TRPML3/BK complex promotes autophagy and bacterial clearance by providing a positive feedback regulation of mTOR via PI3P.

TRPML3 is a Ca2+/Na+ release channel residing in both phagophores and endolysosomal membranes. It is activated by PI3P and PI3,5P2. Its activity can be enhanced by high luminal pH and by replacing luminal Na+ with K+. Here, we report that big-conductance Ca2+-activated potassium (BK) channels form a positive feedback loop with TRPML3. Ca2+ release via TRPML3 activates BK, which in turn facilitates TRPML3-mediated Ca2+ release, potentially through removing luminal Na+ inhibition. We further show that TRPML3/BK and mammalian target of rapamycin (mTOR) form another positive feedback loop to facilitate autophagy induction in response to nutrient starvation, i.e., mTOR inhibition upon nutrient starvation activates TRPML3/BK, and this further reduces mTOR activity, thereby increasing autophagy induction. Mechanistically, the feedback regulation between TRPML3/BK and mTOR is mediated by PI3P, an endogenous TRPML3 activator that is enriched in phagophores and is up-regulated by mTOR reduction. Importantly, bacterial infection activates TRPML3 in a BK-dependent manner, and both TRPML3 and BK are required for mTOR suppression and autophagy induction responding to bacterial infection. Suppressing either TRPML3 or BK helps bacteria survival whereas increasing either TRPML3 or BK favors bacterial clearance. Considering that TRPML3/BK is inhibited by low luminal pH but activated by high luminal pH and PI3P in phagophores, we suggest that TRPML3/BK and mTOR form a positive feedback loop via PI3P to ensure efficient autophagy induction in response to nutrient deprivation and bacterial infection. Our study reveals a role of TRPML3-BK coupling in controlling cellular homeostasis and intracellular bacterial clearance via regulating mTOR signaling.

Modulation of fried spring roll wrapper quality upon treatment of batter with maltogenic amylase, transglutaminase and bromelain.

BACKGROUND: Fried foods are favored for their unique crispiness, golden color and flavor, but they also face great challenge because of their high oil content, high calories and the existence of compounds such as acrylamide and polycyclic aromatic hydrocarbons. Long-term consumption of fried foods may adversely affect health. Therefore, it is necessary to explore fried foods with lower oil contents and a high quality to meet the demand. RESULTS: A method of enzyme treatment was explored to investigate the effects of maltogenic amylase (MA), transglutaminase (TG) and bromelain (BRO) on the physicochemical properties of the batter and the quality of fried spring roll wrapper (FSRW). The results showed that the MA-, TG- or BRO-treated batters had a significant shear-thinning behavior, especially with an increase in viscosity upon increasing TG contents. FSRW enhanced its fracturability from 419.19 g (Control) to 616.50 g (MA-6 U g-1), 623.49 g (TG-0.75 U g-1) and 644.96 g (BRO-10 U g-1). Meanwhile, in comparison with BRO and MA, TG-0.5 U g-1 endowed batter with the highest density and thermal stability. MA-15 U g-1 and TG-0.5 U g-1 displayed FSRW with uniform and dense pores, and significantly reduced its oil content by 18.05% and 25.02%, respectively. Moreover, compared to MA and TG, BRO-50 U g-1 improved the flavor of FSRW. CONCLUSION: MA, TG or BRO played a key role in affecting the physicochemical properties of the batter and the quality of FSRW. TG-0.5 U g-1 remarkly reduced the oil content of FSRW with a great potential in practical application. © 2024 Society of Chemical Industry.

Photocatalytic synthesis of azaheterocycle-fused piperidines and pyrrolidines via tandem difunctionalization of unactivated alkenes.

A variety of azaheterocycle-fused piperidines and pyrrolidines bearing CF3 and CHF2 functionalities were obtained using CF3SO2Na and CHF2SO2Na by visible light photocatalysis. This protocol involves a radical cascade cyclization via tandem tri- and difluoromethylation-arylation of pendent unactivated alkenes. Benzimidazole, imidazole, theophylline, purine, and indole serve as applicable anchors, thereby enriching the structural diversity of piperidine and pyrrolidine derivatives. This method features mild, additive-free and transition metal-free conditions.

