Miracle-dz/UniFAR-FTUs huggingface dataset:
Adjuvant Hepatic Artery Infusion Chemotherapy is Associated With Improved Survival Regardless of KRAS Mutation Status in Patients With Resected Colorectal Liver Metastases: A Retrospective Analysis of 674 Patients.

MINI: Patients with colorectal liver metastases and available KRAS data treated with resection and with or without adjuvant hepatic artery infusion chemotherapy were retrospectively evaluated. Adjuvant hepatic artery infusion was independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant hepatic artery infusion may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM. OBJECTIVE To investigate the impact of adjuvant hepatic artery infusion (HAI) in relation to KRAS mutational status in patients with resected colorectal cancer liver metastases (CRLM). BACKGROUND Patients with KRAS-mutated CRLM have worse outcomes after resection. Adjuvant HAI chemotherapy improves overall survival after liver resection. METHODS Patients with resected CRLM treated at MSKCC with and without adjuvant HAI who had available KRAS status (wild-type, WT; mutated, MUT) were reviewed from a prospectively maintained institutional database. Correlations between KRAS status, adjuvant HAI, clinical factors, and outcomes were analyzed. Cox proportional hazard model was used to adjust for confounders. RESULTS Between 1993 and 2012, 674 patients (418 KRAS-WT, 256 MUT) with a median follow up of 6.5 years after resection were evaluated. Fifty-four percent received adjuvant HAI. Tumor characteristics (synchronous disease, number of lesions, clinical-risk score, 2-stage hepatectomy) were significantly worse in the HAI group; however, there were more patients with resected extrahepatic metastases in the no-HAI group. In KRAS-WT tumors, 5-year survival was 78% for patients treated with HAI versus 57% for patients without HAI [hazard ratio (HR) 0.51, P < 0.001]. In KRAS-MUT tumors, 5-year survival was 59% for patients treated with HAI versus 40% for patients without HAI (HR 0.56, P < 0.001). On multivariate analysis, HAI remained associated with improved OS (HR 0.53, P < 0.002) independent of KRAS status and other clinicopathologic factors. CONCLUSION Adjuvant HAI after resection of CRLM is independently associated with improved outcomes regardless of KRAS mutational status. Adjuvant HAI may mitigate the worse outcomes seen in patients with resectable KRAS-MUT CRLM.
Spinal cord ependymomas and myxopapillary ependymomas in the first 2 decades of life: a clinicopathological and immunohistochemical characterization of 19 cases.

OBJECT Primary spinal cord ependymomas (EPNs) are rare in children, comprising classical WHO Grade II and III tumors and Grade I myxopapillary ependymomas (MEPNs). Despite their benign histology, recurrences and neural-axis dissemination have been reported in up to 33% MEPNs in the pediatric population. Treatment options beyond resection are limited, and little is known about their tumorigenesis. The purpose of this study was to explore the tumor biology and outcomes in a consecutive series of pediatric patients treated at a single institution. METHODS The authors performed a retrospective clinicopathological review of 19 patients at a tertiary referral children's hospital for resection of a spinal cord ependymoma. The population included 8 patients with a pathological diagnosis of MEPN and 11 patients with a pathological diagnosis of spinal EPN (10 cases were Grade II and 1 case was Grade III). The upregulation of the following genes HOXB13, NEFL, PDGFRα, EGFR, EPHB3, AQP1, and JAGGED 1 was studied by immunohistochemistry from archived paraffin-embedded tumor samples of the entire cohort to compare the expression in MEPN versus EPN. RESULTS Gross-total resection was achieved in 75% of patients presenting with MEPNs and in 100% of those with EPNs. The average follow-up period was 79 months for the MEPN subset and 53 months for Grade II/III EPNs. Overall survival for both subsets was 100%. However, event-free survival was only 50% for patients with MEPNs. Of note, in all cases involving MEPNs that recurred, the patients had undergone gross-total resection on initial surgery. In contrast, there were no tumor recurrences in patients with EPNs. Immunohistochemistry revealed no significant differences in protein expression between the two tumor types with the exception of EPHB3, which demonstrates a tendency to be positive in MEPNs (6 reactive tumors of 9) rather than in EPN (2 reactive tumors of 10). CONCLUSIONS The authors' experience shows that, following a gross-total resection, MEPNs are more likely to recur than their higher-grade counterpart, EPNs. This supports the recommendation for close long-term radiological follow-up of pediatric patients with MEPNs to monitor for recurrence, despite the tumor's low-grade histological feature. No significant difference in the protein expression of HOXB13, NEFL, PDGFRα, EGFR, EPHB3, AQP1, and JAGGED 1 was present in this selected cohort of pediatric patients.
Systematic review of quality of life in persons with hereditary thoracic aortic aneurysm and dissection diagnoses

