Category: Nevin Manimala

Phys Med Biol. 2021 Feb 24. doi: 10.1088/1361-6560/abe956. Online ahead of print.

ABSTRACT

Integrated-type proton computed tomography (pCT) measures proton stopping power ratio (SPR) images for proton therapy treatment planning, but its image quality is degraded due to noise and scatter. Although several correction methods have been proposed, techniques that include estimation of uncertainty are limited. This study proposes a novel uncertainty-aware pCT image correction method using a Bayesian convolutional neural network (BCNN). A DenseNet-based BCNN was constructed to predict both a corrected SPR image and its uncertainty from a noisy SPR image. A total 432 noisy SPR images of 6 non-anthropomorphic and 3 head phantoms were collected with Monte Carlo simulations, while true noise-free images were calculated with known geometric and chemical components. Heteroscedastic loss and deep ensemble techniques were performed to estimate aleatoric and epistemic uncertainties by training 25 unique BCNN models. 200-epoch end-to-end training was performed for each model independently. Feasibility of the predicted uncertainty was demonstrated after applying two post-hoc calibrations and calculating spot-specific path length uncertainty distribution. For evaluation, accuracy of head SPR images and water-equivalent thickness (WET) corrected by the trained BCNN models was compared with a conventional method and non-Bayesian CNN model. BCNN-corrected SPR images represent noise-free images with high accuracy. Mean absolute error in test data was improved from 0.263 for uncorrected images to 0.0538 for BCNN-corrected images. Moreover, the calibrated uncertainty represents accurate confidence levels, and the BCNN-corrected calibrated WET was more accurate than non-Bayesian CNN with high statistical significance. Computation time for calculating one image and its uncertainties with 25 BCNN models is 0.7 seconds with a consumer grade GPU. Our model is able to predict accurate pCT images as well as two types of uncertainty. These uncertainties will be useful to identify potential cause of SPR errors and develop a spot-specific range margin criterion, toward elaboration of uncertainty-guided proton therapy.

PMID:33626513 | DOI:10.1088/1361-6560/abe956

J Pharm Biomed Anal. 2021 Feb 10;197:113961. doi: 10.1016/j.jpba.2021.113961. Online ahead of print.

ABSTRACT

Epilepsy is one of the most prevalent neurological disorders, affecting approximately 1% of the world population. Despite the availability of dozens of antiepileptic drugs (AEDs) in clinical practice, the number of patients who do not respond to treatment and/or exhibit high pharmacokinetic variability remains significant, highlighting the importance of therapeutic drug monitoring (TDM). Plasma and serum are the main biological matrices applied for the TDM of AEDs, but the necessity of a specialized professional has been an obstacle to sample collection in ambulatory. Thus, drug quantification in saliva arises as a promising alternative. Herein, a novel highperformance liquid chromatographic (HPLC) technique with diode-array detection (DAD) was developed and fully validated, in order to simultaneously quantify carbamazepine, carbamazepine-10,11-epoxide, S-licarbazepine, lacosamide and levetiracetam in human saliva. The technique was linear in the following concentration ranges: 0.2-6 mg L^-1 for carbamazepine and carbamazepine-10,11-epoxide; 0.3-9 mg L^-1 for S- licarbazepine; 1-30 mg L^-1 for lacosamide; and 0.8-24 mg L^-1 for levetiracetam. The lower limits of the established calibration ranges are below therapeutic margins, attesting a sensitive drug quantification. Accuracy values ranged from -14.76 to 9.35 % and -12.87 and 11.18 % in intra-day and inter-day analysis, respectively. Intra-day values of precision varied between 3.45-10.76% and inter-day values ranged from 3.85 to 13.05 %. This method was subsequently applied to saliva samples of epileptic patients admitted to the Refractory Epilepsy Centre of Centro Hospitalar e Universitário de Coimbra (CHUC EPE, Coimbra). The results of saliva samples were correlated with drug concentrations in plasma from the same patients. Statistically significant correlations were observed (p < 0.05) for carbamazepine (r² = 0.6887; r = 0.8299), carbamazepine-10,11-epoxide (r² = 0.8633; r = 0.9291), S-licarbazepine (r² = 0.5266; r = 0.7257) and levetiracetam (r² = 0.7103; r = 0.8428). Our data support that this method can be used in TDM of AEDs using human saliva samples, constituting a new approach to establish individual therapeutic ranges and assess patient’s adherence to treatment.

PMID:33626445 | DOI:10.1016/j.jpba.2021.113961

Gait Posture. 2021 Feb 13;85:258-265. doi: 10.1016/j.gaitpost.2021.02.004. Online ahead of print.