Surface and Air Contamination With Severe Acute Respiratory Syndrome Coronavirus 2 From Hospitalized Coronavirus Disease 2019 Patients in Toronto, Canada, March-May 2020.

BACKGROUND: We determined the burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in air and on surfaces in rooms of patients hospitalized with coronavirus disease 2019 (COVID-19) and investigated patient characteristics associated with SARS-CoV-2 environmental contamination. METHODS: Nasopharyngeal swabs, surface, and air samples were collected from the rooms of 78 inpatients with COVID-19 at 6 acute care hospitals in Toronto from March to May 2020. Samples were tested for SARS-CoV-2 ribonucleic acid (RNA), cultured to determine potential infectivity, and whole viral genomes were sequenced. Association between patient factors and detection of SARS-CoV-2 RNA in surface samples were investigated. RESULTS: Severe acute respiratory syndrome coronavirus 2 RNA was detected from surfaces (125 of 474 samples; 42 of 78 patients) and air (3 of 146 samples; 3 of 45 patients); 17% (6 of 36) of surface samples from 3 patients yielded viable virus. Viral sequences from nasopharyngeal and surface samples clustered by patient. Multivariable analysis indicated hypoxia at admission, polymerase chain reaction-positive nasopharyngeal swab (cycle threshold of ≤30) on or after surface sampling date, higher Charlson comorbidity score, and shorter time from onset of illness to sampling date were significantly associated with detection of SARS-CoV-2 RNA in surface samples. CONCLUSIONS: The infrequent recovery of infectious SARS-CoV-2 virus from the environment suggests that the risk to healthcare workers from air and near-patient surfaces in acute care hospital wards is likely limited.

Indicator species drive the key ecological functions of microbiota in a river impacted by acid mine drainage generated by rare earth elements mining in South China.

Acid mine drainage (AMD) generated by rare earth elements (REEs) deposits exploration contains high concentrations of REEs, ammonium and sulfates, which is quite different from typical metallic AMD. Currently, microbial responses and ecological functions in REEs-AMD impacted rivers are unknown. Here, 16S rRNA analysis and genome-resolved metagenomics were performed on microbial community collected from a REEs-AMD contaminated river. The results showed that REEs-AMD significantly changed river microbial diversity and shaped unique indicator species (e.g. Thaumarchaeota, Methylophilales, Rhodospirillales and Burkholderiales). The main environmental factors regulating community were pH, ammonium and REEs, among which high concentration of REEs increased REEs-dependent enzyme-encoding genes (XoxF and ExaF/PedH). Additionally, we reconstructed 566 metagenome-assembled genomes covering 70.4% of identifying indicators. Genome-centric analysis revealed that the abundant archaea Thaumarchaeota and Xanthomonadaceae were often involved in nitrification and denitrification, while family Burkholderiaceae were capable of sulfide oxidation coupled with dissimilatory nitrate reduction to ammonium. These indicators play crucial roles in nitrogen and sulfur cycling as well as REEs immobilization in REEs-AMD contaminated rivers. This study confirmed the potential dual effect of REEs on microbial community at the functional gene level. Our investigation on the ecological roles of indicators further provided new insights for the development of REEs-AMD bioremediation.

Safety and efficacy profile of Trastuzumab deruxtecan in solid cancer: pooled reanalysis based on clinical trials.

PURPOSE: This study aimed to explore the efficiency and safety of the new generation antibody-drug conjugate Trastuzumab deruxtecan (DS-8201a) in treating HER2-positive solid cancers. METHOD: By searching PubMed, Medline and Ovid for all clinical trials related to the safety and efficacy of DS-8201a. Event rates were calculated for all adverse events (AEs) to evaluate the safety of DS-8201a. Objective response rate (ORR) and progression-free survival (PFS) were summarized to assess the potency of DS-8201a. RESULT: The AEs with event rates greater than 30% regardless of grades were nausea, decreased appetite, vomiting, fatigue, anemia, decreased neutrophil count, alopecia and diarrhea. In the grade 3 or more, decreased neutrophil count, anemia and decreased white blood cell count were the only three AEs with event rates greater than 10% (20.3, 15.0 and 10.3%). The median PFS of patients with breast cancer, gastric cancer and other HER2-positive solid cancers were 9.0-22.1, 3.0-8.3 and 4.1-11.9 months. The median ORR was 37-79.9% in patients with breast and gastric cancer and 28.3-55% in patients with other HER2-positive cancers. CONCLUSION: DS-8201a plays an active role in treating HER2-positive cancers, especially breast and gastric cancer, which have HER2 amplification. The most common AEs of DS-8201a were related to gastrointestinal and hematological system. Decreased white blood cell count and appetite were the AEs occurred with high grades.

