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IntroductionT cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.MethodsHere, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared “public” T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.ResultsCollectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3–7 = 85.1% [95% CI = 79.9–89.7]; Day 8–14 = 94.8% [90.7–98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1–98.3]).DiscussionThe approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.

Abstract We report the de novo design of small (

The total amount of sugarcane planting in China ranks third in the world, and Guangxi is the largest sugarcane planting base in China. In order to help the Guangxi government and industry better understand the annual planting distribution and scale of sugarcane in the whole region, it is convenient to optimize the planting structure and improve the efficiency of resource utilization, so as to ensure the stable development of Guangxi sugar industry. Based on the satellite-based hyperspectral image data of ' Zhuhai No.1 ', this paper carries out sugarcane recognition and area extraction, which fills the application gap of satellite-based hyperspectral image data in extracting sugarcane area in China. A globally optimized extended random walk model was used to identify and extract sugarcane by combining the spatial-spectral information of hyperspectral imagery. Firstly, the Initial probability estimation is performed using the LOR classifier, and then use the data after MNF dimensionality reduction to construct a weighted graph, and finally the probability optimization and recognition are carried out based on the extended random walk model. The results show that the spatial-spectral joint method based on extended random walk can effectively identify sugarcane, and the sugarcane recognition accuracy of 2021 year image can reach 91.4%, the misrecognition rate is 2.8%; the sugarcane recognition accuracy of 2020 year image can reach 90.5 %, the misrecognition rate is 3.1%.

Gonadal and gonosomal mosaicism describe phenomena in which a seemingly healthy individual carries a genetic variant in a subset of their gonadal tissue or gonadal and somatic tissue(s), respectively, with risk of transmitting the variant to their offspring. In families with one or more affected offspring, occurrence of the same apparently de novo variants can be an indicator of mosaicism in either parent. Panel-based deep sequencing has the capacity to detect low-level mosaic variants with coverage exceeding the typical limit of detection provided by current, readily available sequencing techniques. In this study, we report three families with more than one affected offspring with either confirmed or apparent parental gonosomal or gonadal mosaicism for PIK3CD pathogenic variants. Data from targeted deep sequencing was suggestive of low-level maternal gonosomal mosaicism in Family 1. Through this approach we did not detect pathogenic variants in PIK3CD from parental samples in Family 2 and Family 3. We conclude that mosaicism was likely confined to the maternal gonads in Family 2. Subsequent long-read genome sequencing in Family 3 showed that the paternal chromosome harbored the pathogenic variant in PIK3CD in both affected children, consistent with paternal gonadal mosaicism. Detection of parental mosaic variants enables accurate risk assessment, informs reproductive decision-making, and provides helpful context to inform clinical management in families with PIK3CD pathogenic variants.

This paper designed a kind of satellite deployment mechanism with a boxed structure and passive torsion joints. This deployment mechanism has significant strengths, including a high base frequency and stiffness, a high ratio of deployed and folded space occupation ratios, and self-actuated joints without needing any external power to drive. In order to analyze the dynamic characteristics of this mechanism, a simplified governing equation is proposed and dynamic behavior is studied systematically, including impact response, harmonic response, and modal analysis. Through systematic research, several conclusions are drawn. Firstly, when the deployment mechanism reached the ending stage of unfolding driven by passive torsional joints, the load base installed on top of the deployment mechanism generated a first-order sharp reaction force and multiple low-order shocks followed, and the system entered a stable state after a certain time of vibration. Secondly, the system can generate a high vibration magnitude at low-frequency excitation when the mechanism is in a fully deployed state and at high-frequency excitation when the mechanism is in a folded state. Thirdly, the first sixth-order natural frequency and vibration shape with different wall thicknesses are obtained by modal analysis. The result shows that only with a 2.5 mm wall thickness can the connecting rod satisfy the design requirement. Through dynamic behavior research, the structure characteristics are obtained which can be used for structure optimization and to provide an effective solution for the design of a box-structured satellite-unfolding mechanism with self-actuated torsion joints.

Two-year public colleges educate more than 50% of all U.S. undergraduates, yet graduation rates (29%) fall far below their 4-year counterparts (63%). It is critical for students of 2-year public institutions that their faculty have the appropriate knowledge, skills, and abilities (KSAs) to effectively guide students toward graduation. This study uses technological pedagogical content knowledge (TPACK) theory to evaluate faculty KSAs. Exploratory and confirmatory factor analyses are used to demonstrate reliability, validity, and the 7-factor structure of the data. This instrument may be useful in pre-employment KSA assessment for potential new faculty, as well as identifying professional development opportunities for incumbent faculty.

