In contemporary Iran, the nation's traditional and deeply religious society is currently experiencing swift transformations in its moral, cultural, and social aspects. It is, therefore, not surprising to observe shifts in people's attitudes toward sexuality, largely attributed to the profound impact of widespread social networks, the proliferation of information technology, and increased levels of education. Unmarried young women may potentially face adverse consequences from engaging in extramarital sexual relationships across various aspects of their lives. Acknowledging the pivotal role of self-care in influencing the sexual behaviors of young women, the objective of this study is to compile a comprehensive list of self-care strategies aimed at improving the sexual well-being of young, single Iranian women.The research will unfold in three distinct phases: Phase 1: Explanatory Sequential Mixed-Method Study This initial phase encompasses both quantitative and qualitative aspects. It begins with a cross-sectional survey, where we will gather data from 400 unmarried female students aged 18 to 29 years, utilizing a cluster random sampling method at Kerman University of Medical Sciences. Data collection will involve the use of a researcher-designed questionnaire. Subsequently, the qualitative phase will involve conducting in-depth, semi-structured interviews with female students from the University. To analyze this qualitative data, we will employ the content analysis approach. The findings obtained from both phases will be combined. Phase 2: Narrative Review In the second stage of the study, we will conduct an extensive narrative review to explore existing strategies related to the subject matter comprehensively. This review will serve as the foundational basis for our subsequent analysis. Phase 3: Strategy Prioritization In the final phase, we will prioritize the proposed strategies using a nominal group process, soliciting expert advice. This step will result in the definitive list of strategies that emerge from the study.This study pioneers the field of sexual health, with the goal of developing a protocol for creating self-care strategies based on the perspectives of young, unmarried Iranian women. It offers potential evidence-based insights into current developments in the physical, psychological, and social aspects of sexual health within this demographic. Additionally, it aims to furnish essential information to healthcare policymakers regarding the sexual health of young women. The convergence of the Iranian cultural landscape with the widespread presence of social networks and the growing utilization of information technology has played a significant role in the emergence of extramarital relationships among young women. In this context, fostering sexual health self-care practices can serve as a preventive measure against the potential consequences of such relationships within this demographic.Explanatory Sequential Mixed-Method Follow-up Study: Combining quantitative and qualitative phases.Narrative Review: Involving a review of relevant literature.Strategy Extraction through Expert Opinion: Finalizing strategies via a nominal group process.This research unfolds in three stages:Integrating quantitative and qualitative approaches, this study aims to comprehensively explore the younger generation's perspectives on psychological and social aspects of extramarital relationships, thereby providing robust documentation in this field. Self-care involves the capacity of individuals, families, and communities to support their own health, prevent illnesses, maintain well-being, and manage health conditions, either with or without assistance from healthcare professionals . AdditioWhile self-care unquestionably provides numerous benefits and plays a crucial role in improving community health, it's important to acknowledge that in certain situations, self-care might unintentionally guide individuals toward using traditional or unconventional approaches to manage illnesses and seek treatment. This phenomenon frequently results from a combination of factors such as limited access to necessary healthcare resources, a lack of suitable medical services, and deeply rooted cultural beliefs and practices prevalent within particular communities .The key distinction lies in the significant gap between self-medication and authentic self-care. Self-administering medication without a proper understanding of one's ailment does not align with the principles of self-care; instead, it has the potential to worsen the underlying illness .Moreover, while self-care offers numerous advantages when it lacks support from governments and active involvement of health systems in organizing such care, it can place a financial burden on society. This can lead to increased out-of-pocket costs for individuals .Adolescents are susceptible to participating in sexual activities, including high-risk sexual relationships, which can carry substantial threats to their reproductive and sexual well-being. The reproductive and sexual health of adolescents is impacted by cultural and social factors, and it hinges on their responsible decision-making and behavior, in line with the notion of self-care .Self-care can be considered one of the primary and initial forms of women's healthcare. In today's world, as women become more aware, they actively seek ways to enhance their health, with self-care emerging as a key approach .In a study conducted by Honarvar et al. to assess the attitudes and experiences of unmarried individuals regarding premarital sexual relationships, approximately 34% of the participants expressed their acceptance of such relationships. Shockingly, one out of every two unmarried individuals in the study reported engaging in premarital sexual activity, with nearly half of them having multiple sexual partners. The author highlights the alarming nature of the current situation, emphasizing the early age at which Iranian youth initiate sexual activity, the lack of awareness regarding sexually transmitted diseases, including HIV, and the existence of cultural and social barriers that hinder open discussions about sexuality .Alimoradi et al. conducted a study with the aim of understanding the factors that shape the perceptions of Iranian adolescent girls regarding premarital sexual relationships. The study revealed that parents, teachers, and friends had the most significant influence on the sexual and fertility beliefs and actions of these adolescent girls. Additionally, the study highlighted the presence of peer pressure, which compelled adolescents to seek opposite-sex partners. Another noteworthy finding was the perspective of Iranian adolescents regarding protective societal norms. These norms included restrictions on sexual behaviors, the endorsement of sexual relations only within the bounds of marriage, the avoidance of premarital sex, and refraining from forming friendships with the opposite sex .Engaging in sexual activity outside of marriage is viewed as illegal, irreligious, immoral, and socially taboo in Iran. Risky sexual behaviors, including unprotected sex, having multiple sexual partners, initiating sexual activity at a young age, can have detrimental effects on the health of young individuals. These behaviors may result in harmful health outcomes, as well as negative social and economic consequences .In society, there is a noticeable contradiction and duality when it comes to premarital sexual relationships. While cultural and religious norms advocate for abstinence from such relationships, factors like widespread access to information technology, delayed marriage, and the prevalent use of virtual networks have led to a more discreet approach to sexuality among young people. As a result, this context provides an opportunity to explore and understand self-care practices among young women. The goal is to promote sexual health and, consequently, develop strategies for effective sexual health education programs.The goal of this protocol study is to address the changing dynamics of sexual health among young, unmarried Iranian women in the context of shifting societal norms influenced by global changes. In response to the potential risks associated with extramarital sexual relationships, this research aims to develop a comprehensive set of self-care strategies to improve sexual health. This innovative study, conducted in three phases that include quantitative and qualitative research, a narrative review, and expert consultation, aims to gather evidence-based insights into the physical, psychological, and social changes affecting the sexual health of unmarried young women. Ultimately, its objective is to provide healthcare policymakers with essential knowledge for promoting the sexual well-being of this demographic.The visual diagram depicting the research procedure is presented in Fig. To identify self-care practices and the factors associated with them in young women, with the goal of enhancing sexual health.To provide a comprehensive description of the self-care experiences of young, single Iranian women, as well as insights from other key informants, to promote sexual health.To determine effective self-care strategies for young, single Iranian women to enhance their sexual health.The primary aim of this study is to propose a protocol for developing self-care strategies to improve the sexual health of young, unmarried Iranian women. The overarching objectives of this study are as follows:Stage 1: The initial stage consists of a sequential explanatory mixed-methods study, which includes both quantitative and qualitative phases. The quantitative phase will be conducted first, followed by the qualitative phase, aiming to provide a deeper understanding of respondents' experiences across the spectrum. Subsequently, the results from both phases will be integrated.Stage 2: The second stage involves a narrative review to examine existing strategies found in relevant literature.Stage 3: The third stage involves presenting the list of proposed strategies to a panel of experts. This panel will prioritize and extract the final self-care strategies for young women to enhance their sexual health.This research follows a three-stage approach:The quantitative phase of this study is a 6-month cross-sectional descriptive-analytical survey. This phase will concentrate on unmarried young female students who meet specific inclusion criteria and are enrolled at the Kerman University of Medical Sciences.The minimum sample size needed to estimate self-awareness, self-testing, and self-management variables with a 95% confidence level and a precision level of 2.5, assuming a standard deviation of 25, was calculated using the following formula, resulting in a minimum sample size estimate of 400 individuals.Kerman University of Medical Sciences offers education in various fields, encompassing 16 undergraduate programs, 36 master's degree programs, 3 general physician programs, 25 specialized doctoral programs, 19 clinical residency programs, and 5 sub-specialization programs.A random cluster is selected from each field using a random number table.Students who meet the study's inclusion criteria within the chosen cluster are offered the questionnaire, provided they express interest and consent to participate.After selecting the class, the researcher provides an introductory briefing to the students.Students access the questionnaire through a printed barcode, which they scan with their mobile phones. This allows them to answer the questions online.The informed consent form is located on the first page of the online questionnaire. After granting consent, students proceed to answer the questions.Additionally, the questionnaire includes an option for respondents to indicate "I do not want to answer this question."In this phase, data collection is conducted as follows:Female genderAge between 18 to 29 yearsWillingness to provide informed consentIranian nationalityMeeting the definition of unmarried according to Iran's socio-cultural norms, which entails not having a permanent marriage record on one's birth certificate and registering marriages through official officesEnrollment as a student at any academic level, including undergraduate, master's, doctoral, specialty, and sub-specialty programs.The inclusion criteria for this study are as follows:The sole exclusion criterion for this study is the student's lack of willingness to continue participating in the research.In the initial phase of the quantitative research, we will utilize a researcher-designed questionnaire to assess the perspectives of female university students regarding self-care