To implement a robust and fast stereotactic MR-guided adaptive radiation therapy (SMART) online strategy in locally advanced pancreatic cancer (LAPC).
SMART strategy for plan adaptation was ...implemented with the MRIdian system (ViewRay Inc.). At each fraction, OAR (re-)contouring is done within a distance of 3cm from the PTV surface. Online plan re-optimization is based on robust prediction of OAR dose and optimization objectives, obtained by building an artificial neural network (ANN). Proposed limited re-contouring strategy for plan adaptation (SMART3CM) is evaluated by comparing 50 previously delivered fractions against a standard (re-)planning method using full-scale OAR (re-)contouring (FULLOAR). Plan quality was assessed using PTV coverage (V95%, Dmean, D1cc) and institutional OAR constraints (e.g. V33Gy).
SMART3CM required a significant lower number of optimizations than FULLOAR (4 vs 18 on average) to generate a plan meeting all objectives and institutional OAR constraints. PTV coverage with both strategies was identical (mean V95%=89%). Adaptive plans with SMART3CM exhibited significant lower intermediate and high doses to all OARs than FULLOAR, which also failed in 36% of the cases to adhere to the V33Gy dose constraint.
SMART3CM approach for LAPC allows good OAR sparing and adequate target coverage while requiring only limited online (re-)contouring from clinicians.
Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and ...the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites.MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment.
Peanut or groundnut (Arachis hypogaea L.) is cultivated in the tropical and warm temperate regions of the world. Its production reaches approximately 39.9millionmetrictonsperyear. The major ...producers/exporters of peanuts are the United States, Argentina, Sudan, Senegal, and Brazil. One of the major problems in peanut production worldwide is the contamination with Aspergillus section Flavi and aflatoxins, being these mycotoxins of great concern due to their toxicological effects to human and animals. Different strategies both at pre-harvest and post-harvest stages have been applied to reduce the entry of aflatoxins to the food and feed chains. Nowadays, no single strategy is enough to solve this problem. An integrate management from the field until food or feed processing is necessary to reduce the impact of aflatoxins. This review summarizes the advance in reducing the impact of aflatoxins in different countries where peanuts are cultivated.
•Recent advances in methodologies to prevent aflatoxin contamination in peanuts.•We summarized guidelines and code of practices, mainly on pre-harvest strategies.•Genetic resistance of peanut to Aspergillus infection and aflatoxin accumulation.•Biocontrol, competitive exclusion by genetically well-studied non-toxigenic strains.•Predictive systems should include crop phenology models or in-season observations.
To assess the therapeutic efficacy, required dose, and tolerability of pregabalin in patients with idiopathic restless legs syndrome (RLS).
This was a double-blind, placebo-controlled trial with ...polysomnographic control, providing Class II evidence. Ninety-eight patients underwent a 2-week single-blind period with placebo; 58 were randomized to receive pregabalin or placebo for 12 weeks under a flexible-dose schedule. Endpoints were mean change from baseline in the International Restless Legs Scale (IRLS) total score, Clinical Global Impression (CGI), and RLS-6 scales, as well as changes in periodic limb movements (PLMs) and sleep architecture.
Patients under treatment with pregabalin had a greater improvement in IRLS score than under placebo (63% vs 38.2%; p < 0.05). The mean effective dose of pregabalin at the end of treatment was 322.50 mg/day (+/-98.77), although therapeutic effects were already seen at a mean dose of 139 mg/day. Similarly, improvements were observed on the CGI, RLS-6 scale, and the Medical Outcomes Study sleep scale (all p < 0.01) when compared to placebo. Treatment with pregabalin also resulted in a reduction of the mean (+/-SD) PLM index (p < 0.001). Furthermore, there was a marked improvement in sleep architecture with an increase in slow wave sleep (p < 0.01), and decreases in wake after sleep onset and stages 1 and 2 (p < 0.05). Pregabalin was generally well-tolerated. Adverse events were mild but common, and included unsteadiness, daytime sleepiness, and headache.
This study shows significant therapeutic effects of pregabalin on both sensorial and motor symptoms in restless legs syndrome. Treatment with pregabalin was associated with an improvement of sleep architecture and periodic limb movements. Adverse events included unsteadiness and sleepiness and should be screened carefully in the working population, particularly when pregabalin is administered in the afternoon.
This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.
Fusarium Head Blight (FHB) is a very important fungal disease that affects small grain cereals worldwide. This disease not only causes yield loses but also crops contamination with mycotoxins such as ...deoxynivalenol (DON) and nivalenol (NIV). Species within the Fusarium graminearum species complex have been described as the main causal agents of this disease, however lately there have been few reports of Fusarium cerealis causing the disease in wheat and barley in different parts of the world. This study evaluated the aggressiveness of F. cerealis to durum wheat cultivars and also mycotoxin production in planta. Moreover, the mycotoxin profile of F. cerealis strains was characterized molecularly and chemically. All durum wheat cultivars showed typical FHB symptoms but the disease severity varied among them in levels up to 66%. In addition, seventeen different compounds were detected in the infected heads including DON, NIV and nivalenol-3-β-d-glucose (NIV3G). NIV was detected in all cultivars and was the most produced mycotoxin with levels ranging from 1.04 to 6.8 mg/kg. On the other hand, the molecular analysis of F. cerealis strains showed that all of them possessed NIV genotype while the chemical assessment showed that the strains were able to produce not only this toxin in vitro but also DON, zearalenone and other twenty-one secondary metabolites. The increasing incidence of F. cerealis and the possible contamination of crops with the mycotoxins that it produces are of great concern for food security and world cereal trade since it has been reported that NIV is more toxic for humans and animals than DON.
