PMTPred: machine-learning-based prediction of protein methyltransferases using the composition of k-spaced amino acid pairs.

Protein methyltransferases (PMTs) are a group of enzymes that help catalyze the transfer of a methyl group to its substrates. These enzymes play an important role in epigenetic regulation and can methylate various substrates with DNA, RNA, protein, and small-molecule secondary metabolites. Dysregulation of methyltransferases is implicated in various human cancers. However, in light of the well-recognized significance of PMTs, reliable and efficient identification methods are essential. In the present work, we propose a machine-learning-based method for the identification of PMTs. Various sequence-based features were calculated, and prediction models were trained using various machine-learning algorithms using a tenfold cross-validation technique. After evaluating each model on the dataset, the SVM-based CKSAAP model achieved the highest prediction accuracy with balanced sensitivity and specificity. Also, this SVM model outperformed deep-learning algorithms for the prediction of PMTs. In addition, cross-database validation was performed to ensure the robustness of the model. Feature importance was assessed using shapley additive explanations (SHAP) values, providing insights into the contributions of different features to the model's predictions. Finally, the SVM-based CKSAAP model was implemented in a standalone tool, PMTPred, due to its consistent performance during independent testing and cross-database evaluation. We believe that PMTPred will be a useful and efficient tool for the identification of PMTs. The PMTPred is freely available for download at https://github.com/ArvindYadav7/PMTPred and http://www.bioinfoindia.org/PMTPred/home.html for research and academic use.

1H and 31P Magnetic Resonance Spectroscopic Metabolomic Imaging: Assessing Mitogen-Activated Protein Kinase Inhibition in Melanoma.

The MAPK signaling pathway with BRAF mutations has been shown to drive the pathogenesis of 40-60% of melanomas. Inhibitors of this pathway's BRAF and MEK components are currently used to treat these malignancies. However, responses to these treatments are not always successful. Therefore, identifying noninvasive biomarkers to predict treatment responses is essential for personalized medicine in melanoma. Using noninvasive 1H magnetic resonance spectroscopy (1H MRS), we previously showed that BRAF inhibition reduces lactate and alanine tumor levels in the early stages of effective therapy and could be considered as metabolic imaging biomarkers for drug response. The present work demonstrates that these metabolic changes observed by 1H MRS and those assessed by 31P MRS are also found in preclinical human melanoma models treated with MEK inhibitors. Apart from 1H and 31P MRS, additional supporting in vitro biochemical analyses are described. Our results indicate significant early metabolic correlations with response levels to MEK inhibition in the melanoma models and are consistent with our previous study of BRAF inhibition. Given these results, our study supports the potential clinical utility of noninvasive MRS to objectively image metabolic biomarkers for the early prediction of melanoma's response to MEK inhibition.

Lonidamine Induced Selective Acidification and De-Energization of Prostate Cancer Xenografts: Enhanced Tumor Response to Radiation Therapy.

Prostate cancer is a multi-focal disease that can be treated using surgery, radiation, androgen deprivation, and chemotherapy, depending on its presentation. Standard dose-escalated radiation therapy (RT) in the range of 70-80 Gray (GY) is a standard treatment option for prostate cancer. It could be used at different phases of the disease (e.g., as the only primary treatment when the cancer is confined to the prostate gland, combined with other therapies, or as an adjuvant treatment after surgery). Unfortunately, RT for prostate cancer is associated with gastro-intestinal and genitourinary toxicity. We have previously reported that the metabolic modulator lonidamine (LND) produces cancer sensitization through tumor acidification and de-energization in diverse neoplasms. We hypothesized that LND could allow lower RT doses by producing the same effect in prostate cancer, thus reducing the detrimental side effects associated with RT. Using the Seahorse XFe96 and YSI 2300 Stat Plus analyzers, we corroborated the expected LND-induced intracellular acidification and de-energization of isolated human prostate cancer cells using the PC3 cell line. These results were substantiated by non-invasive 31P magnetic resonance spectroscopy (MRS), studying PC3 prostate cancer xenografts treated with LND (100 mg/kg, i.p.). In addition, we found that LND significantly increased tumor lactate levels in the xenografts using 1H MRS non-invasively. Subsequently, LND was combined with radiation therapy in a growth delay experiment, where we found that 150 µM LND followed by 4 GY RT produced a significant growth delay in PC3 prostate cancer xenografts, compared to either control, LND, or RT alone. We conclude that the metabolic modulator LND radio-sensitizes experimental prostate cancer models, allowing the use of lower radiation doses and diminishing the potential side effects of RT. These results suggest the possible clinical translation of LND as a radio-sensitizer in patients with prostate cancer.

Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma.

Dabrafenib therapy for metastatic melanoma focuses on blocking growth-promoting signals produced by a hyperactive BRAF protein. We report the metabolic differences of four human melanoma cell lines with diverse responses to dabrafenib therapy (30 mg/kg; oral): WM3918 < WM9838BR < WM983B < DB-1. Our goal was to determine if metabolic changes produced by the altered signaling pathway due to BRAF mutations differ in the melanoma models and whether these differences correlate with response to treatment. We assessed metabolic changes in isolated cells using high-resolution proton magnetic resonance spectroscopy (1H MRS) and supplementary biochemical assays. We also noninvasively studied mouse xenografts using proton and phosphorus (1H/31P) MRS. We found consistent changes in lactate and alanine, either in isolated cells or mouse xenografts, correlating with their relative dabrafenib responsiveness. In xenografts, we also observed that a more significant response to dabrafenib correlated with higher bioenergetics (i.e., increased ßNTP/Pi). Notably, our noninvasive assessment of the metabolic status of the human melanoma xenografts by 1H/31P MRS demonstrated early metabolite changes preceding therapy response (i.e., tumor shrinkage). Therefore, this noninvasive methodology could be translated to assess in vivo predictive metabolic biomarkers of response in melanoma patients under dabrafenib and probably other signaling inhibition therapies.

pH-dependent structural characteristics of lonidamine: 1H and 13C NMR study.

Lonidamine (LND) is an anti-cancer drug with great potential as a metabolic modulator of chemotherapy, radiotherapy, hyperthermia, and photodynamic therapy in cancer treatment. LND affects several important aspects of cancer cell metabolism: it inhibits Complex I and II of the electron transport chain (ETC) and pyruvate carriers (mitochondrial), and monocarboxylate transporters in the plasma membrane of the cell. Cancer cells are affected by changes in pH on the molecular level, and so are the drugs used to treat cancer, thus it is important to understand how pH affects their structures and LND is no exception. LND dissolves at a pH of 8.3 in tris-glycine buffer but has limited solubility at pH 7. To understand how pH affects the structure of LND, and its effect as a metabolic modulator on cancer therapy, we made up samples of LND at pH 2, pH 7, and pH 13, and analyzed these samples using 1H and 13C NMR. We looked for ionization sites to explain the behavior of LND in solution. Our results showed considerable chemical shifts between the extremes of our experimental pH range. LND was ionized at its indazole α-nitrogen, however, we did not directly observe the protonation of the carboxyl group oxygen that is expected at pH 2, which may be the result of a chemical-exchange phenomenon.

Microstructural and Microvascular Alterations in Psychotic Spectrum Disorders: A Three-Compartment Intravoxel Incoherent Imaging and Free Water Model.

