ADA2 is a lysosomal deoxyadenosine deaminase acting on DNA involved in regulating TLR9-mediated immune sensing of DNA.

Although adenosine deaminase 2 (ADA2) is considered an extracellular ADA, evidence questions the physiological relevance of this activity. Our study reveals that ADA2 localizes within the lysosomes, where it is targeted through modifications of its glycan structures. We show that ADA2 interacts with DNA molecules, altering their sequences by converting deoxyadenosine (dA) to deoxyinosine (dI). We characterize its DNA substrate preferences and provide data suggesting that DNA, rather than free adenosine, is its natural substrate. Finally, we demonstrate that dA-to-dI editing of DNA molecules and ADA2 regulate lysosomal immune sensing of nucleic acids (NAs) by modulating Toll-like receptor 9 (TLR9) activation. Our results describe a mechanism involved in the complex interplay between NA metabolism and immune response, possibly impacting ADA2 deficiency (DADA2) and other diseases involving this pathway, including autoimmune diseases, cancer, or infectious diseases.

[Effect of donor and recipient HLA mismatched locus on the prognosis of childhood with leukemia after umbilical cord blood transplantation].

Objective: The aim of the study was to investigate the impact of the sites of high-resolution human leukocyte antigen (HLA) mismatch on the prognosis of children with leukemia undergoing umbilical cord blood transplantation (UCBT). Methods: Clinical data and high-resolution HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 locus gene information were collected in the children who underwent the UCBT for the first time at Children's Hospital of Soochow University between January 2016 and June 2023. In each locus, according to whether the two genes were compatible, they were divided into a compatible group (two genes were perfectly matched) and a non-compatible group (one gene was not matched). In different loci, the differences in occurrence, recurrence, non-recurrence death and survival of acute graft versus host disease (aGVHD) were compared between the two groups. Multivariate Cox regression was employed to analyzed the influencing factors for overall survival rate, and Fine-Gray proportional hazards model was employed to analyze the influencing factors of other outcome events. Results: A total of 100 patients were enrolled (55 males and 45 females), whose age [M (Q1, Q3)] at the time of transplantation was 3.9 (2.0, 6.5) years. There were 55 cases in the HLA-A matched group and 45 cases in the mismatched group. The 5-year non-recurrence mortality (NRM) in the HLA-A matched group was lower than that in the mismatched group (P=0.024). The cumulative incidence of aGVHD within 100 days after transplantation in the HLA-A matched group was lower than that in the mismatched group (P=0.017), and there were no statistically significant differences in other outcome events between the groups (all P>0.05). There were 70 cases in the HLA-B matched group and 30 cases in the mismatched group. The 5-year cumulative recurrence rate in the HLA-B matched group was higher than that in the mismatched group (P=0.027). There were 79 cases in the HLA-C matched group and 21 cases in the mismatched group, and there were no statistically difference in the outcome events between the groups (P>0.05). There were 73 cases in HLA-DRB1 matched group and 27 cases in mismatched group. The 5-year overall survival rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.036), the 5-year cumulative recurrence rate in HLA-DRB1 matched group was higher than that in mismatched group (P=0.028), and the 5-year NRM in HLA-DRB1 matched group was lower than that in mismatched group (P=0.008). The cumulative incidence of aGVHD within 100 days after transplantation in the matched group was lower than that in the mismatched group (P=0.010), and and there were no statistically significant difference in other outcome events between the groups (P>0.05). There were 68 cases in HLA-DQB1 matched group and 32 cases in mismatched group. There was no statistical difference in outcome events between the two groups (all P>0.05). The risk of aGVHD in HLA-A mismatched group was higher than that in HLA-A matched group (HR=1.25, 95%CI: 1.12-1.38). The risk of recurrence in HLA-B mismatched group was lower than that in HLA-B matched group (HR=0.77, 95%CI: 0.63-0.91). Mismatched group at HLA-DRB1 compared with matched group at HLA-DRB1, had a higher risk of aGVHD (HR=1.37, 95%CI: 1.26-1.48), a higher risk of non-recurrence death (HR=1.39, 95%CI: 1.28-1.50), and a higher risk of death (HR=1.27, 95%CI: 1.18-1.36). No association was found between HLA-C and HLA-DQB1 locus with the risk of aGVHD, recurrence, non-recurrence death, and survival (all P>0.05). Conclusions: In UCBT, the risk of aGVHD in children with matching HLA-A sites of donor and recipient is lower than that in children with incompatible HLA-A sites. Compared with children with incompatible HLA-DRB1 sites, children with HLA-DRB1 matched sites has a lower risk of acute GVHD, a lower 5-year NRM, and a higher risk of death. The recurrence rate of children with matching HLA-B loci is higher than that of children without matching HLA-B loci.

