Resolving the heterogeneous tumour microenvironment in cardiac myxoma through single-cell and spatial transcriptomics.

BACKGROUND: Cardiac myxoma (CM) is the most common (58%-80%) type of primary cardiac tumours. Currently, there is a need to develop medical therapies, especially for patients not physically suitable for surgeries. However, the mechanisms that shape the tumour microenvironment (TME) in CM remain largely unknown, which impedes the development of targeted therapies. Here, we aimed to dissect the TME in CM at single-cell and spatial resolution. METHODS: We performed single-cell transcriptomic sequencing and Visium CytAssist spatial transcriptomic (ST) assays on tumour samples from patients with CM. A comprehensive analysis was performed, including unsupervised clustering, RNA velocity, clonal substructure inference of tumour cells and cell-cell communication. RESULTS: Unsupervised clustering of 34 759 cells identified 12 clusters, which were assigned to endothelial cells (ECs), mesenchymal stroma cells (MSCs), and tumour-infiltrating immune cells. Myxoma tumour cells were found to encompass two closely related phenotypic states, namely, EC-like tumour cells (ETCs) and MSC-like tumour cells (MTCs). According to RNA velocity, our findings suggest that ETCs may be directly differentiated from MTCs. The immune microenvironment of CM was found to contain multiple factors that promote immune suppression and evasion, underscoring the potential of using immunotherapies as a treatment option. Hyperactive signals sent primarily by tumour cells were identified, such as MDK, HGF, chemerin, and GDF15 signalling. Finally, the ST assay uncovered spatial features of the subclusters, proximal cell-cell communication, and clonal evolution of myxoma tumour cells. CONCLUSIONS: Our study presents the first comprehensive characterisation of the TME in CM at both single-cell and spatial resolution. Our study provides novel insight into the differentiation of myxoma tumour cells and advance our understanding of the TME in CM. Given the rarity of cardiac tumours, our study provides invaluable datasets and promotes the development of medical therapies for CM.

A TFEB-Amplified Renal Cell Carcinoma with Long-Term, Complete Immunotherapy Response: Retrospective Support for the Value of Molecular Classification.

Recent years have seen the recognition and establishment of numerous subtypes of renal cell carcinoma (RCC), including adoption of an entire category of "molecularly defined renal carcinomas" in the fifth Edition of World Health Organization Classification. To add value, new diagnostic entities should be clinicopathologically distinct, or better, imply specific management and treatment angles, especially if adjunctive testing is needed for diagnosis. One such promising future treatment angle for a molecularly defined subtype, TFEB-amplified RCC, is immunotherapy, for which recent scholarship has demonstrated frequent expression of PD-L1. Herein, we report a case of metastatic TFEB-amplified RCC, where the patient experienced a long-term, complete response to PDL1-directed therapy, which had been serendipitously used years ago under a renal tumor subtype-agnostic indication. This promising experience suggests formal exploration of immunotherapy for these tumors.

[Heavy Metal Emissions from Coal-fired Power Plants and Heavy Metal Pollution Characteristics and Health Risks in Surrounding Soils].

The aim of this study was to reveal the influence of heavy metal emissions from the flue gas of coal-fired power plants on the surrounding soil environment. Seven heavy metals, including As, Cd, Cr, Cu, Pb, Hg, and Ni, were detected in the flue gas of six coal-fired power plants in Shijiazhuang, and the heavy metals in the soil surrounding the power plants were analyzed. The source analysis and health risk assessment of the heavy metals were carried out. The results showed that after a series of flue gas pollutant control measures, the emission concentrations of different heavy metals in the flue gas of the coal-fired power plants ranged from 0.11 to 6.32 mg·(MW·h)-1, and Cu, Cr, and Ni were the main pollutants. The total amount of the seven heavy metal elements discharged into the atmosphere by each power plant was 33.56-275.71 kg·a-1. The average contents of Cr, Cu, Pb, Hg, and Ni in the surface soil surrounding the coal-fired power plant were higher than the background values of Hebei soil, and the contents were 1.16-2.32 times higher than the background values. The heavy metal content in the soil around the power plants was proportional to the heavy metal emissions in the flue gas. The heavy metal content in the soil under different wind directions first increased and then decreased gradually with the increase in distance from the power plants. Source analysis showed that coal combustion emissions contributed the most to heavy metals in soil around the power plants (41.4%), followed by industrial emissions (23.6%) and transportation emissions (19.6%). Altogether, human activities played a leading role in soil heavy metal enrichment, accounting for 84.6%. The health risk assessment showed that the overall health risk of metal elements in the soil surrounding the power plant was within acceptable limits.

