tbuckley/cabot-search huggingface dataset:
Incidence of Occult Spinal Dysraphism Among Infants With Cutaneous Stigmata and Proportion Managed With Neurosurgery
Authors: Se Jin Choi, Hee Mang Yoon, Ji Sun Hwang, Chong Hyun Suh, Ah Young Jung, Young Ah Cho, Jin Seong Lee
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Occult spinal dysraphism (OSD) is the most common congenital spinal anomaly. Cutaneous anomalies such as skin dimples or deviated gluteal folds are well known as stigmata of OSD and are indicators for further evaluation; however, the association between cutaneous anomalies and OSD has not been systemically evaluated. <h3>Objective</h3> To evaluate the incidence of OSD and the proportion of OSD cases managed with a neurosurgical intervention among neonates or infants with various cutaneous stigmata. <h3>Data Sources</h3> PubMed and Embase databases were searched for studies published up to July 25, 2018, that evaluated the proportion of OSD cases in neonates or infants with cutaneous stigmata. Search terms included<i>ultrasound, dysraphism, dimple</i>, and<i>infant </i>or<i> neonate</i>. The search was limited to English-language publications. <h3>Study Selection</h3> Two reviewers selected the studies evaluating the incidence of OSD among neonates or infants with cutaneous stigmata. <h3>Data Extraction and Synthesis</h3> The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for data extraction were followed. Pooled proportions of OSD cases and OSD cases that were managed with a neurosurgical intervention were obtained using the generalized linear mixed model and maximum likelihood method. <h3>Main Outcome and Measures</h3> The pooled incidence of OSD and OSD cases managed with neurological surgery among patients with cutaneous stigmata was the primary outcome. This outcome was also evaluated in each subgroup, and heterogeneity was explored using subgroup analysis. <h3>Results</h3> A total of 15 studies, involving 6558 neonate or infant patients with various cutaneous stigmata, were included. The pooled proportion of OSD cases among the patients with cutaneous stigmata was 2.8% (95% CI, 2.1%-3.8%;<i>I</i><sup>2</sup> = 51.6%), and the proportion managed with neurological surgery was 0.6% (95% CI, 0.3%-1.3%;<i>I</i><sup>2</sup> = 66.4%). Cases with combined stigmata showed a significantly higher association with OSD than those with a single stigma (10.5% [95% CI, 6.9%-15.8%] vs 2.3% [%, 95% CI, 1.5%-3.5%];<i>P</i> &lt; .001). The pooled proportion of OSD cases among patients with an atypical dimple was significantly higher than among those with simple dimple (8.8% [95% CI, 4.5%-16.6%] vs 0.6% [95% CI of 1.4%-2.1%];<i>P</i> = .001). <h3>Conclusions and Relevance</h3> The proportion of OSD in healthy, asymptomatic patients with midline cutaneous stigmata was low, and the proportion of patients who underwent a neurosurgical intervention was even lower. However, a careful evaluation as well as potential spinal magnetic resonance imaging is recommended for neonates or infants with combined stigmata or an atypical dimple for possible high-risk lesions.
It Takes a Village to Overcome KRAS Dependence in Pancreatic Cancer
Authors: Ryan M. Carr, Martin E. Fernandez-Zapico
Journal: Cancer Discovery (2020)

Abstract Summary: In this issue, Hou and colleagues present their exciting work demonstrating that, through remodeling of the local tumor microenvironment (TME), pancreatic ductal adenocarcinoma forms a tumor-supportive niche capable of liberating cancer cells from dependence on oncogenic KRAS signaling. Through extensive experimentation both in vitro and in vivo, the authors reveal that the HDAC5–CCL2 axis drives the recruitment of tumor-associated macrophages to the TME to provide trophic signaling. See related article by Hou et al., p. 1058.
Neurologic and Radiographic Findings Associated With COVID-19 Infection in Children
Authors: Omar Abdel-Mannan, Michael Eyre, Ulrike Löbel, Alasdair Bamford, Christin Eltze, Biju Hameed, Cheryl Hemingway, Yael Hacohen
Journal: JAMA Neurology (2020)

