Summary
Cytotoxic T lymphocyte antigen 4 (CTLA‐4) haploinsufficiency (CHAI) and lipopolysaccharide‐responsive beige‐like anchor (LRBA) deficiency (LATAIE) are newly identified inborn errors of ...immunity with shared molecular pathomechanisms and clinical manifestations. In this review, we aimed to provide differential comparisons regarding demographic, clinical, immunological and molecular characteristics between these two similar conditions. A literature search was conducted in PubMed, Web of Science and Scopus databases and included studies were systematically evaluated. Overall, 434 (222 CHAI and 212 LATAIE) patients were found in 101 eligible studies. The CHAI patients were mainly reported from North America and western Europe, while LATAIE patients were predominantly from Asian countries. In CHAI, positive familial history (P < 0·001) and in LATAIE, consanguineous parents (P < 0·001) were more common. In CHAI patients the rates of granulomas (P < 0·001), malignancies (P = 0·001), atopy (P = 0·001), cutaneous disorders (P < 0·001) and neurological (P = 0·002) disorders were higher, while LATAIE patients were more commonly complicated with life‐threatening infections (P = 0·002), pneumonia (P = 0·006), ear, nose and throat disorders (P < 0·001), organomegaly (P = 0·023), autoimmune enteropathy (P = 0·038) and growth failure (P < 0·001). Normal lymphocyte subsets and immunoglobulins except low serum levels of CD9+ B cells (14·0 versus 38·4%, P < 0·001), natural killer (NK) cells (21 versus 41·1%, P < 0·001), immunoglobulin (Ig)G (46·9 versus 41·1%, P = 0·291) and IgA (54·5 versus 44·7%, P = 0·076) were found in the majority of CHAI and LATAIE patients, respectively. The most frequent biological immunosuppressive agents prescribed for CHAI and LATAIE patients were rituximab and abatacept, respectively. Further investigations into the best conditioning and treatment regimens pre‐ and post‐transplantation are required to improve the survival rate of transplanted CHAI and LATAIE patients.
In CHAI patients the rates of granulomas, malignancies, atopy, cutaneous disorders, and neurologic disorders are higher, while LATAIE patients are more commonly complicated with life‐threatening infections, pneumonia, ear‐nose‐throat disorders, organomegaly, autoimmune enteropathy, and growth failure.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
► We examined whether comprehension is impaired with too much information. ► RTs and ERPs revealed that an extra modifier slowed comprehension and produced an N400. ► Data are consistent with the ...Maxim of Quantity.
Speakers often include extra information when producing referring expressions, which is inconsistent with the Maxim of Quantity (
Grice, 1975). In this study, we investigated how comprehension is affected by unnecessary information. The literature is mixed: some studies have found that extra information facilitates comprehension and others reported impairments. We used an attentional-cueing paradigm to assess how quickly participants could orient attention to an object upon hearing a referring expression, such as
the red square. If there are two squares differing in color, then the modifier is required. However, if there is only one (red) square, then the modifier is unnecessary. We also recorded event-related potentials (ERPs) in order to investigate online processing. Reaction times were significantly longer for referring expressions that contained extra information, and ERPs revealed a centroparietal negativity (N400) that emerged approximately 200–300
ms after modifier onset. We conclude that referring expressions with an unnecessary pre-nominal modifier impair comprehension performance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
We aimed to investigate the efficacy, safety, and T regulatory cell response of vitamin D as an adjunct to allergen‐specific immunotherapy (IT).
Methods
Fifty children with asthma and ...receiving pharmacotherapy were randomized into three groups as: subcutaneous IT (SCIT) along with vitamin D supplementation (650 U/day; n: 17), SCIT alone (n: 15), and pharmacotherapy alone (n: 18). All patients were evaluated at baseline, 6th and 12th months for scorings of symptoms and medication, skin prick testing, total IgE, specific IgE, and Der p 1‐specific IgG4. In addition, D. pteronyssinus‐induced CD4+CD25+FOXP3+T regulatory cell percentage, intracellular Foxp3 expression, and peripheral blood mononuclear cell IL‐10 and TGF‐β responses were assessed.