Clopidogrel versus ticagrelor in the treatment of Chinese patients undergoing percutaneous coronary intervention: effects on platelet function assessed by platelet function tests and mean platelet volume.

BACKGROUND: Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated. METHODS: Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2-3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer. RESULTS: The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 µM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P <  0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P <  0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701-0.875, P <  0.001) in receiver-operating characteristic curve analysis. CONCLUSIONS: Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.

LaTaON2 Mesoporous Single Crystals for Efficient Photocatalytic Water Oxidation and Z-Scheme Overall Water Splitting.

LaTaON2 porous single crystals (PSCs), integrating structural coherence and porous microstructures, will warrant promising photocatalytic performance. The absence of grain boundaries in PSCs ensures rapid photocarrier transportation from bulk to the surface, thereby mitigating photocarriers' recombination. Porous microstructures not only provide ample reachable surface to host photochemical reactions but also reinforce photon-matter interactions by additional photon reflection/scattering. Here, we have synthesized LaTaON2 PSCs via a topotactic route and show significantly improved photocatalytic performance. Efficient water oxidation into O2 has been realized by LaTaON2 PSCs with an apparent quantum efficiency as high as 5.7% at 420 ± 20 nm. Stable overall water splitting into stoichiometric H2 and O2 has also been achieved in a Z-scheme setup using LaTaON2 PSCs as the O2 evolution photocatalyst. These results not only prove that PSCs facilitate photocarrier migrations, which in turn deliver exceptional photocatalytic performance, but also imply that PSCs are useful to reinvigorate conventional semiconductor photocatalysts toward efficient solar energy conversions.

Utilization of Multiparametric MRI of Prostate in Patients under Consideration for or Already in Active Surveillance: Correlation with Imaging Guided Target Biopsy.

This study sought to assess the value of multiparametric magnetic resonance image (mp-MRI) in patients with a prostate cancer (PCa) Gleason score of 6 or less under consideration for or already in active surveillance and to determine the rate of upgrading by target biopsy. Three hundred and fifty-four consecutive men with an initial transrectal ultrasound-guided (TRUS) biopsy-confirmed PCa Gleason score of 6 or less under clinical consideration for or already in active surveillance underwent mp-MRI and were retrospectively reviewed. One hundred and nineteen of 354 patients had cancer-suspicious regions (CSRs) at mp-MRI. Each CSR was assigned a Prostate Imaging Reporting and Data System (PI-RADS) score based on PI-RADS v2. One hundred and eight of 119 patients underwent confirmatory imaging-guided biopsy for CSRs. Pathology results including Gleason score (GS) and percentage of specimens positive for PCa were recorded. Associations between PI-RADS scores and findings at target biopsy were evaluated using logistic regression. At target biopsy, 81 of 108 patients had PCa (75%). Among them, 77 patients had upgrading (22%, 77 of 354 patients). One hundred and forty-six CSRs in 108 patients had PI-RADS 3 n = 28, 4 n = 66, and 5 n = 52. The upgraded rate for each category of CSR was for PI-RADS 3 (5 of 28, 18%), 4 (47 of 66, 71%) and 5 (49 of 52, 94%). Using logistic regression analysis, differences in PI-RADS scores from 3 to 5 are significantly associated with the probability of disease upgrade (20%, 73%, and 96% for PI-RADS score of 3, 4, and 5, respectively). Adding mp-MRI to patients under consideration for or already in active surveillance helps to identify undiagnosed PCa of a higher GS or higher volume resulting in upgrading in 22%.

Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel.

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

Deep Neural Networks for the Classification of Pure and Impure Strawberry Purees.

In this paper, a comparative study of the effectiveness of deep neural networks (DNNs) in the classification of pure and impure purees is conducted. Three different types of deep neural networks (DNNs)-the Gated Recurrent Unit (GRU), the Long Short Term Memory (LSTM), and the temporal convolutional network (TCN)-are employed for the detection of adulteration of strawberry purees. The Strawberry dataset, a time series spectroscopy dataset from the UCR time series classification repository, is utilized to evaluate the performance of different DNNs. Experimental results demonstrate that the TCN is able to obtain a higher classification accuracy than the GRU and LSTM. Moreover, the TCN achieves a new state-of-the-art classification accuracy on the Strawberry dataset. These results indicates the great potential of using the TCN for the detection of adulteration of fruit purees in the future.

