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Hossein Derakhshankhah, 1, 2,* Samira Jafari, 1, 2,* Sajad Sarvari, 3 Ebrahim Barzegari, 4 Faezeh Moakedi, 5 Milad Ghorbani, 6 Behrang Shiri Varnamkhasti, 1 Mehdi Jaymand, 7 Zhila Izadi, 1, 8 Lobat Tayebi 9 1Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 2Zistmavad Pharmed Co., Tehran, Iran; 3Department of Pharmaceutical and Pharmacological Science, School of Medicine, West Virginia University, Morgantown, WV, USA; 4Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 5Department of Biochemistry and Molecular Biology, School of Medicine, West Virginia University, Morgantown, WV, USA; 6Department of Chemical Engineering, College of Engineering, University of Tehran, Tehran, Iran; 7Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran; 8Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran; 9Marquette University School of Dentistry, Milwaukee, WI 53201, USA*These authors contributed equally to this workCorrespondence: Zhila Izadi; Lobat Tayebi Email izadi_zh@razi.tums.ac.ir; lobat.tayebi@marquette.eduAbstract: The advent of porous materials, in particular zeolitic nanoparticles, has opened up unprecedented putative research avenues in nanomedicine. Zeolites with intracrystal mesopores are low framework density aluminosilicates possessing a regular porous structure along with intricate channels. Their unique physiochemical as well as physiological parameters necessitate a comprehensive overview on their classifications, fabrication platforms, cellular/macromolecular interactions, and eventually their prospective biomedical applications through illustrating the challenges and opportunities in different integrative medical and pharmaceutical fields. More particularly, an update on recent advances in zeolite-accommodated drug delivery and the prevalent challenges regarding these molecular sieves is to be presented. In conclusion, strategies to accelerate the translation of these porous materials from bench to bedside along with common overlooked physiological and pharmacological factors of zeolite nanoparticles are discussed and debated. Furthermore, for zeolite nanoparticles, it is a matter of crucial importance, in terms of biosafety and nanotoxicology, to appreciate the zeolite-bio interface once the zeolite nanoparticles are exposed to the bio-macromolecules in biological media. We specifically shed light on interactions of zeolite nanoparticles with fibrinogen and amyloid beta which had been comprehensively investigated in our recent reports. Given the significance of zeolite nanoparticles’ interactions with serum or interstitial proteins conferring them new biological identity, the preliminary approaches for deeper understanding of administration, distribution, metabolism and excretion of zeolite nanoparticles are elucidated.Keywords: zeolite, mesoporous, nanostructure, biosafety, biomedical applications

Background: Purple coneflower (Echinaceae purpurea L.) is a perennial herbaceous with astringent properties, disinfectant, antimicrobial and anti intoxication activity. The main objective of this study was to evaluate the antimicrobial activity of shoot essential oil of purple coneflower against some microorganisms including gram positive, gram negative bacteria, filamentous fungi and yeasts. Material and Methods: In this experimental and laboratory investigation, plant samples were collected in full blooming stage. Shoot essential oil was extracted by hydro-distillation technique using Clevenger apparatus. The chemical constitutes of this oil was analyzed by GC and GC/MS method. Anti microbial properties of the essential oil were determined using micro broth dilution and well disk diffusion methods. At the end, data were analyzed by the SPSS version 15 software, using the T-test and Duncan s' test. Results: Twenty nine components were identified by GC and GC/MS in the essential oil of purple coneflower representing 96.21% of total oil. The major components were Germacrene D (53.30%), - Cymene (9.78%), β-Caryophyllene (7.52%), α-Humulene (5.22%), β-Bisabolene (4.43%) and α-Pinene (4.23%), respectively. This oil exhibited strong antifungal activity against filamentous fungi and yeast with average of inhibition zone (AIZ) 39.63. Microorganisms differ in their resistance to purple coneflower oil. All of the bacteria including gram positive and gram negative bacteria are more resistant than fungi; and gram negative bacteria are more resistant than gram positive bacteria. Pseudomonas aeruginosa and Salmonella typhimurium were more resistant than others. Conclusion: The results of this study showed that coneflower essential oil with significant antimicrobial effects and can be used instead of synthetic antibiotics that microbial resistance towards them is increasing. [ABSTRACT FROM AUTHOR]

