p53 Represses the Mevalonate Pathway to Mediate Tumor Suppression.

There are still gaps in our understanding of the complex processes by which p53 suppresses tumorigenesis. Here we describe a novel role for p53 in suppressing the mevalonate pathway, which is responsible for biosynthesis of cholesterol and nonsterol isoprenoids. p53 blocks activation of SREBP-2, the master transcriptional regulator of this pathway, by transcriptionally inducing the ABCA1 cholesterol transporter gene. A mouse model of liver cancer reveals that downregulation of mevalonate pathway gene expression by p53 occurs in premalignant hepatocytes, when p53 is needed to actively suppress tumorigenesis. Furthermore, pharmacological or RNAi inhibition of the mevalonate pathway restricts the development of murine hepatocellular carcinomas driven by p53 loss. Like p53 loss, ablation of ABCA1 promotes murine liver tumorigenesis and is associated with increased SREBP-2 maturation. Our findings demonstrate that repression of the mevalonate pathway is a crucial component of p53-mediated liver tumor suppression and outline the mechanism by which this occurs.

Mutant p53 drives pancreatic cancer metastasis through cell-autonomous PDGF receptor ß signaling.

Missense mutations in the p53 tumor suppressor inactivate its antiproliferative properties but can also promote metastasis through a gain-of-function activity. We show that sustained expression of mutant p53 is required to maintain the prometastatic phenotype of a murine model of pancreatic cancer, a highly metastatic disease that frequently displays p53 mutations. Transcriptional profiling and functional screening identified the platelet-derived growth factor receptor b (PDGFRb) as both necessary and sufficient to mediate these effects. Mutant p53 induced PDGFRb through a cell-autonomous mechanism involving inhibition of a p73/NF-Y complex that represses PDGFRb expression in p53-deficient, noninvasive cells. Blocking PDGFRb signaling by RNA interference or by small molecule inhibitors prevented pancreatic cancer cell invasion in vitro and metastasis formation in vivo. Finally, high PDGFRb expression correlates with poor disease-free survival in pancreatic, colon, and ovarian cancer patients, implicating PDGFRb as a prognostic marker and possible target for attenuating metastasis in p53 mutant tumors.

MDM2 and MDMX promote ferroptosis by PPARα-mediated lipid remodeling.

MDM2 and MDMX, negative regulators of the tumor suppressor p53, can work separately and as a heteromeric complex to restrain p53's functions. MDM2 also has pro-oncogenic roles in cells, tissues, and animals that are independent of p53. There is less information available about p53-independent roles of MDMX or the MDM2-MDMX complex. We found that MDM2 and MDMX facilitate ferroptosis in cells with or without p53. Using small molecules, RNA interference reagents, and mutant forms of MDMX, we found that MDM2 and MDMX, likely working in part as a complex, normally facilitate ferroptotic death. We observed that MDM2 and MDMX alter the lipid profile of cells to favor ferroptosis. Inhibition of MDM2 or MDMX leads to increased levels of FSP1 protein and a consequent increase in the levels of coenzyme Q10, an endogenous lipophilic antioxidant. This suggests that MDM2 and MDMX normally prevent cells from mounting an adequate defense against lipid peroxidation and thereby promote ferroptosis. Moreover, we found that PPARα activity is essential for MDM2 and MDMX to promote ferroptosis, suggesting that the MDM2-MDMX complex regulates lipids through altering PPARα activity. These findings reveal the complexity of cellular responses to MDM2 and MDMX and suggest that MDM2-MDMX inhibition might be useful for preventing degenerative diseases involving ferroptosis. Furthermore, they suggest that MDM2/MDMX amplification may predict sensitivity of some cancers to ferroptosis inducers.