and the factors influencing the maintenance of sexual health in young women. This questionnaire will be developed based on a review of relevant literature and existing tools, including studies by Bourdeau et al. , Barnes Part 1: This section gathers personal information about the study participants, including age, education, parents' education, ethnicity, economic status, internet and virtual network usage, communication with parents, discussions about sexual topics with parents and friends, and questions related to self-care.Part 2: This section focuses on the self-awareness of young female university students in achieving sexual health.Part 3: This section is dedicated to self-testing among young female university students as it pertains to achieving sexual health.Part 4: This section addresses the self-management practices of young female university students in achieving sexual health.The questionnaire consists of four main parts:In the second, third, and fourth sections of the questionnaire, responses will be rated using a 5-point Likert scale, with the following scoring system: completely agree (5), agree (4), neutral (3), disagree (2), and completely disagree (1).Content validity assessment: To assess content validity, the questionnaire will undergo both quantitative and qualitative evaluations by 10 relevant experts. They will use either the Content Validity Ratio (CVR) or Content Validity Index (CVI) methods. Additionally, 10 experts will assess its qualitative content validity, focusing on language, word usage, and item placement. Feedback from these experts will guide necessary revisions in consultation with the research team.Face validity assessment: The questionnaire will be presented to 15 eligible female students to assess face validity. These students will provide feedback on its simplicity, comprehensibility, and clarity. Each question's importance will be rated using a 5-point Likert scale: highly important (score 5), moderately important (score 4), somewhat important (score 3), slightly important (score 2), and not important at all (score 1). An impact score will be calculated, with a criterion for quantitative face validity confirmation being an impact score exceeding 1.5.Reliability assessment: To assess reliability, the test-retest method will be employed.In this phase, a self-care questionnaire specifically designed to enhance sexual health among single young female students will be employed. To ensure the validity and reliability of this questionnaire, the following steps will be taken:These steps will help ensure the questionnaire's validity and reliability for effective data collection.Independent samples t-test to assess relationships between quantitative variables and dichotomous qualitative ones like residence (city or village).Analysis of variance (ANOVA) to identify associations between quantitative variables and qualitative ones with multiple categories, such as education level.Pearson's correlation test to examine connections between two quantitative variables, like self-awareness and age.We will use descriptive statistics like frequency (percentage), mean, and standard deviation to depict demographic and socio-economic characteristics. Inferential statistics will serve these purposes:In the qualitative phase of the study, content analysis will be employed to explore the experiences of single/unmarried young Iranian women and key informants concerning self-care for sexual health. This qualitative approach builds upon insights gathered from the quantitative phase and aims to provide a deeper understanding of self-care strategies for promoting sexual health in young women. Content analysis will help uncover and analyze the narratives and perspectives of the participants, enriching the overall findings of the study.In the qualitative phase of the study, participants will be selected to ensure maximum diversity in background factors. This includes variations in education, age, cultural and social status, religious affiliation, and economic status among the participants.It's important to note that the research community for this project comprises students from the Kerman University of Medical Sciences. This university, categorized as a type 1 institution in Iran, enrolls several thousand students from various regions of the country. Therefore, the sample drawn from these students is not constrained by regional or provincial cultural specificities and can be considered representative of Iranian female students at large.The diversity in participant selection will contribute to a comprehensive understanding of self-care strategies for promoting sexual health among young Iranian women. Data collection will involve in-depth interviews and other qualitative research methods to capture the rich experiences and perspectives of the participants.For this phase of the study, the selection of participating students will be carried out through targeted sampling, and the sampling process will continue until data saturation is achieved.In qualitative research, there is no fixed or predetermined sample size. Instead, the determination of sample size is guided by the principle of data saturation. Data saturation is reached when gathering more data no longer leads to the emergence of new concepts or insights. In other words, it means that the researchers have thoroughly explored and understood the range of experiences and perspectives related to the research topic.The sampling path in qualitative studies is flexible and adaptive, driven by the evolving understanding of the subject matter. If needed, data collection can persist beyond the point of saturation to ensure a comprehensive exploration of the research topic. This approach allows the research to capture a rich and diverse set of experiences and insights from the participants, ensuring that the qualitative phase of the study is thorough and informative .The selection of female university students for the qualitative phase of the study was based on their active participation in the quantitative phase and their strong willingness to continue into the qualitative phase. These students were chosen because of the diversity in their responses regarding self-care practices for sexual health. They will be selected from Kerman University of Medical Sciences and will take part in semi-structured, in-depth interviews. This approach ensures that the qualitative phase captures a wide range of perspectives and experiences related to self-care for sexual health among young Iranian women.When you hear the term “self-care for sexual health promotion,” what comes to mind?What actions do you take to promote sexual health through self-care?Are there any behaviors or practices you avoid to promote sexual health through self-care?What factors or elements contribute to your success in promoting sexual health through self-care?Conversely, what factors or elements hinder you from effectively promoting your sexual health through self-care?The qualitative interview guide for female participants from Kerman University of Medical Sciences is designed to explore their perspectives on achieving sexual health through self-care. The semi-structured interviews will begin with open-ended questions and progress to inquiries about the participants' views on the significance of self-care in achieving sexual health. The interview guide includes the following questions:These questions aim to elicit a comprehensive understanding of the participants' experiences, practices, and perspectives related to self-care for sexual health promotion.In the qualitative phase of the study, all conversations with participants will be recorded with their explicit consent using a digital voice recorder. In addition to interviews with participants, key informants, such as fertility and sexual health experts specializing in sexual self-care for young individuals, will also be interviewed to enrich the study's findings.The choice of interview locations will be based on participant preferences and circumstances to ensure their comfort and convenience. The duration of interviews will be adjusted according to the participant's willingness to engage in discussions and share their experiences during the process, allowing for flexibility in the interview process.Open coding: The data will be analyzed through open coding. This involves systematically reviewing the interview transcripts and identifying categories based on recurring themes in response to the research questions. Open coding is a fundamental step in qualitative content analysis and helps in organizing and categorizing the data.Qualitative content analysis: The overall approach to data analysis is qualitative content analysis. This method allows for the extraction of meaningful insights and patterns from the qualitative data collected during the interviews. It involves a systematic examination of the data to identify themes, patterns, and categories that emerge from the participants' responses.Data analysis for the qualitative phase of the study will begin promptly once data collection commences. The analysis will follow the method proposed by Granheim and Luddmann. Here are the key aspects of the data analysis process:Regarding the integration of quantitative and qualitative data from the first phase, the results will be combined using the connection method. This integration will help provide a comprehensive understanding of self-care practices for sexual health among young Iranian women, drawing on both quantitative and qualitative perspectives.Literature search: Relevant texts will be sourced through keyword searches related to self-care and sexual health across various databases, including MEDLINE, Embase, CINAHL, Cochrane, Scopus, and Web of Science. Additionally, Persian databases such as Irandoc, SID, IranMedex, and Scimed will be queried using Persian keywords and their English equivalents.Comprehensive search: The objective of this stage is to gather insights, strategies, and effective approaches for promoting sexual health among young women on a global scale. To ensure comprehensive coverage, Google Scholar will also be consulted to identify and include relevant studies and texts in the review.The second stage of this study involves a narrative review with the aim of identifying self-care strategies relevant to enhancing sexual health among single/unmarried young women in existing literature. Here is an overview of the methodology:Integration of the results of the first and second stages of the research: Subsequently, the results obtained from the first and second stages of the research will be integrated through a side-by-side merging approach, and a list of the proposed strategies will be developed to be presented to the nominal group in the third stage.Session with Experts: We'll gather sexual health and fertility experts and stakeholders.Sharing Strategies: We'll present proposed self-care strategies developed from previous research stages.Gathering Input: Participants will provide feedback to refine and prioritize the strategies.Compilation and Refinement: Strategies will be fine-tuned based on expert input, ensuring evidence-based effectiveness.In the third research stage, we'll use the nominal group technique to create effective self-care strategies for young women's sexual health. Here's an overview:The nominal group technique leverages collective expertise for informed strategy development.One of the fundamental challenges to the health of young people, especially single women, is engaging in risky sexual behaviors that can have negative consequences on their sexual health and fertility, such as unintended pregnancies, unsafe abortions, sexually transmitted infections, infertility, and more in their future lives , 27.Usually, discussions around sex and gender-related topics create unpleasant feelings in individuals, thus little attention has been paid to these matters. Nevertheless, sexual needs are also human needs that should be addressed through necessary education and enjoyed. Unfortunately, it seems that within Iranian families, due to the lack of awareness and a lack of understanding of how to pass on accurate sexual information to adolescents and young people, sexual problems resulting from these issues are more prevalent . A studySexual health is a field based on knowledge and skill development, so having scientific evidence is essential. Therefore, the results of this study can provide insights into the field of self-care for sexual health among single/unmarried young women and provide national documentation in the field of promoting strategies to relevant policymakers, planners, and program executives.


