Cost-effectiveness Analysis of Triptorelin, Goserelin, and Leuprolide in the Treatment of Patients with Metastatic Prostate Cancer: A Societal Perspective.

OBJECTIVES: Metastatic prostate cancer is the most common malignant cancer and the second leading cause of death due to various types of cancer among men after lung cancer. This study aimed to analyze the cost-effectiveness of triptorelin, goserelin, and leuprolide in the treatment of the patients with metastatic prostate cancer from the societal perspective in Iran in 2020. METHODS: This is a cost-effectiveness study in which a 20-year Markov transition modeling was applied. In this study, local cost and quality-of-life data of each health state were gathered from cohort of patients. The TreeAge pro 2020 and Microsoft Excel 2016 software were used to simulate cost-effectiveness of each treatment in the long term. The one-way and probabilistic sensitivity analyses were also performed to measure robustness of the model outputs. RESULTS: The findings indicated that the mean costs and utility gained over a 20-year horizon for goserelin, triptorelin, and leuprolide treatments were $ 13 539.13 and 6.365 quality-adjusted life-years (QALY), $ 18 124.75 and 6.658 QALY, and $ 26 006.92 and 6.856 QALY, respectively. Goserelin was considered as a superior treatment option, given the estimated incremental cost-effectiveness ratio. The one-way and probabilistic sensitivity analyses confirmed the robustness of the study outcomes. CONCLUSIONS: According to the results of the present study, goserelin was the most effective and cost-effective strategy versus 2 other options. It could be recommended to policy makers of the Iran healthcare system to prioritize it in clinical guidelines and reimbursement policies.

Patterns of case fatality and hospitalization duration among nearly 1 million hospitalized COVID-19 patients covered by Iran Health Insurance Organization (IHIO) over two years of pandemic: An analysis of associated factors.

BACKGROUND: Different populations and areas of the world experienced diverse COVID-19 hospitalization and mortality rates. Claims data is a systematically recorded source of hospitalized patients' information that could be used to evaluate the disease management course and outcomes. We aimed to investigate the hospitalization and mortality patterns and associated factors in a huge sample of hospitalized patients. METHODS: In this retrospective registry-based study, we utilized claim data from the Iran Health Insurance Organization (IHIO) consisting of approximately one million hospitalized patients across various hospitals in Iran over a 26-month period. All records in the hospitalization dataset with ICD-10 codes U07.1/U07.2 for clinically/laboratory confirmed COVID-19 were included. In this study, a case referred to one instance of a patient being hospitalized. If a patient experienced multiple hospitalizations within 30 days, those were aggregated into a single case. However, if hospitalizations had longer intervals, they were considered independent cases. The primary outcomes of study were general and intensive care unit (ICU) hospitalization periods and case fatality rate (CFR) at the hospital. Besides, various demographic and hospitalization-associated factors were analyzed to derive the associations with study outcomes using accelerated failure time (AFT) and logistic regression models. RESULTS: A total number of 1 113 678 admissions with COVID-19 diagnosis were recorded by IHIO during the study period, defined as 917 198 cases, including 51.9% females and 48.1% males. The 61-70 age group had the highest number of cases for both sexes. Among defined cases, CFR was 10.36% (95% CI: 10.29-10.42). The >80 age group had the highest CFR (26.01% [95% CI: 25.75-26.27]). The median of overall hospitalization and ICU days were 4 (IQR: 3-7) and 5 (IQR: 2-8), respectively. Male patients had a significantly higher risk for mortality both generally (odds ratio (OR) = 1.36 [1.34-1.37]) and among ICU admitted patients (1.12 [1.09-1.12]). Among various insurance funds, Foreign Citizens had the highest risk of death both generally (adjusted OR = 2.06 [1.91-2.22]) and in ICU (aOR = 1.71 [1.51-1.92]). Increasing age groups was a risk of longer hospitalization, and the >80 age group had the highest risk for overall hospitalization period (median ratio = 1.52 [1.51-1.54]) and at ICU (median ratio = 1.17 [1.16-1.18]). Considering Tehran as the reference province, Sistan and Balcuchestan (aOR = 1.4 [1.32-1.48]), Alborz (aOR = 1.28 [1.22-1.35]), and Khorasan Razavi (aOR = 1.24 [1.20-1.28]) were the provinces with the highest risk of mortality in hospitalized patients. CONCLUSION: Hospitalization data unveiled mortality and duration associations with variables, highlighting provincial outcome disparities in Iran. Using enhanced registry systems in conjunction with other studies, empowers policymakers with evidence for optimizing resource allocation and fortifying healthcare system resilience against future health challenges.