Mutant p53 disrupts mammary tissue architecture via the mevalonate pathway.

p53 is a frequent target for mutation in human tumors, and mutant p53 proteins can actively contribute to tumorigenesis. We employed a three-dimensional culture model in which nonmalignant breast epithelial cells form spheroids reminiscent of acinar structures found in vivo, whereas breast cancer cells display highly disorganized morphology. We found that mutant p53 depletion is sufficient to phenotypically revert breast cancer cells to a more acinar-like morphology. Genome-wide expression analysis identified the mevalonate pathway as significantly upregulated by mutant p53. Statins and sterol biosynthesis intermediates reveal that this pathway is both necessary and sufficient for the phenotypic effects of mutant p53 on breast tissue architecture. Mutant p53 associates with sterol gene promoters at least partly via SREBP transcription factors. Finally, p53 mutation correlates with highly expressed sterol biosynthesis genes in human breast tumors. These findings implicate the mevalonate pathway as a therapeutic target for tumors bearing mutations in p53.

Translation reinitiation in c.453delC frameshift mutation of KCNH2 producing functional hERG K+ channels with mild dominant negative effect in the heterozygote patient-derived iPSC cardiomyocytes.

The c.453delC (p.Thr152Profs*14) frameshift mutation in KCNH2 is associated with an elevated risk of Long QT syndrome (LQTS) and fatal arrhythmia. Nevertheless, the loss-of-function mechanism underlying this mutation remains unexplored and necessitates an understanding of electrophysiology. To gain insight into the mechanism of the LQT phenotype, we conducted whole-cell patch-clamp and immunoblot assays, utilizing both a heterologous expression system and patient-derived induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) with 453delC-KCNH2. We also explored the site of translational reinitiation by employing LC/MS mass spectrometry. Contrary to the previous assumption of early termination of translation, the findings of this study indicate that the 453delC-KCNH2 leads to an N-terminally truncated hERG channel, a potential from a non-canonical start codon, with diminished expression and reduced current (IhERG). The co-expression with wildtype KCNH2 produced heteromeric hERG channel with mild dominant-negative effect. Additionally, the heterozygote patient-derived iPSC-CMs exhibited prolonged action potential duration and reduced IhERG, which was ameliorated with the use of a hERG activator, PD-118057. The results of our study offer novel insights into the mechanisms involved in congenital LQTS associated with the 453delC mutation of KCNH2. The mutant results in the formation of less functional N-terminal-truncated channels with reduced amount of membrane expression. A hERG activator is capable of correcting abnormalities in both the heterologous expression system and patient-derived iPSC-CMs.

Network of Inorganic Nanocrystals Can Swell: Study of Swelling-Induced Surface Instability.

A unique organic-inorganic hybrid network composed of inorganic nanocores (ranging from semiconductors to metallic ones) interconnected through organic molecules can be produced by crosslinking the organic ligands of colloidal inorganic nanocrystals in assemblies. This work reports that this network, which is conventionally considered an inorganic film, can swell when exposed to a solvent because of the interaction between the solvent and the organic linkage within the network. Intriguingly, this work discovers that drying the solvent of the swollen organic-inorganic hybrid network can significantly affect the morphology owing to the swelling-induced compress stress, which is widely observed in various organic network systems. This work studies the surface instability of crosslinked organic-inorganic hybrid networks swollen by various organic solvents, which led to buckling delamination. Specifically, this work investigates the effects of the i) solvent-network interaction, ii) crosslinking density of the network, and iii) thickness of the film on the delamination behavior of the crosslinked network.

Extending the Operational Lifetime of Electrochemiluminescence Devices by Installing a Floating Bipolar Electrode.

