To assist the ultrasound (US) differential diagnosis of solid breast tumors by using stepwise logistic regression (SLR) analysis of tumor contour features, we retrospectively reviewed 111 medical ...records of digitized US images of breast pathologies. They were pathologically proved benign breast tumors from 40 patients (
i.e., 40 fibroadenomas) and malignant breast tumors from 71 patients (
i.e., 71 infiltrative ductal carcinomas). Radiologists, before analysis by the computer-aided diagnosis (CAD) system, segmented the tumors manually. The contour features were calculated by measuring the radial length of tumor boundaries. The features selection process was accomplished using a stepwise analysis procedure. Then, an SLR model with contour features was used to classify tumors as benign or malignant. In this experiment, cases were sampled with “leave-one-out” test methods to evaluate the SLR performance using a receiver operating characteristic (ROC) curve. The accuracy of our SLR model with contour features for classifying malignancies was 91.0% (101 of 111 tumors), the sensitivity was 97.2% (69 of 71), the specificity was 80.0% (32 of 40), the positive predictive value was 89.6% (69 of 77), and the negative predictive value was 94.1% (32 of 34). The CAD system using SLR can differentiate solid breast nodules with relatively high accuracy and its high negative predictive value could potentially help inexperienced operators to avoid misdiagnoses. Because the SLR model is trainable, it could be optimized if a larger set of tumor images were supplied.
We hypothesized that specific molecular mutations are important biomarkers for response to DNA methyltransferase inhibitors (DNMT inhibitors) and may have prognostic value in patients with ...myelodysplastic syndromes (MDS). Mutational analysis was performed in 92 patients with MDS and related disorders who received 5-azacytidine (n=55), decitabine (n=26) or both (n=11). Mutational status was correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analysis. Risk stratification models were created. TET2, DNMT3A, IDH1/IDH2, ASXL1, CBL, RAS and SF3B1 mutations were found in 18, 9, 8, 26, 3, 2 and 13% of patients, respectively. In multivariate analysis, TET2(MUT) and/or DNMT3A(MUT) (P=0.03), platelets > or = 100 × 10(9)/l (P=0.007) and WBC<3.0 × 10(9)/l (P=0.03) were independent predictors of better response. TET2(MUT) and/or DNMT3A(MUT) (P=0.04) status was also independently prognostic for improved PFS, as were good or intermediate cytogenetic risk (P<0.0001), age<60 (P=0.0001), treatment with both 5-azacytidine and decitabine (P=0.02) and hemoglobin > or = 10 g/dl (P=0.01). Better OS was associated with ASXL1(WT) (P=0.008) and SF3B1(MUT) (P=0.01), and, similar to PFS, cytogenetic risk (P=0.0002), age (P=0.02) and hemoglobin (P=0.04). These data support the role of molecular mutations as predictive biomarkers for response and survival in MDS patients treated with DNMT inhibitors.
The therapeutic effect of ultrasonographically guided aspiration of a ganglion cyst of the shoulder is evaluated. Fifteen patients (nine male, six female) with chronic shoulder pain were enrolled in ...this study. Each patient was referred to rule out rotator cuff lesion. The ultrasonographic examination showed an anechoic cystic lesion in the shoulder region in every patient and abnormality of the rotator cuff in only four patients. Under ultrasonographic guidance, an 18 gauge needle was inserted into the cyst to aspirate the fluid. Initial sonographic imaging showed the cyst, which appeared as a localized fluid accumulation and was located between the deltoid muscle and the subscapularis tendon in seven patients, between the deltoid muscle and the biceps tendon in one patient, below the coracoacromial ligament in five patients, and over suprascapular notch area in one patient. The ganglion cysts ranged in size from 3.5 to 30 mm. The amount of aspirated fluid in each cyst varied from 0.4 to 12 ml (mean, 2.6 ml +/- 3.1) with a clear or light yellowish color and a jelly-like appearance. No major complications occurred during or after this procedure. The symptom (pain) was improved after sonographically guided aspiration in each patient. Follow-up study showed complete relief of pain in four patients, marked improvement in nine patients, and mild improvement but still persistent shoulder pain in two patients. Duration of follow-up study ranged from 2 to 24 months (mean, 6.4 months +/- 6.9). The success rate for sonographically guided aspiration was 86% on the basis of marked symptom improvement or relief. Ultrasonographically guided aspiration of shoulder ganglion cysts is an effective procedure in the management of shoulder pain caused by ganglion cysts.