The number of hypercholesterolemic people is increasing rapidly in the world. Diet and nutrition are important factors in the promotion and maintenance of health throughout life. According to the World Health Organization (WHO) and the Food and Agricultural Organization (FAO), several dietary patterns, along with lifestyle habits (exercise, smoking, and alcohol consumption), constitute major modifiable risk factors in relation to the development of non communicable diseases: cardiovascular diseases (CVD), cancer, type 2 diabetes, obesity, osteoporosis and dental diseases. Improving diet and lifestyle is a critical component of the American Heart Association's (AHA) strategy for cardiovascular disease risk reduction in the general population. Hypercholesterolemia is one of the major risk factors for heart disease. In this review, cholesterol reducing effects of different categories of food are presented. Also technical aspects of adding these functional components to foods are discussed. [ABSTRACT FROM AUTHOR]

Objective: We determined whether socioeconomic status (SES) and sex are associated with functional status (FS) in axial spondyloarthritis (axSpA)., Methods: We conducted a cohort study of patients with axSpA in the Rheumatology Informatics System for Effectiveness (RISE) registry. We performed cross-sectional and longitudinal analyses of FS through the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) using GEE models. Area Deprivation Index (ADI) was used as an SES proxy. The cross-sectional analysis tested for a linear trend across ADI quintiles for MDHAQ. The longitudinal analysis' outcome was functional decline. We reported predictive margins and assessed for interaction with sex. In the longitudinal analysis, we reported odds of functional decline., Results: In the cross-sectional analysis (N=5,658) mean (SD) age was 53.8 years (15.2), 55.8% were female, and 71.4% were non-Hispanic White. Average (SD) MDHAQ was 1.6 (2.0) in men vs. 2.1 (2.2) in women. Predicted mean MDHAQ score was 2.2 (95%CI 1.8-2.7) for the lowest ADI quintile and 1.8 (95%CI 1.4-2.1) for the highest. Women had lower FS compared to men across quintiles. In the longitudinal analysis (N= 2,341) the proportion with FS decline was 14.3% (95% CI 7.6%-25.5%) for the lowest SES quintile compared to 9.6% (95% CI 5.2%-17.1%) for the highest. Women had 1.7 (95%CI 1.3-2.2) times higher odds of functional decline compared to men. There was no interaction with sex., Conclusions: In this large sample of axSpA patients, those with lower SES had worse FS and functional decline. Women had worse FS than men, initially and over time., (This article is protected by copyright. All rights reserved.)

Pomegranate molasses is made from concentrated pomegranate juice with nothing added. Due to its nutritional value, limitation in production, and high production cost, this product may be adulterated by date syrup. This study was done to differentiate various types of pomegranate molasses and investigate the possibility of nonauthenticity detection in pomegranate molasses samples using the hyperspectral imaging (HSI) technique compared with physicochemical measurement analysis. The physicochemical properties (brix index, sucrose, acidity, ash content, pH, and formalin index) of 24 samples were measured as the reference analysis method, and it was found that the formalin index was a good factor for pomegranate molasses authenticity evaluation. Additionally, an HSI system (400-1000 nm) was used as a nondestructive and rapid screening method to capture spectral data of the samples. The evolutionary wavelength selection algorithm was applied to select effective wavelengths in sample clustering based on the obtained Davies-Bouldin index. Next, principal component analysis was used to visually interpret the spectral data of the sample when using the selected wavelengths and the whole spectra of the samples. Finally, an automatic clustering algorithm by the artificial bee colony as an unsupervised method was developed for the clustering of the authentic and nonauthentic samples. The method did not need descriptively labeled samples and obtained agreed satisfactorily with the degree of nonauthenticity in the samples. This study showed that the developed HSI technique coupled with an automatic clustering algorithm could detect date syrup nonauthenticity in pomegranate samples from the level of 5% adulteration., (© 2024 Institute of Food Technologists.)

