AI-Based Automated Lipomatous Tumor Segmentation in MR Images: Ensemble Solution to Heterogeneous Data.

Deep learning (DL) has been proposed to automate image segmentation and provide accuracy, consistency, and efficiency. Accurate segmentation of lipomatous tumors (LTs) is critical for correct tumor radiomics analysis and localization. The major challenge of this task is data heterogeneity, including tumor morphological characteristics and multicenter scanning protocols. To mitigate the issue, we aimed to develop a DL-based Super Learner (SL) ensemble framework with different data correction and normalization methods. Pathologically proven LTs on pre-operative T1-weighted/proton-density MR images of 185 patients were manually segmented. The LTs were categorized by tumor locations as distal upper limb (DUL), distal lower limb (DLL), proximal upper limb (PUL), proximal lower limb (PLL), or Trunk (T) and grouped by 80%/9%/11% for training, validation and testing. Six configurations of correction/normalization were applied to data for fivefold-cross-validation trainings, resulting in 30 base learners (BLs). A SL was obtained from the BLs by optimizing SL weights. The performance was evaluated by dice-similarity-coefficient (DSC), sensitivity, specificity, and Hausdorff distance (HD95). For predictions of the BLs, the average DSC, sensitivity, and specificity from the testing data were 0.72 [Formula: see text] 0.16, 0.73 [Formula: see text] 0.168, and 0.99 [Formula: see text] 0.012, respectively, while for SL predictions were 0.80 [Formula: see text] 0.184, 0.78 [Formula: see text] 0.193, and 1.00 [Formula: see text] 0.010. The average HD95 of the BLs were 11.5 (DUL), 23.2 (DLL), 25.9 (PUL), 32.1 (PLL), and 47.9 (T) mm, whereas of SL were 1.7, 8.4, 15.9, 2.2, and 36.6 mm, respectively. The proposed method could improve the segmentation accuracy and mitigate the performance instability and data heterogeneity aiding the differential diagnosis of LTs in real clinical situations.

Longitudinal stability of JCV antibody index in Natalizumab treated people with multiple sclerosis.

OBJECTIVE: The aim of this study was to evaluate the evolution of JCV index over time in Natalizumab treated people with multiple sclerosis. MATERIALS AND METHODS: We retrospectively reviewed antibody index values from pwMS who were treated with Natalizumab for greater than six months and had at least two antibody results available between 2011 and 2019. Survival analysis was performed on those who were JCV index value negative at baseline to evaluate time to seroconversion. In pwMS who had index values available at 48 and/or 96 months post Natalizumab initiation, t-tests were performed to evaluate change in index over time. RESULTS: 1144 JCV antibody index results were available for 132 pwMS. Median time to seroconversion based on survival analysis was 103 months. Annualised seroconversion rate was 5.8%. Initial antibody index and rate of seroconversion did not differ with regards to age or gender. Antibody index increased significantly over time on treatment for the cohort as a whole, initial antibody index (0.27) to final antibody testing (0.86), t(131)=6.45, p<.0005. There was a significant increase in those with initial positive index value, between first (0.95) and final index (2.14), t(33) = 4.85, p<.0005 over a median of 77 months. CONCLUSIONS: In those who were seronegative at baseline there is a long median duration of treatment with Natalizumab prior to seroconversion. In individuals with positive JCV antibody index at treatment initiation, antibody index increases over time.

Isobaric tags for relative and absolute quantification (iTRAQ)-based quantitative analysis of the salivary proteome during healthy pregnancy and pregnancy gingivitis.

AIM: The present study aimed to investigate the salivary proteome profiles of pregnant women with gingivitis (PG) or without gingivitis (HP) and non-pregnant healthy controls (HC) by employing iTRAQ-based proteomics. MATERIALS AND METHODS: Saliva samples were collected from 30 Chinese women comprising 10 subjects in each of the three groups (PG, HP, and HC). The samples were subjected to iTRAQ-based proteomics analysis, and ELISA was performed to validate the results. The subsequent observations were validated in a cohort of 48 subjects. RESULTS: Pathways associated with neutrophil-mediated immune response and antioxidant defence mechanism were significantly higher in PG than HC. The abundance of salivary cystatins (S, SA, and SN) and antimicrobials were significantly decreased in PG and HP, while cystatin C and D were additionally decreased in PG. Cystatin C was mapped to all the major catabolic pathways and was the most re-wired protein in pregnancy gingivitis. Further validation demonstrated cystatin C to be significantly lower in PG than HC. CONCLUSIONS: While the decrease in levels of salivary cystatins and antimicrobial proteins may predispose healthy pregnant women to pregnancy gingivitis, it may cause persistence of inflammation in pregnant women with gingivitis.