Electrochemiluminescence (ECL) holds significant promise for the development of cost-effective light-emitting devices because of its simple structure. However, conventional ECL devices (ECLDs) have a major limitation of short operational lifetimes, rendering them impractical for real-world applications. Typically, the luminescence of these devices lasts no longer than a few minutes during operation. In the current study, a novel architecture is provided for ECLDs that addresses this luminescence lifespan issue. The device architecture features an ECL active layer between two coplanar driving electrodes and a third floating bipolar electrode. The inclusion of the floating bipolar electrode enables modulating the electrical-field distribution within the active layer when a bias is applied between the driving electrodes. This, in turn, enables the use of opaque yet electrochemically stable noble metals as the driving electrodes while allowing ECL light to escape through the transparent floating bipolar electrode. A significant extension on operational lifetime is achieved, defined as the time required for the initial luminance (>100 cd m-2) to decrease by 50%, surpassing 1 h. This starkly contrasts the short lifetime (<1 min) attained by ECLDs in a conventional sandwich-type architecture with two transparent electrodes. These results provide simple strategies for developing durable ECL-based light-emitting devices.

Aortic carboxypeptidase-like protein, a putative myokine, stimulates the differentiation and survival of bone-forming osteoblasts.

A new target that stimulates bone formation is needed to overcome limitations of current anti-osteoporotic drugs. Myokines, factors secreted from muscles, may modulate it. In this study, we investigated the role of aortic carboxypeptidase-like protein (ACLP), which is highly expressed in skeletal muscles, on bone formation. MC3T3-E1 cells and/or calvaria osteoblasts were treated with recombinant N-terminal mouse ACLP containing a signal peptide [rmACLP (N)]. The expression and secretion of ACLP were higher in skeletal muscle and differentiated myotube than in other tissues and undifferentiated myoblasts, respectively. rmACLP (N) increased bone formation, ALP activity, and phosphorylated p38 mitogen-activated protein (MAP) kinase in osteoblasts; reversal was achieved by pre-treatment with a TGF-ß receptor inhibitor. Under H2 O2 treatment, rmACLP (N) increased osteoblast survival, phosphorylated p38 MAP kinase, and the nuclear translocation of FoxO3a in osteoblasts. H2 O2 treatment caused rmACLP (N) to suppress its apoptotic, oxidative, and caspase-9 activities. rmACLP (N)-stimulated osteoblast survival was reversed by pre-treatment with a p38 inhibitor, a TGF-ß-receptor II blocking antibody, and a FoxO3a shRNA. Conditioned media (CM) from muscle cells stimulated osteoblast survival under H2 O2 treatment, in contrast to CM from ACLP knockdown muscle cells. rmACLP (N) increased the expressions of FoxO3a target anti-oxidant genes such as Sod2, Trx2, and Prx5. In conclusion, ACLP stimulated the differentiation and survival of osteoblasts. This led to the stimulation of bone formation by the activation of p38 MAP kinase and/or FoxO3a via TGF-ß receptors. These findings suggest a novel role for ACLP in bone metabolism as a putative myokine.

Gaussian Process Regression-Based Near-Infrared d-Luciferin Analogue Design Using Mutation-Controlled Graph-Based Genetic Algorithm.

Molecular discovery is central to the field of chemical informatics. Although optimization approaches have been developed that target-specific molecular properties in combination with machine learning techniques, optimization using databases of limited size is challenging for efficient molecular design. We present a molecular design method with a Gaussian process regression model and a graph-based genetic algorithm (GB-GA) from a data set comprising a small number of compounds by introducing mutation probability control in the genetic algorithm to enhance the optimization capability and speed up the convergence to the optimal solution. In addition, we propose reducing the number of parameters in the conventional GB-GA focusing on efficient molecular design from a small database. We generated a target-specific database by combining active learning and iterative design in the evolutionary methodologies and chose Gaussian process regression as the prediction model for molecular properties. We show that the proposed scheme is more efficient for optimization toward the target properties from goal-directed benchmarks with several drug-like molecules compared to the conventional GB-GA method. Finally, we provide a demonstration whereby we designed D-luciferin analogues with near-infrared fluorescence for bioimaging, which is desirable for effective in vivo light sources, from a small-size data set.

Machine learning-based response assessment in patients with rectal cancer after neoadjuvant chemoradiotherapy: radiomics analysis for assessing tumor regression grade using T2-weighted magnetic resonance images.

