Survival of advanced/recurrent gastrointestinal stromal tumors treated with tyrosine kinase inhibitors in Taiwan: a nationwide registry study.

BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.

How substituents tune quantum interference in meta-OPE3 molecular junctions to control thermoelectric transport.

Quantum interference (QI) can strongly affect electric and thermoelectric properties of molecular junctions (MJs). So far, however, a limited number of experimental studies have explored the influence of QI on thermoelectric transport in MJs. To address this open point, we synthesized derivatives of meta-OPE3 with an electron-withdrawing nitro (-NO2) substituent or an electron-donating N,N-dimethyl amine (-NMe2) substituent, attached at two different positions of the central phenylene ring, and systematically studied the electrical conductance and thermopower of the corresponding gold-molecule-gold junctions. We show that (i) the electrical conductance of MJs depends weakly on the polarity of the substituents but strongly on the substitution position and (ii) MJs with the N,N-dimethyl amine group feature a higher thermopower than MJs with the nitro group. We also present calculations based on first principles, which explain these trends and show that the transport properties are highly sensitive to microscopic details in junctions, exhibiting destructive QI features.

A phase 1 study of biweekly nab-paclitaxel/oxaliplatin/S-1/LV for advanced upper gastrointestinal cancers: TCOG T1216 study.

BACKGROUND: Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers. METHODS: A 3 + 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively. CONCLUSION: The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation. CLINICALTRIALS.GOV IDENTIFIER: NCT03162510.

Blocking M2-like macrophage polarization using decoy oligodeoxynucleotide-based gene therapy prevents immune evasion for pancreatic cancer treatment.

M2-like macrophages exhibit immunosuppressive activity and promote pancreatic cancer progression. Reactive oxygen species (ROS) affect macrophage polarization; however, the mechanism remains unclear. This study aimed to elucidate the underlying molecular basis and design a gene therapy to inhibit M2-like polarization. Microarray analysis and IF staining were performed in M1-like and M2-like macrophages to ascertain the expression of CYBB, a major intracellular ROS source. Co-culture assay and syngeneic orthotopic pancreatic cancer mouse models were used to study the mechanism of M2-like skewing. Decoy oligodeoxynucleotides (ODNs) were designed to manipulate CYBB transcription to inhibit M2-like polarization and control tumor growth. Lipopolysaccharide (LPS) treatment polarized U937 cells to M1-like macrophages in which CYBB expression was increased. In contrast, co-culture with PANC-1 cells induced M2-like polarization in U937 cells with CYBB downregulation. High CD204 M2-like expression in combination with low CYBB expression was associated with the worst prognosis in pancreatic cancer patients. STAT6 and HDAC2 in U937 cells were activated by cancer cell-derived IL-4 after coculture and then bound to the CYBB promoter to repress CYBB expression, resulting in M2-like polarization. DPI that inhibits ROS production could block this action. Knockdown of STAT6 and HDAC2 also inhibited M2-like polarization and maintained the M1-like phenotype of U937 cells after coculture. Decoy ODNs interrupting the binding of STAT6 to the CYBB promoter counteracted M2-like polarization and tumor growth and triggered antitumor immunity in vivo. Gene therapy using STAT6-CYBB decoy ODNs can inhibit M2-like polarization, representing a potential therapeutic tool for pancreatic cancer.

Loss of Sigma-2 Receptor/TMEM97 Is Associated with Neuropathic Injury-Induced Depression-Like Behaviors in Female Mice.

Previous studies have shown that ligands that bind to sigma-2 receptor/TMEM97 (s2R/TMEM97), a transmembrane protein, have anxiolytic/antidepressant-like properties and relieve neuropathic pain-like effects in rodents. Despite medical interest in s2R/TMEM97, little affective and pain behavioral characterization has been done using transgenic mice, which limits the development of s2R/TMEM97 as a viable therapeutic target. Using wild-type (WT) and global Tmem97 knock-out (KO) mice, we sought to identify the contribution of Tmem97 in modulating affective and pain-like behaviors using a battery of affective and pain assays, including open field, light/dark preference, elevated plus maze, forced swim test, tail suspension test, and the mechanical sensitivity tests. Our results demonstrate that female Tmem97 KO mice show less anxiety-like and depressive-like behaviors in light/dark preference and tail suspension tests but not in an open field, elevated plus maze, and forced swim tests at baseline. We next performed spared nerve injury in WT and Tmem97 KO mice to assess the role of Tmem97 in neuropathic pain-induced anxiety and depression. WT mice, but not Tmem97 KO mice, developed a prolonged neuropathic pain-induced depressive-like phenotype when tested 10 weeks after nerve injury in females. Our results show that Tmem97 plays a role in modulating anxiety-like and depressive-like behaviors in naive animals with a significant change in the presence of nerve injury in female mice. Overall, these data demonstrate that Tmem97 could be a target to alleviate affective comorbidities of pain disorders.

