Selective and Continuous Oil Removal from Oil-Water Mixtures Using a Superhydrophobic and Superoleophilic Stainless Steel Mesh Tube.

The development of continuous oil-water separation processes has applications in the treatment of industrial oily wastewater and effective management of oil spills. In this research, the performance of a superhydrophobic-superoleophilic (SHSO) membrane in oil-water separation is investigated through dynamic tests. We investigate the effects of the total flow rate and oil concentration on the separation efficiency using an as-fabricated SHSO mesh tube. To construct the SHSO membrane, a tubular stainless steel mesh is dip-coated into a solution, containing a long-chain alkyl silane (Dynasylan F8261) and functionalized silica nanoparticles (AEROSIL R812). The as-prepared SHSO mesh tube illustrates a water contact angle of 164° and an oil contact angle of zero for hexane. A maximum oil separation efficiency (SE) of 97% is obtained when the inlet oil-water mixture has the lowest flow rate (5 mL/min) with an oil concentration of 10 vol %, while the minimum oil SE (86%) is achieved for the scenario with the highest total flow rate (e.g., 15 mL/min) and the highest oil concentration (e.g., 50 vol %). The water SE of about 100% in the tests indicates that the water separation is not affected by the total flow rate and oil concentration, due to the superhydrophobic state of the fabricated mesh. The clear color of water and oil output streams also reveals the high SE of both phases in dynamic tests. The outlet oil flux increases from 314 to 790 (L/m2·h) by increasing the oil permeate flow rate from 0.5 to 7.5 (mL/min). The linear behavior of the cumulative amounts of collected oil and water with time demonstrates the high separation performance of a single SHSO mesh, implying no pore blocking during dynamic tests. The significant oil SE (97%) of the fabricated SHSO membrane with robust chemical stability shows its promising potential for industrial-scale oil-water separation applications.

Blood levels of brain-derived neurotrophic factor (BDNF) in systemic lupus erythematous (SLE): a systematic review and meta-analysis.

OBJECTIVES: BDNF has been implicated in the pathophysiology of systemic lupus erythematosus (SLE), especially its neuropsychiatric symptoms. The purpose of this study was to investigate the profile of blood BDNF levels in patients with SLE. METHODS: We searched PubMed, EMBASE, and the Cochrane Library for papers that compared BDNF levels in SLE patients and healthy controls (HCs). The Newcastle-Ottawa scale was used to assess the quality of the included publications, and statistical analyses were carried out using R 4.0.4. RESULTS: The final analysis included eight studies totaling 323 healthy controls and 658 SLE patients. Meta-analysis did not show statistically significant differences in blood BDNF concentrations in SLE patients compared to HCs (SMD 0.08, 95% CI [ - 1.15; 1.32], P value = 0.89). After removing outliers, there was no significant change in the results: SMD -0.3868 (95% CI [ - 1.17; 0.39], P value = 0.33. Univariate meta-regression analysis revealed that sample size, number of males, NOS score, and mean age of the SLE participants accounted for the heterogeneity of the studies (R2 were 26.89%, 16.53%, 18.8%, and 49.96%, respectively). CONCLUSION: In conclusion, our meta-analysis found no significant association between blood BDNF levels and SLE. The potential role and relevance of BDNF in SLE need to be further examined in higher quality studies.

Clinical efficacy and safety of bispecific antibodies for the treatment of solid tumors: a systematic review and meta-analysis.

INTRODUCTION: Immunotherapy is a promising and progressing treatment approach for cancer. Bispecific antibodies (BsAbs) are antibody constructs that can bind to two different epitopes. The dual-specificity of BsAbs improves their efficacy compared to monoclonal antibodies. AREAS COVERED: Although BsAbs have achieved excellent therapeutic effects in hematologic cancers, no systematic review with meta-analysis evaluated their efficacy in solid tumors. In the present systematic review and meta-analysis, we aimed to establish the clinical efficacy and safety of BsAbs in solid tumors. EXPERT OPINION: BsAbs are not associated with significantly better safety or efficacy outcomes than conventional therapies. BsAb was not associated with improvement in overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). However, BsAb increased the rate of stable disease (SD) significantly. Also, BsAb substantially increased the OS and PFS and resulted in a higher frequency of DCR for uveal melanoma. Furthermore, the safety analysis showed no obvious difference in the rate of any adverse events (AEs), grade ≥3 AEs, serious AEs, and AEs leading to treatment discontinuation in the intervention group compared to controls. Further high-quality randomized controlled trials on BsAbs in solid tumors are highly recommended.

