Our aim is to define the capabilities of radiomics and machine learning in predicting pseudoprogression development from pre-treatment MR images in a patient cohort diagnosed with high grade gliomas. ...In this retrospective analysis, we analysed 131 patients with high grade gliomas. Segmentation of the contrast enhancing parts of the tumor before administration of radio-chemotherapy was semi-automatically performed using the 3D Slicer open-source software platform (version 4.10) on T1 post contrast MR images. Imaging data was split into training data, test data and an independent validation sample at random. We extracted a total of 107 radiomic features by hand-delineated regions of interest (ROI). Feature selection and model construction were performed using Generalized Boosted Regression Models (GBM). 131 patients were included, of which 64 patients had a histopathologically proven progressive disease and 67 were diagnosed with mixed or pure pseudoprogression after initial treatment. Our Radiomics approach is able to predict the occurrence of pseudoprogression with an AUC, mean sensitivity, mean specificity and mean accuracy of 91.49% 86.27%, 95.89%, 79.92% 73.08%, 87.55%, 88.61% 85.19%, 94.44% and 84.35% 80.19%, 90.57% in the full development group, 78.51% 75.27%, 82.46%, 66.26% 57.95%, 73.02%, 78.31% 70.48%, 84.19% and 72.40% 68.06%, 76.85% in the testing group and finally 72.87% 70.18%, 76.28%, 71.75% 62.29%, 75.00%, 80.00% 69.23%, 84.62% and 76.04% 69.90%, 80.00% in the independent validation sample, respectively. Our results indicate that radiomics is a promising tool to predict pseudo-progression, thus potentially allowing to reduce the use of biopsies and invasive histopathology.
► High quality biochar can be produced from safflower seed press cake by pyrolysis. ► Temperature has a stronger effect on structure of biochars than heating rate. ► HHV, pH, fixed carbon, ash and ...carbon contents of biochar increased at 600°C. ► SPC biochar can be used as a chemical feedstock for industrial purpose.
Biochar is carbon-rich product generated from biomass through pyrolysis. In this study, the effects of pyrolysis temperature and heating rate on the yield and physicochemical and morphological properties of biochars obtained from safflower seed press cake were investigated. The results showed that the biochar yield and quality depend principally on the applied temperature where pyrolysis at 600°C leaves a biochar with higher fixed carbon content (80.70%) and percentage carbon (73.75%), and higher heating value (30.27MJkg−1) in comparison with the original feedstock (SPC) and low volatile matter content (9.80%). The biochars had low surface areas (1.89–4.23m2/g) and contained predominantly aromatic compounds. The biochar could be used for the production of activated carbon, in fuel applications, and water purification processes.
Our aim is to investigate the added value of automated machine learning (AutoML) for potential future applications in cancer diagnostics. Using two important diagnostic questions, the non-invasive ...determination of IDH mutation status and ATRX status, we analyze whether it is possible to use AutoML to develop models that are comparable in performance to conventional machine learning models (ML) developed by experts. For this purpose, we develop AutoML models using different feature preselection methods and compare the results with previously developed conventional ML models. The cohort used for our study comprises T2-weighted MRI images of 124 patients with histologically confirmed gliomas. Using AutoML, we were able to develop sophisticated models in a very short time with only a few lines of computer code. In predicting IDH mutation status, we obtained a mean AUC of 0.7400 and a mean AUPRC of 0.8582. ATRX mutation status was predicted with very similar discriminatory power, with a mean AUC of 0.7810 and a mean AUPRC of 0.8511. In both cases, AutoML was even able to achieve a discriminatory power slightly above that of the respective conventionally developed models in a very short computing time, thus making such methods accessible to non-experts in the near future.
Background and objective
The diagnosis and treatment of benign tumors of the gallbladder and bile ducts are difficult due to their anatomical relationships with neighboring vital organs. Hemangiomas ...are non-epithelial benign tumors of the gallbladder. The gallbladder is an extremely rare localization for cavernous hemangiomas. To date, 7 cases of cavernous gallbladder hemangioma have been reported in the literature. Although it is seen very rarely, the main problem is that it mimics malignant lesions. Pre-operative diagnosis of gallbladder hemangiomas is difficult. Ultrasound (US), computed tomography (CT) magnetic resonance imaging(MRI), endoscopic ultrasound (EUS), and angiography are helpful in differential diagnosis.
Here, we aimed to present our case, which is the first case of cavernous gallbladder hemangioma and obstructive jaundice in the literature.
Case presentation
A 49-year-old female patient was admitted with the complaint of pain in the right upper quadrant of her abdomen. Bilirubin levels were high due to obstructive jaundice. Abdominal CT and MRI showed an appearance in favor of hemangioma in the gallbladder. There was an increase in bile duct wall thickness on MRCP, and it was evaluated as suspicious for malignant neoplasia. The patient was operated on, and extrahepatic bile duct resection + Roux-en-Y hepaticojejunostomy procedure was performed. As a result of histopathology, hemangioma was detected in the gallbladder. There was no malignancy in the bile ducts.
