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Introduction: Funding decisions for many health technologies occur without undergoing health technology assessment (HTA), in particular, without assessment of cost effectiveness (CE). Immunoglobulins in Australia are an interesting case study because they have been used for a long time for various rare disorders and their price is publicly available. Undertaking an HTA enables us to assess CE for an intervention for which there is limited clinical and economic evidence. This study presents a post-market review to assess the CE of immunoglobulins for the treatment of multifocal motor neuropathy (MMN) compared with best supportive care., Methods: A Markov model was used to estimate costs and quality-adjusted life-years (QALYs). Input sources included randomised controlled trials, single-arm studies, the Australian clinical criteria for MMN, clinical guidelines, previous Medical Services Advisory Committee (MSAC) reports and inputs from clinical experts. Sensitivity analyses were conducted to assess the uncertainty and robustness of the CE results., Results: The cost per patient of treating MMN with immunoglobulin was AU$275,853 versus AU$26,191when no treatment was provided, with accrued QALYs of 6.83 versus 6.04, respectively. The latter translated into a high incremental cost-effectiveness ratio (ICER) of AU$317,552/QALY. The ICER was most sensitive to the utility weights and the price of immunoglobulins. MSAC advised to continue funding of immunoglobulins on the grounds of efficacy, despite the high and uncertain ICER., Conclusions: Beyond the ICER framework, other factors were acknowledged, including the high clinical need in a patient population for which there are no other active treatments available. This case study highlights the challenges of conducting HTA for already funded interventions, and the efficiency trade-offs required to fund effective high-cost therapies in rare conditions., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Engineered collaborative biochemical techniques and regulated nanomaterials (NMs) offer extraordinary opportunities for improving the analysis performance of lateral flow immunoassay (LFIA). Herein, inspired by the ability of macromolecules (e.g., proteins) to assemble into new functional units and the remarkable optical performance of engineered regulated NMs, goat anti-mouse immunoglobulin (GAMI) serves as the "crosslinker" integrate with gold‑manganese oxide (Au-MnO x) to assemble the "signal tracers (STs)-crosslinker-antibody (mAb)" for elevating the mAb utilization efficiency. Notably, the "STs-crosslinker-mAb" assembly shows ~13.33-folds mAb utilization efficiency enhance, which perfectly response the challenge between limited sensitivity and sufficient signal intensity in competitive-type LFIA. The black color and rough structure of Au-MnO x offer higher colorimetric brightness (~2-folds than AuNPs) and enhanced mAb coupling efficiency (up to 92.47%), which further improves sensitivity under the premise of functional assembly to intensify the competitive immunoreaction. Additionally, the convenient synthesis conditions (~13 min at room temperature) even comparable to direct purchase commercial products indicate that using Au-MnO x undoubtedly increases the cost-effectiveness. Encouragingly, the Au-MnO x -GAMI-mAb based LFIA exhibited high sensitivity (LOD: 0.063 ng mL−1 for clenbuterol (CLE) monitoring) by elevating mAb utilization efficiency with the attendant enhancing immune competition response in a cost-effective manner, which provides an invigorating reference pathway in point-of-care immunoassay. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Food allergy (FA) affects approximately 8% of children and may be immunoglobulin E (IgE)-mediated or non-IgE-mediated. It is recognized clinically that children with both subtypes of FA may present with features of pediatric feeding disorder (PFD); however, there is currently a limited detail of presenting characteristics. Objective: The objective of this study was to synthesize the current evidence regarding the feeding characteristics of children with FA, with a focus on the feeding skills and psychosocial domains of PFD. Method: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. Papers published between 2001 and 2022 describing feeding characteristics in the feeding skills and psychosocial domains in children with FA/history of FA were included. Papers that focused solely on characteristics from the medical or nutritional domains were excluded. Descriptive information regarding demographics, methodology, allergy profile and history, and the characteristics of PFD observed was extracted using a preconceived data extraction form. Results: Overall, 40 papers contained descriptions of feeding characteristics of children with non-IgE-mediated FA (n = 22) and IgE-mediated FA (n = 11), while four were nonspecific. In the psychosocial domain, food refusal/aversion, anxiety with eating, and poor intake were the most frequently reported, regardless of FA subtype. Less information was reported regarding feeding skills, although slowness in eating, immature diet, and delays in oral sensory-motor skills were described. Conclusions: Children with FA/history of FA may present with a range of characteristics that map across the feeding skill and psychosocial domains of PFD. Systematic research is needed to fully describe the feeding characteristics of children with FA. [ABSTRACT FROM AUTHOR]

As of now, more than 60 years have passed since the first determination of protein structures through crystallography, and a significant portion of protein structures can be predicted by computers. This is due to the groundbreaking enhancement in protein structure prediction achieved through neural network training utilizing extensive sequence and structure data. However, substantial challenges persist in structure prediction due to limited data availability, with antibody structure prediction standing as one such challenge. In this paper, we propose a novel neural network architecture that effectively enables structure prediction by reflecting the inherent combinatorial nature involved in protein structure formation. The core idea of this neural network architecture is not solely to track and generate a single structure but rather to form a community of multiple structures and pursue accurate structure prediction by exchanging information among community members. Applying this concept to antibody CDR H3 loop structure prediction resulted in improved structure sampling. Such an approach could be applied in the structural and functional studies of proteins, particularly in exploring various physiological processes mediated by loops. Moreover, it holds potential in addressing various other types of combinatorial structure prediction and design problems. Author summary: In this paper, we propose a new architecture that aims to improve upon protein structure prediction algorithms like AlphaFold or RoseTTAFold by considering the combinatorial nature of protein structure formation. Such an architecture, reflecting the physical principles of nature, is expected to yield beneficial results, particularly in scenarios with limited structure and sequence information. Named ComMat, this architecture does not focus on a single structure but rather on a set of multiple structures—a community—simultaneously. In this process, combinatorial exploration of protein structure is encouraged through information exchange among community members. ComMat is an instance that integrates this idea within the structure module of AlphaFold. Applying ComMat to antibody CDR H3 loop structure prediction yielded outstanding results in structure sampling and prediction when tested on the IgFold set and compared with IgFold and AlphaFold-Multimer. It confirmed that improved structure sampling stems from effective structural exploration. The proposed concept here could potentially be used in the development of various other combinatorial protein structure prediction and protein design methods. [ABSTRACT FROM AUTHOR]