Pneumatosis cystoides intestinalis associated with etoposide in hematological malignancies: a case report and a literature review.

Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by the presence of air collection within the subserosa and/or submucosa of the gastrointestinal wall. Due to the lack of specific symptoms, PCI is likely to be misdiagnosed or missed without the use of imaging techniques or gastrointestinal endoscopy. Here, we report a patient who complained of abdominal distention and constipation after chemotherapy for hematological malignancies, and was diagnosed with secondary PCI via computed tomography (CT) and exploratory laparotomy. Pneumoperitoneum was no longer observed after two weeks of conservative treatments. Notably, the possibility of intra-abdominal pressure (IAP) as a predictor for surgical intervention was proposed. Furthermore, we conducted a literature review on PCI after chemotherapy in hematological malignancies to raise awareness of etoposide-related PCI, while whether PCI could be identified as an adverse event of etoposide requires more evidence.

Clinical and MRI features of sacral insufficiency fractures after radiotherapy in patients with cervical cancer.

BACKGROUND: To determine the incidence, clinical and MRI features of sacral insufficiency fracture (SIF) after radiotherapy (RT) in patients with cervical cancer. METHODS: Our study included 167 patients with cervical cancer after radiotherapy that underwent pelvic MRI for follow-up. MRIs included pre-enhanced T1-weighted, coronal fat-Suppressed T2-weighted (FS-T2W) and enhanced T1-weighted imaging. The clinical and MRI dates were reviewed. The gold standard of SIF was based on radiologic findings, clinical data and follow-up at least 12 months. RESULTS: 28 patients (10.8%) with 47 sites were diagnosed with SIFs, including 9 patients with unilateral SIF and 19 patients with bilateral SIFs. The median age was 60 years (range 41-72 years), and 89.3% (25/28) of patients were postmenopausal. 64.3% (18/28) of patients were symptomatic, and 53.6% of patients (15/28) had concomitant pelvic fractures. The median interval time from RT to SIFs was 10 months (range 3-34 months). For the lesion-wise analysis based on all MR images, all lesions were detected by visualizing bone marrow edema patterns, and fracture lines were detected in 64.6% (31/47) of SIFs. No soft-tissue tumors were founded. For each MRI sequence analysis, coronal FS-T2WI detected the most bone marrow edema pattern and fracture line than T1WI or enhanced T1WI. CONCLUSION: SIF is a common complication in cervical cancer after radiotherapy, which has some certain clinical and MRI features. Coronal FS-T2WI may be more useful to detect and characterize these fractures than other imaging sequences.

Spatiotemporal variations of air pollution and population exposure in Shandong Province, eastern China, 2014-2018.

To clarify the characteristics and interannual variation of air pollution since the implementation of China's clean air actions, hourly in situ measurements of six gaseous and particulate criteria pollutants at 100 sites in Shandong Province were studied during 2014-2018. General decreasing trends in the concentrations of PM2.5, PM10, NO2, SO2, and CO were observed, while O3 increased continuously. In 2018, the annual average PM2.5, PM10, NO2, SO2, and CO concentration in Shandong was 50, 100, 35, 16 µg m-3, and 1.5 mg m-3, representing decreases of 39%, 30%, 24%, 73%, and 35% from 2014, respectively. These decreases occurred throughout the province. Seven "2 + 26" cities (in Beijing-Tianjin-Hebei and its surrounds) in western Shandong had higher average concentrations and greater reductions than other areas. In contrast, O3 concentration rose, with occurrences of the 90th percentile of all daily maximum 8-h averages increasing by 12% from 159 to 181 µg m-3, during 2014-2018. From May to September, O3 pollution dominated as the sole primary pollutant on non-attainment days, and PM2.5 contributed to more than 90% of polluted days in wintertime months. Population exposures were investigated based on high-resolution monitoring data and population distribution, and high exposure to pollution was displayed. The population-weighted exposure to PM2.5 in Shandong was 50 µg m-3, a decrease of 33%. Eighty-nine percentage of the provincial population was exposed to PM2.5 > 35 µg m-3, while for 99.2% of population in the seven "2 + 26" cities, PM2.5 exposure exceeded 50 µg m-3.

