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Edris Kakemam,1 Mohammad Reza Rajabi,2 Pouran Raeissi,3 Lars Holger Ehlers4 1Department of Health Management and Economics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 2Department of Cardiology, Faculty of Medicine, Shahed University, Tehran, Iran; 3Department of Health Services Management, School of Health Management and Information Sciences, Iran University of Medical Sciences, Tehran, Iran; 4Danish Center for Healthcare Improvements, Institute of Business and Management, Faculty of Social Sciences, Aalborg University, Aalborg, DenmarkCorrespondence: Edris Kakemam Department of Health Management and Economics, School of Public HealthTehran University of Medical Sciences, Tehran, IranEmail edriskakemam@gmail.comPurpose: The hospital accreditation system in Iran is relatively young, having been introduced in 2012. Therefore, there is a real need for research on the status and impact of hospital accreditation in Iran. The purpose of this study was to evaluate and compare attitudes towards accreditation and quality improvement activities among hospital employees, specifically the attitudes towards the impact of accreditation on the quality of healthcare and its benefits in Iran.Materials and Methods: A cross-sectional survey was carried out at 23 teaching hospitals in three metropolises in Iran, all of which successfully passed national accreditation surveys. Some 1213 hospital managers, administrative staff, nurses, and para-clinical staff participated in the survey. The main outcome measures were quality results, and the activities related to quality improvement include senior managers’ commitment and support, strategic quality planning, education and training, rewards and recognition, quality management, use of data, the involvement of professionals in accreditation, and accreditation benefits. The questionnaire was applied using a 5-point Likert scale ranging from 1 “strongly disagree” to 5 “strongly agree”. One-way analysis of variance (ANOVA) was used to compare mean values between respondent groups.Results: Among nurses and managers, there was low support for accreditation and even less among para-clinical staff who fail to see accreditation having a positive impact on healthcare quality. Also, nurses’ attitudes toward the accreditation benefits were more positive compared with the two other groups. Staff stated that the main reasons for low support were a lack of education and training to act upon the accreditation survey results and a lack of management visibility and support for quality improvement.Conclusion: Improving quality through means of hospital accreditation is a complex process with high demands for management and employees. Questionnaires on employees’ attitudes and perceptions of the impact of accreditation and quality improvement-related activities in the hospitals can provide valuable information on the current problems of a hospital accreditation program.Keywords: accreditation, quality improvement, employees, surveys, Iran

This research delves into the intricacies of the Iraqi banking sector, focusing on its concentration and competitiveness using the Herfindahl-Hirschmann Index (HHI) as a pivotal tool. In the backdrop of modern financial dynamics and the rapid globalization of banking systems, understanding the concentration and competitiveness of the banking sector becomes paramount, especially for developing nations such as Iraq. Drawing data from government and private banks operating in Iraq from 2005 to 2020, this study provides a comprehensive view of the sector's evolution over these 15 years. The research reveals significant insights into the relationship between banking concentration, as measured by the HHI, and various facets of competitiveness, including lending rates and the overall health of the financial system. Furthermore, external factors, such as regulatory changes, are explored in shaping the competitive landscape. This study concludes with several key findings, most notably the disparities in concentration between government and private banks and the influence of market concentration on the accessibility of financial services to the general populace. Recommendations are put forth, emphasizing the need for regulatory interventions, fostering innovation, and promoting financial inclusion. This research serves as a valuable resource for policymakers, financial institutions, and researchers keen on understanding the dynamics of the Iraqi banking sector. [ABSTRACT FROM AUTHOR]

Investigates the biochemical evidence of apoptosis in uterine epithelial cells using a mouse implantation model. Autocrine/paracrine regulation of apoptosis during blastocyst outgrowth; DNA fragmentation in uterine epithelial cells; Role of anti-transforming growth factor beta in the occurrence of apoptosis.

Background: Due to the numerous complications associated with sickle cell disease (SCD), patients often receive a variety of medications alongside their SCD treatment. However, a notable gap exists in the current literature regarding medication use patterns among them. This study aimed to investigate medication usage patterns in patients with SCD., Research Design and Methods: This cross-sectional study, conducted in Bushehr Province, employed a stratified random sampling method to select eligible participants with SCD. A thorough interview gathered various information, including details about the medications. The Anatomical Therapeutic Chemical classification system was utilized for drug classification. Polypharmacy was defined as the concurrent use of at least five medications., Results: A total of 300 individuals with SCD were included in this study. Polypharmacy was observed in 26.3% (95% CI: 20.8%-32.8%) of the study population. The analyses revealed positive associations between the use of more concurrent medication use and higher age groups and having multimorbidity. Antianemic preparations (86.7%), antineoplastic agents (58.3%), and vitamins (41.0%) were the most frequent medication classes used by the study participants., Conclusions: Our study revealed notable underutilization of hydroxyurea and a high rate of polypharmacy, associated with age and multimorbidity, among patients with SCD in southern Iran.

Background: Obesity is a global health crisis with profound implications on various body systems, contributing to a series of comorbidities. Metabolic Bariatric Surgery (MBS) has emerged as an effective treatment option for severe obesity, with significant weight reduction and potential systemic physiological alterations., Objectives: This narrative review aims to provide a comprehensive analysis of the long-term effects of MBS on a wide array of body systems, including the heart, liver, kidneys, reproductive system, skin, lungs, digestive tract, pancreas, and blood, as well as related cancers of these organs., Methods: A systematic search was conducted in academic databases (PubMed, ISI Web of Science, and Scopus) for observational studies and reviews published between July 2000 and December 2023, investigating the association between MBS and the subsequent function of different organ systems. High-quality studies were prioritized to ensure reliable evidence synthesis., Results: MBS has demonstrated favorable outcomes in reducing cardiovascular disease risk, improving cardiac function, and alleviating heart failure symptoms. It has also been associated with improved respiratory function, remission of obstructive sleep apnea, and reduced cancer incidence and mortality. Additionally, MBS has shown benefits in managing gastrointestinal disorders, enhancing glycemic control, and promoting pancreatic beta-cell regeneration in type 2 diabetes mellitus. However, some methods of MBS are associated with a higher risk of cholelithiasis, GERD, and pancreatic exocrine insufficiency., Conclusion: MBS has far-reaching systemic effects beyond weight loss, offering potential long-term benefits for various organ systems and comorbidities associated with obesity. For many patients with severe obesity, the potential benefits of Metabolic and Bariatric Surgery (MBS) can outweigh the associated risks. However, careful evaluation by a qualified healthcare professional is crucial to determine candidacy and ensure a successful outcome. Further research is needed to fully elucidate the long-term impacts and tailor personalized treatment approaches., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: In response to the COVID-19 crisis, this study aimed to introduce a new virtual teaching model for anatomy education that combines Peer-Assisted Learning (PAL) and flipped classrooms, aligning with constructivist principles., Method: The Flipped Peer Assisted (FPA) method was implemented in a virtual neuroanatomy course for second-year medical students at Birjand University of Medical Sciences via a descriptive study. The method involved small groups of PAL, with peer learning serving as educational assistants and the teacher acting as a facilitator. Educational content was uploaded to the university's learning management system (LMS). The opinion of medical students regarding the teaching method were evaluated using a 15-item questionnaire on a five-point Likert scale., Results: A total of 210 students participated in the instruction using the FPA method. The analysis of students' scores revealed an average score of 26.75 ± 3.67 on the 30-point test. According to student feedback, this teaching method effectively motivated students to study, enhanced teamwork and communication skills, transformed their perspective on the anatomy course, provided opportunities for formative assessment and feedback, and demonstrated the teacher's dedication to education., Conclusion: The FPA model demonstrates its effectiveness in transforming traditional classroom teaching and fostering teaching and learning in virtual environments, particularly during pandemics like COVID-19. This model holds promise for enhancing anatomy education in challenging circumstances., (© 2024. The Author(s).)