The affinity constant, also known as the equilibrium constant, binding constant, equilibrium association constant, or the reciprocal value, the equilibrium dissociation constant (Kd), can be considered as one of the most important characteristics for any antibody–antigen pair. Many methods based on different technologies have been proposed and used to determine this value. However, since a very large number of publications and commercial datasheets do not include this information, significant obstacles in performing such measurements seem to exist. In other cases where such data are reported, the results have often proved to be unreliable. This situation may indicate that most of the technologies available today require a high level of expertise and effort that does not seem to be available in many laboratories. In this paper, we present a simple approach based on standard immunoassay technology that is easy and quick to perform. It relies on the effect that the molar IC50 approaches the Kd value in the case of infinitely small concentrations of the reagent concentrations. A two-dimensional dilution of the reagents leads to an asymptotic convergence to Kd. The approach has some similarity to the well-known checkerboard titration used for the optimization of immunoassays. A well-known antibody against the FLAG peptide, clone M2, was used as a model system and the results were compared with other methods. This approach could be used in any case where a competitive assay is available or can be developed. The determination of an affinity constant should belong to the crucial parameters in any quality control of antibody-related products and assays and should be mandatory in papers using immunochemical protocols. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent advancements in cancer research have proven immunotherapies to be a promising strategy for the treatment of hematological malignancies. The bispecific antibody (BsAb) format was developed to overcome the issues of monoclonal antibody-based therapies. T-cell engagers (TCEs) are BsAbs, which directly activate T-cells and their anti-tumor features, ultimately resulting in the lysis of the targeted tumor cells. In 2014, the FDA approved blinatumomab for treatment of acute lymphoblastic leukemia. As of November 2023, seven clinically approved TCE therapies are on the market. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects. Recent advancements in cancer immunotherapy have made directing the cellular immune response onto cancer cells a promising strategy for the treatment of hematological malignancies. The introduction of monoclonal antibody-based (mAbs) targeted therapy has significantly improved the prognosis for hematological patients. Facing the issues of mAb-based therapies, a novel bispecific antibody (BsAb) format was developed. T-cell engagers (TCEs) are BsAbs, which simultaneously target tumor-associated antigens on tumor cells and CD3 molecules present on T-cells. This mechanism allows for the direct activation of T-cells and their anti-tumor features, ultimately resulting in the lysis of tumor cells. In 2014, the FDA approved blinatumomab, a TCE directed to CD3 and CD19 for treatment of acute lymphoblastic leukemia. Since then, numerous TCEs have been developed, allowing for treating different hematological malignancies such as acute myeloid leukemia, multiple myeloma, and non-Hodgkin lymphoma and Hodgkin lymphoma. As of November 2023, seven clinically approved TCE therapies are on the market. TCE-based therapies still have their limitations; however, improving the properties of TCEs, as well as combining TCE-based therapies with other forms of treatment, give hope to find the cures for currently terminal diseases. In this paper, we summarized the technical basis of the TCE technology, its application in hematology, and its current issues and prospects. [ABSTRACT FROM AUTHOR]

Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Immunotherapy aimed at inhibiting the negative co-stimulatory molecule programmed cell death-ligand 1 (PD-L1) has limited effectiveness, with clinical response rates remaining below 10%-15%. Therefore, new immune checkpoints need to be explored. Our study focused on human endogenous retrovirus H long terminal repeat-associating protein 2 (HHLA2), a highly glycosylated member of the B7 family that is widely expressed in colorectal cancer. HHLA2 expression negatively correlates with the prognosis of colorectal cancer. Glycosylation of HHLA2, which is regulated by the glycosyltransferase STT3 oligosaccharyltransferase complex catalytic subunit A (STT3A), is crucial for protein stability and expression in cell membranes. Additionally, the binding of HHLA2 to the receptors killer cell immunoglobulin-like receptor, three immunoglobulin domains and long cytoplasmic tail 3 (KIR3DL3) and transmembrane and immunoglobulin (Ig) domain containing 2 (TMIGD2) is dependent on N-glycosylation. Moreover, N-glycosylation of HHLA2 promotes immune evasion in colorectal cancer by suppressing the immune response of NK cells. Notably, the STT3A inhibitor NGI-1 enhances the anti-tumor immune response of NK cells. Our findings provide new insights and a molecular basis for targeting HHLA2 in immunotherapy for colorectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The COVID-19 pandemic has tested the technical, scientific, and industrial resources of all countries worldwide. Faced with the absence of pharmacological strategies against the disease, an effective plan for vaccinating against SARS-CoV-2 has been essential. Due to the lack of production means and necessary infrastructure, only a few nations could adequately confront this pathogen with a production, storage, and distribution scheme in place. This disease has become endemic in many countries, especially in those that are developing, thus necessitating solutions tailored to their reality. In this paper, we propose an in silico method to guide the design towards a thermally stable, universal, efficient, and safe COVID-19 vaccine candidate against SARS-CoV-2 using bioinformatics, immunoinformatics, and molecular modeling approaches for the selection of antigens with higher immunogenic potential, incorporating them into the surface of the M13 phage. Our work focused on using phagemid display as peptide array for neutralizing antibodies (PdPANA). This alternative approach might be useful during the vaccine development process, since it could bring improvements in terms of costeffectiveness in production, durability, and ease of distribution of the vaccine under less stringent thermal conditions compared to existing methods. Our results suggest that in the heavily glycosylated region of SARS-CoV-2 Spike protein (aa 344–583), from its inter-glycosylated regions, useful antigenic peptides can be obtained to be used in M13 phagemid display system. PdPANA, our proposed method might be useful to overcome the classic shortcoming posed by the phage-display technique (i.e., the time-consuming task of in vitro screening through great sized libraries with non-useful recombinant proteins) and obtain the most ideal recombinant proteins for vaccine design purposes. [ABSTRACT FROM AUTHOR]

