Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial.

BACKGROUND: It remains unclear whether intensification of the chemotherapy backbone in tandem with an anti-EGFR can confer superior clinical outcomes in a cohort of RAS/BRAF wild-type colorectal cancer (CRC) patients with initially unresectable colorectal liver metastases (CRLM). To that end, we sought to comparatively evaluate the efficacy and safety of cetuximab plus FOLFOXIRI (triplet arm) versus cetuximab plus FOLFOX (doublet arm) as a conversion regimen (i.e., unresectable to resectable) in CRC patients with unresectable CRLM. METHODS AND FINDINGS: This open-label, randomized clinical trial was conducted from April 2018 to December 2022 in 7 medical centers across China, enrolling 146 RAS/BRAF wild-type CRC patients with initially unresectable CRLM. A stratified blocked randomization method was utilized to assign patients (1:1) to either the cetuximab plus FOLFOXIRI (n = 72) or cetuximab plus FOLFOX (n = 74) treatment arms. Stratification factors were tumor location (left versus right) and resectability (technically unresectable versus ≥5 metastases). The primary outcome was the objective response rate (ORR). Secondary outcomes included the median depth of tumor response (DpR), early tumor shrinkage (ETS), R0 resection rate, progression-free survival (PFS), overall survival (not mature at the time of analysis), and safety profile. Radiological tumor evaluations were conducted by radiologists blinded to the group allocation. Primary efficacy analyses were conducted based on the intention-to-treat population, while safety analyses were performed on patients who received at least 1 line of chemotherapy. A total of 14 patients (9.6%) were lost to follow-up (9 in the doublet arm and 5 in the triplet arm). The ORR was comparable following adjustment for stratification factors, with 84.7% versus 79.7% in the triplet and doublet arms, respectively (odds ratio [OR] 0.70; 95% confidence intervals [CI] [0.30, 1.67], Chi-square p = 0.42). Moreover, the ETS rate showed no significant difference between the triplet and doublet arms (80.6% (58/72) versus 77.0% (57/74), OR 0.82, 95% CI [0.37, 1.83], Chi-square p = 0.63). Although median DpR was higher in the triplet therapy group (59.6%, interquartile range [IQR], [50.0, 69.7] versus 55.0%, IQR [42.8, 63.8], Mann-Whitney p = 0.039), the R0/R1 resection rate with or without radiofrequency ablation/stereotactic body radiation therapy was comparable with 54.2% (39/72) of patients in the triplet arm versus 52.7% (39/74) in the doublet arm. At a median follow-up of 26.2 months (IQR [12.8, 40.5]), the median PFS was 11.8 months in the triplet arm versus 13.4 months in the doublet arm (hazard ratio [HR] 0.74, 95% CI [0.50, 1.11], Log-rank p = 0.14). Grade ≥ 3 events were reported in 47.2% (35/74) of patients in the doublet arm and 55.9% (38/68) of patients in the triplet arm. The triplet arm was associated with a higher incidence of grade ≥ 3 neutropenia (44.1% versus 27.0%, p = 0.03) and diarrhea (5.9% versus 0%, p = 0.03). The primary limitations of the study encompass the inherent bias in subjective surgical decisions regarding resection feasibility, as well as the lack of a centralized assessment for ORR and resection. CONCLUSIONS: The combination of cetuximab with FOLFOXIRI did not significantly improve ORR compared to cetuximab plus FOLFOX. Despite achieving an enhanced DpR, this improvement did not translate into improved R0 resection rates or PFS. Moreover, the triplet arm was associated with an increase in treatment-related toxicity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03493048.

Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway.

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.

Central venous-to-arterial carbon dioxide partial pressure difference as a guiding parameter for cardiotonic drug administration in patients with early-stage septic shock.