Marginalised people experience diminished access to pharmaceutical care and worse medication-related outcomes than the general population. Health equity is a global priority. This article explores the key evidence of health inequity and medication use, structures the causes and contributory factors and suggests opportunities that can be taken to advance the pharmaceutical care agenda so as to achieve health equity. The causes of, and contributors to, this inequity are multi-fold, with patient- and person-related factors being the most commonly reported. Limited evidence is available to identify risk factors related to other aspects of a personal medication use system, such as technology, tasks, tools and the internal and the external environments. Multiple opportunities exist to enhance equity in medication-related outcomes through pharmaceutical care research and practice. To optimise the effects and the sustainable implementation of these opportunities, it is important to (1) ensure the meaningful inclusion and engagement of members of marginalised groups, (2) use a person-centred approach and (3) apply a systems-based approach to address all of the necessary components of a system that interact and form a network as work processes that produce system outcomes. Health is a fundamental human right, and the World Health Organization (WHO) states that health equity is realised when all people can attain their full potential for health and wellbeing . TacklinIt is well acknowledged that some of the most powerful influences on health, i.e., social determinants of health, are structural. For example, they derive from social, economic or political structures and are beyond the control of any individual person. Additionally, healthcare professionals’ and other individuals’ unconscious or implicit biases towards specific populations or individuals can further contribute to health inequities . The antImprovement of the benefits that people derive from the use of medicines and the optimisation of medication safety are also global priorities . PharmacWe acknowledge that the literature is abundant in studies of medication outcomes specific to marginalised groups. However, in this paper, to understand the differences in medication outcomes between marginalised groups and the general population and the causes of these differences, we focused on research that compared medication outcomes between marginalised populations and the general population. In comparison to the general population, marginalised people experience health inequity, often associated with their use of medication. This causes an increased risk of adverse outcomes including mortality, morbidity burden, quality of life deficit and patient safety issues ,16,17,18Such inequities in medication-related experiences and outcomes can occur in any stage of the medication use process, such as the prescription, dispensing and administration of medication, and a sample of these issues is presented in Members of sexual minority groups with additional risk factors for health inequity, e.g., mental ill-health, substance misuse and status as a member of an ethnic minority group, experience even worse outcomes, highlighting the extreme vulnerability of these individuals . This isCheraghi-Sohi and colleagues employed a systems-based approach to categorise the potential contributory and causative factors of patient safety issues among marginalised groups. Of the studies reporting on medication issues, the studied populations included care home residents, ethnic minority groups and people experiencing visual or hearing impairment . The fraPotential patient-level factors contributing to inferior medication-related outcomes among people from ethnic minority groups include (mis)beliefs about or misunderstanding of illnesses and medication use, cultural perceptions, health literacy and communication, language proficiency, trust in healthcare providers, social support, e.g., the contributions of family or friends to safety vigilance, and income or health insurance status ,16,17,18People with hearing impairments have reported that pharmacists are not sensitive to their needs and that there is an over-reliance on written information and an absence of accommodation of the communication needs of this community . Those wParand’s review of medication errors caused by informal carers also applied a systems-based approach to categorise causative factors and identified factors at multiple system levels, including the following : the carThe limited evidence regarding people who are in prison or homeless suggests that patient-level factors contribute to pharmaceutical care and medication safety issues. For example, these people experience a higher prevalence of morbidity, polypharmacy, mental health and substance misuse issues than the general population. These patient-level factors add complexity to the individual factors, e.g., the prescriber, and organisational factors, e.g., the integration of information, in these contexts ,25,36,37We found little evidence for the causes of negative pharmaceutical care experiences among members of sexual minority groups. The available evidence highlights the absence of dedicated training and curriculum content in pharmacy programmes ,39. The From the above, it is clear that various authors have attempted to describe the causes and factors contributing to the inequities experienced by marginalised groups in comparison to the general population. In this section, we gather some of this evidence and structure it using the Systems Engineering Initiative for Patient Safety (SEIPS) Model 2.0 . SEIPS hTo the best of our knowledge, the current literature does not provide a complete picture of the patient’s “work system” that can explain the causes of the health inequities of marginalised groups. Few of the papers reviewed provided data on the role of the patients’ internal environments in contributing to health inequities ,42. ThisThe richest data on the causes of inequities in the literature concern the persons involved in the system: patients, informal carers and healthcare providers. Regardless of the study population, the common modifiable patient-related factors contributing to inequity in medication-related outcomes appear to be education, language, communication skills, cultural perceptions and beliefs about illnesses and medication, past experiences and social support. This is supported by qualitative evidence from Ireland and England regarding access to healthcare among marginalised people ,42. ThesFor other people involved in the patient’s system, the contributory factors were heterogenous. For example, informal carer and healthcare provider factors included language proficiency, training, medication prescription or administration skills and healthcare practitioners’ sensitivity to and management of patients’ needs .Health equity, including pharmaceutical care equity, is a fundamental human right and we need to better understand how to achieve this. Globally, there is diversity in cultural and ethnic make-up between countries, driving a requirement for our pharmaceutical care services to accommodate the needs, beliefs and views of varying marginalised groups . To achiThe findings of our review suggest several opportunities for improvement. Across several marginalised groups, a paucity of evidence-based interventions was identified, and there is a clear need to undertake research in this area. For example, a systematic review published in 2010 identified that pharmaceutical care services are associated with positive clinical, humanistic and economic outcomes among racial/ethnic minority groups . HoweverTwo reviews of the pharmaceutical care of people with sensory impairments identified no studies of interventions that sought to improve this care ,48. HoweExamining the available evidence collectively, regardless of the marginalised group studied, low- and middle-income countries (LMIC) are under-represented, with most of the published research cited in this article undertaken in high-income countries. This supports calls for research aiming to enhance medication safety and patient safety in LMIC ,51. In aThe available evidence regarding interventions to promote pharmaceutical care equity among marginalised groups points to three inter-related ingredients: (1) inclusivity and participation, (2) a person-centred tailored approach and (3) a systems-based approach ,18,32,53Researchers and service providers should facilitate the inclusion and engagement of people from marginalised groups in the co-design, co-development and delivery of interventions . This isResearch is needed in order to understand the unique pharmaceutical care needs of marginalised groups and individuals and to develop and implement tailored interventions aiming to address these needs . SeveralThe use of a systems-based framework will be supportive in identifying improvement and implementation opportunities on all relevant system levels . To illuThe health inequity of marginalised groups is acknowledged, and there is a strong body of evidence published over the past decade describing medication-related differences between ethnic minorities and the general population in various countries. However, the literature does not provide many comparisons of medication-related outcomes between other marginalised groups and the general population. The published studies provide little information on the elements of the patient system that may cause these inequities or the types of interventions that should be prioritised in order to transition toward true health equity. Only the characteristics of the patients, their caregivers and health professionals are generally investigated. Further research on the roles of patient system elements in health inequity is needed to define relevant and personalized pharmaceutical care interventions that can help to reduce these inequities. Across all marginalised groups, the bulk of evidence identified in this manuscript seems to derive from high-income countries, and there is therefore a clear need to explore the medication-related experiences and outcomes of these issues among marginalised people in low-and middle-income countries. Much evidence points to disparities in service provision; however, the clinical or humanistic impacts of medication-related challenges experienced by marginalised groups, as well as theirs effect on outcomes and interventions aiming to address them, require further work.