Sodium glucose co-transporter-2 inhibitor-induced diabetic ketoacidosis following tooth extraction: improving awareness among dental practitioners.

Sodium glucose co-transporter-2 inhibitors (SGLT-2i) are a relatively new class of oral glucose lowering agents that improve glycaemic control and also provide significant cardiac and renal benefits. However, SGLT-2i use is associated with a small but significant increased risk of diabetic ketoacidosis (DKA) especially during periods of reduced oral intake such as following dental procedures, bowel preparation for colonoscopy, surgery and concurrent illness. In contrast with typical DKA, in many cases of SGLT2i-associated DKA, the blood glucose is normal or only slightly elevated, giving rise to the term euglycaemic DKA (euDKA). Patients with euDKA often present with non-specific symptoms. Moreover, their normal or only mildly elevated blood glucose levels might lead to delayed diagnosis and treatment and hence potentially life-threatening complications. Not only should patients taking an SGLT-2i be informed about the risk of euDKA, and be provided with SGLT-2i sick day management education, but clinicians should also be alert to this diagnosis.

Managing the COVID-19 Pandemic as a National Radiation Oncology Centre in Singapore.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. It has impacted the world medically, financially, politically and socially, with countries such as China and Italy adopting a full lockdown of their cities to mitigate the transmission. The current mortality rate is 5.4%, with 1 056 159 people infected worldwide. The disease is reminiscent of SARS in 2002, from which the healthcare system of Singapore has garnered many lessons and applied them in the current climate. As a result of the high transmissibility of the virus, hospitals in Singapore have reduced clinic loads and elective treatments to halt propagation of the virus and also to allow redistribution of healthcare workforce to the frontline. Cancer patients, who are often immunocompromised, are at risk of contracting the disease and becoming seriously ill. At the same time, delaying treatment such as radiotherapy in cancer patients can be detrimental. Here, we describe our experience as a large radiation oncology department in Singapore, including the challenges we encountered and how we managed our patient flow.

Photoemission from non-polar aromatic molecules in the gas and liquid phase.

The photoelectron spectra of both liquid and gas phase aromatic molecules are reported. The spectra were obtained using a 34.1 eV source produced by high harmonic generation and analysed with the help of high-level ab initio simulations using the reflection principle combined with path integral molecular dynamics simulations accounting for nuclear quantum effects for the gas phase. We demonstrate the suitability of three trimethylbenzenes (1,3,5-trimethylbenzene, 1,2,3-trimethylbenzene and 1,2,4-trimethylbenzene) as a solvent for liquid photoelectron spectroscopy of solute species. We also discuss the electrokinetic charging of a non-polar liquid jet.

Bactericidal and cytotoxic activity of a diarylheptanoid (etlingerin) isolated from a ginger (Etlingera pubescens) endemic to Borneo.

AIMS: The aim of this study was to investigate the antimicrobial activities of Etlingera pubescens, and to isolate and identify the antimicrobial compound. METHODS AND RESULTS: The crude extracts of E. pubescens were obtained through methanol extraction, and evaluated for antimicrobial activities. From this extract, 1,7-bis(3,4-dihydroxyphenyl)heptan-3-yl acetate (etlingerin) was isolated. When compared to curcumin (a compound with a similar chemical structure), etlingerin showed twofold lower minimum inhibitory concentration values while also being bactericidal. Through time kill assay, etlingerin showed rapid killing effects (as fast as 60 min) against the Gram-positive bacteria (Staphylococcus aureus ATCC 43300 and Bacillus subtilis ATCC 8188). Further assessment revealed that etlingerin caused leakage of intracellular materials, therefore suggesting alteration in membrane permeability as its antimicrobial mechanism. Cytotoxicity study demonstrated that etlingerin exhibited approximately 5- to 12-fold higher IC50 values against several cell lines, as compared to curcumin. CONCLUSIONS: Etlingerin isolated from E. pubescens showed better antibacterial and cytotoxic activities when compared to curcumin. Etlingerin could be safe for human use, though further cytotoxicity study using animal models is needed. SIGNIFICANCE AND IMPACT OF THE STUDY: Etlingerin has a potential to be used in treating bacterial infections due to its good antimicrobial activity, while having potentially low cytotoxicity.

