Development and validation of an ultrasound-based deep learning radiomics nomogram for predicting the malignant risk of ovarian tumours.

BACKGROUND: The timely identification and management of ovarian cancer are critical determinants of patient prognosis. In this study, we developed and validated a deep learning radiomics nomogram (DLR_Nomogram) based on ultrasound (US) imaging to accurately predict the malignant risk of ovarian tumours and compared the diagnostic performance of the DLR_Nomogram to that of the ovarian-adnexal reporting and data system (O-RADS). METHODS: This study encompasses two research tasks. Patients were randomly divided into training and testing sets in an 8:2 ratio for both tasks. In task 1, we assessed the malignancy risk of 849 patients with ovarian tumours. In task 2, we evaluated the malignancy risk of 391 patients with O-RADS 4 and O-RADS 5 ovarian neoplasms. Three models were developed and validated to predict the risk of malignancy in ovarian tumours. The predicted outcomes of the models for each sample were merged to form a new feature set that was utilised as an input for the logistic regression (LR) model for constructing a combined model, visualised as the DLR_Nomogram. Then, the diagnostic performance of these models was evaluated by the receiver operating characteristic curve (ROC). RESULTS: The DLR_Nomogram demonstrated superior predictive performance in predicting the malignant risk of ovarian tumours, as evidenced by area under the ROC curve (AUC) values of 0.985 and 0.928 for the training and testing sets of task 1, respectively. The AUC value of its testing set was lower than that of the O-RADS; however, the difference was not statistically significant. The DLR_Nomogram exhibited the highest AUC values of 0.955 and 0.869 in the training and testing sets of task 2, respectively. The DLR_Nomogram showed satisfactory fitting performance for both tasks in Hosmer-Lemeshow testing. Decision curve analysis demonstrated that the DLR_Nomogram yielded greater net clinical benefits for predicting malignant ovarian tumours within a specific range of threshold values. CONCLUSIONS: The US-based DLR_Nomogram has shown the capability to accurately predict the malignant risk of ovarian tumours, exhibiting a predictive efficacy comparable to that of O-RADS.

Genome-Wide Investigation of the PLD Gene Family in Tomato: Identification, Analysis, and Expression.

Phospholipase Ds (PLDs) are important phospholipid hydrolases in plants that play crucial roles in the regulation of plant growth, development, and stress tolerance. In this study, 14 PLD genes were identified in the tomato genome and were localized on eight chromosomes, and one tandem-duplicated gene pair was identified. According to a phylogenetic analysis, the genes were categorized into four subtypes: SlPLDα, ß, and δ belonged to the C2-PLD subfamily, while SlPLDζ belonged to the PXPH-PLD subfamily. The gene structure and protein physicochemical properties were highly conserved within the same subtype. The promoter of all the SlPLD genes contained hormone-, light-, and stress-responsive cis-acting regulatory elements, but no significant correlation between the number, distribution, and type of cis-acting elements was observed among the members of the same subtype. Transcriptome data showed that the expression of the SlPLD genes was different in multiple tissues. A quantitative RT-PCR analysis revealed that the SlPLD genes responded positively to cold, salt, drought, and abscisic acid treatments, particularly to salt stress. Different expression patterns were observed for different genes under the same stress, and for the same gene under different stresses. The results provide important insights into the functions of SlPLD genes and lay a foundation for further studies of the response of SlPLD genes to abiotic stresses.

Application of Platysma Myocutaneous Flap in Surgical Repair after T2-3 Glottic Carcinoma Resection.

OBJECTIVE: Numerous methods and materials are available for vertical partial laryngectomy. In this study, the reparative effects of the platysma myocutaneous flap (PMF) and ribbon myocutaneous flap (RMF) on the postoperative voice quality of patients were compared to provide a reference for selecting a method conducive to improving postoperative voice quality. METHODS: A retrospective analysis was performed on patients with unilateral T2-3 glottic carcinoma. Following vertical partial laryngectomy, the defect was repaired with a PMF or simple RMF. Twelve months after surgery, voice quality was assessed according to voice acoustics, aerodynamics, and subjective perceptual evaluation, and glottic morphology was recorded using a laryngeal stroboscopy. RESULTS: A total of 70 patients were identified, including 54 in the PMF group and 16 in the RMF group. The PMF group was superior to the RMF group in terms of voice quality assessed by voice acoustics, aerodynamics, and subjective perceptual evaluation. In the PMF group, 72.2% of patients performed phonation with their vocal cords, and approximately 27.8% of patients were affected by supraglottic compression. In the RMF group, 81.3% of patients were affected by supraglottic compression. No significant difference was found in the 5-year survival rate between the two groups. CONCLUSION: For defect repair following vertical partial laryngectomy, a PMF can allow better postoperative voice quality to be achieved than an RMF because a PMF can provide more tissue (including strap muscle under the flap) for padding, which enables the glottic portion corresponding to the vocal cord to close well. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 2024.