Non-COVID-19 hospitalization and mortality during the COVID-19 pandemic in Iran: a longitudinal assessment of 41 million people in 2019-2022.

BACKGROUND: During a COVID-19 pandemic, it is imperative to investigate the outcomes of all non-COVID-19 diseases. This study determines hospital admissions and mortality rates related to non-COVID-19 diseases during the COVID-19 pandemic among 41 million Iranians. METHOD: This nationwide retrospective study used data from the Iran Health Insurance Organization. From September 23, 2019, to Feb 19, 2022, there were four study periods: pre-pandemic (Sept 23-Feb 19, 2020), first peak (Mar 20-Apr 19, 2020), first year (Feb 20, 2020-Feb 18, 2021), and the second year (Feb 19, 2021-Feb 19, 2022) following the pandemic. Cause-specific hospital admission and in-hospital mortality are the main outcomes analyzed based on age and sex. Negative binomial regression was used to estimate the monthly adjusted Incidence Rate Ratio (IRR) to compare hospital admission rates in aggregated data. A logistic regression was used to estimate the monthly adjusted in-hospital mortality Odds Ratio (OR) for different pandemic periods. RESULTS: During the study there were 6,522,114 non-COVID-19 hospital admissions and 139,679 deaths. Prior to the COVID-19 outbreak, the standardized hospital admission rate per million person-month was 7115.19, which decreased to 2856.35 during the first peak (IRR 0.40, [0.25-0.64]). In-hospital mortality also increased from 20.20 to 31.99 (OR 2.05, [1.97-2.13]). All age and sex groups had decreased admission rates, except for females at productive ages. Two years after the COVID-19 outbreak, the non-COVID-19 hospital admission rate (IRR 1.25, [1.13-1.40]) and mortality rate (OR 1.05, [1.04-1.07]) increased compared to the rates before the pandemic. The respiratory disease admission rate decreased in the first (IRR 0.23, [0.17-0.31]) and second years (IRR 0.35, [0.26-0.47] compared to the rate before the pandemic. There was a significant reduction in hospitalizations for pneumonia (IRR 0.30, [0.21-0.42]), influenza (IRR 0.04, [0.03-0.06]) and COPD (IRR 0.39, [0.23-0.65]) during the second year. There was a significant and continuous rise in the hematological admission rate during the study, reaching 186.99 per million person-month in the second year, reflecting an IRR of 2.84 [2.42-3.33] compared to the pre-pandemic period. The mortality rates of mental disorders (OR 2.15, [1.65-2.78]) and musculoskeletal (OR 1.48, [1.20-1.82), nervous system (OR 1.42, [1.26-1.60]), metabolic (OR 1.99, [1.80-2.19]) and circulatory diseases (OR 1.35, [1.31-1.39]) increased in the second year compare to pre-pandemic. Myocardial infarction (OR 1.33, [1.19-1.49]), heart failure (OR 1.59, [1.35-1.87]) and stroke (OR 1.35, [1.24-1.47]) showed an increase in mortality rates without changes in hospitalization. CONCLUSIONS: In the era of COVID-19, the changes seem to have had a long-term effect on non-COVID-19 diseases. Countries should prepare for similar crises in the future to ensure medical services are not suspended.

Two-dimensional heavy fermions in the van der Waals metal CeSiI.