The immunomodulatory (IM) subtype of triple negative breast cancer (TNBC) exhibits high expression of immune cell signaling genes and is more responsive to immunotherapy. However, the specific mechanism underlying this phenomenon remains unclear. One of the potential key genes appears to be the cytotoxic and regulatory T cell molecule (CRTAM). A cohort of 360 previously untreated TNBC patients from Fudan University Shanghai Cancer Center (FUSCC) underwent RNA sequencing analysis of their primary tumor tissue. Combined with three RNA-seq datasets obtained from the GEO database, a LASSO regression analysis was conducted to identify genes specific to the IM type of TNBC. Our findings revealed elevated CRTAM expression in the IM-type TNBC, which correlated with a favorable overall survival and recurrence-free survival in TNBC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated a strong association between CRTAM and immune responses as well as immune system processes. Notably, CRTAM overexpression induced STAT1 phosphorylation and upregulation of interferon-stimulated genes. We also found that CRTAM enhanced tumor-associated immune cell infiltration, especially CD8 + T cells, which may be related to the increased expression of MHC class I molecules caused by CRTAM overexpression. These results suggest that CRTAM may serve as a potential biomarker for predicting the efficacy of immunotherapy in TNBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Sporothrix globosa (S. globosa) is an agricultural activity-related but neglected pathogenic fungus responsible for sporotrichosis. Timely detection is crucial for managing and preventing its spread. However, due to the lack of efficient recognition elements for enriching S. globosa, the current approaches for detecting S. globosa are not simple and/or sensitive enough. This hinders their wider application of fast screening., Results: Herein, we successfully prepared immunoglobulin Y (IgY) targeting S. globosa, and developed a rapid and accurate detection method, improving upon current limited and inadequate detection approaches. Our method combined the use of IgY and loop-mediated isothermal amplification (LAMP) to enhance detection sensitivity and specificity simultaneously. The IgY was fabricated on magnetic beads to specifically concentrate S. globosa in samples, while LAMP amplified the captured target after simple boiling DNA extraction. By using our method, as low as 4.66 × 10 2 Cells mL -1 S. globosa was accurately detected in soil and corn straw samples. We further integrated this assay into a portable toolbox for sample-to-result detection in resource-limited areas. By using this toolbox, we have colorimetrically detected soil and corn straw samples contaminated by S. globosa, suggesting the promising on-site detection potential., Significance and Novelty: A new IgY recognizing S. globosa was prepared. Through the combination of IgY enrichment and LAMP amplification, the detection sensitivity and specificity were improved simultaneously. This method eliminated thermal cycling, simplified the operation, and reduced the analysis time. Compared to existing methods, our approach is more suitable for on-site detection and can significantly improve public health responses to sporotrichosis outbreaks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory immunoreceptor expressed on lymphocytes that serves as a promising target for cancer immunotherapy. In this study, facile synthetic protocols to produce the extracellular domain of TIGIT were investigated for applications of TIGIT in mirror-image screening. During the synthesis via sequential native chemical ligations, we encountered problems with significantly poor solubility of the ligated products. Introducing trityl-type solubilizing auxiliaries, which also functioned as temporary protecting groups for cysteine residues, facilitated a flexible order of ligations and efficient purification protocols. After refolding under appropriate conditions, the synthetic TIGIT showed a sufficient affinity toward its target ligand CD155., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Given the uniquely close relationship between fish and aquatic environments, fish mucosal tissues are constantly exposed to a wide array of pathogenic microorganisms in the surrounding water. To maintain mucosal homeostasis, fish have evolved a distinct mucosal immune system known as mucosal-associated lymphoid tissues (MALTs). These MALTs consist of key effector cells and molecules from the adaptive immune system, such as B cells and immunoglobulins (Igs), which play crucial roles in maintaining mucosal homeostasis and defending against external pathogen infections. Until recently, three primary Ig isotypes, IgM, IgD, and IgT, have been identified in varying proportions within the mucosal secretions of teleost fish. Similar to the role of mucosal IgA in mammals and birds, teleost IgT plays a predominant role in mucosal immunity. Following the identification of the IgT gene in 2005, significant advances have been made in researching the origin, evolution, structure, and function of teleost IgT. Multiple IgT variants have been identified in various species of teleost fish, underscoring the remarkable complexity of IgT in fish. Therefore, this study provides a comprehensive review of the recent advances in various aspects of teleost IgT, including its genomic and structural features, the diverse distribution patterns within various fish mucosal tissues (the skin, gills, gut, nasal, buccal, pharyngeal, and swim bladder mucosa), its interaction with mucosal symbiotic microorganisms, and its immune responses towards diverse pathogens, including bacteria, viruses, and parasites. We also highlight the existing research gaps in the study of teleost IgT, suggesting the need for further investigation into the functional aspects of IgT and IgT + B cells. This research is aimed at providing valuable insights into the immune functions of IgT and the mechanisms underlying the immune responses of fish against infections., Competing Interests: Declaration of competing interest The authors have no conflicting commercial or financial interest in publishing this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute antibodies (AGO-Abs) present as potential biomarkers of the overlap syndrome between NMOSD and other autoimmune diseases. In this paper, we present the case of an adult woman with numbness, tingling, and burning sensations in her arms and subsequent bilateral internuclear ophthalmoplegia. Brain–cervical–thoracic magnetic resonance imaging (MRI) showed T2 hyperintensities in the dorsal brainstem and around the midbrain aqueduct and longitudinally transverse myelitis with homogeneous enhancement on gadolinium-enhanced MRI. The contemporaneous detection of AQP4- and AGO-Abs led to a definite diagnosis of overlap syndrome of NMOSD with AGO-Abs. The patient was treated with immunosuppressive agents, including corticosteroids and immunoglobulins, and achieved remission. This case highlights a novel phenotype of NMOSD with AGO-Abs overlap syndrome, which presents with relapsing brainstem syndrome and longitudinally extensive myelitis with acute severe neurological involvement. The promising prognosis of the disease could serve as a distinct clinical profile. Broad screening for antibodies against central nervous system autoimmune antigens is recommended in suspected patients with limited or atypical clinical manifestations. [ABSTRACT FROM AUTHOR]

Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies to treat Alzheimer's disease are approved, dozens are in the testing phase, and one was withdrawn, and the other halted, likely due to efficacy issues. However, these outcomes should have been evident since these antibodies cannot enter the brain sufficiently due to the blood–brain barrier (BBB) protectant. However, all products can be rejuvenated by binding them with transferrin, preferably as smaller fragments. This model can be tested quickly and at a low cost and should be applied to bapineuzumab, solanezumab, crenezumab, gantenerumab, aducanumab, lecanemab, donanemab, cinpanemab, and gantenerumab, and their fragments. This paper demonstrates that conjugating with transferrin does not alter the binding to brain proteins such as amyloid-β (Aβ) and α-synuclein. We also present a selection of conjugate designs that will allow cleavage upon entering the brain to prevent their exocytosis while keeping the fragments connected to enable optimal binding to proteins. The identified products can be readily tested and returned to patients with the lowest regulatory cost and delays. These engineered antibodies can be manufactured by recombinant engineering, preferably by mRNA technology, as a more affordable solution to meet the dire need to treat neurodegenerative disorders effectively. [ABSTRACT FROM AUTHOR]

Conventional drug production methods are costly. Now, it has been proved that plants are potentially a new source of pharmaceutical proteins, including vaccines, antibodies, blood substitutes, and other therapeutic entities. Unlike mammalian-derived rDNA drugs, plant-derived antibodies, vaccines, and other proteins are particularly advantageous since they are free of mammalian viral vectors and human pathogens. Plants-made therapeutics are cheaper, safer, and can be abundantly produced and easily stored. Recombinant proteins and other metabolites are produced in transgenic plants for industrial or pharmaceutical purposes, which is known as molecular farming. Transgenic plants carry one or more foreign genes transferred through the techniques of transformation. Although initially, these were produced only in a limited number of plant species (e.g., tobacco, petunia, tomato, etc.), later, these could be produced in any plant species, including both dicots and monocots. Transgenic plants resistant to herbicides, insects, viruses, and a host of abiotic stresses have already been produced. These plants have also been produced for improved nutritional quality and are suitable for food processing. The aim of this review paper is to understand plant molecular farming, the advantages and limitations of the process, and biosafety concerns. [ABSTRACT FROM AUTHOR]

The need for performant analytical methodologies to assess mycotoxins is vital, given the negative health impact of these compounds. Biosensors are analytical devices that consist of a biological element for recognizing the analyte and a transducer, which translates the biorecognition event into a signal proportional to the analyte concentration. The biorecognition elements can be enzymes, antibodies, or DNA fragments. The modalities of detection can be optical, electrochemical, thermal, or mass-sensitive. These analytical tools represent viable alternatives to laborious, expensive traditional methods and are characterized by specificity given by the biorecognition element, sensitivity, fast response, portability, multi-modal detection, and the possibility of in situ application. The present paper focuses on a comprehensive view, enriched with a critical, comparative perspective on mycotoxin assay using biosensors. The use of different biorecognition elements and detection modes are discussed comparatively. Nanomaterials with optical and electrochemical features can be exploited in association with a variety of biorecognition elements. Analytical parameters are reviewed along with a broad range of applications. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapeutic synergy represents the cornerstone of the treatment intended for patients with clear-cell renal-cell carcinoma. In most cases, this type of cancer manifests its first symptoms at an advanced stage, thus compromising the use of local therapies such as surgery. This paper aims to describe immune checkpoint proteins, known to suppress an anti-cancer immune response, as well as their inhibitors. Interleukin-2, a cytokine used as a therapeutic option and implicated in the activation of the immune cells, is also discussed. This review further emphasizes the role of the immunotherapeutic combination, not only as an alternative to current treatments devised to counteract the progression and metastasis of ccRCC but also as a valid solution aimed at alleviating the limitations resulting from immune-based monotherapies. Clear-cell Renal-Cell Carcinoma (ccRCC) is the most common type of renal-cell carcinoma (RCC). In many cases, RCC patients manifest the first symptoms during the advanced stage of the disease. For this reason, immunotherapy appears to be one of the dominant treatments to achieve a resolution. In this review, we focus on the presentation of the main immune checkpoint proteins that act as negative regulators of immune responses, such as PD-1, CTLA-4, LAG-3, TIGIT, and TIM-3, and their respective inhibitors. Interleukin-2, another potential component of the treatment of ccRCC patients, has also been covered. The synergy between several immunotherapies is one of the main aspects that unites the conclusions of research in recent years. To date, the combination of several immunotherapies enhances the efficacy of a monotherapy, which often manifests important limitations. Immunotherapy aimed at restoring the anti-cancer immune response in ccRCC, involved in the recognition and elimination of cancer cells, may also be a valid solution for many other types of immunogenic tumors that are diagnosed in the final stages. [ABSTRACT FROM AUTHOR]