Sweet syndrome associated with moderate leukocyte adhesion deficiency type I: a case report and review of the literature.

Sweet syndrome is an acute febrile neutrophilic dermatosis characterized by the infiltration of neutrophils into the skin. It may occur idiopathically or be linked to malignancies, inflammatory or autoimmune diseases. Leukocyte adhesion deficiency type I (LAD-I) is an inborn error immunity wherein leukocytes lack adhesion molecules necessary for migration to infection sites due to mutations in the CD18 gene encoding ß2 integrins. We present a case of a 16-month-old female initially diagnosed and treated for Sweet syndrome based on histopathological findings with recurrent flare episodes. Subsequent workup revealed LAD-I, making this case the first documented association between Sweet syndrome and LAD-I. Moreover, we reviewed the pertinent literatures detailing the concurrence of neutrophilic dermatosis and immunodeficiency disorders. This case underscores the significance of comprehensive evaluation for Sweet syndrome patients who are refractory to conventional treatments.

Development of a machine learning interatomic potential for exploring pressure-dependent kinetics of phase transitions in germanium.

We introduce a data-driven potential aimed at the investigation of pressure-dependent phase transitions in bulk germanium, including the estimate of kinetic barriers. This is achieved by suitably building a database including several configurations along minimum energy paths, as computed using the solid-state nudged elastic band method. After training the model based on density functional theory (DFT)-computed energies, forces, and stresses, we provide validation and rigorously test the potential on unexplored paths. The resulting agreement with the DFT calculations is remarkable in a wide range of pressures. The potential is exploited in large-scale isothermal-isobaric simulations, displaying local nucleation in the R8 to ß-Sn pressure-induced phase transformation, taken here as an illustrative example.

OTULIN-related conditions: Report of a new case and review of the literature using GenIA.

OTULIN encodes an eponymous linear deubiquitinase (DUB) essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway via the regulation of M1-Ub dynamics. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative (DN) effects. In this manuscript, we report the identification of a novel homozygous missense mutation, c.595 T > A; p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype and provide experimental evidence for its pathogenicity. We go on to systematically review the literature for OTULIN-associated conditions by using the GenIA database (www.geniadb.net) to collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. Our comprehensive synthesis of genotypic, phenotypic, and mechanistic data enables a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and inform future variant evaluation, as well as the development of diagnostic and management guidelines. It also identifies current knowledge gaps and raises additional questions warranting future investigation.

OTULIN-related conditions: Report of a new case and review of the literature using GenIA.