Abstract Background We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.

Abstract Transport and transformation of urban air pollutants are among the major factors driving the changes in the atmospheric composition in the downwind rural/remote areas of a megacity. Here, we assess the impacts of urban air pollution in a subtropical forest through characterization of the organic markers in submicron aerosol particles. The aerosol samples were collected and analyzed using TD-PTR-ToF-MS, where 163 ions were detected. The concentration of these extracted ions accounts for 83% of the mass of submicron organic aerosols, which are accordingly characterized by a median formula of C7H10O2. Molecular speciation indicates that urban and biomass burning pollution contributed substantially to the budget of organic aerosols, which were enhanced particularly by the liquid water content and acidity of the aerosols. Our results evidence that the footprint of urban air pollution was extended to its downwind forested areas and caused changes in the concentration and composition of submicron aerosols.

Alopecia areata (AA) presents a challenging and unpredictable condition associated with substantial psychosocial and financial burdens. A chronic, relapsing form of non-scarring hair loss, it affects approximately 0.1–0.2% of the population worldwide with a lifetime risk of 1.0% to 2.1%. The psychosocial implications of AA, including its association with depression, anxiety, social phobia, employment disruption, and relationship challenges are well described. Significant economic costs of AA include those of healthcare, lost income, transportation, psychotherapy, and cosmetic accessories (wigs and hairpieces). However, wigs and hairpieces can contribute to enhanced self-esteem, confidence, and overall quality of life (QOL) in AA patients; these positive outcomes correlating with satisfaction in appearance. This article explores the role of wigs in addressing the aesthetic and emotional impact of AA, emphasizing their importance as potential coping mechanisms for individuals facing hair loss whilst also acknowledging possible barriers to their use. Different types of wigs and hairpieces, their respective advantages and disadvantages, and methods of attachment are thoroughly discussed, providing a comprehensive overview for both patients and healthcare professionals. Considering the economic impact of AA, this article explores the cost of wigs in Australia and available financial assistance programs. Wigs can play a pivotal role in rapidly addressing the multifaceted challenges posed by AA, offering time for psychosocial adaptation and delayed response to medical therapies. This review aims to provide valuable insights to inform evidence-based, practical, and personalized counselling of patients with AA and enable shared decision making about the utility of wigs and other cosmetic interventions for hair loss. Further research is warranted to explore differences in the optimal utilization of wigs between diverse sub-populations with AA.

PurposeThough copy number variants (CNVs) have been suggested to play a significant role in inborn errors of immunity (IEI), the precise nature of this role remains largely unexplored. We sought to determine the diagnostic contribution of CNVs using genome-wide chromosomal microarray analysis (CMA) in children with IEI.MethodsWe performed exome sequencing (ES) and CMA for 332 unrelated pediatric probands referred for evaluation of IEI. The analysis included primary, secondary, and incidental findings.ResultsOf the 332 probands, 134 (40.4%) received molecular diagnoses. Of these, 116/134 (86.6%) were diagnosed by ES alone. An additional 15/134 (11.2%) were diagnosed by CMA alone, including two likely de novo changes. Three (2.2%) participants had diagnostic molecular findings from both ES and CMA, including two compound heterozygotes and one participant with two distinct diagnoses. Half of the participants with CMA contribution to diagnosis had CNVs in at least one non-immune gene, highlighting the clinical complexity of these cases. Overall, CMA contributed to 18/134 diagnoses (13.4%), increasing the overall diagnostic yield by 15.5% beyond ES alone.ConclusionPairing ES and CMA can provide a comprehensive evaluation to clarify the complex factors that contribute to both immune and non-immune phenotypes. Such a combined approach to genetic testing helps untangle complex phenotypes, not only by clarifying the differential diagnosis, but in some cases by identifying multiple diagnoses contributing to the overall clinical presentation.