Heavy-fermion metals are prototype systems for observing emergent quantum phases driven by electronic interactions1-6. A long-standing aspiration is the dimensional reduction of these materials to exert control over their quantum phases7-11, which remains a significant challenge because traditional intermetallic heavy-fermion compounds have three-dimensional atomic and electronic structures. Here we report comprehensive thermodynamic and spectroscopic evidence of an antiferromagnetically ordered heavy-fermion ground state in CeSiI, an intermetallic comprising two-dimensional (2D) metallic sheets held together by weak interlayer van der Waals (vdW) interactions. Owing to its vdW nature, CeSiI has a quasi-2D electronic structure, and we can control its physical dimension through exfoliation. The emergence of coherent hybridization of f and conduction electrons at low temperature is supported by the temperature evolution of angle-resolved photoemission and scanning tunnelling spectra near the Fermi level and by heat capacity measurements. Electrical transport measurements on few-layer flakes reveal heavy-fermion behaviour and magnetic order down to the ultra-thin regime. Our work establishes CeSiI and related materials as a unique platform for studying dimensionally confined heavy fermions in bulk crystals and employing 2D device fabrication techniques and vdW heterostructures12 to manipulate the interplay between Kondo screening, magnetic order and proximity effects.

Dry Needling for Arthrogenic Muscle Inhibition of Quadriceps Femoris in Patients after Reconstruction of Anterior Cruciate Ligament: a Protocol for a Randomized Controlled Trial.

Background: : Dry needling (DN) is recommended as a therapeutic modality for various neuromusculoskeletal disorders. No study has been performed on the impact of DN on arthrogenic muscle inhibition (AMI) after anterior cruciate ligament reconstruction (ACLR). This study protocol is aimed to investigate the impacts of DN on AMI of quadriceps femoris, corticomotor, and spinal reflex excitability in patients with ACLR. Methods: : A double-blind, between-subject, randomized, controlled trial will be conducted to measure changes in AMI after DN. Twenty-four subjects with ACLR will be recruited to receive a DN or a sham DN, providing that they met the inclusion criteria. Three sessions of DN on the quadriceps femoris will be applied during a one-week period. The primary outcome measures are the active motor threshold, motor evoked potential, and Hmax - Mmax ratio. The secondary outcomes are the International Knee Documentation Committee subjective knee form questionnaire score and maximum quadriceps isometric torque. Data will be collected at baseline, immediately after the first session, after the third session, and at the one-month follow-up visit. Discussion: : The results of this study will provide preliminary evidence regarding the effects of DN on AMI of quadriceps femoris in patients with ACLR.

The importance of predictors for in-hospital COVID-19 mortality changes over one month.

BACKGROUND: Risk stratification enables care providers to make the proper clinical decision for the management of patients with COVID-19 infection. We aimed to explore changes in the importance of predictors for inpatient mortality of COVID-19 over one month. METHODS: This research was a secondary analysis of data from in-hospital patients with COVID-19 infection. Individuals were admitted to four hospitals, New York, USA. Based on the length of hospital stay, 4370 patients were categorized into three mutually exclusive interval groups, day 1, day 2-7, and day 8-28. We measured changes in the importance of twelve confirmed predictors for mortality over one month, using principal component analysis. RESULTS: On the first day of admission, there was a higher risk for organ dysfunction, particularly in elderly patients. On day 1, serum aspartate aminotransferase and sodium were also associated with an increased risk of mortality, while normal troponin opposes in-hospital death. With time, the importance of high aspartate aminotransferase and sodium concentrations decreases, while the variable quality of high troponin levels increases. Our study suggested the importance of maintaining normal blood pressure early in the management of patients. High serum concentrations of creatinine and C-reactive protein remain poor prognostic factors throughout the 28 days. The association of age with mortality increases with the length of hospital stay. CONCLUSION: The importance of some patients' characteristics changes with the length of hospital stay. This should be considered in developing and deploying predictive models and the management of patients with COVID-19 infection.

Analysis of the strategies used by iranian nurses for management of provided care for patients with COVID- 19: a qualitative study.