OTULIN encodes an eponymous linear deubiquitinase (DUB), which through the regulation of M1-Ub dynamics, is essential for controlling inflammation as a negative regulator of the canonical NF-κB signaling pathway. Biallelic loss-of-function (LOF) mutations in OTULIN cause an autosomal recessive condition named Otulin-Related Autoinflammatory Syndrome (ORAS), also known as Otulipenia or AutoInflammation, Panniculitis, and Dermatosis Syndrome (AIPDS). Monoallelic OTULIN LOF, also known as OTULIN Haploinsufficiency (OHI) or Immunodeficiency 107 (IMD107), has been linked to an incompletely penetrant, dominantly inherited susceptibility to invasive Staphylococcal infections. At the same time, a recent novel ORAS-like inflammatory syndrome was described in association with a heterozygous missense mutation that appears to exert dominant negative effects. In this manuscript, we report the identification of a novel homozygous missense mutation, c.595T>A; p.(Trp199Arg), in a Moroccan infant with an ORAS phenotype. We go on to systematically review the literature for OTULIN-related human disease phenotypes by using the GenIA database to collect, extract and harmonize all clinical, laboratory and functional data for published patients and variants. Our comprehensive synthesis of genotypic, phenotypic, and mechanistic data enables a more in-depth view of the diverse mechanisms and pathways by which the OTULIN pathogenic variants may lead to human immune disease. This review may help variant classification activities and the drafting of diagnostic and management guidelines; but it also identifies outstanding knowledge gaps and raises additional questions for future investigation.

[Adiponectin improves endometrial receptivity in rats with polycystic ovary syndrome by upregulating the PPARα/HOXA10 pathway].

OBJECTIVE: To explore the role of the PPARα/HOXA10 signaling pathway in mediating the effect of adiponectin (APN) for improving endometrial receptivity in a rat model of polycystic ovary syndrome (PCOS). METHODS: Forty female SD rat models with letrozole-induced PCOS were randomized, with 10 normal rats as the control, into 4 equal groups for treatment with APN alone, APN combined with GW6471 (a specific PPARα inhibitor) or the vehicle for 20 days, or no further treatment (PCOS model group). GW6471 treatment (daily dose of 1 mg/kg) and vehicle treatment were initiated on the 11th day following the start of APN treatment, all administered via intraperitoneal injection. The rats were observed for changes in estrous cycle, body weight, ovarian index and morphology, uterine index and morphology, serum hormone levels and lipid metabolism parameters. Endometrial expressions of PPARα and HOXA10 were detected with immunohistochemistry and Western blotting. The development of endometrial pinopodes was observed under electron microscope, and pregnancies of the rats were recorded. RESULTS: The rat models of PCOS exhibited obvious estrous cycle disorders with significantly prolonged estrous interval, increased body weight and ovarian index, decreased uterine index, disordered serum hormones and lipid metabolism (P < 0.05), and polycystic ovarian changes, and these changes were significantly improved by APN treatment. Endometrial expressions of PPARα and HOXA10 were significantly lowered in PCOS rats and effectively up-regulated after APN treatment, but GW6471 treatment obviously blocked the effect of APN (P < 0.05). APN showed strong protective effect against PCOS-induced impairment of endometrial pinopode development, and this effect was obviously attenuated by GW6471. APN also significantly increased the pregnancy rate and embryo number in PCOS rats, while GW6471 obviously reduced the embryo number and caused developmental retardation of the embryos. CONCLUSION: APN can improve endometrial receptivity in PCOS rats by upregulating the PARα/HOXA10 pathway.

3D Printed Ion-Responsive Personalized Transdermal Patch.

Microneedle patches are easy-to-use medical devices for transdermal administration. However, the insufficient insertion of microneedles due to the gap between planar patches and contoured skin affects drug delivery. Herein, we formulate a prepolymer for high-fidelity three-dimensional (3D) printed personalized transdermal patches. With the excellent photoinitiation ability of 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine (Tz), a high-fidelity and precise microneedle patch is successfully fabricated. Upon irradiation of the white illuminator, the doped gold nanoparticles (AuNPs) in the patch release heat and promisingly induce sweat production. With the introduction of Na+, the dominant component of sweat, the curvature of the produced transdermal patch is observed due to the ion-induced network rearrangement. The alkanethiol-stabilized AuNP with an end group of a carboxyl group causes controlled drug release behavior. Furthermore, the irradiation-induced photothermal heating of AuNP can facilitate the sustainability of drug release thanks to the substantially increased particle size of AuNP. These findings demonstrate that the developed prepolymer is a promising candidate for the production of transdermal patches fitting the curvature of the body surface.