PURPOSE: This study aimed to assess tumor regression grade (TRG) in patients with rectal cancer after neoadjuvant chemoradiotherapy (NCRT) through a machine learning-based radiomics analysis using baseline T2-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: In total, 148 patients with locally advanced rectal cancer(T2-4 or N+) who underwent MR imaging at baseline and after chemoradiotherapy between January 2010 and May 2021 were included. A region of interest for each tumor mass was drawn by a radiologist on oblique axial T2-weighted images, and main features were selected using principal component analysis after dimension reduction among 116 radiomics and three clinical features. Among eight learning models that were used for prediction model development, the model showing best performance was selected. Treatment responses were classified as either good or poor based on the MR-assessed TRG (mrTRG) and pathologic TRG (pTRG). The model performance was assessed using the area under the receiver operating curve (AUROC) to classify the response group. RESULTS: Approximately 49% of the patients were in the good response (GR) group based on mrTRG (73/148) and 26.9% based on pTRG (28/104). The AUCs of clinical data, radiomics models, and combined radiomics with clinical data model for predicting mrTRG were 0.80 (95% confidence interval [CI] 0.73, 0.87), 0.74 (95% CI 0.66, 0.81), and 0.75(95% CI 0.68, 0.82), and those for predicting pTRG was 0.62 (95% CI 0.52, 0.71), 0.74 (95% CI 0.65, 0.82), and 0.79 (95% CI 0.71, 0.87). CONCLUSION: Radiomics combined with clinical data model using baseline T2-weighted MR images demonstrated feasible diagnostic performance in predicting both MR-assessed and pathologic treatment response in patients with rectal cancer after NCRT.

Bisphenol A regulates bladder cells responses via control of G2/M-phase cell cycle, apoptotic signaling, MAPK pathway, and transcription factor-associated MMP modulation.

Bisphenol A (BPA), an exogenous endocrine-disrupting chemical, is widely used to produce polycarbonate plastics. The widely used BPA has been detected in human urine samples, raising public anxiety about the detrimental effects of BPA on the bladder. In this study, we explored regulatory mechanisms for the adverse effects of BPA in human bladder BdFC and T24 cells. BPA induced extrinsic and intrinsic apoptosis and G2/M cell cycle arrest caused by the ATM-CHK1/CHK2-CDC25c-CDC2 signaling, which ultimately inhibited the growth of human bladder cells. We also found that BPA decreased the binding activity of AP-1 and NF-κB transcription factors in human bladder cells, which inhibited migration and invasion through matrix metallopeptidase-2 and -9 inactivation. Phosphorylation of MAPKs was implicated with BPA-mediated detrimental effects in human bladder cells. Collectively, our results provide a novel explanation for the underlying molecular mechanisms that BPA induces cytotoxicity in human bladder cells.

Mitigation of benzyl butyl phthalate toxicity in male germ cells with combined treatment of parthenolide, N-acetylcysteine, and 3-methyladenine.

Benzyl butyl phthalate (BBP) is a widely used plasticizer that poses various potential health hazards. Although BBP has been extensively studied, the direct mechanism underlying its toxicity in male germ cells remains unclear. Therefore, we investigated BBP-mediated male germ cell toxicity in GC-1 spermatogonia (spg), a differentiated mouse male germ cell line. This study investigated the impact of BBP on reactive oxygen species (ROS) generation, apoptosis, and autophagy regulation, as well as potential protective measures against BBP-induced toxicity. A marked dose-dependent decrease in GC-1 spg cell proliferation was observed following treatment with BBP at 12.5 µM. Exposure to 50 µM BBP, approximating the IC50 of 53.9 µM, markedly increased cellular ROS generation and instigated apoptosis, as evidenced by augmented protein levels of both intrinsic and extrinsic apoptosis-related markers. An amount of 50 µM BBP induced marked upregulation of autophagy regulator proteins, p38 MAPK, and extracellular signal-regulated kinase and substantially downregulated the phosphorylation of key kinases involved in regulating cell proliferation, including phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin (mTOR), c-Jun N-terminal kinase. The triple combination of N-acetylcysteine, parthenolide, and 3-methyladenine markedly restored cell proliferation, decreased BBP-induced apoptosis and autophagy, and restored mTOR phosphorylation. This study provides new insights into BBP-induced male germ cell toxicity and highlights the therapeutic potential of the triple inhibitors in mitigating BBP toxicity.

Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.

Future Blood Debt: Projecting Blood Supply and Demand of Korea Based on Subnational Population Projections (2021-2050).

BACKGROUND: South Korea faces a critical challenge with its rapidly declining fertility rates and an increasingly aging population, which significantly impacts the country's blood supply and demand. Despite these nationwide trends, regional disparities in blood supply and demand have not been thoroughly studied. METHODS: This research utilized blood donation data from the Korean Red Cross and blood transfusion data from the Health Insurance Review and Assessment Service. We analyzed these datasets in conjunction with regional population projections to simulate blood supply and demand from 2021 to 2050 across South Korea. Sensitivity analyses were conducted to assess the impact of various factors, including the number of donors, age eligibility criteria for donations, frequency of donations, and blood discard rates. RESULTS: Our projections indicate a decreasing trend in blood supply, from 2.6 million units in 2021 to 1.4 million units by 2050, while demand is expected to peak at 5.1 million units by 2045 before declining. Metropolitan areas, particularly Gyeonggi Province, are projected to experience the most severe shortages. Sensitivity analyses suggest that increasing the donation frequency of existing donors and relaxing age eligibility criteria are more effective strategies in addressing these imbalances than merely increasing the number of new donors. Blood discard rates showed minimal impact on the overall blood shortage. CONCLUSION: The findings emphasize the urgent need for targeted strategies to mitigate national and regional blood supply shortages in South Korea. Encouraging frequent donations from experienced donors and broadening eligibility criteria are critical steps toward stabilizing the blood supply amidst demographic shifts. These strategies must be prioritized to address the impending regional disparities in blood availability.

Endoscopic ultrasound-rendezvous versus percutaneous-endoscopic rendezvous endoscopic retrograde cholangiopancreatography for bile duct access: Systematic review and meta-analysis.

OBJECTIVES: Endoscopic ultrasound (EUS) or percutaneous-assisted antegrade guidewire insertion can be used to achieve biliary access when standard endoscopic retrograde cholangiopancreatography (ERCP) fails. We conducted a systematic review and meta-analysis to evaluate and compare the effectiveness and safety of EUS-assisted rendezvous (EUS-RV) and percutaneous rendezvous (PERC-RV) ERCP. METHODS: We searched multiple databases from inception to September 2022 to identify studies reporting on EUS-RV and PERC-RV in failed ERCP. A random-effects model was used to summarize the pooled rates of technical success and adverse events with 95% confidence interval (CI). RESULTS: In total, 524 patients (19 studies) and 591 patients (12 studies) were managed by EUS-RV and PERC-RV, respectively. The pooled technical successes were 88.7% (95% CI 84.6-92.8%, I2 = 70.5%) for EUS-RV and 94.1% (95% CI 91.1-97.1%, I2 = 59.2%) for PERC-RV (P = 0.088). The technical success rates of EUS-RV and PERC-RV were comparable in subgroups of benign diseases (89.2% vs. 95.8%, P = 0.068), malignant diseases (90.3% vs. 95.5%, P = 0.193), and normal anatomy (90.7% vs. 95.9%, P = 0.240). However, patients with surgically altered anatomy had poorer technical success after EUS-RV than after PERC-RV (58.7% vs. 93.1%, P = 0.036). The pooled rates of overall adverse events were 9.8% for EUS-RV and 13.4% for PERC-RV (P = 0.686). CONCLUSIONS: Both EUS-RV and PERC-RV have exhibited high technical success rates. When standard ERCP fails, EUS-RV and PERC-RV are comparably effective rescue techniques if adequate expertise and facilities are feasible. However, in patients with surgically altered anatomy, PERC-RV might be the preferred choice over EUS-RV because of its higher technical success rate.

