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Angel Moral,1 Victoria Moreno,2 Francisco Girón,3 David El-Qutob,4 José D Moure,5 Manuel Alcántara,6 Antonia Padial,7 Alberto G Oehling,8 Carmen Millán,9 Fernando de la Torre10 1Allergy Service, Hospital Virgen del Valle, Toledo, 2Allergy Service, Hospital Blanca Paloma, Huelva, 3Consulta Privada, Granada, 4Allergy Service, Clínica Atenea, Castellón, 5Pediatric Department, Complejo Hospitalario Universitario de Santiago, A Coruña, 6Allergy Service, Complejo Hospitalario de Jaén, Jaén, 7Allergy Service, Hospital Infanta Sofía, Madrid, 8Centro de Alergia y Asma Balear, Mallorca, 9Consulta Privada, Cádiz, 10ALK-Abelló, SA, Madrid, Spain Background: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy.Patients and methods: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months.Results: The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847).Conclusion: In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. Keywords: sublingual immunotherapy, tolerability, allergic rhinitis, Olea europaea, grass, Dermatophagoides pteronyssinus

Members of the SOX (SRY-related HMG box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular modelsBy providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

Background: The population structure of crop pathogens such as Puccinia striiformis f. sp. tritici (Pst), the cause of wheat stripe rust, is of interest to researchers looking to understand these pathogens on a molecular level as well as those with an applied focus such as disease epidemiology. Cereal rusts can reproduce sexually or asexually, and the emergence of novel lineages has the potential to cause serious epidemics such as the one caused by the 'Warrior' lineage in Europe. In a global context, Pst lineages in Canada were not well-characterized and the origin of foreign incursions was not known. Additionally, while some Pst mating type genes have been identified in published genomes, there has been no rigorous assessment of mating type diversity and distribution across the species., Results: We used a whole-genome/transcriptome sequencing approach for the Canadian Pst population to identify lineages in their global context and evidence tracing foreign incursions. More importantly: for the first time ever, we identified nine alleles of the homeodomain mating type locus in the worldwide Pst population and show that previously identified lineages exhibit a single pair of these alleles. Consistently with the literature, we find only two pheromone receptor mating type alleles. We show that the recent population shift from the 'PstS1' lineage to the 'PstS1-related' lineage is also associated with the introduction of a novel mating type allele (Pst-b3-HD) to the Canadian population. We also show evidence for high levels of mating type diversity in samples associated with the Himalayan center of diversity for Pst, including a single Canadian race previously identified as 'PstPr' (probable recombinant) which we identify as a foreign incursion, most closely related to isolates sampled from China circa 2015., Conclusions: These data describe a recent shift in the population of Canadian Pst field isolates and characterize homeodomain-locus mating type alleles in the global Pst population which can now be utilized in testing several research questions and hypotheses around sexuality and hybridization in rust fungi., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The SOX transcription factor family is pivotal in controlling aspects of development. To identify genotype-phenotype relationships of SOX proteins, we performed a non-biased study of SOX using 1890 open-reading frame and 6667 amino acid sequences in combination with structural dynamics to interpret 3999 gnomAD, 485 ClinVar, 1174 Geno2MP, and 4313 COSMIC human variants. We identified, within the HMG (High Mobility Group)- box, twenty-seven amino acids with changes in multiple SOX proteins annotated to clinical pathologies. These sites were screened through Geno2MP medical phenotypes, revealing novel SOX15 R104G associated with musculature abnormality and SOX8 R159G with intellectual disability. Within gnomAD, SOX18 E137K (rs201931544), found within the HMG box of ~0.8% of Latinx individuals, is associated with seizures and neurological complications, potentially through blood-brain barrier alterations. A total of 56 highly conserved variants were found at sites outside the HMG-box, including several within the SOX2 HMG-box-flanking region with neurological associations, several in the SOX9 dimerization region associated with Campomelic Dysplasia, SOX14 K88R (rs199932938) flanking the HMG box associated with cardiovascular complications within European populations, and SOX7 A379V (rs143587868) within an SOXF conserved far C-terminal domain heterozygous in 0.716% of African individuals with associated eye phenotypes. This SOX data compilation builds a robust genotype-to-phenotype association for a gene family through more robust ortholog data integration.