BACKGROUND AND HYPOTHESIS: Microvascular and inflammatory mechanisms have been hypothesized to be involved in the pathophysiology of psychotic spectrum disorders (PSDs). However, data evaluating these hypotheses remain limited. STUDY DESIGN: We applied a three-compartment intravoxel incoherent motion free water imaging (IVIM-FWI) technique that estimates the perfusion fraction (PF), free water fraction (FW), and anisotropic diffusion of tissue (FAt) to examine microvascular and microstructural changes in gray and white matter in 55 young adults with a PSD compared to 37 healthy controls (HCs). STUDY RESULTS: We found significantly increased PF, FW, and FAt in gray matter regions, and significantly increased PF, FW, and decreased FAt in white matter regions in the PSD group versus HC. Furthermore, in patients, but not in the HC group, increased PF, FW, and FAt in gray matter and increased PF in white matter were significantly associated with poor performance on several cognitive tests assessing memory and processing speed. We additionally report significant associations between IVIM-FWI metrics and myo-inositol, choline, and N-acetylaspartic acid magnetic resonance spectroscopy imaging metabolites in the posterior cingulate cortex, which further supports the validity of PF, FW, and FAt as microvascular and microstructural biomarkers of PSD. Finally, we found significant relationships between IVIM-FWI metrics and the duration of psychosis in gray and white matter regions. CONCLUSIONS: The three-compartment IVIM-FWI model provides metrics that are associated with cognitive deficits and may reflect disease progression.

Functional Outcome of Hemiarthroplasty of the Hip for Unstable Intertrochanteric Fractures of the Femur in Elderly Patients: A Prospective Study.

Introduction It is frequently challenging to treat an unstable intertrochanteric fracture in elderly people by internal fixation because of difficult anatomical reduction, poor bone quality, the need for prolonged bed rest and restricted ambulation. As an alternative to internal fixation, cemented bipolar hemiarthroplasty has been used as a treatment for unstable intertrochanteric fractures to avoid the postoperative immobilization-related complications. The aim of this study was to evaluate the functional and clinical outcomes of primary cemented bipolar hemiarthroplasty for elderly patients with unstable intertrochanteric fractures. Methodology A prospective study was conducted that included 30 patients who were admitted to the apex trauma center at a tertiary care center from January 2019 to August 2020 with unstable intertrochanteric fractures (Association for Osteosynthesis/Orthopaedic Trauma Association, or AO/OTA, types 31-A2.2 and 31-A2.3); patients treated with cemented bipolar hemiarthroplasty, with at least one year of follow-up were included in the study. Basic descriptive statistics were used and the results were presented in frequencies, percentages for categorical variables and means and standard deviations for continuous variables. Results According to the Harris Hip Score, at the end of 12 months, 9 patients (30%) had excellent results, 14 patients (46.67%) had good results, 5 patients (16.67) had fair results, and 2 cases (6.67) had poor results. With cemented hemiarthroplasty, 87.7% of older patients with unstable intertrochanteric fractures were able to walk sooner, and the results were good. Conclusion Hemiarthroplasty of the hip with a cemented bipolar prosthesis appears to be a reliable treatment method for the management of unstable intertrochanteric fractures in elderly patients with osteoporosis; it allows for early ambulation and leads to a favorable functional outcome in most patients following surgery.

Hepatobiliary malformations: proposed updation of classification system, clinicopathological profile and a report of largest pediatric giant choledochal cyst.

BACKGROUND: The present study was aimed to update the classification of hepatobiliary malformations and study the clinicopathological profile of pediatric choledochal cyst (CDC) and pediatric giant choledochal cyst (GCC) patients undergone surgery. METHODS: We have retrospectively analysed the data of 57 consecutive cases of CDCs in paediatric patients from a time period spanning from 2016 to 2020. RESULTS: Revised classification of hepatobiliary malformations was proposed and these were divided into 2 broad headings, choledochal (congenital and acquired) and extra-choledochal spectrum. 57 pediatric patients were diagnosed as having CDC with average age 4.615 years and female to male ratio of 3.7:1. We have also reported one of the largest GCC measuring 23 × 10 × 9 cm size. The classical triad was known to be more common and seen in 60% GCCs as opposed to 14.5% in CDCs. Values of serum bilirubin, SGOT, SGPT, PT/INR were elevated in CDC series and normal in GCC patients. 55 patients (96.5%) underwent cyst excision and Roux-en-Y hepaticojejunostomy. Mortality was seen in 7.01% patients (n = 4) following surgery. CONCLUSION: Simplified and broader classification system for CDCs has been proposed. Clinical studies found that GCC differs considerably from classical CDCs.