Complete Genome Sequence Analysis and Characterization of Selected Iron Regulation Genes of Pasteurella Multocida Serotype A Strain PMTB2.1.

Although more than 100 genome sequences of Pasteurella multocida are available, comprehensive and complete genome sequence analysis is limited. This study describes the analysis of complete genome sequence and pathogenomics of P. multocida strain PMTB2.1. The genome of PMTB2.1 has 2176 genes with more than 40 coding sequences associated with iron regulation and 140 virulence genes including the complete tad locus. The tad locus includes several previously uncharacterized genes such as flp2, rcpC and tadV genes. A transposable phage resembling to Mu phages was identified in P. multocida that has not been identified in any other serotype yet. The multi-locus sequence typing analysis assigned the PMTB2.1 genome sequence as type ST101, while the comparative genome analysis showed that PMTB2.1 is closely related to other P. multocida strains with the genomic distance of less than 0.13. The expression profiling of iron regulating-genes of PMTB2.1 was characterized under iron-limited environment. Results showed significant changes in the expression profiles of iron-regulating genes (p < 0.05) whereas the highest expression of fecE gene (281 fold) at 30 min suggests utilization of the outer-membrane proteins system in iron acquisition at an early stage of growth. This study showed the phylogenomic relatedness of P. multocida and improved annotation of important genes and functional characterization of iron-regulating genes of importance to the bacterial growth.

Psychogenic coma after dental surgery under general anaesthesia.

Delayed awakening after general anaesthesia due to psychogenic coma is a phenomenon that rarely presents to the oral and maxillofacial surgeon. A case of psychogenic coma following general anaesthesia for dental extractions is presented here. It is recommended that patients at risk of conversion disorder should be counselled about the risks of psychogenic coma. Early diagnosis of this condition could lead to better patient management.

Cognitive dysfunction in early multiple sclerosis: a review.

Cognitive impairment is a common and disabling feature of Multiple Sclerosis (MS), including early MS, and may even pre-date any physical symptoms. It contributes even more to withdrawal from work than physical disability. Here, we provide an overview of cognitive impairment in MS, particularly in early MS where it is most commonly under-reported and under-treated. We address the presenting features of CI, its impact on quality of life, and its validated assessments (in particular the use of Brief International Cognitive Assessment in MS for use in a clinical setting). We review the insights radiology has given us into the pathogenesis of cognitive impairment in MS, particularly in early CI and in cognitively preserved MS patients. We review current treatments for cognitive impairment, primarily cognitive rehabilitation. We address the evidence for its associated co-morbidities, which may exacerbate or trigger CI, and should therefore be addressed early in the disease course (smoking, alcohol, mood, fatigue and potential co-existing sleep disorders, exercise, and vitamin D). The article supports the importance for early recognition and management of cognitive impairment in MS, before it becomes an established and irreversible entity.

A role for susceptibility weighted imaging in progressive multifocal leukoencephalopathy.

We report a radiologic finding on magnetic resonance imaging (MRI) of the brain of two cases of progressive multifocal leukoencephalopathy (PML) of hypointense signal of subcortical U-fibres on susceptibility weighted (SW) sequence. The first case is a 50-year-old man recently treated with chemotherapy including rituximab for non-Hodgkin's lymphoma. The second case is a 64-year-old woman with human immunodeficiency virus (HIV) infection. Iron deposition is a likely causative factor. We propose that SWI may be especially useful in the assessment of indeterminate cases to reduce the likelihood of a missed diagnosis of PML.

The oral microbiome community variations associated with normal, potentially malignant disorders and malignant lesions of the oral cavity.