The purpose of this study was to explore the literature on quality of life (QoL) in patients with hereditary thoracic aortic aneurysm and dissection (HTAAD); including Marfan syndrome (MFS), Loeys‐Dietz syndrome (LDS), vascular Ehlers‐Danlos syndrome (vEDS) and other HTAAD diagnoses, critically appraising and synthesizing the relevant literature. A systematic review was performed by searching the published literature using available medical, physical, psychological, social databases and other sources. Studies addressing QoL in persons with an HTAAD diagnosis, published in peer‐reviewed journals were assessed. Of 227 search results, 20 articles satisfied the eligibility criteria. No studies of QoL in LDS, vEDS, or other HTAAD were found, only on MFS. Most studies had been published in the last 3 years. All were cross‐sectional quantitative studies besides one pilot intervention study. Most studies were of small sample size, had low response rate or participants without verified diagnosis. Despite these limitations, most studies indicate that having an HTAAD diagnosis as MFS may negatively impact QoL, but few studies found any associations between the biomedical symptoms and decreased QoL. More research is needed on QoL in samples with verified HTAAD diagnosis to develop evidence‐based knowledge and appropriate guidelines for these diagnoses.
Longitudinal plasma metabolomics of aging and sex

Understanding how metabolites are longitudinally influenced by age and sex could facilitate the identification of metabolomic profiles and trajectories that indicate disease risk. We investigated the metabolomics of age and sex using longitudinal plasma samples from the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a cohort of participants who were dementia free at enrollment. Metabolomic profiles were quantified for 2,316 fasting plasma samples among 1,187 participants, each with up to three study visits. Of 1,097 metabolites tested, 608 (55.4%) were associated with age and 680 (62.0%) with sex after correcting for multiple testing. Approximately twice as many metabolites were associated with age in stratified analyses of women versus men, and 63 metabolite trajectories significantly differed by sex, most notably including sphingolipids, which tended to increase in women and decrease in men with age. Using genome-wide genotyping, we also report the heritabilities of metabolites investigated, which ranged dramatically (0.2-99.2%); however, the median heritability of 36.2% suggests that many metabolites are highly influenced by a complex combination of genomic and environmental influences. These findings offer a more profound description of the aging process and may inform many new hypotheses regarding the role metabolites play in healthy and accelerated aging.
Efficient and Robust Carbon Dioxide Electroreduction Enabled by Atomically Dispersed Snδ+ Sites

Electrocatalytic CO2 reduction at considerably low overpotentials still remains a great challenge. Here, a positively charged single‐atom metal electrocatalyst to largely reduce the overpotentials is designed and hence CO2 electroreduction performance is accelerated. Taking the metal Sn as an example, kilogram‐scale single‐atom Snδ+ on N‐doped graphene is first fabricated by a quick freeze–vacuum drying–calcination method. Synchrotron‐radiation X‐ray absorption fine structure and high‐angle annular dark‐field scanning transmission electron microscopy demonstrate the atomically dispersed Sn atoms are positively charged, which enables CO2 activation and protonation to proceed spontaneously through stabilizing CO2•−* and HCOO−*, affirmed by in situ Fourier transform infrared spectra and Gibbs free energy calculations. Furthermore, N‐doping facilitates the rate‐limiting formate desorption step, verified by the decreased desorption energy from 2.16 to 1.01 eV and the elongated SnHCOO− bond length. As an result, single‐atom Snδ+ on N‐doped graphene exhibits a very low onset overpotential down to 60 mV for formate production and shows a very large turnover frequency up to 11930 h−1, while its electroreduction activity proceeds without deactivation even after 200 h. This work offers a new pathway for manipulating electrocatalytic performance.
Wearable Ultrasound Improves Motor Function in an MPTP Mouse Model of Parkinson's Disease

