aggressive type of cancer that originates in the cells called astrocytes, which support the functioning of nerve cells. It can develop in either the brain or the spinal cord and is also known as glioblastoma multiform. GBM is a highly aggressive cancer that can occur in either the brain or spinal cord. The detection of GBM in biofluids offers potential advantages over current methods for diagnosing and treatment monitoring of glial tumors. Biofluid-based detection of GBM focuses on identifying tumor-specific biomarkers in blood and cerebrospinal fluid. To date, different methods have been used to detect biomarkers of GBM, ranging from various imaging techniques to molecular approaches. Each method has its own strengths and weaknesses. The present review aims to scrutinize multiple diagnostic methods for GBM, with a focus on proteomics methods and biosensors. In other words, this study aims to provide an overview of the most significant research findings based on proteomics and biosensors for the diagnosis of GBM., (© 2023. The Author(s).)

Background: Robust optimization (RO) has been proposed to mitigate breathing motion uncertainty during treatment in intensity-modulated radiation therapy (IMRT) planning for breast or lung cancer. RO is a pessimistic approach that implicitly trades off average-case for worst-case treatment plan quality. Pareto robust optimization (PRO) provides a mechanism for improving nonworst-case plan outcomes, but often remains overly conservative in the average case., Purpose: The goal of this study is to characterize the trade-off between the optimality of robust IMRT plans in the worst case and the treatment quality in nonworst-case realizations of breathing motion. We provide a light Pareto robust optimization (LPRO) method for IMRT and test its clinical viability for improving the average-case plan quality while preserving robustness, in comparison to RO and PRO plans., Methods: Five clinical left-sided breast cancer patients were included in the study, each with an associated 4D-CT dataset approximating their breathing cycle. Using simulation, 50 different breathing patterns were generated for each patient. A first-stage optimization was solved with the objective of cardiac sparing while ensuring robustness on the target dose under breathing uncertainty. Next, a second-stage objective of overdose minimization was considered to improve plan quality in a controlled LPRO framework. For the simulated breathing scenarios, the trade-off between loss of average cardiac sparing at worst-case and the overdose to the breast was quantified by calculating the accumulated dose for each plan in each breathing scenario. Finally, the RO, PRO, and LPRO plans were each evaluated using eight clinical dose-volume criteria on the target and organs at risk., Results: The LPRO models allowed for significantly sharper dose falloffs in the expected dose instances, relative to both RO and PRO models. Plans began looking valid for delivery with average allowances of as little as +0.1 Gy additional dose to the heart, and most patients experienced diminishing returns beyond +0.2 Gy., Conclusions: Without sacrificing robustness, the LPRO approach produces viable plans with true total-target irradiation. Furthermore, the plans produced were able to reduce the nonworst-case downside typical of RO, without the characteristic overdosing or average-case pessimism seen in prior models., (© 2023 American Association of Physicists in Medicine.)