Objective: Accurate identification of lupus nephritis (LN) cases is essential for patient management, research and public health initiatives. However, LN diagnosis codes in electronic health records (EHRs) are underused, hindering efficient identification. We investigated the current performance of International Classification of Diseases (ICD) codes, 9th and 10th editions (ICD9/10), for identifying prevalent LN, and developed scoring systems to increase identification of LN that are adaptable to settings with and without LN ICD codes., Methods: Training and test sets derived from EHR data from a large health system. An external set comprised data from the EHR of a second large health system. Adults with ICD9/10 codes for SLE were included. LN cases were ascertained through manual chart reviews conducted by rheumatologists. Two definitions of LN were used: strict (definite LN) and inclusive (definite, potential or diagnostic uncertainty). Gradient boosting models including structured EHR fields were used for predictor selection. Two logistic regression-based scoring systems were developed ('LN-Code' included LN ICD codes and 'LN-No Code' did not), calibrated and validated using standard performance metrics., Results: A total of 4152 patients from University of California San Francisco Medical Center and 370 patients from Zuckerberg San Francisco General Hospital and Trauma Center met the eligibility criteria. Mean age was 50 years, 87% were female. LN diagnosis codes demonstrated low sensitivity (43-73%) but high specificity (92-97%). LN-Code achieved an area under the curve (AUC) of 0.93 and a sensitivity of 0.88 for identifying LN using the inclusive definition. LN-No Code reached an AUC of 0.91 and a sensitivity of 0.95 (0.97 for the strict definition). Both scoring systems had good external validity, calibration and performance across racial and ethnic groups., Conclusions: This study quantified the underutilisation of LN diagnosis codes in EHRs and introduced two adaptable scoring systems to enhance LN identification. Further validation in diverse healthcare settings is essential to ensure their broader applicability., Competing Interests: Competing interests: ZI is currently employed by BMS. MG reports grants from the National Institutes of Health and NIAMS, outside the submitted work. She is currently employed by Pfizer. CA has received funding from Rheumatology Research Foundation Scientist Development Award. GS reports no conflicts of interest. JY’s work is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155). Outside of this work, she has received research grants or performed consulting for Gilead, BMS Foundation, Pfizer, Aurinia and AstraZeneca., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern., Methods: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types., Results: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes., Conclusion: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study., (© 2023 American College of Rheumatology.)

Cancer is one of the most common diseases and causes of death worldwide. Since common treatment approaches do not yield acceptable results in many patients, developing innovative strategies for effective treatment is necessary. Immunotherapy is one of the promising approaches that has been highly regarded for preventing tumor recurrence and new metastases. Meanwhile, inhibiting immune checkpoints is one of the most attractive methods of cancer immunotherapy. Cytotoxic T lymphocyte-associated protein-4 (CTLA-4) is an essential immune molecule that plays a vital role in cell cycle modulation, regulation of T cell proliferation, and cytokine production. This molecule is classically expressed by stimulated T cells. Inhibition of overexpression of immune checkpoints such as CTLA-4 receptors has been confirmed as an effective strategy. In cancer immunotherapy, immune checkpoint-blocking drugs can be enhanced with nanobodies that target immune checkpoint molecules. Nanobodies are derived from the variable domain of heavy antibody chains. These small protein fragments have evolved entirely without a light chain and can be used as a powerful tool in imaging and treating diseases with their unique structure. They have a low molecular weight, which makes them smaller than conventional antibodies while still being able to bind to specific antigens. In addition to low molecular weight, specific binding to targets, resistance to temperature, pH, and enzymes, high ability to penetrate tumor tissues, and low toxicity make nanobodies an ideal approach to overcome the disadvantages of monoclonal antibody-based immunotherapy. In this article, while reviewing the cellular and molecular functions of CTLA-4, the structure and mechanisms of nanobodies' activity, and their delivery methods, we will explain the advantages and challenges of using nanobodies, emphasizing immunotherapy treatments based on anti-CTLA-4 nanobodies., (© 2024. The Author(s).)

The anticancer properties of curcumin have been broadly examined in several shapes, such as nanoparticles and nanocomposite structures. Despite its benefits, curcumin also has some disadvantages, including rapid metabolism, poor absorption, and rapid systemic excretion. Therefore, numerous strategies have been used to increase curcumin's bioavailability. One of these approaches is the use of porous particles like aerogels as drug carriers. Aerogels are special due to their peculiar physical structure. They have a high specific surface area, a significant amount of porosity, and a solid composition, which make them a good choice for drug delivery systems. In the present study, a pH-sensitive aerogel was constructed and evaluated for targeted drug delivery of curcumin to colon cancer. To control the release of curcumin, trehalose was used as a coating agent, and PLP (poly(l-lysine isophthalamide)) was used as a targeted drug delivery agent. PLP is a pseudo-peptidic polymer that increases the cell permeability. In order to investigate and compare the synthesized aerogel before and after loading curcumin and coating with trehalose, physicochemical characterization analyses were performed. Finally, the efficacy of the final formulation was evaluated on HT29 colon cells using the cell bioavailability test. The results indicated the successful synthesis of the aerogel with porous structure with solitary cavities. The trehalose coating performed well, preventing drug release at lower pH but allowing the drug to be released at its intended site. The designed curcumin-loaded porous particles functionalized with PLP showed significant efficacy due to increasing penetration of curcumin into cells, and has potential for use as a new drug carrier with dual effectivity in cancer therapy., Competing Interests: Declared none., (This journal is © The Royal Society of Chemistry.)