The burden of hepatitis E in Southeast Asia is substantial, influenced by its distinct socio-economic and environmental factors, as well as variations in healthcare systems. The aim of this study was to assess the pooled seroprevalence of hepatitis E across countries within the Southeast Asian region by the UN division. The study analyzed 66 papers across PubMed, Web of Science, and Scopus databases, encompassing data from of 44,850 individuals focusing on anti-HEV seroprevalence. The investigation spanned nine countries, excluding Brunei and East Timor due to lack of data. The pooled prevalence of anti-HEV IgG was determined to be 21.03%, with the highest prevalence observed in Myanmar (33.46%) and the lowest in Malaysia (5.93%). IgM prevalence was highest in Indonesia (12.43%) and lowest in Malaysia (0.91%). The study stratified populations into high-risk (farm workers, chronic patients) and low-risk groups (general population, blood donors, pregnant women, hospital patients). It revealed a higher IgG—28.9%, IgM—4.42% prevalence in the former group, while the latter group exhibited figures of 17.86% and 3.15%, respectively, indicating occupational and health-related vulnerabilities to HEV. A temporal analysis (1987–2023), indicated an upward trend in both IgG and IgM prevalence, suggesting an escalating HEV burden. These findings contribute to a better understanding of HEV seroprevalence in Southeast Asia, shedding light on important public health implications and suggesting directions for further research and intervention strategies. Key points Research Question Investigate the seroprevalence of hepatitis E virus (HEV) in Southeast Asian countries focusing on different patterns, timelines, and population cohorts. Findings Sporadic Transmission of IgG and IgM Prevalence: • Pooled anti-HEV IgG prevalence: 21.03% • Pooled anti-HEV IgM prevalence: 3.49% Seroprevalence among specific groups: High-risk group (farm workers and chronic patients): • anti-HEV IgG: 28.9% • anti-HEV IgM: 4.42% Low-risk group (general population, blood donors, pregnant women, hospital patients): • anti-HEV IgG: 17.86% • anti-HEV IgM: 3.15% Temporal Seroprevalence of HEV: Anti-HEV IgG prevalence increased over decades (1987–1999; 2000–2010; 2011–2023): 12.47%, 18.43%, 29.17% as an anti-HEV IgM prevalence: 1.92%, 2.44%, 5.27% Importance Provides a comprehensive overview of HEV seroprevalence in Southeast Asia. Highlights variation in seroprevalence among different population groups. Reveals increasing trend in HEV seroprevalence over the years. Distinguishes between sporadic and epidemic cases for a better understanding of transmission dynamics. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this paper is to review the literature and compile promising and clinically relevant biomarkers in otolaryngology—head & neck surgery not related to autoimmune disorders. Study Design: Narrative review. Methods: PubMed and Google Scholar were queried using combined key words such as "biomarkers" and "otolaryngology." Additional queries were made with combined key words such as "biomarkers" and a particular subspecialty such as "rhinology" or "otology" to maximize yield of relevant titles. Subsequently, specific biomarkers identified, such as "beta-2 transferrin," were used as key words. Relevant titles were reviewed and selected for abstract review. Applicable abstracts were then selected for review of the full text. Results: Biomarkers currently in clinical use within the field of otolaryngology were included in this review. The compiled biomarkers were then detailed individually regarding their molecular characteristics, function, and clinical significance. Conclusions: The number of biomarkers in use in otolaryngology is rapidly expanding representing a new diagnostic modality for our field. This review defines the key biomarkers that are currently or likely to be soon translated into clinical use within the field of otolaryngology. The majority of these biomarkers are in the form of proteins such as beta-2 transferrin, thyroglobulin, and P16. Given their growing impact on diagnosis, management and surveillance of otolaryngologic disorders periodic surveys are needed for education and to guide further advances and applications of otolaryngologic biomarkers. [ABSTRACT FROM AUTHOR]

The rapid development of vaccines is a crucial objective in modern biotechnology and molecular pharmacology. In this context, conducting research to expedite the selection of a potent immunogen is imperative. The candidate vaccine should induce the production of antibodies that can recognize the immunogenic epitopes of the target protein, resembling the ones found in recovered patients. One major challenge in vaccine development is the absence of straightforward and reliable techniques to determine the extent to which the spectrum of antibodies produced after vaccination corresponds to antibodies found after recovery. This paper describes a newly developed method to detect antibodies specific to immunogenic epitopes of the target protein in blood plasma and to compare them with antibody spectra generated post vaccination. Comparing the antibody pool generated in the human body after recovering from an infectious disease with the pool formed through vaccination can become a universal method for screening candidate vaccines. This method will enable the identification of candidate vaccines that can induce the production of antibodies similar to those generated in response to a natural infection. Implementing this approach will facilitate the rapid development of new vaccines, even when faced with a pandemic. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 serology may be helpful to retrospectively understand infection dynamics in specific settings including kindergartens. We assessed SARS-CoV-2 seroprevalence in individuals connected to kindergartens in Berlin, Germany in September 2021. Children, staff, and household members from 12 randomly selected kindergartens were interviewed on COVID-19 history and sociodemographic parameters. Blood samples were collected on filter paper. SARS-CoV-2 anti-S and anti-N antibodies were assessed using Roche Elecsys. We assessed seroprevalence and the proportion of so far unrecognized SARS-CoV-2 infections. We included 277 participants, comprising 48 (17.3%) kindergarten children, 37 (13.4%) staff, and 192 (69.3%) household members. SARS-CoV-2 antibodies were present in 65.0%, and 52.7% of all participants were vaccinated. Evidence of previous infection was observed in 16.7% of kindergarten children, 16.2% of staff, and 10.4% of household members. Undiagnosed infections were observed in 12.5%, 5.4%, and 3.6%, respectively. Preceding infections were associated with facemask neglect. In conclusion, two-thirds of our cohort were SARS-CoV-2 seroreactive in September 2021, largely as a result of vaccination in adults. Kindergarten children showed the highest proportion of non-vaccine-induced seropositivity and an increased proportion of previously unrecognized SARS-CoV-2 infection. Silent infections in pre-school children need to be considered when interpreting SARS-CoV-2 infections in the kindergarten context. [ABSTRACT FROM AUTHOR]

Deep learning models have been shown to accurately predict protein structure from sequence, allowing researchers to explore protein space from the structural viewpoint. In this paper we explore whether "novel" features, such as distinct loop conformations can arise from these predictions despite not being present in the training data. Here we have used ABodyBuilder2, a deep learning antibody structure predictor, to predict the structures of ~1.5M paired antibody sequences. We examined the predicted structures of the canonical CDR loops and found that most of these predictions fall into the already described CDR canonical form structural space. We also found a small number of "new" canonical clusters composed of heterogeneous sequences united by a common sequence motif and loop conformation. Analysis of these novel clusters showed their origins to be either shapes seen in the training data at very low frequency or shapes seen at high frequency but at a shorter sequence length. To evaluate explicitly the ability of ABodyBuilder2 to extrapolate, we retrained several models whilst withholding all antibody structures of a specific CDR loop length or canonical form. These "starved" models showed evidence of generalisation across CDRs of different lengths, but they did not extrapolate to loop conformations which were highly distinct from those present in the training data. However, the models were able to accurately predict a canonical form even if only a very small number of examples of that shape were in the training data. Our results suggest that deep learning protein structure prediction methods are unable to make completely out-of-domain predictions for CDR loops. However, in our analysis we also found that even minimal amounts of data of a structural shape allow the method to recover its original predictive abilities. We have made the ~1.5 M predicted structures used in this study available to download at https://doi.org/10.5281/zenodo.10280181. [ABSTRACT FROM AUTHOR]