The human oral microbiome has been known to show strong association with various oral diseases including oral cancer. This study attempts to characterize the community variations between normal, oral potentially malignant disorders (OPMD) and cancer associated microbiota using 16S rDNA sequencing. Swab samples were collected from three groups (normal, OPMD and oral cancer) with nine subjects from each group. Bacteria genomic DNA was isolated in which full length 16S rDNA were amplified and used for cloned library sequencing. 16S rDNA sequences were processed and analysed with MOTHUR. A core oral microbiome was identified consisting of Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes and Actinobacteria at the phylum level while Streptococcus, Veillonella, Gemella, Granulicatella, Neisseria, Haemophilus, Selenomonas, Fusobacterium, Leptotrichia, Prevotella, Porphyromonas and Lachnoanaerobaculum were detected at the genus level. Firmicutes and Streptococcus were the predominant phylum and genus respectively. Potential oral microbiome memberships unique to normal, OPMD and oral cancer oral cavities were also identified. Analysis of Molecular Variance (AMOVA) showed a significant difference between the normal and the cancer associated oral microbiota but not between the OPMD and the other two groups. However, 2D NMDS showed an overlapping of the OPMD associated oral microbiome between the normal and cancer groups. These findings indicated that oral microbes could be potential biomarkers to distinguish between normal, OPMD and cancer subjects.

Foot Drop: Looking Beyond Common Peroneal Nerve Palsy: A Neurophysiology Centre Experience.

Foot drop is a complex symptom with a considerable range in aetiology, severity and prognosis. We aim to characterise the aetiologies of foot drop and assess the diagnostic contribution of neurophysiologic testing (NCS/EMG). Retrospective review of consecutive referrals of foot drop to the Neurophysiology Department in Cork University Hospital was performed over a two year period (January 2012 to December 2013). Of a total of 59 referrals, common peroneal nerve (CPN) palsy comprised only slightly more than half of cases; 3(5%) have central origin; 3(5%) have motor neuron disease. Six (10%) have diabetes; 7(12%) have cancer; 5(8%) were bilateral. NCS/EMG altered initial working diagnosis in 14 out of 52 (27%) cases whereby initial diagnosis was provided. However one-third of all cases revealed additional coexistent pathology in an anatomic location remote to that of the primary diagnosis. Foot drop with central and proximal localisations are important and under recognised. NCS/EMG is valuable and also reveals additional pathology which warrants investigation.

Cold plasma inactivation of chronic wound bacteria.

Cold plasma is partly ionized non-thermal plasma generated at atmospheric pressure. It has been recognized as an alternative approach in medicine for sterilization of wounds, promotion of wound healing, topical treatment of skin diseases with microbial involvement and treatment of cancer. Cold plasma used in wound therapy inhibits microbes in chronic wound due to its antiseptic effects, while promoting healing by stimulation of cell proliferation and migration of wound relating skin cells. In this study, two types of plasma systems are employed to generate cold plasma: a parallel plate dielectric barrier discharge and a capillary-guided corona discharge. Parameters such as applied voltage, discharge frequency, treatment time and the flow of the carrier gas influence the cold plasma chemistry and therefore change the composition and concentration of plasma species that react with the target sample. Chronic wound that fails to heal often infected by multidrug resistant organisms makes them recalcitrant to healing. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (Pseudomonas aeruginosa) are two common bacteria in infected and clinically non-infected wounds. The efficacies of the cold plasma generated by the two designs on the inactivation of three different isolates of MRSA and four isolates of P. aeruginosa are reported here.

The Cancer, Lifestyle and Evaluation of Risk Study (CLEAR): Rationale and design of an unmatched "case-spouse control" study of over 10,000 participants in New South Wales, Australia.

