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Purpose: To assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival. Methods: Preoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355). Results: CPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS. Conclusion: CPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.

Summary: In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects. The in vitro organoid responses correlated with both change in pulmonary response and change in sweat chloride concentration. Receiver operating characteristic curves indicated good-to-excellent accuracy of the organoid-based test for defining clinical responses. This study indicates that an in vitro assay using stem cell cultures can prospectively select efficacious treatments for patients and suggests that biobanked stem cell resources can be used to tailor individual treatments in a cost-effective and patient-friendly manner. : Berkers et al. demonstrate that stem cell cultures (organoids) can be a tool for personalized medicine. They show a high correlation between in vitro and in vivo effects of drugs and demonstrate good-to-excellent predictive values of the organoid test for preclinical identification of responders to CFTR modulators. Keywords: organoids, personalized treatment, predicting, drug response, stem cell cultures, cystic fibrosis, CFTR

Background: Deep brain stimulation (DBS) is an established treatment for certain movement disorders and has additionally shown promise for various psychiatric, cognitive, and seizure disorders. However, the mechanisms through which stimulation exerts therapeutic effects are incompletely understood. A technique that may help to address this knowledge gap is functional magnetic resonance imaging (fMRI). This is a non-invasive imaging tool which permits the observation of DBS effects in vivo., Objective: The objective of this review was to provide a comprehensive overview of studies in which fMRI during active DBS was performed, including studied disorders, stimulated brain regions, experimental designs, and the insights gleaned from stimulation-evoked fMRI responses., Methods: We conducted a systematic review of published human studies in which fMRI was performed during active stimulation in DBS patients. The search was conducted using PubMED and MEDLINE., Results: The rate of fMRI DBS studies is increasing over time, with 37 studies identified overall. The median number of DBS patients per study was 10 (range = 1-67, interquartile range = 11). Studies examined fMRI responses in various disease cohorts, including Parkinson's disease (24 studies), essential tremor (3 studies), epilepsy (3 studies), obsessive-compulsive disorder (2 studies), pain (2 studies), Tourette syndrome (1 study), major depressive disorder, anorexia, and bipolar disorder (1 study), and dementia with Lewy bodies (1 study). The most commonly stimulated brain region was the subthalamic nucleus (24 studies). Studies showed that DBS modulates large-scale brain networks, and that stimulation-evoked fMRI responses are related to the site of stimulation, stimulation parameters, patient characteristics, and therapeutic outcomes. Finally, a number of studies proposed fMRI-based biomarkers for DBS treatment, highlighting ways in which fMRI could be used to confirm circuit engagement and refine DBS therapy., Conclusion: A review of the literature reflects an exciting and expanding field, showing that the combination of DBS and fMRI represents a uniquely powerful tool for simultaneously manipulating and observing neural circuitry. Future work should focus on relatively understudied disease cohorts and stimulated regions, while focusing on the prospective validation of putative fMRI-based biomarkers., Competing Interests: Declaration of competing interest R.M. is an employee at General Electric. A.F. serves as a consultant for Medtronic, Abbott, Boston Scientific, Brainlab, Ceregate, and Medtronic, he received research grants, personal fees and non-financial support from Boston Scientific, Brainlab and Medtronic and personal fees from Abbott and Ceregate, all outside the submitted work. A.M.L. serves as a consultant for Medtronic, Abbott, Boston Scientific, and Functional Neuromodulation. The other authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Parents' perceptions of physical activity (PA), in particular, are critically important because children with disabilities are often dependent on their families to be able to engage in physical activities. Thus, adapted physical activity scholars have acknowledged the need for research addressing the perceptions of parents of youth with disabilities regarding their child's PA engagement., Purpose: The purpose of this review was to examine published research literature pertaining to parents' perspectives toward physical activity of youth with disabilities by describing study characteristics and major findings., Methods: Electronic database searches were conducted to identify relevant articles published between January 2007 and January 2018., Results: Thirty-two articles met all inclusion criteria, and relevant data such as participant characteristics, theories, measurements, and dependent variables were extracted from them. Of the 32 studies, 26 were descriptive, and six were correlational. Seventeen studies explicitly stated a theoretical or conceptual framework., Conclusions: Major findings suggest that parents have reported multiple motives to engage their children with disabilities in physical activity. However, numerous barriers (e.g., lack of program, lack of time, children's disability) were reported that negatively impact physical activity participation. As such, parents are calling for the need for training provided by qualified professionals to enhance participation for their children with disabilities., Competing Interests: Declaration of competing interest The author has no conflicts of interest to declare., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Depression following resection of diffuse low-grade glioma has rarely been described. Location of the tumor and surgical route are potential causes. Lesion network mapping (LNM), leveraging high-quality resting-state functional magnetic resonance imaging data from large samples of healthy adults, has been used to explore the broader network connectivity for given lesions. However, LNM has not been applied to large intra-axial masses or surgical lesions. We used LNM to examine a potential cause of postoperative depression in a patient with a cingulate diffuse low-grade glioma (zones I-III)., Case Description: A 34-year-old woman underwent surgery for medically refractory seizures attributable to diffuse low-grade glioma. Near-total resection was attained via a single-stage, transcortical route through the medial prefrontal cortex. Despite freedom from seizure and lack of tumor growth at 42 months of follow-up, she developed symptoms of major depressive disorder soon after surgery that persisted. To identify functional networks potentially engaged by the surgical corridor and tumor resection cavity, both were segmented separately and used as seeds for normative resting-state functional magnetic resonance imaging connectivity mapping. To study depression specifically, networks associated with the tumor and surgical approach were compared with networks associated with subgenual cingulate deep brain stimulation. LNM results suggested that the surgical corridor, rather than the tumor, had greater overlap with deep brain stimulation-based depression networks (32% vs. 8%)., Conclusions: Early postoperative development of major depressive disorder following resection of a cingulate region tumor, although likely multifactorial, should be considered and patients appropriately counseled preoperatively. Further validation of LNM as a viable methodology for correlating symptoms to lesions could make it a valuable tool in selection of surgical approach and patient counseling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In this study, we have evaluated two different ionic liquids (IL) as extractants based on the same cation (trioctylmethylammonium) but bearing the anion thiosalicylate (TOMATS) or salicylate (TOMAS). Both IL have been incorporated as carriers in polymer inclusion membranes (PIMs), and mercury (Hg) has been preconcentrated using a special device. Results show that among the tested IL, TOMATS has given better results. A PIM made of 50% cellulose triacetate, 30% TOMATS and 20% nitrophenyl octyl ether as a plasticizer enabled the effective transport of Hg to a 10 -3 M cysteine solution used as a stripping phase. This novel and simple PIM-device system allows the transport of Hg at low concentration levels in different types of natural waters such as rivers, groundwater and seawater without any previous treatment. Since no matrix effect was observed on Hg transport efficiency with different waters, this newly developed PIM-system could be used as a global detection system for this metal. The effect of biofilm growth on the surface of PIMs has been investigated for the first time, and no significant differences on Hg transport have been found when using a fresh PIM and a PIM deployed for 7 days in a pond., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Anorexia nervosa is characterised by a chronic course that is refractory to treatment in many patients and has one of the highest mortality rates of any psychiatric disorder. Deep brain stimulation (DBS) has been applied to circuit-based neuropsychiatric diseases, such as Parkinson's disease and major depression, with promising results. We aimed to assess the safety of DBS to modulate the activity of limbic circuits and to examine how this might affect the clinical features of anorexia nervosa., Methods: We did a phase 1, prospective trial of subcallosal cingulate DBS in six patients with chronic, severe, and treatment-refractory anorexia nervosa. Eligible patients were aged 20-60 years, had been diagnosed with restricting or binge-purging anorexia nervosa, and showed evidence of chronicity or treatment resistance. Patients underwent medical optimisation preoperatively and had baseline body-mass index (BMI), psychometric, and neuroimaging investigations, followed by implantation of electrodes and pulse generators for continuous delivery of electrical stimulation. Patients were followed up for 9 months after DBS activation, and the primary outcome of adverse events associated with surgery or stimulation was monitored at every follow-up visit. Repeat psychometric assessments, BMI measurements, and neuroimaging investigations were also done at various intervals. This trial is registered with ClinicalTrials.gov, number NCT01476540., Findings: DBS was associated with several adverse events, only one of which (seizure during programming, roughly 2 weeks after surgery) was serious. Other related adverse events were panic attack during surgery, nausea, air embolus, and pain. After 9 months, three of the six patients had achieved and maintained a BMI greater than their historical baselines. DBS was associated with improvements in mood, anxiety, affective regulation, and anorexia nervosa-related obsessions and compulsions in four patients and with improvements in quality of life in three patients after 6 months of stimulation. These clinical benefits were accompanied by changes in cerebral glucose metabolism (seen in a comparison of composite PET scans at baseline and 6 months) that were consistent with a reversal of the abnormalities seen in the anterior cingulate, insula, and parietal lobe in the disorder., Interpretation: Subcallosal cingulate DBS seems to be generally safe in this sample of patients with chronic and treatment-refractory anorexia nervosa., Funding: Klarman Family Foundation Grants Program in Eating Disorders Research and Canadian Institutes of Health Research., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