BACKGROUND: The coagulation system is critical in controlling hemorrhage. Scientific research has proven that SARS-CoV-2 infection leads to the destabilization of the coagulation process. however, very little is known about coagulopathy in the post-SARS-CoV-2 period. this study aimed to investigate prothrombin changes in relationship with anti-SARS-CoV-2 immunoglobulin g (igg) antibodies titers in donors who recovered from the infection. METHODS: Blood was collected from healthy volunteers, aged 25 to 45, who had recovered from coVid-19 3-6 months ago. all donors were allocated into groups based on anti-sars-coV-2 IgG antibodies titer levels: 0 (N.=20), 10±3 (N.=20), 55±5 (N.=20), 65±5 (N.=20), 75±5 (N.=20), 85±5 (N.=20), 95±5 (N.=20), 125±5 (N.=20), and 175±5 (N.=20) Index (S/C). This paper describes the most significant changes in prothrombin parameters among donor groups, depending on the titers of anti-SARS-CoV-2 IgG antibodies. RESULTS: Prothrombin abnormalities may result in the pathologic conversion of fibrinogen to fibrin. We established the differences in various prothrombin parameters in donor groups with titers of anti-SARS-CoV-2 IgG antibodies ≥10±3 Index (S/C) and compared them to a reference point (donor groups with titer of anti-sars-CoV-2 IgG antibodies 0 index [s/c]). CONCLUSIONS: The research demonstrated significant differences in the compounds and functions of prothrombin-origin molecules at all stages of their actions in the hemostasis system. the observed differences in the composition of these molecules indicate a potential change in the functioning of the hemostatic cascade, which can lead to the emergence of pathological conditions in the body. [ABSTRACT FROM AUTHOR]

Lambert–Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX‐1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56‐year‐old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX‐1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow‐up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long‐term follow‐up and screening for occult SCLC in LEMS patients with positive SOX‐1 antibodies are very important. [ABSTRACT FROM AUTHOR]

This perspective sheds light on the transformative impact of recent computational advancements in the field of protein therapeutics, with a particular focus on the design and development of antibodies. Cutting-edge computational methods have revolutionized our understanding of protein–protein interactions (PPIs), enhancing the efficacy of protein therapeutics in preclinical and clinical settings. Central to these advancements is the application of machine learning and deep learning, which offers unprecedented insights into the intricate mechanisms of PPIs and facilitates precise control over protein functions. Despite these advancements, the complex structural nuances of antibodies pose ongoing challenges in their design and optimization. Our review provides a comprehensive exploration of the latest deep learning approaches, including language models and diffusion techniques, and their role in surmounting these challenges. We also present a critical analysis of these methods, offering insights to drive further progress in this rapidly evolving field. The paper includes practical recommendations for the application of these computational techniques, supplemented with independent benchmark studies. These studies focus on key performance metrics such as accuracy and the ease of program execution, providing a valuable resource for researchers engaged in antibody design and development. Through this detailed perspective, we aim to contribute to the advancement of antibody design, equipping researchers with the tools and knowledge to navigate the complexities of this field. [ABSTRACT FROM AUTHOR]

This paper introduces a novel approach for detecting the SARS-CoV-2 recombinant spike protein combining a label free electrochemical impedimetric immunosensor with the use of purified chicken IgY antibodies. The sensor employs three electrodes and is functionalized with an anti-S IgY antibody, ELISA and immunoblot assays confirmed the positive response of chicken immunized with SARS-CoV2 S antigen. The developed immunosensor is effective in detecting SARS-CoV-2 in nasopharyngeal clinical samples from suspected cases. The key advantage of this biosensor is its remarkable sensitivity, and its capability of detecting very low concentrations of the target analyte, with a detection limit of 5.65 pg/mL. This attribute makes it highly suitable for practical point-of-care (POC) applications, particularly in low analyte count clinical scenarios, without requiring amplification. Furthermore, the biosensor has a wide dynamic range of detection, spanning from 11.56 to 740 ng/mL, which makes it applicable for sample analysis in a typical clinical setting. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a neurodegenerative condition marked by the progressive deterioration of cognitive abilities, memory impairment, and the accumulation of abnormal proteins, specifically beta-amyloid plaques and tau tangles, within the brain. Despite extensive research efforts, Alzheimer's disease remains without a cure, presenting a significant global healthcare challenge. Recently, there has been an increased focus on antibody-based treatments as a potentially effective method for dealing with Alzheimer's disease. This paper offers a comprehensive overview of the current status of research on antibody-based molecules as therapies for Alzheimer's disease. We will briefly mention their mechanisms of action, therapeutic efficacy, and safety profiles while addressing the challenges and limitations encountered during their development. We also highlight some crucial considerations in antibody-based treatment development, including patient selection criteria, dosing regimens, or safety concerns. In conclusion, antibody-based therapies present a hopeful outlook for addressing Alzheimer's disease. While challenges remain, the accumulating evidence suggests that these therapies may offer substantial promise in ameliorating or preventing the progression of this debilitating condition, thus potentially enhancing the quality of life for the millions of individuals and families affected by Alzheimer's disease worldwide. [ABSTRACT FROM AUTHOR]

Artificial immune systems (AIS), as nature-inspired algorithms, have been developed to solve various types of problems, ranging from machine learning to optimization. This paper proposes a novel hybrid model of AIS that incorporates cellular automata (CA), known as the cellular automata-based artificial immune system (CaAIS), specifically designed for dynamic optimization problems where the environment changes over time. In the proposed model, antibodies, representing nominal solutions, are distributed across a cellular grid that corresponds to the search space. These antibodies generate hyper-mutation clones at different times by interacting with neighboring cells in parallel, thereby producing different solutions. Through local interactions between neighboring cells, near-best parameters and near-optimal solutions are propagated throughout the search space. Iteratively, in each cell and in parallel, the most effective antibodies are retained as memory. In contrast, weak antibodies are removed and replaced with new antibodies until stopping criteria are met. The CaAIS combines cellular automata computational power with AIS optimization capability. To evaluate the CaAIS performance, several experiments have been conducted on the Moving Peaks Benchmark. These experiments consider different configurations such as neighborhood size and re-randomization of antibodies. The simulation results statistically demonstrate the superiority of the CaAIS over other artificial immune system algorithms in most cases, particularly in dynamic environments. [ABSTRACT FROM AUTHOR]