<italic>Objective:</italic> Low-frequency low-intensity pulsed ultrasound (LIPUS) has emerged as a non-invasive neuromodulation tool. The aim of this study is to examine whether LIPUS stimulation of the motor cortex can improve parkinsonian motor deficit in a mouse model induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). <italic>Methods:</italic> Acute Parkinson's disease (PD) mouse model is built by injection of MPTP (20 mg/kg) every 4 h in a total of four doses in one day. Mice are randomized into control, MPTP, sham-LIPUS+MPTP, and LIPUS+MPTP group. For LIPUS+MPTP group, 7 days of LIPUS (800 kHz, 10% duty cycle, 100-Hz pulse repetition frequency, 40 min/day) is delivered to the motor cortex. An open field test (OFT) is conducted on day 4 and a pole test on day 5, respectively. Striatal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-PX) are measured on day 8. The safety of LIPUS is verified using Hematoxylin and esosin (HE) staining and Nissl staining. <italic>Results:</italic> LIPUS treatment improves rearing number in the OFT on day 4 <inline-formula><tex-math notation="LaTeX">$(n= 8, p= 0.037)$</tex-math></inline-formula> and locomotor activity in the pole test on day 5 <inline-formula><tex-math notation="LaTeX">$(n= 8, p= 0.007)$</tex-math></inline-formula> compared with the sham-LIPUS+MPTP group. Moreover, LIPUS increases T-SOD <inline-formula><tex-math notation="LaTeX">$(n= 7, p= 0.006)$</tex-math></inline-formula> and GSH-PX <inline-formula><tex-math notation="LaTeX">$(n= 7, p= 0.030)$</tex-math></inline-formula> compared with the sham-LIPUS+MPTP group. In addition, HE and Nissl staining shows no brain tissue injury induced by LIPUS. <italic>Conclusion:</italic> These findings demonstrate that LIPUS may have neuromodulation effects in PD mice. <italic>Significance:</italic> LIPUS may provide a novel neuromodulation tool for PD treatment.
Improved detection of active multiple sclerosis lesions: 3D subtraction imaging.

PURPOSE To examine the benefits of using near-isotropic single-slab three-dimensional (3D) magnetic resonance (MR) imaging for the creation of subtraction images and to evaluate their performance in the detection of active multiple sclerosis (MS) brain lesions in comparison with two-dimensional (2D) subtraction images. MATERIALS AND METHODS The study protocol was approved by the local ethics review board and all subjects gave written informed consent before investigation. Three-dimensional MR sequences, including double inversion-recovery, fluid-attenuated inversion recovery, T2-weighted, and T1-weighted magnetization-prepared rapid acquisition gradient-echo (MP-RAGE), and corresponding 2D sequences were performed twice in 14 patients (eight women, six men; mean age, 37.6 years) with MS and nine age-matched healthy control subjects (three women, six men; mean age, 31.7 years). Active lesions were scored by two independent raters, followed by a consensus reading. Lesion counts were evaluated by using negative binomial regression; interrater agreement was evaluated by using intraclass correlation coefficient. RESULTS Three-dimensional subtraction images had less residual misregistration and flow artifacts and depicted higher numbers of active lesions with greater interobserver agreement compared with 2D subtraction images. Among the 3D sequences, MP-RAGE subtraction imaging enabled detection of a significantly higher mean number of positive active MS lesions compared with 2D subtraction imaging (2.8 versus 1.7, P = .012), particularly infratentorial lesions (0.6 vs 0.1, P < .05), and a substantially higher (nonsignificant) mean number of small (<3 mm) lesions (0.6 vs 0.1, P > .05). CONCLUSION Three-dimensional subtraction imaging, after image registration, produced better image quality, leading to increased detection of active MS lesions with greater interobserver agreement in comparison with 2D subtraction imaging; 3D MP-RAGE subtraction imaging represents a promising technique to increase sensitivity in ascertaining lesion dissemination in time and increase the power of MR imaging metrics for the evaluation of treatment effects in clinical trials.
Gastrointestinal neuroimmune disruption in a mouse model of Gulf War illness

