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Abstract In the human genome, heterozygous sites refer to genomic positions with a different allele or nucleotide variant on the maternal and paternal chromosomes. Resolving these allelic differences by chromosomal copy, also known as phasing, is achievable on a short-read sequencer when using a library preparation method that captures long-range genomic information. TELL-Seq is a library preparation that captures long-range genomic information with the aid of molecular identifiers (barcodes). The same barcode is used to tag the reads derived from the same long DNA fragment within a range of up to 200 kilobases (kb), generating linked-reads. This strategy can be used to phase an entire genome. Here, we introduce a TELL-Seq protocol developed for targeted applications, enabling the phasing of enriched loci of varying sizes, purity levels, and heterozygosity. To validate this protocol, we phased 2–200 kb loci enriched with different methods: CRISPR/Cas9-mediated excision coupled with pulse-field electrophoresis for the longest fragments, CRISPR/Cas9-mediated protection from exonuclease digestion for mid-size fragments, and long PCR for the shortest fragments. All selected loci have known clinical relevance: BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, and PKI3CA. Collectively, the analyses show that TELL-Seq can accurately phase 2–200 kb targets using a short-read sequencer.

Abstract Comparing brain structure across species and regions enables key functional insights. Leveraging publicly available data from a novel mass cytometry-based method, synaptometry by time of flight (SynTOF), we applied an unsupervised machine learning approach to conduct a comparative study of presynapse molecular abundance across three species and three brain regions. We used neural networks and their attractive properties to model complex relationships among high dimensional data to develop a unified, unsupervised framework for comparing the profile of more than 4.5 million single presynapses among normal human, macaque, and mouse samples. An extensive validation showed the feasibility of performing cross-species comparison using SynTOF profiling. Integrative analysis of the abundance of 20 presynaptic proteins revealed near-complete separation between primates and mice involving synaptic pruning, cellular energy, lipid metabolism, and neurotransmission. In addition, our analysis revealed a strong overlap between the presynaptic composition of human and macaque in the cerebral cortex and neostriatum. Our unique approach illuminates species- and region-specific variation in presynapse molecular composition.

Abstract Stocking programs have been widely implemented to re-establish extirpated fish species to their historical ranges; when employed in species with complex life histories, such management activities should include careful consideration of resulting hybridization dynamics with resident stocks and corresponding outcomes on recovery initiatives. Genetic monitoring can be instrumental for quantifying the extent of introgression over time, however conventional markers typically have limited power for the identification of advanced hybrid classes, especially at the intra-specific level. Here, we demonstrate a workflow for developing, evaluating and deploying a Genotyping-in-Thousands by Sequencing (GT-seq) SNP panel with the power to detect advanced hybrid classes to assess the extent and trajectory of intra-specific hybridization, using the sockeye salmon (Oncorhynchus nerka) stocking program in Skaha Lake, British Columbia as a case study. Previous analyses detected significant levels of hybridization between the anadromous (sockeye) and freshwater resident (kokanee) forms of O. nerka, but were restricted to assigning individuals to pure-stock or “hybrid”. Simulation analyses indicated our GT-seq panel had high accuracy, efficiency and power (> 94.5%) of assignment to pure-stock sockeye salmon/kokanee, F1, F2, and B2 backcross-sockeye/kokanee. Re-analysis of 2016/2017 spawners previously analyzed using TaqMan® assays and otolith microchemistry revealed shifts in assignment of some hybrids to adjacent pure-stock or B2 backcross classes, while new assignment of 2019 spawners revealed hybrids comprised 31% of the population, ~ 74% of which were B2 backcross or F2. Overall, the GT-seq panel development workflow presented here could be applied to virtually any system where genetic stock identification and intra-specific hybridization are important management parameters.

Abstract The Grade of meningioma has significant implications for selecting treatment regimens ranging from observation to surgical resection with adjuvant radiation. For most patients, meningiomas are diagnosed radiologically, and Grade is not determined unless a surgical procedure is performed. The goal of this study is to train a novel auto-classification network to determine Grade I and II meningiomas using T1-contrast enhancing (T1-CE) and T2-Fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. Ninety-six consecutive treatment naïve patients with pre-operative T1-CE and T2-FLAIR MR images and subsequent pathologically diagnosed intracranial meningiomas were evaluated. Delineation of meningiomas was completed on both MR images. A novel asymmetric 3D convolutional neural network (CNN) architecture was constructed with two encoding paths based on T1-CE and T2-FLAIR. Each path used the same 3 × 3 × 3 kernel with different filters to weigh the spatial features of each sequence separately. Final model performance was assessed by tenfold cross-validation. Of the 96 patients, 55 (57%) were pathologically classified as Grade I and 41 (43%) as Grade II meningiomas. Optimization of our model led to a filter weighting of 18:2 between the T1-CE and T2-FLAIR MR image paths. 86 (90%) patients were classified correctly, and 10 (10%) were misclassified based on their pre-operative MRs with a model sensitivity of 0.85 and specificity of 0.93. Among the misclassified, 4 were Grade I, and 6 were Grade II. The model is robust to tumor locations and sizes. A novel asymmetric CNN with two differently weighted encoding paths was developed for successful automated meningioma grade classification. Our model outperforms CNN using a single path for single or multimodal MR-based classification.

