bluuebunny/crossref_metadata_2025 huggingface dataset:
Polycyclic Aromatic Hydrocarbon Degradation in the Sea-Surface Microlayer at Coastal Antarctica
Authors: Martinez-Varela Alícia , Casas Gemma , Berrojalbiz Naiara , Piña Benjamin , Dachs Jordi , Vila-Costa Maria
Published: July 2022

As much as 400 Tg of carbon from airborne semivolatile aromatic hydrocarbons is deposited to the oceans every year, the largest identified source of anthropogenic organic carbon to the ocean. Microbial degradation is a key sink of these pollutants in surface waters, but has received little attention in polar environments. We have challenged Antarctic microbial communities from the sea-surface microlayer (SML) and the subsurface layer (SSL) with polycyclic aromatic hydrocarbons (PAHs) at environmentally relevant concentrations. PAH degradation rates and the microbial responses at both taxonomical and functional levels were assessed. Evidence for faster removal rates was observed in the SML, with rates 2.6-fold higher than in the SSL. In the SML, the highest removal rates were observed for the more hydrophobic and particle-bound PAHs. After 24 h of PAHs exposure, particle-associated bacteria in the SML showed the highest number of significant changes in their composition. These included significant enrichments of several hydrocarbonoclastic bacteria, especially the fast-growing genera Pseudoalteromonas, which increased their relative abundances by eightfold. Simultaneous metatranscriptomic analysis showed that the free-living fraction of SML was the most active fraction, especially for members of the order Alteromonadales, which includes Pseudoalteromonas. Their key role in PAHs biodegradation in polar environments should be elucidated in further studies. This study highlights the relevant role of bacterial populations inhabiting the sea-surface microlayer, especially the particle-associated habitat, as relevant bioreactors for the removal of aromatic hydrocarbons in the oceans.
Salmonella Phages Affect the Intestinal Barrier in Chicks by Altering the Composition of Early Intestinal Flora: Association With Time of Phage Use
Authors: Zhao Hongze , Li Yue , Lv Peilin , Huang Jinmei , Tai Rong , Jin Xiue , Wang Jianhua , Wang Xiliang
Published: July 2022

Phages show promise in replacing antibiotics to treat or prevent bacterial diseases in the chicken breeding industry. Chicks are easily affected by their environment during early growth. Thus, this study investigated whether oral phages could affect the intestinal barrier function of chicks with a focus on the cecal microbiome. In a two-week trial, forty one-day-old hens were randomly divided into four groups: (1) NC, negative control; (2) Phage 1, 109 PFU phage/day (days 3–5); (3) Phage 2, 109 PFU phage/day (days 8–10); and (4) AMX, 1 mg/mL amoxicillin/day (days 8–10). High-throughput sequencing results of cecal contents showed that oral administration of phages significantly affected microbial community structure and community composition, and increased the relative abundance of Enterococcus. The number of different species in the Phage 1 group was much higher than that in the Phage 2 group, and differences in alpha and beta diversity also indicated that the magnitude of changes in the composition of the cecal microbiota correlated with the time of phage use. Particularly in the first stage of cecal microbiota development, oral administration of bacteriophages targeting Salmonella may cause substantial changes in chicks, as evidenced by the results of the PICRUSt2 software function prediction, reminding us to be cautious about the time of phage use in chicks and to avoid high oral doses of phages during the first stage. Additionally, the Phage 2 samples not only showed a significant increase in the relative abundance of Bifidobacterium and Subdoligranulum, but also improved the intestinal morphology (jejunum) and increased the mRNA expression level of occludin and ZO-1. We concluded that phages do not directly interact with eukaryotic cells. The enhancement of intestinal barrier function by phages in chicks may be related to changes in the intestinal flora induced by phages. This implies that phages may affect intestinal health by regulating the intestinal flora. This study provides new ideas for phage prevention of intestinal bacterial infections and promotes large-scale application of phages in the poultry industry.
Regulation of TIA-1 Condensates: Zn2+ and RGG Motifs Promote Nucleic Acid Driven LLPS and Inhibit Irreversible Aggregation
Authors: West Danella L. , Loughlin Fionna E. , Rivero-Rodríguez Francisco , Vankadari Naveen , Velázquez-Cruz Alejandro , Corrales-Guerrero Laura , Díaz-Moreno Irene , Wilce Jacqueline A.
Published: July 2022

Stress granules are non-membrane bound RNA-protein granules essential for survival during acute cellular stress. TIA-1 is a key protein in the formation of stress granules that undergoes liquid-liquid phase separation by association with specific RNAs and protein-protein interactions. However, the fundamental properties of the TIA-1 protein that enable phase-separation also render TIA-1 susceptible to the formation of irreversible fibrillar aggregates. Despite this, within physiological stress granules, TIA-1 is not present as fibrils, pointing to additional factors within the cell that prevent TIA-1 aggregation. Here we show that heterotypic interactions with stress granule co-factors Zn2+ and RGG-rich regions from FUS each act together with nucleic acid to induce the liquid-liquid phase separation of TIA-1. In contrast, these co-factors do not enhance nucleic acid induced fibril formation of TIA-1, but rather robustly inhibit the process. NMR titration experiments revealed specific interactions between Zn2+ and H94 and H96 in RRM2 of TIA-1. Strikingly, this interaction promotes multimerization of TIA-1 independently of the prion-like domain. Thus, through different molecular mechanisms, these stress granule co-factors promote TIA-1 liquid-liquid phase separation and suppress fibrillar aggregates, potentially contributing to the dynamic nature of stress granules and the cellular protection that they provide.
Cerebral endothelial cell derived small extracellular vesicles improve cognitive function in aged diabetic rats
Authors: Zhang Li , Li Chao , Huang Rui , Teng Hua , Zhang Yi , Zhou Min , Liu Xiangshuang , Fan Baoyan , Luo Hao , He Annie , Zhao Anna , Lu Mei , Chopp Michael , Zhang Zheng Gang
Published: July 2022