Abstract Objective Given the continued spread of coronavirus 2, the early predictors of coronavirus disease 19 (COVID‐19) associated mortality might improve patients' outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuronal injury, have been observed in severe COVID‐19 patients. We investigated whether NfL provides non‐redundant clinical value to previously identified predictors of COVID‐19 mortality. Methods We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID‐19 patients. Results In cohort 1, we found significantly elevated NfL levels only in critically ill COVID‐19 patients. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following the two other prognostic markers of COVID‐19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between ALC and LDH abnormalities and subsequent rise of NfL implicate that the multi‐organ failure is the most likely cause of neuronal injury in severe COVID‐19 patients. The addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3. Interpretation A substantial increase in serum/plasma NfL reproducibly enhanced COVID‐19 mortality prediction. Combined with other prognostic markers, such as ALC and LDH that are routinely measured in ICU patients, NfL measurements might be useful to identify the patients at a high risk of COVID‐19‐associated mortality, who might still benefit from escalated care.

Although a great deal of work has been completed towards the study on geopolymer concrete (GC), most of the efforts have focused on the material mechanical behavior. The objective of this paper is to present the results of an experimental study aimed to investigate the stress-strain behavior of confined fly ash and slag-based GC (FASGC) through the compression testing of a total of fourteen square ambient-cured short columns. The experimental results indicated that the increase in the slag content resulted in higher unconfined compressive strength but more obvious brittle property of confined FASGC. The effectiveness of lateral steel confinement was higher for FASGC than that for ordinary Portland cement-based concrete (OPCC), despite the lateral confinement index Kn of the former one was a little smaller compared to the latter one, the maximum differences in both fcc/fc0 and εcc/εc0 between them were 20.8% and 59.3%, respectively. Both fcc/fc0 and εcc/εc0 were not strongly related to the variation of the spacing of transverse reinforcement. The increase in the diameter of transverse reinforcement was not obviously improve the fcc/fc0 but resulted in the increase in the εcc/εc0, nonetheless, the εcc/εc0 was only increased by 70.9% as the Kn increased 3 times. The models were proposed to predict both ultimate stress and strain and to describe the stress-strain behavior of FASGC with good accuracy, more test data is further need to refine the proposed models. In light of the results, it is recommended to further investigate the effect of the fibers such as steel fiber, FRP fiber on the improvement of the brittle behavior of FASGC.

Abstract The ability of patients with hematologic malignancies (HM) to develop an effective humoral immune response after COVID-19 is unknown. A prospective study was performed to monitor the immune response to SARS-CoV-2 of patients with follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphoproliferative disorders (CLD), multiple myeloma (MM), or myelodysplastic/myeloproliferative syndromes (MDS/MPN). Antibody (Ab) levels to the SARS-CoV-2 nucleocapsid (N) and spike (S) protein were measured at +1, +3, +6 months after nasal swabs became PCR-negative. Forty-five patients (9 FL, 8 DLBCL, 8 CLD, 10 MM, 10 MDS/MPS) and 18 controls were studied. Mean anti-N and anti-S-Ab levels were similar between HM patients and controls, and shared the same behavior, with anti-N Ab levels declining at +6 months and anti-S-Ab remaining stable. Seroconversion rates were lower in HM patients than in controls. In lymphoma patients mean Ab levels and seroconversion rates were lower than in other HM patients, primarily because all nine patients who had received rituximab within 6 months before COVID-19 failed to produce anti-N and anti-S-Ab. Only one patient requiring hematological treatment after COVID-19 lost seropositivity after 6 months. No reinfections were observed. These results may inform vaccination policies and clinical management of HM patients.

Dysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease, including multisystem inflammatory syndrome in children (MIS-C) and chilblain-like lesions (CLLs), otherwise known as “COVID toes,” remains unclear. Studying multinational cohorts, we found that, in CLLs, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs after disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19–affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased NET levels when compared with other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.

Abstract A short‐term (30 days before an earthquake) prediction of an earthquake is a big challenge in seismology. As a first step, we apply deep learning to the ionospheric total electron content (TEC) data between 2003 and 2014 to detect the seismo‐ionospheric precursors of M ≥ 6.0 earthquakes in Taiwan. The bidirectional Long Short‐Term Memory (Bi‐LSTM) network is employed to use observed input data (features) to obtain the sequential TEC variations. The five input features are sequential vectors of TEC, the geomagnetic index Dst, the solar activity index F10.7, sunspot number (SSN), and solar emission index Lyman‐α. The daily values of F10.7, SSN, and Lyman‐α are converted into hourly values, depending on the solar elevation angle. The calculated hourly TEC variations can be more precisely predicted with this data conversion. We calculate the normalized difference of errors between two 15‐day adjacent stages as the “relative error”. Three trained models with the best discrimination between the relative errors of earthquake and no‐earthquake cases are chosen as classifiers. These three classifiers are then used to have a majority vote to declare whether the 30‐day period is related to the preparation of an earthquake or not. The results show that all 22 positive cases (earthquakes) are successfully predicted, giving a true positive rate of 100%. Among the 19 negative cases (normal cases), 10 of them are true negative.” Overall, a high accuracy of 78.05% is obtained.