Clinical Impact of Comprehensive Molecular Profiling in Adolescents and Young Adults with Sarcoma.

Sarcomas are a heterogenous group of tumours that commonly carry poor prognosis with limited therapeutic options. Adolescents and young adults (AYAs) with sarcoma are a unique and understudied patient population that have only achieved modest survival gains compared to other groups. We present our institutional experience of AYAs with sarcoma who underwent comprehensive molecular profiling (CMP) via either large-panel targeted DNA sequencing or whole genome and transcriptome sequencing and evaluated the feasibility and clinical impact of this approach. Genomic variants detected were determined to be clinically relevant and actionable following evaluation by the Molecular Tumour Board. Clinicians provided feedback regarding the utility of testing three months after reporting. Twenty-five patients who were recruited for CMP are included in this analysis. The median time from consent to final molecular report was 45 days (interquartile range: 37-57). Potentially actionable variants were detected for 14 patients (56%), and new treatment recommendations were identified for 12 patients (48%). Pathogenic germline variants were identified in three patients (12%), and one patient had a change in diagnosis. The implementation of CMP for AYAs with sarcoma is clinically valuable, feasible, and should be increasingly integrated into routine clinical practice as technologies and turnaround times continue to improve.

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections.

Introduction: Elderly patients are more prone to develop acute kidney injury during infections and polymyxin B (PMB)-associated nephrotoxicity than young patients. The differential response to PMB between the elderly and young critically ill patients is unknown. We aimed to assess PMB exposure in elderly patients compared with young critically ill patients, and to determine the covariates of PMB pharmacokinetics in critically ill patients. Methods: Seventeen elderly patients (age ≥ 65 years) and six young critically ill patients (age < 65 years) were enrolled. Six to eight blood samples were collected during the 12 h intervals after at least six doses of intravenous PMB in each patient. PMB plasma concentrations were quantified by high-performance liquid chromatography-tandem mass spectrometry. The primary outcome was PMB exposure as assessed by the area under the concentration-time curve over 24 h at steady state (AUCss, 0-24 h). Results and Discussion: The elderly group had lower total body weight (TBW) and higher Charlson comorbidity scores than young group. Neither AUCss, 0-24 h nor normalized AUCss, 0-24 h (adjusting AUC for the daily dose in mg/kg of TBW) was significantly different between the elderly group and young group. The half-life time was longer in the elderly patients than in young patients (11.21 vs 6.56 h respectively, p = 0.003). Age and TBW were the covariates of half-life time (r = 0.415, p = 0.049 and r = -0.489, p = 0.018, respectively). TBW was the covariate of clearance (r = 0.527, p = 0.010) and AUCss, 0-24 h (r = -0.414, p = 0.049). Patients with AUCss, 0-24 h ≥ 100 mg·h/L had higher baseline serum creatinine levels and lower TBW than patients with AUCss, 0-24 h < 50 mg·h/L or patients with AUCss, 0-24 h 50-100 mg·h/L. The PMB exposures were comparable in elderly and young critically ill patients. High baseline serum creatinine levels and low TBW was associated with PMB overdose. Trial registration: ChiCTR2300073896 retrospectively registered on 25 July 2023.

Effect of open surgical and percutaneous dilatational tracheostomy on postoperative wound complications in patients: A meta-analysis.