Conclusion
It should be kept in mind that the mass detected in the gallbladder in a patient with jaundice who is suspected of having a bile duct tumor may also be a hemangioma.
To determine if mexiletine is safe and effective in reducing myotonia in myotonic dystrophy type 1 (DM1).
Myotonia is an early, prominent symptom in DM1 and contributes to decreased dexterity, gait ...instability, difficulty with speech/swallowing, and muscle pain. A few preliminary trials have suggested that the antiarrhythmic drug mexiletine is useful, symptomatic treatment for nondystrophic myotonic disorders and DM1.
We performed 2 randomized, double-blind, placebo-controlled crossover trials, each involving 20 ambulatory DM1 participants with grip or percussion myotonia on examination. The initial trial compared 150 mg of mexiletine 3 times daily to placebo, and the second trial compared 200 mg of mexiletine 3 times daily to placebo. Treatment periods were 7 weeks in duration separated by a 4- to 8-week washout period. The primary measure of myotonia was time for isometric grip force to relax from 90% to 5% of peak force after a 3-second maximum grip contraction. EKG measurements and adverse events were monitored in both trials.
There was a significant reduction in grip relaxation time with both 150 and 200 mg dosages of mexiletine. Treatment with mexiletine at either dosage was not associated with any serious adverse events, or with prolongation of the PR or QTc intervals or of QRS duration. Mild adverse events were observed with both placebo and mexiletine treatment.
Mexiletine at dosages of 150 and 200 mg 3 times daily is effective, safe, and well-tolerated over 7 weeks as an antimyotonia treatment in DM1.
This study provides Class I evidence that mexiletine at dosages of 150 and 200 mg 3 times daily over 7 weeks is well-tolerated and effective in reducing handgrip relaxation time in DM1.
1. The purpose of the present research was to detect the efficacies of various vinegars (aronia, grape and hawthorn) used as marination solutions on the physicochemical, technological, textural and ...sensory properties of spent chicken meat. The pH, colour parameters, cooking loss, marinade absorption, yield, texture (TPA and MORS), characteristics via scanning electron microscopy (SEM) and sensory properties of marinated spent chicken samples were determined.
2. Marination solutions used in the treatment groups were prepared with aronia, grape and hawthorn vinegars. The samples were agitated by hand to provide even dispersion of the solid ingredients in the marinades and were kept at 4°C for 24 h.
3. The pH values of the samples were between 4.70 and 6.04. Marination with various marination solutions caused significant differences in terms of the a* and b* values of samples (P < 0.05). While marination with aronia vinegar decreased the b value of the samples, the use of grape and hawthorn vinegars in the marination solutions increased this value.
4. Hardness and chewiness were the lowest in samples marinated with grape vinegar (P < 0.05) and were 135.14 and 48.79 N, respectively. As a result of marination with various vinegars, there was a significant (P < 0.05) decrease in the MORSF and MORSE values.
5. Marinade absorption values decreased by marination with various vinegars. The highest yield values were found in the samples marinated with hawthorn vinegar (P < 0.05). The SEM indicated that marination with aronia, grape and hawthorn vinegar caused larger gaps between muscle fibres compared to the control samples.
6. Samples marinated with vinegars had higher texture scores compared with the control. Consequently, the marination with vinegars such as aronia, grape and hawthorn has the potential to improve the technical and textural properties of spent chicken meat.
Antagonist anti‐CD28 antibodies prevent T cell costimulation and differentiate from CTLA4Ig since they cannot block CTLA‐4 and PDL‐1 coinhibitory signals. They demonstrated efficacy in suppressing ...effector T cells while enhancing regulatory T cells function and immune tolerance. However, anti‐CD28 antibodies devoid of immunotoxicity and with a good pharmacokinetic profile have not yet been developed. Here, we describe FR104, a novel humanized pegylated anti‐CD28 Fab′ antibody fragment presenting a long elimination half‐life in monkeys. In vitro, FR104 failed to induce human T cell proliferation and cytokines secretion, even in the presence of anti‐CD3 antibodies or when cross‐linked with secondary antibodies. Furthermore, in humanized NOD/SCID mice adoptively transferred with human PBMC, whereas superagonist and divalent antibodies elicited rapid cytokines secretion and human T cell activation, FR104 did not. These humanized mice developed a florid graft‐versus‐host disease, which was prevented by administration of FR104 in a CTLA4‐dependent manner. Interestingly, administration of high doses of CTLA4‐Ig was ineffective to prevent GVHD, whereas administration of low doses was partially effective. In conclusion, we demonstrated that FR104 is devoid of agonist activity on human T cells and thus compatible with a clinical development that might lead to higher therapeutic indexes, by sparing CTLA‐4, as compared to CD80/CD86 antagonists.
FR104 is a novel monovalent Fab′ antagonist anti‐CD28 antibody that shows complete absence of immunotoxicity and demonstrates efficacy to fight acute graft‐versus‐host disease in a humanized mouse model.