Baijiu, fruit wine, rice wine, beer, whisky, etc.), as important fermented food, have been loved by consumers all over the world. This Special Issue includes a total of eleven articles, and nine of them involve research on brewing technology of alcoholic products and brewing microorganisms. This phenomenon indicates that the alcoholic products industry occupies an important position in the field of food fermentation. Therefore, in response to the research content of these nine articles, this editorial mainly explores the research hotspots in the field of alcohol brewing.Food brewing technology is an important technology in the modern worldwide food industry, which uses the specific traits of microorganisms to produce food by traditional or modern engineering techniques. The products produced by food brewing technology have spread all over the world. Among them, alcoholic products , can significantly reduce the concentration of malic acid and total acidity in wines, without negatively impacting the flavor quality. Yang et al. (2022) found that an tability . This stBaijiu and rice wine are traditional Chinese alcoholic products with a long history of brewing. During the brewing process, a variety of brewing microorganisms use sugar, cellulose and other raw materials to grow and produce more than 100 flavor substances, which can form different flavor types of Baijiu and rice wine. Among them, the brewing microorganisms mainly come from Jiuqu, pit mud and fermented grains, and together affect the brewing process and flavor quality of Baijiu and rice wine. Therefore, it is of great significance for standardizing the brewing industry of Baijiu and rice wine in the future to explain the types of brewing microorganisms and their metabolic mechanisms in the brewing process of Baijiu and rice wine. At present, Pu and Yan (2022) found differences in fungal community structures and physicochemical properties in pit mud samples from different spatial positions within Nongxiang Baijiu fermentation cellars, revealing unique characteristic multidimensional pit mud fungal community profiles [Jiuqu and the style of corresponding rice wine from the rim of the Sichuan Basin in Southwest China [ and Yan 022 foundst China .Jiuqu microorganisms also included the metabolic functions of specific microbial communities. For example, the fermentation functional microbiota (FFM) and alcohol functional microbiota (AFM) were obtained by correlating the fermentation ability and alcohol production ability from Jiuqu microbiota of Nongxiang Baijiu, and function predictions indicated that fermentation functional bacterial microbiota was active in metabolic functions related to product synthesis and transport, and the alcohol functional bacterial microbiota was very active in raw material utilization and its own metabolic synthesis [Jiuqu fermentation. Almost all flavor compounds in Jiuqu, including alcohols, esters, phenols, and acids, are derived from the carbohydrate metabolism during fermentation, which is closely related to the growth and material exchange of microorganisms in the fermentation environment. Zhang et al. (2022) studied the changes in microbial functions and the relationship between carbohydrate metabolism-related functional genes and extracellular enzyme activity during the Jiuqu fermentation of Nongxiang Baijiu. The results showed that the pathways related to metabolites were less in the early fermentation stage, but more in the middle and late stages. The expression levels of functional genes related to pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and propanoate metabolism were relatively high in the early and late stages of fermentation, while the expression levels of these genes in start and cross stages were relatively low. The study also found that amino sugar and nucleoside sugar metabolisms were dominant in the middle stage of fermentation [Jiuqu and pit mud in Baijiu and rice wine, which provided the theoretical basis for designing effective strategies to manipulate microbial consortia to improve the quality of Chinese Baijiu and rice wine.In addition, the research emphasis on ynthesis . Meantimentation . The aboNongxiang Baijiu. Therefore, it is an important reason for the development of artificial pit mud (APM) manufacturing technology. APM manufacturing is a directional evolution process of functional consortia under anaerobic conditions. Traditionally, the APM improvement studies mainly focused on the different formulas, functional strains, and cultivation patterns and times due to the scarcity of high-quality PM resources and the frequent degradation of aged PM. The effects of Jiuqu on APM quality received little attention. Here, Mu et al. (2022) used two types of APM manufactured by adding fortified Jiuqu (FJ) and conventional Jiuqu (CJ). The results showed that FJ altered the prokaryotic communities rather than the fungal ones. Correlation analysis suggested that these variations in community structure promoted the formation of hexanoic acid, butyric acid, and the corresponding ethyl esters, and inhibited the formation of lactic acid and ethyl lactate, thus improving the flavor quality of the APM [Jiuqu in APM cultivation and may contribute to the optimization of the APM manufacturing technology and the production of high-quality Nongxiang Baijiu.Of note, the natural evolution of pit mud (PM) microbiota is very slow and needs more than 20 years of uninterrupted domestication to produce high-quality  the APM . SpecifiBaijiu and rice wine, isolation, identification, and purification of microorganisms during the brewing process, as well as the exploration of the related functions, applications, and tolerance mechanisms of single microorganisms, are also the main subjects of current research on brewing microorganisms. For example, Clostridium is the key bacteria that inhabit the pit mud in a fermentation cell during the fermentation of Nongxiang Baijiu. Their activities in the process of Baijiu fermentation are closely related to the niches of pit mud and cells. After multiple rounds of underground fermentation, Clostridium has been domesticated and adapted to the environment. However, the mechanisms of clostridia succession in the pit mud and how they metabolize nutrients in grains are not clear. Herein, 15 Clostridium species including three firstly reported ones  were isolated from the pit mud of Nongxiang Baijiu. Eighty-one percent of these Clostridium strains were motile, and most of them showed chemotaxis to organic acids, glutathione, saccharides and lactic acid bacteria. In a simulated Baijiu fermentation system, Clostridium migrated from pit mud to fermented grains with the addition of chemokine lactic acid, resulting in the production of acetic acid and butyric acid [Clostridium in pit mud, and provides a reference for the regulation of lactic acid level in fermented grains during Baijiu fermentation.In addition to analyzing the overall microbial community structure and functional effects in ric acid . This stBaijiu, and the application of these yeasts in fruit wine fermentation can help improve the flavor of fruit wine. Also, mixed fermentation of fruit wine by Saccharomyces cerevisiae and aroma-producing yeasts is an important means to change the single flavor substances of fruit wine. Cai et al. (2022) screened three aroma-producing yeasts with high ester yields from the fermentation process of special-flavor Baijiu, and applied them to the simulated fermentation process of blueberry wine. The results showed that the content of flavor substances in the blueberry wine fermented with S. cerevisiae and Candida glabrata was the highest, indicating that C. glabrata had the potential to create blueberry wine with a unique flavor [A large number of aroma-producing yeasts are found in the fermentation process of e flavor .Pichia anomala. The ethanol stress might cause the reactive oxygen species burst in P. anomala, thereby promoting the accumulation of malondialdehyde content in the cell membrane, destroying the integrity of the cell membrane and leading to the leakage of intracellular nutrients and electrolytes. Finally, the growth and ester production ability of P. anomala was inhibited [The brewing process of alcoholic products has always been a complex system with dynamic environmental changes of physicochemical factors. With the increase in ethanol concentration during the brewing process, yeast is susceptible to ethanol stress, which affects the fermentation efficiency, leading to the decline of quality and flavor profiles in the finished alcoholic products. Chen et al. (2022) found that ethanol stress could inhibit the growth and ester production metabolism of nhibited .Baijiu and rice wine fermentation, and the diversity of research directions in brewing microorganisms. This has important theoretical and practical significance for the development of the alcoholic products brewing industry in the future.All in all, these nine articles each have their own highlights, revealing the application of the biological deacidification method in fruit wine, the structure and function of microbial communities during (1)Saccharomyces pastorianus G03H8 with the potential to greatly reduce the cost of RNA production and shorten the fermentation cycle via ARTP mutagenesis technology. The highest RNA content of mutant strain G03H8 increased by 40% compared with the parental strain G03. The RNA production and DCW of G03H8 reached 3.58 g/L and 60.58 g/L in fed-batch with molasses flowing. In addition, the reason for high RNA production in mutant strain G03H8 is closely related to the ribosome bio-genesis, yeast meiosis, RNA transport, and longevity regulating pathways.In this study, the author obtained a mutant strain of (2)Antrodia cinnamomea in submerged fermentation and provide a theoretical basis to further improve the sporulation, in this study comparative transcriptomics was used to reveal the regulatory mechanism underlying asexual sporulation of A. cinnamomea induced by nutrient limitation in submerged fermentation. It was found that the signals of nutrient limitation (including carbon and nitrogen starvation) were firstly responded to by the corresponding sensors, such as Rco-3. Then, the sensors cause an effect on the downstream genes, such as areA, tmpA, gluC, and chsD. These genes play a direct or indirect role in enhancing the expression of the genes in the central signaling pathway, such as flbD, brlA, and wetA, thereby promoting the sporulation.In order to complement the mechanism of asexual sporulation of In addition, the abstracts of the other two articles in this Special Issue are as follows ,11:(1)InWe hope that this Special Issue will be useful for all readers in terms of the novel information it provides on food brewing technology and brewing microorganisms, helping us better promote the healthy development of the fermentation industry.


Drug-Coated Balloons have shown promising results as a minimally invasive approach to treat stenotic arteries, but recent animal studies have revealed limited, non-uniform coating transfer onto the arterial lumen. In vitro data suggested that local coating transfer tracks the local Contact Pressure (CP) between the balloon and the endothelium. Therefore, this work aimed to investigate in silico how different interventional and device parameters may affect the spatial distribution of CP during the inflation of an angioplasty balloon within idealized vessels that resemble healthy femoral arteries in size and compliance. An angioplasty balloon computational model was developed, considering longitudinal non-uniform wall thickness, due to its forming process, and the folding procedure of the balloon. To identify the conditions leading to non-uniform CP, sensitivity finite element analyses were performed comparing different values for balloon working length, longitudinally varying wall thickness, friction coefficient on the balloon-vessel interface, vessel wall stiffness and thickness, and balloon-to-vessel diameter ratio. Findings indicate a significant irregularity of contact between the balloon and the vessel, mainly affected by the balloon’s unfolding and longitudinal thickness variation. Mirroring published data on coating transfer distribution in animal studies, the interfacial CP distribution was maximal at the middle of the balloon treatment site, while exhibiting a circumferential pattern of linear peaks as a consequence of the particular balloon-vessel interaction during unfolding. A high ratio of balloon-to-vessel diameter, higher vessel stiffness, and thickness was found to increase significantly the amplitude and spatial distribution of the CP, while a higher friction coefficient at the balloon-to-vessel interface further exacerbated the non-uniformity of CP. Evaluation of balloon design effects revealed that the thicker tapered part caused CP reduction in the areas that