Advanced magnetic resonance imaging and spectroscopy in a case of neurocysticercosis from North America.

Neurocysticercosis (NCC) is a parasitic infection caused by Cysticercus cellulosae, the metacestode of pork tapeworm (Taenia solium). NCC is one of the most common public health problems worldwide. We present a patient harboring a bilobed ring-enhancing lesion with a presumed diagnosis of brain metastasis, who returned to the USA after traveling to an endemic region. The diagnosis of NCC was established based on a characteristic resonance of succinate on proton magnetic resonance spectroscopy. Also, higher mean diffusivity and lower fractional anisotropy along with relative cerebral blood volume were observed from the lesion compared to contralateral normal brain regions. Multiparametric analysis may improve the differential diagnosis of ring-enhancing intracranial lesions such as NCC.

A dual-channel optical chemical sensing system for selective detection of nerve agent simulant DFP.

This paper reports a novel optical chemical sensing system for selective detection of diisopropylfluorophosphate (DFP), a simulant of fluorine-containing nerve agents (Sarin and Soman). Contrary to the reported methods involving only single sensing probe, this sensing system is comprised of two molecular sensing probes (1 and 2) having intrinsic affinities for reactive subunits of DFP (electrophilic phosphorus and fluoride ion). On exposure to DFP, two molecular probes react in tandem with electrophilic phosphorus and fluoride ion (by-product of the initial phosphorylation reaction) to induce a unique modulation in the optical properties of the sensing system which leads to selective detection of DFP in solution as interferents like phosphorus-containing compounds, acids, and anions were unable to induce similar optical modulation due to lack of both electrophilic phosphorus and fluorine in the same molecule. Calibration curve between the amount of DFP added and the absorption intensity revealed the colorimetric detection limit of the system to be 4.50 µM which was further lowered to 2.22 µM by making use of a self-immolative fluoride sensing probe 5.

Assessment of knowledge and opinion regarding breastfeeding practices during COVID-19 pandemic among paediatricians and obstetricians in India: an online survey.

Coronavirus disease 19 (COVID-19) is a novel coronavirus infection that has a wide spectrum of disease severity. The virus has not been known to pass through the placenta and has not been reported in the breastmilk of affected mothers. As the cases are still on a rise, it is expected that the number of pregnant females would also rise in the coming times. Among many queries during pregnancy, to breastfeed or not is an important question that needs to be answered. We conducted this survey to assess the knowledge regarding breastfeeding practices among Indian paediatricians and obstetricians during the COVID-19 pandemic. An online survey was conducted among paediatricians and obstetricians from all over India. Only 294 (54.1%) participants have adequate knowledge regarding breastfeeding recommendations. The gap in knowledge between paediatricians and obstetricians was found statistically significant with a p value of <0.01. Only 30% healthcare providers associated with perinatal care received this information through a seminar. On the other hand, 15% of participants were not aware of any guidelines on breastfeeding during the COVID-19 pandemic. More rigorous dissemination of information on breastfeeding practices in COVID-19 case management needs to be adopted.

Functional connectivity of the default mode, dorsal attention and fronto-parietal executive control networks in glial tumor patients.