Tracheostomy is one of the most common operations. The two main methods of tracheostomy are open surgical tracheostomy (OST) and percutaneous dilatational tracheostomy (PDT). In critical cases, the combination of these two approaches is especially crucial, with the possibility of successful outcomes and low complications. Thus, the purpose of this system is to analyse the effects of both methods on the outcome of postoperative wound. In this research, we performed a systematic review of Cochrane Library, PubMed, Web of Science and Embase, to determine all randomized controlled trials (RCTs) that are comparable in terms of postoperative injury outcomes. Eleven RCTs were found after screening. This study will take the necessary data from the selected trials and evaluate the documentation for RCTs. PDT was associated with a lower incidence of infection at the wound site than OST (OR, 4.46; 95% CI: 2.84-7.02 p < 0.0001), and PDT decreased blood loss (OR, 2.88; 95% CI: 1.62-5.12 p = 0.0003). But the operation time did not differ significantly in both PDT to OST (MD, 4.65; 95% CI: -1.19-10.48 p = 0.12). The meta-analyses will assist physicians in selecting the best operative procedure for critical cases of tracheostomy. These data can serve as guidelines for clinical management and in the design of future randomized, controlled studies.

QTL mapping and transcriptomic analysis of fruit length in cucumber.

A total of 151 recombinant inbred lines (RILs) were derived from the cross between 'Cucumis sativus L. hardwickii' (HW) and a cultivated Northern Chinese inbred line 'XinTaiMiCi' (XTMC). We used resequencing to construct the genetic map and analyze the genetic background of RIL population, and combined with the phenotypes of RIL population and the analysis of RNA-seq data, we located the major loci controlling the fruit length of cucumber and related analysis. A genetic map containing 600 bin markers was constructed via re-sequencing. Based on the phenotype data collected in two different seasons (spring 2021 and autumn 2022), the major quantitative trait loci (QTLs) controlling cucumber fruit length were located and their transcriptomic analysis carried out. The results revealed three QTLs (Fl2.1, Fl4.1, and Fl6.1) detected repeatedly in the two seasons, of which Fl4.1 was the dominant QTL. From the functional annotation of corresponding genes there, we discovered the gene Csa4G337340 encoding an auxin efflux carrier family protein. The expression of that gene was significantly lower in XTMC and the long-fruit RIL lines than in HW and the short-fruit RIL lines; hence, we speculated the gene could be negatively correlated with the fruit length of cucumber. Transcriptomic analysis showed that 259 differentially expressed genes (DEGs) were enriched in the plant hormone signal transduction pathway. In addition, among those DEGs, 509 transcription factors were detected, these distributed in several transcription factor gene families, such as bHLH, AP2/ErF -ERF, C2H2, and NAC. Therefore, we concluded that the major gene controlling the fruit length of cucumber is located in the interval of Fl4.1, whose gene Csa4G337340 may be involved in the negative regulation of fruit length. Further, genes related to plant hormone signal transduction and several transcription factors were also found involved in the regulation of cucumber fruit length. Our results provide a reference for the fine mapping of major genes and analyzing the mechanism of cucumber fruit length.

Targeting homologous recombination deficiency in uterine leiomyosarcoma.

BACKGROUND: Uterine leiomyosarcoma (uLMS) is a rare and aggressive gynaecological malignancy, with individuals with advanced uLMS having a five-year survival of < 10%. Mutations in the homologous recombination (HR) DNA repair pathway have been observed in ~ 10% of uLMS cases, with reports of some individuals benefiting from poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) therapy, which targets this DNA repair defect. In this report, we screened individuals with uLMS, accrued nationally, for mutations in the HR repair pathway and explored new approaches to therapeutic targeting. METHODS: A cohort of 58 individuals with uLMS were screened for HR Deficiency (HRD) using whole genome sequencing (WGS), whole exome sequencing (WES) or NGS panel testing. Individuals identified to have HRD uLMS were offered PARPi therapy and clinical outcome details collected. Patient-derived xenografts (PDX) were generated for therapeutic targeting. RESULTS: All 13 uLMS samples analysed by WGS had a dominant COSMIC mutational signature 3; 11 of these had high genome-wide loss of heterozygosity (LOH) (> 0.2) but only two samples had a CHORD score > 50%, one of which had a homozygous pathogenic alteration in an HR gene (deletion in BRCA2). A further three samples harboured homozygous HRD alterations (all deletions in BRCA2), detected by WES or panel sequencing, with 5/58 (9%) individuals having HRD uLMS. All five individuals gained access to PARPi therapy. Two of three individuals with mature clinical follow up achieved a complete response or durable partial response (PR) with the subsequent addition of platinum to PARPi upon minor progression during initial PR on PARPi. Corresponding PDX responses were most rapid, complete and sustained with the PARP1-specific PARPi, AZD5305, compared with either olaparib alone or olaparib plus cisplatin, even in a paired sample of a BRCA2-deleted PDX, derived following PARPi therapy in the patient, which had developed PARPi-resistance mutations in PRKDC, encoding DNA-PKcs. CONCLUSIONS: Our work demonstrates the value of identifying HRD for therapeutic targeting by PARPi and platinum in individuals with the aggressive rare malignancy, uLMS and suggests that individuals with HRD uLMS should be included in trials of PARP1-specific PARPi.