interacted with the extremities of the balloon, whereas total length only weakly impacted the CP. Taken together, this study offers a deeper understanding of the factors influencing the irregularity of balloon-tissue contact, a key step toward uniformity in drug-coating transfer and potential clinical effectiveness.The online version contains supplementary material available at 10.1007/s10439-023-03359-y. Cardiovascular diseases are the primary cause of death globally, with heart attack and stroke contributing to 85% of all cardiovascular diseases’ deaths in 2019 . AtherosDrug-coated balloons (DCBs) have emerged as a promising, minimally invasive therapeutic intervention for the treatment of arterial stenosis and have shown promising results in the treatment of peripheral artery disease. During the treatment, antiproliferative drug particles are delivered to the media and adventitia layers of the arterial wall to foster the inhibition of smooth muscle cell proliferation. The drug is encapsulated within an excipient layer that is designed to be transferred and remain attached to the arterial endoluminal surface of the diseased vessel, acting as a long-term drug depot for the lesion area . TherefoAlthough some clinical cohorts have shown promising results, a clinical study revealed that the efficacy of the treatment can be limited by calcification . HoweverHowever, as highlighted in a recent review, the biophysical forces affecting coating transfer have received less attention . EffortsTherefore, in this study, we were interested in exploiting finite element simulations to investigate the interaction between angioplasty balloons and simplified vessels that resemble femoral arteries, to compare the findings with previous animal experiments on coating transfer .In this effort, it is critical to adopt a suitable balloon numerical model able to capture the details of the contact modalities. Over the past 20 years, various models have been developed in literature to simulate the mechanical behavior of angioplasty balloons. These models range from simple to complex approaches of high stiffness cylinders , 58, 60,Given the factors previously mentioned, the current study aimed to examine the potential of contact non-uniformity arising during balloon inflation, attributed to the balloon folding and longitudinal thickness variation. To this end, the balloon interaction with idealized vessels were considered, in order to avoid the introduction of other sources of contact non-uniformity . Due to parameters variability, a sensitivity analysis was performed to study the impact of various procedural conditions on the balloon-vessel interaction. To investigate these, numerical models of a generic peripheral balloon catheter, incorporating its folding process, were adopted and expanded within idealized vessels, straight and cylindrical, resembling healthy femoral arteries in terms of diameter, wall thickness, and compliance. The models were used to generate CP maps in different conditions, considering various balloon and vessel characteristics, including (i) the balloon working length, (ii) the balloon’s longitudinal wall thickness variation, (iii) the vessel wall stiffness, (iv) the vessel wall thickness, (v) the friction coefficient on the balloon-vessel interface, and (vi) the balloon-to-vessel diameter ratio.Angioplasty balloons can be categorized into three types according to their radial compliance: compliant, semi-compliant, and non-compliant. Drug-coated balloons (DCBs) typically fall under the semi-compliant category, which means these balloons can expand by up to 30% of their original diameter when they reach their rated burst pressure. In this work, a standard semi-compliant balloon catheter, which is the usual substrate for DCB catheters , was emphttps://www.l2mtech.de/?page_id=462). Moreover, in a recent numerical study comparing Nylon and Pebax balloons, a Young’s modulus of 414 MPa was adopted to mechanically describe the performance of the Pebax [ρ = 916 kg/m3 are here used for the balloon’s material [Pebax materials are typically used for semi-compliant balloons. These materials exhibit a linear and isotropic behavior for stretch up to 25%, demonstrating also a softer behavior compared to Nylon, another material frequently adopted for angioplasty balloons . Nehe Pebax , which imaterial .Shell elements, as adept at capturing the inter-elemental bending stiffness, were used in the numerical representation of the balloon to simulate the balloon's response to the highly bending conditions introduced during the folding process. In particular, reduced integration linear elements were adopted: the element distribution was carefully analyzed, and a mesh sensitivity study was performed on the control case simulation of balloon inflation in a vessel . By increasing the number of elements on the circumference and using a finer mesh in the tapered region, the curve inner pressure-maximum diameter and the CP showed minimal variation, when the number of elements exceeded 300 circumferentially. Adopting the aforementioned meshing approach, the 10-, 20-, and 50-mm balloons were each discretized using a total mesh of 51000, 81000, and 171600 four-noded, reduced integration, isoparametric elements, respectively  the balloon’s folding process to acquire its folded configuration, (ii) the balloon’s free expansion to describe its unfolding process and compliance, and (iii) the balloon’s inflation in idealized vessels to investigate the balloon-vessel interaction. The balloon folded geometry and its unfolding process determine the initial contact with the vessel, hence in this work particular attention was devoted to simulating the two steps. The folding process of the catheter as described by Ref.  was emplFor the contact between the vessel lumen wall and the external surface of the balloon, different values of the friction coefficient were tested . The pressure variations on the internal surface of the balloon were modeled using a "smooth step" function to minimize abrupt transitions and minimize dynamic effects. The pressure initiated at a value of 0 atm, decreased to − 1 atm during the folding process and then increased until a maximum value of 13 atm during the expansion.A suite of numerical simulations was conducted to evaluate the impact of various procedural and modeling factors on the modalities of balloon-vessel interaction Table . A baselz-axis, and the circumferential and radial axis as the θ and r axis, respectively. The script produces a map that utilizes a color code to depict the intensity of the stress at each point. The pixel number of the map corresponded to the number of nodes along the vessel endoluminal surface.A script was developed utilizing the programming language MATLAB to facilitate the post-processing of data generated from this study examining the pressure distribution along the cylindrical vessel structure. This script was designed to receive as input the CP values determined at the nodes of the mesh along the vessel structure. The location of each point was specified using a cylindrical coordinate system defined by the longitudinal center axis of the vessel as the In Fig. After analyzing the control case simulation, the two-dimensional CP maps of the vessel wall surface revealed non-uniform CP on the vessel endoluminal surface, both longitudinally and circumferentially Fig. . At low Average CP across the entire area of interaction between the vessel and the working length of the balloon was 10 to 60 times lower than the concurrent IP for the suite of simulations described in Table The CP distribution color maps display linear patterns in all four cases of DR, which become increasingly pronounced as the level of DR increases, even at higher IP levels Fig. a. The prExamination of the effect of three different friction coefficients on the distribution of CP maps reveals a progression of irregularity as friction coefficients increase Fig. b. With aBy averaging the longitudinal rings of elements along the working length of the DCB Fig. , left, iPlotting of mean CP along the vessel circumference Fig. , right, The objective of this study was to detect and characterize potential non-uniformities in contact patterns when an angioplasty balloon expands within an idealized vessel, with size and compliance resembling a femoral artery. A sensitivity analysis on various parameters revealed a repetitive trend of CP non-uniformity, with certain balloon features identified as key drivers. The results of the analyses further suggest CP as a driving force for coating transfer onto the arterial wall surface, and as a potential causative factor of non-uniform coating transfer in healthy pig arteries in vivo .The folded configuration of the balloon was accounted to adequately describe the mechanical and geometrical response of the balloon and was consistent with with the experimental cross-section found by micro-CT . During The balloon folding process resulted in linear patterned distributions of augmented CP concentration on the vessel mural surface. These findings are qualitatively consistent with images of in vivo transfer distribution on healthy pig arteries . The corRemarkably, even slight wall thickness variations across the working length of the balloon can result in significant variations in contact interaction. The results underscore the necessity of accurately modeling balloon membrane thickness in numerical studies of DCB angioplasty. Nevertheless, in all the thickness cases, the ends of the cylindrical area of the balloon, exhibited a decrease in the transfer of CP onto the mural surface.As arterial stiffness and thickness vary with disease, we also investigated their impact on the CP developed during DCB angioplasty. As expected, the findings demonstrated that greater vessel stiffness and thickness were associated with a consistent rise in CP. This comes in agreement with the hypothesis that age-related arterial stiffening could lead to higher pressure during drug release  and, in The current study had several limitations and certain assumptions were made in the numerical calculations. The adopted approach with respect to the parameter variation represents a limited exploration of the parameters space. However, the purpose of this sensitivity analysis was precisely to understand how the individual parameter under investigation can impact the simulation results in terms of contact pressure patterns and to observe whether the contact heterogeneity results were systematic. The obtained results, although representative of only a small portion of the entire parameter space, were considered sufficient for a semi-quantitative elucidation of the drivers of CP spatial patterns. The non-uniform thickness of the balloon was found to have a substantial impact on the distribution of CPs, however, the exact distribution along the length of the balloon was not fully described and the adopted thickness variations may not reflect real values. The non-uniform wall thickness of the balloon has also been implemented in stent expansion simulations and by applying an approximately 30% thickness variation from the distal to the proximal area along the longitudinal axis of the balloon resulted in a non-uniform stent deployment .The balloon and vessel models considered in this study were modeled as single-layer, homogeneous, and isotropic materials with linear elastic and hyperelastic behavior, respectively. However, in reality, the balloon may exhibit an anisotropic non-linear response, although these effects may be negligible at low stretch values . To accuIn essence, the objective of this study was to investigate the underlying causes of the patterns of coating transfer observed in animal studies . This waIn this study, an evaluation of the interplay between the vessel wall and the surface of an angioplasty balloon during its expansion was performed. The results indicated a significant irregularity of contact between the balloon and the vessel, affected by various conditions. More specifically, balloon to vessel ratio and vessel stiffness emerged as key parameters impacting the amplitude and distribution pattern of the developed CP. Furthermore, the thickness of the vessel wall exhibited a comparable influence, albeit with a lesser magnitude of impact, while the friction coefficient at the interface between the balloon and the vessel and the non-uniform wall thickness of the balloon may cause the concentration of the CP in certain regions of the vessel. Simulations identified the balloon’s folded configuration and its longitudinal thickness variation as major contributors to the observed irregularity of contact. This can explain the reduced and sporadic coating transfer to healthy porcine femoral arteries in vivo and ultimately result in the ineffectiveness of the treatment.Supplementary file1 (PDF 596 kb)Below is the link to the electronic supplementary material.