PURPOSE: Resting state functional magnetic resonance imaging (rsfMRI) is an emerging tool to explore the functional connectivity of different brain regions. We aimed to assess the disruption of functional connectivity of the Default Mode Network (DMN), Dorsal Attention Network(DAN) and Fronto-Parietal Network (FPN) in patients with glial tumors. METHODS: rsfMRI data acquired on 3T-MR of treatment-naive glioma patients prospectively recruited (2015-2019) and matched controls from the 1000 functional-connectomes-project were analyzed using the CONN functional toolbox. Seed-Based Connectivity Analysis (SBCA) and Independent Component Analysis (ICA, with 10 to 100 components) were performed to study reliably the three networks of interest. RESULTS: 35 patients with gliomas (17 WHO grade I-II, 18 grade III-IV) and 70 controls were included. Global increased DMN connectivity was consistently found with SBCA and ICA in patients compared to controls (Cluster1: Precuneus, height: p < 10-6; Cluster2: subcallosum; height: p < 10-5). However, an area of decreased connectivity was found in the posterior corpus callosum, particularly in high-grade gliomas (height: p < 10-5). The DAN demonstrated small areas of increased connectivity in frontal and occipital regions (height: p < 10-6). For the FPN, increased connectivity was noted in the precuneus, posterior cingulate gyrus, and frontal cortex. No difference in the connectivity of the networks of interest was demonstrated between low- and high-grade gliomas, as well as when stratified by their IDH1-R132H (isocitrate dehydrogenase) mutation status. CONCLUSION: Altered functional connectivity is reliably found with SBCA and ICA in the DMN, DAN, and FPN in glioma patients, possibly explained by decreased connectivity between the cerebral hemispheres across the corpus callosum due to disruption of the connections.

A Novel Deep Learning-based Whale Optimization Algorithm for Prediction of Breast Cancer

HIGHLIGHTS Novel whale optimization algorithm is proposed for prediction of breast cancer. Deep learning-based WOA adjusts the CNN structure as per maximum detection accuracy. Proposed method achieves 92.4% accuracy in comparison to 90.3%. Validity of method is evaluated with magnifying factors like 40x, 100 x, 200x, 400x.

Abstract Breast cancer is one of the most common cancers among women that cause billions of deaths worldwide. Identification of breast cancer often depends on the examination of digital biomedical photography such as the histopathological images of various health professionals, and clinicians. Analyzing histopathological images is a unique task and always requires special knowledge to conclude investigating these types of images. In this paper, a novel efficient technique has been proposed for the detection and prediction of breast cancer at its early stage. Initially, the dataset of images is used to carry out the pre-processing phase, which helps to transform a human pictorial image into a computer photographic image and adjust the parameters appropriate to the Convolutional neural network (CNN) classifier. Afterward, all the transformed images are assigned to the CNN classifier for the training process. CNN classifies incoming breast cancer clinical images as malignant and benign without prior information about the occurrence of cancer. For parameter optimization of CNN, a deep learning-based whale optimization algorithm (WOA) has been proposed which proficiently and automatically adjusts the CNN network structure by maximizing the detection accuracy. We have also compared the obtained accuracy of the proposed algorithm with a standard CNN and other existing classifiers and it is found that the proposed algorithm supersedes the other existing algorithms.

Assessment of Potential Drug-Drug Interactions in Hospitalized Cardiac Patients of a Secondary Care Hospital in the United Arab Emirates.

OBJECTIVE: To identify the types, severity, and documentation grades of potential drug-drug interactions (pDDIs) and to identify the predictors of pDDIs among hospitalized cardiac patients. METHODS: This was a cross-sectional study. All the patients who were admitted for >24 h in a cardiology ward of a general hospital of the United Arab Emirates and prescribed with cardiac medications were included. The occurrence of any pDDI between cardiac medications and other coprescribed medications was identified using Micromedex database 2.0® and graded and documented based on the severity and documentation. FINDINGS: A total of 842 pDDIs were identified in 155 patients. The overall relevant frequency for the occurrence of pDDIs was found to be 87.74%. A total of 79 pairs of pDDIs were identified. Among identified pDDIs, 41.33% and 56.65% were major and moderate severity type, respectively, whereas 12.32% were excellent and 36.81% were good documentation grade. The majority of pDDIs were between aspirin-bisoprolol (11.64%). Patients taking more than seven drugs (odds ratio [OR] = 9.90; 95% confidence interval [CI]: 2.28-42.99), polypharmacy (OR = 3.86; 95% CI: 0.93-16.08), and number of medical conditions (OR 0.25; 95% CI: 0.09-0.68) were significant predictors of pDDIs. CONCLUSION: The study fosters the importance of regular and close monitoring for pDDIs among cardiac patients. Thus, multicenter interventional studies are required to determine the exact nature and types of pDDIs in the local population.