Targeted Protein Modification (TPM) is an umbrella term encompassing numerous tools and approaches that use bifunctional agents to induce a desired modification over the POI. The most well-known TPM mechanism is PROTAC-directed protein ubiquitination. PROTAC-based targeted degradation offers several advantages over conventional small-molecule inhibitors, has shifted the drug discovery paradigm, and is acquiring increasing interest as over ten PROTACs have entered clinical trials in the past few years. Targeting the protein of interest for proteasomal degradation by PROTACS was the pioneer of various toolboxes for selective protein degradation. Nowadays, the ever-increasing number of tools and strategies for modulating and modifying the POI has expanded far beyond protein degradation, which phosphorylation and de-phosphorylation of the protein of interest, targeted acetylation, and selective modification of protein O-GlcNAcylation are among them. These novel strategies have opened new avenues for achieving more precise outcomes while remaining feasible and minimizing side effects. This field, however, is still in its infancy and has a long way to precede widespread use and translation into clinical practice. Herein, we investigate the pros and cons of these novel strategies by exploring the latest advancements in this field. Ultimately, we briefly discuss the emerging potential applications of these innovations in cancer therapy, neurodegeneration, viral infections, and autoimmune and inflammatory diseases., 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 Masson SAS. All rights reserved.)

Parkinson's disease (PD) is a progressive disorder that belongs to a class of neurodegenerative disorders (NDs) called Synucleinopathies. It has characterized by the misfolding and aggregation of a-synuclein. Our understanding of PD continues to evolve, and so does our approach to treatment. including therapies aimed at delaying pathology, quitting neuronal loss, and shortening the course of the disease by selectively targeting essential proteins suspected to play a role in PD pathogenesis. One emerging approach that is generating significant interest is Targeted Protein Degradation (TPD). TPD is an innovative method that allows us to specifically break down certain proteins using specially designed molecules or peptides, like PROteolysis-TArgeting-Chimera (PROTACs). This approach holds great promise, particularly in the context of NDs. In this review, we will briefly explain PD and its pathogenesis, followed by discussing protein degradation systems and TPD strategy in PD by reviewing synthesized small molecules and peptides. Finally, future perspectives and challenges in the field are discussed., Competing Interests: Declaration of Competing Interest Authors declare no conflict of interest in the present work., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Spermatogenesis is significantly influenced by the thyroid gland. Thyroid disorders can be caused by a variety of factors. Traditionally, Ellettaria cardamomum has been used to treat a variety of ailments. The effects of E. cardamomum extract (ECE) on spermatogenesis in hypothyroid mice were investigated in this study., Methods: In this study 42 male mice, weighing (25-35 g) were randomly divided in six groups: control group (taking normal saline, 0.5 mL/day, by oral gavage [P.O.]), hypothyroid group (taking 0.1% propylthiouracil in drinking water for 2 weeks), hypothyroid groups treated by levothyroxine (15 mg/kg/day, P.O.) and hypothyroid groups treated by ECE (100, 200 and 400 mg/kg/day, P.O.). After the end of experiments the mice were anaesthetised and blood samples were collected for hormonal analysis., Results: The sperm count and microscopic studies of testes were done also. Our results showed that the T 3 , T 4 , testosterone levels and spermatogenesis in hypothyroid animals decreased and thyroid-stimulating hormone, follicle-stimulating hormone and luteinizing hormone increased compared with control group. Treatment by ECE reverse these effects in comparison with hypothyroid group., Conclusions: According to our findings, the ECE may stimulates thyroid gland function and increases testosterone and spermatogenesis., (© 2023 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Objectives: This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial., Methods: A total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded., Results: At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects., Conclusion: Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19., Trial Registration: This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138)., Competing Interests: Declaration of Competing Interest No conflict of interest exists for any of the authors associated with the manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Perfluorocarbon (PFC) are biocompatible compounds, chemically and biologically inert, and lacks toxicity as oxygen carriers. PFCs nanoemulsions and nanoparticles (NPs) are highly used in diagnostic imaging and enable novel imaging technology in clinical imaging modalities to notice and image pathological and physiological alterations. Therapeutics with PFCs such as the innovative approach to preventing thrombus formation, PFC nanodroplets utilized in ultrasonic medication delivery in arthritis, or PFC-based NPs such as Perfluortributylamine (PFTBA), Pentafluorophenyl (PFP), Perfluorohexan (PFH), Perfluorooctyl bromide (PFOB), and others, recently become renowned for oxygenating tumors and enhancing the effects of anticancer treatments as oxygen carriers for tumor hypoxia. In this review, we will discuss the recent advancements that have been made in PFC's applications in theranostic (therapeutics and diagnostics) as well as assess the benefits and drawbacks of these applications., 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. The reviewer HD declared a shared affiliation with the NK, RA, MA, GM, and ZI to the handling editor at the time of review., (Copyright © 2023 Kakaei, Amirian, Azadi, Mohammadi and Izadi.)