An efficient calculation method of large-region dynamic traffic noise maps based on hybrid modeling.

The construction of noise maps is of great significance for the management and control of urban noise and the protection of residents' physical and mental health. The European Noise Directive recommends using computational methods to construct strategic noise maps when possible. The current noise maps based on model calculation rely on complex noise emission and propagation models, and their huge number of regional grids needs to consume a lot of calculation time. This seriously restricts the update efficiency of noise maps, making it difficult to realize large-scale application and real-time dynamic update of noise maps. In order to improve the computational efficiency of noise maps, based on big data-driven technology, this paper combines the traditional CNOSSOS-EU noise emission modeling method with the multivariate nonlinear regression modeling method, and proposes an efficient calculation method of large-region dynamic traffic noise maps based on hybrid modeling method. First, this paper constructs the (daily and nightly) noise contribution prediction models of road sources with different classes, considering the daily and nightly periods and different urban road classes. Parameters of the proposed model are evaluated by using the multivariate nonlinear regression method to replace the complex nonlinear acoustic mechanism modeling. On this basis, in order to further improve the computational efficiency, noise contribution attenuations of the constructed models are parameterized and evaluated quantitatively. And then, the database containing the index table of the road noise sources-receivers and the corresponding noise contribution attenuations is constructed. The experimental results show that compared with the traditional calculation methods based on acoustic mechanism model, the noise map calculation method based on hybrid model proposed in this paper greatly reduces the model computations of noise map, improves the efficiency of noise mapping. It will provide technical support for constructing dynamic noise maps of large urban regions.

A novel method for real-time prediction of the shelf life of pork at different storage temperatures using front-face fluorescence excitation-emission matrices.

This study presents a novel method for predicting the shelf life of pork in real-time based on front-face fluorescence excitation-emission matrices (EEMs). The total viable count (TVC) of bacteria was used as the indicator of microbial spoilage in the pork samples. Modified Gompertz and square root equations were used to establish models for the trends in microbial growth and for predicting the shelf life, the R2 values of the fitting equation at different temperatures were all greater than 0.95. The fluorescence intensity ratio of oxidation product to tryptophan (FOX/Trp) was highly correlated with the quality deterioration of pork and was therefore used to establish a quantitative model of TVC values by linear regression with Rc2 and Rp2 values of 0.914 and 0.906, respectively. The mean absolute errors between the remaining shelf life predicted by fluorescence EEMs and the measured values at three storage temperatures were less than 1 day.

Effect of empirical antifungal treatment on mortality in non-neutropenic critically ill patients: a propensity-matched retrospective cohort study.

To evaluate the effect of empirical antifungal treatment (EAFT) on mortality in critically ill patients without invasive fungal infections (IFIs). This was a single-center propensity score-matched retrospective cohort study involving non-transplanted, non-neutropenic critically ill patients with risk factors for invasive candidiasis (IC) in the absence of IFIs. We compared all-cause hospital mortality and infection-attributable hospital mortality in patients who was given EAFT for suspected IC as the cohort group and those without any systemic antifungal agents as the control group. Among 640 eligible patients, 177 patients given EAFT and 177 control patients were included in the analyses. As compared with controls, EAFT was not associated with the lower risks of all-cause hospital mortality [odds ratio (OR), 0.911; 95% CI, 0.541-1.531; P = 0.724] or infection-attributable hospital mortality (OR, 1.149; 95% CI, 0.632-2.092; P = 0.648). EAFT showed no benefit of improvement of infection at discharge, duration of mechanical ventilation, and antibiotic-free days. However, the later initiation of EAFT was associated with higher risks of all-cause hospital mortality (OR, 1.039; 95% CI, 1.003 to 1.076; P = 0.034) and infection-attributable hospital mortality (OR, 1.046; 95% CI, 1.009 to 1.085; P = 0.015) in patients with suspected IC. This effect was also found in infection-attributable hospital mortality (OR, 1.042; 95% CI, 1.005 to 1.081; P = 0.027) in septic patients with suspected IC. EAFT failed to decrease hospital mortality in non-neutropenic critically ill patients without IFIs. The timing may be critical for EAFT to improve mortality in these patients with suspected IC. ChiCTR2000038811, registered on Oct 3, 2020.