Background: Elevated C-peptide has been suggested as a risk factor for coronary artery disease (CAD). Elevated urinary C-peptide to creatinine ratio (UCPCR) as an alternative measurement is shown to be related to insulin secretion dysfunction; however, data regarding UCPCR predictive value for CAD in diabetes mellitus (DM) are scarce. Therefore, we aimed to assess the UCPCR association with CAD in type 1 DM (T1DM) patients., Methods: 279 patients previously diagnosed with T1DM included and categorized into two groups of CAD (n = 84) and without-CAD (n = 195). Furthermore, each group was divided into obese (body mass index (BMI) ≥ 30) and non-obese (BMI < 30) groups. Four models utilizing the binary logistic regression were designed to evaluate the role of UCPCR in CAD adjusted for well-known risk factors and mediators., Results: Median level of UCPCR was higher in CAD group compared to non-CAD group (0.07 vs. 0.04, respectively). Also, the well-acknowledged risk factors including being active smoker, hypertension, duration of diabetes, and body mass index (BMI) as well as higher levels of haemoglobin A1C (HbA1C), total cholesterol (TC), low-density lipoprotein (LDL) and estimated glomeruli filtration rate (e-GFR) had more significant pervasiveness in CAD patients. Based on multiple adjustments by logistic regression, UCPCR was a strong risk factor of CAD among T1DM patients independent of hypertension, demographic variables (gender, age, smoking, alcohol consumption), diabetes-related factors (diabetes duration, FBS, HbA1C), lipid profile (TC, LDL, HDL, TG) and renal-related indicators (creatinine, e-GFR, albuminuria, uric acid) in both patients with BMI≥30 and BMI < 30., Conclusion: UCPCR is associated with clinical CAD, independent of CAD classic risk factors, glycaemic control, insulin resistance and BMI in type 1 DM patients., (© 2023 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Introduction: There is a controversy regarding the relationship between blood eosinophil count and COPD exacerbation. We aimed to determine whether peripheral eosinophils upon COPD diagnosis could affect the frequency and severity of annual acute exacerbation of COPD (AECOPD)., Methods: This prospective study was conducted on 973 newly diagnosed COPD patients who were under 1-year follow-up in a pulmonology center in Iran. The Cox proportional model, polynomial regression, and receiver operator characteristic curves were conducted to evaluate the impact of the eosinophil levels on AECOPD. A linear regression model was conducted to evaluate the continuous association of eosinophilic count with AECOPDs., Results: Patients with eosinophil >200 cells/microliter were higher pack-year smokers with more pulmonary hypertension prevalence compared to COPD patients with <200 cells/microliter. There was a positive correlation between the eosinophilic count and the frequency of AECOPDs. Eosinophil >900 cells/microliter and eosinophil >600 cells/microliter had a sensitivity of 71.1% and 64.3%, respectively, in predicting the occurrence of more than one AECOPD. Eosinophilic count cutoff of 800 cells/microliter had the highest Youden index with sensitivity and specificity of 80.2% and 76.6%, respectively, for incident AECOPD in newly diagnosed patients. Using a linear model, increasing 180 cells/microliter in serum eosinophils was associated with further exacerbation. Evaluating gender, BMI, smoking pack-year, FEV1/FVC, CAT score, GOLD score, pulmonary hypertension, annual influenza, pneumococcal vaccinations, leukocytosis, and blood eosinophils, only blood eosinophils (hazard ratio (HR) = 1.44; 95% confidence interval = 1.33-2.15; p value = 0.03) and GOLD score (HR = 1.19; 95% CI = 1.30-1.52; p value = 0.03) were found as independent risk factors of AECOPD >3 episodes/year. Requirement for ICU admission, invasive ventilation, and mortality rate due to AECOPDs was similar between eosinophilic and noneosinophilic groups., Conclusion: Eosinophilia upon COPD diagnosis is a factor of recurrent AECOPDs. To reduce the risk of AECOPDs and the burden of disease, clinicians may consider inhaler corticosteroids and domiciliary oxygen with a lower threshold for eosinophilic-COPD patients regardless of their clinical status., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Arda Kiani et al.)