[Research progress on chemical constituents and pharmacological activities of Morus alba].

Morus alba, a traditional economic crop, is also a significant medicinal plant. The branches(Mori Ramulus), leaves(Mori Folium), roots and barks(Mori Cortex), and fruits(Mori Fructus) of M. alba are rich in chemical components, such as alkaloids, flavonoids, flavanols, anthocyanins, benzofurans, phenolic acids, and polysaccharides, and possess hypoglycemic, hypolipidemic, anti-inflammatory, anti-tumor, anti-microbial, liver protective, immunoregulatory, and other pharmacological activities. This study analyzed the sources, classification, and functions of the main chemical components in M. alba and systematically summarized the latest research results of essential active components in M. alba and their pharmacological effects to provide references for in-depth research and further development as well as utilization of active components in M. alba.

Sensitivity of Nasopharyngeal Swabs and Saliva for the Detection of Severe Acute Respiratory Syndrome Coronavirus 2.

We enrolled 91 consecutive inpatients with COVID-19 at 6 hospitals in Toronto, Canada, and tested 1 nasopharyngeal swab/saliva sample pair from each patient using real-time RT-PCR for severe acute respiratory syndrome coronavirus 2. Sensitivity was 89% for nasopharyngeal swabs and 72% for saliva (P = .02). Difference in sensitivity was greatest for sample pairs collected later in illness.

Household Transmission of Carbapenemase-producing Enterobacterales in Ontario, Canada.

BACKGROUND: Data on household transmission of carbapenemase-producing Enterobacterales (CPE) remain limited. We studied risk of CPE household co-colonization and transmission in Ontario, Canada. METHODS: We enrolled CPE index cases (identified via population-based surveillance from January 2015 to October 2018) and their household contacts. At months 0, 3, 6, 9, and 12, participants provided rectal and groin swabs. Swabs were cultured for CPE until September 2017, when direct polymerase chain reaction (PCR; with culture of specimens if a carbapenemase gene was detected) replaced culture. CPE risk factor data were collected by interview and combined with isolate whole-genome sequencing to determine likelihood of household transmission. Risk factors for household contact colonization were explored using a multivariable logistic regression model with generalized estimating equations. RESULTS: Ninety-five households with 177 household contacts participated. Sixteen (9%) household contacts in 16 (17%) households were CPE-colonized. Household transmission was confirmed in 3/177 (2%) cases, probable in 2/177 (1%), possible in 9/177 (5%), and unlikely in 2/177 (1%). Household contacts were more likely to be colonized if they were the index case's spouse (odds ratio [OR], 6.17; 95% confidence interval [CI], 1.05-36.35), if their index case remained CPE-colonized at household enrollment (OR, 7.00; 95% CI, 1.92-25.49), or if they had at least 1 set of specimens processed after direct PCR was introduced (OR, 6.46; 95% CI, 1.52-27.40). CONCLUSIONS: Nine percent of household contacts were CPE-colonized; 3% were a result of household transmission. Hospitals may consider admission screening for patients known to have CPE-colonized household contacts.

Differentiation of small (≤ 3 cm) hepatocellular carcinomas from benign nodules in cirrhotic liver: the added additive value of MRI-based radiomics analysis to LI-RADS version 2018 algorithm.