BACKGROUND: Nurses have been at the center of managing the COVID-19 outbreak through direct bedside care in respiratory, emergency and intensive care environments, managing hospital units, providing Covid-19 testing, vaccination and contact tracing. Thus, the present study aimed to analysis the strategies used by Iranian nurses for management of Provided Care for patients with COVID- 19. METHODS: The present study was conducted based on the conventional content analysis method and Graneheim & Lundman approach. The participants included the nurses working in the COVID-19 wards and were recruited by purposeful sampling and based on inclusion criteria. The data were collected by conducting semi-structured, in-depth, one-to-one interviews until reaching data saturation. RESULTS: In-depth interviews with 10 nurses represented four main categories and fifteen subcategories. Four main categories emerged in this study i.e. "justice in human resources management", "The art and science of comprehensive nursing care", "managers as agents of change in crisis" and "challenges and its management". CONCLUSION: The nurses' experiences of management strategies showed that paying attention to the financial, psychological, educational, equipment needs of nurses and maintaining their safety make the suitable environment for providing high quality care for patients with covid-19.

Economic burden of cervical cancer and premalignant lesions associated with human papilloma virus: a societal perspective.

BACKGROUND: Cervical cancer is one of the most common cancers in women, the cause of which is mostly human papilloma virus (HPV). The aim of this study was to determine the economic burden of cervical cancer and premalignant lesions associated with HPV infection from a societal perspective. METHODS: The study is a partial economic evaluation (cost of illness), which was conducted cross-sectionally in the referral university clinic in Fars province in 2021. The prevalence-based and bottom-up approaches used to calculate the costs, the indirect costs were calculated by human capital approach. RESULTS: The mean cost of premalignant lesions associated with HPV infection was USD 2,853 per patient, which 68.57% was direct medical costs. In addition, the mean cost of cervical cancer was USD 39,327 per patient, the largest share of which (57.9%) was related to indirect costs. The mean annual cost of cervical cancer patients in the country was estimated at USD 40,884,609 as well. CONCLUSION: Cervical cancer and premalignant lesions associated with HPV infection imposed a significant economic burden on the health system and patients. The results of the present study can help health policymakers with efficient and equitable prioritization and allocation of resources.

A few-layer covalent network of fullerenes.

The two natural allotropes of carbon, diamond and graphite, are extended networks of sp3-hybridized and sp2-hybridized atoms, respectively1. By mixing different hybridizations and geometries of carbon, one could conceptually construct countless synthetic allotropes. Here we introduce graphullerene, a two-dimensional crystalline polymer of C60 that bridges the gulf between molecular and extended carbon materials. Its constituent fullerene subunits arrange hexagonally in a covalently interconnected molecular sheet. We report charge-neutral, purely carbon-based macroscopic crystals that are large enough to be mechanically exfoliated to produce molecularly thin flakes with clean interfaces-a critical requirement for the creation of heterostructures and optoelectronic devices2. The synthesis entails growing single crystals of layered polymeric (Mg4C60)∞ by chemical vapour transport and subsequently removing the magnesium with dilute acid. We explore the thermal conductivity of this material and find it to be much higher than that of molecular C60, which is a consequence of the in-plane covalent bonding. Furthermore, imaging few-layer graphullerene flakes using transmission electron microscopy and near-field nano-photoluminescence spectroscopy reveals the existence of moiré-like superlattices3. More broadly, the synthesis of extended carbon structures by polymerization of molecular precursors charts a clear path to the systematic design of materials for the construction of two-dimensional heterostructures with tunable optoelectronic properties.

Does covid-19 pandemic tell us something about time and space to meet our being, belonging and becoming needs?

BACKGROUND: People's perceptions of events like a pandemic are shaped by individual experiences within their socio-cultural context. Attributing negative or positive meanings to an experience may influence the sense of Being, Belonging and Becoming. AIM AND OBJECTIVES: To investigate the impact of the isolation/social distancing measures on people's sense of Being, Belonging, Becoming and overall sense of Occupational Wholeness compared to the time before the Covid-19 Pandemic as it is perceived by an Iranian population. METHODS: The Model of Occupational Wholeness used to inform the theoretical basis of this study and development of the survey questions. An internet-based survey using a convenient and snowball sampling method was conducted. A self-administered questionnaire was published using a software named Porsline. A sample of 1624 members of the general population in Iran (67% response rate) completed the questionnaire within the first four weeks of the isolation/social distancing period starting on 18 March 2020. The Data was analysed by the SPSS 22. RESULTS: The participants showed a more positive perceived level of Being and Belonging as well as an overall sense of Occupational Wholeness, and no difference in the perceived sense of Becoming during the isolation/social distancing period compared to the time before the Covid 19 pandemic. CONCLUSIONS: The findings show that the isolation/social distancing measures were perceived by participants as an opportunity to meet some of their Being, and Belonging needs that contribute to an overall sense of OccupationalWholeness.This highlights the role that Occupational science and Occupational therapy may have in helping people in situations when they need to rethink and replan for what they Do and the way they attribute meaning to their experiences.