Small extracellular vesicles (sEVs) mediate cell-cell communication by transferring their cargo biological materials into recipient cells. Diabetes mellitus (DM) induces cerebral vascular dysfunction and neurogenesis impairment, which are associated with cognitive decline and an increased risk of developing dementia. Whether the sEVs are involved in DM-induced cerebral vascular disease, is unknown. Therefore, we studied sEVs derived from cerebral endothelial cells (CEC-sEVs) of aged DM rats (DM-CEC-sEVs) and found that DM-CEC-sEVs robustly inhibited neural stem cell (NSC) generation of new neuroblasts and damaged cerebral endothelial function. Treatment of aged DM-rats with CEC-sEVs derived from adult healthy normal rats (N-CEC-sEVs) ameliorated cognitive deficits and improved cerebral vascular function and enhanced neurogenesis. Intravenously administered N-CEC-sEVs crossed the blood brain barrier and were internalized by neural stem cells in the neurogenic region, which were associated with augmentation of miR-1 and –146a and reduction of myeloid differentiation primary response gene 88 and thrombospondin 1 proteins. In addition, uptake of N-CEC-sEVs by the recipient cells was mediated by clathrin and caveolin dependent endocytosis signaling pathways. The present study provides ex vivo and in vivo evidence that DM-CEC-sEVs induce cerebral vascular dysfunction and neurogenesis impairment and that N-CEC-sEVs have a therapeutic effect on improvement of cognitive function by ameliorating dysfunction of cerebral vessels and increasing neurogenesis in aged DM rats, respectively.
Incidence, Risk Factors, and Effect on Allograft Survival of Glomerulonephritis Post-transplantation in a United Kingdom Population: Cohort Study
Authors: Aguiar Rute , Bourmpaki Elli , Bunce Catey , Coker Bola , Delaney Florence , de Jongh Leonardo , Oliveira Giovani , Weir Alistair , Higgins Finola , Spiridou Anastasia , Hasan Syed , Smith Jonathan , Mulla Abdulrahim , Glampson Ben , Mercuri Luca , Montero Rosa , Hernandez-Fuentes Maria , Roufosse Candice A. , Simmonds Naomi , Clatworthy Menna , McLean Adam , Ploeg Rutger , Davies Jim , Várnai Kinga Anna , Woods Kerrie , Lord Graham , Pruthi Rishi , Breen Cormac , Chowdhury Paramit
Published: July 2022

Background

Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature.

Methods

This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed.

Results

In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival.

Conclusions

PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist.
Novel Missense CNTNAP2 Variant Identified in Two Consanguineous Pakistani Families With Developmental Delay, Epilepsy, Intellectual Disability, and Aggressive Behavior
Authors: Badshah Noor , Mattison Kari A. , Ahmad Sohail , Chopra Pankaj , Johnston H. Richard , Ahmad Shakoor , Khan Sher Hayat , Sarwar Muhammad Tahir , Cutler David J. , Taylor Micheal , Vadlamani Gayatri , Zwick Michael E. , Escayg Andrew
Published: July 2022

We report the genetic analysis of two consanguineous pedigrees of Pakistani ancestry in which two siblings in each family exhibited developmental delay, epilepsy, intellectual disability and aggressive behavior. Whole-genome sequencing was performed in Family 1, and we identified ~80,000 variants located in regions of homozygosity. Of these, 615 variants had a minor allele frequency ≤ 0.001, and 21 variants had CADD scores ≥ 15. Four homozygous exonic variants were identified in both affected siblings: PDZD7 (c.1348_1350delGAG, p.Glu450del), ALG6 (c.1033G>C, p.Glu345Gln), RBM20 (c.1587C>G, p.Ser529Arg), and CNTNAP2 (c.785G>A, p.Gly228Arg). Sanger sequencing revealed co-segregation of the PDZD7, RBM20, and CNTNAP2 variants with disease in Family 1. Pathogenic variants in PDZD7 and RBM20 are associated with autosomal recessive non-syndromic hearing loss and autosomal dominant dilated cardiomyopathy, respectively, suggesting that these variants are unlikely likely to contribute to the clinical presentation. Gene panel analysis was performed on the two affected siblings in Family 2, and they were found to also be homozygous for the p.Gly228Arg CNTNAP2 variant. Together these families provide a LOD score 2.9 toward p.Gly228Arg CNTNAP2 being a completely penetrant recessive cause of this disease. The clinical presentation of the affected siblings in both families is also consistent with previous reports from individuals with homozygous CNTNAP2 variants where at least one allele was a nonsense variant, frameshift or small deletion. Our data suggests that homozygous CNTNAP2 missense variants can also contribute to disease, thereby expanding the genetic landscape of CNTNAP2 dysfunction.
Vitamin C Intake and Ischemic Stroke
Authors: Tang Xiaolong , Liu Hanguang , Xiao Yuan , Wu Lei , Shu Peng
Published: July 2022