Results
In the SCIT + vitamin D and SCIT alone groups, total asthma symptom score (TASS), total symptom score (TSS), and total medication scores (TMS) were significantly lower than pharmacotherapy group at the end of 1 year. While the comparison of delta values (Δ 6th and Δ 12th month − baseline) of those scores revealed no significant differences between the two IT groups, TASS at the 6th month was lower in the SCIT + vitamin D group compared with others. There was a significant and positive trend in the levels of Der p 1‐specific IgG4 in both IT groups throughout the study period. Whereas the levels of Der p 1‐induced IL‐10 and TGF‐β were similar between IT groups, the mean fluorescence intensity of Foxp3 was highest in the SCIT + vitamin D group compared with others at the 12th month. The rate of discontinuation of inhaled corticosteroid (ICS) was 6/17 in SCIT + vitamin D, 3/15 in SCIT, and 0/18 in the pharmacotherapy group (P = 0.02).
Conclusion
Both SCIT groups fared better than pharmacotherapy alone at the end of 1 year. Although the clinical and immunologic outcomes were mostly similar between the two IT groups, some favorable outcomes of vitamin D warrant further investigation in more selected populations with varying doses as adjunct to IT.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Obstructive sleep apnea (OSA) is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to episodic desaturation. OSA patients often show symptoms of ...anxiety. Our study aimed to examine the presence and levels of anxiety in OSA and simple snoring relative to control subjects and to investigate the correlation between anxiety scores and polysomnographic, demographic, and sleepiness parameters.
The study included 80 OSA, 30 simple snoring, and 98 control cases. Demographic, anxiety, and sleepiness data of all subjects were acquired. The Beck Anxiety Inventory (BAI) was used to determine the level of anxiety. The Epworth Sleepiness Scale (ESS) was used to evaluate the sleepiness level of participants. In addition, polysomnography recordings of those in the OSA and the simple snoring group were acquired.
Significantly higher anxiety scores were found in patients with obstructive sleep apnea and simple snoring compared to the control group (p<0.01, p<0.01, respectively). From the polysomnographic data obtained from OSA and simple snoring subjects, the CT90 values (cumulative percentage of the time spent at saturations below 90%) and the AHI showed a weak positive correlation between the level of anxiety (p=0.004, r=0.271; p=0.04, r=0.196, respectively).
Our study concluded that polysomnographic data showing the depth and duration of hypoxia may be more reliable in showing neuropsychological disorder and hypoxia-related comorbidities in OSA. The CT90 value can be used as a measure in the assessment of anxiety in OSA. Its advantage is that it can be measured with overnight pulse oximetry along with in-laboratory PSG and HSAT (home sleep apnea test).
Recently autosomal recessively inherited mutations in the gene encoding Jagunal homolog 1 (JAGN1) was described as a novel disease-causing gene of severe congenital neutropenia (SCN)
JAGN1
-mutant ...neutrophils were characterized by abnormality in endoplasmic reticulum structure, absence of granules, abnormal N-glycosylation of proteins and susceptibility to apoptosis. These findings imply the role of JAGN1 in neutrophil survival. Here, we report two siblings with a homozygous mutation in
JAGN1
gene, exhibiting multisystemic involvement.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Specific allergen immunotherapy is the only treatment modality that might change the natural course of allergic diseases in childhood. We sought to prospectively compare the long-term clinical and ...immunological effects of sublingual (SLIT) and subcutaneous (SCIT) immunotherapy compared with pharmacotherapy alone.
In this single-center, prospective randomized controlled trial, 48 children with mild persistent asthma with/without rhinitis, monosensitized to house dust mites (HDMs) were followed for 3 years. At baseline and years 1 and 3 of follow-up, patients were evaluated and compared for total rhinitis (TRSS) and asthma (TASS) symptom scores, total symptom scores (TSS), total medication scores (TMS), safety profiles, skin-nasal-bronchial reactivity, and immunological parameters.
A significant reduction was observed in TASS for both HDM-SCIT and HDM-SLIT at year 3 of treatment compared with baseline and controls (P<.05 for both), with significant improvement in rhinitis symptoms for both groups compared with controls (P=.01 for both). TSS decreased significantly in both HDM-SCIT and HDM-SLIT at year 3 compared with baseline (P=.007 and P=.04, respectively) and controls (P<.01 for both). A significant reduction in TMS was observed in HDM-SCIT and HDM-SLIT compared with baseline and controls (P=.01 in all cases), with a reduction in skin reactivity to HDM (P<.05). Finally, a significant increase in allergen specific IgG4 was observed in the SCIT group at year 3 compared with baseline, the SLIT group, and controls (P<.001 in all cases).
HDM-sensitized asthmatic children treated for at least 3 years with either SCIT or SLIT showed sustained clinical improvement.
