Mixed group divisible designs with three groups and block size 4

AbstractA group divisible design (GDD) with three groups and block size 4 is called even, odd, or mixed if the sizes of the non-empty intersections of any of its blocks with any of the three groups are always even, always odd, or always mixed. It has been shown that the necessary conditions for the existence of GDDs of these three types are also sufficient except possibly for the minimal case of mixed designs for group size 5t (t>1). In this paper, we complete the undetermined families of mixed GDDs using two constructions based on idempotent self-orthogonal Latin squares and skew Room squares

Statistical properties of eigenstate amplitudes in complex quantum systems

We study the eigenstates of quantum systems with large Hilbert spaces, via their distribution of wavefunction amplitudes in a real-space basis. For single-particle 'quantum billiards', these real-space amplitudes are known to have Gaussian distribution for chaotic systems. In this work, we formulate and address the corresponding question for many-body lattice quantum systems. For integrable many-body systems, we examine the deviation from Gaussianity and provide evidence that the distribution generically tends toward power-law behavior in the limit of large sizes. We relate the deviation from Gaussianity to the entanglement content of many-body eigenstates. For integrable billiards, we find several cases where the distribution has power-law tails.Comment: revised version, with appendices; 15 pages, 10 figure

Uncertainty-inspired Open Set Learning for Retinal Anomaly Identification

Failure to recognize samples from the classes unseen during training is a major limit of artificial intelligence (AI) in real-world implementation of retinal anomaly classification. To resolve this obstacle, we propose an uncertainty-inspired open-set (UIOS) model which was trained with fundus images of 9 common retinal conditions. Besides the probability of each category, UIOS also calculates an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieved an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external testing set and non-typical testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicted high uncertainty scores, which prompted the need for a manual check, in the datasets of rare retinal diseases, low-quality fundus images, and non-fundus images. This work provides a robust method for real-world screening of retinal anomalies

Caspase-11 Controls Interleukin-1 beta Release through Degradation of TRPC1

Caspase-11 is a highly inducible caspase that controls both inflammatory responses and cell death. Caspase-11 controls interleukin 1 beta (IL-1 beta) secretion by potentiating caspase-1 activation and induces caspase-1-independent pyroptosis downstream of noncanonical NLRP3 inflammasome activators such as lipopolysaccharide (LPS) and Gram-negative bacteria. However, we still know very little about the downstream mechanism of caspase-11 in regulating inflammation because the known substrates of caspase-11 are only other caspases. Here, we identify the cationic channel subunit transient receptor potential channel 1 (TRPC1) as a substrate of caspase-11. TRPC1 deficiency increases the secretion of IL-1 beta without modulating caspase-1 cleavage or cell death in cultured macrophages. Consistently, trpc1(-/-) mice show higher IL-1 beta secretion in the sepsis model of intraperitoneal LPS injection. Altogether, our data suggest that caspase-11 modulates the cationic channel composition of the cell and thus regulates the unconventional secretion pathway in a manner independent of caspase-1

Serological analysis of allergic components of house dust mite provides more insight in epidemiological characteristics and clinical symptom development in North China

BackgroundHouse dust mite (HDM) is the most common airborne source causing complex allergy symptoms. There are geographic differences in the allergen molecule sensitization profiles. Serological testing with allergen components may provide more clues for diagnosis and clinical management.ObjectiveThis study aims to investigate the sensitization profile of eight HDM allergen components in a large number of patients enrolled in the clinic and to analyze the relation of gender, age, and clinical symptoms in North China.MethodsThe 548 serum samples of HDM-allergic patients (ImmunoCAP® d1 or d2 IgE ≥0.35) were collected in Beijing City and divided in four different age groups and three allergic symptoms. The specific IgE of HDM allergenic components, Der p 1/Der f 1, Der p 2/Der f 2, Der p 7, Der p 10, Der p 21, and Der p 23, was measured using the micro-arrayed allergen test kit developed by Hangzhou Zheda Dixun Biological Gene Engineering Co., Ltd. The new system was validated by comparing to single-component Der p 1, Der p 2, and Der p 23 tests by ImmunoCAP in 39 sera. The epidemiological study of these IgE profiles and the relation to age and clinical phenotypes were analyzed.ResultsA greater proportion of male patients was in the younger age groups, while more female patients were in the adult groups. Both the sIgE levels and the positive rates (approximately 60%) against Der p 1/Der f 1 and Der p 2/Der f 2 were higher than for the Der p 7, Der p 10, and Der p 21 components (below 25%). The Der f 1 and Der p 2 positive rates were higher in 2–12-year-old children. The Der p 2 and Der f 2 IgE levels and positive rates were higher in the allergic rhinitis group. The positive rates of Der p 10 increased significantly with age. Der p 21 is relevant in allergic dermatitis symptom, while Der p 23 contributes to asthma development.ConclusionHDM groups 1 and 2 were the major sensitizing allergens, with group 2 being the most important component relevant to respiratory symptoms in North China. The Der p 10 sensitization tends to increase with age. Der p 21 and Der p 23 might be associated with the development of allergic skin disease and asthma, respectively. Multiple allergen sensitizations increased the risk of allergic asthma