Inborn Errors of Immunity and Worries During the Monkeypox Outbreak.

Inborn errors of immunity (IEI) are disorders characterized by the impaired development and functioning of the immune system components. These errors can affect cellular immunity, humoral immunity, or both, predisposing patients to localized and systemic manifestations (for the most recent update on the classification of IEI, see [1](#ref-0001)). Among various signs and symptoms, increased susceptibility to infections and autoimmune and inflammatory conditions with a high tendency to involve the skin, lungs, and gut are most-documented. With the re-emergence of the monkeypox (MPX) outbreak in 2022 and a new picture that it has presented, i.e., the global spread of the disease and the high prevalence in patients with human immunodeficiency syndrome (HIV) [2](#ref-0002), worries are increasing about the possible threat of monkeypox virus (MPXV) to affect patients with IEI. As of November 04, 2022, 109 countries reported a total of more than 78,000 MPXV-infected cases, with a death rate of about 0.01% [3](#ref-0003). During this outbreak, males who have sex with other males (MSM) have constituted the majority of the MPXV-infected population [4,5](#ref-0004). Moreover, people with HIV account for about 40% of this population and exhibit a more severe disease course, as represented in the higher need for hospitalization [6](#ref-0006). To date, no infection with MPXV has been reported in patients with IEI; however, high susceptibility of immunocompromised people to this infection is alarming for people with IEI and their caregivers. Below address a few important questions concerning patients with IEI during this outbreak. This article is protected by copyright. All rights reserved.

The pro-tumorigenic responses in metastatic niches: an immunological perspective

Metastasis is the leading cause of mortality related to cancer. In the course of metastasis, cancer cells detach from the primary tumor, enter the circulation, extravasate at secondary sites, and colonize there. All of these steps are rate limiting and decrease the efficiency of metastasis. Prior to their arrival, tumor cells can modify the secondary sites. These favorable microenvironments increase the probability of successful dissemination and are referred to as pre-metastatic niches. Cancer cells use different mechanisms to induce and maintain these niches, among which immune cells play prominent roles. The immune system, including innate and adaptive, enhances recruitment, extravasation, and colonization of tumor cells at distant sites. In addition to immune cells, stromal cells can also contribute to forming pre-metastatic niches. This review summarizes the pro-metastatic responses conducted by immune cells and the assistance of stromal cells and endothelial cells in the induction of pre-metastatic niches (AU)

The Role of Ketogenic Diet in the Treatment of Neuroblastoma.

The ketogenic diet (KD) was initially used in 1920 for drug-resistant epileptic patients. From this point onward, ketogenic diets became a pivotal part of nutritional therapy research. To date, KD has shown therapeutic potential in many pathologies such as Alzheimer's disease, Parkinson's disease, autism, brain cancers, and multiple sclerosis. Although KD is now an adjuvant therapy for certain diseases, its effectiveness as an antitumor nutritional therapy is still an ongoing debate, especially in Neuroblastoma. Neuroblastoma is the most common extra-cranial solid tumor in children and is metastatic at initial presentation in more than half of the cases. Although Neuroblastoma can be managed by surgery, chemotherapy, immunotherapy, and radiotherapy, its 5-year survival rate in children remains below 40%. Earlier studies have proposed the ketogenic diet as a possible adjuvant therapy for patients undergoing treatment for Neuroblastoma. In this study, we seek to review the possible roles of KD in the treatment of Neuroblastoma.

Nanotechnology-based diagnostics and therapeutics in acute lymphoblastic leukemia: a systematic review of preclinical studies.