Objective: The American College of Rheumatology's (ACR) 2020 guidelines for the management of gout recommend using a treat-to-target approach to lower serum urate (SU). Using the ACR's Rheumatology Informatics System for Effectiveness registry, we examined the use of a treat-to-target approach among gout patients receiving long-term urate-lowering therapy (ULT) and followed longitudinally by rheumatologists., Methods: Included patients had one or more diagnoses for gout in 2018-2019 and continuous use of ULT for ≥12 months. We assessed the proportions of patients with SU monitoring and, among those tested, who achieved SU <6.0 mg/dl during the measurement year. Multilevel logistic regression adjusting for sociodemographics, comorbidities, region, and health care utilization was used to determine factors associated with SU monitoring and achievement of target SU., Results: A total of 9,560 were included. The mean ± SD age was 67.2 ± 12.7 years, 73.5% of patients were male, and 32.3% were non-White. Fifty-six percent of patients had at least 1 SU recorded during the measurement year; among patients with at least 1 SU recorded, 74% achieved the SU target. In multivariate analyses, non-White patients were slightly less likely to be tested or achieve a target SU., Conclusion: Among gout patients receiving long-term ULT followed longitudinally by rheumatologists, more than half had a documented SU, and among those tested, three-quarters achieved the recommended SU target. Routine monitoring of SU is a first step toward improving quality of care for patients with gout., (© 2022 American College of Rheumatology.)

In this study, the composition of amino acids, nutritional characteristics, degree of hydrolysis (DH), antioxidant properties, and antibacterial activity of proteins and hydrolysates of bellflower (Campanula latifolia), Persian willow (Salix aegyptiaca), and bitter orange (Citrus aurantium L.) were investigated under the influence of different proteases (Alcalase: Al, trypsin: Tr, pancreatin: Pa, and pepsin: Pe). Evaluation of the structural features of the proteins showed amide regions (amide A, B, I-III) and secondary structures. Hydrophobic amino acids (∼38%), antioxidants (∼21%), and essential types (∼46%) form a significant part of the structure of flower pollen. The digestibility and nutritional quality (PER) of the hydrolyzed samples (CP: 1.67; CA: 1.89, and PW: 1.93) were more than the original protein. Among proteins and peptides, the highest degree of hydrolysis (34.6%: Al-PWH), inhibition of free radicals DPPH (84.2%: Al-CPH), ABTS (95.2%: Pa-CPH), OH (86.7%: Tr-CAH), NO (57.8%: Al-CPH), reducing power (1.31: Pa-CPH), total antioxidant activity (1.46: Pa-CPH), and chelation of iron ions (80%: Al-CPH and Al-CAH) and copper (50.3%: Pa-CAH) were affected by protein type, enzyme type, and amino acid composition. Also, the highest inhibition of the growth of Escherichia coli (25 mm) and Bacillus cereus (24 mm) were related to CP and PW hydrolysates, respectively. The results of this research showed that hydrolyzed flower pollens can be used as a rich source of essential amino acids as well as natural antioxidants and antibacterial in food and dietary products. PRACTICAL APPLICATION: Enzymatic hydrolysis of Campanula latifolia, Persian willow, and Citrus aurantium pollen proteins was performed. The hydrolyzed ones had high nutritional quality and digestibility (essential amino acids and PER index). Antioxidant properties and chelation of metal ions of peptides were affected by the type of protein and enzyme. The hydrolysates showed inhibitory activity against the growth of Esherichia coli and Bacillus cereus., (© 2023 Institute of Food Technologists.)