Gulf War illness (GWI) is a chronic multisymptom disorder that is prominent in Gulf War veterans. Major unexplained symptoms of GWI include functional gastrointestinal disorders and undiagnosed illnesses, including neurologic disorders. Exposure to the antinerve gas drug pyridostigmine bromide (PB) is linked to the development of GWI, but the exact mechanisms remain unclear. Here, we tested the hypothesis that PB alters gut function by disrupting the neural and immune systems of the intestine. We exposed male and female mice to physiologically comparable amounts of PB that match the dose, route, and time frame of exposure experienced by Gulf War veterans and assessed the acute and chronic impacts on gastrointestinal functions, the functional architecture of the enteric nervous system, and immune responses in the gut and brain. Exposure to PB drove acute alterations to colonic motility and structure in both male and female mice that transitioned to chronic changes in gut functions. PB drove acute alterations to enteric neural and glial activity, glial reactivity, and neuron survival with glial reactivity persisting into the chronic phase in male mice. Despite having no effect on colonic permeability, exposure to PB caused major shifts in the expression of proinflammatory cytokines and chemokines in the colon and brain that suggest immunosuppressive effects. Interestingly, immune disruption was still evident in the colon and brain in female animals at 1 mo following exposure to PB. Together, our results show that the paradigm of PB exposure experienced by veterans of the Persian Gulf War contributes to long‐lasting pathophysiology by driving enteric neuroinflammation, promoting immunosuppression, and altering functional anatomy of the colon in a sex‐dependent manner. —Hernandez, S. , Fried, D. E. , Grubišić, V. , McClain, J. L. , Gulbransen, B. D. Gastrointestinal neuroimmune disruption in a mouse model of Gulf War illness. FASEB J. 33, 6168–6184 (2019). www.fasebj. org
Applying cartoon animation techniques to graphical user interfaces

If judiciously applied, animation techniques can enhance the look and feel of computer applications that present a graphical human interface. Such techniques can smooth the rough edges and abrupt transitions common in many current graphical interfaces, and strengthen the illusion of direct manipulation that many interfaces strive to present. To date, few applications include such animation techniques. One possible reason is that animated interfaces are difficult to implement: they are difficult to design, place great burdens on programmers, and demand high-performance from underlying graphics systems.This article describes how direct manipulation human computer interfaces can be augmented with techniques borrowed from cartoon animators. In particular, we wish to improve the visual feedback of a direct manipulation interface by smoothing the changes of an interface, giving manipulated objects a feeling of substance and providing cues that anticipate the result of a manipulation. Our approach is to add support for animation techniques such as object distortion and keyframe interpolation, and to provide prepackaged animation effects such as animated widgets for common user interface interactions.To determine if these tools and techniques are practical and effective, we built a prototype direct manipulation drawing editor with an animated interface and used the prototype editor to carry out a set of human factors experiments. The experiments show that the techniques are practical even on standard workstation hardware, and that the effects can indeed enhance direct manipulation interfaces.
Multi-reference spectral library yields almost complete coverage of heterogeneous LC-MS/MS data sets

Spectral libraries play a central role in the analysis of data-independent-acquisition (DIA) proteomics experiments. A main assumption in current spectral library tools is that a single characteristic intensity pattern (CIP) suffices to describe the fragmentation of a peptide in a particular charge state (peptide charge pair). However, we find that this is often not the case. We carry out a systematic evaluation of spectral variability over public repositories and in-house datasets. We show that spectral variability is widespread and partly occurs under fixed experimental conditions. Using clustering of preprocessed spectra, we derive a limited number of Multiple Characteristic Intensity Patterns (MCIPs) for each peptide charge pair, which allow almost complete coverage of our heterogeneous dataset without affecting the false discovery rate. We show that a MCIP library derived from public repositories performs in most cases similar to a “custom-made” spectral library, which has been acquired under identical experimental conditions as the query spectra. We apply the MCIP approach to a DIA data set and observe a significant increase in peptide recognition. We propose the MCIP approach as an easy-to-implement addition to current spectral library search engines and as a new way to utilize the data stored in spectral repositories.
Immune cell and other noncardiomyocyte regulation of cardiac hypertrophy and remodeling.