OBJECTIVE: This study aimed to investigate the effect of the central venous-to-arterial carbon dioxide partial pressure difference (Pcv-aCO2) on the administration of cardiotonic drugs in patients with early-stage septic shock. METHODS: A retrospective study was conducted on 120 patients suffering from septic shock. At admission, the left ventricular ejection fraction (LVEF) and Pcv-aCO2 of the patients were obtained. On the premise of mean arterial pressure (MAP) ≥ 65 mmHg, the patients were divided into two groups according to the treatment approaches adopted by different doctors-Control group: LVEF ≤50%; Observation group: Pcv-aCO2 ≥ 6. Both groups received cardiotonic therapy. RESULTS: The two groups of patients had similar general conditions and pre-resuscitation conditions (P > 0.05). Compared to the Control group, the Observation group had a higher MAP, Lac clearance rate, and urine output after six hours of resuscitation (P < 0.05), but a lower absolute value of Lac, total fluid intake in 24 hours, and a lower number of patients receiving renal replacement therapy during hospitalization (P < 0.05). After six hours of resuscitation, the percentages of patients meeting central venous oxygen saturation and central venous pressure targets were not significantly different between the Control and Observation groups (P > 0.05). There was no difference in the 28-day mortality rate between the two groups (P > 0.05). CONCLUSION: Pcv-aCO2 is more effective than LVEF in guiding the administration of cardiotonic drugs in the treatment of patients with septic shock.

Mechanosynthesis of Pyrrole-2-carboxylic Acids via Copper-Catalyzed Spiroannulation/Ring-Opening Aromatization of 4-Arylidene Isoxazol-5-ones with Enamino Esters.

An efficient and practical tandem reaction of 4-arylidene isoxazol-5-ones with enamino esters catalyzed by an inexpensive copper salt has been established in a ball mill. This innovative approach yields a diverse array of structurally novel pyrrole-2-carboxylic acids, showing excellent tolerance toward different functional groups. By integrating spiroannulation and ring-opening aromatization processes, this protocol introduces a facile and cost-effective strategy for synthesizing highly functionalized pyrrole derivatives.

Two {CuI[P4Mo6]2}-Based Coordination Polymers Incorporating In Situ Converted Tetrapyridyl Ligands for Trace Analysis of Nitrofuran Antibiotics.

Nitrofurans are important synthetic broad-spectrum antibacterial drugs with the basic structure of 5-nitrofuran. Due to their toxicity, it is essential to develop a sensitive sensor with strong anti-interference capabilities for their detection. In this work, two {P4Mo6O31}12--based compounds, [H4(HPTTP)]2{CuI[Mo12O24(OH)6(PO4)3(HPO4)(H2PO4)4]}·xH2O (x = 13 for (1), 7 for (2); HPTTP = 4,4',4″,4‴-(1H-pyrrole-2,3,4,5-tetrayl)tetrapyridine), exhibiting similar coordination but distinct stacking modes. Both compounds were synthesized and used for the electrochemical detection of nitrofuran antibiotics. The tetrapyridine-based ligand was generated in situ during assembly, and its potential mechanism was discussed. Composite electrode materials, formed by mixing graphite powder with compounds 1-2 and physically grinding them, proved to be highly effective in the electrochemical trace detection of furazolidone (FZD) and furaltadone hydrochloride (FTD·HCl) under optimal conditions. Besides, the possible electrochemical detection mechanisms of two nitro-antibiotics were studied.