Background and Aims: Considering the rapid spread and transmission of COVID-19 and its high mortality rate, self-care practices are of special importance during this pandemic to prevent and control the spread of the virus. In this regard, electronic health systems can play a major role in improving self-care practices related to coronavirus disease. This study aimed to review the electronic health technologies used in each of the constituent elements of the self-care (self-care maintenance, self-care monitoring, and self-care management) during the COVID-19 pandemic., Methods: This scoping review was conducted based on Arksey and O'Malley's framework. In this study, the specific keywords related to "electronic health," "self-care," and "COVID-19" were searched on PubMed, Web of Science, Scopus, and Google., Results: Of the 47 articles reviewed, most articles (27 articles) were about self-care monitoring and aimed to monitor the vital signs of patients. The results showed that the use of electronic health tools mainly focuses on training in the control and prevention of coronavirus disease during this pandemic, in the field of self-care maintenance, and medication management, communication, and consultation with healthcare providers, in the field of self-care management. Moreover, the most commonly used electronic health technologies were mobile web applications, smart vital signs monitoring devices, and social networks, respectively., Conclusion: The study findings suggested that the use of electronic health technologies, such as mobile web applications and social networks, can effectively improve self-care practices for coronavirus disease. In addition, such technologies can be applied by health policymakers and disease control and prevention centers to better manage the COVID-19 pandemic., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Alzheimer's disease (AD) is the most common type of dementia that affects millions of individuals worldwide. It is an irreversible neurodegenerative disorder that is characterized by memory loss, impaired learning and thinking, and difficulty in performing regular daily activities. Despite nearly two decades of collective efforts to develop novel medications that can prevent or halt the disease progression, we remain faced with only a few options with limited effectiveness. There has been a recent growth of interest in the role of nutrition in brain health as we begin to gain a better understanding of what and how nutrients affect hormonal and neural actions that not only can lead to typical cardiovascular or metabolic diseases but also an array of neurological and psychiatric disorders. Vitamins and minerals, also known as micronutrients, are elements that are indispensable for functions including nutrient metabolism, immune surveillance, cell development, neurotransmission, and antioxidant and anti-inflammatory properties. In this review, we provide an overview on some of the most common vitamins and minerals and discuss what current studies have revealed on the link between these essential micronutrients and cognitive performance or AD.

Here, we prepared a magnetic nanocomposite system composed of a cluster of magnetite nanoparticles coated with silica shell (MSNPs) with an average diameter of 140 ± 20 nm and conjugated with CD9 antibody (AntiCD9) using different strategies including adsorption or chemical conjugation of antibody molecules to either aminated MSNPs (AMSNPs) or carboxylated MSNPs (CMSNPs). Then, MSNPs were employed to isolate exosomes from ultracentrifuge-enriched solution, PC3 cell-culture medium, or exosome-spiked simulated plasma samples. Quantitative tests using nanoparticle-tracking analysis confirmed antibody-covalently conjugated MSNPs, i.e. the AntiCD9-AMSNPs and AntiCD9-CMSNPs enabled >90% recovery of exosomes. Additionally, the exosomes isolated with AntiCD9-CMSNPs showed higher recovery efficiency compared to the AntiCD9-AMSNPs. For both nanoadsorbents, lower protein impurities amounts were obtained as compared to that of exosomes isolated by ultracentrifugation and Exocib kit. The mean diameter assessment of the isolated exosomes indicates that particles isolated by using AntiCD9-AMSNPs and AntiCD9-CMSNPs have smaller sizes (136 ± 2.64 nm and 113 ± 11.53 nm, respectively) than those obtained by UC-enriched exosomes (140.9 ± 1.6 nm) and Exocib kit (167 ± 10.53 nm). Such promising results obtained in the isolation of exosomes recommend magnetic nanocomposite as an efficient tool for the simple and fast isolation of exosomes for diagnosis applications., (© 2023 IOP Publishing Ltd.)

Case reports indicate that magnets in smartphones could be a source of electromagnetic interference (EMI) for active implantable medical devices (AIMD), which could lead to device malfunction, compromising patient safety. Recognizing this challenge, we implemented a high-fidelity 3D magnetic field mapping (spatial resolution 1 mm) setup using a three-axis Hall probe and teslameter, controlled by a robot (COSI Measure). With this setup, we examined the stray magnetic field of an iPhone 13 Pro, iPhone 12, and MagSafe charger to identify sources of magnetic fields for the accurate risk assessment of potential interferences with AIMDs. Our measurements revealed that the stray fields of the annular array of magnets, the wide-angle camera, and the speaker of the smartphones exceeded the 1 mT limit defined by ISO 14117:2019. Our data-driven safety recommendation is that an iPhone 13 Pro should be kept at least 25 mm away from an AIMD to protect it from unwanted EMI interactions. Our study addresses safety concerns due to potential device-device interactions between smartphones and AIMDs and will help to define data-driven safety guidelines. We encourage vendors of electronic consumer products (ECP) to provide information on the magnetic fields of their products and advocate for the inclusion of smartphones in the risk assessment of EMI with AIMDs.