The single nucleotide polymorphism (SNP) genotyping is currently considered as a particularly valuable tool for the diagnosis of different pathologies. For this reason, over the past several years a ...great deal of effort has been devoted to developing accurate, rapid, and cost-effective technologies for SNP analysis. Although a large number of distinct approaches has been reported each laboratory use one of the published methods based on their technical and economical capacity. This article presents an application of an in-house assay, tetra-primer ARMS PCR assay, and its application in SNP genotyping. We have shown that this assay could be more advantageous when compared with PCR-RFLP, real time PCR, and DNA sequencing. We have shown that the assay is successful in genotyping using archived paraffin-embedded tissues, heparinated samples and amniotic fluids with meconium. These low-costed (3$/reaction) assays could be completed within 3–4 h after specimen receipt allowing for a reasonable turn-around time in the laboratory. Since tetra-primer ARMS PCR assay does not require any special equipment, the assay could be set up in most clinical diagnostic laboratories.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
A simple yet accurate model for the transmission of surface plasmon polaritons (SPPs) in a finite metal–insulator–metal (MIM) waveguide to the sides of the apertures is proposed and ...demonstrated to be more accurate than the available models. It is as simple as using a magnetic current density across the plane of the aperture whose value is defined by the SPPs with any number of modes in the waveguide through the equivalence principle. Then, the generated SPPs on both sides of the aperture are extracted from the convolution integral of the equivalent current density and Green’s function. As a result, the model provides the transmission coefficients of the SPPs in the MIM waveguide to the side walls of the aperture accurately and efficiently; not only for symmetric MIM waveguides with a single isolating layer but also non-symmetric ones with multi-layered insulating materials. The results are in very good agreement with those obtained by the finite-difference time-domain method and better than the other approximations available in literature for a wide range of aperture widths.
Background
Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is a rare, genetically heterogeneous, autosomal recessive disorder. Patients suffer from recurrent infections ...caused by reduced levels or absence of serum immunoglobulins. Genetically, 4 subtypes of ICF syndrome have been identified to date: ICF1 (DNMT3B mutations), ICF2 (ZBTB24 mutations), ICF3 (CDCA7 mutations), and ICF4 (HELLS mutations).
Aim
To study the mutation spectrum in ICF syndrome.
Materials and methods
Genetic studies were performed in peripheral blood lymphocyte DNA from suspected ICF patients and family members.
Results
We describe 7 ICF1 patients and 6 novel missense mutations in DNMT3B, affecting highly conserved residues in the catalytic domain. We also describe 5 new ICF2 patients, one of them carrying a homozygous deletion of the complete ZBTB24 locus. In a meta‐analysis of all published ICF cases, we observed a gender bias in ICF2 with 79% male patients.
Discussion
The biallelic deletion of ZBTB24 provides strong support for the hypothesis that most ICF2 patients suffer from a ZBTB24 loss of function mechanism and confirms that complete absence of ZBTB24 is compatible with human life. This is in contrast to the observed early embryonic lethality in mice lacking functional Zbtb24. The observed gender bias seems to be restricted to ICF2 as it is not observed in the ICF1 cohort.
Conclusion
Our study expands the mutation spectrum in ICF syndrome and supports that DNMT3B and ZBTB24 are the most common disease genes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
This review explores the transformative impact of artificial intelligence (AI) in breast imaging, driven by a global rise in breast cancer cases. Propelled by deep learning techniques, AI shows ...promise in refining diagnostic processes, yet adoption rates vary. Its ability to manage extensive datasets and process multidimensional information holds potential for advancing precision medicine in breast cancer research. However, integration faces challenges, from data-related obstacles to ensuring transparency and trust in decision-making. Legal considerations, including the formation of AI teams and intellectual property protection, influence health care's adoption of AI. Ethical dimensions underscore the need for responsible AI implementation, emphasizing autonomy, well-being, safety, transparency, and accessibility. Establishing a robust legal and ethical framework is crucial for conscientiously deploying AI, ensuring positive impacts on patient safety and treatment efficacy. As nations and organizations aspire to engage in global competition, not merely as consumers, the review highlights the critical importance of developing legal regulations. A comprehensive approach, from AI team formation to end-user processes, is essential for navigating the complex terrain of AI applications in breast imaging. Legal experts play a key role in ensuring compliance, managing risks, and fostering resilient integration. The ultimate goal is a harmonious synergy between technological advancements and ethical considerations, ushering in enhanced breast cancer diagnostics through responsible AI utilization. Keywords: Artificial Intelligence, Breast, Deep Learning, Imaging, Medical Law
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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