Background: Hydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided., Objective: We developed and piloted an electronic health record-based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ., Methods: Patients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021., Results: At the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (-0.06; 95% CI -0.08 to -0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (-0.06; 95% CI -0.08 to -0.05)., Conclusions: The use of an electronic health record-based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ., (©Anna Montgomery, Gary Tarasovsky, Zara Izadi, Stephen Shiboski, Mary A Whooley, Jo Dana, Iziegbe Ehiorobo, Jennifer Barton, Lori Bennett, Lorinda Chung, Kimberly Reiter, Elizabeth Wahl, Meera Subash, Gabriela Schmajuk. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 12.05.2023.)

The main purpose of this study is to synthesize and characterize Persian gum-based hydrogel composited with gentamicin (Gen)-loaded natural zeolite (Clinoptilolite) and to evaluate its biological properties. Clinoptilolite (CLN) was decorated with Gen, and the conjugation was confirmed using computational and experimental assessments. The Monte Carlo adsorption locator module was used to reveal the physicochemical nature of the adsorption processes of Gen on CLN and ALG and gum on Gen@ CLN in Materials Studio 2017 software. Based on the high negative results, the adsorption process was found to be endothermic in all studied cases, and the interaction energies were in the range of physisorption for Gen on CLN and ALG and gum on Gen@CLN. Dynamic light scattering (DLS) and zeta potential analysis showed that the size of pristine CLN was around 2959 nm and the conjugation decreased the size significantly to approximately 932 nm. The hydrogel characterizations showed that the Gen-decorated CLNs are homogenously dispersed into the hydrogel matrix, and the resultant hydrogels have a porous structure with interconnected pores. The release kinetics evaluation showed that around 80 % of Gen was released from the nanocomposite drug during the first 10 h. In vitro studies revealed hemocompatibility and cytocompatibility of the nanocomposite. Microbial assessments indicated dose-dependent antibacterial activity of the hydrogel against gram (+) and gram (-) bacteria. The results showed that the fabricated hydrogel nanocomposite exhibits favorable physicochemical and biological properties., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hadi Samadian reports financial support was provided by Kermanshah University of Medical Sciences., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bone tissue engineering integrates biomaterials, cells, and bioactive agents to propose sophisticated treatment options over conventional choices. Scaffolds have central roles in this scenario, and precisely designed and fabricated structures with the highest similarity to bone tissue have shown promising outcomes. On the other hand, using nanotechnology and nanomaterials as the enabling options confers fascinating properties to the scaffolds, such as precisely tailoring the physicochemical features and better interactions with cells and surrounding tissues. Among different nanomaterials, polymeric nanofibers and carbon nanofibers have attracted significant attention due to their similarity to bone extracellular matrix (ECM) and high surface-to-volume ratio. Moreover, bone ECM is a biocomposite of collagen fibers and hydroxyapatite crystals; accordingly, researchers have tried to mimic this biocomposite using the mineralization of various polymeric and carbon nanofibers and have shown that the mineralized nanofibers are promising structures to augment the bone healing process in the tissue engineering scenario. In this paper, we reviewed the bone structure, bone defects/fracture healing process, and various structures/cells/growth factors applicable to bone tissue engineering applications. Then, we highlighted the mineralized polymeric and carbon nanofibers and their fabrication methods.