Objective: To determine age-related risk factors for chronic rhinosinusitis (CRS) with asthma. Methods: Data were obtained from a national survey of non-hospitalized civilians conducted by the Korean Center for Disease Control and Prevention. CRS diagnosis was based on the guidelines of the European Position Paper on Rhinosinusitis and Nasal Polyps 2020. Asthma was judged based on whether the patient had been diagnosed with asthma in the past. Of the 45,811 survey participants, 26,335 were included in the cross-sectional study. Participants included in the study were divided into the control, CRS, and CRS with asthma groups. Age-related risk factors were analyzed in patients aged < 60 or > 60 years. Univariate logistic analyses were performed to evaluate the relationship between groups. Risk factors included age, sex, household income, residence, education level, occupation, and body mass index (BMI). Results: Education level (Odds Ratio [OR]: 0.342, P =.0003), BMI (OR: 1.09, P =.0082), and total IgE (TIgE) levels (OR: 5.582, P =.003) were significantly different between the control and the CRS with asthma group. Education level (OR: 0.478, P =.0016) and TIgE levels (OR: 4, P =.0218) were significantly different between the CRS and CRS with asthma groups under 60 years of age. BMI (OR: 1.087, P =.0443; OR: 1.104, P =.0224) showed a significant difference between all three groups with age > 60 years. Conclusion: Progression to CRS with asthma is influenced by education level, occupation, and TIgE levels in patients under 60 years of age. BMI was the only influencing factor associated with the progression to CRS with asthma in those aged > 60 years. [ABSTRACT FROM AUTHOR]

Dye-encoded bead-based assays are widely used for diagnostics. Multiple bead populations are required for multiplexing and can be produced using different dye colors, labeling levels, or combinations of dye ratios. Ready-to-use multiplex bead populations restrict users to specific targets, are costly, or require specialized instrumentation. In-house methods produce few bead plexes or require many fine-tuning steps. To expand bead encoding strategies, we present a simple, safe, and cost-effective bench-top system for generating bead populations using photobleaching. By photobleaching commercially available dye-encoded magnetic beads for different durations, we produce three times as many differentiable bead populations on flow cytometry from a single dye color. Our photobleaching system uses a high-power LED module connected to a light concentrator and a heat sink. The beads are photobleached in solution homogeneously by constant mixing. We demonstrate this photobleaching method can be utilized for cross-testing antibodies, which is the first step in developing immunoassays. The assay uses multiple photobleached encoded beads conjugated with capture antibodies to test many binding pairs simultaneously. To further expand the number of antibodies that can be tested at once, several antibodies were conjugated to the same bead, forming a pooled assay. Our assay predicts the performance of antibody pairs used in ultrasensitive Simoa assays, narrowing the number of cross-tested pairs that need to be tested by at least two-thirds and, therefore, providing a rapid alternative for an initial antibody pair screening. The photobleaching system can be utilized for other applications, such as multiplexing, and for photobleaching other particles in solution. [ABSTRACT FROM AUTHOR]

In vitro display technologies such as yeast display have been instrumental in developing the selection of new antibodies, antibody fragments or nanobodies that bind to a specific target, with affinity towards the target being the main factor that influences selection outcome. However, the roles of mechanical forces are being increasingly recognized as a crucial factor in the regulation and activation of effector cell function. It would thus be of interest to isolate binders behaving optimally under the influence of mechanical forces. We developed a microfluidic assay allowing the selection of yeast displaying nanobodies through antigen-specific immobilization on a surface under controlled hydrodynamic flow. This approach enabled enrichment of model yeast mixtures using tunable antigen density and applied force. This new force-based selection method opens the possibility of selecting binders by relying on both their affinity and force resistance, with implications for the design of more efficient immunotherapeutics. [ABSTRACT FROM AUTHOR]

For many years, space human factors research has focused on the impact of microgravity on human physiology and the health risks astronauts face during space flights of various durations. Our review paper reveals that microgravity leads to both reversible and non-reversible effects on astronauts' oral health. In addition to oral health concerns, astronauts often experience muscle degeneration during space missions, which is closely tied to bone loss. Despite our knowledge of high bone resorption and rapid mineral and calcium loss in microgravity, the exact underlying mechanisms remain unclear. However, to fully understand these processes and develop effective strategies to counteract the consequences of microgravity, more research is needed. This includes a deeper exploration of how these molecules and other biomarkers work, identification of early mechanotransduction sensors, and a comprehensive understanding of the physiological effects of weightlessness. Current solutions primarily involve administering antioxidants, regular exercise, and appropriate nutrition. Additionally, innovative approaches such as experimental drug therapies using anti -myostatin antibodies and r-irisin have gained attention. Further large-scale, long-term studies are required to understand the effects of microgravity on the oral cavity and prevent its adverse consequences. • Impact of Microgravity on Dental Health: Discuss the physiological changes experienced by astronauts in microgravity environments, including fluid redistribution, decreased mechanical loading, and altered bone metabolism, and their implications for oral health. • Weight-Bearing vs. Non-Weight-Bearing Bones: Examines the relationship between microgravity and bone loss, with a focus on distinguishing its effects on weight-bearing and non-weight-bearing bones. • Comprehensive Impact Assessment: Calls for comprehensive research on how microgravity affects various bones in both animals and humans, including analyses of bone structure, density, and strength. • Bone Loss and Tooth Mobility: Examine how microgravity-induced bone loss affects the integrity of the jawbone, leading to increased tooth mobility and potential dental complications such as loosened crowns, dental implants, or even tooth loss. • Differential Recovery: Investigates how weight-bearing and non-weight-bearing bones recover following bone loss in microgravity conditions and the underlying mechanisms at play. • Addressing Inconsistencies: Highlights the need to resolve inconsistencies in existing literature regarding the influence of microgravity on osteogenic proliferation and differentiation. • Osteocytes and Osteoclasts in Microgravity: Emphasises the importance of understanding the roles of osteocytes and osteoclasts in microgravity-induced bone loss to identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Mucosal antibodies in the upper respiratory tract are the earliest and most critical responders to prevent respiratory infections, providing an indication for the rapid evaluation of immune protection. Here, we report a microfluidic particle counter that directly visualizes mucosal antibody levels in nasal mucus. The mucosal anti-SARS-CoV-2 spike receptor binding domain (RBD) antibodies in nasal secretions first react with magnetic microparticles (MMPs) and polystyrene microparticles (PMPs) that are surface-modified to form a "MMPs-anti-spike RBD IgG-PMPs" complex when RBD is present. After magnetic separation and loading into the microfluidic particle counter, the free PMPs, which are reduced with increasing anti-spike RBD IgG antibody levels, are trapped by a microfluidic particle dam and accumulate in the trapping channel. A sensitive mode [limit of detection (LOD): 14.0 ng mL−1; sample-to-answer time: 70 min] and an equipment-free rapid mode (LOD: 37.4 ng mL−1; sample-to-answer time: 20 min) were achieved. Eighty-seven nasal secretion (NS) samples from vaccinees were analyzed using our microfluidic particle counter, and the results closely resemble those of the gold-standard enzyme-linked immunosorbent assay (ELISA). The analysis shows that higher antibody levels were found in convalescent volunteers compared to noninfected volunteers. Together, we demonstrate a rapid kit that directly indicates immune status, which can guide vaccine strategy for individuals and the government. [ABSTRACT FROM AUTHOR]

