Longitudinal automated detection of white-matter and cortical lesions in relapsing-remitting multiple sclerosis

Magnetic Resonance Imaging(MRI) plays an important role for lesion assessment in early stages of Multiple Sclerosis(MS). This work aims at evaluating the performance of an automated tool for MS lesion detection, segmentation and tracking in longitudinal data, only for use in this research study. The method was tested with images acquired using both a "clinical" and an "advanced" imaging protocol for comparison. The validation was conducted in a cohort of thirty-two early MS patients through a ground truth obtained from manual segmentations by a neurologist and a radiologist. The use of the "advanced protocol" significantly improves lesion detection and classification in longitudinal analyses

Surgical technical experience of adult aortic coarctation concomitant with poststenotic aneurysm or dissection.

Aortic coarctation (COA) in adults combined with poststenotic aneurysm (PA) or poststenotic dissection (PD) is rare and challenging to manage. The existence of multiple factors such as kinking, comorbidities, previous surgical history, and descending aortic lesions increases the difficulty of treatment, and there are currently few clinical reports. The purpose of this study was to present our surgical experience in dealing with such patients. A retrospective study was conducted on 20 consecutive patients with COA combined with PA or PD who were treated in our center from December 2015 to April 2019. The basic principles, methods, and short- and mid-term prognosis of surgery are present carefully. This paper introduces the individualized treatment scheme as well as its advantages and disadvantages in detail. The condition of the included patients was complicated, including 12 cases of PA and 8 of PD. Although different surgical schemes were adopted, procedural success rate was 100%. There were no other surgical complications except 2 cases of anastomotic bleeding and 1 case of spinal cord injury. The results of computed tomography angiography (CTA) demonstrated that 9 cases achieved anatomical correction, 10 cases of PA or PD were eliminated or thrombosed to varying degrees, and only 1 case of PA had no obvious change. Up to the follow-up period, except for 1 patient who had a slight cerebrovascular accident and 1 who had no change in PA underwent cheatham platinum (CP) stent surgery, no other cardiovascular adverse events occurred and all patients recovered well. The optimal surgical strategy developed collaboratively by cardiac surgeons and endovascular specialists has achieved satisfactory short- and mid-term results for COA patients combined with PA or PD. Further research is still necessary, due to the limited number of cases

Case Report: Lasting complete response to pembrolizumab in mismatch repair-deficient cardiac sarcoma: a genomic characterization.

Sarcomas are traditionally considered "cold" tumors with poor response to immunotherapy. However, evidence accumulating over the last years shows that immune checkpoint inhibitors (ICIs) may have a role in selected sarcoma patients according to predictive markers. Here, we report the case of a woman diagnosed with a primary cardiac undifferentiated sarcoma. Following failure of standard first line chemotherapy, high-throughput sequencing (HTS) revealed a high tumor mutational burden (TMB), pathogenic mutations in FAT1 and NOTCH2 and a microsatellite instability (MSI)-associated signature. Immunohistochemistry confirmed mismatch repair-deficiency (MMRd) and abundant CD8+ tumor-infiltrating lymphocytes (TILs), in the absence of tertiary lymphoid structures. The patient was, therefore, treated with the ICI pembrolizumab, reaching a complete response that continues to persist at last follow-up, more than seven years from initial diagnosis and nearly six years from initiation of ICI treatment. This case illustrates the importance of performing HTS in rare sarcomas given the availability of efficient therapies, such as those for tumors displaying high TMB or MMRd/MSI. In agreement with other reports, it supports the contention that MMRd/MSI status and high numbers of TILs are valuable predictive markers of response to immunotherapy in sarcomas

Ability of FFR-CT to detect the absence of hemodynamically significant lesions in patients with high-risk NSTE-ACS admitted in the emergency department with chest pain, study design and rationale.

In the era of High-sensitive troponin (hs-Tn), up to 50% of patients with a mild increase of hs-Tn will finally have a normal invasive coronary angiogram. Fractional Flow Reserve (FFR) derived from coronary computed tomographic angiography (FFR-CT) has never been used as a non-invasive tool for the diagnosis of coronary artery disease in patients with high-risk acute coronary syndrome without ST segment elevation (NSTE-ACS). The study aims to determine the role of coronary CT angiography and FFR-CT in the setting of high-risk NSTE-ACS. We will conduct a prospective trial, enrolling 250 patients admitted with high-risk NSTE-ACS who will rapidly undergo a coronary CT angiography and then a coronary angiography with FFR measurements. Results of coronary CT, FFR-CT and coronary angiography (± FFR) will be compared. In conclusion, non-invasive identification of patients with high-risk NSTE-ACS who could avoid coronary angiography would reduce procedure related risks and medical costs

Impact of thoracoabdominal imaging on diagnosis and management in patients with suspected infective endocarditis.