This study aimed to predict the impact of changing hydro-climatic variables and land use changes on the future health status of the Safaroud Watershed, northern Iran. It also sought to explore the significance of hydro-climatic and land use variables in prioritizing sub-watersheds based on the watershed health index. The study involved extracting key characteristics related to anthropogenetic, climatic, and hydrological factors for pressure, state, and response indicators. The current watershed health index was calculated, followed by predictions of watershed health based on dynamic hydro-climatic and land-use variables for the next 10 and 20 years. The Safaroud Watershed health assessment and zoning showed that the average value and standard deviation of the current pressure index were equal to 0.573 and 0.185, respectively. The lowest value of this index was around 0.290 and related to sub-watershed 5, and the highest value was around 0.840 and related to sub-watershed 11. The initial evaluation of the classification indicated the prevalence of moderate and high-pressure conditions with a range of about 79%. Finally, the physical factors of sub-watersheds (time of concentration with 15.72%) had the lowest role. In general, among the criteria used to calculate the pressure index in the current period, anthropogenetic and climatic factors showed the highest percentage of participation in determining the pressure index. The quantification of the current watershed health status and the 10- and 20-year-forecast periods showed that the values of the watershed health index were similar. However, the changes in the health index in the sub-watersheds at the beginning of the study period ranged from relatively unhealthy favorable conditions to moderately positive and moderately negative conditions., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aim: Malnutrition among intensive care unit (ICU) patients is associated with a higher risk of mortality and prolonged hospitalization. However, the influence of malnutrition on severe outcomes of ICU patients with coronavirus disease 2019 (COVID-19) is unclear. By evaluating the effect of malnutrition on the outcomes of COVID-19 in the ICU in older adult patients, this study will contribute to new knowledge of assessing the nutritional status and recovery of these patients., Methods: In the current single center prospective study, 310 critically ill COVID-19 patients with an age range of ≥65 years were recruited. Data on demographic characteristics, laboratory parameters, comorbidities, medications, and types of mechanical ventilation were collected in the first 24 h of ICU admission. Malnutrition was defined based on the two-step approach of the Global Leadership Initiative on Malnutrition (GLIM) scale at baseline. During the 45 days after the baseline, we collected data on delirium incidence, mortality, invasive mechanical ventilation (IMV) requirement, length of ICU and hospital admission, and re-hospitalization., Results: In this study, the prevalence of malnutrition was 63.4% among critically ill COVID-19 patients. During the 45-day follow-up, 190 (61.3%) COVID-19 deaths were recorded among the baseline 310 patients. After controlling for potential confounders, malnutrition was associated with an increased risk of delirium so malnourished COVID-19 patients had a significantly 35% higher risk of delirium than those without malnutrition (HR: 1.35, 95% CI: 1.01-1.83). Such a significant association was not for COVID-19 mortality and IMV requirement. In addition, malnutrition was associated with a significantly 84% greater odds of prolonged ICU admission (OR: 1.84, 95% CI: 1.09-3.10). No significant association was seen between malnutrition and re-hospitalization and also prolonged hospital admission., Conclusion: Malnutrition was associated with an increased risk of delirium and prolonged ICU admission among critically ill older adult COVID-19 patients. Prevention, diagnosis, and treatment of malnutrition could be a key component in improving outcomes in these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gholi, Rezaei, Vahdat Shariatpanahi, Momen, Fallah Bagher Shaidaei, Gholami, Aghaee, Eskandari Sabzi and Rajabi.)

Recent work in immersive analytics suggests benefits for systems that support work across both 2D and 3D data visualizations, i.e., cross-virtuality analytics systems. Here, we introduce HybridAxes, an immersive visual analytics system that enables users to conduct their analysis either in 2D on desktop monitors or in 3D within an immersive AR environment - while enabling them to seamlessly switch and transfer their graphs between modes. Our user study results show that the cross-virtuality sub-systems in HybridAxes complement each other well in helping the users in their data-understanding journey. We show that users preferred using the AR component for exploring the data, while they used the desktop to work on more detail-intensive tasks. Despite encountering some minor challenges in switching between the two virtuality modes, users consistently rated the whole system as highly engaging, user-friendly, and helpful in streamlining their analytics processes. Finally, we present suggestions for designers of cross-virtuality visual analytics systems and identify avenues for future work.

The 17 th Workshop on Recent Issues in Bioanalysis (17 th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17 th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) are published in volume 16 of Bioanalysis, issues 8 and 9 (2024), respectively.

The 17 th Workshop on Recent Issues in Bioanalysis (17 th WRIB) took place in Orlando, FL, USA on 19-23 June 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with these NEW Regulations" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17 th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication (Part 2) covers the recommendations on Biomarkers, IVD/CDx, LBA and Cell-Based Assays. Part 1A (Mass Spectrometry Assays and Regulated Bioanalysis/BMV), P1B (Regulatory Inputs) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 9 and 7 (2024), respectively.

The 17 th Workshop on Recent Issues in Bioanalysis (17 th WRIB) took place in Orlando, FL, USA on June 19-23, 2023. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 17 th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.Moreover, in-depth workshops on "EU IVDR 2017/746 Implementation and impact for the Global Biomarker Community: How to Comply with this NEW Regulation" and on "US FDA/OSIS Remote Regulatory Assessments (RRAs)" were the special features of the 17 th edition.As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues.This 2023 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2023 edition of this comprehensive White Paper has been divided into three parts for editorial reasons.This publication covers the recommendations on Mass Spectrometry Assays, Regulated Bioanalysis/BMV (Part 1A) and Regulatory Inputs (Part 1B). Part 2 (Biomarkers, IVD/CDx, LBA and Cell-Based Assays) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 16 of Bioanalysis, issues 7 and 8 (2024), respectively.