Rare antinuclear antibody (ANA) pattern recognition has been a widely applied technology for routine ANA screening in clinical laboratories. In recent years, the application of deep learning methods in recognizing ANA patterns has witnessed remarkable advancements. However, the majority of studies in this field have primarily focused on the classification of the most common ANA patterns, while another subset has concentrated on the detection of mitotic metaphase cells. To date, no prior research has been specifically dedicated to the identification of rare ANA patterns. In the present paper, we introduce a novel attention-based enhancement framework, which was designed for the recognition of rare ANA patterns in ANA-indirect immunofluorescence images. More specifically, we selected the algorithm with the best performance as our target detection network by conducting comparative experiments. We then further developed and enhanced the chosen algorithm through a series of optimizations. Then, attention mechanism was introduced to facilitate neural networks in expediting the learning process, extracting more essential and distinctive features for the target features that belong to the specific patterns. The proposed approach has helped to obtained high precision rate of 86.40%, 82.75% recall, 84.24% F1 score and 84.64% mean average precision for a 9-category rare ANA pattern detection task on our dataset. Finally, we evaluated the potential of the model as medical technologist assistant and observed that the technologist's performance improved after referring to the results of the model prediction. These promising results highlighted its potential as an efficient and reliable tool to assist medical technologists in their clinical practice. [ABSTRACT FROM AUTHOR]

Specific and rapid detection of live Staphylococcus aureus (S.A) in environmental and food samples is critically important for protecting human health. In order to fulfill this purpose, two kinds of novel egg yolk antibody (IgY) immobilized immunomagnetic beads (IMBs; mSiO2-IgY and mMOF-IgY), with core–shell mSiO2 and mMOF as substrate, were prepared for selectively enriching S.A from samples. Furthermore, the IMBs with captured S.A were collected and re-dissolved in 0.5 mL PBS. After that, a cotton swab coated with sodium dodecylsulfate (SDS) was put in the solution to lyse S.A cells and emit ATP bioluminescence of the luciferin/luciferase system. Finally, a portable bioluminescence detector was used for quantification of ATP corresponding to S.A concentration. The results demonstrated that mMOF-IgY can enrich more S.A than mSiO2-IgY and emit a stronger signal. The reasons may be due to the higher immobilization amount of IgY on the IMBs. Under optimal conditions, the calibration line of S.A concentration was 10–105 CFU mL−1 by mMOF-IgY within 30 min. The low detection limit of S.A was 3 CFU mL−1. The results demonstrated that the assay takes much shorter time than plate counting. Its portability and excellent detection capability are suitable for rapid monitoring of specific pathogens in foods. [ABSTRACT FROM AUTHOR]

The effects of immunotherapeutics on interactions between immune and cancer cells are modulated by multiple components in the tumour microenvironment (TME), including endothelium and tumour stroma, which provide both a physical barrier and immunosuppressive stimuli. Herein, we report a recirculating chip to enable continuous immune cell recirculation through a microfluidic cell array to include these crucial players. This system consists of a three-layered cell array (μFCA) spatially emulating the TME, with tailored fluidic circuits establishing T cell recirculation. This platform enables the study of dynamics among the TME, immune cells in a circulatory system and cancer cell responses thereof. Through this system, we found that tumour endothelium hindered T cell infiltration into the reconstructed breast cancer tumour compartment. This negative effect was alleviated when treated with anti-human PD-L1 (programmed cell death ligand 1) antibody. Another key stromal component – cancer associated fibroblasts – attenuated T cell infiltration, compared against normal fibroblasts, and led to reduced apoptotic activity in cancer cells. These results confirm the capability of our tumour-on-a-chip system in identifying some key axes to target in overcoming barriers to immunotherapy by recapitulating immune cell interactions with the reconstructed TME. Our results also attest to the feasibility of scaling up this system for high-throughput cancer immunotherapeutic screening. [ABSTRACT FROM AUTHOR]

An intrusion detection method using rough-fuzzy set and parallel quantum genetic algorithm (RFS-QGAID) is proposed in this paper. The RFS-QGAID is applied to solve the serious problems of determining the optimal antibodies subsets used to detect an anomaly. To obtain a simplified antibodies collection for high dimensional Log data sets, RFS is applied to delete the redundant antibody features and obtain the optimal antibodies features combination. Then, the optimal attitudes are entered into the QGA classifier for learning and training in the following stage. At last, the detected Log antigens are fed into RFS-QGAID, and we can classify the intrusion types. With RFS-QGAID, we give the simulations, the results on real Log data sets show that: the higher detection accuracy of RFS-QGAID is higher detection accuracy, but the false negative rate is lower for small samples sets, the adaptive performance is higher than other detection algorithms. [ABSTRACT FROM AUTHOR]

Bronchiectasis is a chronic disease syndrome manifested by a productive cough, subsequent to structural changes in the bronchial walls resulting from bacterial infection and leading to the retention of secretions. In some patients, the cause of bronchiectasis is chronic diseases, such as cystic fibrosis, ciliary dyskinesia, α1-antitrypsin deficiency, or congenital immune disorders. However, there are cases of bronchiectasis without underlying chronic disease, e.g. as a consequence of severe lower respiratory tract infection (bacterial or viral) or local airway obstruction, caused by foreign body aspiration or external pressure. Currently, it is believed that in some patients bronchial deformations may be reversible with a sufficiently quick diagnosis and implementation of treatment. The paper presents the cases of 3 children in whom the resolution of dilated lesions was confirmed by computed tomography. [ABSTRACT FROM AUTHOR]