Da-Chai-Hu-Tang Formula inhibits the progression and metastasis in HepG2 cells through modulation of the PI3K/AKT/STAT3-induced cell cycle arrest and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Chai-Hu-Tang (DCHT), a Chinese traditional herbal compound, has been utilized for the treatment of Hepatic diseases in China for over 1800 years. The DCHT formula contains eight herbals: Bupleurum chinense DC. (chaihu), Scutellaria baicalensis Georgi (huangqin), Paeonia lactiflora Pall. (baishao), Pinellia ternata (Thunb.) Makino (banxia), Rheum officinale Baill. (dahuang), Citrus × aurantium L. (zhishi), Zingiber officinale Roscoe (shengjiang), Ziziphus jujuba Mill. (dazao). Clinical studies have demonstrated the effectiveness of DCHT in hepatocellular carcinoma (HCC) and its ability to enhance the immunity of patients with hepatocellular carcinoma. A total of 20 Chinese articles have been published on the use of DCHT in treating HCC. AIM OF THE STUDY: The study aimed to validate the effect of DCHT in HCC cells and to identify related targets (TP53, AKT1, BCL2, STAT3) in treating HCC by DCHT in vitro experiments. MATERIALS AND METHODS: Cell proliferation and migration were investigated in vitro. Flow cytometry analysis was used to evaluate the cell cycle and apoptosis. Apoptotic bodies in HepG2 cells were observed using a confocal microscope. Biochemical detection was employed to analyze LDH release, MDA levels, and SOD levels. Bioinformatics analysis was used to predict core targets between DCHT and HCC, as well as potential signaling pathways. The protein levels of metastasis-associated, apoptosis, and PI3K, AKT, p-AKT, and STAT3 were further determined through Western blotting. RESULTS: Following treatment with DCHT, the inhibition of viability, migration, and G2/M arrest was observed in HepG2 cells. Flow cytometry analysis and Morphological apoptosis studies provided evidence that DCHT could induce apoptosis in HepG2 cells. Biochemical detection revealed that DCHT could increase LDH release and the level of MDA, and inhibit the viability of the SOD. Bioinformatics analysis identified key targets such as TP53, AKT1, BCL2, STAT3. The PI3K/AKT/STAT3 signaling pathway emerged as a critical pathway in the KEGG enrichment analysis. Western blotting results indicated that DCHT could enhance the expression of E-cadherin, p53, and Bax, while reducing the content of N-cadherin, Bcl-2, PI3K, p-AKT, AKT1, and STAT3. CONCLUSIONS: The results proved that DCHT could inhibit the progression and metastasis of HCC by regulating the expression of E-cadherin, N-cadherin, p53, Bax, Bcl-2, PI3K, p-AKT, AKT, and STAT3 through the PI3K/AKT/STAT3 signaling pathway.

STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179.

Thyrotropin (TSH) is the master regulator of thyroid gland growth and function. Resistance to TSH (RTSH) describes conditions with reduced sensitivity to TSH. Dominantly inherited RTSH has been linked to a locus on chromosome 15q, but its genetic basis has remained elusive. Here we show that non-coding mutations in a (TTTG)4 short tandem repeat (STR) underlie dominantly inherited RTSH in all 82 affected participants from 12 unrelated families. The STR is contained in a primate-specific Alu retrotransposon with thyroid-specific cis-regulatory chromatin features. Fiber-seq and RNA-seq studies revealed that the mutant STR activates a thyroid-specific enhancer cluster, leading to haplotype-specific upregulation of the bicistronic MIR7-2/MIR1179 locus 35 kb downstream and overexpression of its microRNA products in the participants' thyrocytes. An imbalance in signaling pathways targeted by these micro-RNAs provides a working model for this cause of RTSH. This finding broadens our current knowledge of genetic defects altering pituitary-thyroid feedback regulation.

An Organodiphosphate-Containing Polyoxoniobate Ring and Its Assembly into a Three-Dimensional Framework through Hydrogen Bonding.

In this work, a novel organodiphosphate-containing inorganic-organic hybrid polyoxoniobate (PONb) ring {(PO3CH2CH2PO3H)4Nb8O16}4- (Nb8P8) has been achieved by a one-pot hydrothermal method. The ring is constructed from a tetragonal {Nb8O36} motif and four {PO3CH2CH2PO3H} ligands. Interestingly, Nb8P8 can be joined together via K-H2O clusters {K2(H2O)4(OH)2} to form one-dimensional chains {[K2(H2O)4(OH)2]Nb8P8}n and further linked by {Cu(en)2}2+ (en = ethylenediamine) complexes, resulting in a three-dimensional supramolecular framework {[Cu(en)2]2[K2(H2O)4(OH)2]Nb8P8}·3en·H2O (1). 1 exhibits good chemical and thermal stability and has a high water vapor adsorption capacity of ≤224 cm3 g-1 (22.71 mol·mol-1) at 298 K, outperforming most of the known polyoxometalate-based materials. Impedance measurements prove that 1 can transfer protons with moderate conductivity. This study not only contributes to the structural diversity of organodiphosphate-containing PONbs and PONb rings but also provides a reference for the development of PONb-based materials with unique performance.

Discovery of novel cholinesterase inhibitors easily crossing the blood-brain barrier via structure-property relationship investigation: Methylenedioxy-cinnamicamides containing tertiary amine side chain.