Study on Subjective Evaluation of Acoustic Environment in Urban Open Space Based on "Effective Characteristics".

With the continuous expansion of urban scale with dense population and traffic and the gradual improvement of residents' requirements for environmental quality, the traditional evaluation method relying on acoustic energy is not enough to reflect the feelings of urban crowds about acoustic environment quality. The acoustic environment quality evaluation method based on human subjective perception has gradually become one of the research focuses in the field of environmental noise control. In recent years, various subjective and objective acoustic characteristic parameters have been introduced into the study of acoustic environment assessment in the global literature. However, the extraction of "effective characteristics" from a large number of physical and psychoacoustic characteristics contained in acoustic signals and the creation of a scientific and efficient subjective evaluation model have always been key technical problems in the field of acoustic environment evaluation. Based on subjective human perceptions, the overall acoustic environment quality evaluation of urban open spaces is studied in this paper. Based on the "effective characteristic" parameters and the subjective characteristic proposed in the previous research, including equivalent continuous A-weighted sound pressure level (LA), the difference between median noise and ambient background noise (L50 - L90), Sharpness (Sh), as well as satisfaction (Sat), the multivariable linear regression algorithm is used to further study the intrinsic correlation between the proposed "effective characteristics" and subjective perception. Then, a satisfaction evaluation model of the acoustic environment based on "effective characteristics" is built in this paper. Furthermore, the soundwalk evaluation experiment and the MATLAB numerical simulation experiment are carried out, which verify that the prediction accuracy of the proposed model is more than 92%, the consistency of satisfaction level is more than 88%, as well as the changes in the values of Sh and L50 - L90 have a significant impact on the satisfaction prediction of the proposed model. It shows that the proposed "effective characteristics" more comprehensively describe the quality level of the regional acoustic environment in urban open space compared with a single LA index, and the proposed acoustic environment satisfaction evaluation model based on "effective characteristics" has significant accuracy superiority and regional applicability.

The Relationship between Gestational Newborn Weight Loss and Hospitalization in the First Week after Birth.

Objective: To investigate the association of weight loss daily of term infants with hospitalization in the first week after birth. Methods: This prospective cohort study was conducted among 1865 infants from May 2020 to June 2021, born in the Department of Obstetrics, Kunshan's First People's Hospital Affiliated to Jiangsu University and Huai'an Maternal and Child Health Care Center. The infants' weight was collected daily in the hospital, and the weight loss was calculated daily. According to the weight loss daily, the infants were divided into 3 groups. Group A: the weight loss per day was less than 2% of birth weight, and the total weight loss was less than 10%. Group B: the weight loss per day was between 2 and 4% of the birth weight, and the total weight loss was less than 10%. Group C: the weight loss per day was more than 4% of the birth weight, or the total weight was more than 10%. The infants in group C were monitored carefully in the hospital or Outpatient Department (OPD) daily. The primary outcome was the incidence of hospitalization. Results: Of the 1865 term infants enrolled, 1052 were completed on the 7th day (356 in group A, 513 in group B, and 183 in group C). There was no significant difference among the three groups of subjects in terms of infant data, including birth weight, gender, Apgar scores, and gestational age. The number of C-sections and primiparas was substantially higher in groups C and B than in group A. The incidence of hospitalization in group C was significantly higher than that in group A and group B (30.6%, 12.1%, and 12.5%, respectively). The incidence of exclusive breastfeeding in group C was significantly lower than that in group A and group B (28.4%, 41%, and 38.4%, respectively). There was no significant difference between group A and group B in the incidence of hospitalization and exclusive breastfeeding. Most of the hospitalization was because of hyperbilirubinemia, and in group C, there were 2 babies because of dehydration fever and 3 because of hypoglycemia. Conclusions: The neonates whose weight loss daily after birth was more than 4% of the total weight loss of more than 10% had higher hospitalization rates.

