Machine learning predictive performance evaluation of conventional and fuzzy radiomics in clinical cancer imaging cohorts.

BACKGROUND: Hybrid imaging became an instrumental part of medical imaging, particularly cancer imaging processes in clinical routine. To date, several radiomic and machine learning studies investigated the feasibility of in vivo tumor characterization with variable outcomes. This study aims to investigate the effect of recently proposed fuzzy radiomics and compare its predictive performance to conventional radiomics in cancer imaging cohorts. In addition, lesion vs. lesion+surrounding fuzzy and conventional radiomic analysis was conducted. METHODS: Previously published 11C Methionine (MET) positron emission tomography (PET) glioma, 18F-FDG PET/computed tomography (CT) lung, and 68GA-PSMA-11 PET/magneto-resonance imaging (MRI) prostate cancer retrospective cohorts were included in the analysis to predict their respective clinical endpoints. Four delineation methods including manually defined reference binary (Ref-B), its smoothed, fuzzified version (Ref-F), as well as extended binary (Ext-B) and its fuzzified version (Ext-F) were incorporated to extract imaging biomarker standardization initiative (IBSI)-conform radiomic features from each cohort. Machine learning for the four delineation approaches was performed utilizing a Monte Carlo cross-validation scheme to estimate the predictive performance of the four delineation methods. RESULTS: Reference fuzzy (Ref-F) delineation outperformed its binary delineation (Ref-B) counterpart in all cohorts within a volume range of 938-354987 mm3 with relative cross-validation area under the receiver operator characteristics curve (AUC) of +4.7-10.4. Compared to Ref-B, the highest AUC performance difference was observed by the Ref-F delineation in the glioma cohort (Ref-F: 0.74 vs. Ref-B: 0.70) and in the prostate cohort by Ref-F and Ext-F (Ref-F: 0.84, Ext-F: 0.86 vs. Ref-B: 0.80). In addition, fuzzy radiomics decreased feature redundancy by approx. 20%. CONCLUSIONS: Fuzzy radiomics has the potential to increase predictive performance particularly in small lesion sizes compared to conventional binary radiomics in PET. We hypothesize that this effect is due to the ability of fuzzy radiomics to model partial volume effects and delineation uncertainties at small lesion boundaries. In addition, we consider that the lower redundancy of fuzzy radiomic features supports the identification of imaging biomarkers in future studies. Future studies shall consider systematically analyzing lesions and their surroundings with fuzzy and binary radiomics.

AI-enhanced simultaneous multiparametric 18F-FDG PET/MRI for accurate breast cancer diagnosis.

PURPOSE: To assess whether a radiomics and machine learning (ML) model combining quantitative parameters and radiomics features extracted from simultaneous multiparametric 18F-FDG PET/MRI can discriminate between benign and malignant breast lesions. METHODS: A population of 102 patients with 120 breast lesions (101 malignant and 19 benign) detected on ultrasound and/or mammography was prospectively enrolled. All patients underwent hybrid 18F-FDG PET/MRI for diagnostic purposes. Quantitative parameters were extracted from DCE (MTT, VD, PF), DW (mean ADC of breast lesions and contralateral breast parenchyma), PET (SUVmax, SUVmean, and SUVminimum of breast lesions, as well as SUVmean of the contralateral breast parenchyma), and T2-weighted images. Radiomics features were extracted from DCE, T2-weighted, ADC, and PET images. Different diagnostic models were developed using a fine Gaussian support vector machine algorithm which explored different combinations of quantitative parameters and radiomics features to obtain the highest accuracy in discriminating between benign and malignant breast lesions using fivefold cross-validation. The performance of the best radiomics and ML model was compared with that of expert reader review using McNemar's test. RESULTS: Eight radiomics models were developed. The integrated model combining MTT and ADC with radiomics features extracted from PET and ADC images obtained the highest accuracy for breast cancer diagnosis (AUC 0.983), although its accuracy was not significantly higher than that of expert reader review (AUC 0.868) (p = 0.508). CONCLUSION: A radiomics and ML model combining quantitative parameters and radiomics features extracted from simultaneous multiparametric 18F-FDG PET/MRI images can accurately discriminate between benign and malignant breast lesions.