Background: Leukemia is a malignant disease that threatens human health and life. Nano-delivery systems improve drug solubility, bioavailability, and blood circulation time, and release drugs selectively at desired sites using targeting or sensing strategies. As drug carriers, they could improve therapeutic outcomes while reducing systemic toxicity. They have also shown promise in improving leukemia detection and diagnosis. The study aimed to assess the potential of nanotechnology-based diagnostics and therapeutics in preclinical human acute lymphoblastic leukemia (h-ALL). Methods: We performed a systematic search through April 2022. Articles written in English reporting the toxicity, efficacy, and safety of nanotechnology-based drugs (in the aspect of treatment) and specificity, limit of detection (LOD), or sensitivity (in the aspect of the detection field) in preclinical h-ALL were included. The study was performed according to PRISMA instructions. The methodological quality was assessed using the QualSyst tool. Results: A total of 63 original articles evaluating nanotechnology-based therapeutics and 35 original studies evaluating nanotechnology-based diagnostics were included in this review. As therapeutics in ALL, nanomaterials offer controlled release, targeting or sensing ligands, targeted gene therapy, photodynamic therapy and photothermic therapy, and reversal of multidrug-resistant ALL. A narrative synthesis of studies revealed that nanoparticles improve the ratio of efficacy to the toxicity of anti-leukemic drugs. They have also been developed as a vehicle for biomolecules (such as antibodies) that can help detect and monitor leukemic biomarkers. Therefore, nanomaterials can help with early diagnostics and personalized treatment of ALL. Conclusion: This review discussed nanotechnology-based preclinical strategies to achieve ALL diagnosis and therapy advancement. This involves modern drug delivery apparatuses and detection devices for prompt and targeted disease diagnostics. Nonetheless, we are yet in the experimental phase and investigational stage in the field of nanomedicine, with many features remained to be discovered as well as numerous problems to be solved.

Insights on Mpox virus infection immunopathogenesis.

An immunocompromised status has been associated with more odds of being infected with Mpox virus (MPXV) and progressing to severe disease. This aligns with the importance of immune competence for MPXV control and clearance. We and others have previously reviewed parallels between MPXV and other viruses belonging to the Poxviridae in affecting the immune system. This article reviews studies providing direct evidence of the MPXV-immune interactions. The wide-ranging effects of MPXV on the immune system, from stimulation to modulation to memory, are broadly categorised, followed by a detailing of these effects on the immune cells and molecules, including natural killer cells, macrophages, neutrophils, lymphocytes, cytokines, interferons, chemokines, and complement.

Brain-derived neurotrophic factor in diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor expressed in several tissues, including the brain, gut, and pancreas. Activation of the BDNF/TrkB/CREB reduces hepatic gluconeogenesis, induces hepatic insulin signal transduction, and protects against pancreatic beta-cell loss in diabetes mellitus (DM). Several studies have investigated the possible association between BDNF and DM and its complications, but the results have been conflicting. AIM: In the present study, we aimed at systematically reviewing the literature on the serum and plasma levels of BDNF in DM and its subgroups such as T2DM, DM patients with depression, and patients with retinopathy. METHODS: A comprehensive search was conducted in PubMed, Scopus, and Web of Science. We identified 28 eligible studies and calculated the standardized mean difference (SMD) of outcomes as an effect measure. RESULTS: The meta-analysis included 2734 patients with DM and 6004 controls. Serum BDNF levels were significantly lower in patients with DM vs. controls (SMD = -1.00, P<0.001). Plasma BDNF levels were not different in patients with DM compared with controls. When conducting subgroup analysis, serum BDNF levels were lower among patients with T2DM (SMD = -1.26, P<0.001), DM and depression (SMD = -1.69, P<0.001), and patients with diabetic retinopathy (DR) vs. controls (SMD = -1.03, P = 0.01). CONCLUSIONS: Serum BDNF levels were lower in patients with DM, T2DM, DM with depression, and DM and DR than the controls. Our findings are in line with the hypothesis that decreased BDNF levels might impair glucose metabolism and contribute to the pathogenesis of DM and its complications.