Hypercalcaemic crisis is a rare manifestation of hyperparathyroidism and occurs in 1.6-6% of patients with primary hyperparathyroidism (pHPT). Although such high serum calcium levels (>14mg/dl) are ...attributed to malignancy, it is also associated with benign disease of the parathyroid glands. The aim of this study was to evaluate the clinical features and treatment modalities of patients with severe hypercalcaemia who underwent surgery for pHPT.
The medical records of 537 patients who underwent parathyroidectomy in our department for pHPT between 2005 and 2019 were reviewed retrospectively. Twenty-four (4.4%) of the patients were described as having severe hypercalcaemia.
Among 24 patients, 71% were female and the mean age was 55.7 years (range: 40-71 years). The mean serum calcium level at time of diagnosis was 15.9mg/dl (range: 14-22.7mg/dl). According to postoperative pathology reports, solitary adenoma, parathyroid cancer and parathyromatosis were diagnosed with the rates of 87.5%, 8.3% and 4.1% respectively. The mean weight of the solitary parathyroid lesions was 14.9g (standard deviation: 8.9g, range: 4-38g). The mean longest diameter was 2.87cm (standard deviation: 1.4cm, range: 1-5.5cm). Serum calcium levels were within the normal range on the first postoperative day in 75% of the cases.
Severe hypercalcaemia is a rare but urgent condition of pHPT and requires prompt management. Accelerated surgery after adequate medical treatment should be performed. It is important to emphasise that giant adenoma, which is a benign disease, may be a more common cause of severe hypercalcaemia than carcinoma, unlike previously thought.
Regarding the 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors, the isocitrate dehydrogenase (
) mutation status is one of the most important factors for CNS ...tumor classification. The aim of our study is to analyze which of the commonly used magnetic resonance imaging (MRI) sequences is best suited to obtain this information non-invasively using radiomics-based machine learning models. We developed machine learning models based on different MRI sequences and determined which of the MRI sequences analyzed yields the highest discriminatory power in predicting the
mutation status.
In our retrospective IRB-approved study, we used the MRI images of 106 patients with histologically confirmed gliomas. The MRI images were acquired using the T1 sequence with and without administration of a contrast agent, the T2 sequence, and the Fluid-Attenuated Inversion Recovery (FLAIR) sequence. To objectively compare performance in predicting the
mutation status as a function of the MRI sequence used, we included only patients in our study cohort for whom MRI images of all four sequences were available. Seventy-one of the patients had an
mutation, and the remaining 35 patients did not have an
mutation (
wild-type). For each of the four MRI sequences used, 107 radiomic features were extracted from the corresponding MRI images by hand-delineated regions of interest. Data partitioning into training data and independent test data was repeated 100 times to avoid random effects associated with the data partitioning. Feature preselection and subsequent model development were performed using Random Forest, Lasso regression, LDA, and Naïve Bayes. The performance of all models was determined with independent test data.
Among the different approaches we examined, the T1-weighted contrast-enhanced sequence was found to be the most suitable for predicting
mutations status using radiomics-based machine learning models. Using contrast-enhanced T1-weighted MRI images, our seven-feature model developed with Lasso regression achieved a mean area under the curve (AUC) of 0.846, a mean accuracy of 0.792, a mean sensitivity of 0.847, and a mean specificity of 0.681. The administration of contrast agents resulted in a significant increase in the achieved discriminatory power.
Our analyses show that for the prediction of the
mutation status using radiomics-based machine learning models, among the MRI images acquired with the commonly used MRI sequences, the contrast-enhanced T1-weighted images are the most suitable.
Selective targeting of CD28 might represent an effective immunomodulation strategy by preventing T cell costimulation, while favoring coinhibition since inhibitory signals transmitted through CTLA‐4; ...PD‐L1 and B7 would not be affected. We previously showed in vitro and in vivo that anti‐CD28 antagonists suppress effector T cells while enhancing regulatory T cell (Treg) suppression and immune tolerance. Here, we evaluate FR104, a novel antagonist pegylated anti‐CD28 Fab' antibody fragment, in nonhuman primate renal allotransplantation. FR104, in association with low doses of tacrolimus or with rapamycin in a steroid‐free therapy, prevents acute rejection and alloantibody development and prolongs allograft survival. However, when FR104 was associated with mycophenolate mofetil and steroids, half of the recipients rejected their grafts prematurely. Finally, we observed an accumulation of Helios‐negative Tregs in the blood and within the graft after FR104 therapy, confirmed by Treg‐specific demethylated region DNA analysis. In conclusion, FR104 reinforces immunosuppression in calcineurin inhibitor (CNI)‐low or CNI‐free protocols, without the need of steroids. Accumulation of intragraft Tregs suggested the promotion of immunoregulatory mechanisms. Selective CD28 antagonists might become an alternative CNI‐sparing strategy to B7 antagonists for kidney transplant recipients.
This study reports the effect of a novel selective CD28 antagonist that preserves CTLA‐4 immunomodulatory signals in association with CNI‐free or CNI‐low regimen in nonhuman primate kidney allotransplantation.
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