Serum chloride as a novel marker for adding prognostic information of mortality in chronic heart failure.

BACKGROUND: Serum chloride concentrations have clinical significance in the prognosis of heart failure (HF). Little is known regarding the prognostic value of serum chloride in patients with chronic heart failure (CHF). This study sought to investigate the prognostic ability of admission serum chloride for long-term mortality in CHF patients. METHODS: We identified 1021 consecutive patients diagnosed with CHF. Participants were followed up for all-cause mortality at 21 ±â€¯9 months to establish the survival models and analyze the association between admission serum chloride concentrations and death risk. RESULTS: Of the 1021 patients, 905(88.6%) available cases were obtained. Admission serum chloride concentrations of patients were independently and inversely associated with long-term mortality (hazard ratio [HR]: 0.890; 95% CI: 0.863 to 0.918; p < 0.001). After multivariable risk adjustment for age, male sex, history of diabetes, LVEF, loop diuretic use, beta-blocker use, ACEI or ARB use, eGFR and NT-proBNP, chloride concentrations remained independently associated with mortality (HR:0.922; 95% CI:0.887 to 0.958; p < 0.001) but not independent of sodium concentrations (HR: 0.953; 95% CI: 0.900 to 1.009; p = 0.095). The optimal cut-off value of chloride concentrations predicting death was 102.8 mmol/l with an area under the curve (AUC) value of 0.686 (95% CI: 0.635 to 0.737; p < 0.001), with a sensitivity of 62% and specificity of 70%. The lower chloride concentrations could significantly increase the risk ratio of CHF patients in the setting of hyponatremia (p < 0.001). The cumulative survival estimates significantly differed across Na/Cl quartiles (log-rank χ2 19.14, p < 0.001), with higher mortality for higher Na/Cl ratio. Correlation analysis showed a positive correlation between serum chloride concentrations and sodium concentrations (r = 0.598; p < 0.001). An increased AUC was observed by combining chloride and sodium (AUC = 0.704, 95% CI:0.655-0.754, p < 0.001) compared to sodium only (AUC = 0.689, 95% CI:0.639-0.739, p < 0.001). CONCLUSIONS: In a Chinese Han population, admission serum chloride concentrations are inversely associated with all-cause mortality of CHF patients and provide incremental prognostic information of serum sodium.

Diagnosis of typical and atypical transition zone prostate cancer and its mimics at multiparametric prostate MRI.

Many of the current clinical screening methods for prostate cancer (PCa) such as prostate-specific antigen (PSA) testing or transrectal ultrasound-guided prostate biopsy lack sensitivity and specificity for diagnosis of PCa of the transition zone (TZ). Recent technical advances in multiparametric-MRI have markedly improved detection of PCa of the TZ. However, there are many diagnostic challenges that we still encounter in our daily practice that compromise the accuracy of the diagnosis. By performing both MRI-guided and ultrasound/MRI fusion-guided biopsies, we have gained extensive experience in the diagnosis of PCa of the TZ. Biopsy-proven examples including but not limited to typical and atypical PCa of the TZ as well as a wide variety of its mimics will be presented. Recognition of the MR features of typical and atypical PCa of the TZ and its mimics on multiparametric-MRI along with findings that help to differentiate these mimics from PCa is important in establishing an accurate diagnosis and in guiding clinical management.

A novel PROS1 mutation, c.74dupA, was identified in a protein S deficiency family.

Protein S is a vitamin K-dependent plasma glycoprotein that acts as an anticoagulant, and its deficiency usually predisposes individuals to venous thromboembolism. Hereditary protein S deficiency is an autosomal dominant disorder caused by a PROS1 mutation. Herein, we described a novel PROS1 frameshift mutation, c.74dupA, in a hereditary protein S deficiency family. Interestingly, both of the proband and his mother carried the mutation and had a protein S deficiency, however, only the proband suffered a pulmonary embolism while his mother had no history of any thrombosis, suggesting that a triggering event might have been involved in the thrombus formation. Therefore, genetic testing of PROS1 appeared important for the early diagnosis of hereditary protein S deficiency, and it allowed the application of prophylactic interventions to prevent the incidence of severe thrombosis.