XPO1 expression worsens the prognosis of unfavorable DLBCL that can be effectively targeted by selinexor in the absence of mutant p53

Additional file 1. Table S1: Clinicopathologic and molecular characteristics of DLBCL patients with high or low XPO1 expression. Table S2: Significantly differentially expressed genes between XPO1high and XPO1low DLBCL patients with concurrent TP53 mutation and high MYC expression. Figure S1: Biomarker study for XPO1 and selinexor. (A–B) XPO1high expression showed significant adverse prognostic impact in the ABC subtype but not the GCB subtype of DLBCL. (C) XPO1high expression showed a trend of unfavorable prognostic effect on PFS in MYC-rearranged (MYC-R+) DLBCL. (D) XPO1high expression was associated with significantly poorer survival in DLBCL patients with wild type (Wt) TP53. (E) ABC-DLBCL and GCB-DLBCL cells showed similar sensitivity to the cytotoxicity of selinexor. (F) TP53 mutation (Mut-TP53) significantly reduced the anti-lymphoma efficacy of selinexor in HGBCL-DH cells. IC50 values were calculated by GraphPad Prism 8 based on the cell viability data after 72-hour treatment

Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma

Combination of Decitabine and a Modified Regimen of Cisplatin, Cytarabine and Dexamethasone: A Potential Salvage Regimen for Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Treatment Failure

ObjectiveThe prognosis for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R-DLBCL) after second-line treatment failure is extremely poor. This study prospectively observed the efficacy and safety of decitabine with a modified cisplatin, cytarabine, and dexamethasone (DHAP) regimen in R/R-DLBCL patients who failed second-line treatment.MethodsTwenty-one R/R-DLBCL patients were enrolled and treated with decitabine and a modified DHAP regimen. The primary endpoints were overall response rate (ORR) and safety. The secondary endpoints were progression-free survival (PFS) and overall survival (OS).ResultsORR reached 50% (complete response rate, 35%), five patients (25%) had stable disease (SD) with disease control rate (DCR) of 75%. Subgroup analysis revealed patients over fifty years old had a higher complete response rate compared to younger patients (P = 0.005), and relapsed patients had a better complete response rate than refractory patients (P = 0.031). Median PFS was 7 months (95% confidence interval, 5.1-8.9 months). Median OS was not achieved. One-year OS was 59.0% (95% CI, 35.5%-82.5%), and two-year OS was 51.6% (95% confidence interval, 26.9%-76.3%). The main adverse events (AEs) were grade 3/4 hematologic toxicities such as neutropenia (90%), anemia (50%), and thrombocytopenia (70%). Other main non-hematologic AEs were grade 1/2 nausea/vomiting (40%) and infection (50%). No renal toxicity or treatment-related death occurred.ConclusionDecitabine with a modified DHAP regimen can improve the treatment response and prognosis of R/R-DLBCL patients with good tolerance to AEs, suggesting this regimen has potential as a possible new treatment option for R/R-DLBCL patients after second-line treatment failure.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT03579082

The DNA Methylome of Human Peripheral Blood Mononuclear Cells

Analysis across the genome of patterns of DNA methylation reveals a rich landscape of allele-specific epigenetic modification and consequent effects on allele-specific gene expression