Abstract Sexual dimorphism in gene regulation, including DNA methylation, is the main driver of sexual dimorphism in phenotypes. However, the questions of how and when sex shapes DNA methylation remain unresolved. Recently, using mice with different combinations of genetic and phenotypic sex, we identified sex-associated differentially methylated regions (sDMRs) that depended on the sex phenotype. Focusing on a panel of validated sex-phenotype dependent male- and female-biased sDMRs, we tested the developmental dynamics of sex bias in liver methylation and the impacts of mutations in the androgen receptor, estrogen receptor alpha, or the transcriptional repressor Bcl6 gene. True hermaphrodites that carry both unilateral ovaries and contralateral testes were also tested. Our data show that sex bias in methylation either coincides with or follows sex bias in the expression of sDMR-proximal genes, suggesting that sex bias in gene expression may be required for demethylation at certain sDMRs. Global ablation of AR, ESR1, or a liver-specific loss of BCL6, all alter sDMR methylation, whereas presence of both an ovary and a testis delays the establishment of male-type methylation levels in hermaphrodites. Moreover, the Bcl6-LKO shows dissociation between expression and methylation, suggesting a distinct role of BCL6 in demethylation of intragenic sDMRs.

Abstract Evaluation of transcriptome data in combination with QTL information has been applied in many crops to study the expression of genes responsible for specific phenotypes. In oil palm, the mesocarp oil extracted from E. oleifera × E. guineensis interspecific hybrids is known to have lower palmitic acid (C16:0) content compared to pure African palms. The present study demonstrates the effectiveness of transcriptome data in revealing the expression profiles of genes in the fatty acid (FA) and triacylglycerol (TAG) biosynthesis processes in interspecific hybrids. The transcriptome assembly yielded 43,920 putative genes of which a large proportion were homologous to known genes in the public databases. Most of the genes encoding key enzymes involved in the FA and TAG synthesis pathways were identified. Of these, 27, including two candidate genes located within the QTL associated with C16:0 content, showed differential expression between developmental stages, populations and/or palms with contrasting C16:0 content. Further evaluation using quantitative real-time PCR revealed that differentially expressed patterns are generally consistent with those observed in the transcriptome data. Our results also suggest that different isoforms are likely to be responsible for some of the variation observed in FA composition of interspecific hybrids.

Abstract A dramatic band gap narrowing of 1.61 eV has been observed in Co-doped nanocrystals of CeO2 (ceria), as a result of thermal annealing, without changing the ceria crystal structure and the Co concentration. As demonstrated by x-ray absorption fine structures, thermal annealing incurs an oxygen coordination rearrangement around Co atoms from an octahedral coordination to a square-planar coordination. First principle calculation using density functional theory reveals two stable oxygen coordination types surrounding Co, consistent with the experimental observation. The band gap values calculated for the two stable coordination types differ dramatically, reproducing the experimentally observed band gap narrowing. These prominent effects due to local structure rearrangement around dopant atoms can lead to unprecedented methods for band gap engineering in doped nanocrystal oxides.

Abstract The Vavilov Institute of Plant Genetic Resources (VIR), in St. Petersburg, Russia, houses a unique genebank, with historical collections of landraces. When they were collected, the geographical distribution and genetic diversity of most crops closely reflected their historical patterns of cultivation established over the preceding millennia. We employed a combination of genomics, computational biology and phenotyping to characterize VIR’s 147 chickpea accessions from Turkey and Ethiopia, representing chickpea’s center of origin and a major location of secondary diversity. Genotyping by sequencing identified 14,059 segregating polymorphisms and genome-wide association studies revealed 28 GWAS hits in potential candidate genes likely to affect traits of agricultural importance. The proportion of polymorphisms shared among accessions is a strong predictor of phenotypic resemblance, and of environmental similarity between historical sampling sites. We found that 20 out of 28 polymorphisms, associated with multiple traits, including days to maturity, plant phenology, and yield-related traits such as pod number, localized to chromosome 4. We hypothesize that selection and introgression via inadvertent hybridization between more and less advanced morphotypes might have resulted in agricultural improvement genes being aggregated to genomic ‘agro islands’, and in genotype-to-phenotype relationships resembling widespread pleiotropy.

Abstract Fatty acid (FA) metabolism directly influences the functional capabilities of T cells in tumor microenvironments. Thus, developing tools to interrogate FA-uptake by T cell subsets is important for understanding tumor immunosuppression. Herein, we have generated a novel FA-Qdot 605 dye conjugate with superior sensitivity and flexibility to any of the previously commercially available alternatives. For the first time, we demonstrate that this nanoparticle can be used as a specific measure of fatty acid uptake by T cells both in-vitro and in-vivo. Flow cytometric analysis shows that both the location and activation status of T cells determines their FA uptake. Additionally, CD4+ Foxp3+ regulatory T cells (Tregs) uptake FA at a higher rate than effector T cell subsets, supporting the role of FA metabolism for Treg function. Furthermore, we are able to simultaneously detect glucose and fatty acid uptake directly within the tumor microenvironment. Cumulatively, our results suggest that this novel fluorescent probe is a powerful tool to understand FA utilization within the tumor, thereby providing an unprecedented opportunity to study T cell FA metabolism in-vivo.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Value co-creation can be defined as the joint benefit that is created by patients and medical service providers through the integration of their respective resources. Participation and interaction between doctors and patients can generate an outcome that benefits both sides. Relevant studies of value co-creation in the healthcare field are limited. This study established hypotheses to explore the association between doctor interaction behavior, patient participation in value co-creation, and patient satisfaction. A cross-sectional survey was conducted with 637 patients (outpatients and inpatients) at a tertiary-level hospital in Guangzhou, China. The analysis result indicated that doctor interaction behavior could stimulate patient participation in value co-creation then increase patient satisfaction. The standardized total effect, direct effect, and indirect effect were 0.641 (95%CI: 0.055 ~ 0.067), 0.546 (95%CI: 0.044 ~ 0.059), and 0.095 (95%CI: 0.032 ~ 0.166), respectively. Patient participation in value co-creation mediated the relationship between doctor interaction behavior and patient satisfaction. Among the different dimensions of doctor interaction behavior, access, risk assessment and transparency dimensions were associated with positive patient participation in value co-creation. During the treatment process, doctor interaction and patient participation can get satisfying results., (© 2024. The Author(s).)