Purpose of Review: The purpose of this review is to provide an update on the intriguing relationships between allergies, allergen immunotherapy, cancer, and immune disorders. Allergic diseases and cancer are increasing in incidence and prevalence and a potential relationship, or not, between these diseases have been suggested for many years., Recent Findings: Recent findings suggest that there may be some causative effects between certain types of cancer and allergic diseases, as described in the text. Some types of cancer may be more linked to the presence of an allergic disease, than others. However, epigenetic factors, such as tobacco smoke alcohol and toxic substances should also be taken into consideration., Summary: The association between allergy and cancer is complex and depends on the specific allergy and the specific organ under consideration. Regarding pancreatic cancer, colorectal cancer (CRC), and glioma, all types of allergies were shown to be a protective factor. Conversely, asthma is a risk factor for lung cancer as is atopic dermatitis for skin cancer. Despite extensive research, no definite relationship has been determined, and no clear relationship, either positive or negative, to allergies can be observed. These results should be corroborated with large epidemiological well designed prospective studies due to some weaknesses in the previous investigations., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Polymerized allergens conjugated to non-oxidized mannan (PM-allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM-allergoids are readily taken up by DCs and induce Treg cells. This first-in-human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM-allergoid (PM-HDM) administered subcutaneously (SC) or sublingually (SL)., Methods: In a randomized, double-blind, double-dummy, placebo-controlled trial, 196 subjects received placebo or PM-HDM at 500, 1000, 3000, or 5000 mannan-conjugated therapeutic units (mTU)/mL in 9-arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers., Results: No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups., Conclusions: PM-HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml., (© 2022 Inmunotek SL. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Immune-mediated inflammatory diseases (IMID) predispose to a higher infection risk by modifying the host's immune response, which acts as a key factor in SARS-CoV-2 infection resolution. Recent publications show that IMID patients and its treatments do not worsen the outcome of SARS-CoV-2 infection., Objectives: To describe the clinical characteristics and outcomes of patients with IMID who required hospital admission due to SARS-CoV-2 infection. Secondly, to compare clinical characteristics and outcomes between patients who required hospital admission due to SARS-CoV-2 infection with IMID and those who were not affected., Methods: We performed an observational retrospective cohort study, including admitted patients with suspected SARS-CoV-2 infection, treated according to medical criteria and local protocols based on the best available scientific evidence. Clinical data were collected from their electronical clinical history. Statistical analysis determined the differences in the characteristics and clinical outcome of the infection in IMID patients., Results: Of a total number of 612 revised patients, 23 had an IMID and 9 of them were positive for the SARS-CoV-2 infection. We did not observe a correlation between these two disorders. There was a higher frequency of obesity and cardiovascular disease among IMID patients, but without statistical significance. The clinical outcomes were no different between hospitalized IMID and non IMID patients., Conclusion: IMID and its treatments do not determine the outcome of patients admitted with SARS-CoV-2 infection., (Copyright © 2021 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Long-distance migration and host adaptation by transboundary plant pathogens often brings detrimental effects to important agroecosystems. Efficient surveillance as a basis for responding to the dynamics of such pathogens is often hampered by a lack of information on incursion origin, evolutionary pathways and the genetic basis of rapidly evolving virulence across larger timescales. Here, we studied these genetic features by using historical isolates of the obligate biotrophic pathogen Puccinia striiformis f. sp. tritici (Pst), which causes one of the most widespread and devastating diseases, stripe (yellow) rust, of wheat. Through a combination of genotypic, phenotypic and genomic analyses, we assigned eight Pst isolates representing putative exotic Pst incursions into Australia to four previously defined genetic groups, PstS0, PstS1, PstS10 and PstS13. We showed that isolates of an additional incursion of P. striiformis, known locally as P. striiformis f. sp. pseudo-hordei, had a new and unique multilocus SSR genotype (MLG). We provide results of overall genomic variation of representative Pst isolates from each genetic group by comparative genomic analyses. We showed that isolates within the PstS1 and PstS13 genetic groups are most distinct at the whole-genome variant level from isolates belonging to genetic group PstS0, whereas the isolate from the PstS10 genetic group is intermediate. We further explored variable gene content, including putative effectors, representing both shared but also unique genetic changes that have occurred following introduction, some of which may additionally account for local adaptation of these isolates to triticale. Our genotypic and genomic data revealed new genetic insights into the evolution of diverse phenotypes of rust pathogens following incursion into a geographically isolated continental region., (© 2021 John Wiley & Sons Ltd.)