UK and Ireland survey of MPharm student and staff experiences of mental health curricula, with a focus on Mental Health First Aid.

BACKGROUND: One in four people experience a mental health problem every year and improving mental health care is an international priority. In the course of their work, pharmacists frequently encounter people with mental health problems. The experience of mental health teaching, including Mental Health First Aid (MHFA) training, in undergraduate pharmacy (MPharm) students in the UK and Ireland is not well documented. Students' viewpoints, contextualised with curricular overviews provided by staff, were analysed to understand their experience. METHODS: An anonymous, online questionnaire was distributed to MPharm students and staff in the UK and Ireland. Students were asked closed questions regarding their course and exposure to MHFA, which were analysed using descriptive statistics. Open questions were included to enable explanations and these data were used to contextualise the quantitative findings. One member of staff from each university was invited to answer a modified staff version of the questionnaire, to provide a curriculum overview and staff perspective. RESULTS: 232 students and 13 staff, from 22 universities, responded. Three-quarters of students did not agree with the statement that 'mental health was embedded throughout the MPharm'. Most students (80.6%) stated that they were taught neuropharmacology whilst 44.8% stated that their course included communicating with people about their mental health. One-third (33.2%) of students stated that their degree 'adequately prepared them to help people with their mental health'. Twenty-six students (11.6%) had completed MHFA training of which 89% would endorse inclusion of this within the MPharm. Of those who had not completed the training, 81% expressed a desire to do so. Those who completed MHFA training self-reported greater preparedness than those who did not, but student numbers were small. CONCLUSIONS: Mental health teaching for pharmacy undergraduates is more focussed on theoretical aspects rather than applied skills. MHFA was viewed by students as one way to enhance skill application. The association of the increased self-reported preparedness of those who completed MHFA could be confounded by a positive environmental cultural. MPharm programmes need sufficient focus on real-world skills such as communication and crisis response, to complement the fundamental science.

Coronary artery bypass graft surgery in a young female with systemic lupus erythematosus and its operative challenges: A case report.

We understand that autoimmune disorders such as Systemic Lupus Erythematosus increases the likelihood of developing coronary heart disease. However, its implications on patients undergoing cardiac surgery is not well understood. Here we present a female patient with SLE who developed coronary artery disease at a young age and underwent coronary artery bypass graft surgery. As SLE is associated with vasculitis, we wanted to understand regarding the choice of conduit as well as its long term patency. Also whether percutaneous angioplasty has a role to play in patients with SLE.

Impact of motion compensation and partial volume correction for 18F-NaF PET/CT imaging of coronary plaque.

Recent studies have suggested that 18F-NaF-PET enables visualization and quantification of plaque micro-calcification in the coronary tree. However, PET imaging of plaque calcification in the coronary arteries is challenging because of the respiratory and cardiac motion as well as partial volume effects. The objective of this work is to implement an image reconstruction framework, which incorporates compensation for respiratory as well as cardiac motion (MoCo) and partial volume correction (PVC), for cardiac 18F-NaF PET imaging in PET/CT. We evaluated the effect of MoCo and PVC on the quantification of vulnerable plaques in the coronary arteries. Realistic simulations (Biograph TPTV, Biograph mCT) and phantom acquisitions (Biograph mCT) were used for these evaluations. Different uptake values in the calcified plaques were evaluated in the simulations, while three 'plaque-type' lesions of 36, 31 and 18 mm3 were included in the phantom experiments. After validation, the MoCo and PVC methods were applied in four pilot NaF-PET patient studies. In all cases, the MoCo-based image reconstruction was performed using the STIR software. The PVC was obtained from a local projection (LP) method, previously evaluated in preclinical and clinical PET. The results obtained show a significant increase of the measured lesion-to-background ratios (LBR) in the MoCo + PVC images. These ratios were further enhanced when using directly the tissue-activities from the LP method, making this approach more suitable for the quantitative evaluation of coronary plaques. When using the LP method on the MoCo images, LBR increased between 200% and 1119% in the simulated data, between 212% and 614% in the phantom experiments and between 46% and 373% in the plaques with positive uptake observed in the pilot patients. In conclusion, we have built and validated a STIR framework incorporating MoCo and PVC for 18F-NaF PET imaging of coronary plaques. First results indicate an improved quantification of plaque-type lesions.