The reuse of waste water (WW) in agriculture is challenging as a potential strategy for sustainable agriculture development. However, its high content of heavy metals may cause damage to ecosystems. The property of biochar (BC) to minimize heavy metals accumulation into the soil was studied taking as a case study peppermint (Mentha x piperita L., Lamiaceae) irrigated with WW. Application of BC and WW, separately, promoted height, shoot number, crown diameter, internode length, leaf number, leaf length, leaf width, fresh (FW) and dry aerial parts weights (DW), root FW and root DW of peppermint. Also an increment in canopy diameter was observed. BC application considerably increased N, Mg, Mn, Fe and Zn, while WW increased N, P, K and Fe levels. Irrigation of peppermint with WW led to an increase of chlorophyll (Chl) a, Chl b, Chl a+b, carotenoids, anthocyanins, photosynthetic rate, transpiration, stomatal conductance, relative water content (RWC), and crop yield. On the other hand, BC application led to a decrease of Cd and Pb accumulation in plants. BC and WW application, separately, increased the essential oil content, the total phenol content, and the antioxidant capacity. Regardless of BC levels, irrigation of plants with WW decreased the percentage of menthone, menthofuran, isomenthone and pulegone in the essential oil, and increased the percentage of menthol and carvone. Similarly, BC application raised the percentage of menthol, and decreased that of pulegone. Overall, the application of BC in the culture medium is able to decrease the heavy metal concentration and improves the essential oil quality and quantity of peppermint under WW irrigation., 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.)

Objective: To accelerate the use of outcome measures in rheumatology, we developed and evaluated a natural language processing (NLP) pipeline for extracting these measures from free-text outpatient rheumatology notes within the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry., Methods: We included all patients in RISE (2015-2018). The NLP pipeline extracted scores corresponding to 8 measures of rheumatoid arthritis (RA) disease activity (DA) and functional status (FS) documented in outpatient rheumatology notes. Score extraction performance was evaluated by chart review, and we assessed agreement with scores documented in structured data. We conducted an external validation of our NLP pipeline using data from rheumatology notes from an academic medical center that is not included in the RISE registry., Results: We processed over 34 million notes from 854,628 patients, 158 practices, and 24 electronic health record (EHR) systems from RISE. Manual chart review revealed a sensitivity, positive predictive value (PPV), and F1 score of 95%, 87%, and 91%, respectively. Substantial agreement was observed between scores extracted from RISE notes and scores derived from structured data (κ = 0.43-0.68 among DA and 0.86-0.98 among FS measures). In the external validation, we found a sensitivity, PPV, and F1 score of 92%, 69%, and 79%, respectively., Conclusion: We developed an NLP pipeline to extract RA outcome measures from a national registry of notes from multiple EHR systems and found it to have good internal and external validity. This pipeline can facilitate measurement of clinical- and patient-reported outcomes for use in research and quality measurement., (© 2022 American College of Rheumatology.)

Some commonly used chemicals have teratogenic effects. Perchloroethylene (PCE) is a liquid that is widely used in various industries and drying clothes. In this study, the teratogenic effects of PCE in rat embryos were investigated. In this experimental study, 32 adult Wistar female rats in the weight range of 230-250 g were used. Female rats were randomly divided into 4 groups ( n  = 8). Control group (without PCE inhalation), experimental group G(I) (exposed to PCE 18 days prior to mating), experimental group G(II) (exposed to PCE 18 days after mating) and experimental group G(III) (exposed to PCE 18 days before and 18 days after mating). Pregnant rats were anesthetized on the 18th day of gestation and then serum and embryos were removed for the required studies. Embryos were examined for number, weight, sex, morphometric parameters of organs, and tissue samples were prepared for histological studies. Serum isolated from dams were evaluated for sexual and gonadal hormones. The results of this study showed that PCE has teratogenic effects on rat embryos. Infertility and reduced birth rate were other effects of PCE in rats. PCE has teratogenic effects and impairs the reproductive system of rats.

Experts have noted a concerning gap between clinical natural language processing (NLP) research and real-world applications, such as clinical decision support. To help address this gap, in this viewpoint, we enumerate a set of practical considerations for developing an NLP system to support real-world clinical needs and improve health outcomes. They include determining (1) the readiness of the data and compute resources for NLP, (2) the organizational incentives to use and maintain the NLP systems, and (3) the feasibility of implementation and continued monitoring. These considerations are intended to benefit the design of future clinical NLP projects and can be applied across a variety of settings, including large health systems or smaller clinical practices that have adopted electronic medical records in the United States and globally., (©Suzanne Tamang, Marie Humbert-Droz, Milena Gianfrancesco, Zara Izadi, Gabriela Schmajuk, Jinoos Yazdany. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 03.01.2023.)