Requirement of ß subunit for the reduced voltage-gated Na+ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of SCN5A.

Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.

O-GlcNAc transferase regulates p21 protein levels and cell proliferation through the FoxM1-Skp2 axis in a p53-independent manner.

The protein product of the CDKN1A gene, p21, has been extensively characterized as a negative regulator of the cell cycle. Nevertheless, it is clear that p21 has manifold complex and context-dependent roles that can be either tumor suppressive or oncogenic. Most well studied as a transcriptional target of the p53 tumor suppressor protein, there are other means by which p21 levels can be regulated. In this study, we show that pharmacological inhibition or siRNA-mediated reduction of O-GlcNAc transferase (OGT), the enzyme responsible for glycosylation of intracellular proteins, increases expression of p21 in both p53-dependent and p53-independent manners in nontransformed and cancer cells. In cells harboring WT p53, we demonstrate that inhibition of OGT leads to p53-mediated transactivation of CDKN1A, while in cells that do not express p53, inhibiting OGT leads to increased p21 protein stabilization. p21 is normally degraded by the ubiquitin-proteasome system following ubiquitination by, among others, the E3 ligase Skp-Cullin-F-box complex; however, in this case, we show that blocking OGT causes impairment of the Skp-Cullin-F-box ubiquitin complex as a result of disruption of the FoxM1 transcription factor-mediated induction of Skp2 expression. In either setting, we conclude that p21 levels induced by OGT inhibition correlate with cell cycle arrest and decreased cancer cell proliferation.

Prediction of intradialytic hypotension using pre-dialysis features-a deep learning-based artificial intelligence model.

BACKGROUND: Intradialytic hypotension (IDH) is a serious complication of hemodialysis (HD) that is associated with increased risks of cardiovascular morbidity and mortality. However, its accurate prediction remains a clinical challenge. The aim of this study was to develop a deep learning-based artificial intelligence (AI) model to predict IDH using pre-dialysis features. METHODS: Data from 2007 patients with 943 220 HD sessions at seven university hospitals were used. The performance of the deep learning model was compared with three machine learning models (logistic regression, random forest and XGBoost). RESULTS: IDH occurred in 5.39% of all studied HD sessions. A lower pre-dialysis blood pressure (BP), and a higher ultrafiltration (UF) target rate and interdialytic weight gain in IDH sessions compared with non-IDH sessions, and the occurrence of IDH in previous sessions was more frequent among IDH sessions compared with non-IDH sessions. Matthews correlation coefficient and macro-averaged F1 score were used to evaluate both positive and negative prediction performances. Both values were similar in logistic regression, random forest, XGBoost and deep learning models, developed with data from a single session. When combining data from the previous three sessions, the prediction performance of the deep learning model improved and became superior to that of other models. The common top-ranked features for IDH prediction were mean systolic BP (SBP) during the previous session, UF target rate, pre-dialysis SBP, and IDH experience during the previous session. CONCLUSIONS: Our AI model predicts IDH accurately, suggesting it as a reliable tool for HD treatment.

Solitalea agri sp. nov., a new member of the genus Solitalea isolated from rhizospheric soil of a jujube tree.