Vitamin C is an essential micronutrient with important antioxidant properties. Ischemic stroke is a major public health problem worldwide. Extensive evidence demonstrates that vitamin C has protective effects against cardiovascular disease, and there is a close relationship between vitamin C intake and ischemic stroke risk. Based on the evidence, we conducted this umbrella review to clarify the relationship between vitamin C intake and ischemic stroke risk from four perspectives: cellular mechanisms, animal experiments, clinical trials, and cohort studies.
Metabolomic Assay, Computational Screening, and Pharmacological Evaluation of Caulerpa racemosa as an Anti-obesity With Anti-aging by Altering Lipid Profile and Peroxisome Proliferator-Activated Receptor-γ Coactivator 1-α Levels
Authors: Permatasari Happy Kurnia , Nurkolis Fahrul , Hardinsyah Hardinsyah , Taslim Nurpudji Astuti , Sabrina Nindy , Ibrahim Faisal Maulana , Visnu Jodi , Kumalawati Dian Aruni , Febriana Sri Awalia , Sudargo Toto , Tanner Melvin Junior , Kurniatanty Isma , Yusuf Vincentius Mario , Rompies Ronald , Bahar Muhammad Rahimi , Holipah Holipah , Mayulu Nelly
Published: July 2022

Obesity is associated with an accelerated aging process, which prevents healthy aging. Both obesity and aging were manifested in the peroxisome proliferator-activated receptor-γ coactivator α (PGC-1α) level. These studies fulfill the scientific gap in assembled pharmacological activity assay of Caulerpa racemosa done in a previous preclinical trial. Six major compounds from sea grape (C. racemosa) extract were evaluated using an in silico approach against human pancreatic lipase, a-glucosidase, and a-amylase to predict prospective anti-obesity candidates. The lipase inhibitory activity of the extract reached 90.30 ± 0.40%, 1.75% lower than orlistat. The a-amylase inhibitory assay of the extract was 84.07 ± 5.28%, while the inhibitory activity against a-glucosidase was 81.67 ± 1.54%; both were lower than acarbose. We observe the effect of C. racemosa extract as anti-obesity with anti-aging by evaluating the obesity parameters in the human body for a 4-week period. There was a significant decrease in blood glucose, total cholesterol, low-density lipoprotein (LDL), triglycerides (TG), waist circumference, waist-hip ratio, and body weight (p < 0.05); PGC-1α and high-density lipoprotein (HDL) increased significantly (p = 0.000), in Group B when compared with Group A. Our study revealed that sea grape extract is a potent anti-obesity with an anti-aging reagent that does not produce any significant adverse effects.
High Carbohydrate Antigen 19-9 Levels Indicate Poor Prognosis of Upper Tract Urothelial Carcinoma
Authors: Jeong Seung-hwan , Han Jang Hee , Jeong Chang Wook , Kim Hyeon Hoe , Kwak Cheol , Yuk Hyeong Dong , Ku Ja Hyeon
Published: July 2022

Upper tract urothelial carcinoma (UTUC) occurs in urothelial cells from the kidney and the ureters. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker for pancreatic and gastrointestinal cancers, and its high levels are associated with poor prognosis in bladder cancer. In this study, prospective patients enrolled in the registry of Seoul National University were retrospectively examined to determine the clinical significance of CA 19-9 in UTUC. In 227 patients, high serum CA 19-9 levels reflected a high tumor burden represented by high T and N stages, leading to adverse prognosis in metastasis-free or overall survival. Subsequently, propensity score matching analysis showed that the CA 19-9 level is an independent prognostic factor of UTUC.
Comprehensive Analysis of Molecular Clusters and Prognostic Signature Based on m7G-related LncRNAs in Esophageal Squamous Cell Carcinoma
Authors: Zhao Fangchao , Dong Zefang , Li Yishuai , Liu Shiquan , Guo Pengfei , Zhang Dengfeng , Li Shujun
Published: July 2022

N7-Methylguanosine (m7G) and long non-coding RNAs (lncRNAs) have been widely reported to play an important role in cancer. However, there is little known about the relationship between m7G-related lncRNAs and esophageal squamous cell carcinoma (ESCC). In this study, we aimed to find new potential biomarkers and construct an m7G-related lncRNA prognostic signature for ESCC. Three molecular clusters were identified by consensus clustering of 963 m7G-related lncRNAs, of which cluster B is preferentially related to poorer prognosis, higher immune and stromal scores, higher mRNA levels of immune checkpoints, and higher immune infiltrate level. We constructed a robust and effective m7G-related lncRNA prognostic signature (m7G-LPS, including 7 m7G-related prognostic lncRNAs) and demonstrated its prognostic value and predictive ability in the GEO and TCGA cohorts. The risk score was able to serve as an independent risk factor for patients with ESCC and showed better prediction than the traditional clinical risk factors. The immune score, stromal score, the infiltration level of immune cells and expression of immune checkpoints were significantly higher in the high-risk subgroup compared to the low-risk subgroup. The establishment of nomogram further improved the performance of m7G-LPS and facilitated its clinical application. Finally, we used GTEx RNA-seq data and qRT-PCR experiments to verify the expression levels of 7 m7G-related lncRNAs. To a certain degree, m7G-lncRNAs can be used as prognostic markers and therapeutic targets for ESCC patients.
Metabolic Rewiring in Glioblastoma Cancer: EGFR, IDH and Beyond
Authors: El Khayari Abdellatif , Bouchmaa Najat , Taib Bouchra , Wei Zhiyun , Zeng Ailiang , El Fatimy Rachid
Published: July 2022