•All durum wheat cultivars inoculated with Fusarium cerealis showed FHB symptoms.•Seventeen compounds were detected in the inoculated ears, including deoxynivalenol.•Nivalenol was the most produced mycotoxin in planta.•All strains presented NIV genotype and were able to produce the toxin in vitro.•F. cerealis strains produced several compounds in vitro, including deoxynivalenol.
Precision medicine is an approach to disease diagnosis, treatment, and prevention that relies on quantitative biomarkers that minimize the variability of individual patient measurements. The aim of ...this study was to assess the intersite variability after harmonization of a high-angular-resolution 3T diffusion tensor imaging protocol across 13 scanners at the 11 academic medical centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury multisite study.
Diffusion MR imaging was acquired from a novel isotropic diffusion phantom developed at the National Institute of Standards and Technology and from the brain of a traveling volunteer on thirteen 3T MR imaging scanners representing 3 major vendors (GE Healthcare, Philips Healthcare, and Siemens). Means of the DTI parameters and their coefficients of variation across scanners were calculated for each DTI metric and white matter tract.
For the National Institute of Standards and Technology diffusion phantom, the coefficients of variation of the apparent diffusion coefficient across the 13 scanners was <3.8% for a range of diffusivities from 0.4 to 1.1 × 10
mm
/s. For the volunteer, the coefficients of variations across scanners of the 4 primary DTI metrics, each averaged over the entire white matter skeleton, were all <5%. In individual white matter tracts, large central pathways showed good reproducibility with the coefficients of variation consistently below 5%. However, smaller tracts showed more variability, with the coefficients of variation of some DTI metrics reaching 10%.
The results suggest the feasibility of standardizing DTI across 3T scanners from different MR imaging vendors in a large-scale neuroimaging research study.
► The mushrooms contained between 1 and 6
mg of phenolics per gram of dried matter. ► The total flavonoid concentration ranged between 0.9 and 3
mg per gram (DM). ► Homogentisic acid was the free ...phenolic acid significantly present in all mushrooms. ► Flavonoids, such as myricetin and catechin, are also detected. ►
C. cibarius is the most effective inhibiting linoleic acid oxidation.
Total phenolic and flavonoid contents occurring in eight types of edible mushrooms (
Agaricus bisporus,
Boletus edulis,
Calocybe gambosa,
Cantharellus cibarius,
Craterellus cornucopioides,
Hygrophorus marzuolus,
Lactarius deliciosus and
Pleurotus ostreatus) have been respectively evaluated by the Folin–Ciocalteau assay and by the colorimetric reaction with NaNO
2 and AlCl
3 in a basic media. Generally, the assayed mushrooms contained between 1 and 6
mg of phenolics per gram of dried mushroom, depending on the species, while the flavonoid concentrations ranged between 0.9 and 3.0
mg per gram of dried matter. The profile and concentration of individual phenolics was determined by means of high performance liquid chromatography. Homogentisic acid was the free phenolic acid significantly present in all mushrooms although the content varied considerably among the analysed species. Flavonoids, such as myricetin and catechin were also detected in the mushrooms studied. The antioxidant properties of the methanolic extracts from mushrooms were evaluated by monitoring the linoleic acid autoxidation, and all the mushrooms species showed inhibition, with
C. cibarius being the most effective against lipid oxidation (74% of inhibition) and
A. bisporus the species with lowest antioxidant activity (10% of inhibition).
To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC.
...Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited.
Multicenter, retrospective, matched cohort 1:2 study.
42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3-142) months.
The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001).
Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.
With the prevalence of obesity rapidly increasing worldwide, understanding the processes leading to excessive eating behavior becomes increasingly important. Considering the widely recognized crucial ...role of reward processes in food intake, we examined the white matter wiring and integrity of the anatomical reward network in obesity. Anatomical wiring of the reward network was reconstructed derived from diffusion weighted imaging in 31 obese participants and 32 normal-weight participants. Network wiring was compared in terms of the white matter volume as well as in terms of white matter microstructure, revealing lower number of streamlines and lower fiber integrity within the reward network in obese subjects. Specifically, the orbitofrontal cortex and striatum nuclei including accumbens, caudate and putamen showed lower strength and network clustering in the obesity group as compared to healthy controls. Our results provide evidence for obesity-related disruptions of global and local anatomical connectivity of the reward circuitry in regions that are key in the reinforcing mechanisms of eating-behavior processes.
•This study analyzes the structural connectivity of the reward system in obesity.•The highly homogeneous sample consists of metabolically healthy young participants.•Obesity group shows lower volume and integrity in the reward system pathways.•Results evidence affected reward system connectivity in obesity.•Results suggest a neuroanatomical substrate for reward related to eating behavior.
A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic ...cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm (“very early”) in which results after LT can be acceptable. Twenty‐nine patients comprised the study group, eight of whom had a “very early” iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the “very early” iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1‐, 3‐ and 5‐year actuarial survival of those in the “very early” iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5‐year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.
This multicenter study analyzes the outcome of patients transplanted for hepatocellular carcinoma who were found to have an intrahepatic cholangiocarcinoma at pathology examination, and focuses on the excellent posttransplant outcome of patients with single intrahepatic cholangiocarcinomas ≤2 cm.
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