Causal inference and mechanism for unraveling the removal of four pesticides from lettuce (Lactuca sativa L.) via ultrasonic processing and various immersion solutions.

This study explores the reduction of carbamates (CAs) and pyrethroids (PYs) - commonly used pesticides - in lettuce using various immersion solutions and ultrasonic processing. It also examines the role of machine learning and molecular docking in understanding the mechanisms of pesticide reduction. The results revealed that the highest reduction of both CAs and PYs exceeded 80 % on lettuce leaves. In most samples, the reduction increased with the power of ultrasonic processing and processing time. The results of machine learning models (XGBoost and SHAP) showed that during the immersion cleaning of CAs and PYs, as well as during both immersion cleaning and ultrasonic processing of CAs + PYs, the reduction was most influenced by the initial pesticide levels and immersion time. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of lettuce's wax layer identified 24 compounds, including fatty alcohols, fatty acids, fatty acid esters, and triterpenoids. Despite the absence of active sites, the lipophilic nature of long-chain aliphatic compounds aids in pesticide binding, while triterpenoids form strong hydrogen bonds with pesticides, indicating a robust adsorption on the lettuce surface. This study aims to offer insights into the efficient removal of chemical pesticide residues from fruits and vegetables, addressing critical concerns for food safety and human health.

Fully human chitinase-3 like-1 monoclonal antibody inhibits tumor growth, fibrosis, angiogenesis, and immune cell remodeling in lung, pancreatic, and colorectal cancers.

Considering the limited efficacy of current therapies in lung, colorectal, and pancreatic cancers, innovative combination treatments with diverse mechanisms of action are needed to improve patients' outcomes. Chitinase-3 like-1 protein (CHI3L1) emerges as a versatile factor with significant implications in various diseases, particularly cancers, fostering an immunosuppressive tumor microenvironment for cancer progression. Therefore, pre-clinical validation is imperative to fully realize its potential in cancer treatment. We developed phage display-derived fully human monoclonal CHI3L1 neutralizing antibodies (nAbs) and verified the nAbs-antigen binding affinity and specificity in lung, pancreatic and colorectal cancer cell lines. Tumor growth signals, proliferation and migration ability were all reduced by CHI3L1 nAbs in vitro. Orthotopic or subcutaneous tumor mice model and humanized mouse model were established for characterizing the anti-tumor properties of two CHI3L1 nAb leads. Importantly, CHI3L1 nAbs not only inhibited tumor growth but also mitigated fibrosis, angiogenesis, and restored immunostimulatory functions of immune cells in pancreatic, lung, and colorectal tumor mice models. Mechanistically, CHI3L1 nAbs directly suppressed the activation of pancreatic stellate cells and the transformation of macrophages into myofibroblasts, thereby attenuating fibrosis. These findings strongly support the therapeutic potential of CHI3L1 nAbs in overcoming clinical challenges, including the failure of gemcitabine in pancreatic cancer.

Progress in Rice Breeding Based on Genomic Research.

The role of rice genomics in breeding progress is becoming increasingly important. Deeper research into the rice genome will contribute to the identification and utilization of outstanding functional genes, enriching the diversity and genetic basis of breeding materials and meeting the diverse demands for various improvements. Here, we review the significant contributions of rice genomics research to breeding progress over the last 25 years, discussing the profound impact of genomics on rice genome sequencing, functional gene exploration, and novel breeding methods, and we provide valuable insights for future research and breeding practices.

PlantMine: A Machine-Learning Framework to Detect Core SNPs in Rice Genomics.

As a fundamental global staple crop, rice plays a pivotal role in human nutrition and agricultural production systems. However, its complex genetic architecture and extensive trait variability pose challenges for breeders and researchers in optimizing yield and quality. Particularly to expedite breeding methods like genomic selection, isolating core SNPs related to target traits from genome-wide data reduces irrelevant mutation noise, enhancing computational precision and efficiency. Thus, exploring efficient computational approaches to mine core SNPs is of great importance. This study introduces PlantMine, an innovative computational framework that integrates feature selection and machine learning techniques to effectively identify core SNPs critical for the improvement of rice traits. Utilizing the dataset from the 3000 Rice Genomes Project, we applied different algorithms for analysis. The findings underscore the effectiveness of combining feature selection with machine learning in accurately identifying core SNPs, offering a promising avenue to expedite rice breeding efforts and improve crop productivity and resilience to stress.