This study spanned 6 years and 4 generations, involving the progressive crossbreeding of South African Kalahari Goat (SK) and Guizhou Black Goat (GB) over three generations, followed by cross fixation F3 with F1 in the fourth generation, accompanied by the use of molecular markers technology to select a high fertility population, resulting in the creation of a hybrid goat, BKF4 (11/16 SK lineage and 5/16 GB lineage). A comparative evaluation of the BKF4 hybrid breed and its parental breeds was conducted. Reproductive and production parameters of GB, SK, and BKF4 goat groups were monitored, including lambing rate (LR), survival rate (SR), daily weight gain at 3 months of age (DWG), and adult body weight (ABW) (n = 110, 106, 112 per group). In addition, dressing percentage (DP) (n = 12 per group) and analyses of amino acids (n = 8, 6, 10 per group) and fatty acids (n = 6 per group) were conducted to evaluate meat quality indicators. Results: (1) Reproductive and production performance: The index of LR reached 199%, significantly higher than GB and SK (p ≤ 0.001), with a SR of 95.0%, markedly higher than SK (p ≤ 0.001); DWG was 276.5 g, ABW reached 56.6 kg and with a dressing percentage (DP) of 54.5%, they are significantly surpassing GB (p ≤ 0.001). (2) Regarding meat quality: pH 45 -value and crude protein content (CP) increased, while intramuscular fat content increased compared to GB and ash content decreased. The amino acid composition was similar to GB, but the taste was more similar to SK. However, there were some negative impacts on fatty acid composition and functionality. (3) PCA analysis revealed that: BKF4 exhibited superior meat quality compared to GB and SK, influenced by two key factors contributing 83.49% and 16.51% to the explained variance, respectively. The key factors affecting meat quality include intramuscular fat (IMF), nutrient index (NI), PUFAs/MUFAs, n-6FAs, and drip loss (DL)., (© 2024. The Author(s).)

The role of neoadjuvant chemotherapy and its benefits in patients with triple-negative breast cancer (TNBC) and small tumors are unclear. This study aims to compare survival differences between clinical T1 TNBC receiving neoadjuvant chemotherapy (NAC) and adjuvant chemotherapy (AC). Data for patients with clinical T1 TNBC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized according to whether they received chemotherapy before or after surgery. Propensity Score Matching (PSM) was used to minimize the influence of confounding factors. OS and BCSS were compared between the two treatment sequences using Kaplan-Meier and univariate and multivariable Cox proportional hazards regression analyses. The study included 6249 women with T1 TNBC. In multivariate analysis, compared with that in the AC group, the hazard ratio for death in the NAC group was 1.54 (95% confidence interval 1.26-1.89, p < 0.001). NAC offers no additional benefits in any age group or T, N subgroups. Our findings suggest that NAC does not provide additional benefit to patients with clinical T1 TNBC, even in the presence of lymph node metastasis, or T1c., (© 2024. The Author(s).)

The interleukin (IL)-23 pathway is a pathogenic driver in psoriasis, psoriatic arthritis, and inflammatory bowel disease. Currently, no oral therapeutics selectively target this pathway. JNJ-77242113 is a peptide targeting the IL-23 receptor with high affinity (K D : 7.1 pM). In human cells, JNJ-77242113 potently and selectively inhibited proximal IL-23 signaling (IC 50 : 5.6 pM) without impacting IL-12 signaling. JNJ-77242113 inhibited IL-23-induced interferon (IFN)γ production in NK cells, and in blood from healthy donors and psoriasis patients (IC 50 : 18.4, 11 and 9 pM, respectively). In a rat trinitrobenzene sulfonic acid-induced colitis model, oral JNJ-77242113 attenuated disease parameters at doses ≥ 0.3 mg/kg/day. Pharmacologic activity beyond the gastrointestinal tract was also demonstrated. In blood from rats receiving oral JNJ-77242113, dose-dependent inhibition of ex vivo IL-23-stimulated IL-17A production was observed. In an IL-23-induced rat skin inflammation model, JNJ-77242113 inhibited IL-23-induced skin thickening and IL-17A, -17F and -22 gene induction. Oral dosing of JNJ-77242113 in healthy human volunteers inhibited ex vivo IL-23-stimulated IFNγ production in whole blood. Thus, JNJ-77242113 provided selective, systemic IL-23 pathway inhibition in preclinical models which translated to pharmacodynamic activity in healthy human volunteers, supporting the potential for JNJ-77242113 as a selective oral therapy for IL-23-driven immune-mediated diseases., (© 2024. The Author(s).)