Neurological manifestations have been reported in adults with coronavirus disease 2019 (COVID-19), which is caused by the highly pathogenic virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).To report the neurological manifestations of children with COVID-19.In this case-series study, patients younger than 18 years who presented with SARS-CoV-2 infection and neurological symptoms to Great Ormond Street Hospital for Children (London, UK) between March 1, 2020, and May 8, 2020, were included after infection was confirmed by either a quantitative reverse transcription-polymerase chain reaction assay by nasopharyngeal swab or a positive test result for IgG antibodies against SARS-CoV-2 in serum.Clinical and paraclinical features were retrieved from electronic patient records.Of the 27 children with COVID-19 pediatric multisystem inflammatory syndrome, 4 patients (14.8%) who were previously healthy had new-onset neurological symptoms. Symptoms included encephalopathy, headaches, brainstem and cerebellar signs, muscle weakness, and reduced reflexes. All 4 patients required intensive care unit admission for the treatment of COVID-19 pediatric multisystem inflammatory syndrome. Splenium signal changes were seen in all 4 patients on magnetic resonance imaging of the brain. In the 2 patients whose cerebrospinal fluid was tested, samples were acellular, with no evidence of infection on polymerase chain reaction or culture (including negative SARS-CoV-2 polymerase chain reaction results) and negative oligoclonal band test results. In all 3 patients who underwent electroencephalography, a mild excess of slow activity was found. Tests for N-methyl-d-aspartate receptor, myelin oligodendrocyte glycoprotein, and aquaporin-4 autoantibodies had negative results in all patients. In all 3 patients who underwent nerve conduction studies and electromyography, mild myopathic and neuropathic changes were seen. Neurological improvement was seen in all patients, with 2 making a complete recovery by the end of the study.In this case-series study, children with COVID-19 presented with new neurological symptoms involving both the central and peripheral nervous systems and splenial changes on imaging, in the absence of respiratory symptoms. Additional research is needed to assess the association of neurological symptoms with immune-mediated changes among children with COVID-19.
Early Ultrafast Ultrasound Imaging of Cerebral Perfusion correlates with Ischemic Stroke outcomes and responses to treatment in Mice
Authors: Vincent Hingot, Camille Brodin, Florent Lebrun, Baptiste Heiles, Audrey Chagnot, Mervé Yetim, Maxime Gauberti, Cyrille Orset, Mickael Tanter, Olivier Couture, Thomas Deffieux, Denis Vivien
Journal: Theranostics (2020)

In the field of ischemic cerebral injury, precise characterization of neurovascular hemodynamic is required to select candidates for reperfusion treatments.It is thus admitted that advanced imaging-based approaches would be able to better diagnose and prognose those patients and would contribute to better clinical care.Current imaging modalities like MRI allow a precise diagnostic of cerebral injury but suffer from limited availability and transportability.The recently developed ultrafast ultrasound could be a powerful tool to perform emergency imaging and long term follow-up of cerebral perfusion, which could, in combination with MRI, improve imaging solutions for neuroradiologists.Methods: In this study, in a model of in situ thromboembolic stroke in mice, we compared a control group of non-treated mice (N=10) with a group receiving the gold standard pharmacological stroke therapy (N=9).We combined the established tool of magnetic resonance imaging (7T MRI) with two innovative ultrafast ultrasound methods, ultrafast Doppler and Ultrasound Localization Microscopy, to image the cerebral blood volumes at early and late times after stroke onset and compare with the formation of ischemic lesions.Results: Our study shows that ultrafast ultrasound can be used through the mouse skull to monitor cerebral perfusion during ischemic stroke.In our data, the monitoring of the reperfusion following thrombolytic within the first 2 h post stroke onset matches ischemic lesions measured 24 h.Moreover, similar results can be made with Ultrasound Localization Microscopy which could make it applicable to human patients in the future. Conclusion:We thus provide the proof of concept that in a mouse model of thromboembolic stroke with an intact skull, early ultrafast ultrasound can be indicative of responses to treatment and cerebral tissue fates following stroke.It brings new tools to study ischemic stroke in preclinical models and is the first step prior translation to the clinical settings.
Safety of endoscopic retrograde cholangiopancreatography in the pediatric population: a multicenter study
Authors: Clémence Mercier, Mathieu Pioche, Eliane Albuisson, Thierry Ponchon, Jean-Michel Gonzalez, Marc Barthet, Isabelle Boytchev, Geoffroy Vanbiervliet, Clement Fortier Beaulieu, Frederic Prat, Arthur Belle, Julien Branche, Phillipe Grandval, Jean-Christophe Valats, Franz Rudler, Timothee Wallenhorst, Stephane Koch, Aurélie Comte, Nicolas Williet, Nicolas Musquer, Emmanuel Coron, Aline Derosiere, Jean-Phillippe Le Mouel, Marion Schaefer, Caroline Chabot, Isabelle Scheers, Pierre H. Deprez, Jean-Baptiste Chevaux
Journal: Endoscopy (2020)