MGMT Gene rs1625649 Polymorphism in Iranian Patients with Brain Glioblastoma: A Case Control Study.

Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor with poor prognosis and high potential of dispersion to other brain tissues in adult. Effective and modern choices of treatment including chemotherapy with alkylating agents marginally extend survival of GBM. However, alkylating agents can lead to highly harmful mismatch during DNA replication causing apoptosis and cell death. Accordingly, O6-Methylguanine-DNA methyltransferase (MGMT) removes alkyl adducts, thereby causing resistance to alkylating drugs. Single-Nucleotide Polymorphisms (SNPs) in MGMT promoter region may play a role in the regulation of MGMT expression and prediction of glioma development risk. In order to evaluate the clinical significance of rs1625649 SNP in the MGMT promoter region of glioblastoma, genomic DNA from a series of 54 patients with GBM and 50 healthy individuals in Iranian population were collected for tetra ARMS PCR amplification. None of the "A" or "C" alleles were associated with tumor occurrence, the "AA" genotype was more frequent in healthy subjects, and the "AC" genotype was 4.6 times more common in patients with GBM. The longest survival time was observed in the "CC" genotype; however, this difference was not statistically significant. On the other hand, homozygous rs1625649 (AA genotype) was significantly associated with a better survival than the cases with heterozygous rs1625649 (CA genotype) or wild type rs1625649 (CC genotype), predicting better response to temozolomide-based chemotherapy.

Central nervous system hydatidosis around the world: a systematic review.

INTRODUCTION: Echinococcosis is a chronic disease caused by Echinococcus species. The central nervous system (CNS) hydatidosis is still a major concern, especially in endemic countries, due to non-specific features and late diagnosis and treatment. This study aimed to provide a systematic review to elucidate the epidemiology and clinical characteristics of CNS hydatidosis worldwide over the past decades. EVIDENCE ACQUISITION: PubMed, Scopus, EMBASE, Web of Science, Ovid, and Google Scholar were systematically searched. The gray literature and the references of included studies were searched as well. EVIDENCE SYNTHESIS: Our results showed that the CNS hydatid cyst was more prevalent in the male gender, and it is known as a recurrent disease with a rate of 26.5%. CNS hydatidosis was more common in the supratentorial region and was also significantly common in developing countries, including Turkey and Iran. CONCLUSIONS: It was demonstrated that the disease would be more prevalent in developing countries. Also, there would be a trend toward a male predominance of CNS hydatid cyst, younger age involvement, and the recurrence rate of 25% in general. There is no consensus about chemotherapy unless in recurrent disease and the patients who experienced cyst rupture intraoperatively, recommended for a wide range of 3 to 12 months.

Current therapeutic approaches and promising perspectives of using bioengineered peptides in fighting chemoresistance in triple-negative breast cancer.

Breast cancer is a collation of malignancies that manifest in the mammary glands at the early stages. Among breast cancer subtypes, triple-negative breast cancer (TNBC) shows the most aggressive behavior, with apparent stemness features. Owing to the lack of response to hormone therapy and specific targeted therapies, chemotherapy remains the first line of the TNBC treatment. However, the acquisition of resistance to chemotherapeutic agents increase therapy failure, and promotes cancer recurrence and distant metastasis. Invasive primary tumors are the birthplace of cancer burden, though metastasis is a key attribute of TNBC-associated morbidity and mortality. Targeting the chemoresistant metastases-initiating cells via specific therapeutic agents with affinity to the upregulated molecular targets is a promising step in the TNBC clinical management. Exploring the capacity of peptides as biocompatible entities with the specificity of action, low immunogenicity, and robust efficacy provides a principle for designing peptide-based drugs capable of increasing the efficacy of current chemotherapy agents for selective targeting of the drug-tolerant TNBC cells. Here, we first focus on the resistance mechanisms that TNBC cells acquire to evade the effect of chemotherapeutic agents. Next, the novel therapeutic approaches employing tumor-targeting peptides to exploit the mechanisms of drug resistance in chemorefractory TNBC are described.