Direct endoscopic necrosectomy (DEN) is a challenging procedure for the debridement of walled-off pancreatic necrosis (WOPN), which may be complicated by several adverse events, primarily bleeding which may require radiological embolization or even surgery. The lack of dedicated devices for this purpose largely affects the possibility of safely performing DEN which increases the risk of complications. We present the case of a 63 years-old man who underwent an endoscopic ultrasound (EUS)-guided drainage of a WOPN, and who was readmitted one month after stent removal with clinical, endoscopic, and radiological signs of infected necrosis involving the splenic artery. A second EUS-guided drainage was performed, with clear visualization of the arterial vessel in the midst of a large amount of solid necrosis. Due to the high risk of major bleeding during DEN, a hybrid procedure in the angiographic room was performed, in order to identify and avoid, under fluoroscopic control, the splenic artery during the entire procedure guide, which was successfully performed using the EndoRotor system. We hereby review the current literature regarding DEN using the EndoRotor system. The case reported, with a literature overview, may help the management of these patients affected by benign but life-threatening conditions which involve a multidisciplinary setting. In recent decades, especially after the introduction on the market of dedicated devices, Endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs), which represent a complication of acute pancreatitis (AP) (as described by the revised Atlanta classification) , has graMoreover, although it can be performed using a combination of different techniques, to date no specifically dedicated devices have been designed for DEN and several endoscopic accessories have been used . Especially when there is a high amount of solid necrosis inside the collection, major vessels potentially involved can be hidden and the lack of dedicated devices largely affects the potential to safely perform DEN, increasing the risk of severe bleeding. Preventive coil embolization has been described for arterial bleeding prevention during DEN, although it could be affected by ischemic injuries . During We present the case of a 63 years-old man who in January 2020 underwent an EUS-guided drainage of a WOPN using an electrocautery-enhanced lumen-apposing metal stent (EC-LAMS), which was removed after repeated DEN over a period of three weeks.One month after stent removal, the patient was readmitted to our unit due to the onset of fever and abdominal pain. A computed tomography (CT)-scan showed the presence of WOPN recurrence with signs of infection . TherefoNo post-procedural complications were observed, and at a 6th month follow-up, no evidence of recurrence was highlighted .The Endorotor System has been introduced in the market in 2016, after demonstration of its technical properties and therapeutic potential in live animals , and it To date, eight studies have been published regarding DEN using the EndoRotor system, which include three case reports ,17,18, oThe first report of its use for the debridement of necrotic tissue dates to 2018, when Van der Wiel et al. described their first experience in two patients with acute necrotizing pancreatitis with signs of infected necrosis, successfully treated with this device and without AEs .In 2020, the same author  publisheIn 2020, the first Italian case of a large WOPN treated with Endorotor has been reported , in whicAmong the reports, there is also one about the use of this device in a percutaneous setting  for a yo3, and the median percentage of necrotic debris within WOPN was 75%. After EUS-guided drainage with stent placement , and >50% gland necrosis as negative predictors for success of the procedure . We can The effectiveness of DEN is currently limited by the lack of dedicated tools. The EndoRotor system has been demonstrated to maximize the debridement of a large amount of necrosis. We reported for the first time a case of a large WOPN with an arterial vessel inside successfully managed by a dual endoscopic and radiological interventional approach, minimizing the possibility of bleeding without the need for prophylactic embolization of the SA, thus avoiding an additional invasive procedure. In our opinion, the description of our challenging case, together with a literature overview on this topic, may help in real-life for the management and clinical decisions of this group of patients affected by benign but nevertheless life-threatening conditions which involve a multidisciplinary setting, particularly gastroenterologists/endoscopists, radiologists, and surgeons, who must work together in order to reach the optimal clinical outcome. Further investigations are needed to clearly define the safety and effectiveness of this intervention, as well as the spectrum of indications in which the use of dedicated but costly devices can add an edge.


Human immunodeficiency virus (HIV) in the Middle East and North Africa (MENA) region is severely understudied despite the region’s increase in new HIV infections since 2010. A key population that is particularly affected, due to the lack of adequate knowledge and proper interventional implementation, includes people who inject drugs (PWID). Furthermore, the paucity of HIV data  worsens an already critical situation in this region. A scoping review was conducted to address the scarcity of information and to synthesize the available data on HIV prevalence rates within the key population of PWID throughout the MENA region. Information was sourced from major public health databases and world health reports. Of the 1864 articles screened, 40 studies discussed the various factors contributing to the under-reporting of HIV data in the MENA region among PWID. High and overlapping risk behaviors were cited as the most prevalent reason why HIV trends were incomprehensible and hard to characterize among PWID, followed by lack of service utilization, lack of intervention-based programs, cultural norms, lack of advanced HIV surveillance systems, and protracted humanitarian emergencies. Overall, the lack of reported information limits any adequate response to the growing and unknown HIV trends throughout the region. The Middle East and North Africa (MENA) region has been a blind spot throughout existing HIV research due to the lack of HIV data on populations living in this region ,2,3. TheAccording to UNAIDS data, the unique aspects of the HIV epidemic in the MENA region are ambiguous compared to other regions of the world . HIV infThe MENA region is home to several major drug trafficking routes and has been a major transit point of illicit drugs. As a result, this has had an indirect causal effect on the HIV/AIDS epidemic within the region by increasing access and usage of illicit drugs . For exaEvidence exists of concentrated epidemics among PWID in Iran and Morocco, and these concentration trends are regionally specific ,17. In IAssessing the impact of the dearth of HIV data on PWID in MENA is both timely and critical ,22. WhilA scoping review was conducted to synthesize the available data on HIV prevalence rates within the PWID key population throughout the MENA region. The aim was to address the under-reporting gap of HIV/AIDS within this population. This review was guided by the “Arksey and O’Malley” framework and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) checklist to ensure a comprehensive appraisal of eligible articles ,24.Studies were included if they met the following criteria: (i) conducted in the MENA region; (ii) included PWID; (iii) addressed HIV prevalence and treatment; (iv) addressed under-reporting of HIV data, through either quantitative or qualitative studies; (v) published in English or had translated versions available for non-English articles; and, (vi) the study took place between 2007 and 2022. No limitations were placed on the study design or type of articles assessed. Studies were excluded if they: (i) excluded PWID; (ii) did not address factors contributing to under-reporting; (iii) focused on HCV, HBV, tuberculosis, and other communicable diseases; (iv) were not conducted in the MENA region; and (v) included no measure of HIV infection rate in PWID.The literature search was conducted in the following databases: PubMed, MEDLINE, Embase, APA PsycInfo, Cochrane Library, Global Health (Ovid), Web of Science ; and the Cumulative Index to Allied Health Literature (CINAHL). Gray literature from the following databases were used: UNAIDS Report, World Drug Report, Harm-Reduction Advocacy Brief for the MENA region, abstracts from the International Aids Society (IAS); and posters from international conferences. All citations were managed using EndNote 20, a bibliographic management program.A comprehensive search strategy was developed to identify studies that met the predefined inclusion criteria. Multiple MENA countries were included, as defined by the UNAIDS , and Yemen). The literature search was conducted on 29 April 2022. The full search strategy is provided in All citations were downloaded to Covidence for screening. Retrieved articles were reviewed and assessed separately by two pairs of reviewers to reduce bias. Each pair of reviewers screened the same articles independently to determine if the inclusion criteria were met by assessing the title and abstract. Title abstract screening, assessment, and extraction were conducted by A.K., M.A., J.F. Articles were randomly assigned where two would screen and third would resolve disagreements. After confirming that the preselected articles met the criteria, a Google Form see  was utilData were extracted as follows: (i) a descriptive table of the included studies and location where the study took place; (ii) a table narrating the state of the epidemic , HIV-prevalence in PWID and amount of evidence supporting the finding; and (iii) reporting of descriptive analysis, such as population and HIV prevalence estimates from 2007 to 2022. Studies were reviewed for reporting on under-reporting directly or indirectly regarding HIV among PWID within the MENA region. An initial search retrieved 2955 articles, with 1864 articles remaining after removing duplicates. Screening of title and abstract further excluded 1381 articles, with an additional 331 duplicates removed. In total, 152 full-text articles were assessed, of which 38 studies and 2 reports were extracted and included in the results. The screening, elimination process, and reason for excluding articles are outlined in the PRISMA chart see . In total, 40 studies were conducted across 20 MENA countries, with Iran as the leading location appearing in 34 studies. Of the 40 studies, 28 cited high and overlapping risk behaviors as a contributing factor to the under-reporting of HIV data in the MENA region, followed by a lack of service utilization in 28 studies, a lack of intervention-based programs targeting PWID reported in 26 studies, cultural norms in 24 studies, a lack of advanced HIV surveillance systems in 17 studies, and protracted humanitarian emergencies reported in 2 studies see .High and overlapping risk behaviors among PWID within the MENA region play an instrumental role in the spread of