Background: Colorectal cancer is one of the most prevalent gastrointestinal cancers in Iran i.e., the fourth and the second prevalent cancer among Iranian males and females, respectively. A routine screening program is effective in the early detection of disease which can reduce the cancer burden both for individuals and society. In 2015, Iran's Package of Essential Non- communicable Diseases program had been piloted in Shahreza city in Isfahan province. Colorectal cancer screening for the population aged 50-70 was a part of this program. So far, there was no study about the cost and outcomes of that program. Thus, this study aimed to analyze the costs and outcomes of colorectal cancer screening done from 2016 to 2019 in Shahreza., Methods: This cost-outcome description study used the data of 19,392 individuals who were 50-70 years old experienced a fecal immunochemical test (FIT) and had an electronic health record. All direct costs including personnel, building space, equipment, training, etc. were extracted from the financial documents existing in the Isfahan province Health Center. The outcome was defined as positive FIT, detection of adenoma or malignancy as recorded in the E-integrated health system., Results: The results of this study indicated that the direct costs of the colorectal cancer screening program during the years 2016-2019 were 7,368,707,574 Rials (321,029 PPP$) in Shahreza, Isfahan province. These costs resulted in identifying 821 people with a positive FIT test, of those 367 individuals were undergone colonoscopy. Of whom 8 cases of colorectal cancer, and 151 cases with polyps were diagnosed., Conclusion: This study showed that by paying a small amount of 320 thousand international dollars we could prevent 151 cases of polyps to be progressed to colorectal cancer,resulting in a significant reduction in colorectal cancer incidence., (© 2023. The Author(s).)

Background: In vivo drug screening in animal models is contrary to ethical values, costly and time-consuming. Traditional static in vitro models do not reflect the basic characteristics of bone tumor microenvironments; therefore, perfusion bioreactors, in particular, would be an applicable choice due to their advantages to regenerate versatile bone tumor models for studying in vitro novel drug delivery systems., Methods: In this study, an optimal drug formulation of liposomal doxorubicin was prepared, and the release kinetics of the drug and its toxicity effect on MG-63 bone cancer cell line were investigated in two-dimensional, static three-dimensional media on a PLGA/β-TCP scaffold and also in a dynamic media in a perfusion bioreactor. In this assay, the efficacy of the IC 50 of this formulation which had been obtained in two-dimensional cell culture (= 0.1 μg/ml), was studied in static and dynamic threedimensional media after 3 and 7 days. Liposomes with good morphology and encapsulation efficiency of 95% had release kinetics of the Korsmeyer-Peppas model., Results: The results of cell growth before treatment and cell viability after treatment in all three environments were compared. Cell growth in 2D was rapid, while it was slow in static 3D conditions. In the dynamic 3D environment, it was significant compared to the static tumor models. Cell viability after 3 and 7 days from treatment was 54.73% and 13.39% in 2D conditions, 72.27% and 26.78% in the static 3D model, while 100% and 78.92% in the dynamic culture indicating the effect of drug toxicity over time, but drug resistance of 3D models compared to 2D culture. In the bioreactor, the formulation used in the mentioned concentration showed very small cytotoxicity demonstrating the dominance of mechanical stimuli on cell growth over drug toxicity., Conclusion: Increasing drug resistance in 3D models compared to 2D models indicates the superiority of liposomal Dox over free form to reduce IC 50 concentration., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author's keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is "self-destroy and rebuild", which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms' clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)