3D-Double-Inversion recovery detects perilesional gliosis better than 3D-FLAIR and postcontrast T1 imaging in calcified neurocysticercosis.

BACKGROUND: Perilesional gliosis is an important substrate for seizures in patients harboring a calcified neurocysticercosis (NCC) lesion and magnetic resonance imaging (MRI) is useful for evaluating gliosis. AIMS: The purpose of this study was to evaluate the usefulness of double-inversion recovery (DIR) sequence for identifying perilesional gliosis. SETTINGS AND DESIGN: Hospital-based cross-sectional study. METHODS AND MATERIALS: Forty-five patients with seizures were included in this study and a total of 88 calcified lesions identified on susceptibility weighted imaging (SWI) were evaluated on 3D-fluid attenuating inversion recovery (FLAIR), 3D-DIR, and 3D-postcontrast T1-weighted imaging on a 3T MRI for the presence of perilesional signal changes/enhancement. Perilesional signal was rated on a semiquantitative scale from grade 0 to 2 by independent raters. STATISTICAL ANALYSIS USED: Friedman, Wilcoxon signed rank, and Kappa tests were used. RESULTS: 3D-DIR sequence performed better than both 3D-FLAIR and postcontrast 3D-T1W sequences as more number of lesions showed perilesional signal change on DIR sequence. DIR sequence showed perilesional signal abnormality in 24 lesions in which 3D-FLAIR was normal, whereas in another 18 lesions, it demonstrated perilesional signal changes better than 3D-FLAIR. In only three lesions, FLAIR was found to be superior to DIR sequence, whereas postcontrast T1W images showed rim enhancement in five cases where no perilesional signal change was seen on FLAIR/DIR sequences. CONCLUSIONS: Combining 3D-DIR with 3D-FLAIR, and postcontrast 3D-T1W sequences is beneficial for evaluation of calcified NCC lesions and 3D-DIR sequence is better than other two sequences for perilesional signal abnormalities.

How Different is AMAN from AIDP in Childhood GBS? A Prospective Study from North India.

OBJECTIVES: To compare the clinical profile and short-term outcome of children with axonal and demyelinating subtypes of childhood Guillain Barré syndrome (GBS). METHODS: This is a prospective observational study conducted in a tertiary care teaching hospital in North India. Consecutive children with Guillain Barré syndrome were recruited to compare the clinical profile and short term outcome among the subtypes. RESULTS: Among 9847 children admitted to the emergency, 95 had acute flaccid paralysis; 57 of whom had GBS. Electrophysiological studies were completed in 57; of whom 20 had acute inflammatory demyelinating polyneuropathy (AIDP); 19 had acute motor axonal neuropathy (AMAN); 12 had non-reactive nerves; five were unclassifiable; 1 had acute motor sensory axonal neuropathy (AMSAN). More children in AMAN group had preceding gastroenteritis (4 vs. 2), while AIDP group had upper respiratory infections (12 vs. 7). Ataxia was only seen in AIDP subtype while wrist drop, foot drop and hyperreflexia were seen only with AMAN subtype. Respiratory muscle involvement (6 vs. 3) and artificial ventilation (5 vs. 2) was more in AMAN. At discharge, children with AIDP were less likely to be non-ambulant (12 vs. 6, p = 0.036). Mean disability scores at hospital discharge (4.9 ± 1.2 vs. 4 ± 0.9, p = 0.015) and at last follow-up (0.7 ± 1.01 vs. 0.05 ± 0.2, p = 0.016) were higher in AMAN. Children with AIDP were more likely to achieve normalcy on follow-up (19 vs. 12, p = 0.023). CONCLUSIONS: Children with AMAN appear to have a more severe clinical course; higher short-term morbidity; and slower recovery than those with AIDP.