Background: This study was performed to evaluate the protective effects of chrysin (CH) on metabolic impairment and pancreatic injury caused by sub-chronic chlorpyrifos (CPF) intoxication in male rats., Methods: Forty male Wistar rats were randomly allocated into five groups (n=8). Intraperitoneal injections of chrysin (12.5, 25 and 50 mg/kg for 45 days) and CPF (10 mg/kg for 45 days) gavage were performed. Present findings indicated that the serum levels of glucose, total cholesterol, and lowdensity lipoprotein-cholesterol, as well as body weight, were increased in the CPF-exposed group., Results: It was also found that CPF decreased superoxide dismutase activity as well as increased malondialdehyde and nitric oxide levels in the pancreatic tissue of exposed animals. Histopathological examination also confirmed the toxic effects of CPF on pancreatic tissue as mostly evidenced by infiltration of inflammatory cells and necrosis. CH (50 mg/kg) decreased blood glucose concentration (p < 0.05), TG (p < 0.05), and LDL-C in CPF-exposed animals. CH decreased the pancreas levels of MDA in all treated CPF-exposed groups versus the non-treated CPF-exposed group (p < 0.05, p < 0.001, p < 0.001, respectively). A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. A significant difference was not seen in the NO and MDA levels and SOD activity between CHtreated (50 mg/kg) animals exposed to CPF and controls., Conclusion: A significant difference was not seen in the NO and MDA levels and SOD activity between CH-treated (50 mg/kg) animals exposed to CPF and controls. In conclusion, CH could prevent initiate and progress of CPF-induced metabolic impairment by modulating oxidative stress in pancreatic tissue as a target organ of organophosphorus pesticides., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: "Partnership Care Model (PCM)", which is the first partnership conceptual framework founded on the Iranian culture to control chronic diseases, has been recently used in different fields of nursing research with no levels of valid evidence to support its application. Therefore, this systematic review and meta-analysis sought to clarify the impacts of interventions developed based on PCM on quality of life (QoL), sleep quality, anxiety, and depression among adults and children with chronic diseases., Methods: International data sources (e.g., PubMed, Web of Science, Scopus) and national databases (e.g., SID, MagIran, IranDoc, IRCT) were searched from 2001 to September 23, 2023, to find Randomized Controlled Trials (RCTs) on PCM-driven interventions for the experimental groups versus no intervention or standard care groups. The studies' methodological quality and evidence quality were rated utilizing the Cochrane risk of bias instruction and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were pooled by a random-effects approach employing STATA (vers. 11.2)., Result: Eighteen RCTs, reported in 22 publications, were qualified. The PCM compared to the standard care significantly improved the QoL among both adults (10 effect sizes [ESs], mean difference [MD]: 3.17, P < 0.001) and children (4 ESs, MD: 4.45, P < 0.001). Likewise, the intervention enhanced adults' sleep quality (3 ESs, MD: 7.15, P < 0.001). The anxiety of adults and children was also significantly lower in the PCM group (4 ESs, MD: -4.52, P = 0.001; 2 ESs, MD: -4.04, P < 0.001, respectively). However, regarding depression, a significant effect of PCM was found only among children (3 ESs, MD: -7.99, P = 0.011). The methodological quality of the studies and the evidence quality were undesirable., Conclusion: The PCM had a promising influence on the caring of adults and children suffering from chronic diseases. However, additional high-quality RCTs are needed to generate a higher quality of evidence concerning the clinical benefits of the PCM., Prospero No: CRD42021253790., 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. Published by Elsevier Inc.)

Increasing evidence suggests that organic vanadium compounds are bioavailable and safe therapeutic agents with insulin-mimetic and insulin-enhancing features. The objective of the current study was to examine the effect of vanadium-enriched yeast (VEY) supplementation on the gene expression level of insulin receptor substrates and clinical manifestations of obese type 2 diabetic mellitus (T2DM) patients. In this randomized, double-blind, placebo-controlled clinical trial, 44 obese T2DM patients were randomly allocated into either VEY (0.9 mg/day vanadium pentoxide) or placebo group for 12 weeks. The mRNA expression level of protein tyrosine phosphatase 1B (PTP1B), phosphatase and tensin homolog (PTEN), mitogen-activated protein kinase (MAPK), ribosomal protein S6 kinase (S6K), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFƘB) genes in the peripheral blood mononuclear cells, serum levels of metabolic parameters, anthropometric indices, as well as the quality of life, and dietary intake were collected at pre- and post-intervention phases. Analysis of covariance was performed to obtain the corresponding effect size. Results showed that VEY administration significantly decreased anthropometric indices and glycemic parameters and increased insulin sensitivity after adjusting for potential covariates (p < 0.05), in comparison to the placebo group. Additionally, VEY supplementation was significantly effective on MAPK, PTP1B, and NFƘB gene expression level, compared to the placebo group. No significant changes were noticed for dietary intake, quality of life, and lipid profile in the VEY group, compared to the placebo group. Overall, VEY supplementation can be considered as a promising safe adjunct therapy for improving anthropometric indices and glycemic parameters in T2DM patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The 16 th Workshop on Recent Issues in Bioanalysis (16 th WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on the ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16 th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1A) covers the recommendations on Mass Spectrometry and ICH M10. Part 1B covers the Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine. Part 2 (LBA, Biomarkers/CDx and Cytometry) and Part 3 (Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity) are published in volume 15 of Bioanalysis, issues 15 and 14 (2023), respectively.

Evolving immunogenicity assay performance expectations and a lack of harmonized neutralizing antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. A team of experts within the American Association of Pharmaceutical Scientists' Therapeutic Product Immunogenicity Community across industry and the Food and Drug Administration addressed challenges unique to cell-based and non-cell-based neutralizing antibody assays. Harmonization of validation expectations and data reporting will facilitate filings to health authorities and are described in this manuscript. This team provides validation testing and reporting strategies and tools for the following assessments: (1) format selection; (2) cut point; (3) assay acceptance criteria; (4) control precision; (5) sensitivity including positive control selection and performance tracking; (6) negative control selection; (7) selectivity/specificity including matrix interference, hemolysis, lipemia, bilirubin, concomitant medications, and structurally similar analytes; (8) drug tolerance; (9) target tolerance; (10) sample stability; and (11) assay robustness., (© 2023. The Author(s).)

The 2022 16th Workshop on Recent Issues in Bioanalysis (WRIB) took place in Atlanta, GA, USA on September 26-30, 2022. Over 1000 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 16th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on ICH M10 BMV final guideline (focused on this guideline training, interpretation, adoption and transition); mass spectrometry innovation (focused on novel technologies, novel modalities, and novel challenges); and flow cytometry bioanalysis (rising of the 3rd most common/important technology in bioanalytical labs) were the special features of the 16th edition. As in previous years, WRIB continued to gather a wide diversity of international, industry opinion leaders and regulatory authority experts working on both small and large molecules as well as gene, cell therapies and vaccines to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance, and achieving scientific excellence on bioanalytical issues. This 2022 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2022 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Gene Therapy, Cell therapy, Vaccines and Biotherapeutics Immunogenicity. Part 1 (Mass Spectrometry and ICH M10) and Part 2 (LBA, Biomarkers/CDx and Cytometry) are published in volume 15 of Bioanalysis, issues 16 and 15 (2023), respectively.