ABSTRACT

BACKGROUND: Several multi-segment foot models have been developed to evaluate foot and ankle motion using skin-marker motion analysis. However, few multi-segment models have been evaluated against a reference standard to establish kinematic accuracy.

RESEARCH QUESTION: How accurately do skin-markers estimate foot and ankle motion for the modified Shriners Hospitals for Children Greenville (mSHCG) multi-segment foot model when compared against the reference standard, dual fluoroscopy (DF), during gait, in asymptomatic participants?

METHODS: Five participants walked overground as full-body skin-marker trajectory data and DF images of the foot and shank were simultaneously acquired. Using the mSHCG model, ankle and midfoot angles were calculated throughout stance for both motion analysis techniques. Statistical parametric mapping assessed differences in joint angles and marker positions between skin-marker and DF motion analysis techniques. Paired t tests, and linear regression models were used to compare joint angles and range of motion (ROM) calculated from the two techniques.

RESULTS: In the coronal plane, the skin-marker model significantly overestimated ROM (p = 0.028). Further, the DF model midfoot ROM was significantly positively related to differences between DF and skin-marker midfoot angles (p = 0.035, adjusted R² = 0.76). In the sagittal plane, skin-markers underestimated ankle angles by as much as 7.26°, while midfoot angles were overestimated by as much as 9.01°. However, DF and skin-marker joint angles were not significantly different over stance. Skin-markers on the tibia, calcaneus, and fifth metatarsal had significantly different positions than the DF markers along the direction of walking for isolated portions that were less than 10 % of stance. Euclidean distances between DF and skin-markers positions were less than 9.36 mm.

SIGNIFICANCE: As the accuracy of the mSHCG model was formerly unknown, the results of this study provide ranges of confidence for key angles calculated by this model.

PMID:33626450 | DOI:10.1016/j.gaitpost.2021.02.004

J Contam Hydrol. 2021 Jan 22;238:103774. doi: 10.1016/j.jconhyd.2021.103774. Online ahead of print.

ABSTRACT

In the densely urbanised Milan Metropolitan area (northern Italy), the long history of anthropogenic activities still exerts a significant pressure on groundwater resource. One of the most serious threats to the water quality of urban aquifers is attributed to diffuse contamination, which is caused by a series of unknown small sources (i.e., multiple point sources) distributed over large areas. In the study area and in many industrialised regions of the world, tetrachloroethylene [PCE], trichloroethylene [TCE] and hexavalent chromium [Cr(VI)] represent the common example of long-standing and persistent pollution in groundwater. In the Milan Metropolitan area, high levels of PCE + TCE and Cr(VI) were detected in the shallow aquifer as well as in the deep aquifer. To assess and map the shallow and deep aquifers susceptibility to PCE + TCE and Cr(VI) contamination at a regional scale, the Weights of Evidence modelling technique has been applied. This method has been used to objectively evaluate the spatial correlation between the high presence of these pollutants in each aquifer and hydrogeological and land use factors that can potentially influence the contamination. Moreover, the results allowed us to quantify on a large scale the effect that preferential flowpaths, due to both thickness variation in the aquitard and the areal density of multi aquifer wells, have in reducing the protection of the underlying deep aquifer. The end-products of the study constitute a key tool to be used by water-resource managers and decision-makers for the improvement of groundwater management and protection strategies.

PMID:33626464 | DOI:10.1016/j.jconhyd.2021.103774

Am Heart J. 2021 Feb 21:S0002-8703(21)00057-0. doi: 10.1016/j.ahj.2021.01.020. Online ahead of print.

ABSTRACT

BACKGROUND: Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear.

METHODS AND RESULTS: In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n=908) versus those who did not (Controls, n=1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; p<0.001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; p=0.001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], p<0.001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], p<0.05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile).

CONCLUSION: In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.

PMID:33626384 | DOI:10.1016/j.ahj.2021.01.020

Life Sci. 2021 Feb 21:119265. doi: 10.1016/j.lfs.2021.119265. Online ahead of print.

ABSTRACT

The objective of the current study was examining early and late (3, 24 h) responses to acute, chronic swimming exercise as muscle damage and regeneration in gastrocnemius-soleus muscle complexes. We also aimed to reveal the signaling pathways involved. 8-12 weeks old mice were grouped as control, exercise. Exercising groups were firstly divided into two as acute and chronic, later every group was again divided in terms of time (3, 24 h) passed from the last exercise session until exsanguination. Acute exercise groups swam 30 min, while chronic swimming groups exercised 30 min/day, 5 days/week, 6 weeks. Histological investigations were performed to determine muscle damage and regeneration. Whole-genome expression analysis was applied to total RNA samples. Microarray data was confirmed by quantitative real-time PCR. Exercising mice muscle revealed enhanced damage, leukocyte infiltration. Increments in acute and chronic 3 h groups were statistically significant. Car3, Neb, Obscn, Ttn, Igfbp5, Igfbp7, Gsk3β, and Usp2 were down-regulated in muscles of swimming mice. The exercise-induced signaling pathways involved in muscle damage and regeneration were drawn. Our findings demonstrate that swimming induces muscle damage. Samples were obtained at 3 and 24 h following exercise, this time duration seems not sufficient for the development of myofibrillogenesis.