HIV and are major contributors to the discrepancy in the region’s HIV data. High-risk practices, especially within PWID, expose them to infectious diseases  through contaminated injection equipment and unprotected sex . Specifi2. Various studies investigating risky behaviors in female PWID revealed that study participants exhibit a riskier injection profile than their male counterparts, which could be partially attributed to the population’s greater experience of stigmatization and difficulties in accessing harm-reduction services [The reporting of high and overlapping risk behaviors significantly contributes to the discrepancy of available data within the region and remains the most cited issue in the studies. A significant portion of PWID exhibited high-risk behaviors including, but not limited to, having multiple sexual partners with inconsistent condom use, the sharing of injecting equipment, and needle and syringe sharing between partners. A study assessing male drug injection behaviors revealed that study participants engaged in drug injection at a rate of approximately one to two injections per day . Moreoveservices ,46.In another study, which conducted a national bio-behavioral survey in Cairo, Egypt, between 2013 and 2017, investigators found that certain sociodemographic factors played an instrumental role in the frequency of certain high-risk behaviors being exhibited more than others . The surIn addition to the sharing of injection equipment being a major mode of HIV transmission, the percentage of transmission of HIV due to unsafe sex has seen a considerable increase from 1984–2015 . In OmanOf the twenty 20) MENA countries studied, fourteen have strict punitive laws criminalizing the possession or use of small amounts of drugs ,11,20. T MENA couWithin the MENA region particularly, both male and female PWID experience varying levels of stigma. Additionally, female PWID are highly stigmatized and are considered one of the hardest-to-reach populations, which explains the lack of data on this specific key population ,31,46,50While Iran has been successful in curbing the HIV epidemic within its PWID key population, the country still faces barriers as it pertains to HIV care. The socio-cultural stigma within several communities across the country creates barriers to accessing essential health and harm-reduction services ,51. AddiMost studies have cited that the severe punitive approach to curb the HIV epidemic has not only exacerbated the HIV crisis but has also led to a genesis of widespread stigma toward, and a lack of support for, various treatment programs, compounded by the internalized fear and stigma associated with having HIV and being an injection drug user . This isFourteen countries have mentioned harm reduction and PWID in their national policy documents. Of those fourteen (14) countries, five (5)  adopted harm reduction policies in their national AIDS strategic plan, and seven (7)  highlight PWID as the key population to target ,11. AccoIran has served as a model for implementing progressive HIV care interventions targeting PWID. In Iran, the initiation of triangular clinics integrating services for treatment and prevention of injection drug practices has contributed to the decrease in HIV incidence within the PWID key population. This contribution is in addition to other interventions implemented within Iran, such as: (i) drop-in centers; (ii) integration of substance-use treatment; and (iii) HIV prevention in rural primary health care systems . Yet, deAs for other MENA countries, there remains an urgent need to emulate Iran’s controlling and monitoring of the current and unknown epidemic within their own respective key populations. Iran remains a leader in the implementation of harm reduction with an estimated net coverage of approximately 55–77% among PWID (as of 2014), with Morocco coming in second as one of the only few countries with an operational OAT and NSP program . Given tSeveral studies have noted the dearth of data pertaining to treatment adherence and linkage within the MENA region. According to the MENA Harm-Reduction advocation briefing report, only 38% of PLWH are accessing treatment and prevention services. This coverage is not only lacking behind other regions throughout the world, but is also considerably short of reaching the UNAIDS 2025 AIDS targets of 95% of PLWH on ART. In a study focused on Sudan’s efforts to improve linkage to and retention in care, there was an implementation of a search and rescue strategy to actively identify hard-to-reach key populations to reduce attrition . HoweverStudies have also noted the limited access of needles, syringes, and condoms as major gaps in HIV prevention across all different subgroups of PWID. The inaccessibility of these services poses serious threats to harm reduction programs tailored toward PWID, and it restricts the potential existing services in curbing the HIV epidemic within the MENA region. Despite the availability of free-of-charge programs—such as NSPs, OAT, and condom distribution services in Iran—PWID continue to engage in high-risk practices due to the poor quality of services of pre-existing programs .PWID have low perceived risk of HIV, high stigma around drug injection and use, and low access to harm reduction education and prevention services. Consequently, the effective implementation of intervention programs may prove to be beneficial in enhancing the transmission of knowledge and service utilization within this key population. The continuing global economic crisis and lack of resources within certain areas, compounded by continuing conflicts within the region, prevent MENA countries from prioritizing internal issues above external factors . The addThe compounding of various factors on the already fragile healthcare systems disrupts HIV programs and services as well as accessibility to the services. Consider, once again, Syria, where the National AIDS program estimates up to a 99% reduction in HIV surveillance efforts among key populations—including PWID and female sex workers—following the onset of conflict . FurtherWith the paucity of HIV data, including the lack of integrated biological and behavioral surveillance surveys (IBBSS) within the health infrastructure, PWID is particularly evident in eight (8) countries: Algeria, Qatar, United Arab Emirates, Iraq, Djibouti, Somalia, Sudan, and Yemen . FurtherHIV prevalence in PWID was estimated in eleven 11) MENA countries see  and, of  MENA couHowever, in some parts of the region, HIV surveillance activities have been sustained for a period to keep track of the HIV trends in key populations. Surveillance data have shown a decline in HIV incidence and prevalence within PWID in Iran, which could be explained by the extensive harm-reduction programs that have been implemented in the country ,57,58. HTo the best of our knowledge, this scoping review is the first to examine the predominant lack of research focused on understanding the factors contributing to the lack of quality HIV data on PWID in the MENA region. Moreover, this review summarizes the current evidence and provides an updated understanding of the trends within the MENA region regarding PWID and steps forward in addressing these key issues contributing to the growing and unknown HIV epidemic throughout the MENA region. We found that most studies were conducted in Iran, with a few in other countries within the region see . Where HPWID are considered a highly stigmatized and hard-to-reach key population within the region. Across all MENA countries included in this scoping review, it is evident that overlapping risk behaviors—such as low condom use and sharing of injection equipment—is very common among this group. In addition, endemic to certain areas within the region seems to be the sparsely documented HIV trends occurring within the key population. In addition to the stigma associated with this key population, the humanitarian emergencies occurring within the region contribute to an already fragile health infrastructure. These events impede access to HIV treatment by impacting HIV incidence, further spreading the possibility of transmission between different countries or groups of individuals, making it difficult to gather accurate HIV data on population sizes and prevalence. Most at risk are mobile populations that endure poorer living conditions and limited access to HIV treatment services. The migration rate of individuals within MENA is unusually higher than any other region in the world due to recent conflicts that expand the displacement of refugee populations, thereby contributing to the lack of accurate HIV data within the region ,59. FinaWith various socio-political conflicts within the region, HIV is de-prioritized because of competition from other urgent priorities . FurtherIntensified surveillance and massively expanded HIV testing will be key to controlling the epidemic. The failure to capture key data on risk behaviors, improve treatment adherence among PWID, and the introduction of drug resistance from unknown populations is a missed opportunity to further understand epidemic. Such data can inform policies to lower HIV incidence and mortality by helping target resources to where the largest impact could be expected . Building on successful local programming is essential to improving the HIV infrastructure within the region. The funding and scalability for HIV programs is essential to reaching hard-to-reach key populations. Within the region, especially in conflict-ridden areas, there is high staff turnover and major disruptions in HIV testing and volunteering efforts for HIV programs . These rFinally, the development of a central mechanism to report on HIV trends occurring within the region is essential to overcoming the discrepancies in HIV data. The MENA region suffers from misinformation and accurate data to inform future policy decisions and interventional implementations ,60. ThisBased on this research, there is a predominant lack of research focused on understanding the lack of quality HIV data on PWID in the MENA region. Given the paucity of data on the key populations, the information gathered allows for the identification of key factors that must be addressed to inform the development of future regional policies and programs.The data synthesized from this review were used to provide an updated classification of the state of the HIV epidemic in all the countries within MENA for which data were available. These findings suggest that PWID play an instrumental role in the spread of HIV infections due to their high-risk practices and behaviors. The window of opportunity to control the epidemic should not be ignored, and it is essential that HIV care and prevention among PWID be made a priority in this region. Furthermore, there is a need to further understand the current state of the epidemic of all countries within the region to appropriately structure existing HIV programs and national policies to curb the budding and growing epidemics occurring within this key population. The improvement of HIV programs within MENA is not only essential to the PWID population but will also confront the growing HIV problem in other key populations, where the HIV epidemic is not yet known.


