Abstract In accordance with Article 43 of Regulation (EC) No 396/2005, the European Commission requested EFSA to carry out a consumer exposure assessment in relation to the maximum residue levels (MRLs) for chlordecone in products of animal origin recommended by the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) in an assessment performed in 2018. The MRL proposals under assessment are lower than the current EU MRLs established under Regulation (EC) 396/2005. The...
04:28
In the United States, the five-year survival rate from colorectal cancer (CRC) for Latinos is lower than it is for White, non-Latinos. Differences in survival are due in part to Latinos being diagnosed at a later stage. An ethnic gap in the use of CRC screening contributes to the difference in survival. We developed, implemented and evaluated a targeted CRC screening intervention to increase CRC screening uptake by sex, ethnicity and geography. We measured actual CRC screening uptake in both arms...
Tue Mar 03, 2020 20:43
Abstract Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral/neurodevelopmental disorder. Some early studies indicated that increased intake of added sugars might have a role in ADHD. In the present study, we tested this possibility by evaluating the urinary excretion of oligosaccharides and glycosaminoglycans (GAGs) in ADHD and control subjects. Forty ADHD subjects matched with 34 controls were enrolled in the study. The subjects underwent a standardized...
02:00
Abstract Pompe disease, a rare, autosomal, recessive, inherited, lysosomal storage disorder, is caused by mutations in the acid α-glucosidase (GAA) gene leading to a deficiency of the lysosomal GAA enzyme. Some GAA mutations eliminate all enzymatic activities, causing severe infantile Pompe disease; others allow residual GAA activity and lead to middle adulthood forms. Here, we report a cohort of 12 patients, belonging to 11 unrelated families, with infantile Pompe disease. The...
Tue Mar 03, 2020 02:00
Abstract Previously, we showed that Src-mediated EGF receptor transactivation/ERK activation mediates ammonia-induced astrocyte swelling, which represents a major component of brain edema in hyperammonemic disorders. Here, we tested the role of PKC in the induction of this signaling pathway and its involvement in ammonia-mediated cell swelling. We found that incubating astrocytes with bisindolylmaleimide (BIM, an inhibitor of classical and novel PKC isoforms) or rottlerin, a PKCδ-specific...
Tue Mar 03, 2020 02:00
Abstract Whether blood amyloid-β (Aβ) could be a peripheral biomarker of Alzheimer’s disease (AD) remains in dispute. In the present study, we conducted a meta-analysis with 19 citations searched from Embase, PubMed, and the Cochrane Library database. Weighted mean difference (WMD) with 95% confidence intervals (CIs) was used to estimate the effect size. We firstly analyzed the plasma Aβ40, Aβ42, and Aβ42/Aβ40 ratio in AD and control group subjects. However, only a lower level...
Tue Mar 03, 2020 02:00
Abstract Local adaptation patterns have been found in many plants and animals, highlighting the genetic heterogeneity of species along their range of distribution. In the next decades, global warming is predicted to induce a change in the selective pressures that drive this adaptive variation, forcing a reshuffling of the underlying adaptive allele distributions. For species with low dispersion capacity and long generation time such as trees, the rapidity of the change could imped the migration...
04:23
Abstract Sperm cells exhibit extraordinary phenotypic diversity and rapid rates of evolution, yet the adaptive value of most sperm traits remains equivocal. Recent findings suggest that to understand how selection targets ejaculates we must recognize that female‐imposed physiological conditions often alter sperm phenotypes. These phenotypic changes may influence the relationships among sperm traits and their association with fitness. Here, we show that chemical substances released by eggs (known...
04:23
Abstract Background & objective Tracheostomy patients often have cough and early post‐operative pain problems. Typically, patients will receive a normal sterile saline (NSS) nebulizer via a tracheostomy tube. The goal of this research was to establish whether the use of lidocaine together with NSS nebulization through a tracheostoma would be more effective at reducing the cough and pain symptoms compared to the standard NSS nebulization. Materials & methods This prospective,...