BACKGROUND: Accurate characterization of small nodules in a cirrhotic liver is challenging. We aimed to determine the additive value of MRI-based radiomics analysis to Liver Imaging Reporting and Data System version 2018 (LI-RADS v 2018) algorithm in differentiating small (≤ 3 cm) hepatocellular carcinomas (HCCs) from benign nodules in cirrhotic liver. METHODS: In this retrospective study, 150 cirrhosis patients with histopathologically confirmed small liver nodules (HCC, 112; benign nodules, 44) were evaluated from January 2013 to October 2018. Based on the LI-RADS algorithm, a LI-RADS category was assigned for each lesion. A radiomics signature was generated based on texture features extracted from T1-weighted, T2W, and apparent diffusion coefficient (ADC) images by using the least absolute shrinkage and selection operator regression model. A nomogram model was developed for the combined diagnosis. Diagnostic performance was assessed using receiver operating characteristic curve (ROC) analysis. RESULTS: A radiomics signature consisting of eight features was significantly associated with the differentiation of HCCs from benign nodules. Both LI-RADS algorithm (area under ROC [Az] = 0.898) and the MRI-Based radiomics signature (Az = 0.917) demonstrated good discrimination, and the nomogram model showed a superior classification performance (Az = 0.975). Compared with LI-RADS alone, the combined approach significantly improved the specificity (97.7% vs 81.8%, p = 0.030) and positive predictive value (99.1% vs 92.9%, p = 0.031) and afforded comparable sensitivity (97.3% vs 93.8%, p = 0.215) and negative predictive value (93.5% vs 83.7%, p = 0.188). CONCLUSIONS: MRI-based radiomics analysis showed additive value to the LI-RADS v 2018 algorithm for differentiating small HCCs from benign nodules in the cirrhotic liver.

Nomograms for predicting cancer-specific and overall survival in patients with invasive extramammary Paget's disease.

Aim: To develop nomograms for predicting cancer-specific survival (CSS) and overall survival (OS) in patients with invasive extramammary Paget's disease (iEMPD). Patients & methods: Retrospective data of 1955 patients with iEMPD were collected from the Surveillance, Epidemiology, and End Results database. Nomograms for predicting CSS and OS were established using competing risk regression and Cox regression, respectively, and were internally validated. Results: Five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) clinicopathological factors were utilized to construct nomograms for predicting CSS and OS, respectively. The concordance indices of the nomograms for predicting CSS and OS were 0.78 and 0.73, respectively. The validation of the nomograms showed good calibration and discrimination. The decision curve analyses confirmed the clinical utility of these nomograms. Conclusion: The nomograms can be a reliable tool for treatment design and prognostic evaluation of iEMPD.

Lay abstract Invasive extramammary Paget's disease (iEMPD) is a rare type of cutaneous malignancy with a heterogeneous prognosis. The prognostic factors remain poorly described, resulting in unclear risk stratification of the patients with iEMPD. The purpose of this study is to identify the prognostic factors associated with cancer-specific and overall survival rates in iEMPD and to develop accurate risk stratification models to guide the design of individualized treatment regimens. Clinicopathological data of 1955 patients pathologically diagnosed with iEMPD were retrospectively collected from the Surveillance, Epidemiology, and End Results database, and were utilized for analysis and construction of models for predicting the long-term survival in patients with iEMPD. Eventually, five (age, surgery, tumor location, stage and concurrent malignancy) and eight (gender, age, race, marital status, surgery, tumor location, stage and lymph node metastasis) factors were chosen to develop models for predicting cancer-specific and overall survival, respectively. The prediction accuracy and clinical utility of the established models were confirmed in subsequent evaluation. Because iEMPD is an extremely rare disease that a lot of clinical practitioners might not be familiar with, the availability of these quantifiable predictive models will provide convenience in daily practice.

Study on preparation of acylated soy protein and stability of emulsion.

BACKGROUND: Protein can be used as an emulsifier to improve emulsion stability at the interface of water-in-oil emulsion. However, natural soybean protein isolate (SPI) does not meet the high demands as an emulsifier in the food industry. The effect of acylation modification by ethylenediaminetetraacetic dianhydride (EDTAD; 0-300 g kg-1 ) on the physicochemical properties of SPI was studied. RESULTS: The results of the Fourier transform infrared spectra analyses showed that carboxyl groups were introduced into the SPI structure by the EDTAD treatment. The carboxyl concentration of SPI was increased by 30-74.07% with an increase in EDTAD addition from 50 to 300 g kg-1 . When 150 g kg-1 EDTAD was added, the surface hydrophobicity, the emulsifying activity, and the absolute value of the zeta potential were increased by 213%, 120%, and 68% respectively, and the particle size decreased to 247 nm. The droplet size of emulsion decreased to 10 µm when pH was 6. At the same concentration of SPI and pH, the absolute value of zeta potential of the emulsion was biggest. A comparison of the emulsions during storage showed the improvement of emulsion stability was related to the increase in the zeta potential and the decrease in the average particle size. The experimental group showed no destabilization on day 21, and no obvious aggregation phenomenon was observed. CONCLUSION: Acylation modification by EDTAD changed the emulsifying properties of SPI and enhanced the stability of the SPI emulsion. © 2021 Society of Chemical Industry.