Introduction The aims of this retrospective multicenter study were to assess the technical success and adverse events of endoscopic retrograde cholangiopancreatography (ERCP) procedures in children in French and Belgian centers. Methods All children aged 1 day to 17 years who underwent ERCP between January 2008 and March 2019 in 15 tertiary care hospitals were retrospectively included. Results 271 children underwent 470 ERCP procedures. Clinical long-term follow-up was available for 72 % of our patients (340/470 procedures). The median age at intervention was 10.9 years. ERCP was therapeutic in 90 % (423/470) and diagnostic in cases of neonatal cholestasis in 10 % of the patients. The most common biliary indication was choledocholithiasis; the most common pancreatic indication was chronic pancreatitis. Biliary cannulation was successful in 92 % of cases (270/294); pancreatic cannulation in 96 % of cases (169/176); and planned therapeutic procedures in 92 % of cases (388/423). The overall complication rate was 19 % (65/340). The most common complication was post-ERCP pancreatitis (PEP) in 12 % of cases (40/340) and sepsis in 5 % (18/340). On univariate analyses, pancreatic stent removal was protective against PEP (odds ratio [OR] 0.1, 95 % confidence interval [CI] 0.01 – 0.75; P = 0.03), and sepsis was associated with history of liver transplantation (OR 7.27, 95 %CI 1.7 – 31.05; P = 0.01). Five patients had post-ERCP hemorrhage and two had intestinal perforation. All complications were managed with supportive medical care. There was no procedure-related mortality. Conclusion Our cohort demonstrates that ERCP can be performed safely with high success rates in many pancreaticobiliary diseases of children. The rate of adverse events was similar to that in previous reports.
Abstract IA11: Women at high risk for ovarian cancer: Novel strategies for identification and prevention
Authors: Karen H. Lu
Journal: Clinical Cancer Research (2020)

Abstract Most women carry a lifetime risk of 1.4% of ovarian cancer. However, certain women with germline mutations in BRCA1, BRCA2, or other hereditary cancer genes have elevated lifetime risks, some as high as 50%. Identification of these unaffected, high-risk women, followed by patient-centered prevention strategies, is key to decreasing overall mortality from ovarian cancer. A number of barriers exist for identification—including cost, patient preference, and availability of genetics services. In an effort to decrease these barriers, novel delivery systems of genetic testing have been developed. We are currently testing an on-line genetic counseling and testing strategy in a study called Making Genetic Testing Accessible (MAGENTA). We hypothesize that online genetic education and testing with access to board-certified genetic counselors could improve access to genetic testing while maintaining test quality and clinical utility. In this prospective, randomized, national clinical trial, over 3,000 women with a family history of breast or ovarian cancer will undergo genetic testing. We will compare the effectiveness of online genetic education with optional telephone counseling with three other strategies: online genetic education with required pretest telephone genetic counseling, online genetic education with required post-test telephone genetic counseling, and online genetic education with required pre- and post-test telephone genetic counseling. The primary outcome is cancer risk distress at 3 months post disclosure of genetic test results. Additional endpoints include testing completion rate (defined as receiving results), genetics knowledge, cognitive outcomes (i.e., decisional satisfaction, decisional regret), and behavioral outcomes. We currently have women enrolled from all 50 states in the United States. Preliminary data from this study will be presented. In addition, we will discuss our prospective, multicenter surgical prevention study that has enrolled over 200 women nationwide who have undergone either a salpingectomy or risk-reducing salpingo-oophorectomy (RRSO). The concept of salpingectomy with delayed oophorectomy as a cancer-prevention strategy for high-risk women is based on multiple studies implicating the fallopian tube epithelia as the cell of origin for BRCA-associated high-grade serous ovarian cancer. This information, coupled with high-risk women’s desire to minimize side effects associated with surgical menopause from RRSO, forms the rationale for the study. Finally, we will discuss plans for a prospective, international trial of salpingectomy in high-risk women that will be powered for a cancer efficacy endpoint. Citation Format: Karen H. Lu. Women at high risk for ovarian cancer: Novel strategies for identification and prevention [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr IA11.
Downregulated miR-18b-5p triggers apoptosis by inhibition of calcium signaling and neuronal cell differentiation in transgenic SOD1 (G93A) mice and SOD1 (G17S and G86S) ALS patients
Authors: Ki Yoon Kim, Yu Ri Kim, Kyung Won Choi, Mijung Lee, Somyung Lee, Wooseok Im, Je-Young Shin, Jin Young Kim, Yoon Ho Hong, Manho Kim, Jong-Il Kim, Jung-Joon Sung
Journal: Translational Neurodegeneration (2020)