INTRODUCTION: The New South Wales (NSW) Cancer, Lifestyle and Evaluation of Risk Study (CLEAR) is an open epidemiological bioresource, using an all cancer unmatched case-spouse control design. Participant characteristics and selected confirmed associations are compared to published estimates: current smoking and lung cancer; country of birth and melanoma; body mass index (BMI) and bowel cancer; and paternal history of prostate cancer and prostate cancer, to illustrate the validity of this design. MATERIAL AND METHODS: Cases are NSW residents, ≥18 years, with an incident cancer of any type. Controls are cancer-free spouses of cases. Participants complete a consent form, a questionnaire, and provide an optional blood sample. For analyses, odds ratios for males and females are calculated for cancers and exposures of interest, by sex-matching controls to cases. RESULTS: 10,816 participants (8569 cases, 2247 controls, 54% female) recruited to-date, median age: 61.6 y cases, 61.3 y controls. The top five cancer types are female breast (n=1691), prostate (n=1102), bowel (n=888), melanoma (n=608), and lung (n=265). Adjusted odds ratios (OR) were: 20.65 (95% CI: 13.25-32.19) for lung cancer in current versus never smokers; 1.16 (1.05-1.28) for bowel cancer per 5 kg/m(2) increment in BMI; 1.41 (1.01-1.96) for melanoma in Australian-born compared to those born in UK/Ireland; and 2.47 (1.82-3.37) for prostate cancer in men with versus without a paternal history of prostate cancer. DISCUSSION: This study design, where controls are the spouses of cases diagnosed with a variety of cancers and which are analysed unmatched, avoids potential biases due to overmatching, considered problematic in standard case-spouse control studies, and illustrates that risk estimates analysed are consistent with the published literature. CLEAR methodology provides a practical design to advance local knowledge on the causes of various leading and emerging cancers.

Second Toe Systolic Pressure Measurements are Valid Substitutes for First Toe Systolic Pressure Measurements in Diabetic Patients: A Prospective Study.

OBJECTIVE: Toe systolic pressure is a component of the standard vascular and diabetic foot assessment. Until now,clinicians have measured only first toe pressure given a lack of evidence for measurements of the other toes. In diabetic patients, first toe measurements are often not possible because of ulceration or amputation. It was hypothesized that the adjacent second toe systolic pressure measurements would be interchangeable with those of the first toe. METHODS: A prospective study was performed on 100 participants with diabetes mellitus. Duplicate systolic toe pressures were measured in the first toe and adjacent second toe using the Systoe Automated Toe Pressure System, Systoe Photophlethysmograph Sensor Cuff, and occlusion cuffs measuring 120 x 25 mm for the first toe and 90 x 15 mm for the second toe. Correlation analysis was followed by Ordinary Least Products regression to detect and distinguish fixed and proportional bias between the two toe measurements. The acceptable limits of interchangeable results were defined as 5-10 mmHg. RESULTS: Correlation coefficient r » 0.908; p < 0.001. Eighty-two percent of the variations in the second toe measurements were accounted for by knowing the first toe measurements and vice versa. Ordinary Least Products regression showed no fixed or proportional bias between the two methods of measurement: second toe systolic pressure = (-0.579) + (1.038) * first toe systolic pressure. Repeatability analysis showed a 0.5%variation between duplicate measurements. CONCLUSIONS: This is the first study which demonstrates that second toe systolic pressures are interchangeable with those of the first toe. Second toe pressures can be used in diabetic patients whose first toe pressures cannot be assessed.

Graft-vs-tumor effect in patients with advanced nasopharyngeal cancer treated with nonmyeloablative allogeneic PBSC transplantation.

While nonmyeloablative peripheral blood stem cell transplantation (NST) has shown efficacy against several solid tumors, it is untested in nasopharyngeal cancer (NPC). In a phase II clinical trial, 21 patients with pretreated metastatic NPC underwent NST with sibling PBSC allografts, using CY conditioning, thymic irradiation and in vivo T-cell depletion with thymoglobulin. Stable lymphohematopoietic chimerism was achieved in most patients and prophylactic CYA was tapered at a median of day +30. Seven patients (33%) showed partial response and three (14%) achieved stable disease. Four patients were alive at 2 years and three showed prolonged disease control of 344, 525 and 550 days. With a median follow-up of 209 (4-1147) days, the median PFS was 100 days (95% confidence interval (CI), 66-128 days), and median OS was 209 days (95% CI, 128-236 days). Patients with chronic GVHD had better survival-median OS 426 days (95% CI, 194-NE days) vs 143 days (95% CI, 114-226 days) (P=0.010). Thus, NST may induce meaningful clinical responses in patients with advanced NPC.

Modulation of oxidative stress by Chlorella vulgaris in streptozotocin (STZ) induced diabetic Sprague-Dawley rats.