Abstract SARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds.

Background: The success of clinical trials in Epidermolysis Bullosa (EB) is dependent upon the availability of a valid and reliable scoring tool that can accurately assess and monitor disease severity. The Epidermolysis Bullosa Disease Activity and Scarring Index (EBDASI) and Instrument for Scoring Clinical Outcomes of Research for Epidermolysis Bullosa (iscorEB) were independently developed and validated against the Birmingham Epidermolysis Bullosa Severity Score but have never been directly compared. Objective: To compare the reliability, convergent validity, and discriminant validity of the EBDASI and iscorEB scoring tools. Methods: An observational cohort study was conducted in 15 patients with EB. Each patient was evaluated using the EBDASI and iscorEB-clinician scoring tools by 6 dermatologists with expertise in EB. Quality of life was assessed using the iscorEB-patient and Quality of Life in EB measures. Results: The intraclass correlation coefficients for interrater reliability were 0.942 for the EBDASI and 0.852 for the iscorEB-clinician. The intraclass correlation coefficients for intrarater reliability was 0.99 for both scores. The two tools demonstrated strong convergent validity with each other. Conclusion: Both scoring tools demonstrate excellent reliability. The EBDASI appears to better discriminate between EB types and disease severities.

The antibody profile against autoantigens previously associated with autoimmune diseases and other human proteins in patients with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) remains poorly defined. Here we show that 30% of adults with COVID-19 had autoantibodies against the lung antigen KCNRG, and 34% had antibodies to the SLE-associated Smith-D3 protein. Children with COVID-19 rarely had autoantibodies; one of 59 children had GAD65 autoantibodies associated with acute onset of insulin-dependent diabetes. While autoantibodies associated with SLE/Sjögren’s syndrome (Ro52, Ro60, and La) and/or autoimmune gastritis (gastric ATPase) were detected in 74% (40/54) of MIS-C patients, further analysis of these patients and of children with Kawasaki disease (KD), showed that the administration of intravenous immunoglobulin (IVIG) was largely responsible for detection of these autoantibodies in both groups of patients. Monitoring in vivo decay of the autoantibodies in MIS-C children showed that the IVIG-derived Ro52, Ro60, and La autoantibodies declined to undetectable levels by 45-60 days, but gastric ATPase autoantibodies declined more slowly requiring >100 days until undetectable. Further testing of IgG and/or IgA antibodies against a subset of potential targets identified by published autoantigen array studies of MIS-C failed to detect autoantibodies against most (16/18) of these proteins in patients with MIS-C who had not received IVIG. However, Troponin C2 and KLHL12 autoantibodies were detected in 2 of 20 and 1 of 20 patients with MIS-C, respectively. Overall, these results suggest that IVIG therapy may be a confounding factor in autoantibody measurements in MIS-C and that antibodies against antigens associated with autoimmune diseases or other human proteins are uncommon in MIS-C.

Accurate prediction of traffic flow plays an important role in ensuring public traffic safety and solving traffic congestion. Because graph convolutional neural network (GCN) can perform effective feature calculation for unstructured data, doing research based on GCN model has become the main way for traffic flow prediction research. However, most of the existing research methods solving this problem are based on combining the graph convolutional neural network and recurrent neural network for traffic prediction. Such research routines have high computational cost and few attentions on impaction of different time and nodes. In order to improve the accuracy of traffic flow prediction, a gated attention graph convolution model based on multiple spatiotemporal channels was proposed in this paper. This model takes multiple time period data as input and extracts the features of each channel by superimposing multiple gated temporal and spatial attention modules. The final feature vector is obtained by means of weighted linear superposition. Experimental results on two sets of data show that the proposed method has good performance in precision and interpretability.