Embolic events (EEs) are a common complication of infective endocarditis (IE) and their presence can impact diagnosis and modify the therapeutic plan. The present study aimed to describe the role of thoracoabdominal imaging, either thoracoabdominal-pelvic Computed Tomography or <sup>18</sup> F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography, on diagnosis and management of patients with suspected IE. This study was conducted at a university hospital, from January 2014 to June 2022. EEs and IE were defined according to modified Duke criteria. Among 966 episodes with suspected IE and thoracoabdominal imaging, 528 (55%) patients were asymptomatic. At least one EE was found in 205 (21%) episodes. Based on thoracoabdominal imaging findings, the diagnosis was reclassified from rejected to possible or from possible to definite IE in 6 (1%) and 10 (1%) episodes, respectively. Among the 413 patients with IE, at least one EE was found on thoracoabdominal imaging in 143 (35%) episodes. Together with the presence of left-side valvular vegetation >10 mm, the results of thoracoabdominal imaging established a surgical indication (prevention of embolism) in 15 (4%) episodes, 7 of which were asymptomatic. Thoracoabdominal imaging performed in asymptomatic patients with suspected IE improved the diagnosis in only a small proportion of patients. Thoracoabdominal imaging led to a new surgical indication (in association with left-side valvular vegetation >10 mm) in only a small percentage of patients

Action spectroscopy of gas-phase carboxylate anions by multiple photon IR electron detachment/attachment

We report on a form of gas-phase anion action spectroscopy based on infrared multiple photon electron detachment and subsequent capture of the free electrons by a neutral electron scavenger in a Fourier Transform Ion Cyclotron Resonance (FTICR) mass spectrometer. This method allows one to obtain background-free spectra of strongly bound anions, for which no dissociation channels are observed. The first gas-phase spectra of acetate and propionate are presented using SF6 as electron scavenger and a free electron laser as source of intense and tunable infrared radiation. To validate the method, we compare infrared spectra obtained through multiple photon electron detachment/attachment and multiple photon dissociation for the benzoate anion. In addition, different electron acceptors are used, comparing both associative and dissociative electron capture. The relative energies of dissociation (by CO2 loss) and electron detachment are investigated for all three anions by DFT and CCSD(T) methods. DFT calculations are also employed to predict vibrational frequencies, which provide a good fit to the infrared spectra observed. The frequencies of the symmetric and antisymmetric carboxylate stretching modes for the aliphatic carboxylates are compared to those previously observed in condensed-phase IR spectra and to those reported for gas-phase benzoate, showing a strong influence of the solution environment and a slight substituent effect on the antisymmetric stretch.Comment: Revised version, Submitted to J Phys Chem

Bi-Directional Effect of Cholecystokinin Receptor-2 Overexpression on Stress-Triggered Fear Memory and Anxiety in the Mouse

Fear, an emotional response of animals to environmental stress/threats, plays an important role in initiating and driving adaptive response, by which the homeostasis in the body is maintained. Overwhelming/uncontrollable fear, however, represents a core symptom of anxiety disorders, and may disturb the homeostasis. Because to recall or imagine certain cue(s) of stress/threats is a compulsory inducer for the expression of anxiety, it is generally believed that the pathogenesis of anxiety is associated with higher attention (acquisition) selectively to stress or mal-enhanced fear memory, despite that the actual relationship between fear memory and anxiety is not yet really established. In this study, inducible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice, different stress paradigms, batteries of behavioral tests, and biochemical assays were used to evaluate how different CCKergic activities drive fear behavior and hormonal reaction in response to stresses with different intensities. We found that in IF-CCKR-2 tg mice, contextual fear was impaired following 1 trial of footshock, while overall fear behavior was enhanced following 36 trials of footshock, compared to their littermate controls. In contrast to a standard Yerkes-Dodson (inverted-U shaped) stress-fear relationship in control mice, a linearized stress-fear curve was observed in CCKR-2 tg mice following gradient stresses. Moreover, compared to 1 trial, 36 trials of footshock in these transgenic mice enhanced anxiety-like behavior in other behavioral tests, impaired spatial and recognition memories, and prolonged the activation of adrenocorticotropic hormone (ACTH) and glucocorticoids (CORT) following new acute stress. Taken together, these results indicate that stress may trigger two distinctive neurobehavioral systems, depending on both of the intensity of stress and the CCKergic tone in the brain. A “threshold theory” for this two-behavior system has been suggested

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N=1,384) of medication-free individuals with first episode and recurrent MDD (N=685) in a current depressive episode of at least moderate severity, but not treatment resistant depression, as well as healthy controls (N=699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N=359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions which exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N=290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N=395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%), but limited changes following placebo (28.6%); in contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (β=-18.3, 95% CI (-34.3 to -2.3), p=0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that comprise MDD and predict treatment response

Unprecedented High-Modulus High-Strength Tapes and Films of Ultrahigh Molecular Weight Polyethylene via Solvent-Free Route

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Macromolocules, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see: http://dx.doi.org/10.1021/ma200667