Under the condition that the working face was directly covered with hard roof, the abrupt breaking of hard roof release significant amount of energy, thus prone to triggering dynamic disasters such as roadway instability or rockburst. This paper based on the engineering background of the Xieqiao Coal Mine's 11,618 working face, a numerical simulation method was put forward to study the dynamic response of roadway under the disturbance of hard roof breaking and proposed an evaluation index I C for roadway stability. Research indicates that the elastic energy released during the periodic weighting of the hard roof is higher than that released during the first weighting. Under the dynamic disturbance caused by hard roof breaking, the peak stresses of the roadway was slight decreased, accompanied by a significant increase in the range of stress concentration and plastic zone expansion. Roadway deformation patterns are significantly influenced by hard roof breaking, with noticeable increases in deformation on the roof and right side. During the period of hard roof breaking, the possibility of instability of the roadway increase significantly due to the disturbance caused by the dynamic load. The research results reveal the instability mechanism of roadway under the condition of hard roof, and provide a more reliable basis for evaluating the stability of roadway., (© 2024. The Author(s).)

Coronary atherosclerotic heart disease (CAD) is among the most prevalent chronic diseases globally. Circadian rhythm disruption (CRD) is closely associated with the progression of various diseases. However, the precise role of CRD in the development of CAD remains to be elucidated. The Circadian rhythm disruption score (CRDscore) was employed to quantitatively assess the level of CRD in CAD samples. Our investigation revealed a significant association between high CRDscore and adverse prognosis in CAD patients, along with a substantial correlation with CAD progression. Remarkably distinct CRDscore distributions were also identified among various subtypes. In summary, we have pioneered the revelation of the relationship between CRD and CAD at the single-cell level and established reliable markers for the development, treatment, and prognosis of CAD. A deeper understanding of these mechanisms may offer new possibilities for incorporating "the therapy of coronary heart disease based circadian rhythm" into personalized medical treatment regimens., (© 2024. The Author(s).)

Coagulation alterations manifest early after severe burns and are closely linked to mortality outcomes. Nevertheless, the precise characterization of coagulation changes associated with early mortality remains elusive. We examined alterations in indicators linked to mortality outcomes at both the transcriptomic and clinical characteristic levels. At the transcriptomic level, we pinpointed 28 differentially expressed coagulation-related genes (DECRGs) following burn injuries and endeavored to validate their causal relationships through Mendelian randomization. DECRGs tied to survival exhibit a significant association with neutrophil function, wherein the expression of CYP4F2 and P2RX1 serves as robust predictors of fatal outcomes. In terms of clinical indicators, early levels of D-dimer and alterations in serum calcium show a strong correlation with mortality outcomes. Coagulation depletion and fibrinolytic activation, stemming from the hyperactivation of coagulation pathways post-severe burns, are strongly linked to patient mortality. Monitoring these early coagulation markers with predictive value can effectively identify individuals necessitating priority critical care., (© 2024. The Author(s).)

The survival significance of the number of positive lymph nodes in salivary gland carcinoma remains unclear. Thus, the current study aimed to determine the effect of the number of positive lymph nodes on disease-specific survival (DSS) and overall survival (OS) in cN0 mucoepidermoid carcinoma (MEC) of the major salivary gland. Patients surgically treated for MEC of the major salivary gland between 1975 and 2019 were retrospectively enrolled from the surveillance, epidemiology, and end results database. The total population was randomly divided into training and test groups (1:1). Primary outcome variables were DSS and OS. Prognostic models were constructed based on the independent prognostic factors determined using univariate and multivariate Cox analyses in the training group and were validated in the test group using C-index. A total of 3317 patients (1624 men and 1693 women) with a mean age of 55 ± 20 years were included. The number of positive lymph nodes was an independent prognostic factor for both DSS and OS, but the effect began when at least two positive lymph nodes for DSS and three positive lymph nodes for OS were found. Predictive models for DSS and OS in the training group had C-indexes of 0.873 (95% confidence interval [CI] 0.853-0.893) and 0.835 (95% CI 0.817-0.853), respectively. The validation of the test group showed C-indexes of 0.877 (95% CI 0.851-0.902) for DSS and 0.820 (95% CI 0.798-0.842) for OS. The number of positive lymph nodes was statistically associated with survival in cN0 major salivary gland MEC. The current prognostic model could provide individualized follow-up strategies for patients with high reliability., (© 2024. The Author(s).)

Epidemiological studies have reported a positive association between chronic inflammation and cancer risk. However, the causal association between chronic inflammation and breast cancer (BC) risk remains unclear. Here, we performed a Mendelian randomization study to investigate the etiological role of chronic inflammation in BC risk. We acquired data regarding C-reactive protein (CRP), interleukin (IL)-1a, IL-1b, and IL-6 expression and BC related to single nucleotide polymorphisms (SNPs) from two larger consortia (the genome-wide association studies and the Breast Cancer Association Consortium). Next, we conducted the two-sample Mendelian randomization study to investigate the relationship of the abovementioned inflammatory factors with the incidence of BC. We found that genetically predicted CRP, IL-6, and IL-1a levels did not increase BC incidence (odds ratio (OR) CRP 1.06, 95% confidence interval (CI) 0.98-1.12, P = 0.2059, OR IL-6 1.05, 95% CI 0.95-1.16, P = 0.3297 and OR IL-1a 1.01, 95% CI 0.99-1.03, P = 0.2167). However, in subgroup analysis, genetically predicted IL-1b levels increased ER + BC incidence (OR 1.15, 95% CI 1.03-1.27, P = 0.0088). Our study suggested that genetically predicted IL-1b levels were found to increase ER + BC susceptibility. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, which deserves further research., (© 2024. The Author(s).)