BK virus (BKV)-hemorrhagic cystitis (HC) is a well-known and rarely fatal complication of hematopoietic stem cell transplantation (HSCT). Treatment for BKV-HC is limited, but virus-specific T-cells (VST) represent a promising therapeutic option feasible for use posttransplant. We report on the case of a 16-year-old male with dedicator of cytokinesis 8 (DOCK8) deficiency who underwent haploidentical HSCT complicated by severe BKV-HC, catastrophic renal hemorrhage, and VST-associated cytokine release syndrome (CRS). Gross hematuria refractory to multiple interventions began with initiation of posttransplant cyclophosphamide (PT/Cy). Complete left renal arterial embolization (day +43) was ultimately indicated to control intractable renal hemorrhage. Subsequent infusion of anti-BK VSTs was complicated by CRS and progressive multiorgan failure, with postmortem analysis confirming diagnosis of hepatic sinusoidal obstruction syndrome (SOS). This case illustrates opportunities for improvement in the management of severe BKV-HC posttransplant while highlighting rare and potentially life-threatening complications of BKV-HC and VST therapy.

Abstract Background Europeans and American Indians were major genetic ancestry of Hispanics in the U.S. These ancestral groups have markedly different incidence rates and outcomes in many types of cancers. Therefore, the genetic admixture may cause biased genetic association study with cancer susceptibility variants specifically in Hispanics. For example, the incidence rate of liver cancer has been shown with substantial disparity between Hispanic, Asian and non-Hispanic white populations. Currently, ancestry informative marker (AIM) panels have been widely utilized with up to a few hundred ancestry-informative single nucleotide polymorphisms (SNPs) to infer ancestry admixture. Notably, current available AIMs are predominantly located in intron and intergenic regions, while the whole exome sequencing (WES) protocols commonly used in translational research and clinical practice do not cover these markers. Thus, it remains challenging to accurately determine a patient’s admixture proportion without additional DNA testing. Results In this study we designed an unique AIM panel that infers 3-way genetic admixture from three distinct and selective continental populations (African (AFR), European (EUR), and East Asian (EAS)) within evolutionarily conserved exonic regions. Initially, about 1 million exonic SNPs from selective three populations in the 1000 Genomes Project were trimmed by their linkage disequilibrium (LD), restricted to biallelic variants, and finally we optimized to an AIM panel with 250 SNP markers, or the UT-AIM250 panel, using their ancestral informativeness statistics. Comparing to published AIM panels, UT-AIM250 performed better accuracy when we tested with three ancestral populations (accuracy: 0.995 ± 0.012 for AFR, 0.997 ± 0.007 for EUR, and 0.994 ± 0.012 for EAS). We further demonstrated the performance of the UT-AIM250 panel to admixed American (AMR) samples of the 1000 Genomes Project and obtained similar results (AFR, 0.085 ± 0.098; EUR, 0.665 ± 0.182; and EAS, 0.250 ± 0.205) to previously published AIM panels (Phillips-AIM34: AFR, 0.096 ± 0.127, EUR, 0.575 ± 0.290, and EAS, 0.330 ± 0.315; Wei-AIM278: AFR, 0.070 ± 0.096, EUR, 0.537 ± 0.267, and EAS, 0.393 ± 0.300). Subsequently, we applied the UT-AIM250 panel to a clinical dataset of 26 self-reported Hispanic patients in South Texas with hepatocellular carcinoma (HCC). We estimated the admixture proportions using WES data of adjacent non-cancer liver tissues (AFR, 0.065 ± 0.043; EUR, 0.594 ± 0.150; and EAS, 0.341 ± 0.160). Similar admixture proportions were identified from corresponding tumor tissues. In addition, we estimated admixture proportions of The Cancer Genome Atlas (TCGA) collection of hepatocellular carcinoma (TCGA-LIHC) samples (376 patients) using the UT-AIM250 panel. The panel obtained consistent admixture proportions from tumor and matched normal tissues, identified 3 possible incorrectly reported race/ethnicity, and/or provided race/ethnicity determination if necessary. Conclusions Here we demonstrated the feasibility of using evolutionarily conserved exonic regions to infer admixture proportions and provided a robust and reliable control for sample collection or patient stratification for genetic analysis. R implementation of UT-AIM250 is available at https://github.com/chenlabgccri/UT-AIM250.