Cost of Illness of COVID-19 and Its Consequences on Health and Economic System.

The outbreak of COVID-19 has had destructive influences on social and economic systems as well as many aspects of human life. In this study, we aimed to estimate the economic effects of COVID-19 at the individual and societal levels during a fiscal year. This cost of illness analysis was used to estimate the economic burden of COVID-19 in Iran. Data of the COVID-19 patients referred to the hospitals affiliated to Bushehr University of Medical Sciences in 2021 were collected through the Hospital Information System (HIS). The study methodology was based upon the human capital approach and bottom-up technique. The COVID-19 pandemic has resulted in 9711 confirmed hospital cases and 717 deaths in Bushehr province during the study period. The direct and indirect costs were estimated to be $1446.06 and $3081.44 per patient. The economic burden for the province and country was estimated to be $43.97 and $2680.88 million. The results showed that the economic burden of this disease particularly premature death costs is remarkably high. Therefore, in order to increase the resiliency of the health system and the stability in service delivery, preventive-oriented strategies have to be more seriously considered by policymakers.

Epigenetic regulation in myocardial infarction: Non-coding RNAs and exosomal non-coding RNAs.

Myocardial infarction (MI) is one of the leading causes of deaths globally. The early diagnosis of MI lowers the rate of subsequent complications and maximizes the benefits of cardiovascular interventions. Many efforts have been made to explore new therapeutic targets for MI, and the therapeutic potential of non-coding RNAs (ncRNAs) is one good example. NcRNAs are a group of RNAs with many different subgroups, but they are not translated into proteins. MicroRNAs (miRNAs) are the most studied type of ncRNAs, and have been found to regulate several pathological processes in MI, including cardiomyocyte inflammation, apoptosis, angiogenesis, and fibrosis. These processes can also be modulated by circular RNAs and long ncRNAs via different mechanisms. However, the regulatory role of ncRNAs and their underlying mechanisms in MI are underexplored. Exosomes play a crucial role in communication between cells, and can affect both homeostasis and disease conditions. Exosomal ncRNAs have been shown to affect many biological functions. Tissue-specific changes in exosomal ncRNAs contribute to aging, tissue dysfunction, and human diseases. Here we provide a comprehensive review of recent findings on epigenetic changes in cardiovascular diseases as well as the role of ncRNAs and exosomal ncRNAs in MI, focusing on their function, diagnostic and prognostic significance.

Economic burden of major depressive disorder: a case study in Southern Iran.

BACKGROUND: Depression disorders are a leading cause of disability in the world which imposes a significant economic burden on patients and societies The present study aimed to determine the economic burden of Major Depressive Disorder (MDD) on the patients referred to the reference psychiatric single-specialty hospitals in southern Iran in 2020. METHODS: This cross-sectional research is a partial economic evaluation and a cost-of-illness study conducted in southern Iran in 2020. A total of 563 patients were enrolled through the census method, and a researcher-made data collection form was used to gather the required information. The prevalence-based and the bottom-up approaches were also used to collect the cost information and calculate the costs, respectively. The data on direct medical, direct non-medical, and indirect costs were obtained using the information in the patients' medical records and insurance bills as well as their self-reports or those of their companions. To calculate the indirect costs, the human capital approach was used as well. RESULTS: The results showed that the annual cost of MDD was $ 2717.41 Purchasing Power Parity (PPP) (USD 2026.13) per patient in 2020. Direct medical costs accounted for the largest share of the costs (73.68%), of which hoteling and regular beds expenses were the highest (57.70% of the total direct medical costs). The shares of direct non-medical and indirect costs were 7.52 and 18.80%, respectively, and the economic burden of the disease in the country was estimated at $7,120,456,596 PPP (USD 5,309,088,699). CONCLUSION: In general, due to the high prevalence of MDD and the chronicity of the disease, the costs of its treatment can impose a heavy economic burden on the society, healthcare system, insurance system, and the patients themselves. Therefore, it is suggested that health policymakers and managers should take appropriate measures to increase the basic and supplemental insurance coverage of these patients. In addition, in order to reduce the costs, proper and equitable distribution of psychiatrists and psychiatric beds, expansion of home care services, and use of Internet-based technologies and the cyberspace to follow up the treatment of these patients are recommended.