Background: Mesenchymal stem cells (MSCs) are utilized as a carrier of anti-tumor agents in targeted anti-cancer therapy. Despite the improvements in this area, there are still some unsolved issues in determining the appropriate dose, method of administration and biodistribution of MSCs. The current study aimed to determine the influence of toll-like receptor 3 (TLR3) stimulation on the potential of MSCs migration to the neoplasm environment in the mouse melanoma model., Methods and Results: Adipose-derived MSCs (ADMSCs) were isolated from the GFP + transgenic C57BL/6 mouse and treated with different doses (1 µg/ml and 10 µg/ml) of polyinosinic-polycytidylic acid, the related TLR3 agonist, at various time points (1 and 4 h). Following the treatment, the expression of targeted genes such as α4, α5, and β1 integrins and TGF-β and IL-10 anti-inflammatory cytokines was determined using real-time PCR. In vivo live imaging evaluated the migration index of the intraperitoneally (IP) injected treated ADMSCs in a lung tumor-bearing mouse (C57BL/6) melanoma model (n = 5). The presented findings demonstrated that TLR3 stimulation enhanced both migration of ADMSCs to the tumor area compared with control group (n = 5) and expression of α4, α5, and β1 integrins. It was also detected that the engagement of TLR3 resulted in the anti-inflammatory behavior of the cells, which might influence the directed movement of ADMSCs., Conclusion: This research identified that TLR3 activation might improve the migration via the stimulation of stress response in the cells and depending on the agonist concentration and time exposure, this activated pathway drives the migratory behavior of MSCs., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Organisations need to develop long-term strategies to ensure they incorporate innovation for environmental sustainability (IES) to remain competitive in the market. This can be challenging given the high level of uncertainty regarding the future (e.g., following the COVID pandemic). Supplier selection is an important decision that organisations make and can be designed to support IES. While the literature provides various criteria in the field of IES strategies, it does not identify the criteria which can be utilised to assist organisations in their supplier selection decisions. Moreover, the literature in this field does not consider uncertainty related to the occurrence of possible future events which may influence the importance of these criteria. To address this gap, this paper develops a novel criteria decision framework to assist supplier evaluation in organisations, taking into consideration different events that may occur in the future. The framework that combines three decision-making methods: the stratified multi-criteria decision-making method, best worst method, and technique for order of preference by similarity to ideal solution. The framework, proposed in this paper, can also be adopted to enable effective and sustainable decision making under uncertainty in various fields., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Epilepsy is a life-threatening neurological disease that affects approximately 70 million people worldwide. Although the vast majority of patients may be successfully managed with currently used antiseizure medication (ASM), the search for alternative therapies is still necessary due to pharmacoresistance in about 30% of patients with epilepsy. Here, we review the effects of ASMs on stem cell treatment when they could be, as expected, co-administered. Indeed, it has been reported that ASMs produce significant effects on the differentiation and determination of stem cell fate. In addition, we discuss more recent findings on mesenchymal stem cells (MSCs) in pre-clinical and clinical investigations. In this regard, their ability to differentiate into various cell types, reach damaged tissues and produce and release biologically active molecules with immunomodulatory/anti-inflammatory and regenerative properties make them a high-potential therapeutic tool to address neuroinflammation in different neurological disorders, including epilepsy. Overall, the characteristics of MSCs to be genetically engineered, in order to replace dysfunctional elements with the aim of restoring normal tissue functioning, suggested that these cells could be good candidates for the treatment of epilepsy refractory to ASMs. Further research is required to understand the potential of stem cell treatment in epileptic patients and its interaction with ASMs.

Background: The immunomodulatory properties of mesenchymal stem cells (MSCs) have made them a prospective treatment option for inflammatory and autoimmune disorders. Recent studies have found an association between the immunomodulatory function of MSCs and Toll-like receptors (TLRs). Here, we investigated the effect of priming with lipopolysaccharide (LPS) as TLR4 ligand or polyinosinic:polycytidylic acid (poly I:C) as TLR3 ligand on the immunomodulatory function of adipose-derived MSCs (ADMSCs) in vitro and for the first time in an adjuvant-induced arthritis model (AIA)., Methods: ADMSCs were treated with LPS or poly I:C for 1 h. Splenocyte proliferation in the presence of primed ADMSCs was assessed in vitro using an MTT assay. Next, we investigated the therapeutic effect of primed ADMSCs in vivo. Male Wistar rats were infused with complete Freund's adjuvant (CFA) to develop arthritis and then intraperitoneally treated with not-primed, poly I:C- or LPS-primed ADMSCs. Clinical signs, histopathological alteration, and serum and spleen cytokine levels were analyzed., Results: Poly I:C-primed ADMSCs significantly reduced splenocytes proliferation, while ADMSCs primed with LPS increased splenocytes proliferation. Furthermore, poly I:C-primed ADMSCs significantly alleviated the clinical and histopathological severity and the secretion of inflammatory cytokines associated with Th17/Th1 such as IL-17 and IFN-γ. Poly I:C-primed ADMSCs also increased cytokines IL-10 and TGF-β. TNF-α and IL-6 Levels were also markedly diminished in the serum of AIA animals treated with poly I:C-primed ADMSCs. In contrast, priming ADMSCs with LPS significantly reduced the therapeutic effect of ADMSCs in AIA animals., Conclusion: As a result of these findings, poly I:C priming may be a new technique for improving the therapeutic effects of MSCs in arthritic disorders., (© 2022. The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.)

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "Context of Use - COU"); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and, critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 2 (ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry) are published in volume 14 of Bioanalysis, issues 9 and 10 (2022), respectively.

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "Context of Use - COU"); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and, critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 1A) covers the recommendations on Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC. Part 1B covers the Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine. Part 2 (ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry) and Part 3 (TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparabil ity & Cut Point Appropriateness) are published in volume 14 of Bioanalysis, issues 10 and 11 (2022), respectively.

The 15th edition of the Workshop on Recent Issues in Bioanalysis (15th WRIB) was held on 27 September to 1 October 2021. Even with a last-minute move from in-person to virtual, an overwhelmingly high number of nearly 900 professionals representing pharma and biotech companies, contract research organizations (CROs), and multiple regulatory agencies still eagerly convened to actively discuss the most current topics of interest in bioanalysis. The 15th WRIB included three Main Workshops and seven Specialized Workshops that together spanned 1 week in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy, cell therapy and vaccines. Moreover, in-depth workshops on biomarker assay development and validation (BAV) (focused on clarifying the confusion created by the increased use of the term "context of use" [COU]); mass spectrometry of proteins (therapeutic, biomarker and transgene); state-of-the-art cytometry innovation and validation; and critical reagent and positive control generation were the special features of the 15th edition. This 2021 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2021 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations on ISR for Biomarkers, Liquid Biopsies, Spectral Cytometry, Inhalation/Oral & Multispecific Biotherapeutics, Accuracy/LLOQ for Flow Cytometry. Part 1A (Endogenous Compounds, Small Molecules, Complex Methods, Regulated Mass Spec of Large Molecules, Small Molecule, PoC), Part 1B (Regulatory Agencies' Inputs on Bioanalysis, Biomarkers, Immunogenicity, Gene & Cell Therapy and Vaccine) and Part 3 (TAb/NAb, Viral Vector CDx, Shedding Assays; CRISPR/Cas9 & CAR-T Immunogenicity; PCR & Vaccine Assay Performance; ADA Assay Comparability & Cut Point Appropriateness) are published in volume 14 of Bioanalysis, issues 9 and 11 (2022), respectively.

Recent studies have reported conflicting findings on the antianxiety, antidepressant, and anti-stress properties of Rosa Damascena Mill (RDM). Therefore, the present systematic review and meta-analysis were conducted on the effects of RDM for treating anxiety, depression, and stress amongst adults. The online data sources of Cochrane Central Register of Controlled Trials, PubMed, Scopus, Web of Science, Embase, ProQuest, and Scientific Information Database were searched from inception to June 30, 2021. The randomized controlled trials (RCTs), which examined the effects of RDM (in any form of administration) on adults' anxiety, depression, and stress, were included. A random-effects model was applied to pool the data, and a total of 32 publications were included. The results of the meta-analysis revealed that administration of RDM significantly reduced state anxiety (effect size [ES]: 24, standardized mean difference [SMD]: -1.74, 95% confidence interval [CI]: -2.29, -1.20; p < .001), depression (ES: 7, SMD: -0.87, 95% CI: -1.47, -0.28; p = .004), and stress (ES: 4, SMD: -1.33, 95% CI: -1.98, -0.69; p < .001). However, the treatment had no significant effect on trait anxiety (ES: 6, weighted mean difference: -0.75, 95% CI: -1.93, 0.43; p = .214). The association between the total administration dosage and/or duration of RDM and the changes in state anxiety and depression was not dose-dependent. Most RCTs had a fair methodological quality based on the Cochrane risk of bias assessment tool. Besides, the quality of evidence ranged from very low to moderate according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Hence, further high-quality RCTs are needed to draw reliable conclusions regarding the use of RDM for treating adults' anxiety, depression, and stress., (© 2021 John Wiley & Sons Ltd.)