Dynamic Changes in the Aorta During the Cardiac Cycle Analyzed by ECG-Gated Computed Tomography.

Background: To characterize the difference in aortic dimensions during the cardiac cycle with electrocardiogram (ECG)-gated computed tomography angiography (CTA) and to determine whether other parameters in comparison to diameter could potentially provide a more accurate size reference for stent selection at the aortic arch and the proximal thoracic descending aorta. Methods: The CTA imaging of 90 patients during the cardiac cycle was reviewed. Three anatomic locations were selected for analysis (level A: 1 cm proximal to the innominate artery; level B: 1 cm distal to the left common carotid artery; and level C: 1 cm distal to the left subclavian artery). We measured the maximum diameter, the minimum diameter, the lumen area, the lumen perimeter, and the diameter derived from the lumen area, and the changes of each parameter at each level during the cardiac cycle were compared. Results: The mean age was 60.9 ± 12.4 years (range, 16-78 years). There was a significant difference in the aortic dimensions during the cardiac cycle (p < 0.001). The diameter derived from the lumen area at all three levels was changed least over time when compared to the area, perimeter, and the maximum aortic diameter (all p < 0.01). Conclusion: The aortic dimensional differences during the cardiac cycle are significant. The aortic diameter derived from the lumen area over other parameters may provide a better evaluation for selecting the size of the stent at the aortic arch and the proximal thoracic descending aorta. A prospective study comparing these different measurement parameters regarding the outcomes is still needed to evaluate the clinical implications.

Role of PGC-1α in fiber type conversion in the palatopharyngeus muscle of OSA patients.

BACKGROUND: Obstructive sleep apnea (OSA) has a high incidence and is harmful to health. It is characterized by repeated collapse of the upper airway. However, the mechanism underlying upper airway collapse is unclear. METHODS: Patients with OSA and chronic tonsillitis were studied. Pathological changes in palatopharyngeus muscle were detected. The expression of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1) in muscles was detected by PCR and Western blotting. Immunofluorescence staining was used to detect the expression of type I and type II myofibril. RESULTS: The structure of the palatopharyngeus muscle was changed, and the expression of PGC-1α and NRF-1 was decreased in the OSA group compared with that in the control group. The expression of PGC-1α, NRF-1, and type I myofibril in C2C12 myoblasts was decreased by intermittent hypoxia exposure. The expression of type I myofibril was decreased when knocking down PGC-1α. CONCLUSION: OSA patients exhibited pathological damage in palatopharyngeus muscle. PGC-1α was involved in the fiber type conversion in palatopharyngeus muscle caused by intermittent hypoxia.

Dietary folate drives methionine metabolism to promote cancer development by stabilizing MAT IIA.

Folic acid, served as dietary supplement, is closely linked to one-carbon metabolism and methionine metabolism. Previous clinical evidence indicated that folic acid supplementation displays dual effect on cancer development, promoting or suppressing tumor formation and progression. However, the underlying mechanism remains to be uncovered. Here, we report that high-folate diet significantly promotes cancer development in mice with hepatocellular carcinoma (HCC) induced by DEN/high-fat diet (HFD), simultaneously with increased expression of methionine adenosyltransferase 2A (gene name, MAT2A; protein name, MATIIα), the key enzyme in methionine metabolism, and acceleration of methionine cycle in cancer tissues. In contrast, folate-free diet reduces MATIIα expression and impedes HFD-induced HCC development. Notably, methionine metabolism is dynamically reprogrammed with valosin-containing protein p97/p47 complex-interacting protein (VCIP135) which functions as a deubiquitylating enzyme to bind and stabilize MATIIα in response to folic acid signal. Consistently, upregulation of MATIIα expression is positively correlated with increased VCIP135 protein level in human HCC tissues compared to adjacent tissues. Furthermore, liver-specific knockout of Mat2a remarkably abolishes the advocating effect of folic acid on HFD-induced HCC, demonstrating that the effect of high or free folate-diet on HFD-induced HCC relies on Mat2a. Moreover, folate and multiple intermediate metabolites in one-carbon metabolism are significantly decreased in vivo and in vitro upon Mat2a deletion. Together, folate promotes the integration of methionine and one-carbon metabolism, contributing to HCC development via hijacking MATIIα metabolic pathway. This study provides insight into folate-promoted cancer development, strongly recommending the tailor-made folate supplement guideline for both sub-healthy populations and patients with cancer expressing high level of MATIIα expression.