Glioblastoma multiforme (GBM), a highly invasive and incurable tumor, is the humans’ foremost, commonest, and deadliest brain cancer. As in other cancers, distinct combinations of genetic alterations (GA) in GBM induce a diversity of metabolic phenotypes resulting in enhanced malignancy and altered sensitivity to current therapies. Furthermore, GA as a hallmark of cancer, dysregulated cell metabolism in GBM has been recently linked to the acquired GA. Indeed, Numerous point mutations and copy number variations have been shown to drive glioma cells’ metabolic state, affecting tumor growth and patient outcomes. Among the most common, IDH mutations, EGFR amplification, mutation, PTEN loss, and MGMT promoter mutation have emerged as key patterns associated with upregulated glycolysis and OXPHOS glutamine addiction and altered lipid metabolism in GBM. Therefore, current Advances in cancer genetic and metabolic profiling have yielded mechanistic insights into the metabolism rewiring of GBM and provided potential avenues for improved therapeutic modalities. Accordingly, actionable metabolic dependencies are currently used to design new treatments for patients with glioblastoma. Herein, we capture the current knowledge of genetic alterations in GBM, provide a detailed understanding of the alterations in metabolic pathways, and discuss their relevance in GBM therapy.
Genomic Features of Organ-Specific Metastases in Lung Adenocarcinoma
Authors: Feng Alei , Li Yanjun , Li Guangxu , Wang Yu , Wen Qiang , Yang Zhe , Tian Kaihua , Lv Hongying , Guo Lijie , Zhang Shanshan , Liu Xiaoyan , Jiang Da
Published: July 2022

Background

The genomic features of cancer cells may confer the metastatic ability of lung adenocarcinoma (LUAD) to metastasize to specific organs. We aimed to identify the differences in genomic alterations between patients with primary LUAD with and without metastases and to elucidate the metastatic biology that may help developing biomarker-directed therapies for advanced or metastatic disease.

Methods

A retrospective cohort of 497 patients with LUAD including 388 primary tumors (PR), 53 bone metastases (MT-bone), 30 liver metastases (MT-liver), and 26 brain metastases (MT-brain) was tested for genomic alterations by a next-generation sequencing assay.

Results

The EGFR, TP53, TERT, LRP1B, CDKN2A, ERBB2, ALK, and KMT2C genes had a high frequency of mutations, and the mutations were shared by PR and metastases groups. TP53 and EGFR were the most common mutated genes. In comparison with PR, KRAS, STK11, ATM, NPM1, and ROS1 were significantly mutated in MT-brain, and TP53, MYC, RSPO2, CDKN2a, and CDKN2B were significantly mutated in MT-liver. The frequencies of TP53, CDKN2A, MTAP, PRKCI, and APC mutations were higher in MT-bone than that in PR. The ERBB, phosphoinositide-3-kinase/protein kinase B (PI3K-AKT), cell cycle, Fibroblast growth factor (FGF), and homologous recombination deficiency signaling pathways were affected in both PR and metastases, and there is higher frequency of mutations in metastases. Moreover, the co-mutations in patients with PR and metastasis were respectively analyzed. In addition, the programmed death ligand 1 (PD-L1) level was obviously related to tumor stage and tumor metastases, and the tumor mutational burden was correlated to clinicopathological features including age, gender, pathological stages, and tumor metastases. FGFR1, KAT6A, MYC, RAD21, TP53, and DAXX were also dramatically correlated to the tumor mutational burden.

Conclusion

Metastases are the most devastating stage of tumors and the main cause of cancer-related deaths. Our results provided a clinically relevant view of the tumor-intrinsic mutational landscape of patients with metastatic LUAD.
Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation Supported by Third-Party Cord Blood Versus Human Leukocyte Antigen-Matched Sibling Peripheral Blood Stem Cell Transplantation in Hematologic Malignancy Patients
Authors: Cheng Tingting , Chen Yan , Liu Yi , Ma Xia , Zeng Cong , Chen Xu , Wang Shiyu , Xu Yajing
Published: July 2022