Machine learning algorithms were used to analyze the odds and predictors of complications of thyroid damage after radiation therapy in patients with head and neck cancer. This study used decision tree (DT), random forest (RF), and support vector machine (SVM) algorithms to evaluate predictors for the data of 137 head and neck cancer patients. Candidate factors included gender, age, thyroid volume, minimum dose, average dose, maximum dose, number of treatments, and relative volume of the organ receiving X dose (X: 10, 20, 30, 40, 50, 60 Gy). The algorithm was optimized according to these factors and tenfold cross-validation to analyze the state of thyroid damage and select the predictors of thyroid dysfunction. The importance of the predictors identified by the three machine learning algorithms was ranked: the top five predictors were age, thyroid volume, average dose, V50 and V60. Of these, age and volume were negatively correlated with thyroid damage, indicating that the greater the age and thyroid volume, the lower the risk of thyroid damage; the average dose, V50 and V60 were positively correlated with thyroid damage, indicating that the larger the average dose, V50 and V60, the higher the risk of thyroid damage. The RF algorithm was most accurate in predicting the probability of thyroid damage among the three algorithms optimized using the above factors. The Area under the receiver operating characteristic curve (AUC) was 0.827 and the accuracy (ACC) was 0.824. This study found that five predictors (age, thyroid volume, mean dose, V50 and V60) are important factors affecting the chance that patients with head and neck cancer who received radiation therapy will develop hypothyroidism. Using these factors as the prediction basis of the algorithm and using RF to predict the occurrence of hypothyroidism had the highest ACC, which was 82.4%. This algorithm is quite helpful in predicting the probability of radiotherapy complications. It also provides references for assisting medical decision-making in the future., (© 2023. The Author(s).)

Knowledge tracking is to analyze the mastery of students' knowledge through the learning track. This is very important for online education, since it can determine a learner's current knowledge level by analyzing the learning history and then make recommendations for future learning. In the past, the commonly used model for knowledge tracking is the convolutional neural network, but it has long-term sequence dependencies. With the invention of Transformer, it has excellent performance in long-sequence modeling by virtue of the attention mechanism, and is gradually introduced into the field of knowledge tracking. However, through our research, some knowledge tracking data sets have a large number of continuous and repetitive training, which will cause Transformer model to ignore the potential connections between some knowledge points. To overcome this problem, we introduce a convolutional attention mechanism to help the model perceive contextual information better. In addition, we simulate the forgetting phenomenon of students during the learning process by calculating the forgetting factor, and fuse it with the weight matrix generated by the model to improve the accuracy of the model. As a result, a Transformer-based Convolutional Forgetting Knowledge Tracking (TCFKT) model is presented in this paper. According to the experimental results conducted on the real world ASSITments2012, ASSISTments2017, KDD a, STATIC datasets, the TCFKT model outperforms other knowledge tracking models., (© 2023. The Author(s).)

Copper Zinc Tin Sulphide (CZTS) is a propitious semiconductor for active absorber material in thin-film solar cells (SCs). Here, SC architecture comprising FTO/ZnS/CZTS/variable HTLs/Au is discussed. Fluorine-doped tin oxide (FTO) and gold (Au) are used as front and back contacts, respectively. Zinc sulphide (ZnS) is used as an active electron transport layer (ETL), while different Cu-based materials (Cu 2 O, CuO, CuI, and CuSCN) are used as hole transport layers (HTL). A one-dimensional solar cell capacitance simulator (SCAPS-1D) is utilized to simulate the SC structure. Among different Cu-based HTLs, Cu 2 O is preferred as a potential candidate for high cell performance of CZTS-based SC. The effects of various layer parameters such as thickness, doping density, and carrier concentrations, electron affinity of HTL and absorber, respectively, are also discussed. After optimization of the device, variation of operating temperature and the effect of series and shunt resistance are also taken into consideration. The optimized results of thickness and acceptor concentration (N A ) of absorber material are 1.5 µm and approx. 1.0 × 10 19  cm -3 , respectively. In addition, the function of HTL (with and without) in the designed SC structure is also studied. Capacitance-voltage (C-V) characteristics are also discussed to get an insight of built-in potential. We have achieved cell performances viz. efficiency = 31.86%, short circuit current density = 32.05 mA/cm 2 , open circuit voltage = 1.19 V, and fill factor = 83.37%., (© 2023. The Author(s).)

Inhibin subunit beta A (INHBA) is a member of the transforming growth factor-beta (TGF-β) superfamily that plays a fundamental role in various cancers. However, a systematic analysis of the exact role of INHBA in patients with gastric cancer (GC) has not yet been conducted. We evaluated the expression levels of INHBA and the correlation between INHBA and GC prognosis in GC. The relationship between INHBA expression, immune infiltration levels, and type markers of immune cells in GC was also explored. In addition, we studied INHBA mutations, promoter methylation, and functional enrichment analysis. Besides, high expression levels of INHBA in GC were significantly related to unfavorable prognosis. INHBA was negatively correlated with B cell infiltration, but positively correlated with macrophage and most anticancer immunity steps. INHBA expression was positively correlated with the type markers of CD8+ T cells, neutrophils, macrophages, and dendritic cells. INHBA has a weak significant methylation level change between tumor and normal tissues and mainly enriched in cancer-related signaling pathways. The present study implies that INHBA may serve as a potential biomarker for predicting the prognosis of patients with GC. INHBA is a promising predictor of immunotherapy response, with higher levels of INHBA indicating greater sensitivity., (© 2023. The Author(s).)