On differentiation between vasogenic edema and non-enhancing tumor in high-grade glioma patients using a support vector machine classifier based upon pre and post-surgery MRI images.

PURPOSE: High grade gliomas (HGGs) are infiltrative in nature. Differentiation between vasogenic edema and non-contrast enhancing tumor is difficult as both appear hyperintense in T2-W/FLAIR images. Most studies involving differentiation between vasogenic edema and non-enhancing tumor consider radiologist-based tumor delineation as the ground truth. However, analysis by a radiologist can be subjective and there remain both inter- and intra-rater differences. The objective of the current study is to develop a methodology for differentiation between non-enhancing tumor and vasogenic edema in HGG patients based on T1 perfusion MRI parameters, using a ground truth which is independent of a radiologist's manual delineation of the tumor. MATERIAL AND METHODS: This study included 9 HGG patients with pre- and post-surgery MRI data and 9 metastasis patients with pre-surgery MRI data. MRI data included conventional T1-W, T2-W, and FLAIR images and DCE-MRI dynamic images. In this study, the authors hypothesize that surgeried non-enhancing FLAIR hyperintense tissue, which was obtained using pre- and post-surgery MRI images of glioma patients, should be largely comprised of non-enhancing tumor. Hence this could be used as an alternative ground truth for the non-enhancing tumor region. Histological examination of the resected tissue was done for validation. Vasogenic edema was obtained from the non-enhancing FLAIR hyperintense region of metastasis patients, as they have a clear boundary between enhancing tumor and edema. DCE-MRI data analysis was performed to obtain T1 perfusion MRI parameters. Support Vector Machine (SVM) classification was performed using T1 perfusion MRI parameters to differentiate between non-enhancing tumor and vasogenic edema. Receiver-operating-characteristic (ROC) analysis was done on the results of the SVM classifier. For improved classification accuracy, the SVM output was post-processed via neighborhood smoothing. RESULTS: Histology results showed that resected tissue consists largely of tumorous tissue with 7.21 ±â€¯4.05% edema and a small amount of healthy tissue. SVM-based classification provided a misclassification error of 8.4% in differentiation between non-enhancing tumor and vasogenic edema, which was further reduced to 2.4% using neighborhood smoothing. CONCLUSION: The current study proposes a semiautomatic method for segmentation between non-enhancing tumor and vasogenic edema in HGG patients, based on an SVM classifier trained on an alternative ground truth to a radiologist's manual delineation of a tumor. The proposed methodology may prove to be a useful tool for pre- and post-operative evaluation of glioma patients.

18F-Fluorocholine-Positron Emission Tomography/Computerised Tomography is Useful in Localising 99mTc-Sesta-methoxyisobutylisonitrile-Negative Parathyroid Cyst Causing Normocalcemic Primary Hyperparathyroidism.

Parathyroid cysts are extremely rare and are rarely associated with primary hyperparathyroidism (PHPT), which are difficult to localise, as they are 99mTc-sesta-methoxyisobutylisonitrile (sestaMIBI) negative. We report for the first time the utility of 18F-fluorocholinepositron emission tomography/computerised tomography (PC-PET/CT) in localising parathyroid cyst causing normocalcemic PHPT. A 76-year-old lady with progressively worsening osteoporosis from 2014-2017 (in spite of annual zolendronic acid infusions, daily calcium and vitamin-D supplementation) with persistently normal serum calcium and vitamin D, but elevated parathyroid hormone, had normal sestaMIBI scans of the neck on multiple occasions. FC-PET/CT finally revealed soft tissue uptake, suggestive of right superior parathyroid adenoma/ hyperplasia. Surgical removal of the culprit lesion resulted in resolution of hyperparathyroidism, histopathologic evaluation of which revealed a cystic lesion lined by chief cell variant parathyroid cells without any nuclear atypia, capsular or vascular invasion. FC-PET/CT is useful in localising culprit parathyroid lesions, especially when they are sestaMIBI negative. PC-PET/CT is useful in localising parathyroid hyperplasia and ectopic parathyroids, which are frequently missed by sestaMIBI. There is an urgent need for comparative studies between sestaMIBI and FC-PET/CT in PHPT. We report for the first time the usefulness of FC-PET/CT in localising sestaMIBI-negative functional parathyroid cyst causing normocalcemic PHPT.