Evolving immunogenicity assay performance expectations and a lack of harmonized anti-drug antibody validation testing and reporting tools have resulted in significant time spent by health authorities and sponsors on resolving filing queries. Following debate at the American Association of Pharmaceutical Sciences National Biotechnology Conference, a group was formed to address these gaps. Over the last 3 years, 44 members from 29 organizations (including 5 members from Europe and 10 members from FDA) discussed gaps in understanding immunogenicity assay requirements and have developed harmonization tools for use by industry scientists to facilitate filings to health authorities. Herein, this team provides testing and reporting strategies and tools for the following assessments: (1) pre-study validation cut point; (2) in-study cut points, including procedures for applying cut points to mixed populations; (3) system suitability control criteria for in-study plate acceptance; (4) assay sensitivity, including the selection of an appropriate low positive control; (5) specificity, including drug and target tolerance; (6) sample stability that reflects sample storage and handling conditions; (7) assay selectivity to matrix components, including hemolytic, lipemic, and disease state matrices; (8) domain specificity for multi-domain therapeutics; (9) and minimum required dilution and extraction-based sample processing for titer reporting., (© 2021. The Author(s).)

Introduction: P53, as a tumor suppressor gene, is believed to be one of the most mutated genes in cancer cells. The mutant forms of this protein often play a tumorigenic role in cancer cells. Recent evidence shows that p53 plays a critical role in the migration, metastasis, and invasion of cancer cells. The present article aims to investigate the molecular mechanism that induces metastasis in cancer cells generated by the mutant P53, and to highlight the compounds targeting mutant-p53 together with their clinical applications., Methods: A detailed literature search was conducted to find information about the role of the mutant-p53 in the processes involved in metastasis in various databases., Results: A growing body of evidence suggests that Mutant-p53 enhances tumor metastasis affecting the Epithelial-mesenchymal transition (EMT) process, cancer stem cells, angiogenesis, autophagy, anoikis, and any other mechanisms regarding metastasis., Conclusions: Taken together, targeting mutant-p53 by altering the processes involved in metastasis could be a potential therapeutic strategy in the treatment of metastatic cancer., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The use of validated questionnaires to assess the perception of teamwork can be an early step in improving team training activities. Team-STEPPS® Teamwork Perception Questionnaire (T-TPQ) has been adapted and validated for hospital setting use in several countries. Due to linguistic and cultural differences, there is need to test the psychometrics of the adapted versions. However, no research have not yet assessed the psychometric properties of the Persian T-TPQ. Therefore, this study aims to assess the internal consistency reliability and construct validity of an Iranian version of the Team-STEPPS® Teamwork Perception Questionnaire (IR-T-TPQ)., Methods: To conduct this study, we undertook a cross-sectional survey approach between May 2020 and January 2021. In total, 404 nurses were recruited by convenience sampling technique from 10 teaching hospitals in Tabriz, Iran. Internal consistency reliability was analyzed using Cronbach's alpha coefficient. Confirmatory factor analysis was performed to test the construct validity of the instrument., Results: Cronbach's alpha coefficients for each subscale were acceptable, ranging from 0.84 to 0.92, as well as for the total IR-T-TPQ (α = 0.96). The confirmatory factor analysis demonstrated a five-factor model, all of whose fit indices were acceptable, except for the goodness-of-fit index and normed fit index (χ2 (df) 1332 (550), p < 0.001, Normed chi-square (χ2/df) = 2.423, RMSEA = 0.059, TLI = 0.897, CFI = 0.904, AGFI = 0.814)., Conclusions: The psychometric properties of the IR-T-TPQ resulted in acceptable levels of internal consistency reliability and construct validity, respectively, in Iranian hospital nurses. Further study is needed to compare the teamwork level of nurses in various settings or to evaluate the effectiveness of the teamwork intervention using this validated and reliable tool., (© 2021. The Author(s).)

Aim: This study sought to describe the experiences of critical care nurses caring for patients infected by coronavirus disease 2019 (COVID-19)., Design: A qualitative phenomenological design was used., Methods: We enrolled 15 nurses who provided care for patients infected by COVID-19 purposively and through snowballing, using a phenomenological approach in critical care units of Iran's public hospitals between May and June 2020. The semi-structured interviews were carried out either via face-to-face or telephone and were analyzed using the 7-step method of Colaizzi., Results: The experiences of nurses caring for patients infected with COVID-19 were categorized into four challenges, including psychological (eight subthemes), organizational (six subthemes), social (six subthemes), and professional (five subthemes). In general, based on the current classification, there seems to be a mixture of positive and negative effects on the psychological, social, and professional challenges and the negative effect only on the organizational challenges., Conclusions: Positive and negative emotions and experiences have coexisted for the critical care nurses since the COVID-19 outbreak. Emotional support and psychological counseling play an important role in maintaining nurses' optimal mental health during the COVID-19 crisis. Adequate protective equipment, financial and nonfinancial supports, effective communication, training and hiring of staff, and appropriate work shifts are also required to reduce nurses' negative experiences when providing care for the affected individuals., (© 2021 Wiley Periodicals LLC.)

Background: Patient safety culture is an important factor in determining hospitals' ability to address and reduce the occurrence of adverse events (AEs). However, few studies have reported on the impact of nurses' perceptions of patient safety culture on the occurrence of AEs. Our study aimed to assess the association between nurses' perception of patient safety culture and their perceived proportion of adverse events., Methods: A cross-sectional survey was carried out among 2295 nurses employed in thirty-two teaching hospitals in Iran. Nurses completed the Persian version of the hospital survey of patients' safety culture between October 2018 and September 2019., Results: Positive Response Rates of overall patient safety culture was 34.1% and dimensions of patient safety culture varied from 20.9 to 43.8%. Also, nurses estimated that the occurrence of six adverse events varied from 51.2-63.0% in the past year. The higher nurses' perceptions of "Staffing", "Hospital handoffs and transitions", "Frequency of event reporting", "Non-punitive response to error", "Supervisor expectation and actions promoting safety", "Communication openness", "Organizational learning continuous improvement", "Teamwork within units", and "Hospital management support patient safety" were significantly related to lower the perceived occurrence at least two out of six AEs (OR = 0.69 to 1.46)., Conclusions: Our findings demonstrated that nurses' perception regarding patient safety culture was low and the perceived occurrence of adverse events was high. The research has also shown that the higher level of nurses' perception of patient safety culture was associated with lowered occurrence of AEs. Hence, managers could provide prerequisites to improve patient safety culture and reduce adverse events through different strategies, such as encouraging adverse events' reporting and holding training courses for nurses. However, further research is needed to assess how interventions addressing patient safety culture might reduce the occurrence of adverse events.

The 14 th edition of the Workshop on Recent Issues in Bioanalysis (14 th WRIB) was held virtually on June 15-29, 2020 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. The 14 th WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy and vaccine. Moreover, a comprehensive vaccine assays track; an enhanced cytometry track and updated Industry/Regulators consensus on BMV of biotherapeutics by LCMS were special features in 2020. As in previous years, this year's WRIB continued to gather a wide diversity of international industry opinion leaders and regulatory authority experts working on both small and large molecules to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance and achieving scientific excellence on bioanalytical issues. This 2020 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop and is aimed to provide the Global Bioanalytical Community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2020 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations on Vaccine, Gene/Cell Therapy, NAb Harmonization and Immunogenicity). Part 1 (Innovation in Small Molecules, Hybrid LBA/LCMS & Regulated Bioanalysis), Part 2A (BAV, PK LBA, Flow Cytometry Validation and Cytometry Innovation) and Part 2B (Regulatory Input) are published in volume 13 of Bioanalysis, issues 4 and 5 (2020), respectively.