GenCLiP 3: mining human genes' functions and regulatory networks from PubMed based on co-occurrences and natural language processing.

SUMMARY: We present a web server, GenCLiP 3, which is an updated version of GenCLiP 2.0 to enhance analysis of human gene functions and regulatory networks, with the following improvements: i) accurate recognition of molecular interactions with polarity and directionality from the entire PubMed database; ii) support for Boolean search to customize multiple-term search and to quickly retrieve function related genes; iii) strengthened association between gene and keyword by a new scoring method; and iv) daily updates following literature release at PubMed FTP. AVAILABILITY: The server is freely available for academic use at: http://ci.smu.edu.cn/genclip3/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

G9a promotes cell proliferation and suppresses autophagy in gastric cancer by directly activating mTOR.

As an important methyltransferase, G9a has been reported to be abnormally expressed in various human cancers and plays essential roles in tumorigenesis. However, the biologic functions and molecular mechanisms of G9a in gastric cancer (GC) remain unclear. GC is the fifth most frequent cancer around the world and seriously threatens human health, especially in developing countries. Here, our results showed that high expression of G9a was intensively correlated with poor prognosis and more advanced stages of GCs. Knockdown of G9a or treatment with its inhibitor, BIX01294, significantly reduced cell growth by cell cycle arrest and autophagy. In addition, the mechanistic target of rapamycin (mTOR) was evidently decreased after G9a silencing or inhibition, and mTOR activation partially rescued the effects of cell proliferation inhibition and autophagy induced by G9a knockdown or inhibition. Down-regulation of G9a effectively inhibited mTOR expression and tumor growth in the xenograft tumor model of GC cells. We also showed that G9a regulates mTOR and cell proliferation and autophagy depending on its histone methylase activity. Using chromatin immunoprecipitation analysis, we found that mTOR expression was associated with promoter methylation and an enrichment for mono- and dimethylated histone 3 lys 9 (H3K9). G9a knockdown revealed an apparent decrease in H3K9 monomethylation levels, but no apparent change in H3K9 dimethylation levels at the mTOR promoter. These results indicate that G9a is a novel and promising therapeutic target for GC treatment.-Yin, C., Ke, X., Zhang, R., Hou, J., Dong, Z., Wang, F., Zhang, K., Zhong, X., Yang, L., Cui, H. G9a promotes cell proliferation and suppresses autophagy in gastric cancer by directly activating mTOR.

Pelvic insufficiency fracture or bone metastasis after radiotherapy for cervical cancer? The added value of DWI for characterization.

OBJECTIVES: We sought to determine the added value of diffusion-weighted magnetic resonance imaging (DWI) in the differentiation of pelvic insufficiency fracture (PIF) from bone metastasis after radiotherapy in cervical cancer patients. METHODS: In the present study, 42 cervical cancer patients after radiotherapy with 61 bone lesions (n = 40, PIFs; n = 21, bone metastasis) were included. Conventional MRI and DWI were performed in all patients. For qualitative imaging diagnosis, two sets of images were reviewed independently by three observers, including a conventional MRI set (unenhanced T1-weighted, T2-weighted, and enhanced T1-weighted images) and a DWI set (conventional MRIs, DW images, and ADC maps). The mean ADC value of each lesson was measured on ADC maps. The diagnostic performance was assessed by using the area under the receiver operating characteristic curve (Az), and sensitivity and specificity were determined. RESULTS: For all observers, the Az value and sensitivity of the DWI set showed improvement compared with the conventional MRI set. The observer who had the least experience (3 years) demonstrated significant improvement in diagnostic performance with the addition of DWI; Az value increased from 0.804 to 0.915 (p = 0.042) and sensitivity increased from 75.0 to 92.5% (p = 0.035). The mean ADCs of the PIFs were significantly higher than the bone metastases (p < 0.001); ADC values > 0.97 × 10-3 mm2/s yielded an Az of 0.887, a sensitivity of 92.5%, and a specificity of 76.2%. CONCLUSIONS: The addition of DWI to conventional MRI improved the differentiation of PIF from bone metastasis after RT in patients with cervical cancer. KEY POINTS: • DWI showed additive value to conventional MRI in the differentiation of PIF from bone metastasis after RT. • For qualitative diagnosis, the addition of DWI can improve diagnostic performance compared with conventional MRI alone and can particularly improve the sensitivity. • Quantitative ADC assessment showed potential value for identifying PIF from bone metastasis.