In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19 µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72 ± 93.56 ng/g) after dosing 30 min. Its half-life in the serum is 331 min (5.52 h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24 hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.

Experimental Generation of Spin-Photon Entanglement in Silicon Carbide.

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

Activation of PPARδ in bone marrow endothelial progenitor cells improves their hematopoiesis-supporting ability after myelosuppressive injury.

Dysfunctional bone marrow (BM) endothelial progenitor cells (EPCs) with high levels of reactive oxygen species (ROS) are responsible for defective hematopoiesis in poor graft function (PGF) patients with acute leukemia or myelodysplastic neoplasms post-allotransplant. However, the underlying mechanism by which BM EPCs regulate their intracellular ROS levels and the capacity to support hematopoiesis have not been well clarified. Herein, we demonstrated decreased levels of peroxisome proliferator-activated receptor delta (PPARδ), a lipid-activated nuclear receptor, in BM EPCs of PGF patients compared with those with good graft function (GGF). In vitro assays further identified that PPARδ knockdown contributed to reduced and dysfunctional BM EPCs, characterized by the impaired ability to support hematopoiesis, which were restored by PPARδ overexpression. Moreover, GW501516, an agonist of PPARδ, repaired the damaged BM EPCs triggered by 5-fluorouracil (5FU) in vitro and in vivo. Clinically, activation of PPARδ by GW501516 benefited the damaged BM EPCs from PGF patients or acute leukemia patients in complete remission (CR) post-chemotherapy. Mechanistically, we found that increased expression of NADPH oxidases (NOXs), the main ROS-generating enzymes, may lead to elevated ROS level in BM EPCs, and insufficient PPARδ may trigger BM EPC damage via ROS/p53 pathway. Collectively, we found that defective PPARδ contributes to BM EPC dysfunction, whereas activation of PPARδ in BM EPCs improves their hematopoiesis-supporting ability after myelosuppressive therapy, which may provide a potential therapeutic target not only for patients with leukemia but also for those with other cancers.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Mental health problems of front-line medical staff in the early stage of public health emergencies.

In the face of the unprecedented public health crisis caused by the novel coronavirus pneumonia epidemic, front-line health workers are under enormous mental pressure. This paper aims to explore the mental health challenges faced by front-line health workers in the early stages of a public health emergency, such as stress, anxiety, and depression. At the same time, the factors that increase their mental stress are analyzed, and practical measures are put forward to prevent and manage mental health problems, aiming at improving the quality of medical treatment during public health emergencies. This paper has some reference value for people engaged in mental health prevention.

Patterns, Risk Factors, and Outcomes of Recurrence After Hepatectomy for Hepatocellular Carcinoma with and without Microvascular Invasion.

Purpose: The patterns and risk factors of postsurgical recurrence of patient with hepatocellular carcinoma (HCC) with microvascular invasion (MVI) are not clarified. This study aimed to decipher and compare the postoperative recurrent patterns and the risk factors contributing to recurrence between MVI positive (MVI(+)) and MVI negative (MVI(-)) HCC after hepatectomy. Patients and methods: Patients with HCC who underwent hepatectomy in three Chinese academic hospitals between January 1, 2009, and December 31, 2018, were enrolled. Recurrent patterns included early (≤2 years) or late (>2 years) recurrence, recurrent sites and number, and risk factors of recurrence were compared between the MVI(+)and MVI(-) groups by propensity score-matching (PSM). Results: Of 1756 patients included, 581 (33.1%) were MVI(+), and 875 (49.8%) patients developed early recurrence. Compared with the MVI(-) group, the MVI(+) group had a higher 2-year recurrence rate in the PSM cohort (hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.59-2.10; P < 0.001), and more patients with multiple tumor recurrence. Patients with early recurrence in the MVI(+) group had a worse overall survival (OS) than those in the MVI(-) group (HR, 1.24; 95% CI, 1.02-1.50; P = 0.034). Resection margin (RM) ≤1.0 cm is a surgical predictor of early recurrence for the MVI(+) group (HR, 0.68; 95% CI, 0.54-0.87; P = 0.002), but not for the MVI(-) group. Conclusion: Compared to MVI(-) HCC, MVI(+) HCC tends to be early, multiple recurrence and lung and lymph node metastasis after resection. RM ≤1.0 cm is a surgical risk factor of early recurrence for patient with MVI.