Recent studies have shown that haploidentical hematopoietic stem cell transplantation supported by third-party cord blood (haplo-cord-HSCT) results in rapid hematopoietic recovery, low incidences of graft-versus-host disease (GVHD), and relapse of hematologic malignancies. However, few reports on haploidentical peripheral blood stem cell transplantation supported by third-party cord blood (haplo-cord-PBSCT) have been published. To evaluate the outcomes of patients who underwent haplo-cord-PBSCT or human leukocyte antigen (HLA)-matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT), we retrospectively reviewed the clinical data of patients with hematologic malignancies who underwent haplo-cord-PBSCT (n = 93) or MSD-PBSCT (n = 72) in our hospital from March 2017 to December 2020. In the haplo-cord-PBSCT and MSD-PBSCT groups, the median time for neutrophil and platelet engraftment was 13 vs. 12 days (p = 0.07) and 16 vs. 13 days (p = 0.06), respectively. The 30-day cumulative incidences of neutrophil engraftment were 100.0% and 98.6% (p = 0.12). The 100-day cumulative incidences of platelet engraftment were 96.8% and 98.6% (p = 0.01). The 100-day cumulative incidences of grade II–IV and grade III–IV acute GVHD were 29.1% vs. 23.6% (p = 0.42) and 9.7% vs. 4.2% (p = 0.18). The cumulative incidences of total and moderate/severe chronic GVHD at 1 year were 26.5% vs. 17.4% and 8.1% vs. 4.5%, respectively, and at 3 years were 34.7% vs. 34.3% (p = 0.60) and 13.6% vs. 10.6% (p = 0.49), respectively. The cumulative incidences of relapse at 1 year were 9.3% and 7.2% and at 3 years were 17.0% and 17.0% (p = 0.98). Non-relapse mortality (NRM) at 1 year was 14.6% and 8.6% and at 3 years was 17.4% and 8.6% (p = 0.13) in two groups. The probabilities of overall survival (OS), disease-free survival (DFS), and GVHD-free/relapse-free survival (GRFS) at 1 year were 81.7% vs. 88.6%, 76.1% vs. 84.2%, and 71.7% vs. 79.7%, respectively, and at 3 years were 78.7% vs. 79.0%, 65.6% vs. 74.4%, and 55.5% vs. 63.6%, respectively, in the corresponding group, p > 0.05. In conclusion, for patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and acute lymphoid leukemia (ALL), haplo-cord-PBSCT results in similar outcomes compared with MSD-PBSCT, and it may be a valid alternative transplantation method.
Noninvasively Assessed Portal Hypertension Grade Predicts Post-Hepatectomy Liver Failure in Patients With HepatocellCarcinoma: A Multicenter Study
Authors: Wang Jitao , Zhang Zhanguo , Shang Dong , Li Jinlong , Liu Chengyu , Yu Peng , Wang Mingguang , Liu Dengxiang , Miao Hongrui , Li Shuang , Zhang Biao , Huang Anliang , Zhang Yewei , Chen Shubo , Qi Xiaolong
Published: July 2022

Purpose

To determine the predictive value of portal hypertension (PH) for the development of post-hepatectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC).

Patients and methods

This study enrolled a total of 659 patients with HCC that received hepatectomy as a first-line therapy. PH was classified as grade 0, 1, and 2 according to whether the indirect criteria for PH were met: 1) patients had obvious varicose veins and 2) splenomegaly was present and platelet count < 100 × 109/L. The effects of each variable on the occurrence of PHLF were assessed using univariate and multivariate analyses.

Results

PH grade 2 (odds ratio [OR] = 2.222, p = 0.011), higher age (OR = 1.031, p = 0.003), hepatitis C infection (OR = 3.711, p = 0.012), open surgery (OR = 2.336, p < 0.001), portal flow blockage (OR = 1.626, p = 0.023), major hepatectomy (OR = 2.919, p = 0.001), hyperbilirubinemia (≥ 17.2 μmol/L, OR = 2.113, p = 0.002), and high levels of alpha-fetoprotein (> 400n g/ml, OR = 1.799, p = 0.008) were significantly associated with PHLF occurrence. We performed a subgroup analysis of liver resection and found that the extent of liver resection and PH grade were good at distinguishing patients at high risk for PHLF, and we developed an easy-to-view roadmap.

Conclusion

PH is significantly related to the occurrence of PHLF in patients who underwent hepatectomy. Noninvasively assessing PH grade can predict PHLF risk.
Semi-supervised learning in cancer diagnostics
Authors: Eckardt Jan-Niklas , Bornhäuser Martin , Wendt Karsten , Middeke Jan Moritz
Published: July 2022

In cancer diagnostics, a considerable amount of data is acquired during routine work-up. Recently, machine learning has been used to build classifiers that are tasked with cancer detection and aid in clinical decision-making. Most of these classifiers are based on supervised learning (SL) that needs time- and cost-intensive manual labeling of samples by medical experts for model training. Semi-supervised learning (SSL), however, works with only a fraction of labeled data by including unlabeled samples for information abstraction and thus can utilize the vast discrepancy between available labeled data and overall available data in cancer diagnostics. In this review, we provide a comprehensive overview of essential functionalities and assumptions of SSL and survey key studies with regard to cancer care differentiating between image-based and non-image-based applications. We highlight current state-of-the-art models in histopathology, radiology and radiotherapy, as well as genomics. Further, we discuss potential pitfalls in SSL study design such as discrepancies in data distributions and comparison to baseline SL models, and point out future directions for SSL in oncology. We believe well-designed SSL models to strongly contribute to computer-guided diagnostics in malignant disease by overcoming current hinderances in the form of sparse labeled and abundant unlabeled data.
FGD1 Variant Associated With Aarskog–Scott Syndrome
Authors: Zhu Yilin , Chen Qingqing , Lin Haiyan , Lu Huifei , Qu Yangbin , Yan Qingfeng , Wang Chunlin
Published: July 2022

Background

Aarskog–Scott syndrome, a rare X-linked genetic disorder, is identified by combined clinical manifestations of short stature, facial, skeletal, and genital anomalies. Annually, two or three new cases are diagnosed with Aarskog–Scott syndrome, which is associated with FGD1 variants. However, there is no specific treatment for Aarskog–Scott syndrome due to its unclear mechanism.