Capecitabine is an orally administered pro-drug of 5-fluorouracil that confers superior disease-free survival and presumably has a more favourable side-effect profile. Here we report on a patient who ...developed acute necrotising pancreatitis and very high triglyceride levels as well as hand-foot syndrome after receiving capecitabine for colonic cancer. Increased awareness of this potential side-effect and close monitoring of lipid levels may be warranted, especially in patients who have other conditions predisposing them to severe secondary hyperlipidaemia when using this drug.
Background: To describe the prevalence and sonographic findings and ultrasound diagnostic accuracy of the right side colonic diverticulitis in patients having right lower abdominal pain with ...indeterminate nature.
Methods: A total of 934 patients with acute right lower abdominal pain of clinically indeterminate nature were referred for ultrasound examination (US). US studies were performed with 3.5 to 7.0 (or occasionally 10) MHz transducers using graded compression method. Twenty-three patients were finally diagnosed to have an uncomplicated acute diverticulitis of the right colon. The gray-scale sonographic images were reviewed. A retrospective study was undertaken to evaluate diagnostic contribution of US.
Results: The prevalence of acute right side colonic diverticulitis was 2.5% in patients with clinically indeterminate acute right lower abdominal pain. Locations of the inflamed diverticula include cecum in 6 patients, proximal ascending colon in 15 patients, and distal ascending colon in only 2 patients. Sonography detected 21 inflammed diverticula with 1 false positive and 2 false negative results. The most typical sonographic feature of an inflamed diverticulum of right side colon was a rounded or oval-shaped hypoechoic or nearly anechoic structure (52%) protruding out from the segmentally thickened colonic wall. Some of them might contain strong echoes representing gas or feces (43%), or stone in the lumen (5%). Regional pericolic or peridiverticular fat thickening was noted in 57% of patients, and segmental colon wall thickening in 38%. US examination yielded a sensitivity of 91.3%, a specificity of 99.8%, an overall accuracy of 99.5%, a positive predictive value of 95.5%, and a negative predictive value of 99.7%. A positive sonogram made the likelihood of acute right side diverticulitis 456.5 times greater compared with the pretest clinical impression. US differentiated acute right side colonic diverticulitis from acute appendicitis with a 100% accuracy.
Conclusions: Ultrasound can be extremely useful in diagnosing acute right side colonic diverticulitis. Careful ultrasound evaluation of the right colon and the cecum may facilitate a correct diagnosis and help differentiate from acute apprendicitis, and steer the surgeon to a more effective management.
The purpose of this study was to evaluate the morphologic changes in the ulnar nerve in cubital tunnel syndrome with high-resolution ultrasonography. The mean values of the short axis (cm) x long ...axis (cm) at the arm, epicondyle, and forearm levels were 0.057 +/- 0.01, 0.068 +/- 0.019, and 0.062 +/- 0.01 in control group; 0.069 +/- 0.04, 0.139 +/- 0.06, and 0.066 +/- 0.023 in the symptomatic side in patients with cubital tunnel syndrome; and 0.063 +/- 0.029, 0.068 +/- 0.029, and 0.057 +/- 0.012 in the normal side in patients with cubital tunnel syndrome. No significant difference was found in the area (short axis x long axis) of the ulnar nerve at the arm, epicondyle and forearm levels between the left and right ulnar nerve in the control group and between the control group and the normal side in symptomatic patients. However, the mean value of the area of the ulnar nerve at the epicondyle level in symptomatic patients was significantly larger than that of the control group and that of the contralateral side in patients, and the P value was less than 0.001. High resolution ultrasonography can detect morphologic changes in the ulnar nerve accurately, and it could therefore be useful as a screening and even follow-up modality in patients with cubital tunnel syndrome.