CYP2C19 expression modulates affective functioning and hippocampal subiculum volume-a large single-center community-dwelling cohort study.

Given controversial findings of reduced depressive symptom severity and increased hippocampus volume in CYP2C19 poor metabolizers, we sought to provide empirical evidence from a large-scale single-center longitudinal cohort in the community-dwelling adult population-Colaus|PsyCoLaus in Lausanne, Switzerland (n = 4152). We looked for CYP2C19 genotype-related behavioral and brain anatomy patterns using a comprehensive set of psychometry, water diffusion- and relaxometry-based magnetic resonance imaging (MRI) data (BrainLaus, n = 1187). Our statistical models tested for differential associations between poor metabolizer and other metabolizer status with imaging-derived indices of brain volume and tissue properties that explain individuals' current and lifetime mood characteristics. The observed association between CYP2C19 genotype and lifetime affective status showing higher functioning scores in poor metabolizers, was mainly driven by female participants (ß = 3.9, p = 0.010). There was no difference in total hippocampus volume between poor metabolizer and other metabolizer, though there was higher subiculum volume in the right hippocampus of poor metabolizers (ß = 0.03, pFDRcorrected = 0.036). Our study supports the notion of association between mood phenotype and CYP2C19 genotype, however, finds no evidence for concomitant hippocampus volume differences, with the exception of the right subiculum.

Virus, Exosome, and MicroRNA: New Insights into Autophagy.

Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.

Cost-effectiveness analysis of hearing screening program for primary school children in southern Iran, Shiraz.

BACKGROUND: Hearing loss is the second most common chronic disease, the diagnosis and treatment of which can be faster through screening. In addition, early interventions will save significant costs for the education and health systems. Therefore, the present study aimed to evaluate the cost-effectiveness of hearing screening for primary school children in Shiraz. METHODS: This cross-sectional economic evaluation of cost-effectiveness was conducted from the perspective of the health system. The study population comprised all seven-year-old children participating in the screening program in Shiraz. The present study dealt only with direct costs. The expected costs and outcomes, as well as the ICER index were estimated using the decision tree model. The study outcomes included averted disability-adjusted life years (DALY) and true identification of hearing loss cases. The robustness of the results was evaluated using the one-way sensitivity analysis. The TreeAge 2020 and Excel 2016 software were also used to analyze the collected data. RESULTS: The hearing screening data obtained during 6 years (2015-2020) showed that every year, an average of 22,853 children in Shiraz were examined for hearing, of which 260 were true positive (%1.1). The costs of screening and lack of screening were estimated at $30.32 Purchasing Power Parity (PPP) and $13.75 PPP per child, respectively. The averted DALY due to performing hearing screening was estimated at 7 years for each child. The ICER was positive and equal to $ 0.06 PPP for the identified cases and $ 2.37 PPP per averted DALY. The sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: According to the results, although hearing screening for primary school children had more costs and effectiveness, it was considered cost-effective. Therefore, universal screening with high quality and accuracy is recommended.

The cross-talk between soluble "Find me" and "Keep out" signals as an initial step in regulating efferocytosis.