04:22
Abstract The authors provide an updated, systematic and comprehensive summary of the literature concerning management of the N0 neck in patients for whom primary irradiation for squamous cell carcinoma of the larynx has been unsuccessful and salvage surgery in the form of total laryngectomy (TL) advocated. Bibliographic databases MEDLINE, Cochrane, Pubmed and EMBASE were searched from inception to April 2019, with no language restrictions. The Preferred Reporting Items for Systematic Reviews...
04:22
Overexpression of transcription factor 3 in Alveolar soft part sarcoma(ASPS) results in upregulation of cell proliferation pathways. No standard treatment algorithm exists for ASPS; multi-kinase inhibitors(TKI) and immune checkpoint inhibitors(ICI) have shown clinical benefit. To date, no studies have reported on management strategies or sequencing of therapy. We evaluated ASPS treatment patterns and responses in an experimental therapeutics clinic. Genomic and morphoproteomic analysis was performed...
Tue Mar 03, 2020 16:59
This first-in-human phase 1 study evaluated the pharmacokinetics, safety, and preliminary efficacy of telisotuzumab, formerly called ABT-700, an antagonistic antibody directed against c-Met. For dose-escalation (3+3 design), three to six patients with advanced solid tumors were enrolled into four dose cohorts (5-25 mg/kg). In the dose-expansion phase, a subset of patients were prospectively selected for MET amplification (FISH screening). Patients received telisotuzumab intravenously on day 1 every...
Tue Mar 03, 2020 16:59
Expression of the DNA/RNA helicase schlafen family member 11 (SLFN11) has been identified as a sensitizer of tumor cells to DNA damaging agents including platinum chemotherapy. We assessed the impact of SLFN11 expression on response to platinum chemotherapy and outcomes in patients with metastatic castration-resistant prostate cancer (CRPC). Tumor expression of SLFN11 was assessed in 41 CRPC patients treated with platinum chemotherapy by RNAseq of metastatic biopsy tissue (n=27) and/or immunofluorescence...
Tue Mar 03, 2020 16:59
There is a need to develop novel approaches to improve the balance between efficacy and toxicity for transcription factor targeted therapies. In this study, we exploit context dependent differences in RNAPII processivity as an approach to improve the activity and limit the toxicity of the EWS-FLI1 targeted small molecule, mithramycin, for Ewing sarcoma. The clinical activity of mithramycin for Ewing sarcoma is limited by off-target liver toxicity that restricts the serum concentration to levels...
Tue Mar 03, 2020 16:59
The development of efficacious therapies targeting metastatic spread of breast cancer to the brain represents an unmet clinical need. Accordingly, an improved understanding of the molecular underpinnings of central nervous system spread and progression of breast cancer brain metastases (BCBM) is required. In this study, the clinical burden of disease in BCBM was investigated, as well as the role of aldehyde dehydrogenase 1A3 (ALDH1A3) in the metastatic cascade leading to BCBM development. Initial...
Tue Mar 03, 2020 16:59
Gastrointestinal stromal tumor (GIST), the most common sarcoma, is characterized by KIT protein overexpression, and tumors are frequently driven by oncogenic KIT mutations. Targeted inhibition of KIT revolutionized GIST therapy and ushered in the era of precision medicine for the treatment of solid malignancies. Here, we present the first use of a KIT-specific DNA aptamer for targeted labeling of GIST. We found that an anti-KIT DNA aptamer bound cells in a KIT-dependent manner and was highly specific...
Tue Mar 03, 2020 16:59
Abstract Objectives To assess the supraspinal working mechanisms of the Burst spinal cord stimulation (SCS)‐mode we used functional magnetic resonance imaging (fMRI) in chronic neuropathic rats. We hypothesized that active recharge Burst SCS would induce a more profound BOLD signal increase in areas associated with cognitive‐emotional aspects of pain, as compared to Tonic SCS. Materials and Methods Sprague Dawley Rats (n=17) received a unilateral partial sciatic nerve ligation which...
04:19
Abstract The underlying mechanism of Seborrheic dermatitis (SD) is poorly understood but major scientific progress has been made in recent years related to microbiology, immunology and genetics. In light of this, the major goal of this article was to summarize the most recent articles on SD, specifically related to underlying pathophysiology. SD results from Malassezia hydrolyzation of free fatty acids with activation of the immune system by the way of pattern recognition receptors, inflammasome,...