The 14 th edition of the Workshop on Recent Issues in Bioanalysis (14 th WRIB) was held virtually on June 15-29, 2020 with an attendance of over 1000 representatives from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. The 14 th WRIB included three Main Workshops, seven Specialized Workshops that together spanned 11 days in order to allow exhaustive and thorough coverage of all major issues in bioanalysis, biomarkers, immunogenicity, gene therapy and vaccine. Moreover, a comprehensive vaccine assays track; an enhanced cytometry track and updated Industry/Regulators consensus on BMV of biotherapeutics by LCMS were special features in 2020. As in previous years, this year's WRIB continued to gather a wide diversity of international industry opinion leaders and regulatory authority experts working on both small and large molecules to facilitate sharing and discussions focused on improving quality, increasing regulatory compliance and achieving scientific excellence on bioanalytical issues. This 2020 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the Global Bioanalytical Community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2020 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication covers the recommendations on (Part 2A) BAV, PK LBA, Flow Cytometry Validation and Cytometry Innovation and (Part 2B) Regulatory Input. Part 1 (Innovation in Small Molecules, Hybrid LBA/LCMS & Regulated Bioanalysis), Part 3 (Vaccine, Gene/Cell Therapy, NAb Harmonization and Immunogenicity) are published in volume 13 of Bioanalysis, issues 4, and 6 (2021), respectively.

Background: Coronaviruses are a large family of viruses that have symptoms ranging from simple symptoms of colds to severe respiratory syndromes. In December 2019, cases of unknown pneumonia first appeared in Wuhan, China., Objective: The purpose of this study was to investigate the relationship between occupation and COVID-19 in the Ardabil Imam Khomeini hospital., Methods: This research was conducted as a cross-sectional and descriptive study. The questionnaires used in this study included demographic information to obtain the required information such as age, sex, clinical symptoms, underlying disease, type of drug used, smoking, occupation, hours of work, number of daily clients, use of mask or shield, type of working hours, weight and height and body mass index, number family, place of residence, role in the family, presence of an infected person in the family, communication with the suspect, observance or non-observance of health protocols. Our sample size consisted of 774 subjects, all patients at the Ardabil Imam Khomeini Hospital. The subjects were selected randomly., Results: The results of this study showed that the mean age of patients was 56.70 years, with a standard deviation of 18.20 years. Three hundred and sixty participants (46.5%) were female, and 414 (53.5%) were male. In terms of occupation distribution, 317 patients (41%) were housewives. In addition, 57 people (7.4%) were farmers or ranchers., Conclusion: In general, it can be concluded that due to severity of infection and threat posed by Coronavirus and the risk of infections between different occupations like the taxi driver and medical staff, it is very important to find out what jobs are in the big threat.

Background and Purpose: Cancer stem cells (CSCs), as the subpopulation of cancer cells, are associated with carcinogenesis, chemoresistance, and metastasis in malignancies. Also, CSCs are considered as the major reason for treatment failure in prostate cancer (PCa). Alantolactone (ALT), exerts anticancer activity in different types of cancers. In the present study, the relationship between ALT and CSCs in PCa metastasis and the molecular mechanisms involved in the progression of PCa were investigated., Experimental Approach: In this study, to evaluate cell viability, MTT assay was performed. Then, PC3 cells were treated with nontoxic concentrations of ALT and after this step wound-healing assay, colony-formation assay and chemosensitization assay were applied to determine cell migration, the ability of colony formation, and chemoresistance, respectively. Also, real-time polymerase chain reaction and western blotting were used for the determination of genes and protein expression, respectively., Findings/results: Our finding showed that ALT at nontoxic concentrations (0.01 and 0.1 μM) for 72 h suppressed the STAT3 phosphorylation and signaling pathway. Also, ALT was able to modulate the stemness of PCa cells through downregulation of expression of SOX2, Oct-4, Nanog, CD133, CD44, and upregulation of p53 expression. On the other hand, we further found that ALT in nontoxic concentrations sensitized PCa cells to cisplatin., Conclusion and Implications: ALT combated the stemness of cancer cells and metastasis by antagonizing of STAT3 signaling pathway. In addition, ALT exhibited anti-metastatic properties and may have potential as a new chemotherapy agent for the reduction of PCa metastasis., (Copyright: © 2020 Research in Pharmaceutical Sciences.)

Background: There is an acute shortage of nurses worldwide including Iran. Quality of work life is important for nurses as it affects the safety and quality of care provided for patients as well as organizational factors. The aim of this study was to describe the status of quality of work life and to explore its predictors among nurses in Iran., Methods: A cross-sectional study was conducted on 2391 nurses in 85 Iranian public hospitals, selected through the convenience sampling. Data were collected using demographic information and the quality of work life questionnaires., Results: The mean score for total quality of work life was 2.58, indicating a low level of self-reported quality of work life, with 69.3% of nurses dissatisfied with their work life. The major influencing factors were inadequate and unfair payment, lack of solving staff problems by organization and poor management support, job insecurity, high job stress, unfair promotion policies, and inadequate involvement in the decision-making. Significant predictors in the multivariate analysis for lower quality of work life were male gender, being single, older age, having lower educational levels, and working in teaching hospitals., Conclusion: The quality of nursing work life was at a low level and needs improvement interventions. The predictors identified allow for more targeted interventions. Nursing managers and policymakers should develop and implement successful strategies appropriately to improve the quality of work life. This includes the payments, organizational and managerial support, job security, fair promotion policies, and measures to reduce job stress.

Background: Medical malpractice represents a serious problem in the health system and is one of the risk factors for patient safety which damages the patient and increases costs for the patient and the health care provider. The importance of these complaints against physicians is that litigation may continue for a long time and become problematic for patients and physicians. The objective of this study was to investigate the complaints of medical malpractices which were referred to Iran Medical Council to provide solutions to reduce the complaints and improve service delivery. Methods: Embase, PubMed/MEDLINE, ISI/Web of Science (WOS), Scopus, and Iranian databases, such as MagIran, SID, and Irandoc, were searched from 01/01/1990 to 07/01/2018. Also, the grey literature (via Google Scholar) was searched. Studies written in English or in Persian were searched, and keywords used included malpractice, negligence, medical malpractice, physician impairment, Iran, and professional impairment. Results: Nearly 1455 complaints (36%) of the total number of 3977 complaints were proved to be medical malpractice, and physicians were acquitted in 2542 (64%) cases. Most complaints were from gynaecologists, accounting for 43% of all complaints, followed by orthopaedic specialists who ranked second with 21.4% of the total complaints. The most type of failure was due to lack of skill (30.4%), followed by negligence (29.2%). Imprudence or indiscretion (26.3%) and noncompliance with governmental requirements (14.1%) were also in the next ranks, respectively. Conclusion: Improving patient and physician relationships, observing medical ethics, increasing the scientific and technical skills of the medical staff, and following the guidelines and medical protocols will prevent medical malpractice. Therefore, health policymakers can reduce errors and failures by adopting continuing education on medical, ethical, and legal issues., (© 2019 Iran University of Medical Sciences.)