Objective: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE)., Methods: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders., Results: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36-5.53]) and Hispanic (OR 2.76 [95% CI 1.34-5.69]) individuals had higher odds of more severe outcomes than White individuals., Conclusion: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population., (© 2022 The Authors. Arthritis Care & Research published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Data on the onset of lupus manifestations across multiple organ domains and in diverse populations are limited. The objective was to analyze racial and ethnic differences in the risk of end-organ lupus manifestations following systemic lupus erythematosus (SLE) diagnosis in a multiethnic cohort., Methods: The California Lupus Epidemiology Study (CLUES) is a longitudinal study of SLE. Data on major end-organ lupus manifestations were collected and categorized by organ system: renal, hematologic, neurologic, cardiovascular, and pulmonary. Multiorgan disease was defined as manifestations in ≥2 of these distinct organ systems. Kaplan-Meier curves assessed end-organ disease-free survival, and Cox proportional hazards regression estimated the rate of end-organ disease following SLE diagnosis, adjusting for age at diagnosis, sex, and self-reported race and ethnicity (White, Hispanic, Black, and Asian)., Results: Of 326 participants, 89% were female; the mean age was 45 years. Self-reported race and ethnicity were 30% White, 23% Hispanic, 11% Black, and 36% Asian. Multiorgan disease occurred in 29%. Compared to White participants, Hispanic and Asian participants had higher rates, respectively, of renal (hazard ratio [HR] 2.9 [95% confidence interval (95% CI) 1.8-4.7], HR 2.9 [95% CI 1.9-4.6]); hematologic (HR 2.7 [95% CI 1.3-5.7], HR 2.1 [95% CI 1.0-4.2]); and multiorgan disease (HR 3.3 [95% CI 1.8-5.9], HR 2.5 [95% CI 1.4-4.4]) following SLE diagnosis., Conclusion: We found heightened risks of developing renal, hematologic, and multiorgan disease following SLE diagnosis among Hispanic and Asian patients with SLE, as well as a high burden of multiorgan disease among CLUES participants., (© 2022 American College of Rheumatology.)

Ischemic stroke accompanies oxidative stress and cell death in the cerebral tissue. The microRNA miR-34a plays a pivotal role in this molecular pathology. This study presents the rational repositioning of aminoglycosidic antibiotics as miR-34a antagonists in order to assess their efficiency in protecting the PC12 stroke model cells from oxidative stress occurring under cerebral ischemic conditions. A library of 29 amino-sugar compounds were screened against anticipated structural models of miR-34a through molecular docking. MiR-ligand interactions were mechanistically studied by molecular dynamics simulations and free-energy calculations. Cultured PC12 cells were treated by H 2 O 2 alone or in combination with gentamycin and neomycin as selected drugs. Cell viability and apoptosis were detected by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) and annexin V-FITC/propidium iodate (PI) double staining assays, respectively. The expression levels of key factors involved in cell proliferation, oxidative stress, and apoptosis in treated PC12 cells were measured through a quantitative real-time polymerase chain reaction and flow cytometric annexin V-FITC/PI double staining assays. A stable and energetically favorable binding was observed for miR-34a with gentamycin and neomycin. Gentamycin pretreatments followed by H 2 O 2 oxidative injury led to increased cell viability and protected PC12 cells against H 2 O 2 -induced apoptotic events. This study will help in further understanding how the suppression of miR-34a in neural tissue affects the cell viability upon stroke., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The main aim of the current study is to fabricate an osteocompatible, bioactive, porous, and degradable bone tissue engineering scaffold. For this purpose, bioactive glasses (BGs) were chosen due to their similarity to bone's natural mineral composition, and the effect of replacing Ca ions with Sr on their properties were considered. First, strontium-containing BGs (Sr-BGs) were synthesized using the electrospinning technique and assembled by the sol-gel method, then they were incorporated into the alginate (Alg) matrix. Photographs of the scanning electron microscope (SEM) showed that the BG nanofibers have a diameter of 220 ± 36 nm, which was smaller than the precursor nanofibers (275 ± 66 nm). The scaffolds possess a porous internal microstructure (230-330 nm pore size) with interconnected pores. We demonstrated that the scaffolds could be degraded in the acetate sodium buffer and phosphate-buffered saline. The osteoactivity of the scaffolds was confirmed via visual inspection of the SEM illustrations after seven days of immersing them in the SBF solution. In vitro assessments disclosed that the produced Alg-based composites including Sr-BGs (Alg/Sr-BGs) are blood-compatible and biocompatible. Accumulating evidence shows that Alg/Sr-BG (5%, 10%, and 15%) hydrogels could be a promising scaffold for bone regeneration.