Caltech Conte Center, a multimodal data resource for exploring social cognition and decision-making.

This data release of 117 healthy community-dwelling adults provides multimodal high-quality neuroimaging and behavioral data for the investigation of brain-behavior relationships. We provide structural MRI, resting-state functional MRI, movie functional MRI, together with questionnaire-based and task-based psychological variables; many of the participants have multiple datasets from retesting over the course of several years. Our dataset is distinguished by utilizing open-source data formats and processing tools (BIDS, FreeSurfer, fMRIPrep, MRIQC), providing data that is thoroughly quality checked, preprocessed to various extents and available in multiple anatomical spaces. A customizable denoising pipeline is provided as open-source code that includes tools for the generation of functional connectivity matrices and initialization of individual difference analyses. Behavioral data include a comprehensive set of psychological assessments on gold-standard instruments encompassing cognitive function, mood and personality, together with exploratory factor analyses. The dataset provides an in-depth, multimodal resource for investigating associations between individual differences, brain structure and function, with a focus on the domains of social cognition and decision-making.

BCAA-BCKA axis regulates WAT browning through acetylation of PRDM16.

The link between branched-chain amino acids (BCAAs) and obesity has been known for decades but the functional role of BCAA metabolism in white adipose tissue (WAT) of obese individuals remains vague. Here, we show that mice with adipose tissue knockout of Bcat2, which converts BCAAs to branched-chain keto acids (BCKAs), are resistant to high-fat diet-induced obesity due to increased inguinal WAT browning and thermogenesis. Mechanistically, acetyl-CoA derived from BCKA suppresses WAT browning by acetylation of PR domain-containing protein 16 (PRDM16) at K915, disrupting the interaction between PRDM16 and peroxisome proliferator-activated receptor-γ (PPARγ) to maintain WAT characteristics. Depletion of BCKA-derived acetyl-CoA robustly prompts WAT browning and energy expenditure. In contrast, BCKA supplementation re-establishes high-fat diet-induced obesity in Bcat2 knockout mice. Moreover, telmisartan, an anti-hypertension drug, significantly represses Bcat2 activity via direct binding, resulting in enhanced WAT browning and reduced adiposity. Strikingly, BCKA supplementation reverses the lean phenotype conferred by telmisartan. Thus, we uncover the critical role of the BCAA-BCKA axis in WAT browning.

Thoracic Endovascular Aortic Repair for Retrograde Type A Intramural Hematoma With Intimal Disruption in the Descending Aorta.

PURPOSE: To evaluate the safety and efficacy of thoracic endovascular aortic repair (TEVAR) for retrograde type A intramural hematoma (IMH) with intimal disruption in the descending aorta and report our endovascular therapeutic experience. MATERIALS AND METHODS: From January 2014 to October 2020, a total of 24 consecutive patients with retrograde type A IMH with intimal disruption (intimal tear or ulcer-like projection) in the descending aorta underwent TEVAR. The demographics, clinical characteristics, treatment details, imaging information, and follow-up results were reviewed. RESULTS: Among all patients with retrograde type A IMH, 13 (54.2%) patients presented with ulcer-like projection and 11 (45.8%) with intimal tear (aortic dissection) in the descending aorta. Successful TEVAR was achieved in all patients. There was no 30-day mortality. During a mean follow-up of 37.5 months, 1 patient (4.2%) developed permanent paralysis, 1 patient (4.2%) underwent reintervention due to the expansion of the aorta distal to the stent resulting from the enlargement of distal intimal tear at the 2 month follow up, and no other adverse events were observed. The latest computed tomographic angiography images showed that the maximum diameter of the ascending aorta and descending aorta significantly decreased after TEVAR (both p<0.001), and the IMH/false lumen in the ascending aorta and the descending thoracic aorta were completely absorbed. CONCLUSION: Thoracic endovascular aortic repair for selected patients with retrograde type A intramural hematoma that presented with intimal disruption in the descending aorta is feasible and efficient, but close surveillance is needed to manage aortic-related adverse events.