PMID:33626393 | DOI:10.1016/j.lfs.2021.119265

Eur J Oncol Nurs. 2021 Feb 15;51:101908. doi: 10.1016/j.ejon.2021.101908. Online ahead of print.

ABSTRACT

PURPOSE: To test the effectiveness of henna in the management of palmar-plantar erythrodysesthesia (PPE) in patients receiving treatment with capecitabine or pegylated liposomal doxorubicin (PLD).

METHOD: This was a randomized controlled feasibility study in three specialized tertiary cancer centers with 56 patients with a PPE grade 1 or above and various cancer diagnoses. The intervention included the local application of henna to the affected areas. The control group followed the same process with a henna inert. Primary outcome was PPE grade and secondary outcomes were the EORTC QLQ-C30, PPE-related QoL (HFS-14), activities of daily living (ECOG) and pain. Patients in both groups were assessed at baseline and then weekly at four follow-ups.

RESULTS: PPE grade in the intervention group (1-3.8%) was lower compared to the control group (4-13.38%) and also lower levels of pain were reported by the patients in the intervention group (2.46 ± 1.17) compared to the control (5.57 ± 2.01). ECOG status in the intervention group was improved compared to the control (p = 0.039). The intervention group, experienced higher Global Health Status (p ≤ 0.008), Physical function (p ≤ 0.001), Emotional Function (p = 0.029), Social function (p ≤ 0.001) and lower Fatigue (p ≤ 0.001) and Pain (p ≤ 0.001) compared to the Control group. A statistically significant interaction was found between Group and Time over the weekly measurements of HFS-14 scores (F = 5,009, p ≤ 0.002) indicating the significant effect of the intervention throughout the weekly assessments.

CONCLUSION: The trial provided preliminary evidence on henna’s effectiveness for treating PPE during treatment with capecitabine or PLD, with lower PPE grades, better performance status and better HRQoL observed in the henna group. CLINICALTRIALS.

GOV IDENTIFIER: NCT01751893.

PMID:33626423 | DOI:10.1016/j.ejon.2021.101908

Pregnancy Hypertens. 2021 Feb 14;24:13-21. doi: 10.1016/j.preghy.2021.02.001. Online ahead of print.

ABSTRACT

Hypertensive disorders in pregnancy (HDP) are associated with various maternal and fetal adverse outcomes and become an increasingly significant threat to Chinese pregnant women. Yet, the prevalence of HDP in China is not clear. We conducted this meta-analysis to estimate the prevalence of HDP and specific subtypes in China. We searched PubMed, Embase, Web of Science, CNKI, Wangfang, and CMB for studies on prevalence of HDP and specific subtypes, published from 1990 to Jan 21, 2020, without language restrictions. We included all studies reported the prevalence of HDP and specific subtypes in Chinese pregnant women. We excluded qualitative studies, case reports, reviews, conference presentations, and studies only provided abstracts. We using a standard self-developed form to extract information from eligible studies. We did meta-analyses by random-effect models and estimated the pooled prevalence of HDP and specific subtypes. In order to explore potential sources of heterogeneity and subgroup effects, we did and meta-regression and subgroup analyses by pre-specified covariates. This study is registered with PROSPERO, number CRD42020166001. We initially identified 4179 records, of which 92 studies with 1,377,448 participants were eligible in the final systematic review and meta-analyses. The pooled prevalence (95% CI) of HDP, gestational hypertension, preeclampsia, mild preeclampsia, severe preeclampsia, eclampsia, chronic hypertension, and chronic hypertension with superimposed preeclampsia were 7.30% (6.60%-8.00%), 3.30% (2.90%-3.70%), 4.50% (4.00%-5.00%), 2.00% (1.70%-2.30%), 2.60% (2.10%-3.00%), 0.11% (0.08%-0.15%), 0.60% (0.30%-0.90%), and 0.60% (0.40%-0.80%), respectively. No publication bias was identified, although heterogeneity was high (I² statistics: 92.0%-99.3%). High prevalence of HDP and the subtypes frequently reported in Western and Northern China. Pregnant women who were aged 35 years and above had high prevalence of HDP and subtypes; women who were overweight or obese had high prevalence of HDP, gestational hypertension and preeclampsia. The prevalence of HDP and the subtypes vary in different areas in China. Given to increasingly prevalent of the risk factors, such as overweight, obesity, and advance maternal age, strategies to prevent and manage HDP need to be improved, especially for women living in Western and Northern China.