The Metal-Insulator Transition in Vanadium Oxide Nanofilms Enables Microkelvin-Resolution Thermometry.

High-resolution thermometry is critical for probing nanoscale energy transport. Here, we demonstrate how high-resolution thermometry can be accomplished using vanadium oxide (VOx), which features a sizable temperature-dependence of its resistance at room temperature and an even stronger dependence at its metal-insulator-transition (MIT) temperature. We microfabricate VOx nanofilm-based electrical resistance thermometers that undergo a metal-insulator-transition at ∼337 K and systematically quantify their temperature-dependent resistance, noise characteristics, and temperature resolution. We show that VOx sensors can achieve, in a bandwidth of ∼16 mHz, a temperature resolution of ∼5 µK at room temperature (∼300 K) and a temperature resolution of ∼1 µK at the MIT (∼337 K) when the amplitude of temperature perturbations is in the microkelvin range, which, in contrast to larger perturbations, is found to avoid hysteric resistance responses. These results demonstrate that VOx-based thermometers offer a ∼10-50-fold improvement in resolution over widely used Pt-based thermometers.

Impact of previous S-1 treatment on efficacy of liposomal irinotecan plus 5-fluorouracil and leucovorin in patients with metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Liposomal irinotecan plus 5-fluorouracil and leucovorin (nal-IRI + 5-FU/LV) provides survival benefits for metastatic pancreatic adenocarcinoma (mPDAC) refractory to gemcitabine-based treatment, mainly gemcitabine plus nab-paclitaxel (GA), in current practice. Gemcitabine plus S-1 (GS) is another commonly administered first-line regimen before nab-paclitaxel reimbursement; however, the efficacy and safety of nal-IRI + 5-FU/LV for mPDAC after failed GS treatment has not been reported and was therefore explored in this study. METHODS: In total, 177 patients with mPDAC received first-line GS or GA treatment, followed by second-line nal-IRI + 5-FU/LV treatment (identified from a multicenter retrospective cohort in Taiwan from 2018 to 2020); 85 and 92 patients were allocated to the GS and GA groups, respectively. Overall survival (OS), time-to-treatment failure (TTF), and adverse events were compared between the two groups. RESULTS: The baseline characteristics of the two groups were generally similar; however, a higher median age (67 versus 62 years, p < 0.001) and fewer liver metastases (52% versus 78%, p < 0.001) were observed in the GS versus GA group. The median OS was 15.0 and 15.9 months in the GS and GA groups, respectively (p = 0.58). The TTF (3.1 versus 2.8 months, p = 0.36) and OS (7.6 versus 6.7 months, p = 0.83) after nal-IRI treatment were similar between the two groups. More patients in the GS group developed mucositis during nal-IRI treatment (15% versus 4%, p = 0.02). CONCLUSIONS: The efficacy of second-line nal-IRI +5-FU/LV treatment was unaffected by prior S-1 exposure. GS followed by nal-IRI treatment is an alternative treatment sequence for patients with mPDAC.

Stromal Rigidity Stress Accelerates Pancreatic Intraepithelial Neoplasia Progression and Chromosomal Instability via Nuclear Protein Tyrosine Kinase 2 Localization.

Because the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and phosphorylated Ser-139 residue of the histone variant H2AX (γH2AX) foci linked to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3-µm micropores. To search for pancreatic cancer cell-of-origin, analysis of single-cell data sets revealed that the extracellular matrix shaped an alternate route of acinar-ductal transdifferentiation of acinar cells into topoisomerase II α (TOP2A)-overexpressing cancer cells and derived subclusters with copy number amplifications in MYC-PTK2 (protein tyrosine kinase 2) locus and PIK3CA. High-PTK2 expression is associated with 171 differentially methylated CpG loci, 319 differentially expressed genes, and poor overall survival in The Cancer Genome Atlas-Pancreatic Adenocarcinoma cohort. Abolished RGD-integrin signaling by disintegrin KG blocked the PTK2 phosphorylation, increased cancer apoptosis, decreased vav guanine nucleotide exchange factor 1 (VAV1) expression, and prolonged overall survival in the KPC mice. Reduction of α-smooth muscle actin deposition in the CD248 knockout KPC mice remodeled the tissue stroma and down-regulated TOP2A expression in the epithelium. In summary, stromal stiffness induced the onset of cancer cells-of-origin by ectopic TOP2A expression, and the genomic amplification of MYC-PTK2 locus via alternative transdifferentiation of pancreatic progenitor cells is the vulnerability useful for disintegrin KG treatment.