Multiparametric prostate MRI: focus on T2-weighted imaging and role in staging of prostate cancer.

Multiparametric MRI (mpMRI) represents a growing modality for the non-invasive evaluation of prostate cancer (PCa) and is increasingly being used for patients with persistently elevated PSA and prior negative biopsies, for monitoring patients in active surveillance protocols, for preoperative characterization of cancer for surgical planning, and in planning for MRI-targeted biopsy. The focus of this work is twofold. First, we review the key role of T2-weighted imaging (T2WI) in mpMRI, specifically outlining how it is used for anatomic evaluation of the prostate, detection of clinically significant PCa, assessment of extraprostatic extension (EPE), and mimics of PCa on this sequence. We will also discuss optimal technical acquisition parameters for this sequence and recent technical advancements in T2WI. Second, we will delineate the role that mpMRI plays in the staging of PCa and describe the implications of the information that mpMRI can provide in determining the most appropriate management plan for the patient with PCa.

Benign causes of diffusion restriction foci in the peripheral zone of the prostate: diagnosis and differential diagnosis.

Multiparametric-MRI is an important tool in the diagnosis of prostate cancer (PCa), particularly diffusion-weighted imaging for peripheral zone (PZ) cancer in the untreated prostate. However, there are many benign entities that demonstrate diffusion restriction in the PZ mimicking PCa resulting in diagnostic challenges. Fortunately, these benign entities usually have unique MR features that may help to distinguish them from PCa. The purpose of this pictorial review is to discuss benign entities with diffusion restriction in the PZ and to emphasize the key MR features of these entities that may help to differentiate them from PCa.

Pictorial review. Diagnosis of recurrent prostate cancer and its mimics at multiparametric prostate MRI.

Biochemical recurrence after treatment for prostate cancer (PCa) is a significant issue. Early diagnosis of local recurrence is important for making prompt treatment decisions and is strongly associated with patient prognosis. Without salvage therapy, the average time from development of local recurrence to distant metastasis is approximately 3 years. Biochemical recurrence does not differentiate local recurrence from systemic disease; there is no reliable way to clinically diagnose local recurrence. Recent advances in multiparametric MRI (mp-MRI) techniques have markedly improved detection of local recurrence following therapy. However, a wide variety of entities can mimic recurrent PCa at mp-MRI. Therefore, the purpose of this pictorial review is to discuss the MRI findings of locally recurrent PCa and its mimics, emphasizing the key MRI features that help to differentiate local recurrence from its mimics.

Differences in the predictive value of red cell distribution width for the mortality of patients with heart failure due to various heart diseases.

BACKGROUND: Increased red blood cell distribution width (RDW) is associated with adverse outcomes in patients with heart failure (HF). The objective of this study was to compare the differences in the predictive value of RDW in patients with HF due to different causes. METHODS: We retrospectively investigated 1,021 HF patients from October 2009 to December 2011 at Fuwai Hospital (Beijing, China). HF in these patients was caused by three diseases; coronary heart disease (CHD), dilated cardiomyopathy (DCM) and valvular heart disease (VHD). Patients were followed-up for 21 ± 9 months. RESULTS: The RDW, mortality and survival duration were significantly different among the three groups. Kaplan-Meier analysis showed that the cumulative survival decreased significantly with increased RDW in patients with HF caused by CHD and DCM, but not in those with HF patients caused by VHD. In a multivariable model, RDW was identified as an independent predictor for the mortality of HF patients with CHD (P < 0.001, HR 1.315, 95% CI 1.122-1.543). The group with higher N-terminal pro-brain natriuretic peptide (NT-proBNP) and higher RDW than median had the lowest cumulative survival in patients with HF due to CHD, but not in patients with HF due to DCM. CONCLUSIONS: RDW is a prognostic indicator for patients with HF caused by CHD and DCM; thus, RDW adds important information to NT-proBNP in CHD caused HF patients.

Pancreatitis in patients with pancreas divisum: imaging features at MRI and MRCP.