Heterosis and correlation in interspecific and intraspecific hybrids of cotton.

Interspecific and intraspecific hybrids show varying degrees of heterosis for yield and yield components. Yield-component traits have complex genetic relationships with each other. To determine the relationship of yield-component traits and fiber traits with seed cotton yield, six lines (Bt. CIM-599, CIM-573, MNH-786, CIM-554, BH-167, and GIZA-7) and three test lines (MNH-886, V4, and CIM-557) were crossed in a line x tester mating design. Heterosis was observed for seed cotton yield, fiber traits, and for other yield-component traits. Heterosis in interspecific hybrids for seed cotton yield was more prominent than in intraspecific hybrids. The interspecific hybrid Giza-7 x MNH-886 had the highest heterosis (114.77), while among intraspecific hybrids, CIM-554 x CIM-557 had the highest heterosis (61.29) for seed cotton yield. A major trait contributing to seed cotton yield was bolls/plant followed by boll weight. Correlation studies revealed that bolls/plant, boll weight, lint weight/boll, lint index, seed index, lint/seed, staple length, and staple strength were significantly and positively associated with seed cotton yield. Selection based on boll weight, boll number, lint weight/boll, and lint index will be helpful for improving cotton seed yield.

Mycotic bronchial artery aneurysmal rupture in the early stage of lung abscess: A case report.

Symptomatic bronchial artery aneurysm warrants urgent intervention. It has a known association with pulmonary infection caused by Staphylococcus aureus. We hereby report an elderly lady with a ruptured left superior bronchial artery mycotic aneurysm. She was in the early stages of treatment for a left lung abscess. She had multiple episodes of haemoptysis following which she underwent a left lower lobectomy. Presentation of lung abscess with a concurrent ruptured mycotic aneurysm warrants early surgical intervention and can be curative as seen in this case.

Nitric oxide production mediates oligogalacturonide-triggered immunity and resistance to Botrytis cinerea in Arabidopsis thaliana.

Nitric oxide (NO) regulates a wide range of plant processes from development to environmental adaptation. In this study, we investigated the production and/or function of NO in Arabidopsis thaliana leaf discs and plants elicited by oligogalacturonides (OGs) and challenged with Botrytis cinerea. We provided evidence that OGs triggered a fast and long lasting NO production which was Ca(2+) dependent and involved nitrate reductase (NR). Accordingly, OGs triggered an increase of both NR activity and transcript accumulation. NO production was also sensitive to the mammalian NO synthase inhibitor L-NAME. Intriguingly, we showed that L-NAME affected NO production by interfering with NR activity, thus questioning the mechanisms of how this compound impairs NO synthesis in plants. We further demonstrated that NO modulates RBOHD-mediated reactive oxygen species (ROS) production and participates in the regulation of OG-responsive genes such as anionic peroxidase (PER4) and a ß-1,3-glucanase. Mutant plants impaired in PER4 and ß-1,3-glucanase, as well as Col-0 plants treated with the NO scavenger cPTIO, were more susceptible to B. cinerea. Taken together, our investigation deciphers part of the mechanisms linking NO production, NO-induced effects and basal resistance to B. cinerea.

Inhibition of gamma-secretase induces G2/M arrest and triggers apoptosis in breast cancer cells.