Comprehensive pan-cancer analysis: essential role of ABCB family genes in cancer.

Background: The adenosine triphosphate-binding-cassette (ABC) transporter orchestrates the transmembrane transport of diverse substrates with the aid of ATP as an energy source. ABC transporter constitutes a widespread superfamily of transporters prominently present on the cellular membrane of organisms. Advancements in understanding have unveiled additional roles beyond mere intracellular or extracellular transport functions for the ABC protein family, encompassing involvement in DNA repair, protein translation, and gene expression regulation. Yet its role in tumors is still unknown. Methods: This study drew support from multiple databases, including Gene Expression Omnibus (GEO), European Genome-phenome Archive (EGA), The Cancer Genome Atlas (TCGA), and employed multidimensional bioinformatics analyses, incorporating online databases and the R-project. Through a comprehensive analysis, we seek to discern transcriptional-level disparities among genes and their consequential impacts on prognosis, tumor microenvironment (TME), stemness score, immune subtypes, clinical characteristics, and drug sensitivity across human cancers. Results: ABC transporter subfamily B (ABCB) family genes exhibited heightened expression across diverse tumors, demonstrating a significant correlation with overall prognosis in pan-cancer contexts. Notably, gene expression levels manifested substantial associations with TME, stemness score, immune subtypes, clinical characteristics, and drug sensitivity in specific cancers, including kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD). Within this subset, transporter associated with antigen processing 1 (TAP1), TAP2, and ABCB6 emerged as noteworthy oncogenes. Conclusions: The outcomes of this study contribute to a comprehensive understanding of the implications of ABCB family genes in tumor progression, offering insights into potential therapeutic targets for cancer. Notably, the identification of ABCB6 as a significant oncogene suggests promising avenues for targeted therapies in KIRP, LIHC, and PAAD.

The Role of Oxidative Stress and Natural Products in Maintaining Human Health.

Since 1985, when oxidative stress was first defined as the oxidative damage caused to cells and organs, a large number of studies have shown that oxidative stress is a significant risk factor for various diseases, including tumors [...].

Diagnostic Value of Clear Cell Likelihood Score v1.0 and v2.0 for Common Subtypes of Small Renal Masses: A Multicenter Comparative Study.

BACKGROUND: Clear cell likelihood score (ccLS) is reliable for diagnosing small renal masses (SRMs). However, the diagnostic value of Clear cell likelihood score version 1.0 (ccLS v1.0) and v2.0 for common subtypes of SRMs might be a potential score extension. PURPOSE: To compare the diagnostic performance and interobserver agreement of ccLS v1.0 and v2.0 for characterizing five common subtypes of SRMs. STUDY TYPE: Retrospective. POPULATION: 797 patients (563 males, 234 females; mean age, 53 ± 12 years) with 867 histologically proven renal masses. FIELD STRENGTH/SEQUENCES: 3.0 and 1.5 T/T2 weighted imaging, T1 weighted imaging, diffusion-weighted imaging, a dual-echo chemical shift (in- and opposed-phase) T1 weighted imaging, multiphase dynamic contrast-enhanced imaging. ASSESSMENT: Six abdominal radiologists were trained in the ccLS algorithm and independently scored each SRM using ccLS v1.0 and v2.0, respectively. All SRMs had definite pathological results. The pooled area under curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the diagnostic performance of ccLS v1.0 and v2.0 for characterizing common subtypes of SRMs. The average κ values were calculated to evaluate the interobserver agreement of the two scoring versions. STATISTICAL TESTS: Random-effects logistic regression; Receiver operating characteristic analysis; DeLong test; Weighted Kappa test; Z test. The statistical significance level was P < 0.05. RESULTS: The pooled AUCs of clear cell likelihood score version 2.0 (ccLS v2.0) were statistically superior to those of ccLS v1.0 for diagnosing clear cell renal cell carcinoma (ccRCC) (0.907 vs. 0.851), papillary renal cell carcinoma (pRCC) (0.926 vs. 0.888), renal oncocytoma (RO) (0.745 vs. 0.679), and angiomyolipoma without visible fat (AMLwvf) (0.826 vs. 0.766). Interobserver agreement for SRMs between ccLS v1.0 and v2.0 is comparable and was not statistically significant (P = 0.993). CONCLUSION: The diagnostic performance of ccLS v2.0 surpasses that of ccLS v1.0 for characterizing ccRCC, pRCC, RO, and AMLwvf. Especially, the standardized algorithm has optimal performance for ccRCC and pRCC. ccLS has potential as a supportive clinical tool. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Wildfires and social media discourse: exploring mental health and emotional wellbeing through Twitter.