AIM: To determine the magnetic resonance cholangiopancreatography (MRCP) and magnetic resonance imaging (MRI) features of pancreatitis with pancreas divisum (PD) and the differences vs pancreatitis without divisum. METHODS: Institutional review board approval was obtained and the informed consent requirement was waived for this HIPAA-compliant study. During one year period, 1439 consecutive patients underwent successful MRCP without injection of secretin and abdominal MRI studies for a variety of clinical indications using a 1.5 T magnetic resonance scanner. Two experienced radiologists retrospectively reviewed all the studies in consensus. Disputes were resolved via consultation with a third experienced radiologist. The assessment included presence and the imaging findings of PD, pancreatitis, and distribution of abnormalities. The pancreatitis with divisum constituted the study group while the pancreatitis without divisum served as the control group. MRCP and MRI findings were correlated with final diagnosis. Fisher exact tests and Pearson × 2 tests were performed. RESULTS: Pancreatitis was demonstrated at MRCP and MRI in 173 cases (38 cases with and 135 cases without divisum) among the 1439 consecutive cases. The recurrent acute pancreatitis accounted for 55.26% (21 of 38) in pancreatitis patients associated with PD, which was higher than 6.67% (9 of 135) in the control group, whereas the chronic pancreatitis was a dominant type in the control group (85.19%, 115 of 135) when compared to the study group (42.11%, 16 of 38) (χ(2) = 40.494, P < 0.0001). In cases of pancreatitis with PD, the dorsal pancreatitis accounted for a much higher percentage than that in pancreatitis without PD (17 of 38, 44.74% vs 30 of 135, 22.22%) (χ(2) = 7.257, P < 0.05). CONCLUSION: MRCP and MRI can depict the features of pancreatitis associated with divisum. Recurrent acute pancreatitis and isolated dorsal involvement are more common in patients with divisum.

MRI in the workup of biliary tract filling defects.

Recent advances in magnetic resonance imaging (MRI) have made imaging the biliary tract faster while providing excellent anatomic reproduction of this duct system. MRI/MR-cholangiopancreatography (MRCP) has now become the first-line imaging procedure for many biliary tract problems. This work briefly discusses the MR techniques for biliary tree imaging and reviews MRI's role in the numerous diagnoses of filling defects in the biliary tract.

Novel one-component positive-tone chemically amplified i-line molecular glass photoresists.

Maleopimaric acid, cycloaddition reaction product of rosin with maleic anhydride, was reacted with hydroxylamine to afford N-hydroxy maleopimarimide, which was then further esterified with 2-diazo-1-naphthoquinone-4-sulfonyl chloride (2,1,4-DNQ-Cl) to give N-hydroxy maleopimarimide sulfonate. The carboxylic acid group of the compound was then protected by the reaction of this compound with vinyl ether compounds to give the corresponding molecular glass compounds. Upon irradiation to 365 nm light, the 2,1,4-DNQ group undergo photolysis not only to be converted into indene carboxylic acid but also generate a few amount of sulfonic acid which can catalyze the deprotection of the acid labile group. So, novel one-component positive-tone chemically amplified i-line photoresists can be formed by the molecular glass compounds. The lithographic performance of the resists was evaluated using i-line exposure system with high photosensitivity and resolution.

Blunt bowel and mesenteric injury: MDCT diagnosis.

Multidetector computed tomography (MDCT) has emerged as the imaging modality of choice for evaluating the abdomen and pelvis in trauma patients. MDCT readily detects injury of the solid organs as well as direct and indirect features of bowel and/or mesenteric injury-an important advance given that unrecognized bowel and mesenteric injuries may result in high morbidity and mortality. Nonetheless, challenges persist in the interpretation of abdominal and pelvic CT images in trauma patients. Difficulty in interpretation may result from lack of familiarity with or misunderstanding of CT features of bowel and/or mesenteric injury. Moreover, due to major technical advances afforded by MDCT, new CT features of bowel and/or mesenteric injuries have been recognized. Beading and termination of mesenteric vessels indicating surgically important mesenteric injury is an example of one of these new features. MDCT also allows for the detection of small or trace amounts of isolated intraperitoneal fluid in trauma patients, although the clinical management of these patients is still controversial. This pictorial essay illustrates the spectrum of typical, atypical, and newly reported MDCT features of bowel and mesenteric injuries due to blunt trauma. The features that help to differentiate these injuries from pitfalls are emphasized in these proven cases.