PURPOSE: Chlorella vulgaris (CV), a fresh water alga has been reported to have hypoglycemic effects. However, antioxidant and anti-inflammatory effects of CV in diabetic animals have not been investigated to date. The aim of the present study was to investigate the role of CV in inflammation and oxidative damage in STZ-induced diabetic rats. MATERIALS AND METHODS: Male Sprague-Dawley rats (300 - 400g) were divided into 4 groups: control, CV, STZ-induced diabetic rats, and STZ rats treated with CV (150mg/kg body wt). Blood samples were drawn from orbital sinus at 1 and 4 weeks for determination of oxidative cellular damage (DNA damage and lipid peroxidation [malondialdehyde, MDA]), inflammation (tumour necrosis factor alpha, TNF-α) and antioxidant status (catalase, CAT, and superoxide dismutase, SOD). RESULTS: CV did not have any effects on glucose levels in diabetic rats, over the 4 weeks of treatment. However, it reduced significantly DNA damage and blood MDA levels in STZ-induced diabetic rats compared to the control group. Plasma levels of TNF-α however did not show any significant changes in STZ-induced diabetic rats fed with CV. Antioxidant enzyme SOD showed no significant changes in all groups but CAT activity was reduced in STZ-induced diabetic rats compared to the control. CONCLUSIONS: CV did not have hypoglycaemic effect but it has a protective role in STZ-induced diabetic rats by reducing oxidative DNA damage, and lipid peroxidation.

Complications and mortality in older surgical patients in Australia and New Zealand (the REASON study): a multicentre, prospective, observational study.

We conducted a prospective study of non-cardiac surgical patients aged 70 years or more in 23 hospitals in Australia and New Zealand. We studied 4158 consecutive patients of whom 2845 (68%) had pre-existing comorbidities. By day 30, 216 (5%) patients had died, and 835 (20%) suffered complications; 390 (9.4%) patients were admitted to the Intensive Care Unit. Pre-operative factors associated with mortality included: increasing age (80-89 years: OR 2.1 (95% CI 1.6-2.8), p < 0.001; 90+ years: OR 4.0 (95% CI 2.6-6.2), p < 0.001); worsening ASA physical status (ASA 3: OR 3.1 (95% CI 1.8-5.5), p < 0.001; ASA 4: OR 12.4 (95% CI 6.9-22.2), p < 0.001); a pre-operative plasma albumin < 30 g.l⁻¹ (OR: 2.5 (95% CI 1.8-3.5), p < 0.001); and non-scheduled surgery (OR 1.8 (95% CI 1.3-2.5), p < 0.001). Complications associated with mortality included: acute renal impairment (OR 3.3 (95% CI 2.1-5.0), p < 0.001); unplanned Intensive Care Unit admission (OR 3.1 (95% CI 1.9-4.9), p < 0.001); and systemic inflammation (OR 2.5 (95% CI 1.7-3.7), p < 0.001). Patient factors often had a stronger association with mortality than the type of surgery. Strategies are needed to reduce complications and mortality in older surgical patients.

Molecular and pharmacodynamic properties of estrogenic extracts from the traditional Chinese medicinal herb, Epimedium.

The Chinese medicinal herb, Epimedium, used traditionally for bone health exerts estrogenic activity (EA) in vitro. A genetically characterized Epimedium brevicornum (EB) extract induced biphasic responses in the mRNA and protein expression of the estrogen-regulated progesterone receptor gene in breast cancer (MCF-7) cells. These changes were mirrored changes in estrogenic receptor (ERalpha) content. In male Sprague-Dawley rats, administration of the estrogenic prodrug, estradiol valerate increased area-under-curve of serum effects for ERalpha (AUC difference: 18,900EA(ERalpha) min; 95% CI: 0-37,800; p = 0.05) and breast cancer cell (MCF-7) growth (AUC difference: 30,200EA(MCF-7) min; 95% CI: 24,200-36,200; p<0.001), compared to placebo. Oral administration of Epimedium brevicornum increased ERalpha activity (1320EA(ERalpha) min, p<0.01). Our data indicate that estrogen-responsive bioassays can measure the pharmacokinetic/pharmacodynamics of estrogenic activity in serum. Epimedium brevicornum extract increases estrogenic activity in serum and human studies are required to evaluate whether Epimedium extracts have utility for estrogen replacement therapy.