The MAVEN SupraThermal And Thermal Ion Compostion (STATIC) instrument is designed to measure the ion composition and distribution function of the cold Martian ionosphere, the heated suprathermal tail ...of this plasma in the upper ionosphere, and the pickup ions accelerated by solar wind electric fields. STATIC operates over an energy range of 0.1 eV up to 30 keV, with a base time resolution of 4 seconds. The instrument consists of a toroidal “top hat” electrostatic analyzer with a
360
∘
×
90
∘
field-of-view, combined with a time-of-flight (TOF) velocity analyzer with
22.5
∘
resolution in the detection plane. The TOF combines a
−
15
kV
acceleration voltage with ultra-thin carbon foils to resolve
H
+
,
He
+
+
,
He
+
,
O
+
,
O
2
+
, and
CO
2
+
ions. Secondary electrons from carbon foils are detected by microchannel plate detectors and binned into a variety of data products with varying energy, mass, angle, and time resolution. To prevent detector saturation when measuring cold ram ions at periapsis (
∼
10
1
1
eV/cm
2
s
sr
eV
), while maintaining adequate sensitivity to resolve tenuous pickup ions at apoapsis (
∼
10
3
eV/cm
2
s
sr
eV
), the sensor includes both mechanical and electrostatic attenuators that increase the dynamic range by a factor of
10
3
. This paper describes the instrument hardware, including several innovative improvements over previous TOF sensors, the ground calibrations of the sensor, the data products generated by the experiment, and some early measurements during cruise phase to Mars.
Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and ...myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation.
Therapeutic mRNAs and vaccines are being developed for a broad range of human diseases, including COVID-19. However, their optimization is hindered by mRNA instability and inefficient protein ...expression. Here, we describe design principles that overcome these barriers. We develop an RNA sequencing-based platform called PERSIST-seq to systematically delineate in-cell mRNA stability, ribosome load, as well as in-solution stability of a library of diverse mRNAs. We find that, surprisingly, in-cell stability is a greater driver of protein output than high ribosome load. We further introduce a method called In-line-seq, applied to thousands of diverse RNAs, that reveals sequence and structure-based rules for mitigating hydrolytic degradation. Our findings show that highly structured "superfolder" mRNAs can be designed to improve both stability and expression with further enhancement through pseudouridine nucleoside modification. Together, our study demonstrates simultaneous improvement of mRNA stability and protein expression and provides a computational-experimental platform for the enhancement of mRNA medicines.
Nanostructured mesoscale materials find wide-ranging applications in medicine and energy. Top-down manufacturing schemes are limited by the smallest dimension accessible; therefore, we set out to ...study a bottom-up approach mimicking biological systems, which self-assemble into systems that orchestrate complex energy conversion functionalities. Inspired by nature, we turned toward protein-based nanoparticle structures formed by plant viruses, specifically the cowpea mosaic virus (CPMV). We report the formation of hierarchical CPMV nanoparticle assemblies on colloidal-patterned, conducting polymer arrays using a protocol combining colloidal lithography, electrochemical polymerization, and electrostatic adsorption. In this approach, a hexagonally close-packed array of polystyrene microspheres was assembled on a conductive electrode to function as the sacrificial colloidal template. A thin layer of conducting polypyrrole material was electrodeposited within the interstices of the colloidal microspheres and monitored in situ using electrochemical quartz crystal microbalance with dissipation (EC-QCM-D). Etching the template revealed an inverse opaline conducting polymer pattern capable of forming strong electrostatic interactions with CPMV and therefore enabling immobilization of CPMV on the surface. The CPMV–polymer films were characterized by atomic force microscopy (AFM) and X-ray photoelectron spectroscopy (XPS). Furthermore, molecular probe diffusion experiments revealed selective ion transport properties as a function of the presence of the CPMV nanoparticles on the surface. Lastly, by utilizing its electromechanical behavior, the polymer/protein membrane was electrochemically released as a free-standing film, which can potentially be used for developing high surface area cargo delivery systems, stimuli-responsive plasmonic devices, and chemical and biological sensors.
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