Background: Cisplatin (Cispt) is a common anticancer drug for the treatment of several malignancies, including hepatocarcinoma. However, this drug suffers from instability in aqueous solutions. The study aimed to evaluate cisplatin efficacy on HepG2 and E. coli cells under an acidic condition. Methods: Acidic Cispt was prepared via incubation in acidic condition (pH=2) for a month duration. The chemical structure of the acidic Cispt was evaluated by using Fourier Transform Infrared Spectroscopy (FTIR) method. The cytotoxicity of the standard and acidic Cispt were then determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and minimum inhibitory concentration (MIC) assays on HepG2 and E. coli cells, respectively. Results: After preparing of acidic Cispt, its chemical structure was determined by FTIR method. In addition, cytotoxicity effects of Cispt in the standard and acidic forms were calculated 58 ± 2.9 and 65 ± 3.25 μM, respectively. MIC results also confirmed the results of MTT assay. MIC results for the standard and acidic Cispt were estimated 9.5 ± 0.47 and 9.8 ± 0.49 μM, respectively. Conclusion: Preparing Cispt in acidic condition not only did not degrade the drug, but also kept the potency of the drug approximately equal to parent drug. Regarding the instability issues of Cispt, keeping Cispt in acidic condition could be a promising approach to preserve its efficacy., (Creative Commons Attribution License)

Energy is one of the essential resources for human life and mainly classified as non-renewable resources. Since huge amounts of energy are consumed in the agriculture sector, an energy audit is an essential strategy in countries. Conservation agriculture as a tool for sustainable development can lead to saving agricultural resources. In the current investigation, energy audit for wheat conservation and conventional production systems was performed. For this purpose, 48 farms were selected randomly in 2016, and their energy performance was evaluated and compared. The data were analyzed to calculate energy parameters. Also, data envelopment analysis technique was used to identify the possible ways to achieve higher efficiency in farms. To this end, current and optimum situations and saving energy in different cultivation systems were determined using Charnes, Cooper, and Rhodes (CCR) model. The research results showed that the average energy ratio, net energy gain, specific energy, and energy productivity for conservation farms were 4.31, 137,656 MJ ha -1 , 5.56 MJ kg -1 , and 0.18 kg MJ -1 , respectively. Corresponded values for conventional farms were measured to be 3.03, 90,101 MJ ha -1 , 7.69 MJ kg -1 , and 0.13 kg MJ -1 , respectively. Data envelopment analysis results revealed that the highest saving energy in conventional system belongs to diesel fuel and irrigation inputs, and the least amount of energy saving was seen in human labor input. While for the conservation system, the highest and the least amount of energy saving belongs to nitrogen and human labor, respectively.

Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10μg/mL of Arctium lappa root extract and 5 μM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies., (Creative Commons Attribution License)

Small non-coding RNAs named microRNAs (miRNAs) modulate some functions and signaling pathways in skin epithelial cells and melanocytes. They also function as oncogenes or tumor suppressors in malignancies and tumor metastasis. We investigated the expression patterns of miRNAs, including miR-10b, 21, 200c, 373 and 520c, which regulate epithelial-to-mesenchymal transition (EMT) and metastasis in isolated cancer stem cells (CSCs) and non- CSCs. Six melanoma cell lines were tested for the expressions of stem cell markers. Melanoma stem cells were enriched via fluorescence-activated cell sorting (FACS) using the CD133 cell surface marker or spheroid culture. They were then characterized based on colony and sphere formation, and the expressions of stemness and EMT regulator genes and their invasion potential were assessed using real-time qRT-PCR and invasion assay. Our results indicate that cells enriched via sphere formation expressed all the stemness-related genes and had an enhanced number of colonies, spheres and invaded cells compared to cells enriched using the CD133 cell surface marker. Moreover, miRNAs controlling metastasis increased in the melanospheres. This may be related to the involvement of CSCs in the metastatic process. However, this must be further confirmed through the application of knockdown experiments. The results show that sphere formation is a useful method for enriching melanoma stem cells. Melanospheres were found to upregulate miR-10b, 21, 200c, 373 and 520c, so we suggest that they may control both metastasis and stemness potential.

Aims: The present study aimed to compare the gene-expression profiling of CD133(+) and CD133(-) D10 cells., Materials & Methods: Cancer stem cell-like properties and gene-expression profiling of CD133(+) D10 cells versus CD133(-) cells were evaluated., Results: The CD133(+) D10 cells showed significantly higher clonogenic and spheroid forming potential, also higher expression of stemness genes NANOG and OCT4A compared with the CD133(-) cells. Gene-expression profiling of CD133(+) versus CD133(-) D10 cells revealed that 130 genes including ABC transporter superfamily (ABCC1, ABCG2 and ABCC6) were upregulated, while 61 genes including apoptosis modifying genes (CASP8 and TNFRSF4) were downregulated., Conclusion: We conclude that many genes involved in drug resistance and tumor aggressiveness are upregulated in CD133(+) D10 cells and targeting them might be an efficient strategy for treatment of melanoma.

Background: esophageal diverticula are classified as 2 types: true diverticula and pseudodiverticula. These disorders result in clinical manifestations such as dysphagia and esophageal reflux. In this study, we evaluated the results of surgical treatment for diverticula., Methods: all patients suffering from symptomatic esophageal diverticulum, who underwent surgical treatment in Ghaem Hospital from 2000 to 2012 and were followed up for at least for one year, were included in the study. Age, sex, clinical manifestations, location, surgical approach, and mortality were evaluated. There were 25 patients (15 men and 10 women) with a mean age of 41 ± 8.3 years., Results: the most common site of involvement was inferior (epiphrenic diverticulum). Barium swallow was diagnostic. After surgical treatment, complications occurred in 4 (16%) patients, comprising anastomosis site leakage, hoarseness, atelectasis, and wound infection; all were treated medically. There was no postoperative mortality. All patients experienced an improvement in symptoms during one year of follow-up., Conclusion: due to the good results and minimal complications postoperatively, surgical treatment is recommended for patients with symptomatic esophageal diverticulum., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background: Helicobacter pylori infection is associated with gastritis and in some cases with gastric and duodenal ulcers, and even adenocarcinoma. Antibiotic therapy has significant limitations, such as the high cost and the emergence of antibiotic-resistant strains, generating the need for new treatments. The administration of antibody against H. pylori is a new effective therapeutic strategy. In this study, we successfully developed a single-variable domain of heavy chain antibody against recombinant UreC., Methods: A VHH phagemid library was constructed from immune camel heavy chain antibodies. The nanobodies were displayed on M13 phage. Library selection was performed against UreC recombinant protein. A specific single-variable domain of heavy chain antibody against UreC was screened in five rounds of panning. The nanobody with the highest score in the phage ELISA was selected for soluble expression. The nanobody was purified with a nickel-nitrilotriacetic acid (Ni-NTA) column and confirmed with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting. Affinity, specificity, and urease inhibitory properties of the nanobody were assayed., Results: Here we showed the isolation and purification of a specific nanobody with high affinity against UreC recombinant protein that can inhibit urease activity., Conclusions: The isolated UreC nanobody can specifically detect and bind to UreC and inhibit urease activity. This nanobody could be a novel class of treatment measure against H. pylori infection., (Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Public awareness of organ donation fundamentally affects the organ transplantation programs. This study was performed to assess the attitude and willingness of high school adolescents regarding organ donation. The study population consisted of 416 high school girls who were studying in four grades of three educational courses. Data were collected by a questionnaire and included demographic variables and attitude and willingness, which were assessed based on the Likert scale. The SPSS v.16 was used for data analysis. The mean age of the study subjects was 16.26 ± 1.06 years, 31% studied in grade-1, 27% in grade-2 (25% natural sciences, 27% mathematics and 48% humanities), 26% in grade-3 (30% natural sciences, 34% mathematics and 36% humanities) and 16% in pre-university stage (32% natural sciences, 42% mathematics and 26% humanities). The students had a highly positive attitude toward organ donation (mean score 4.2 ± 0.54). The greatest willingness for organ donation was concerning the kidney (88%) and heart (84%), followed by the liver (83.4%), pancreas (79.6%), cornea (67.8%) and skin (51%). Willingness for deceased as well as living organ donation was indicated by 92% and 47%, respectively, of the participants. Organ donation was considered acceptable only to relatives by 5% of the participants when the donors were deceased donors and by 16% of the participants when the donors were living donors; donation to all needy persons from deceased donors was accepted by 87% of the participants and from living donors by 31%. The purpose of donation was stated as lending help to others by 89% and progression of science by 40.2% of the participants. Willingness for organ donation from a deceased relative was declared by 63% of the students. There was significant positive correlation between willingness for organ donation and attitude (P <0.001). In addition, attitude and willingness had positive correlation with educational levels, age and educational courses. Our study suggests that Iranian adolescents have a great attitude and willingness toward organ donation, which reflects favorable knowledge of transplantation. Further research on public awareness in both genders and various age ranges is needed.