[Analysis of clinical characteristics of children with adenoid hypertrophy and pharyngolaryngeal reflux].

Objectives: To explore the clinical characteristics of children with adenoid hypertrophy (AH) and laryngopharyngeal reflux (LPR) by detecting the expression of pepsin in adenoids as a standard for AH with LPR. Methods: A total of 190 children who were admitted for surgical treatment due to AH were included in the study. The main clinical symptoms of the patients were recorded, and the degree of adenoid hypertrophy was evaluated. Before the surgery, Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were used to evaluate the reflux symptoms. After the surgery, pepsin immunohistochemical staining was performed on the adenoid tissue, and according to the staining results, the patients were divided into study group (pepsin staining positive) and control group (pepsin staining negative). SPSS 19.0 software was used for statistical analysis. Quantitative data conforming to normal distribution between the two groups were tested by two-independent sample t test, and quantitative data with skewed distribution were tested by Mann-Whitney U test. Results: The positive rate of pepsin staining in the 190 AH patients was 78.4% (149/190). The study group had higher levels of preoperative symptoms such as erythema and/or congestion of the pharynx(2.1±0.7 vs. 1.8±0.6,t=2.23), vocal cord edema[1.0(0, 1.0) vs. 1.0(0, 1.0), Z=2.00], diffuse laryngeal edema[0(0, 1.0) vs. 0(0, 0), Z=2.48], posterior commissure hypertrophy[(1.4±0.6 vs. 1.1±0.5), t=2.63], and a higher total score on the RFS scale than the control group(6.2±2.7 vs. 5.0±2.6, t=2.47), with statistical differences (P<0.05). The sensitivity and specificity of RFS score in diagnosing AH with LPR were 24.8% and 80.5%, respectively. When RFS>5 was used as the positive threshold, the sensitivity and specificity of RFS score in diagnosing AH with LPR were 61.1% and 58.5%, respectively. There was a statistical difference in the number of positive cases of RFS score between the study group and the control group(91 vs. 17,χ2=5.04,P=0.032). Conclusions: LPR is common in AH children. Children with AH and LPR have specific performance in electronic laryngoscopy, such as erythema with edema in the pharynx, posterior commissure hypertrophy, and vocal cord edema.

Disease-associated AIOLOS variants lead to immune deficiency/dysregulation by haploinsufficiency and redefine AIOLOS functional domains.

AIOLOS, also known as IKZF3, is a transcription factor that is highly expressed in the lymphoid lineage and is critical for lymphocyte differentiation and development. Here, we report on 9 individuals from 3 unrelated families carrying AIOLOS variants Q402* or E82K, which led to AIOLOS haploinsufficiency through different mechanisms of action. Nonsense mutant Q402* displayed abnormal DNA binding, pericentromeric targeting, posttranscriptional modification, and transcriptome regulation. Structurally, the mutant lacked the AIOLOS zinc finger (ZF) 5-6 dimerization domain, but was still able to homodimerize with WT AIOLOS and negatively regulate DNA binding through ZF1, a previously unrecognized function for this domain. Missense mutant E82K showed overall normal AIOLOS functions; however, by affecting a redefined AIOLOS protein stability domain, it also led to haploinsufficiency. Patients with AIOLOS haploinsufficiency showed hypogammaglobulinemia, recurrent infections, autoimmunity, and allergy, but with incomplete clinical penetrance. Altogether, these data redefine the AIOLOS structure-function relationship and expand the spectrum of AIOLOS-associated diseases.

GenIA, the Genetic Immunology Advisor database for inborn errors of immunity.