As healthcare tools increasingly move towards a more digital and computational format, there is an increasing need for sensor-based technologies that allow for rapid screening and/or diagnostics . BiospecThere is now a large body of extensive studies examining the applicability and efficacy of biospectroscopy techniques in potential healthcare settings; these have already been applied to multiple endpoints , includi2 windows). Increasingly, from being an academic laboratory-based tool, biospectroscopy has evolved to facilitate clinical translation. For initial screenings of large numbers of patients, this is important. This initial biospectroscopic triage would then allow the targeting of subsets of queried patients with more detailed analyses .Despite this apparent methodological complexity, the emerging evidence is that biospectroscopy techniques have a potential role in healthcare settings because, ultimately, for the end-user, their application is more about technical consistency and less about a deep understanding of the aforementioned individual steps. Technical consistency, in this case, refers to the standardisation of sample preparation and consistent delivery to the sensor, something which standard operating procedures can be readily developed for and which healthcare systems use already in routine practice. A major driver in the push towards the implementation of biospectroscopy techniques in healthcare is the increasing processing power of desktop computers (or even mobile phones) that allow for the rapid harnessing of sophisticated computational algorithms and the developing usage of databases in an increasingly digital era; this means that there is an increasing acceptance amongst healthcare professionals of remote algorithm-based outputs on which clinical decisions, such as patient triage or diagnosis, can be made. In combination with its general applicability to a range of screening and/or diagnostic scenarios , one would envisage that biospectroscopy platforms could be readily embedded into healthcare point-of-care screening and/or diagnostics settings at a cost consideration not dissimilar to current practice; this is a critically important point. For instance, pathology laboratories use glass slides because they are cheap, easy to use, and robust, thus allowing a typical laboratory to process hundreds to thousands of in-house samples per day. A replacement approach should not necessitate the inclusion of an expensive component such as gold-coated slides (maybe >100 times the price compared to ordinary slides) or fragile materials . While the acquisition of point spectra allows one to determine the classification of normal versus variant  or predictive analysis for screening and/or diagnosis, the use of spectral maps allows one to construct an image of the cell and/or tissue architecture ,25 or evretation . Again, An area where biospectroscopy techniques have already made significant inroads is in the application (primarily of Raman spectroscopy) of real-time intra-operative assessment of tumour margins ,34,35. BAlthough much work applying and investigating the usefulness of biospectroscopy has been undertaken in the oncology field, the methodology has also been successfully studied in many other areas, including cardiology , infecti


PLoS Medicine’s Special Issue dedicated to AMR, Balasubramanian and colleagues shed light on the global magnitude of hospital-associated infections due to hospital acquired resistant infections (HARI) [Antimicrobial resistance (AMR) is among the top ten global public health threats, demanding immediate attention and action . To effes (HARI) .One of the strengths of the study is the combination of data from hospital-based point prevalence surveys (PPS) with estimates of hospitalization rates, resistance prevalence, and country population size to predict the number of HARIs globally, across country income categories, and within nations. Using this approach, the authors estimated approximately 136 million HARI annually worldwide between 2010–2020. To our knowledge, these are among the first global incidence estimates of HARI. However, as acknowledged by the authors, results heavily rely on the availability of PPS data, which is limited in some regions and countries. According to the authors, only 11 low- and middle-income countries report this information, often based on small sample sizes, which may introduce bias and limit the generalizability of their findings. Additionally, the study relies on extrapolating country-level infection rates and resistance prevalence from available but scarce data at the hospital level, thus introducing uncertainties and assumptions that could impact the accuracy of the results. The heterogeneity of data from various sources and countries, with differences in data collection methods, diagnostic criteria, and reporting practices, could also affect the reliability of the estimates. Furthermore, due to the lack of available data, the study reports infections in an aggregated manner, without distinguishing specific infectious syndromes, which hampers the identification of more targeted syndrome-based interventions.Acinetobacter spp., E. coli, K. pneumoniae, Salmonella spp., S. aureus, Streptococcus pneumoniae, Shigella spp., and N. gonorrhoeae) and blood, urine, feces, and urethral and cervical swabs as priority specimen types for routine AMR surveillance and reporting to WHO [Recent AMR burden estimates indicate that in 2019, 1.27 million deaths were attributed to drug resistant bacterial infections . Comparig to WHO . These cg to WHO . A complg to WHO , althougpassive surveillance of AMR in clinical samples from patients with suspected infections and (2) actively conducting periodic nationally representative surveys to measure the prevalence and trends of AMR [The estimates from Balasubramanian et al.  further s of AMR .Continuous AMR surveillance models are typically passive necessitating regular reporting of event data by all facilities that consult patients or test specimens. Routine and continuous surveillance systems for AMR improve access to timely and appropriate treatment, rapid detection of outbreaks and real-time monitoring of trends and effectiveness of interventions. However, where capacity for high-quality and high- coverage is lacking, continuous surveillance may come with significant biases. Reporting to WHO GLASS shows that coverage of adequate microbiological diagnostic services varies greatly between countries and is often scarce in resource-limited settings . Other cActive AMR surveillance through periodic national AMR prevalence surveys offers a reliable, direct measurement of the prevalence of AMR for countries lacking high-quality and high-coverage surveillance systems. This is achieved through inclusion of a subset of surveillance sites selected using statistically meaningful probability sampling methods, to achieve national representativeness and data accuracy. Surveys are typically implemented following key scientific quality standards and standardized methods which ensure that the resultant data will be comparable within and between countries and over time. These surveys use the same active systematic syndrome-based approach for case finding and enhance national technical capacity, leading to improved patient management and development of robust continuous surveillance systems in the longer term. Alternative AMR surveillance options for countries that do not yet have continuous AMR surveillance systems of high-quality and high coverage, include the establishment of a sentinel system or lot quality assurance sampling. However, unlike the periodic nationally representative surveys, these approaches do not accurately measure the magnitude and trends of AMR in a country population and consequently do not fulfil the objectives of national and global monitoring of AMR. Finally, mathematical modelling can accelerate the availability of evidence on a global scale, but its value is contingent upon the quality and representativeness of the data used and the validation of its estimates.It is crucial to consider service coverage or the attrition in the “cascade” from diagnosis to cure, when interpreting AMR surveillance and evaluating the impact of AMR. WHO guidance on the methodological principles of nationally representative AMR prevalence surveys considers the patient pathway within the healthcare setting when measuring the prevalence of AMR , focusinWhile much work remains to be done to implement reliable and timely AMR surveillance systems needed to control this silent pandemic, the estimates being generated by Balasubramanian et al., and other investigators, are a valuable starting point. These data help communicate the urgency and gravity of the problem and hopefully motivate countries to implement robust surveillance systems for generating reliable data to inform public health action.


Identification of environmental stress sensors is one of the most important research topics in plant abiotic stress research. Traditional strategies to identify stress sensors or early signaling components based on the cell membrane as a primary site of sensing and calcium signal as a second messenger have had only limited successes. Therefore, the current theoretical framework underlying stress sensing in plants should be reconsidered and additional mechanisms need to be introduced. Recently, accumulating evidence has emerged to suggest that liquid-liquid phase separation (LLPS) is a major mechanism for environmental stress sensing and response in plants. In this review, we briefly introduce LLPS regarding its concept, compositions, and dynamics, and then summarize recent progress of LLPS research in plants, emphasizing the contribution of LLPS to the sensing of various environmental stresses, such as dehydration, osmotic stress, and low and high temperatures. Finally, we propose strategies to identify key proteins that sense and respond to environmental stimuli on the basis of LLPS, and discuss the research directions of LLPS in plant abiotic stress responses and its potential application in enhancing stress tolerance in crops. In the natural environments, plants often suffer a variety of adverse environmental stresses, such as high salinity, drought, low and high temperatures, any of which can become a major constraint on plant growth and even cause plant death Zhu . In orde2+] increases 1) were identified and reported as osmotic and salt stress sensors, respectively  sphingolipids, an integral part of the plasma membrane. In moca1 mutants, GIPCs are obviously reduced, leading to a deficiency in salt-triggered Ca2+ spikes. The conclusion that GIPCs function in salt sensing is based on data showing that GIPCs can directly bind to Na+. Although GIPCs are considered as a salt sensor, the calcium channel mediating the GIPCs-regulated Ca2+ influx under salt stress is still unknown  triggers the phase separation of TERMINATING FLOWER (TMF) via an oxidative modification, and the condensation of TMF promotes its binding to the promoter of a floral identity gene ANANTHA to repress its expression -dependent activation of FLC plays a key role in the regulation of flowering time , functions as a circadian rhythm-dependent temperature-responsive transcriptional repressor , maize (Zea mays), common wheat (Triticum aestivum), Chinese cabbage (Brassica rapa ssp. Pekinensis), and tomato (Solanum lycopersicum). These candidate phase-separation proteins can be a valuable resource to identify proteins that sense environmental stresses in plants.In addition to the computational prediction of IDR-containing proteins, experimental approaches to identify phase-separation proteins have also been applied in plants. Recently, Zhang et al. performed a mass spectrometry analysis to identify proteins with a potential to undergo phase separation by using a small molecule biotinylated isoxazole (b-isox) (Zhang et al. SGs and PBs have been shown to be crucial for the regulation of stress tolerance in plants (Solis-Miranda et al. 2+ is an important second messenger that is widely explored by plants to respond to environmental stresses, and currently little is known about the involvement of Ca2+ signaling in LLPS formation. In future, the proteins harboring both IDRs and calcium binding domain can be selected to investigate the relationship between Ca2+ signaling and LLPS. Despite the membrane-less property of LLPS, the interplay between membranes and LLPS has recently been raised as an interesting research topic (Agudo-Canalejo et al. The biological functions of LLPS and the mechanisms underlying their formation are relatively well characterized in human and yeast, but the study of LLPS in plants has just emerged in the last few years. Considering the importance of LLPS in the regulation of a wide range of biological processes, large efforts are needed to study the functional mechanisms of LLPS in the context of plant biology, which will substantially advance our understanding of basic life activities in plants. In the field of plant abiotic stress, the introduction of LLPS provides a great potential to identify key components that regulate stress tolerance. In the future, more proteins that undergo phase separation under stress conditions need to be identified and functionally characterized. The elucidation of the mode of action of these phase-separation proteins will greatly enrich our understanding of how plants sense and respond to environmental stresses. In addition, the LLPS-driven formation of biomolecular condensates has been implicated in the regulation of mRNA metabolism via the formation of mRNA-ribonucleoprotein complexes (Chantarachot and Bailey-Serres Currently, most of the studies on LLPS in plants were performed in the model plant Arabidopsis, and the knowledge of LLPS in crops is still scarce. As mounting evidence supports that LLPS plays important roles in stress tolerance in plants, the identification of stress-related phase-separation proteins in crops will provide valuable genetic resources for the engineering of stress-tolerant crops. Based on computational predictions and experimental approaches (Zhang et al. Regarding the application of LLPS in improving stress tolerance in crops, several strategies can be explored. One of the typical properties of LLPS is that the formation of condensates is protein abundance-dependent, so overexpression of the LLPS-related genes can confer obvious effects on the condensation of phase-separation proteins, and thus enhance stress responses. It has been known that the IDRs in the phase-separation proteins evolved faster than structural domains (Hatzianestis et al.