High-density lipoprotein cholesterol to low-density lipoprotein cholesterol ratio in early assessment of disease severity and outcome in patients with acute pancreatitis admitted to the ICU.

BACKGROUND: Patients with acute pancreatitis usually exhibit dyslipidemia and oxidative stress. However, the significance of high-density lipoprotein cholesterol (HDL-C) level, low-density lipoprotein cholesterol (LDL-C) level and the HDL-C/LDL-C ratio (H/L ratio) as markers for disease progression remain unknown. AIM: The aim of this study was to evaluate the role of HDL-C levels, LDL-C levels and the H/L ratio as markers of disease progression in patients admitted to the intensive cate unit with acute pancreatitis. METHODS: This retrospective study was conducted at a tertiary critical care center in China. Plasma HDL-C and LDL-C levels were measured in 166 patients with acute pancreatitis. The associations between HDL-C, LDL-C, H/L ratio, as well as other inflammatory index and mortality, were analyzed. Multivariate cox analysis based on two models was used to determine the independent prognostic factor. Predictive ability of in-hospital mortality for variables was determined using the receiver operating characteristics curves. RESULTS: Significantly higher H/L ratios at admission were observed in patients with acute pancreatitis who died compared with survivors (0.93 vs. 0.64, p < 0.001). The area under the ROC curve for H/L ratio-based prediction of mortality was 0.658. When clinical confounders were included in multivariable cox regression analysis, the association was preserved (Model A HR = 1.587, p = 0.011; Model B HR = 1.332, p = 0.032). The mortality risk in different groups defined by an H/L ratio cutoff value was significantly different, based on survival curve analysis. CONCLUSION: The H/L ratio at the time of admission to the ICU appears to be a biomarker of disease progression in patients with acute pancreatitis.

Cervical spine osteoradionecrosis or bone metastasis after radiotherapy for nasopharyngeal carcinoma? The MRI-based radiomics for characterization.

BACKGROUND: To develop and validate an MRI-based radiomics nomogram for differentiation of cervical spine ORN from metastasis after radiotherapy (RT) in nasopharyngeal carcinoma (NPC). METHODS: A radiomics nomogram was developed in a training set that comprised 46 NPC patients after RT with 95 cervical spine lesions (ORN, n = 51; metastasis, n = 44), and data were gathered from January 2008 to December 2012. 279 radiomics features were extracted from the axial contrast-enhanced T1-weighted image (CE-T1WI). A radiomics signature was created by using the least absolute shrinkage and selection operator (LASSO) algorithm. A nomogram model was developed based on the radiomics scores. The performance of the nomogram was determined in terms of its discrimination, calibration, and clinical utility. An independent validation set contained 25 consecutive patients with 47 lesions (ORN, n = 25; metastasis, n = 22) from January 2013 to December 2015. RESULTS: The radiomics signature that comprised eight selected features was significantly associated with the differentiation of cervical spine ORN and metastasis. The nomogram model demonstrated good calibration and discrimination in the training set [AUC, 0.725; 95% confidence interval (CI), 0.622-0.828] and the validation set (AUC, 0.720; 95% CI, 0.573-0.867). The decision curve analysis indicated that the radiomics nomogram was clinically useful. CONCLUSIONS: MRI-based radiomics nomogram shows potential value to differentiate cervical spine ORN from metastasis after RT in NPC.