Introduction: The rise in global temperatures due to climate change has escalated the frequency and intensity of wildfires worldwide. Beyond their direct impact on physical health, these wildfires can significantly impact mental health. Conventional mental health studies predominantly rely on surveys, often constrained by limited sample sizes, high costs, and time constraints. As a result, there is an increasing interest in accessing social media data to study the effects of wildfires on mental health. Methods: In this study, we focused on Twitter users affected by the California Tubbs Fire in 2017 to extract data signals related to emotional well-being and mental health. Our analysis aimed to investigate tweets posted during the Tubbs Fire disaster to gain deeper insights into their impact on individuals. Data were collected from October 8 to October 31, 2017, encompassing the peak activity period. Various analytical methods were employed to explore word usage, sentiment, temporal patterns of word occurrence, and emerging topics associated with the unfolding crisis. Results: The findings show increased user engagement on wildfire-related Tweets, particularly during nighttime and early morning, especially at the onset of wildfire incidents. Subsequent exploration of emotional categories using Linguistic Inquiry and Word Count (LIWC) revealed a substantial presence of negative emotions at 43.0%, juxtaposed with simultaneous positivity in 23.1% of tweets. This dual emotional expression suggests a nuanced and complex landscape, unveiling concerns and community support within conversations. Stress concerns were notably expressed in 36.3% of the tweets. The main discussion topics were air quality, emotional exhaustion, and criticism of the president's response to the wildfire emergency. Discussion: Social media data, particularly the data collected from Twitter during wildfires, provides an opportunity to evaluate the psychological impact on affected communities immediately. This data can be used by public health authorities to launch targeted media campaigns in areas and hours where users are more active. Such campaigns can raise awareness about mental health during disasters and connect individuals with relevant resources. The effectiveness of these campaigns can be enhanced by tailoring outreach efforts based on prevalent issues highlighted by users. This ensures that individuals receive prompt support and mitigates the psychological impacts of wildfire disasters.

Large-Scale Integration of the Ion-Reinforced Phytic Acid Layer Stabilizing Magnesium Metal Anode.

Rechargeable magnesium batteries (RMBs) have garnered significant attention for their potential in large-scale energy storage applications. However, the commercial development of RMBs has been severely hampered by the rapid failure of large-sized Mg metal anodes, especially under fast and deep cycling conditions. Herein, a concept proof involving a large-scale ion-reinforced phytic acid (PA) layer (100 cm × 7.5 cm) with an excellent water-oxygen tolerance, high Mg2+ conductivity, and favorable electrochemical stability is proposed to enable rapid and uniform plating/stripping of Mg metal anode. Guided by even distributions of Mg2+ flux and electric field, the as-prepared large-sized PA-Al@Mg electrode (5.8 cm × 4.5 cm) exhibits no perforation and uniform Mg plating/stripping after cycling. Consequently, an ultralong lifespan (2400 h at 3 mA cm-2 with 1 mAh cm-2) and high current tolerance (300 h at 9 mA cm-2 with 1 mAh cm-2) of the symmetric cell using the PA-Al@Mg anode could be achieved. Notably, the PA-Al@Mg//Mo6S8 full cell demonstrates exceptional stability, operating for 8000 cycles at 5 C with a capacity retention of 99.8%, surpassing that of bare Mg (3000 cycles, 74.7%). Moreover, a large-sized PA-Al@Mg anode successfully contributes to the stable pouch cell (200 and 750 cycles at 0.1 and 1 C), further confirming its significant potential for practical utilization. This work provides valuable theoretical insights and technological support for the practical implementation of RMBs.