Biochemical, Oxidative, and Physiological Changes Caused by Acute Exposure of Fentanyl and Its 3 Analogs in Rodents.

Synthesis and bioefficacy of fentanyl and its 8 new 1-substituted analogs (1-8) were earlier reported by us. Of these 8 compounds, N-(1-(2-phenoxyethyl)-4-piperidinyl)propionanilide (2), N-isopropyl-3-(4-( N-phenylpropionamido)piperidin-1-yl)propanamide (5), and N- t-butyl-3-(4-( N-phenylpropionamido)piperidin-1-yl) propanamide (6) were found to be more effective and less toxic compared to fentanyl. The present study reports the acute effect of fentanyl (0.50 Median Lethal Dose (LD50); intraperitoneal) and its 3 analogs (2, 5, and 6) on various biochemical and oxidative parameters in mice and various physiological parameters in rats. Blood alkaline phosphatase (1 hour and 7 days) and urea levels (1 hour) were significantly elevated by fentanyl, while alanine aminotransferase levels (1 hour) were increased by both fentanyl and analog 2 compared to the corresponding control. Increase in partial pressure of carbon dioxide and decrease in partial pressure of oxygen were also caused by fentanyl and analog 2 (1 hour). Analog 6 alone elevated malondialdehyde levels in the brain, liver, and kidney tissues (7 days). The LD50 of fentanyl and analogs 2, 5, and 6 were found to be 0.879, 87.88, 69.80, and 55.44 mg/kg, respectively, in rats. Significant decrease in heart rate, mean arterial pressure, respiratory rate (RR), and neuromuscular transmission was produced by fentanyl and analog 2, while analog 5 decreased the RR alone. The changes, particularly the respiratory depression, were found to be reversed by naloxone, a µ-receptor antagonist. Thereby, indicating involvement of µ-receptor mediated effects of the compounds. To conclude, all the analogs were found to be less toxic compared to fentanyl, suggesting their possible role in pain management.

Differentiation of grade II/III and grade IV glioma by combining "T1 contrast-enhanced brain perfusion imaging" and susceptibility-weighted quantitative imaging.

PURPOSE: MRI is a useful method for discriminating low- and high-grade glioma using perfusion MRI and susceptibility-weighted imaging (SWI). The purpose of this study is to evaluate the usefulness of T1-perfusion MRI and SWI in discriminating among grade II, III, and IV gliomas. METHODS: T1-perfusion MRI was used to measure relative cerebral blood volume (rCBV) in 129 patients with glioma (70 grade IV, 33 grade III, and 26 grade II tumors). SWI was also used to measure the intratumoral susceptibility signal intensity (ITSS) scores for each tumor in these patients. rCBV and ITSS values were compared to seek differences between grade II vs. grade III, grade III vs. grade IV, and grade III+II vs. grade IV tumors. RESULTS: Significant differences in rCBV values of the three grades of the tumors were noted and pairwise comparisons showed significantly higher rCBV values in grade IV tumors as compared to grade III tumors, and similarly increased rCBV was seen in the grade III tumors as compared to grade II tumors (p < 0.001). Grade IV gliomas showed significantly higher ITSS scores on SWI as compared to grade III tumors (p < 0.001) whereas insignificant difference was seen on comparing ITSS scores of grade III with grade II tumors. Combining the rCBV and ITSS resulted in significant improvement in the discrimination of grade III from grade IV tumors. CONCLUSION: The combination of rCBV values derived from T1-perfusion MRI and SWI derived ITSS scores improves the diagnostic accuracy for discrimination of grade III from grade IV gliomas.