BACKGROUND: To date, no publicly accessible platform has captured and synthesized all of the layered dimensions of genotypic, phenotypic, and mechanistic information published in the field of inborn errors of immunity (IEIs). Such a platform would represent the extensive and complex landscape of IEIs and could increase the rate of diagnosis in patients with a suspected IEI, which remains unacceptably low. OBJECTIVE: Our aim was to create an expertly curated, patient-centered, multidimensional IEI database that enables aggregation and sophisticated data interrogation and promotes involvement from diverse stakeholders across the community. METHODS: The database structure was designed following a subject-centered model and written in Structured Query Language (SQL). The web application is written in Hypertext Preprocessor (PHP), Hypertext Markup Language (HTML), Cascading Style Sheets (CSS), and JavaScript. All data stored in the Genetic Immunology Advisor (GenIA) are extracted by manually reviewing published research articles. RESULTS: We completed data collection and curation for 24 pilot genes. Using these data, we have exemplified how GenIA can provide quick access to structured, longitudinal, more thorough, comprehensive, and up-to-date IEI knowledge than do currently existing databases, such as ClinGen, Human Phenotype Ontology (HPO), ClinVar, or Online Mendelian Inheritance in Man (OMIM), with which GenIA intends to dovetail. CONCLUSIONS: GenIA strives to accurately capture the extensive genetic, mechanistic, and phenotypic heterogeneity found across IEIs, as well as genetic paradigms and diagnostic pitfalls associated with individual genes and conditions. The IEI community's involvement will help promote GenIA as an enduring resource that supports and improves knowledge sharing, research, diagnosis, and care for patients with genetic immune disease.

The Effect of Histogram Analysis of DCE-MRI Parameters on Differentiating Renal Tumors.

BACKGROUND: We aimed to assess the role of histogram analysis of DCE-MRI parameters for accurately distinguishing renal clear cell carcinoma from renal hamartoma with minimal fat. METHODS: Patients with renal tumors were enrolled from January 2013 to December 2015, including renal clear cell carcinoma (n = 39) and renal hamartoma (n = 10). Preoperative DCE-MR Imaging was performed, and whole-tumor regions of interest were drawn to obtain the corresponding histogram parameters, including skewness, kurtosis, frequency size, energy, quartile, etc. Histogram parameters differences between renal clear cell car-cinoma and renal hamartoma with minimal fat were compared. The diagnostic value of each significant parameter in predicting malignant tumors was determined. RESULTS: Histogram parameters of the DCE map contributed to differentiating the benign from malignant renal tumor groups. Histogram analysis of DCE maps could effectively present the heterogeneity of renal tumors and aid in differentiating benign and malignant tumors. ROC analysis results indicated that when frequency size = 1,732 was set as the threshold value, favorable diagnostic performance in predicting malignant tumors was achieved (AUC - 0.964; sensitivity - 84.6%; specificity - 100%), followed by skewness, Energy, Entropy, Uniformity, quartile 5, quartile 50, and kurtosis. CONCLUSIONS: Histogram analysis of DCE-MRI shows promise for differentiating benign and malignant renal tumors. Frequency size was the most significant parameter for predicting renal clear cell carcinoma.

Next generation sequencing (NGS)-based approach to diagnosing Algerian patients with suspected inborn errors of immunity (IEIs).

The advent of next-generation sequencing (NGS) technologies has greatly expanded our understanding of both the clinical spectra and genetic landscape of inborn errors of immunity (IEIs). Endogamous populations may be enriched for unique, ancestry-specific disease-causing variants, a consideration that significantly impacts molecular testing and analysis strategies. Herein, we report on the application of a 2-step NGS-based testing approach beginning with targeted gene panels (TGPs) tailored to specific IEI subtypes and reflexing to whole exome sequencing (WES) if negative for Northwest Algerian patients with suspected IEIs. Our overall diagnostic yield of 57% is comparable to others broadly applying short-read NGS to IEI detection, but data from our localized cohort show some similarities and differences from NGS studies performed on larger regional IEI cohorts. This suggests the importance of tailoring diagnostic strategies to local demographics and needs, but also highlights ongoing concerns inherent to the application of genomics for clinical IEI diagnostics.