Background: Hypervolemia is a common complication in patients on hemodialysis (HD). To determine the effect of volume change on blood pressure in HD population, this cohort was conducted., Materials and Methods: The study population was composed of 60 non-diabetic patients on maintenance HD, with mean age of 59.95±15.28 years. They were divided into hypertensive group A (n=26) and normotensive group B (n=34). Data were collected by a questionnaire. Pre and post-dialysis blood levels of urea, sodium, total protein, and hemoglobin were measured and intradialytic change of plasma volume were calculated. Data analyses were performed by the SPSS v.16., Results: Out of 60 patients, 58.3% were male and 41.7% female. Post-dialysis systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly lower than pre-dialysis values in both groups (P=0.001, each). No correlation was found between intradialytic change in plasma volume or body weight and alterations of SBP or DBP during HD in the study groups (P>0.05, each). Intradialytic changes of body weight did not correlate to intradialytic changes of plasma volume (P=0.15)., Conclusion: HD effectively reduces blood pressure and volume expansion, however, intradialytic changes of plasma volume and body weight do not influence on SBP and DBP.

Patients with a thoracoabdominal stab wound may have hidden diaphragmatic injuries that could finally lead to chronic diaphragmatic hernia. In this study, we analyzed 30 patients with penetrating thoracoabdominal injuries that were stable hemodynamically and did not need emergency exploration. They underwent thoracoscopy in order to find a probable diaphragmatic injury from March 2005 to October 2007. The mean age was 26.2 years and the M/F ratio was 5:1. We observed five occult diaphragmatic injuries (16.7%) in thoracoscopic evaluations. Three cases (9.9%) were repaired through a thoracoscopic approach while laparatomy was inevitable in two (6.6%) patients. Pulmonary parenchymal lacerations were observed in two patients (6.6%) which were repaired through thoracoscopy and intra-abdominal injury was observed in one patient (3.3%) which was repaired via laparatomy. We performed thoracoabdominal CT-scan 6 months later and chronic diagrammatic hernias were not reported. Diagnostic accuracy of thoracoscopy was 100%. Owing to the high diagnostic accuracy rate, minimal invasiveness and therapeutic potency of thoracoscopy we recommend it to be performed in all clinically stable patients with penetrating thoracoabdominal penetrating injury especially in the 8th intercostal space.

There is an increasing interest in the application of nanobodies such as VHH in the field of therapy and imaging. In the present study a stable genetically engineered cell line of Chinese hamster ovary (CHO) origin transfected using two sets of expression vectors was constructed in order to permit the cytoplasmic and extracellular expression of single domain antibody along with green fluorescent protein (GFP) as reporter gene. The quality of the constructs were examined both by the restriction map as well as sequence analysis. The gene transfection and protein expression was further examined by reverse transcription-polymerase chain reaction (RT-PCR). The transfected cells were grown in 200 microg/mL hygromycin containing media and the stable cell line obtained showed fluorescent activity for more than a period of 180 days. The production of fusion protein was also detected by fluorescent microscopy, fluorescent spectroscopy as well as by enzyme-linked immunosorbent assay (ELISA) analysis. This strategy allows a rapid production of recombinant fluobodies involving VHH, which can be used in various experiments such as imaging and detection in which a primary labeled antibody is required.

The overall objective of this research was to find a new way to valorize rye bran, by producing a gellifier from the enzymatic solubilization of arabinoxylans (AX). The effects of three pure endo-xylanases from Aspergillus niger (Xyl-1), Talaromyces emersonii (Xyl-2), and Bacillus subtilis (Xyl-3) and of Grindamyl S100 (GS100), a commercial enzyme preparation containing a Xyl-1 type endo-xylanase, were tested on rye bran to study the solubilization of water-unextractable arabinoxylans (WUAX). Eight different extrusion-treated rye brans were also used as substrates to find the best physical treatment to facilitate enzymatic arabinoxylan (AX) solubilization. Arabinoxylans were better solubilized from the bran extruded at high temperature using Xyl-3. This enzyme was then tested in combination with pure (1,4)-beta-d-arabinoxylan arabinofuranohydrolase (AXH) and endo-beta-d-glucanase or ferulic acid esterase (FAE), from A. niger. Only beta-glucanase in combination with Xyl-3 improved the AX extraction, but it did not have a marked effect on the viscosity of the extracts. Xyl-3 was then tested on a high-shear-treated rye bran, and results were compared to those obtained with the high-temperature-extruded rye bran. The high-shear treatment did not improve the bran AX enzymatic solubilization. The combination of FAE with Xyl-1 or Xyl-3 did not improve the AX extraction from untreated and high-shear-treated rye bran. Finally, to study the gelation capacity of the enzymatically solubilized AX, the effect of the hydrogen peroxide/horseradish peroxidase (H(2)O(2)/POD) was tested on the Xyl-3 high-temperature-extruded bran extracts. Solubilized AX did not gel in the presence of the oxidizing system.

A monoclonal antibody (MAb) was generated by immunizing BALB/c mice with homogenized breast cancerous tissues. This antibody (PR81) was found to be of IgG(1) class and subclass, containing kappa light chain. PR81 reacted with either the membrane extracts of several breast cancerous tissues or the cell surface of some MUC1 positive cell lines (MCF-7, BT-20 and T-47D) tested by enzyme immunoassay and for MCF-7 by immunofluorescence method. PR81 also reacted with two synthetic 27 and 16-amino acid peptides, TSA-P1-24 and A-P1-15, respectively, which included the core tandem repeat sequence of MUC1. However, this antibody did not react with a synthetic 14 amino acid peptide that has no similarity with tandem repeat found in MUC1. The generated antibody had good and similar affinities (2.19 x 10(8) M(-1)) toward TSA-P1-24 and A-P1-15, which are mainly shared in the hydrophilic sequence of PDTRPAP. Through Western blot analysis of homogenized breast tissues, PR81 recognized only a major band of 250 kDa. This band is stronger in malignant tissue than benign and normal tissues.