PMID:33626437 | DOI:10.1016/j.preghy.2021.02.001

Neurotoxicol Teratol. 2021 Feb 21:106963. doi: 10.1016/j.ntt.2021.106963. Online ahead of print.

ABSTRACT

Methylmercury (MeHg) is a persistent environmental neurotoxicant that may cause adverse neurodevelopmental effects. Previous studies showed that developmental MeHg exposure caused damage to brain functions that were unmasked after a silent period of years or decades. However, the underlying mechanisms of the latent neurotoxicity associated with MeHg exposure from earlier developmental stages have yet to be fully understood. Herein, we established a Caenorhabditis elegans (C. elegans) model of developmental MeHg latent toxicity. Synchronized L1 stage worms were exposed to MeHg (0, 0.05, 0.5 and 5 μM) for 48 h. Swimming moving speeds at adulthood were analyzed in worms exposed to MeHg exposure at early larvae stages. Worms developmentally exposed to MeHg had a significant decline in swimming moving speed on day 10 adult stage, but not on day 1 or 5 adult stage, even though the mercury level in the worms exposed to 0.05 or 0.5 μM MeHg were below the quantification limit on day 10 adult. Day 10 adult worms treated with MeHg showed a significant decrease in bending angle and bending frequency during swimming. Furthermore, their reduced moving speeds tended to increase during the 300-s swimming experiment. Dopamine signaling is known to be involved in the regulation of worms’ moving speed. Accordingly, the moving speed of worms with cat-2 (mammalian tyrosine hydroxylase homolog) mutation or dat-1 deletion were assayed on day 10 adult. The cat-2 mutant worms did not show a decline in moving speeds, body bends or bending angles during swimming on day 10 adult stage. Analyses of moving speeds of worms with dat-1 deletion showed that the moving speeds were further reduced after MeHg exposure. However, the effects of MeHg and dat-1 deletion were not synergistic, as the interaction between these parameters did not attain statistical significance. Altogether, our results suggest that developmental MeHg exposure reduced moving speed, and this latent toxicity was less pronounced in the context of deficient production of dopamine synthesis. Tyrosine hydroxylase plays an important role in regulating dopamine-mediated modulation of neurobehavioral functions. These findings uncovered a pivotal role of dopamine and its metabolism in the latent neurotoxic effects of MeHg.

PMID:33626374 | DOI:10.1016/j.ntt.2021.106963

Ann Oncol. 2021 Jan 21:S0923-7534(21)00014-4. doi: 10.1016/j.annonc.2021.01.006. Online ahead of print.

ABSTRACT

BACKGROUND: We predicted cancer mortality statistics for 2021 for the European Union (EU) and its five most populous countries plus the UK. We also focused on pancreatic cancer and female lung cancer.

MATERIALS AND METHODS: We obtained cancer death certifications and population data from the World Health Organization and Eurostat databases for 1970-2015. We predicted numbers of deaths and age-standardized (world population) rates for 2021 for total cancers and 10 major cancer sites, using a joinpoint regression model. We calculated the number of avoided deaths over the period 1989-2021.

RESULTS: We predicted 1,267,000 cancer deaths for 2021 in the EU, corresponding to age-standardized rates of 130.4/100,000 men (-6.6% since 2015) and 81.0 for women (-4.5%). We estimated further falls in male lung cancer rates, but still trending upward in women by +6.5%, reaching 14.5/100,000 in 2021. Breast cancer predicted rate in the EU was 13.3 (-7.8%). Rates for stomach and leukaemias in both sexes and for bladder in males are predicted to fall by over 10%; trends for other cancer sites were also favourable, except for pancreas, which showed stable patterns in both sexes, with predicted rates of 8.1/100,000 men and 5.6 for women. Rates for pancreas in EU men aged 25-49 and 50-64 declined, respectively, by 10% and 1.8%, while for those aged 65+ increased by 1.3%. Rates fell for young women only (-3.4%). Over 1989-2021, about 5 million cancer deaths were avoided in the EU27 compared with peak rates in 1988.

CONCLUSION: Overall cancer mortality continues to fall in both sexes. However, specific focus is needed on pancreatic cancer, which shows some hint of decline for young men only. Tobacco control remains a priority for the prevention of pancreatic and other tobacco-related cancers, which account for a third of the total EU cancer deaths, especially in women, who showed less favourable trends.

PMID:33626377 | DOI:10.1016/j.annonc.2021.01.006