The multi-functional Smc5/6 complex in genome protection and disease.

Structural maintenance of chromosomes (SMC) complexes are ubiquitous genome regulators with a wide range of functions. Among the three types of SMC complexes in eukaryotes, cohesin and condensin fold the genome into different domains and structures, while Smc5/6 plays direct roles in promoting chromosomal replication and repair and in restraining pathogenic viral extra-chromosomal DNA. The importance of Smc5/6 for growth, genotoxin resistance and host defense across species is highlighted by its involvement in disease prevention in plants and animals. Accelerated progress in recent years, including structural and single-molecule studies, has begun to provide greater insights into the mechanisms underlying Smc5/6 functions. Here we integrate a broad range of recent studies on Smc5/6 to identify emerging features of this unique SMC complex and to explain its diverse cellular functions and roles in disease pathogenesis. We also highlight many key areas requiring further investigation for achieving coherent views of Smc5/6-driven mechanisms.

[Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia].

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.

[Challenges and countermeasures in the development of artificial intelligence research in ophthalmology].

The advent of artificial intelligence (AI) technology has led to revolutionary advancements in the diagnosis and treatment of ophthalmic diseases, introducing a novel AI-assisted diagnostic approach for ophthalmology that is rich in imaging diagnostic technologies. However, as clinical applications continue to evolve, AI research in ophthalmology faces challenges such as the lack of standardized datasets and innovative algorithm models, insufficient cross-modal information fusion, and limited clinical interpretability. In response to the growing demand for AI research in ophthalmology, it is essential to establish ophthalmic data standards and sharing platforms, innovate core algorithms, and develop clinical logic interpretable models for the screening, diagnosis, and prediction of eye diseases. Additionally, the deep integration of cutting-edge technologies such as 5G, virtual reality, and surgical robots would advance the development of ophthalmic intelligent medicine into a new phase.

Correlation research of serum substance P, CCK-8, and 5-HT values with depression levels in stroke survivors.

OBJECTIVE: This study aimed to investigate the correlation of serum octapeptide cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptryptamine (5-HT) values with depression levels in patients with post-stroke depression (PSD). It also aimed to explore the potential approach for the early diagnosis of PSD. PATIENTS AND METHODS: A correlation research between patients' biochemical indicators and depression levels was performed among 70 stroke patients during hospitalization from June 2021 to February 2022. The 70 stroke patients were selected and divided into post-stroke depression and non-depression groups according to the Hamilton Depression Scale (HAMD) score. The concentrations of CCK-8, SP, and 5-HT in both groups were measured, and the relationship between the values of CCK-8, SP, 5-HT and the depression levels was analyzed. RESULTS: Among the 70 stroke survivors, 35 were in the depression group and 35 were in the non-depression group. Significant differences were observed in the concentration of CCK-8, SP, and 5-HT between the patients in the depression and non-depression group (p < 0.05). Accompanied by an increase in the depression level, the SP value gradually increased, but the CCK-8 and 5-HT values gradually decreased. Spearman correlation analysis indicated that the order of the correlation between CCK-8, 5-HT, SP, and the depression levels was CCK-8 > SP > 5-HT. CONCLUSIONS: All the CCK-8, SP and 5-HT values were correlated with the depression levels in stroke survivors. Furthermore, the correlation between CCK-8, SP, and post-stroke depression levels was higher than that of 5-HT, suggesting that the early diagnosis of PSD may be reflected more precisely through the detection of CCK-8, and SP values, thus providing potential priority for biochemical detection in the diagnosis of PSD.

Characterization data of reference materials used for phase II of the priority program DFG SPP 2005 "Opus Fluidum Futurum - Rheology of reactive, multiscale, multiphase construction materials".