Cardiac hypertrophy and remodeling are pathological features of many cardiac diseases, with underlying causes including hypertension, cardiomyopathy, valvular dysfunction, and myocardial infarction. In these diseases, ventricular hypertrophy occurs in response to pathological stimuli such as pressure and volume overload, sarcomere gene mutations, and neurohumoral activation, and a major consequence of prolonged and uncontrolled hypertrophic remodeling is cardiac dysfunction, which can lead to heart failure or cardiac arrest resulting from arrhythmia. Despite the various pathological stimuli, there are many common features in the hypertrophic response in different cardiac diseases. In addition to increased cardiomyocyte mass, sarcomere rearrangement, and extracellular matrix deposition, other common features have recently been appreciated, including inflammatory signaling and immune cell activation. Numerous cell types are involved in orchestrating this complex pathological response. The heart consists of a heterogeneous population of cells, including cardiomyocytes and noncardiomyocytes, and it is now clear that intercellular signaling and communication between these cell types are critical in the pathophysiology of ventricular hypertrophy and remodeling (Figure 1). Figure 1. Overview of cardiomyocyte and noncardiomyocyte interactions during cardiac hypertrophy and remodeling. Cardiomyocytes respond to pathogenic stimuli by secreting inflammatory cytokines, chemokines, and damage-associated molecular pattern molecules (DAMPs), which are recognized by local noncardiomyocyte cells. This induces activation and expansion of resident macrophages and fibroblasts and recruits bone marrow–derived immune cells from the circulation. Activated immune cells and fibroblasts secrete both prohypertrophic and profibrotic cytokines, which induce cardiomyocyte hypertrophy and promote fibroblast differentiation, matrix deposition, and interstitial fibrosis. ECM indicates extracellular matrix. Noncardiomyocytes display phenotypic changes during the development of cardiac hypertrophy. There is still much to be revealed about the specific roles of these cell types and their overall contribution to the hypertrophic response. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and transforming growth factor-β (TGF-β) and neurohumoral factors such as …
Involvement of CXCR4 in Normal and Abnormal Development

CXC motif chemokine receptor type 4 (CXCR4) is associated with normal and abnormal development, including oncogenesis. The ligand of CXCR4 is stromal cell-derived factor (SDF), also known as CXC motif ligand (CXCL) 12. Through the SDF-1/CXCR4 axis, both homing and migration of hematopoietic (stem) cells are regulated through niches in the bone marrow. Outside of the bone marrow, however, SDF-1 can recruit CXCR4-positive cells from the bone marrow. SDF/CXCR4 has been implicated in the maintenance and/or differentiation of stemness, and tissue-derived stem cells can be associated with SDF-1 and CXCR4 activity. CXCR4 plays a role in multiple pathways involved in carcinogenesis and other pathologies. Here, we summarize reports detailing the functions of CXCR4. We address the molecular signature of CXCR4 and how this molecule and cells expressing it are involved in either normal (maintaining stemness or inducing differentiation) or abnormal (developing cancer and other pathologies) events. As a constituent of stem cells, the SDF-1/CXCR4 axis influences downstream signal transduction and the cell microenvironment.
A systematic comparison of contemporary automatic speech recognition engines for conversational clinical speech

Conversations especially between a clinician and a patient are important sources of data to support clinical care. To date, clinicians act as the sensor to capture these data and record them in the medical record. Automatic speech recognition (ASR) engines have advanced to support continuous speech, to work independently of speaker and deliver continuously improving performance. Near human levels of performance have been reported for several ASR engines. We undertook a systematic comparison of selected ASRs for clinical conversational speech. Using audio recorded from unscripted clinical scenarios using two microphones, we evaluated eight ASR engines using word error rate (WER) and the precision, recall and F1 scores for concept extraction. We found a wide range of word errors across the ASR engines, with values ranging from 65% to 34%, all falling short of the rates achieved for other conversational speech. Recall for health concepts also ranged from 22% to 74%. Concept recall rates match or exceed expectations given measured word error rates suggesting that vocabulary is not the dominant issue.