Methods

Clinical data were collected when the patient first visited the hospital. Trio whole-exome sequencing and Sanger sequencing were performed for the genetic cause of disease. To evaluate the pathogenicity of the variants in vitro, stable cell lines were constructed using lentivirus infection in 143B cell. Furthermore, Western blot was used to verify the expression of signaling pathway-related proteins, and the transcription levels of osteogenic-related genes were verified by luciferase reporter gene assay.

Results

A 7-year-old boy was manifested with facial abnormalities, intellectual disability, and short stature (−3.98 SDS) while the growth hormone level of stimulation test was normal. Trio whole-exome sequencing and Sanger sequencing identified a variant (c.1270A>G, p.Asn424Asp) in FGD1 gene. The Asn424 residue was highly conserved and the hydrogen bond in the FGD1 variant protein has changed, which led to decrease in the interaction with CDC42 protein. In vitro study showed that the Asn424Asp variant significantly decreased the transcription levels of OCN, COL1A1, and ALP activity, and it activated the phosphorylation of JNK1.

Conclusion

Molecular biological mechanisms between abnormal expression of FGD1and Aarskog–Scott syndrome remain poorly understood. In our study, c.1270A>G variant of FGD1 resulted in Aarskog–Scott syndrome, and the analysis of pathogenicity supports the deleterious effect of the variant. Furthermore, we demonstrated the weakened affinity of the mutant FGD1 and CDC42. Decreased expression of osteogenic-related gene and abnormal activation of JNK1 were also shown in this work.
Relevance of Intestinal Microbiota in Immunoglobulin A Vasculitis With Abdominal Involvement
Authors: Zhang Linqian , Jia Xinyi , Lai Panjian , Wang Kang , Bao Yunguang , Li Xiaobing
Published: July 2022

Background

We explored the intestinal microbiota changes in IgAV with abdominal involvement (IgAV-GI) at the acute and convalescent stages and evaluated the role of intestinal microbiota in the clinical course of patients with IgAV.

Methods

A total of 37 patients with IgAV were included, and the control group comprised 37 age- and sex-matched healthy children. Stool samples were collected from 28 children with IgAV-GI (19 in the acute stage and 9 in the recovery stage) and from nine children with non-abdominal involvement. Fecal specimens were selected and DNA was obtained using an extraction kit which was then subjected to high-throughput sequencing and analysis.

Results

There was no significant difference in the community structure of the intestinal microbiota among the IgAV-GI acute, IgAV-GI convalescence, and IgAV-non-GI stages. The abundance of Veillonella in the acute stage of IgAV-GI was significantly higher than that in IgAV-non-GI and convalescence stages, and Ruminococcus was the most abundant in IgAV-GI convalescence. The α-diversity of children with IgAV was significantly lower than that of healthy children, and healthy children had higher intestinal microbiota richness and more evenly distributed species. In terms of changes in intestinal microbial diversity in patients with IgAV at the genus level, obligate anaerobes such as Bifidobacterium, Prevotella, Coprobacter, Prevotella_9, Blautia, Romboutsia, Parabacteroide, Subdoligranulum, and Roseburia were significantly reduced, and the enrichment of facultative anaerobe was represented by Bacteroides, Lachnoclostridium, and Alistipe.

Conclusion

Different bacterial species may be involved in the pathogenesis of different types of IgAV-GI. Differences were observed in the intestinal microbiota between healthy children and children with IgAV.
Charge Collection Dynamics of the ARCADIA Passive Pixel Arrays: Laser Characterization and TCAD Modeling
Authors: Corradino Thomas , Dalla Betta G.-F. , Neubüser C. , Pancheri L.
Published: July 2022

Monolithic Active Pixel Sensors (MAPS) represent one of the most promising technologies for the next generation of radiation detectors. The ARCADIA project aims at the development of Fully Depleted (FD) MAPS employing a production process compatible with a 110 nm commercial CMOS technology. The first engineering run of the project included matrices of active pixels with embedded analog and digital frontend electronics and passive test structures such as passive pixel arrays, MOS capacitors and backside diodes. Although the produced samples were already characterized from the electrical point of view, a thorough study of the charge collection dynamics of the passive pixel arrays was still missing. In this paper we show the results of the dynamic characterization of a group of passive pixel arrays with different pixel pitches (50, 25 and 10 μm) and different pixel layouts. The tested samples have been illuminated from the backside with an infrared and a red laser with wavelengths equal to 1,060 nm and 660 nm, respectively. The pixel arrays have been mounted on a custom readout PCB connected to an external amplifier with 1 GHz bandwidth and the signals have been acquired through a fast digital oscilloscope. We employed both focused and unfocused laser spots to evaluate the change in the measured signal as a function of the laser spot position and the average response of the pixel arrays. An excellent agreement has been demonstrated by comparing the measured signals with the results of transient TCAD simulations and a time for 50% charge collection of 7.8, 4.2 and 2.6 ns has been predicted and experimentally validated in pixels with 50, 25 and 10 μm pitch, respectively.
JSwarm: A Jingulu-Inspired Human-AI-Teaming Language for Context-Aware Swarm Guidance
Authors: Abbass Hussein A. , Petraki Eleni , Hunjet Robert
Published: July 2022

Bi-directional communication between humans and swarm systems begs for efficient languages to communicate information between the humans and the Artificial Intelligence (AI)-enabled agents in a manner that is most appropriate for the context. We discuss the criteria for effective teaming and functional bi-directional communication between humans and AI, and the design choices required to create effective languages. We then present a human-AI-teaming communication language inspired by the Australian Aboriginal language of Jingulu, which we call JSwarm. We present the motivation and structure of the language. An example is used to demonstrate how the language operates for a shepherding swarm guidance task.
Estimation of Characteristic Parameters of Grape Clusters Based on Point Cloud Data
Authors: Liu Wentao , Wang Chenglin , Yan De , Chen Weilin , Luo Lufeng
Published: July 2022