Fates and models for exposure pathways of pyrethroid pesticide residues: A review.

Pyrethroids (PYs) are widely applied pesticides whose residues pose potential health risks. This review describes current knowledge on PY chemical properties, usage patterns, environmental and food contamination, and human exposure models. It evaluates life cycle assessment (LCA), chemical alternatives assessment (CAA), and high-throughput screening (HTS) as tools for pesticide policy. Despite efforts to mitigate PY presence, their pervasive residues in the environment and food persist. And the highest concentrations ranged from 54,360 to 80,500 ng/L in water samples from agricultural fields. Food processing techniques variably reduce PY levels, yet no method guarantees complete elimination. This review provides insights into the fates and exposure pathways of PY residues in agriculture and food, and highlights the necessity for improved PY management and alternative practices to safeguard health and environment.

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan.

BACKGROUND: Cancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population. METHODS: Exome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHRmut, including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy. RESULTS: Overall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0-43.7), the median overall survival (OS) was not significantly different among patients with gHRmut, non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHRmut. Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7-33.7) versus 9.6 months (95% CI 5.9-17.6), P = 0.001. However, the median OS of patients without gHRmut was 14.5 months (95% CI 13.2-16.9) and 12.6 months (95% CI 10.8-14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis. CONCLUSIONS: Our study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis.

Detecting pancreatic duct adenocarcinoma (PDAC) in its early stages and predicting late-stage patient prognosis undergoing chemotherapy is challenging. This work shows that the activation of specific oncogenes leads to elevated expression of mRNAs and their corresponding proteins in extracellular vesicles (EVs) circulating in blood. Utilizing an immune lipoplex nanoparticle (ILN) biochip assay, these findings demonstrate that glypican 1 (GPC1) mRNA expression in the exosomes-rich (Exo) EV subpopulation and GPC1 membrane protein (mProtein) expression in the microvesicles-rich (MV) EV subpopulation, particularly the tumor associated microvesicles (tMV), served as a viable biomarker for PDAC. A combined analysis effectively discriminated early-stage PDAC patients from benign pancreatic diseases and healthy donors in sizable clinical from multiple hospitals. Furthermore, among late-stage PDAC patients undergoing chemotherapy, lower GPC1 tMV-mProtein and Exo-mRNA expression before treatment correlated significantly with prolonged overall survival. These findings underscore the potential of vesicular GPC1 expression for early PDAC screenings and chemotherapy prognosis.

Sampling complex topology structures for spiking neural networks.

Spiking Neural Networks (SNNs) have been considered a potential competitor to Artificial Neural Networks (ANNs) due to their high biological plausibility and energy efficiency. However, the architecture design of SNN has not been well studied. Previous studies either use ANN architectures or directly search for SNN architectures under a highly constrained search space. In this paper, we aim to introduce much more complex connection topologies to SNNs to further exploit the potential of SNN architectures. To this end, we propose the topology-aware search space, which is the first search space that enables a more diverse and flexible design for both the spatial and temporal topology of the SNN architecture. Then, to efficiently obtain architecture from our search space, we propose the spatio-temporal topology sampling (STTS) algorithm. By leveraging the benefits of random sampling, STTS can yield powerful architecture without the need for an exhaustive search process, making it significantly more efficient than alternative search strategies. Extensive experiments on CIFAR-10, CIFAR-100, and ImageNet demonstrate the effectiveness of our method. Notably, we obtain 70.79% top-1 accuracy on ImageNet with only 4 time steps, 1.79% higher than the second best model. Our code is available under https://github.com/stiger1000/Random-Sampling-SNN.

CD204-positive M2-like tumor-associated macrophages increase migration of gastric cancer cells by upregulating miR-210 to reduce NTN4 expression.