Incorporating knowledge graphs into recommendation systems has attracted wide attention in various fields recently. A Knowledge graph contains abundant information with multi-type relations among multi-type nodes. The heterogeneous structure reveals not only the connectivity but also the complementarity between the nodes within a KG, which helps to capture the signal of potential interest of the user. However, existing research works have limited abilities in dealing with the heterogeneous nature of knowledge graphs, resulting in suboptimal recommendation results. In this paper, we propose a new recommendation method based on iterative heterogeneous graph learning on knowledge graphs (HGKR). By treating a knowledge graph as a heterogeneous graph, HGKR achieves more fine-grained modeling of knowledge graphs for recommendation. Specifically, we incorporate the graph neural networks into the message passing and aggregating of entities within a knowledge graph both at the graph and the semantic level. Furthermore, we designed a knowledge-perceiving item filter based on an attention mechanism to capture the user's potential interest in their historical preferences for the enhancement of recommendation. Extensive experiments conducted on two datasets in the context of two recommendations reveal the excellence of our proposed method, which outperforms other benchmark models., (© 2023. The Author(s).)

The convergence-confinement method (CCM) is a simplified widely utilised tool for assessing the interplay between the rock mass behaviour and the support effect, so it is quite helpful for tunnel support design purposes. However, the direct application of this technique has shown some limitations, many of which are directly related to the three-dimensionality issue. Indeed, the CCM tries to solve the three-dimensional (3D) problem of tunnel advance deformation and support response, by means of a series of two-dimensional (2D) plane strain analyses. So, regardless purely elastic cases, certain deviation is observed when comparing CCM and 3D numerical modelling results. The reasons behind this deviation have been studied from different points of views, but they seem to be still not well understood. With the aim of advancing towards a better knowledge of this issue, this paper discusses the limitation of CCM to correctly reflect the 3D tunnelling effect by comparing CCM and 3D numerical deformation, support pressure and liner load results in a typical tunnel case for various geological conditions. The reasons for CCM results in different rock deformation and support pressure in comparing to the 3D numerical modelling are explained. Some guidelines are eventually given recommending when the use of CCM can be acceptable according to the rock mass strength and tunnel depth, and when a more rigorous 3D approach is convenient., (© 2023. The Author(s).)

Protective equipment in war plays a vital role in the safety of soldiers, the threat to soldiers from brain damage caused by deformation at the back of the helmet cannot be ignored, so research on reduce blunt post-cranial injury has great significance and value. This study first conducted gunshot experiments, used rifle bullets impact bulletproof plate and different density liner foam to record the incident process and internal response of craniocerebral model. After verifying the accuracy of finite element model through experimental data, optimization model is established based on response surface method to optimize the structure of gradient foam, analyze the cranial strain and energy absorption to select the best density and thickness distribution of each foam layer. Optimization results show that liner foam which designed to have lower density and thicker thickness for impact and brace layers, higher density and thinner thickness for middle layer can significantly improve the energy absorption efficiency. Compared to the 40.65 J of energy absorption before optimization, the optimized gradient foam can absorb 109.3 J of energy, with a 169% increase in the absorption ratio. The skull strain in the craniocerebral model was reduced from 1.260 × 10 -2 to 1.034 × 10 -2 , with a reduction of about 22%. This study provides references for the design and development of protective equipment and plays an important role in ensuring the safety of soldiers in the battlefield environment., (© 2022. The Author(s).)

To date, more than 263 million people have been infected with SARS-CoV-2 during the COVID-19 pandemic. In many countries, the global spread occurred in multiple pandemic waves characterized by the emergence of new SARS-CoV-2 variants. Here we report a sequence and structural-bioinformatics analysis to estimate the effects of amino acid substitutions on the affinity of the SARS-CoV-2 spike receptor binding domain (RBD) to the human receptor hACE2. This is done through qualitative electrostatics and hydrophobicity analysis as well as molecular dynamics simulations used to develop a high-precision empirical scoring function (ESF) closely related to the linear interaction energy method and calibrated on a large set of experimental binding energies. For the latest variant of concern (VOC), B.1.1.529 Omicron, our Halo difference point cloud studies reveal the largest impact on the RBD binding interface compared to all other VOC. Moreover, according to our ESF model, Omicron achieves a much higher ACE2 binding affinity than the wild type and, in particular, the highest among all VOCs except Alpha and thus requires special attention and monitoring., (© 2022. The Author(s).)

Aldolase A (ALDOA) is an enzyme that plays an important role in glycolysis and gluconeogenesis, which is closely related to tumor metabolism. In this study, the overall roles of ALDOA in pan-cancer have been investigated from several aspects using databases and online analysis tools. Using the ONCOMINE database, the expression of ALDOA in various cancers was analyzed. The prognostic role of ALDOA was explored by PrognoScan, GEPIA, and Kaplan-Meier Plotter. The immune-related role of ALDOA and its downstream substrates was decided by TIMER, cBioPortal and String. Our data indicate that ALDOA expression level in lung adenocarcinoma, liver hepatocellular carcinoma, head and neck squamous cell carcinoma is higher than that in normal tissues. Increased expression of ALDOA often indicates a poor prognosis for patients. The correlation between ALDOA and immune infiltration among different tumors is very different. We also investigate the relationship between ALDOA and its upstream/downstream proteins. Our results showed that ALDOA could be used as a biomarker for the tumor prognosis, and could be correlated with the infiltrating levels of macrophages, CD4+ T cells and CD8+ T cells., (© 2022. The Author(s).)