Abstract Background MicroRNAs (miRNAs) are endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level and are key modulators in neurodegenerative diseases. Overexpressed miRNAs play an important role in ALS; however, the pathogenic mechanisms of deregulated miRNAs are still unclear. Methods We aimed to assess the dysfunction of RNAs or miRNAs in fALS (SOD1 mutations). We compared the RNA-seq of subcellular fractions in NSC-34 WT (hSOD1) and MT (hSOD1 (G93A)) cells to find altered RNAs or miRNAs. We identified that Hif1α and Mef2c were upregulated, and Mctp1 and Rarb were downregulated in the cytoplasm of NSC-34 MT cells. Results SOD1 mutations decreased the level of miR-18b-5p. Induced Hif1α which is the target for miR-18b increased Mef2c expression as a transcription factor. Mef2c upregulated miR-206 as a transcription factor. Inhibition of Mctp1 and Rarb which are targets of miR-206 induces intracellular Ca 2+ levels and reduces cell differentiation, respectively. We confirmed that miR-18b-5p pathway was also observed in G93A Tg, fALS (G86S) patient, and iPSC-derived motor neurons from fALS (G17S) patient. Conclusions Our data indicate that SOD1 mutation decreases miR-18b-5p, which sequentially regulates Hif1α, Mef2c, miR-206, Mctp1 and Rarb in fALS-linked SOD1 mutation. These results provide new insights into the downregulation of miR-18b-5p dependent pathogenic mechanisms of ALS.
Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic
Authors: Gianluca Ianiro, Benjamin H Mullish, Colleen R Kelly, Zain Kassam, Ed J Kuijper, Siew C Ng, Tariq H Iqbal, Jessica R Allegretti, Stefano Bibbò, Harry Sokol, Faming Zhang, Monika Fischer, Samuel Paul Costello, Josbert J Keller, Luca Masucci, Joffrey van Prehn, Gianluca Quaranta, Mohammed Nabil Quraishi, Jonathan Segal, Dina Kao, Reetta Satokari, Maurizio Sanguinetti, Herbert Tilg, Antonio Gasbarrini, Giovanni Cammarota
Journal: Gut (2020)

The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.
Pre-existing immunity to SARS-CoV-2: the knowns and unknowns
Authors: Alessandro Sette, Shane Crotty
Journal: Nature reviews. Immunology (2020)

T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that this reflects T cell memory to circulating 'common cold' coronaviruses. It will be important to define specificities of these T cells and assess their association with COVID-19 disease severity and vaccine responses. Recent studies have shown T cell reactivity to SARS-CoV-2 in 20–50% of unexposed individuals; it is speculated that this is due to T cell memory to common cold coronaviruses. Here, Crotty and Sette discuss the potential implications of these findings for disease severity, herd immunity and vaccine development.
Multimodality Imaging Features of a Misleading Sacral Giant Cell Tumor in 18F-FDG PET/CT, Bone Scan, and MRI
Authors: Sebastien Dejust, Pascaline Jallerat, Pauline Soibinet-Oudot, Christelle Jouannaud, David Morland
Journal: Clinical Nuclear Medicine (2020)