It is well-known that a correct diagnosis is necessary for effective treatment. In the case of allergic rhinitis due to mites, imprecise diagnosis with effective but improvable methods means that in many cases an optimal result is not reached in patients. The diagnosis of allergic rhinitis due to mite sensitization have to require more homogeneously reproducible diagnostic tests that try to encompass many more of the protein antigens contained in them. With the few proteins that the problem has usually focused on, there is no they would cover many of the clinically relevant allergens in a large proportion of patients. In this mini-review we try to highlight the importance of having good allergenic sources and briefly gather information on various allergenic proteins included in mites that could be clinically relevant. All this to try to get closer to a more accurate diagnosis. We are also talking about two diagnostic tools that are clearly out of use and that should be promoted in the consultations to obtain an even greater and better outcome in patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 González-Pérez, El-Qutob, Letrán and Matheu.)

Multiseptated gallbladder (MSG) (also known as "Honeycomb gallbladder") is a rare condition that was first described by Knetsch in 1952, and there are around 150 cases described over the world. MSG has been described as a congenital anomaly in most of the cases and as acquired in a few. Moreover, the phenomenon was described with a variety of different symptoms and management. The aim of this article is to have better understanding of this condition and management approach. We are reporting a 4-year-old girl, who presented to Sidra Medicine, Qatar with MSG. We have also included 97 cases for review and analysis. The median age of presentation of the condition was 27 years but may present in neonates and in the elderly, while gender was not a risk factor. Abdominal pain is the most common presenting symptom, but it can present without symptoms. Certain congenital anomalies were detected in the pancreaticobiliary system in few patients with MSG. Medical treatment was reported in eight symptomatic patients, four of whom failed therapy. Cholecystectomy was performed in 40 patients, which resulted in resolutions of symptoms in 13 of them. Based on the available literature, congenital MSG is probably due to in-pouching of gallbladder wall to its own cavity forming septa containing muscular fibers. MSG can be diagnosed solely via imaging, and ultrasound appears to be an effective and feasible mode of diagnosis. Medical treatment efficacy is not well-known, but cholecystectomy has resulted in complete resolution in symptomatic patients., (© 2021 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Several descriptive cohort studies of patients affected by COVID-19 have been published., Objective: To describe the characteristics of patients with SARS-CoV-2 infection who were admitted to Hospital Universitario la Plana, Castellón, Spain., Methods: Retrospective, observational cohort study that included 18-year-old or older patients who were consecutively admitted with SARS-CoV2 confirmed infection. Demographic characteristics, comorbidities, clinical symptoms, laboratory results and radiological tests are described., Results: The study included 255 patients with a mean age of 70 years; 54.9 % were males. Most common comorbidities were high blood pressure (58 %), dyslipidemia (42.4 %), diabetes (25.5 %) and obesity (24.3 %). Median number of days from the onset of clinical symptoms prior to hospital admission was seven. Most common manifestations prior to admission were fever (74.5 %), dry cough (61.2 %), malaise (51.8 %) and dyspnea (51.0 %); 19 patients (7.4 %) were admitted to the intensive care unit, where mortality was 50 %; overall mortality was 16.9 %., Conclusions: Our cohort reflects similar characteristics to those of other European series. Mortality was lower than that in similar studies., (Copyright: © 2020 Permanyer.)

SARS-CoV-2 (COVID-19) has infected millions of people worldwide, with lethality in hundreds of thousands. The rapid publication of information, both regarding the clinical course and the viral biology, has yielded incredible knowledge of the virus. In this review, we address the insights gained for the SARS-CoV-2 proteome, which we have integrated into the Viral Integrated Structural Evolution Dynamic Database, a publicly available resource. Integrating evolutionary, structural, and interaction data with human proteins, we present how the SARS-CoV-2 proteome interacts with human disorders and risk factors ranging from cytokine storm, hyperferritinemic septic, coagulopathic, cardiac, immune, and rare disease-based genetics. The most noteworthy human genetic potential of SARS-CoV-2 is that of the nucleocapsid protein, where it is known to contribute to the inhibition of the biological process known as nonsense-mediated decay. This inhibition has the potential to not only regulate about 10% of all biological transcripts through altered ribosomal biology but also associate with viral-induced genetics, where suppressed human variants are activated to drive dominant, negative outcomes within cells. As we understand more of the dynamic and complex biological pathways that the proteome of SARS-CoV-2 utilizes for entry into cells, for replication, and for release from human cells, we can understand more risk factors for severe/lethal outcomes in patients and novel pharmaceutical interventions that may mitigate future pandemics.