BACKGROUND: Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment and portend poor prognosis. However, the molecular mechanisms underlying the tumor promotion of TAMs have not been fully elucidated. METHODS: Coculture of gastric cancer cells with U937 cells was performed to investigate the impact of TAMs on cancer cell behavior. MicroRNA (miRNA) microarray and bioinformatics were applied to identify the involved miRNAs and the functional target genes. The regulation of the miRNA on its target gene was studied using anti-miRNA and miRNA mimic. RESULTS: Coculture with CD204+ M2-like TAMs increased proliferation, migration, and epithelial-mesenchymal transition of gastric cancer cells. MiR-210 was the most upregulated miRNA in cancer cells identified by miRNA microarray after coculture. In gastric cancer tissues, miR-210 expression was positively correlated with CD204+ M2-like TAM infiltration. Inactivation of miR-210 by antimir attenuated CD204+ M2-like TAMs-induced cancer cell migration. Using pharmacological inhibitors and neutralizing antibodies, CD204+ M2-like TAMs-secreted TNFα was found to upregulate miR-210 through NF-κB/HIF-1α signaling. Bioinformatics analysis showed netrin-4 (NTN4) as a potential target of miR-210 to suppress gastric cancer cell migration. We also found an inverse expression between miR-210 and NTN4 in cancer cells after coculture or in tumor xenografts. Anti-miR-210 increased NTN4 expression, while miR-210 mimics downregulated NTN4 in cancer cells. Reporter luciferase assays showed that MiR-210 mimics suppressed NTN4 3' untranslated region-driven luciferase activity in cancer cells, but this effect was blocked after mutating miR-210 binding site. CONCLUSIONS: CD204+ M2-like TAMs can utilize the TNF-α/NF-κB/HIF-1α/miR-210/NTN4 pathway to facilitate gastric cancer progression.

GINv2.0: a comprehensive topological network integrating molecular interactions from multiple knowledge bases.

Knowledge bases have been instrumental in advancing biological research, facilitating pathway analysis and data visualization, which are now widely employed in the scientific community. Despite the establishment of several prominent knowledge bases focusing on signaling, metabolic networks, or both, integrating these networks into a unified topological network has proven to be challenging. The intricacy of molecular interactions and the diverse formats employed to store and display them contribute to the complexity of this task. In a prior study, we addressed this challenge by introducing a "meta-pathway" structure that integrated the advantages of the Simple Interaction Format (SIF) while accommodating reaction information. Nevertheless, the earlier Global Integrative Network (GIN) was limited to reliance on KEGG alone. Here, we present GIN version 2.0, which incorporates human molecular interaction data from ten distinct knowledge bases, including KEGG, Reactome, and HumanCyc, among others. We standardized the data structure, gene IDs, and chemical IDs, and conducted a comprehensive analysis of the consistency among the ten knowledge bases before combining all unified interactions into GINv2.0. Utilizing GINv2.0, we investigated the glycolysis process and its regulatory proteins, revealing coordinated regulations on glycolysis and autophagy, particularly under glucose starvation. The expanded scope and enhanced capabilities of GINv2.0 provide a valuable resource for comprehensive systems-level analyses in the field of biological research. GINv2.0 can be accessed at: https://github.com/BIGchix/GINv2.0 .

Prediction of surgical outcomes in severe encapsulating peritoneal sclerosis using a computed tomography scoring system.

BACKGROUND/PURPOSE: Encapsulating peritoneal sclerosis (EPS) is a rare and potential lethal complication of peritoneal dialysis characterized by bowel obstruction. Surgical enterolysis is the only curative therapy. Currently, there are no tools for predicting postsurgical prognosis. This study aimed to identify a computed tomography (CT) scoring system that could predict mortality after surgery in patients with severe EPS. METHODS: This retrospective study enrolled patients with severe EPS who underwent surgical enterolysis in a tertiary referral medical center. The association of CT score with surgical outcomes including mortality, blood loss, and bowel perforation was analyzed. RESULTS: Thirty-four patients who underwent 37 procedures were recruited and divided into a survivor and non-survivor group. The survivor group had higher body mass indices (BMIs, 18.1 vs. 16.7 kg/m2, p = 0.035) and lower CT scores (11 vs. 17, p < 0.001) than the non-survivor group. The receiver operating characteristic curve revealed that a CT score of ≥15 could be considered a cutoff point to predict surgical mortality, with an area under the curve of 0.93, sensitivity of 88.9%, and specificity of 82.1%. Compared with the group with CT scores of <15, the group with CT scores of ≥15 had a lower BMI (19.7 vs. 16.2 kg/m2, p = 0.004), higher mortality (4.2% vs. 61.5%, p < 0.001), greater blood loss (50 vs. 400 mL, p = 0.007), and higher incidence of bowel perforation (12.5% vs. 61.5%, p = 0.006). CONCLUSION: The CT scoring system could be useful in predicting surgical risk in patients with severe EPS receiving enterolysis.