T helper 17 and regulatory T-cell profile and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation in pediatric patients with beta-thalassemia.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment option for hereditary hemoglobin disorders, such as beta-thalassemia; However, this procedure is not without constraints, mainly engendering complications such as acute graft-versus-host disease (aGvHD), chronic GvHD (cGvHD), and susceptibility to infections. The clinical outcomes of allo-HSCT are highly dependant on the quality and quantity of T-cell subsets reconstitution. Following the allo-HSCT of six pediatric patients afflicted with beta-thalassemia, their mononuclear cells were isolated, and then cultured with a combination of phorbol myristate acetate (PMA)/ionomycin and Brefeldin A. The content of CD4 T-cell subsets, including T helper 17 (Th17) cells and regulatory T cells (Tregs), were determined by specific conjugated-monoclonal antibodies three and six months post-HSCT. An increased frequency of total CD4 T-cells, Tregs and Th17 cells was observed at day 90 and 180 after allo-HSCT, albeit the numbers were still lower than that of our healthy controls. In patients who developed cGvHD, a lower Th17/Treg ratio was observed, owing it to a decreased proportion of Th17 cells. In conclusion, creating balance between Th17 and Treg subsets may prevent acute and chronic GvHD in patients after allo-HSCT.

Demographic, clinical, immunological, and molecular features of iranian national cohort of patients with defect in DCLRE1C gene.

BACKGROUND: DCLRE1C gene mutation leads to Artemis deficiency, a severe form of combined immunodeficiency (SCID). Impaired DNA repair and block in early adaptive immunity maturation results in T-B-NK+ immunodeficiency associated with radiosensitivity. Recurrent infections early in life are the main characteristic of Artemis patients. METHOD: Among 5373 registered patients, 9 Iranian patients (33.3% female) with confirmed DCLRE1C mutation were identified since 1999-2022. The demographic, clinical, immunological and genetic features were collected through retrospective investigation of medical records and using next generation sequencing. RESULTS: Seven patients were born in a consanguineous family (77.8%). The median age of onset was 6.0 (5.0-17.0) months. Severe combined immunodeficiency (SCID) was clinically detected at a median (IQR) age of 7.0 (6.0-20.5) months, following a median diagnostic delay of 2.0 (1.0-3.5) months The most typical first presentation was pneumonia (44.4%) and otitis media (3.33%), followed by BCG lymphadenitis (22.2%) and gastroenteritis (11.1%). The most prevalent manifestations were respiratory tract infections (including otitis media) (66.6%) and chronic diarrhea (66.6%). In addition, juvenile idiopathic arthritis (P5) and celiac disease and idiopathic thrombocytopenic purpura (P9) as autoimmune disorders were reported in 2 patients. All patients had reduced B CD19+ and CD4+ cell counts. IgA deficiency occurred in 77.8% of individuals. CONCLUSION: Recurrent infections particulary respiratory tract infection and chronic diarrhea during the first months of life in patients born to consanguineous parents should raise the suspicion for inborn errors of immunity, even in the presence of normal growth and development.

The Autoimmune Manifestations in Patients with Genetic Defects in the B Cell Development and Differentiation Stages.

PURPOSE: Primary B cell defects manifesting as predominantly antibody deficiencies result from variable inborn errors of the B cell lineage and their development, including impairments in early bone marrow development, class switch recombination (CSR), or terminal B cell differentiation. In this study, we aimed to investigate autoimmunity in monogenic patients with B cell development and differentiation defects. METHODS: Patients with known genetic defects in the B cell development and differentiation were recruited from the Iranian inborn errors of immunity registry. RESULTS: A total of 393 patients with a known genetic defect in the B cell development and differentiation (257 males; 65.4%) with a median age of 12 (6-20) years were enrolled in this study. After categorizing patients, 109 patients had intrinsic B cell defects. More than half of the patients had defects in one of the ATM (85 patients), BTK (76 patients), LRBA (34 patients), and DOCK8 (33 patients) genes. Fifteen patients (3.8%) showed autoimmune complications as their first manifestation. During the course of the disease, autoimmunity was reported in 81 (20.6%) patients at a median age of 4 (2-7) years, among which 65 patients had mixed intrinsic and extrinsic and 16 had intrinsic B cell defects. The comparison between patients with the mentioned four main gene defects showed that the patient group with LRBA defect had a significantly higher frequency of autoimmunity compared to those with other gene defects. Based on the B cell defect stage, 13% of patients with early B cell defect, 17% of patients with CSR defect, and 40% of patients who had terminal B cell defect presented at least one type of autoimmunity. CONCLUSION: Our results demonstrated that gene mutations involved in human B cell terminal stage development mainly LRBA gene defect have the highest association with autoimmunity.