Pathogen avirulence (Avr) effectors interplay with corresponding plant resistance (R) proteins and activate robust plant immune responses. Although the expression pattern of Avr genes has been tied to their functions for a long time, it is still not clear how Avr gene expression patterns impact plant-microbe interactions. Here, we selected PsAvr3b, which shows a typical effector gene expression pattern from a soybean root pathogen Phytophthora sojae. To modulate gene expression, we engineered PsAvr3b promoter sequences by in situ substitution with promoter sequences from Actin (constitutive expression), PsXEG1 (early expression), and PsNLP1 (later expression) using the CRISPR/Cas9. PsAvr3b driven by different promoters resulted in distinct expression levels across all the tested infection time points. Importantly, those mutants with low PsAvr3b expression successfully colonized soybean plants carrying the cognate R gene Rps3b. To dissect the difference in plant responses to the PsAvr3b expression level, we conducted RNA-sequencing of different infection samples at 24 h postinfection and found soybean immune genes, including a few previously unknown genes that are associated with resistance. Our study highlights that fine-tuning in Avr gene expression impacts the compatibility of plant disease and provides clues to improve crop resistance in disease control management., (© 2019 Institute of Botany, Chinese Academy of Sciences.)

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is an important disease in Canada. The worldwide genetic structure of Pst populations have been characterized, excluding Canada. Here, we elucidated the genetic structure of the western Canadian Pst population using molecular markers, revealing the presence of four divergent lineages with predominantly clonal structure. In the worldwide context, two previously reported lineages were identified: PstS0 (22%), representing an old Northwestern-European and PstS1 (35%), an invasive warm-temperature adapted. Additionally, two new, unreported lineages, PstPr (9%) and PstS1-related (35%), were detected, which produced more telia than other lineages and had double the number of unique recombination events. The PstPr was a recent invasion, and likely evolved in a diverse, recombinant population as it was closely related to the PstS5, PstS7/Warrior, PstS8/Kranich, and PstS9 lineages originating from sexually recombining populations in the centre of diversity. The DNA methylation analysis revealed DNA-methyltransferase1-homologs, providing compelling evidence for epigenetic regulation and as a first report, an average of ∼5%, 5hmC in the Puccinia epigenome merits further investigation. The divergent lineages in the Canadian Pst population with the potential for genetic recombination, as well as epigenetic regulation needs consideration in the context of pathogen adaptation and management., (© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: Despite adequate adherence and completion of anti-asthmatic treatment, many patients remain poorly controlled or uncontrolled. Asthma management is based on the use of medication to reverse the bronchial obstruction and eliminate the airway inflammation. New drug development is expected in the future as a consequence of discoveries in the pathophysiology and mechanisms of asthma. Currently, a good and effective set of treatments is available for these diseases. However, the search for new treatment modalities to improve the currently available is especially important for those patients unresponsive to current therapy., Objective: In this review, we summarize new anti-cytokines therapies, anti-leucotrienes molecules, immunomodulatory and anti-inflammatory agents, researched for treatment of asthma., Method: Database patents were used for searching new patents from 2015 and from the beginning of 2016 about treatment of asthma., Conclusion: Pharmacogenomic point of view is now being considered by most major pharmaceutical companies as line of investigation without end in the nearest horizon. Pharmacogenomics has the potential to notably improve the safety and effectiveness of medications.