An automated headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-ion trap/mass spectrometry (GC-IT/MS) was developed in order to quantify a large number of volatile compounds in wines such as alcohols, ester, norisoprenoids and terpenes. The procedures were optimized for SPME fiber selection, pre-incubation temperature and time, extraction temperature and time, and salt addition. A central composite experimental design was used in the optimization of the extraction conditions. The volatile compounds showed optimal extraction using a DVB/CAR/PDMS fiber, incubation of 5 ml of wine with 2g NaCl at 45 °C during 5 min, and subsequent extraction of 30 min at the same temperature. The method allowed the identification of 64 volatile compounds. Afterwards, the method was validated successfully for the most significant compounds and was applied to study the volatile composition of different white wines., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Direct infusion electrospray ionization mass spectrometry (ESI-MS) approaches were developed for rapid identification of impurity compounds formed from octylphenyl-(N,N-(diisobutyl)carbamoylmethyl) phosphine oxide (CMPO) during alpha and gamma irradiation experiments of this compound in dodecane. CMPO is an aggressive Lewis base, and produces extremely abundant metal complex ions in the ESI-MS analysis that make identification of low abundance compounds that are less nucleophilic challenging. Radiolysis products were identified using several approaches including restricting ion trapping so as to exclude the abundant natiated CMPO ions, extraction of acidic products using aqueous NaOH, and extraction of basic products using HNO(3). These approaches generated protonated, natiated and deprotonated species derived from CMPO degradation products formed via radiolytic cleavages of several different bonds. Cleavages of the amide and methylene-phosphoryl bonds appear to be favored by both alpha and gamma irradiation, while alpha irradiation also appears to induce cleavage of the methylene-carbonyl bond. The degradation products observed are formed from recombination of the initially formed radicals with hydrogen, methyl, isopropyl and hydroxyl radicals that are derived either from CMPO, contacted aqueous nitric acid, or the dodecane solvent., (Copyright © 2012 Elsevier B.V. All rights reserved.)

We sought to evaluate survival of liver transplant candidates living in geographic areas with limited access to specialized transplant centers (TxC). We analyzed survival outcome among candidates listed for liver transplant in United Network of Organ Sharing (UNOS) Region 4 from 2004 to 2010. Candidates were stratified into three groups according to the distance from the patient's residence to the closest hospital with a liver transplant program: Group 1 (Gr 1) <30 miles (m), Group 2 (Gr 2) 30-60 m and Group 3 (Gr 3) >60 m. Of the 5673 patients included in the study, 49% resided >30 m from a TxC. Eight percent of the cohort experienced death or dropped out of the list due to medical condition deterioration, with worse outcomes for Gr 2 and Gr 3 (8.5% and 9.9%, respectively, vs. 6.5% for Gr 1 [p < 0.001]). Among patients with a MELD score <20, mortality was higher in Gr 2 and Gr 3 compared to Gr 1 (p < 0.001). We conclude that for Region 4, the mortality risk in patients living >30 m from a TxC is higher. We suggest that the variable "distance from a TxC" should be used to improve the estimate of the mortality risk for patients on the waiting list., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Octyl(phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) is an extractant proposed for selective separation of radionuclide metals from used nuclear fuel solutions using solvent extraction. Radiolysis reactions can degrade CMPO and reduce separation performance and hence methods for measuring the concentration of CMPO are needed. A novel high performance liquid chromatography (HPLC) method was developed for measuring CMPO in dodecane that featured a low pH buffer, octanol as a co-solvent with 2-propanol, and ultraviolet (UV) detection. Validation data indicated that the HPLC-UV method for CMPO determination provided good linearity, sensitivity, accuracy and precision. Method performance was evaluated using CMPO samples that had undergone radiolysis, and the results showed a decrease in CMPO concentration and the appearance of degradation products. The degradation products were identified using electrospray ionization mass spectrometry, which also showed formation of CMPO-nitric acid complexes that account for the apparent loss of CMPO in an acidic environment, independent of irradiation., (Copyright © 2012 Elsevier B.V. All rights reserved.)