This study investigated the effect of poor balance and sarcopenia on vertebral spinal osteoporotic fracture (VOPF) in female rheumatoid arthritic (RA) patients. A total of 195 female RA and 126 normal subjects were enrolled, and the correlations between sarcopenia, poor balance and VOPF were analyzed. Furthermore, we explored the relationships between sarcopenia or poor balance with disease related indexes of female RA. Binary logistic regression analyses were performed to identify potential risk factors for VOPF in female RA. We found that female RA had an increased risk of sarcopenia, poor balance (Berg balance scale, BBS ≤ 40) and VOPF than controls (P < 0.0001). Female RA with VOPF were more likely to have poor balance and sarcopenia than those without VOPF (P < 0.0001-0.05). Meanwhile, female RA with sarcopenia and poor balance often had higher disease activity, more serious joint damage and worse joint function (P < 0.05) compared with those without sarcopenia and poor balance. Binary logistic regression analysis (LR backwald) revealed that age (OR = 1.112, 95% CI 1.065-1.160, P < 0.0001), OP (OR = 10.137, 95% CI 4.224-24.330, P < 0.0001) and GCs usage (OR = 3.532, 95% CI 1.427-8.741, P = 0.006) were risk factors, while SMI (OR = 0.386, 95% CI 0.243-0.614, P < 0.0001) and BBS (OR = 0.952, 95% CI 0.929-0.976, P < 0.0001) were protective factors for VOPF in female RA. Hence, sarcopenia and poor balance are associated with a higher risk for VOPF and are closely related to disease activity and joint structure damage of female RA., (© 2022. The Author(s).)

The focus of this study was to explore the association between the non-HDL-cholesterol to HDL-cholesterol (non-HDLc/HDLc) ratio and mortality in septic patients. This was a retrospective cohort study of patients with sepsis in the eICU Collaborative Research Database (eICU-CRD) from 208 distinct ICUs across the United States between 2014 and 2015 that explored. All-cause mortality within 28 days after ICU admission. A multivariable logistic regression model was used to estimate the risk of death. Of the 724 patients with a median age of 68 years, 43 (5.94%) died within 28 days after ICU admission. When the non-HDLc/HDLc ratio was < 3.3, the mortality rate decreased with an adjusted odds ratio (OR) of 0.60 (95% CI 0.37-0.99, P = 0.043) for every 1 increment in the non-HDLc/HDLc ratio. When the non-HDLc/HDLc ratio was ≥ 3.3, the mortality rate increased with an adjusted OR of 1.28 (95% CI 1.01-1.62, P = 0.039) for every one increment in the non-HDLc/HDLc ratio. For patients with sepsis, the association between the non-HDLc/HDLc ratio and the 28-day mortality risk was a U-shaped curve. A higher or lower non-HDLc/HDLc ratio was associated with an increased risk of 28-day mortality., (© 2022. The Author(s).)

Using deep learning models to analyze patients with intracranial tumors, to study the image segmentation and standard results by clinical depiction complications of cerebral edema after receiving radiotherapy. In this study, patients with intracranial tumors receiving computer knife (CyberKnife M6) stereotactic radiosurgery were followed using the treatment planning system (MultiPlan 5.1.3) to obtain before-treatment and four-month follow-up images of patients. The TensorFlow platform was used as the core architecture for training neural networks. Supervised learning was used to build labels for the cerebral edema dataset by using Mask region-based convolutional neural networks (R-CNN), and region growing algorithms. The three evaluation coefficients DICE, Jaccard (intersection over union, IoU), and volumetric overlap error (VOE) were used to analyze and calculate the algorithms in the image collection for cerebral edema image segmentation and the standard as described by the oncologists. When DICE and IoU indices were 1, and the VOE index was 0, the results were identical to those described by the clinician.The study found using the Mask R-CNN model in the segmentation of cerebral edema, the DICE index was 0.88, the IoU index was 0.79, and the VOE index was 2.0. The DICE, IoU, and VOE indices using region growing were 0.77, 0.64, and 3.2, respectively. Using the evaluated index, the Mask R-CNN model had the best segmentation effect. This method can be implemented in the clinical workflow in the future to achieve good complication segmentation and provide clinical evaluation and guidance suggestions., (© 2022. The Author(s).)

Psoriasis is a chronic, inflammatory skin disease. Although the precise etiology of psoriasis remains unclear, gut-microbiota axis might play a role in the pathogenesis of the disease. Here we investigated whether the composition of microbiota in the intestine and skin is altered in the imiquimod (IMQ)-treated mouse model of psoriasis. Topical application of IMQ to back skin caused significant changes in the composition of microbiota in the intestine and skin of IMQ-treated mice compared to control mice. The LEfSe algorithm identified the species Staphylococcus lentus as potential skin microbial marker for IMQ group. Furthermore, there were correlations for several microbes between the intestine and skin, suggesting a role of skin-gut-microbiota in IMQ-treated mice. Levels of succinic acid and lactic acid in feces from IMQ-treated mice were significantly higher than control mice. Moreover, the predictive functional analysis of the microbiota in the intestine and skin showed that IMQ caused alterations in several KEGG pathways. In conclusion, the current data indicated that topical application with IMQ to skin alters the composition of the microbiota in the gut and skin of host. It is likely that skin-gut microbiota axis plays a role in pathogenesis of psoriasis.