04:19
This study applied a social representations approach to investigate the ways in which constructions of perceived political disagreement and the prevailing opinion climate were implicated in people's construals of political participation in the context of the United Kingdom European Union referendum of 2016. Interviews were conducted with 19 residents of the United Kingdom who voted to remain in the referendum, located in constituencies which represented diverse opinion climates in relation to the...
04:18
Alterations in DNA damage response (DDR) genes are common in advanced prostate tumors and are associated with unique genomic and clinical features. ATM is a DDR kinase that has a central role in coordinating DNA repair and cell cycle response following DNA damage, and ATM alterations are present in approximately 5% of advanced prostate tumors. Recently, inhibitors of poly (ADP-ribose) polymerase (PARP) have demonstrated activity in advanced prostate tumors harboring DDR gene alterations, particularly...
Tue Mar 03, 2020 17:14
Although genome-wide association studies (GWAS) have identified more than 100 colorectal cancer (CRC) risk loci, most of the biological mechanisms associated with these loci remain unclear. Here we first performed a comprehensive expression quantitative trait loci (eQTL) analysis in CRC tissues adjusted for multiple confounders to test the determinants of germline variants in established GWAS susceptibility loci on mRNA and long non-coding RNA (lncRNA) expression. Combining integrative functional...
Tue Mar 03, 2020 17:14
RING-finger E3 ligases are instrumental in the regulation of inflammatory cascades, apoptosis, and cancer. However, their roles are relatively unknown in TGF-β/SMAD signaling. SMAD3 and its adaptors, such as β2SP, are important mediators of TGF-β signaling and regulate gene expression to suppress stem cell-like phenotypes in diverse cancers, including hepatocellular carcinoma (HCC). Here, PJA1, an E3 ligase, promoted ubiquitination and degradation of phosphorylated SMAD3 and impaired a SMAD3/β2SP-dependent...
Tue Mar 03, 2020 17:14
The recent success of checkpoint blockade therapies has established immunotherapy as one of the most promising treatments for melanoma. Nonetheless, a complete curative response following immunotherapy is observed only in a fraction of patients. To identify what factors limit the efficacy of immunotherapies, we established mouse models that cease to respond to immunotherapies once their tumors exceed a certain stage. Analysis of the immune systems of the organisms revealed that the numbers of tumor-infiltrating...
Tue Mar 03, 2020 17:14
Purpose Structure‐guided total variation is a recently introduced prior that allows reconstruction of images using knowledge of the location and orientation of edges in a reference image. In this work, we demonstrate the advantages of a variant of structure‐guided total variation known as directional total variation (DTV), over traditional total variation (TV), in the context of compressed‐sensing reconstruction and super‐resolution. Methods We compared TV and DTV in retrospectively undersampled...
04:14
Purpose To develop an accelerated, robust, and accurate diffusion MRI acquisition and reconstruction technique for submillimeter whole human brain in vivo scan on a clinical scanner. Methods We extend the ultra‐high resolution diffusion MRI acquisition technique, gSlider, by allowing undersampling in q‐space and radiofrequency (RF)‐encoding space, thereby dramatically reducing the total acquisition time of conventional gSlider. The novel method, termed gSlider‐SR, compensates for the...
04:14
Purpose Quantitative susceptibility mapping (QSM) has been employed for both iron evaluation and segmentation of deep gray matter (DGM), but QSM sequences are not typically used in standard brain volumetric studies, which use T1‐weighted magnetization‐prepared rapid acquisition with gradient echo (MPRAGE) with short TE. Here, QSM produced directly from standard MPRAGE phase () is evaluated for segmentation and quantification of highly iron‐rich DGM regions. Methods Simulations were used...
04:14
Purpose A model‐based reconstruction framework is proposed for motion‐corrected and high‐resolution anatomically assisted (MOCHA) reconstruction of arterial spin labeling (ASL) data. In this framework, all low‐resolution ASL control‐label pairs are used to reconstruct a single high‐resolution cerebral blood flow (CBF) map, corrected for rigid‐motion, point‐spread‐function blurring and partial volume effect. Methods Six volunteers were recruited for CBF imaging using pseudo‐continuous...