Immunogenicity of Different Types of Adjuvants and Nano-Adjuvants in Veterinary Vaccines: A Comprehensive Review.

Vaccination is the best way to prevent and reduce the damage caused by infectious diseases in animals and humans. So, several vaccines are used for prophylactic purposes before the pathogen infects, while therapeutic vaccines strengthen the immune system after infection with the pathogen. Adjuvants are molecules, compounds, or macromolecules that enhance non-specific immunity and, in collaboration with antigen(s), can improve the body's immune responses and change the type of immune response. The potential and toxicity of adjuvants must be balanced to provide the safest stimulation with the fewest side effects. In order to overcome the limitations of adjuvants and the effective and controlled delivery of antigens, attention has been drawn to nano-carriers that can be a promising platform for better presenting and stimulating the immune system. Some studies show that nanoparticles have a more remarkable ability to act as adjuvants than microparticles. Because nano-adjuvants inactively target antigen-presenting cells (APCs) and change their chemical surface, nanoparticles also perform better in targeted antigen delivery because they cross biological barriers more easily. We collected and reviewed various types of nano-adjuvants with their specific roles in immunogenicity as a prominent strategy used in veterinary vaccines in this paper.

Investigation of the female infertility risk associated with anti-cancer therapy.

Female infertility is a significant health issue worldwide with a rising incidence. Anti-cancer therapy is one of the most important reasons for increasing infertility. Although anti-cancer treatment increases the rate of survival, it decreases the quality of life through its side effects. The most substantial side effects are sexual dysfunction and infertility. Breast cancer is the most common cancer. The first-line treatment of breast cancer is chemotherapy by alkylating agents like cyclophosphamide, which leads to infertility. For instance, persistent chemotherapy-induced amenorrhea among breast cancer patients could affect almost half of the patients that undergo such therapy. However, some agents or therapeutic methods can ameliorate these intoxicating effects. Chemotherapy plus gonadotropin-releasing hormone agonist, in breast cancer patients, can not only improve overall survival but also reduce ovarian toxicity. Age plays an essential role in chemotherapy-induced amenorrhea. Chemotherapy at a younger age can reduce the risk of infertility. Gynecological cancers including uterine and ovarian cancer, which have high mortality rates, are the most related cancers to infertility. Surgery is the primary treatment of gynecological cancers. Studies demonstrated that fertility-sparing surgery is a better option than radical surgery. In addition, neoadjuvant chemotherapy is mostly a better option than primary cytoreductive surgery in terms of survival and fertility. Immune checkpoint inhibitors (ICIs) have recently played a major role in treating various cancer types. However, ICIs are associated with hypophysitis, which affects ovaries and can lead to infertility. There are some options for ovarian preservation such as embryo cryopreservation, oocyte cryopreservation, ovarian transposition, ovarian tissue cryopreservation, and ovarian suppression by GnRH agonists. Anti-müllerian hormone level can be utilized to monitor the ovarian reserve. Moreover, to avoid fertility loss, approaches such as using transplantation of human placenta mesenchymal stem cells, administrating anti-inflammatory agents and hormone therapy are under investigation.

How do nuclear factor kappa B (NF-κB)1 and NF-κB2 defects lead to the incidence of clinical and immunological manifestations of inborn errors of immunity?