Ragweeds are flowering plants in the genus Ambrosia in the aster family, Asteraceae. They are distributed in the tropical and subtropical regions of the New World, especially North America. Short ragweed is the most important weed. The ragweed flowering occurs late in the summer and the pollination period extends from the beginning of August to mid-October. Sensitization to ragweed pollen has risen in United States in the past decade and probably worldwide. The major allergenic compound in the pollen has been identified as Amb a 1. Ragweed allergies usually cause allergic rhinitis and asthma. Ragweed allergic patients may show signs of oral allergy syndrome caused by crossreactivity between ragweed allergens and food allergens. In the present article, an update about vaccine development and new knowledge for ragweed allergy is exhaustively revised.

Mucosal immunity is the first line of defence of the organism against several pathogens and, at the same time, it is of critical importance in allergic diseases. Oral vaccines have been developed with the aim of enhancing the immune response to pathogens and for the treatment of allergic diseases. One of the major issues concerning oral vaccines is the use of oral adjuvants which could facilitate antigen presentation with the consequent induction of an effective immune response. The present review consists of an analysis, point by point, of the different patents that have been presented in the last 12 months in the different agencies: European (EP), US, and World Intellectual Property Organization (WIPO) and a general analysis of the future developments and trends in this emerging area.

Allergen specific immunotherapy (ASIT) and environmental control are the only etiologic treatments of allergic rhino-conjunctivitis, asthma and atopic dermatitis. The clinical benefit of ASIT relies on the selection of the patients and the identification and administration of the allergen, or allergens. Different routes of administration have been investigated, including subcutaneous, intradermal, epicutaneous, sublingual, inhaled, or intra-lymphatic. While subcutaneous and sublingual allergen specific immunotherapy may require from 3 to 5 years of treatment, clinical efficacy with intra-lymphatic treatment can be achieved after 3 injections. The most severe side effect of ASIT is anaphylaxis. Novel approaches are being investigated to reduce the allergenicity of immunotherapy vaccines, maintaining immunogenicity. Peptide immunotherapy has been directed mostly against autoimmune diseases, but the use of synthetic peptides for ASIT is a promising field in basic science, applied immunology and in clinical development. Short synthetic peptides bear allergen-specific CD4 T-cell epitopes which induce tolerance by stimulating regulatory (Treg) and Th1 cells. In the present patent review, we describe new trends in allergen immunotherapy using peptides, which, from a clinical point of view, are promising.

The aim of this work was to map and identify the Phytophthora sojae Avr1c gene. Progeny from a cross of P. sojae strains ACR10×P7076 were tested for virulence on plants carrying Rps1c. Results indicate that avirulence segregates as a dominant trait. We mapped the Avr1c locus by performing whole genome re-sequencing of composite libraries created from pooled samples. Sequence reads from avirulent (Pool1) and virulent (Pool2) samples were aligned to the reference genome and single nucleotide polymorphisms (SNP) were identified for each pool. High quality SNPs were filtered to select for positions where SNP frequency was close to expected values for each pool. Only three SNP positions fit all requirements, and these occurred in close proximity. Additional DNA markers were developed and scored in the F₂ progeny, producing a fine genetic map that places Avr1c within the Avr1a gene cluster. Transient expression of Avr1c or Avr1a triggers cell death on Rps1c plants, but Avr1c does not trigger cell death on Rps1a plants. Sequence comparisons show that the RXLR effector genes Avr1c and Avr1a are closely related paralogs. Gain of virulence on Rps1c in P. sojae strain P7076 is achieved by gene deletion, but in most other strains this is accomplished by gene silencing. This work provides practical tools for crop breeding and diagnostics, as the Rps1c gene is widely deployed in commercial soybean cultivars.

Allergic diseases are a major health problem worldwide. The therapeutic approaches to treat allergic rhinitis (AR) and allergic asthma (AA) fall in three major categories. The first step is allergen avoidance, or reduction of exposure to the offending allergen(s). The second and most widely used therapeutic practice is the prescription of relevant medication to reduce symptoms. The third therapeutic element is specific allergy vaccination, also known as allergen specific immunotherapy. Allergen-specific immunotherapy (SIT) is the only etiologic treatment of allergic disorders that can alter the natural course of the disease. In this review, recent advances in immunotherapy and relevant patents are presented. General vaccine modifications could be applied for any type of allergen. New specific modifications in allergic vaccines have been developed for a variety of allergies such as house dust mites, horse, cat, parvalbumin and from birch, ragweed and parietaria pollen.