A thorough characterization of base materials is the prerequisite for further research. In this paper, the characterization data of the reference materials (CEM I 42.5 R, limestone powder, calcined clay and a mixture of these three components) used in the second funding phase of the priority program 2005 of the German Research Foundation (DFG SPP 2005) are presented under the aspects of chemical and mineralogical composition as well as physical and chemical properties. The data were collected based on tests performed by up to eleven research groups involved in this cooperative program.

Common Variable Immunodeficiency: More Pathways than Roads to Rome.

Fifty years have elapsed since the term common variable immunodeficiency (CVID) was introduced to accommodate the many and varied antibody deficiencies being identified in patients with suspected inborn errors of immunity (IEIs). Since then, how the term is understood and applied for diagnosis and management has undergone many revisions, though controversy persists on how exactly to define and classify CVID. Many monogenic disorders have been added under its aegis, while investigations into polygenic, epigenetic, and somatic contributions to CVID susceptibility have gained momentum. Expansion of the overall IEI landscape has increasingly revealed genotypic and phenotypic overlap between CVID and various other immunological conditions, while increasingly routine genotyping of CVID patients continues to identify an incredible diversity of pathophysiological mechanisms affecting even single genes. Though many questions remain to be answered, the lessons we have already learned from CVID biology have greatly informed our understanding of adaptive, but also innate, immunity.

[Characteristics and related factors of viral nucleic acid negative conversion in children infected with Omicron variant strain of SARS-CoV-2].

Objective: To understand the characteristics and associated factors of viral nucleic acid conversion in children infected with Omicron variant strain of SARS-CoV-2 in Shanghai. Methods: The clinical symptoms, laboratory results and other data of 177 children infected with SARS-CoV-2 who were hospitalized in Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University (designated hospital for SARS-CoV-2 infection in Shanghai) from April 25 to June 8, 2022 were retrospectively analyzed. According to the chest imaging findings, the children were divided into mild and common type groups. According to their age, the unvaccinated children were divided into<3 years old group and 3-<18 years old group. According to the vaccination status, the children aged 3-<18 year were divided into non-vaccination group, 1-dose vaccination group and 2-dose vaccination group. Comparison between groups was performed by independent sample t-test and analysis of variance, and multivariate linear regression analysis was used for multivariate analysis. Results: Among the 177 children infected with Omicron variant of SARS-CoV-2, 96 were males and 81 were females, aged 3 (1, 6) years. The time of viral nucleic acid negative conversion was (10.3±3.1) days. The 177 children were 138 cases of mild type and 39 cases of common type. Among the children aged 3-<18 years old, 55 cases were not vaccinated, 5 cases received 1-dose and 36 cases received 2-dose vaccination. Among the 36 children who received 2 doses of vaccination, the time of viral nucleic acid negative conversion was shorter in those vaccinated within 6 months than those over 6 months ((7.1±1.9) vs. (10.8±3.0) d, t=-3.23, P=0.004). Univariate analysis showed that the time of nucleic acid negative conversion of SARS-CoV-2 was associated with age, underlying diseases, gastrointestinal symptoms, white blood cell count, proportion of neutrophils, proportion of lymphocytes, and the number of doses of SARS-CoV-2 vaccine (t=3.87, 2.55, 2.04, 4.24, 3.51, 2.92, F=16.27, all P<0.05). Multiple linear regression analysis showed that older age (ß=-0.33, 95% CI -0.485--0.182, P<0.001) and more doses of vaccination (ß=-0.79, 95% CI -1.463--0.120, P=0.021) were associated with shortened nucleic acid negative conversion time in children, while lower lymphocyte proportion (ß=-0.02, 95% CI -0.044--0.002, P=0.031) and underlying diseases (ß=1.52, 95% CI 0.363-2.672, P=0.010) were associated with prolonged nucleic acid negative conversion time in children. Conclusion: The children infected with Omicron variant of SARS-CoV-2 with reduced lymphocyte proportion and underlying diseases may have longer time of viral nucleic acid negative conversion,while children with older age and more doses of vaccination may have shorter time of viral nucleic acid negative conversion.