INTRODUCTION: Genetic defects affect the manner of the immune system's development, activation, and function. Nuclear factor-kappa B subunit 1 (NF-κB1) and NF-κB2 are involved in different biological processes, and deficiency in these transcription factors may reveal clinical and immunological difficulties. AREAS COVERED: This review article gathers the most frequent clinical and immunological remarkable characteristics of NF-κB1 and NF-κB2 deficiencies. Afterward, an effort is made to describe the biological mechanism, which is likely to be the cause of these clinical and immunological abnormalities. EXPERT OPINION: The present review article has explained the mechanism of contributions of the NF-κB1 and NF-κB2 deficiency in revealing immunodeficiency symptoms, specifically immunological and clinical manifestations. These mechanisms demonstrate the importance of NF-κB1 and NF-κB2 signaling pathways for B and T cell development, activation, antibody production, and immunotolerance. The manifestation of a mutation can range from no symptoms to severe complications in a family.

NF-κB1 and NF-κB2 are the transcription factors that have an essential role in the development and function of the immune system. Several mutations in the NF-κBs could lead to inborn errors of immune manifestations.There are different reports of NF-κB mutations with various clinical and immunological manifestations, whereas the mechanisms behind the appearance of these have been less discussed. We collected frequent clinical and immunological manifestations from the literature and discussed the likely biological cause of their occurrence. Here we clarify the potential mechanism that defects in NF-κB1 and NF-κB2 signaling lead to inadequate B and T cells function, specifically, insufficient switched memory B cells and class-switched antibodies and autoimmunity. We also focused on the straight correlation between deficiencies in immune system responses caused by defects in NF-κB and susceptibility to recurrent infections and other clinical problems.Since our understanding of the mechanisms of signaling pathways such as NF-κB deficiencies from genetic mutations to clinical manifestations in PIDs is limited, further in vitro and animal model studies are necessary to assess these pathways' comprehensive roles in immunodeficiency more accurately. [Figure: see text].

Brain and Spinal Cord Tumors Among the Life-Threatening Health Problems: An Introduction.

As one of the global concerns, cancers, including brain and spinal cord tumors, are responsible for mortalities and irreversible morbidities in the affected patients. Although advancements in molecular pathology and imaging of tumors may have influenced the incidence rate due to higher diagnosis in early stages, exposure to environmental risk factors could be another explanation for increased incidence of these tumors over the past decades. Similar to many other tumors, the CNS tumors begin in cellular dimension with activation of different molecular pathways. Several genetic, epigenetic, and immunologic pathways and processes are already discovered to play roles in pathophysiology of these tumors, which mostly will eventually become symptomatic. Each of these tumors may exhibit imaging characteristics, making it possible to list a series of differential diagnosis before histopathologic examination. Advances in molecular pathology have resulted in better understanding and categorization of CNS tumors, leading to better decision-making on the most appropriate therapeutic approach for each category, as well as proposing new therapeutic modalities to treat these tumors. As an introduction to the 2-volume book, this chapter addressed different types of human brain and spinal cord tumors based on the fifth version of WHO classification of CNS tumors.

The Epidemiology of Brain and Spinal Cord Tumors.

CNS tumors are a diverse group of neoplasms that emerge from a variety of different CNS cell types. These tumors may be benign, malignant, or borderline in nature. The majority of high grade glial tumors are fatal, with the exception of pilocytic astrocytoma. Primary malignant CNS tumors occur at a global annual rate of 2.1 to 5.8 per 100,000 persons. Males are more likely to develop malignant brain tumors than females, whereas benign meningiomas are more common in adult females. Additionally, gender inequalities in non-malignant tumors peak between the ages of 25 and 29 years. Only a small number of genetic variants have been associated with survival and prognosis. Notably, central nervous system (CNS) tumors exhibit significant age, gender, and race variation. Race is another factor that affects the incidence of brain and spinal cord tumors. Different races exhibit variation in terms of the prevalence of brain and CNS malignancies. This chapter discusses ongoing research on brain and spinal cord tumor epidemiology, as well as the associated risks and accompanied disorders.