Azoospermia is divided into two categories of obstructive azoospermia and non-obstructive azoospermia. Before 1995, couples with a male partner diagnosed with non-obstructive azoospermia had to choose sperm donation or adoption to have a child. Currently, testicular sperm aspiration or micro-dissection testicular sperm extraction combined with intracytoplasmic sperm injection allows patients with non-obstructive azoospermia to have biological offspring. The sperm retrieval rate is significantly higher in micro-dissection testicular sperm extraction compared with testicular sperm aspiration. Additionally, micro-dissection testicular sperm extraction has the advantages of minimal invasion, safety, limited disruption of testicular function, a low risk of postoperative intratesticular bleeding, and low serum testosterone concentrations. Failed micro-dissection testicular sperm extraction has significant emotional and financial implications on the involved couples. Testicular sperm aspiration and micro-dissection testicular sperm extraction have the possibility of failure. Therefore, predicting the sperm retrieval rate before surgery is important. This narrative review summarizes the existing data on testicular sperm aspiration and micro-dissection testicular sperm extraction to identify the possible factor(s) that can predict the presence of sperm to guide clinical practice. The predictors of surgical sperm retrieval in patients with non-obstructive azoospermia have been widely studied, but there is no consensus.

Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN–, type II IFN–, and NF-κB–dependent whole-blood transcriptional signatures. A broad inflammatory signature was observed, implicating activation of various immune and nonhematopoietic cell subsets. Discordance between IFN-α2a protein and IFNA2 transcript levels in blood suggests that type I IFNs during COVID-19 may be primarily produced by tissue-resident cells. Multivariable analysis of patients’ first samples revealed 12 biomarkers (CCL2, IL-15, soluble ST2 [sST2], NGAL, sTNFRSF1A, ferritin, IL-6, S100A9, MMP-9, IL-2, sVEGFR1, IL-10) that when increased were independently associated with mortality. Multivariate analyses of longitudinal biomarker trajectories identified 8 of the aforementioned biomarkers (IL-15, IL-2, NGAL, CCL2, MMP-9, sTNFRSF1A, sST2, IL-10) and 2 additional biomarkers (lactoferrin, CXCL9) that were substantially associated with mortality when increased, while IL-1α was associated with mortality when decreased. Among these, sST2, sTNFRSF1A, IL-10, and IL-15 were consistently higher throughout the hospitalization in patients who died versus those who recovered, suggesting that these biomarkers may provide an early warning of eventual disease outcome.

Air pollution is a serious environmental and health issue that necessitates accurate and timely air-quality monitoring to provide timely health warnings to affected demographics and as a regulatory tool for reduction of emission. Thus, a high-density sensor array was developed for detection and quantification of NO2, SO2, and O3—three contributing air pollutants used for monitoring Air Quality Index (AQI). The gas sensor array operates on the principle of chemiresistive gas sensing with light-tunable selectivity and sensitivity which was achieved by combining the chemical selectivity and photoactive property of macrocyclic compounds with the chemical and electrical sensitivity of semiconducting single-walled carbon nanotubes (SWNTs). More specifically, sensing materials comprising hybrid nanostructures of SWNTs functionalized with either a metallophthalocyanine (MPc) derivative or a metalloporphyrin (MPor) derivative were formulated into printable inks. Each sensor in the array was fabricated by ink-jet printing of sensing materials onto interdigitated platinum electrodes. The sensor array demonstrated tunable sensitivity (in the range of sub-ppm to tens of ppm) to NO2, SO2, and O3 under different combinations of illumination conditions and specific sensing materials.

In this work, we used a template-free method to synthesize zinc sulfide (ZnS) materials. The photocatalytic performances of the samples were evaluated, and the physical natures of the ZnS nanocrystals were determined by photoluminescence (PL). Interestingly, the temperature-dependent PL variations of the samples were very different in connection with the synthesis condition. Combined with a series of catalytic experiments, it suggested that the intrinsic self-absorption of PL and photon recycling play key roles in photocatalysis. This work gives a new idea for understanding the photocatalysis and presents a new strategy to design ZnS related photocatalysts for further applications.

Research during the last decade has given many new insights into factors contributing to the development and evolution of atopic dermatitis (AD). Factors identified include skin barrier defects, proinflammatory predispositions, anomalies in the microbiome, and some environmental influences. There is now the possibility of personalizing therapy and potentially, of disease prevention. However, discerning the respective roles of early factors leading to AD development is complex. Stringent analysis for confounders must precede attribution of causality to any factor. This review examines current understandings of AD pathogenesis and related research approaches in AD primary prevention.