The measurement of grapevine phenotypic parameters is crucial to quantify crop traits. However, individual differences in grape bunches pose challenges in accurately measuring their characteristic parameters. Hence, this study explores a method for estimating grape feature parameters based on point cloud information: segment the grape point cloud by filtering and region growing algorithm, and register the complete grape point cloud model by the improved iterative closest point algorithm. After estimating model phenotypic size characteristics, the grape bunch surface was reconstructed using the Poisson algorithm. Through the comparative analysis with the existing four methods (geometric model, 3D convex hull, 3D alpha-shape, and voxel-based), the estimation results of the algorithm proposed in this study are the closest to the measured parameters. Experimental data show that the coefficient of determination (R2) of the Poisson reconstruction algorithm is 0.9915, which is 0.2306 higher than the coefficient estimated by the existing alpha-shape algorithm (R2 = 0.7609). Therefore, the method proposed in this study provides a strong basis for the quantification of grape traits.
Application of High-Throughput Sequencing on the Chinese Herbal Medicine for the Data-Mining of the Bioactive Compounds
Authors: Liu Xiaoyan , Gong Xun , Liu Yi , Liu Junlin , Zhang Hantao , Qiao Sen , Li Gang , Tang Min
Published: July 2022

The Chinese Herbal Medicine (CHM) has been used worldwide in clinic to treat the vast majority of human diseases, and the healing effect is remarkable. However, the functional components and the corresponding pharmacological mechanism of the herbs are unclear. As one of the main means, the high-throughput sequencing (HTS) technologies have been employed to discover and parse the active ingredients of CHM. Moreover, a tremendous amount of effort is made to uncover the pharmacodynamic genes associated with the synthesis of active substances. Here, based on the genome-assembly and the downstream bioinformatics analysis, we present a comprehensive summary of the application of HTS on CHM for the synthesis pathways of active ingredients from two aspects: active ingredient properties and disease classification, which are important for pharmacological, herb molecular breeding, and synthetic biology studies.
Effective Mechanisms for Improving Seed Oil Production in Pennycress (Thlaspi arvense L.) Highlighted by Integration of Comparative Metabolomics and Transcriptomics
Authors: Johnston Christopher , García Navarrete Leidy Tatiana , Ortiz Emmanuel , Romsdahl Trevor B. , Guzha Athanas , Chapman Kent D. , Grotewold Erich , Alonso Ana Paula
Published: July 2022

Pennycress is a potentially lucrative biofuel crop due to its high content of long-chain unsaturated fatty acids, and because it uses non-conventional pathways to achieve efficient oil production. However, metabolic engineering is required to improve pennycress oilseed content and make it an economically viable source of aviation fuel. Research is warranted to determine if further upregulation of these non-conventional pathways could improve oil production within the species even more, which would indicate these processes serve as promising metabolic engineering targets and could provide the improvement necessary for economic feasibility of this crop. To test this hypothesis, we performed a comparative biomass, metabolomic, and transcriptomic analyses between a high oil accession (HO) and low oil accession (LO) of pennycress to assess potential factors required to optimize oil content. An evident reduction in glycolysis intermediates, improved oxidative pentose phosphate pathway activity, malate accumulation in the tricarboxylic acid cycle, and an anaplerotic pathway upregulation were noted in the HO genotype. Additionally, higher levels of threonine aldolase transcripts imply a pyruvate bypass mechanism for acetyl-CoA production. Nucleotide sugar and ascorbate accumulation also were evident in HO, suggesting differential fate of associated carbon between the two genotypes. An altered transcriptome related to lipid droplet (LD) biosynthesis and stability suggests a contribution to a more tightly-packed LD arrangement in HO cotyledons. In addition to the importance of central carbon metabolism augmentation, alternative routes of carbon entry into fatty acid synthesis and modification, as well as transcriptionally modified changes in LD regulation, are key aspects of metabolism and storage associated with economically favorable phenotypes of the species.
Moisture Dynamics of Wood-Based Panels and Wood Fibre Insulation Materials
Authors: De Ligne Liselotte , Van Acker Joris , Baetens Jan M. , Omar Salah , De Baets Bernard , Thygesen Lisbeth G. , Van den Bulcke Jan , Thybring Emil E.
Published: July 2022

Moisture performance is an important factor determining the resistance of wood-based building materials against fungal decay. Understanding how material porosity and chemistry affect moisture performance is necessary for their efficient use, as well as for product optimisation. In this study, three complementary techniques (X-ray computed tomography, infrared and low-field NMR spectroscopy) are applied to elucidate the influence of additives, manufacturing process and material structure on the liquid water absorption and desorption behaviour of a selection of wood-based panels, thermally modified wood and wood fibre insulation materials. Hydrophobic properties achieved by thermal treatment or hydrophobic additives such as paraffin and bitumen, had a major influence on water absorption and desorption rates. When hydrophobic additives did not play a role, pore distributions and manufacturing process had a decisive influence on the amount and rate of absorption and desorption. In that case, a higher porosity resulted in a higher water absorption rate. Our results show that there is a clear potential for tailoring materials towards specific moisture performance by better understanding the influence of different material characteristics. This is useful both for achieving desired moisture buffering as well as to increase service life of wood-based materials. From a sustainability perspective, fit-for-purpose moisture performance is often easier to achieve and preferred than wood protection by biocide preservative treatments.
Identification of QTL for Stem Traits in Wheat (Triticum aestivum L.)
Authors: Niu Yanan , Chen Tianxiao , Zhao Chenchen , Guo Ce , Zhou Meixue
Published: July 2022