Gamma-secretase activity is vital for the transmembrane cleavage of Notch receptors and the subsequent migration of their intracellular domains to the nucleus. Notch overexpression has been associated with breast, colon, cervical and prostate cancers. We tested the effect of three different gamma-secretase inhibitors (GSIs) in breast cancer cells. One inhibitor (GSI1) was lethal to breast cancer cell lines at concentrations of 2 muM and above but had a minimal effect on the non-malignant breast lines. GSI1 was also cytotoxic for a wide variety of cancer cell lines in the NCI60 cell screen. GSI1 treatment resulted in a marked decrease in gamma-secretase activity and downregulation of the Notch signalling pathway with no effects on expression of the gamma-secretase components or ligands. Flow cytometric and western blot analyses indicated that GSI1 induces a G2/M arrest leading to apoptosis, through downregulation of Bcl-2, Bax and Bcl-XL. GSI1 also inhibited proteasome activity. Thus, the gamma-secretase inhibitor GSI1 has a complex mode of action to inhibit breast cancer cell survival and may represent a novel therapy in breast cancer.

Allogeneic bone marrow transplantation in beta-thalassaemia--single centre study.

OBJECTIVE: To evaluate outcome of allogeneic BMT in beta-Thalassaemia at the Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan from August 2001 to November 2003. METHODS: Nineteen patients with beta-Thalassaemia underwent allogeneic BMT/PBSC transplantation from HLA identical sibling donors. Patients were classified in three groups according to Pesaro (Italy) risk classification. Class-I (n = 9) and Class-II (n = 7) patients received conditioning with busulphan/cyclophosphamide, whereas Class-III (n = 3) patient received conditioning with hydroxyurea, azathioprine, fludarabine, along with Bu14 / Cy 200. Cyclosporine, prednisolone and methotrexate were given for GvHD prophylaxis. Stem cells dose infused was >4.0 x 10(8)/kg body weight of the patient. RESULTS: Engraftment was achieved in all Class-I patients, whereas in Class-II and Class-III , graft rejection was observed in one patient from each class. Median time to achieve absolute neutrophil recovery (> 0.5 x 10(9)/l) was 13 days, platelet count (> 20 x 10(9)/1) was 15 days and reticulocyte count (>0.5%) was 15 days. Acute GvHD was observed in 15 patients. One patient developed grade IV GvHD (liver and skin) and died within 30 days post BMT. Post transplant infectious complications were pseudomonas septicemia, disseminated fungal infection, CMV pneumonia and tuberculosis. Three patients died of these complications during post transplant period (31-90 days). Median stay in hospital was 25 days. CONCLUSION: Allogeneic BMT is the only curative therapy for beta-Thalassaemia patients, however the success rate can be increased if the patients are selected carefully and transplanted at an early age.

Electrochemical measurement and speciation of inorganic arsenic in groundwater of Bangladesh.

The presence of arsenic in groundwater above the maximum permissible limit of 50 mug l(-1) has threatened the health of more than 50 million people in Bangladesh and neighboring India. We report here the development of an inexpensive anodic stripping voltammetric (ASV) technique for routine measurement and speciation of arsenic in groundwater. The measurements are validated by more expensive atomic absorption, atomic emission and other techniques. To understand the present situation in Bangladesh, we measured As(III) in 960 water samples collected from 18 districts. A random distribution of 238 samples was used to measure both As(III) and As(V). The results from the present study indicate that most toxic form of inorganic arsenic, As(III), has the broad range of 30-98%. It shows 60% of the samples have 10 mug l(-1) and 44% of the samples have 50 mug l(-1) or more As(III). The fractional distribution pattern shows significant skew towards high percent occurrence which may indicate a progressive reduction process with a single source or a single mechanism for the formation of As(III). For direct consumption, this is possibly one of the most toxic groundwater known today. Speciation distribution at groundwater pH value shows H(3)AsO(3) is the predominant species including H(2)AsO(4)(-) and H(2)AsO(4)(2-) whose distribution is significantly pH dependent. This is also supported by E(h)-pH measurements. The depth distribution for Kushtia shows most of the As(III) is located within 100-200 ft deep aquifers. Similar fractional distribution of As(III) is found in deeper aquifers and may indicate contamination by leakage from upper aquifer. This study clearly demonstrates the aquifer environment is reductive and conducive to the formation of As(III) species.

The safety of epidural analgesia in labour and its effect on delivery--a case control study in Pakistani women.