A Gram-stain negative, aerobic, rod-shaped and creamy pink-coloured bacterium, designated MAHUQ-68T, was isolated from rhizospheric soil of a jujube tree. Colonies grew at 10-40 °C (optimum, 28 °C), pH 6.0-9.0 (optimum pH, 7.0) and in the presence of 0-1.5 % NaCl (optimum 0-0.5 %). Positive for both catalase and oxidase activity. Strain MAHUQ-68T hydrolysed casein, starch, aesculin and l-tyrosine. Based on the results of phylogenetic analysis using 16S rRNA gene and genome sequences, strain MAHUQ-68T clustered together within the genus Solitalea. The closest members were Solitalea longa HR-AVT (98.8 % sequence similarity), Solitalea canadensis DSM 3403T (96.9 %) and Solitalea koreensis R2A36-4T (94.0 %). The genome of strain MAHUQ-68 T was 4 250 173 bp long with 68 scaffolds and 3 570 protein-coding genes. The genomic DNA G+C content of the type strain was 38.0 mol%. The average nucleotide identity and in silico DNA-DNA hybridization values between strain MAHUQ-68T and its closest relatives were 72.0-81.4% and 19.8-24.3 %, respectively. The major cellular fatty acids were iso-C15 : 0 and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c). The main respiratory quinone was menaquinone-7. The polar lipids comprised phosphatidylethanolamine, an unidentified aminolipid and four unidentified lipids. Based on these data, strain MAHUQ-68T represents a novel species in the genus Solitalea, for which the name Solitalea agri sp. nov. is proposed. The type strain is MAHUQ-68T (=KACC 22249T=CGMCC 1.19062T).

Differentiation of autoimmune pancreatitis from pancreatic adenocarcinoma using CT characteristics: a systematic review and meta-analysis.

OBJECTIVES: To determine informational CT findings for distinguishing autoimmune pancreatitis (AIP) from pancreatic ductal adenocarcinoma (PDAC) and to review their diagnostic accuracy. METHODS: A systematic and detailed literature review was performed through PubMed, EMBASE, and the Cochrane library. Similar descriptors to embody the identical image finding were labeled as a single CT characteristic. We calculated the pooled diagnostic odds ratios (DORs) of each CT characteristic using a bivariate random-effects model. RESULTS: A total of 145 various descriptors from 15 studies (including 562 AIP and 869 PDAC patients) were categorized into 16 CT characteristics. According to the pooled DOR, 16 CT characteristics were classified into three groups (suggesting AIP, suggesting PDAC, and not informational). Seven characteristics suggesting AIP were diffuse pancreatic enlargement (DOR, 48), delayed homogeneous enhancement (DOR, 46), capsule-like rim (DOR, 34), multiple pancreatic masses (DOR, 16), renal involvement (DOR, 15), retroperitoneal fibrosis (DOR, 13), and bile duct involvement (DOR, 8). Delayed homogeneous enhancement showed a pooled sensitivity of 83% and specificity of 85%. The other six characteristics showed relatively low sensitivity (12-63%) but high specificity (93-99%). Four characteristics suggesting PDAC were discrete pancreatic mass (DOR, 23), pancreatic duct cutoff (DOR, 16), upstream main pancreatic duct dilatation (DOR, 8), and upstream parenchymal atrophy (DOR, 7). CONCLUSION: Eleven CT characteristics were informational to distinguish AIP from PDAC. Diffuse pancreatic enlargement, delayed homogeneous enhancement, and capsule-like rim suggested AIP with the highest DORs, whereas discrete pancreatic mass suggested PDAC. However, pooled sensitivities of informational CT characteristics were moderate. CLINICAL RELEVANCE STATEMENT: This meta-analysis underscores eleven distinctive CT characteristics that aid in differentiating autoimmune pancreatitis from pancreatic adenocarcinoma, potentially preventing misdiagnoses in patients presenting with focal/diffuse pancreatic enlargement. KEY POINTS: • Diffuse pancreatic enlargement (pooled diagnostic odds ratio [DOR], 48), delayed homogeneous enhancement (46), and capsule-like rim (34) were CT characteristics suggesting autoimmune pancreatitis. • The CT characteristics suggesting autoimmune pancreatitis, except delayed homogeneous enhancement, had a general tendency to show relatively low sensitivity (12-63%) but high specificity (93-99%). • Discrete pancreatic mass (pooled diagnostic odds ratio, 23) was the CT characteristic suggesting pancreatic ductal adenocarcinoma with the highest pooled DORs.