Early detection of Primary Immunodeficiencies Disorders (PIDDs) is of paramount importance for effective treatment and disease management. Many PIDDs would be strong candidates for newborn screening (NBS) if robust screening methods could identify patients from dried blood spots (DBS) during the neonatal period. As majority of congenital PIDDs result in the reduction or absence of specific proteins, direct quantification of these target proteins represents an attractive potential screening tool. Unfortunately, detection is often limited by the extremely low protein concentrations in blood cells and limited blood volume present in DBS. We have recently developed a robust novel method for quantification of low abundance proteins in DBS for PIDDs using peptide immunoaffinity enrichment coupled to selected reaction monitoring (immuno-SRM). Here, we further generated a multiplexed Immuno-SRM panel for simultaneous screening of eight signature peptides representing five PIDD-specific and two cell-type specific proteins from DBS. In samples from 28 PIDD patients including two carriers, representing X-Linked Agammaglobulinemia (XLA), Wiskott-Aldrich Syndrome (WAS), X-Linked Chronic Granulomatous Disease (XL-CGD), DOCK8 Deficiency and ADA deficiency, peptides representing each disease are significantly reduced relative to normal controls and patient identification had excellent agreement with clinical and molecular diagnosis. Also included in the multiplex panel are cell specific markers for platelets (CD42) and Natural Killer Cells (CD56). In patients with WAS, CD42 levels were found to be significantly reduced consistent with characteristic thrombocytopenia. A patient with WAS analyzed before and after bone marrow transplant showed normalized WAS protein and platelet CD42 after treatment highlighting the ability of immuno-SRM to monitor the effects of PIDD treatment. The assay was readily reproduced in two separate laboratories with similar analytical performance and complete agreement in patient diagnosis demonstrating the effective standardized methods. A high-throughput Immuno-SRM method screens PIDD-specific peptides in a 2.5-min runtime meeting high volume NBS workflow requirements was also demonstrated in this report. This high-throughput method returned identical results to the standard Immuno-SRM PIDD panel. Immuno-SRM peptide analysis represents a robust potential clinical diagnostic for identifying and studying PIDD patients from easily collected and shipped DBS and supports a significant potential for early PIDD diagnosis through newborn screening.

In today's society, displays are indispensable for digital interaction and personal contact. Therefore, the development of displays is an urgent need for the next generation. Leading the commercialization trends is the development of industrial, high-resolution, portable, and multifunctional displays. Moreover, for small-size portable displays, the most critical factor affecting future applications is their flexibility. Among the various materials that can act as the channel layer, low-temperature polycrystalline silicon (LTPS) is a potential candidate for next-generation portable displays, which require high resolution and stable reliability, and which can achieve virtual reality applications. This article is a review of the development of the LTPS thin-film transistors (TFTs) on soft and flexible electronics, especially the effect of mechanical strain. This article starts by providing an overview of the difficulties in fabricating LTPS TFTs on flexible substrates. The physical mechanism corresponding to each degradation caused by mechanical stress is presented next. Finally, to support the development of the flexible technologies and realize their commercialization, methods to overcome these mechanical strain-induced degradations are reported in three different aspects by understanding the physical degradation model. Keywords: Flexible LTPS TFT, Mechanical stress, Active layer design and mechanical absorption layer, Gate insulator quality improvement