Lodging in wheat (Triticum aestivum L.) is a complicated phenomenon that is influenced by physiological, genetics, and external factors. It causes a great yield loss and reduces grain quality and mechanical harvesting efficiency. Lodging resistance is contributed by various traits, including increased stem strength. The aim of this study was to map quantitative trait loci (QTL) controlling stem strength-related features (the number of big vascular bundles, stem diameter, stem wall thickness) using a doubled haploid (DH) population derived from a cross between Baiqimai and Neixiang 5. Field experiments were conducted during 2020–2022, and glasshouse experiments were conducted during 2021–2022. Significant genetic variations were observed for all measured traits, and they were all highly heritable. Fifteen QTL for stem strength-related traits were identified on chromosomes 2D, 3A, 3B, 3D, 4B, 5A, 6B, 7A, and 7D, respectively, and 7 QTL for grain yield-related traits were identified on chromosomes 2B, 2D, 3D, 4B, 7A, and 7B, respectively. The superior allele of the major QTL for the number of big vascular bundle (VB) was independent of plant height (PH), making it possible to improve stem strength without a trade-off of PH, thus improving lodging resistance. VB also showed positive correlations with some of the yield components. The result will be useful for molecular marker-assisted selection (MAS) for high stem strength and high yield potential.
Associations Between Child Maltreatment, Inflammation, and Comorbid Metabolic Syndrome to Depressed Mood in a Multiethnic Urban Population: The HELIUS Study
Authors: Willemen Fabienne E. M. , van Zuiden Mirjam , Zantvoord Jasper B. , de Rooij Susanne R. , van den Born Bert-Jan H. , Hak A. Elisabeth , Thomaes Kathleen , Segeren Menno , Elsenburg Leonie K. , Lok Anja
Published: July 2022

Background

Child maltreatment is a common negative experience and has potential long-lasting adverse consequences for mental and physical health, including increased risk for major depressive disorder (MDD) and metabolic syndrome. In addition, child maltreatment may increase the risk for comorbid physical health conditions to psychiatric conditions, with inflammation as an important mediator linking child maltreatment to poor adult health. However, it remains unresolved whether experiencing child maltreatment increases the risk for the development of comorbid metabolic syndrome to MDD. Therefore, we investigated whether child maltreatment increased the risk for comorbid metabolic syndrome to depressed mood. Subsequently, we examined whether C-reactive protein (CRP), as an inflammatory marker, mediated this association. In addition, we investigated whether effects differed between men and women.

Methods

Associations were examined within cross-sectional data from the multiethnic HELIUS study (N = 21,617). Adult residents of Amsterdam, Netherlands, self-reported on child maltreatment (distinct and total number of types experienced before the age of 16 years) as well as current depressed mood (PHQ-9 score ≥ 10), and underwent physical examination to assess metabolic syndrome. The CRP levels were assessed in N = 5,998 participants. Logistic and linear regressions were applied for binary and continuous outcomes, respectively. All analyses were adjusted for relevant demographic, socioeconomic, and lifestyle characteristics, including ethnicity.

Results

A higher number of maltreatment types as well as distinct types of emotional neglect, emotional abuse, and sexual abuse were significantly associated with a higher risk for current depressed mood. Child maltreatment was not significantly associated with the risk for metabolic syndrome in the whole cohort, nor within individuals with depressed mood. As child maltreatment was not significantly associated with the CRP levels, subsequent mediation analyses were not performed. No significant moderating effects by sex were observed.

Conclusion

In this multiethnic urban cohort, child maltreatment was associated with a higher risk for depressed mood. Contrary to our expectations, child maltreatment was not significantly associated with an increased risk for metabolic syndrome, neither in the whole cohort nor as a comorbid condition in individuals with depressed mood. As the data were cross-sectional and came from a non-clinical adult population, longitudinal perspectives in relation to various stages of the investigated conditions were needed with more comprehensive assessments of inflammatory markers.
Learner engagement in the flipped foreign language classroom: Definitions, debates, and directions of future research
Authors: Li Zhiyong , Li Jiaying
Published: July 2022

Flipped classrooms have attracted widespread attention and interest from English for foreign language (EFL) practitioners and researchers and are regarded as a promising pedagogical approach to increase learning outcomes and facilitate learner engagement. This article takes stock of the publications on learner engagement in flipped EFL classrooms. In so doing, we aim to clarify the engagement construct specific to the EFL classroom setting, summarize the effect that flipped classrooms have on EFL learners’ engagement, and identify factors affecting engagement. We find that there has been a range of debates and tensions regarding flipped classrooms and learner engagement in EFL settings, and that more theory-grounded empirical studies are needed to delineate learner engagement in localized flipped learning and teaching contexts. We would argue that in future research, multiple variables, including learner dynamics and social-psychological factors, should be considered while flipping the EFL course so that practitioners can provide tailor-made support to improve learners’ engagement levels.