The rapid clearance of apoptotic cells (ACs), known as efferocytosis, prompts the inhibition of inflammatory responses and autoimmunity and maintains homeostatic cell turnover by controlling the release of intracellular contents. The fast clearance of ACs requires professional and nonprofessional phagocytic cells that can accurately and promptly recognize ACs and migrate towards them. Cells undergoing apoptosis alarm their presence by releasing special soluble chemotactic factors, such as lactoferrin, that act as "Find me," "Keep out," or "Stay away" signals to recruit phagocytic cells, such as macrophages or prevent granulocyte migration. Efferocytosis effectively serves to prevent damage-associated molecular pattern release and secondary necrosis and inhibit inflammation/autoimmunity at the very first step. Since less attention has been given to the cross-talk and balance of "Find me" and "Keep out" signals released from ACs in efferocytosis, we set out to investigate the current knowledge of the roles of "Find me" and "Keep out" signals in the efferocytosis process.

MicroRNAs and Efferocytosis: Implications for Diagnosis and Therapy.

About 10-100 billion cells are generated in the human body in a day, and accordingly, 10- 100 billion cells predominantly die for maintaining homeostasis. Dead cells generated by apoptosis are also rapidly engulfed by macrophages (Mθs) to be degraded. In case of the inefficient engulfment of apoptotic cells (ACs) via Mθs, they experience secondary necrosis and thus release intracellular materials, which display damage-associated molecular patterns (DAMPs) and result in diseases. Over the last decades, researchers have also reflected on the significant contribution of microRNAs (miRNAs) to autoimmune diseases through the regulation of Mθs functions. Moreover, miRNAs have shown intricate involvement with completely adjusting basic Mθs functions, such as phagocytosis, inflammation, efferocytosis, tumor promotion, and tissue repair. In this review, the mechanism of efferocytosis containing "Find-Me", "Eat-Me", and "Digest-Me" signals is summarized and the biogenesis of miRNAs is briefly described. Finally, the role of miRNAs in efferocytosis is discussed. It is concluded that miRNAs represent promising treatments and diagnostic targets in impaired phagocytic clearance, which leads to different diseases.

Chloroaluminate Anion Intercalation in Graphene and Graphite: From Two-Dimensional Devices to Aluminum-Ion Batteries.

A rechargeable aluminum-ion battery based on chloroaluminate electrolytes has received intense attention due to the high abundance and chemical stability of aluminum. However, the fundamental intercalation processes and dynamics in these battery systems remain unresolved. Here, the energetics and dynamics of chloroaluminate ion intercalation in atomically thin single crystal graphite are investigated by fabricating mesoscopic devices for charge transport and operando optical microscopy. These mesoscopic measurements are compared to the high-performance rechargeable Al-based battery consisting of a few-layer graphene-multiwall carbon nanotube composite cathode. These composites exhibit a 60% capacity enhancement over pyrolytic graphite, while an ∼3-fold improvement in overall ion diffusivity is also obtained exhibiting ∼1% of those in atomically thin single crystals. Our results thus establish the distinction between intrinsic and ensemble electrochemical behavior in Al-based batteries and show that engineering ion transport in these devices can yet lead to vast improvements in battery performance.

The role of efferocytosis in neuro-degenerative diseases.

Efferocytosis has a critical role in maintaining tissues and organs' homeostasis by removing apoptotic cells. It is essential for human health, and disturbances in efferocytosis may result indifferent illnesses. In case of inadequate clearance of the dead cells, the content in the cells would be released. In fact, it induces some damages to the tissue and leads to the prolonged inflammation, so unsuitable phagocytosis of the apoptotic cells is involved in occurrence as well as expansion of numerous human chronic inflammatory diseases. Studies have shown age dependence of the neuro-degenerative diseases, which are largely due to the neuro-inflammation and the loss of neurons and thus cause the brain's functional disorders. Efferocytosis is coupled to anti-inflammatory responses that contribute to the elimination of the dying neurons in neuro-degenerative diseases, so its disruption may make a risk factor in numerous human chronic inflammatory diseases such as multiple sclerosis, Alzheimer's disease, glioblastoma, and Rett syndrome. This study is a review of the efferocytosis molecular pathways and their role in neuro-degenerative diseases in order to discover a new treatment option to cure patients.