Papraoxonase-1 (PON1) is a hydrolytic lactonase enzyme that is synthesized in the liver and circulates attached to high-density lipoproteins (HDL). Clinical studies have demonstrated an association between diminished PON-1 and the progression of chronic kidney disease (CKD). However, whether decreased PON-1 is mechanistically linked to renal injury is unknown. We tested the hypothesis that the absence of PON-1 is mechanistically linked to the progression of renal inflammation and injury in CKD. Experiments were performed on control Dahl salt-sensitive rats (SSMcwi, hereafter designated SS rats) and Pon1 knock-out rats (designated SS-Pon1em1Mcwi, hereafter designated SS-PON-1 KO rats) generated by injecting a CRISPR targeting the sequence into SSMcwi rat embryos. The resulting mutation is a 7 bp frameshift insertion in exon 4 of the PON-1 gene. First, to examine the renal protective role of PON-1 in settings of CKD, ten-week-old, age-matched male rats were maintained on a high-salt diet (8% NaCl) for up to 5 weeks to initiate the salt-sensitive hypertensive renal disease characteristic of this model. We found that SS-PON-1 KO rats demonstrated several hallmarks of increased renal injury vs. SS rats including increased renal fibrosis, sclerosis, and tubular injury. SS-PON-1 KO also demonstrated increased recruitment of immune cells in the renal interstitium, as well as increased expression of inflammatory genes compared to SS rats (all p < 0.05). SS-PON-1 KO rats also showed a significant (p < 0.05) decline in renal function and increased renal oxidative stress compared to SS rats, despite no differences in blood pressure between the two groups. These findings suggest a new role for PON-1 in regulating renal inflammation and fibrosis in the setting of chronic renal disease independent of blood pressure.

Freshwater harmful algal blooms (HABs) are increasing in number and severity worldwide. These HABs are chiefly composed of one or more species of cyanobacteria, also known as blue-green algae, such as Microcystis and Anabaena. Numerous HAB cyanobacterial species produce toxins (e.g., microcystin and anatoxin—collectively referred to as HAB toxins) that disrupt ecosystems, impact water and air quality, and deter recreation because they are harmful to both human and animal health. Exposure to these toxins can occur through ingestion, inhalation, or skin contact. Acute health effects of HAB toxins have been well documented and include symptoms such as nausea, vomiting, abdominal pain and diarrhea, headache, fever, and skin rashes. While these adverse effects typically increase with amount, duration, and frequency of exposure, susceptibility to HAB toxins may also be increased by the presence of comorbidities. The emerging science on potential long-term or chronic effects of HAB toxins with a particular emphasis on microcystins, especially in vulnerable populations such as those with pre-existing liver or gastrointestinal disease, is summarized herein. This review suggests additional research is needed to define at-risk populations who may be helped by preventative measures. Furthermore, studies are required to develop a mechanistic understanding of chronic, low-dose exposure to HAB toxins so that appropriate preventative, diagnostic, and therapeutic strategies can be created in a targeted fashion.

Abstract This paper discusses the development challenges of an offshore fluvial oil reservoir with horizontal wells. In highly productive sandstone reservoirs, horizontal wells suffer from uneven flow profile and subsequent premature coning effects because of sand heterogeneity and heel to toe effect. Moreover, excessively increasing the production rate or horizontal well length can increase the risk of limited sweep efficiency, resulting in remaining oil in the toe or poor sand with low permeability. First, we analyze the characters of fluvial oil reservoir focusing on sand architecture and heterogeneity. Second, the sweep efficiency was calculated by the production data. Finally, we optimize inflow control device (ICD) for several wells and compare the response of ICD wells with conventional screen completion wells.

Magmatic sill intrusions into organic-rich sediments cause the release of thermogenic CH4 and CO2. Pore fluids from the Guaymas Basin (Gulf of California), a sedimentary basin with recent magmatic activity, were investigated to constrain the link between sill intrusions and fluid seepage as well as the timing of sill-induced hydrothermal activity. Sampling sites were close to a hydrothermal vent field at the northern rift axis and at cold seeps located up to 30 km away from the rift. Pore fluids close to the active hydrothermal vent field showed a slight imprint by hydrothermal fluids and indicated a shallow circulation system transporting seawater to the hydrothermal catchment area. Geochemical data of pore fluids at cold seeps showed a mainly ambient diagenetic fluid composition without any imprint related to high temperature processes at greater depth. Seep communities at the seafloor were mainly sustained by microbial methane, which rose along pathways formed earlier by hydrothermal activity, driving the anaerobic oxidation of methane (AOM) and the formation of authigenic carbonates.Overall, our data from the cold seep sites suggest that at present, sill-induced hydrothermalism is not active away from the ridge axis, and the vigorous venting of hydrothermal fluids is restricted to the ridge axis. Using the sediment thickness above extinct conduits and carbonate dating, we calculated that deep fluid and thermogenic gas flow ceased 28 to 7 kyr ago. These findings imply a short lifetime of hydrothermal systems, limiting the time of unhindered carbon release as suggested in previous modeling studies. Consequently, activation and deactivation mechanisms of these systems need to be better constrained for the use in climate modeling approaches.