We fabricated tantalum pentoxide (Ta 2 O 5 ) channel waveguides and used them to experimentally demonstrate higher-order mode supercontinuum (SC) generation. The Ta 2 O 5 waveguide has a high nonlinear refractive index which was in an order magnitude of 10 -14 cm 2 /W and was designed to be anomalously dispersive at the pumping wavelength. To the best of our knowledge, this is the first time a higher-order mode femtosecond pump based broadband SC has been measured from a nonlinear waveguide using the phase-matching method. This enabled us to demonstrate a SC spectrum spanning from 842 to 1462 nm (at - 30 dB), which corresponds to 0.83 octaves, when using the TM 10 waveguide mode. When using the TE 10 mode, the SC bandwidth is slightly reduced for the same excitation peak power. In addition, we theoretically estimated and discussed the possibility of using the broadband higher-order modes emitted from the Ta 2 O 5 waveguide for trapping nanoparticles. Hence, we believe that demonstrated Ta 2 O 5 waveguide are a promising broadband light source for optical applications such as frequency metrology, Raman spectroscopy, molecular spectroscopy and optical coherence tomography.

Early life stress (ELS) has been shown to have a significant impact on typical brain development and the manifestation of psychological disorders through epigenetic modifications that alter gene expression. Line1, a retrotransposon associated with genetic diversity, has been linked with various psychological disorders that are associated with ELS. Our previous work demonstrated altered Line1 DNA copy number in the neonatal period following stressful experiences; we therefore chose to investigate whether early life stress altered Line1 retrotransposition persists into the juvenile period of development. Our study uses a neonatal predator odor exposure (POE) paradigm to model ELS in rats. We examined Line1 using qPCR to assess Line1 expression levels and DNA copy number in the male and female juvenile amygdala, hippocampus and prefrontal cortex-areas chosen for their association with affective disorders and stress. We report a sex difference in Line1 levels within the juvenile amygdala. We also find that ELS significantly increases Line1 DNA copy number within the juvenile amygdala which correlates with reduced juvenile social play levels, suggesting the possibility that Line1 may influence juvenile social development.

Despite the established roles of the epigenetic factor UHRF1 in oncogenesis, no UHRF1-targeting therapeutics have been reported to date. In this study, we use fragment-based ligand discovery to identify novel scaffolds for targeting the isolated UHRF1 tandem Tudor domain (TTD), which recognizes the heterochromatin-associated histone mark H3K9me3 and supports intramolecular contacts with other regions of UHRF1. Using both binding-based and function-based screens of a ~ 2300-fragment library in parallel, we identified 2,4-lutidine as a hit for follow-up NMR and X-ray crystallography studies. Unlike previous reported ligands, 2,4-lutidine binds to two binding pockets that are in close proximity on TTD and so has the potential to be evolved into more potent inhibitors using a fragment-linking strategy. Our study provides a useful starting point for developing potent chemical probes against UHRF1.

The fourth outbreak of the Coronaviruses, known as the COVID-19, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dynamic transmission routes of this outbreak in mainland China over January 31-February 19, 2020. Our results demonstrate that the influential inter-location routes from Hubei have become unidentifiable since February 4, 2020, whereas the self-transmission in each provincial-level administrative region (location, hereafter) was accelerating over February 4-15, 2020. From February 16, 2020, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19, 2020. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in locations with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of COVID-19.

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10 -5 ; C allele, OR = 1.32, P = 8.1 × 10 -4 ). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.

Surveillance of human immunodeficiency virus (HIV) molecular diversity and drug resistance-associated mutations (DRMs) among treatment-naïve blood donors is critical for monitoring viral evolution and blood safety. From 2016-2017, 199 plasma samples were collected from 24 blood centers and confirmed as HIV viral load positive or serologically reactive in National Centers for Clinical Laboratories (NCCL), of which 179 were sequenced and subtyped in the gag, protease (PR)-reverse transcriptase (RT), integrase (IN) and/or envelope (env) regions. DRMs in PR-RT and IN regions were analyzed in Stanford HIVdb Program. The majority of subtypes were circulating recombinant form (CRF) 07&#95;BC (34.6%) and CRF01&#95;AE (32.4%); many unique recombinant forms (URFs) (39, 21.8%) and other rare CRFs were observed in the study. Notably, CRF02&#95;AG and CRF06&#95;cpx strains typically found in Africa were firstly identified amongst Chinese blood donors. DRMs were common, with 28 of 179 (15.6%) specimens carrying DRMs, including the PR N88S and RT K103N mutations, which have been implicated in elevated resistance to antiretroviral drugs. Furthermore, 4 HIV-1 isolates (2.4%, 4/168) had surveillance drug-resistance mutation (SDRM), including 3 nonnucleosidereverse transcriptase inhibitors (NNRTI) SDRMs (1 K101E, 2 K103N) and 1 protease inhibitor (PI) SDRM (M46I). The HIV viral diversity among blood donors observed in this study suggest that ongoing HIV-1 recombination is becoming progressively complex in China, and lots of DRMs found in the study exacerbate the primary drug resistance landscape, which highlight the necessity of timely genotypic drug resistance monitoring and molecular surveillance of HIV-1 among blood donors.