04:14
Purpose In this study, we sought to develop a self‐navigation strategy for improving the reconstruction of diffusion weighted 3D multishot echo planar imaging (EPI). We propose a method for extracting the phase correction information from the acquisition itself, eliminating the need for a 2D navigator, further accelerating the acquisition. Methods In‐vivo acquisitions at 3T with 0.9 mm and 1.5 mm isotropic resolutions were used to evaluate the performance of the self‐navigation strategy....
04:14
Objectives/Hypothesis Empty nose syndrome (ENS) is a controversial disorder and the change of histopathology has never been discussed. This study aimed to conduct a structured histological review to improve the diagnosis and understanding of ENS. Further immunohistochemical staining of transient receptor potential channel melastatin 8 (TRPM8) was performed. Study Design A prospective case–control study in a tertiary medical center. Methods Consecutive patients with ENS who were...
04:09
Objectives/Hypothesis Systemic infusions of lidocaine have been widely used as perioperative analgesic adjuvants. The aim of this randomized, double‐blinded, controlled trial was to investigate the effect of perioperative lidocaine infusion on postoperative early recovery quality in upper airway surgery. Study Design Prospective, randomized, double‐blinded, placebo‐controlled trial. Methods A total of 99 patients were randomly assigned to the lidocaine group (group L) or the...
04:09
Objectives/Hypothesis Otolaryngologic symptoms of obstructive sleep apnea (OSA) and their diagnostic utility are not well studied. We aimed to elucidate the prevalence of otolaryngologic symptoms among patients being evaluated for OSA. Given findings that the Reflux Symptom Index (RSI) was strongly associated with OSA status, we evaluated the diagnostic utility of the RSI for predicting OSA status. Study Design Cross‐sectional. Methods We recruited 101 adults presenting for...
04:09
Abstract Combined training (CT) has been associated with positive responses in the clinical status of patients with chronic heart failure (CHF). Other non‐pharmacological tools, such as amino acid supplementation, may further enhance its adaptation. However, the effects of β‐alanine and L‐histidine supplementation in CHF remain unclear. In the present study, the aim was to test whether supplementing carnosine precursors with CT could present improved responses in the functional capacity and echocardiographic...
04:09
NEW FINDINGS What is the central question of this study? A bout of exercise increases subsequent insulin‐stimulated vasodilation; however, the mechanisms remain to be elucidated. A potential role for Angiotensin‐(1‐7), a vasoactive peptide of the Renin‐Angiotensin System, in this effect has not been previously reported. What is the main finding and its importance? We show that Angiotensin‐(1‐7) through Mas receptor participates in enhanced insulin‐induced vasorelaxation after exercise...
04:09
Abstract Background The influence of concomitant brain pathologies on the progression rate in PSP is unclear. Objectives To analyze the frequency and severity of copathologies and their impact on the progression in PSP. Methods We analyzed clinic‐pathological features of 101 PSP patients. Diagnoses and stages of copathologies were established according to standardized criteria, including Alzheimer's disease–related pathology, argyrophilic grains, Lewy‐related pathology,...
04:08
Abstract The impacts of road infrastructure on wildlife are of mounting concern. Amidst a growing body of literature on vehicle–wildlife collisions, few studies focus on primates. We examined a long-term dataset (2000–2018) of community-reported welfare cases for four species of monkeys: colobus (Colobus angolensis palliatus), Sykes’s monkey (Cercopithecus mitis albogularis), vervet (Chlorocebus pygerythrus hilgerti), and baboon (Papio cynocephalus cynocephalus). We analyzed collision...
02:00
Evidence Level 5 Technical Efficacy Stage 1
04:06
Level of Evidence 5. Technical Efficacy Stage 2
04:06
Abstract Objectives We aimed to determine the impact of washout period in patients with multiple myeloma between bortezomib‐based induction regimens and the collection of stem cells. Methods This was a single center historical prospective study, including all sequential newly diagnosed patients with myeloma between 2012 and 2017 that were given a first line bortezomib‐based induction therapy (≤6 cycles) followed by stem cell collection (n=75). Results We found a statistically...
04:03
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