To assess the safety and effect of epidural analgesia on the course of labour and delivery in Pakistani women, a retrospective case control study was conducted from November, 1986 to November, 1991 (5 years) at the Aga Khan University Medical Centre, Karachi. All patients (n = 64) who received epidural analgesia for labour (cases) were compared with randomly selected patients (n = 18) who did not receive epidural analgesia during labour (controls). The cases and controls were matched for age, height, body mass index, parity, use of oxytocin, presentation and weight of the foetus. There was no significant difference (P > 0.05) between the two groups in duration of labour, caesarean section rate and foetal apgar scores at 1 and 5 minutes after birth. The incidence of malposition of foetal vertex at delivery and that of instrumental (forceps) deliveries was significantly higher (P < 0.05 and < 0.01 respectively) in the epidural group as compared to controls. The incidence of complications was low and the acceptance and tolerance of epidural analgesia was good in our patients.

Experience with screening for abnormal glucose tolerance in pregnancy: maternal and perinatal outcome.

In order to determine the prevalence of glucose intolerance in pregnancy, 2,230 consecutive women attending the antenatal clinic at the Aga Khan University Medical Centre in Karachi, Pakistan were subjected on the first antenatal visit, irrespective of gestational age, to a 75 g glucose challenge followed 2 hr later by plasma glucose determination. The test, was repeated at 28-32 weeks of gestation for those patients who had an abnormal initial screen at less than 28 weeks gestation followed by a normal glucose tolerance test and for those who had a risk factor for gestational diabetes even though the initial screen at less than 28 weeks gestation was normal. The initial glucose challenge test was abnormal (2 hr plasma glucose greater than 140 mg%) in 8.6% of the screened population. An oral glucose tolerance test on these patients revealed a prevalence for the entire population of 3.5% of gestational diabetes and 1.9% of impaired glucose tolerance test based on the modified O'Sullivan criteria. Patients with abnormal glucose tolerance test were older, had higher parity, a past history of macrosomia and a family history of diabetes compared to the controls. These patients also had a higher incidence of preterm labour and caesarean section. In the neonates hypoglycemia and hyperbilirubinemia were similarly higher. The fetal abnormality rate was 5.6% and the perinatal mortality was 28/1,000 which were higher than the controls.

Cervical cancer screening program in a Muslim country: three-year experience at the Aga Khan University Medical Center, Karachi.

A systematic cervical cancer screening program was initiated in January 1987 at The Aga Khan University Medical Center, Karachi, Pakistan. The 8,784 cervical smears obtained in 3 subsequent years from 8,412 consecutive women attending the gynecology and antenatal clinics were reviewed. "Positive" smears were found in 111 (1.3%) patients; 107 (1.27%) smears showed squamous epithelial dysplasia and 4 smears showed adenocarcinoma. The highest incidence of abnormal smears was found in the 45-54 years age group. Colposcopy and biopsy was performed on all patients with "positive" smears except on those with atypical or mildly dysplastic ones, in whom only the persistence of the abnormality on repeated smears was considered an indication for tissue evaluation. The histopathologic diagnosis of these biopsy specimens revealed cervical intra-epithelial neoplasia in 60 patients and invasive cervical cancer in 6 patients.

Rubella susceptibility and continuing risk of infection in pregnancy.

Sera of 2000 pregnant women attending the antenatal clinic of the Aga Khan University Hospital were tested for rubella antibodies. Of these 1684 (84.2%) were immune and 316 (15.8%) were susceptible to rubella. Majority (99.8%) of the women were Asian in origin. Susceptibility decreased with increasing age and parity. We conclude that apart from vaccination of all young children greater attention should be paid to immunization of women of child-bearing age.

[Treatment of penetrating wounds of the heart]. / Lechenie pronikaiushchikh ranenii serdtsa.

An analysis of results of treatment of 43 victims with knife and gunshot wounds of the heart has shown that treatment of the trauma disease in these patients is dependent on the trauma mechanism, character and localization of the myocardium wounds and intensity of bleeding. These factors taken into consideration will improve results of the treatment. General lethality among patients with injuries of the heart made up 25.5%.