Abstract We report the case of an asymptomatic 66-year-old woman referred for initial staging of an invasive ductal breast carcinoma. Initial workup incidentally revealed a bone tumor of right sacral wing corresponding to a giant cell tumor (GCT). We present the imaging characteristics of GCT on 99m Tc-HDP bone scan (doughnut sign), 18 F-FDG PET/CT (intense and heterogeneous uptake of a prominent geographic lytic lesion with partial rupture of cortical), and MRI (hyposignal with gadolinium enhancement on T1-weighted images and heterogeneous hypersignal on T2-weighted images). GCT is a benign but locally aggressive primary bone tumor, constituting a pitfall and diagnostic challenge.
Engineered Perineural Vascular Plexus for Modeling Developmental Toxicity
Authors: Gaurav Kaushik, Kartik Gupta, Victoria Harms, Elizabeth Torr, Jonathan Evans, Hunter J. Johnson, Cheryl Soref, Suehelay Acevedo‐Acevedo, Jessica Antosiewicz‐Bourget, Daniel Mamott, Peyton Uhl, Brian P. Johnson, Sean P. Palecek, David J. Beebe, James A. Thomson, William T. Daly, William L. Murphy
Journal: Advanced Healthcare Materials (2020)

Abstract There is a vital need to develop in vitro models of the developing human brain to recapitulate the biological effects that toxic compounds have on the brain. To model perineural vascular plexus (PNVP) in vitro, which is a key stage in embryonic development, human embryonic stem cells (hESC)‐derived endothelial cells (ECs), neural progenitor cells, and microglia (MG) with primary pericytes (PCs) in synthetic hydrogels in a custom‐designed microfluidics device are cocultured. The formation of a vascular plexus that includes networks of ECs (CD31+, VE‐cadherin+), MG (IBA1+), and PCs (PDGFR β +), and an overlying neuronal layer that includes differentiated neuronal cells ( β III Tubulin+, GFAP+) and radial glia (Nestin+, Notch2NL+), are characterized. Increased brain‐derived neurotrophic factor secretion and differential metabolite secretion by the vascular plexus and the neuronal cells over time are consistent with PNVP functionality. Multiple concentrations of developmental toxicants (teratogens, microglial disruptor, and vascular network disruptors) significantly reduce the migration of ECs and MG toward the neuronal layer, inhibit formation of the vascular network, and decrease vascular endothelial growth factor A (VEGFA) secretion. By quantifying 3D cell migration, metabolic activity, vascular network disruption, and cytotoxicity, the PNVP model may be a useful tool to make physiologically relevant predictions of developmental toxicity.
Non-memory led dementias: care in the time of covid-19
Authors: Aida Suárez-González, Nicola Zimmermann, Claire Waddington, Olivia Wood, Emma Harding, Emilie Brotherhood, Nick C Fox, Sebastian J Crutch
Journal: BMJ (2020)

Carter raises concerns about the vulnerability of people living in care homes, including those with dementia.1 Non-memory led dementias account for around 15% of all dementia cases.2 They are relatively more common in younger people (under 65 years) who do not fit with societal perceptions of dementia, making their disability and support needs less noticeable. Dementias such as behavioural variant frontotemporal dementia (bvFTD), posterior cortical atrophy (PCA), and primary progressive aphasia (PPA) have phenotype specific symptoms that increase the challenges of …
Transcutaneous carbon dioxide monitoring as a valid complementary method in acute respiratory failure
Authors: Lukas Perkhofer, Anika Strobel, Daniel Gagiannis, Thomas Seufferlein, Katarina Schmidt, Benjamin Mayer, Alexander Kleger, Martin Müller
Journal: European Respiratory Journal (2020)

Concise monitoring of patients suffering from acute respiratory failure is mandatory, but highly labour-intensive; thus, tying up personnel and organisational resources due to the requirement for repetitive arterial blood gas analyses (aBGA). More than anything the current COVID-19 crisis unveiled the real scarcity in staff resources and consequently shortage of surveillance capacity. Based on published data transcutaneous capnometry (TcCO2) is not suitable to fully replace aBGA. In line, a recently published article from Mummery et al . [1] critically assesses value and reliability of TcCO2 in an emergency care unit, revealing that TcCO2 cannot concordantly detect very slight changes in arterial carbon dioxide tension ( P aCO2) values defined within the range ±0.25 kPa (1.88 mmHg). Transcutaneous capnometry can be used as a valid complementary method in monitoring patients with acute respiratory failure in a non-critical care setting <https://bit.ly/2Bhgtw4>
Stem Cell Transcription Factor Sox2 Is Expressed in a Subset of Folliculo-stellate Cells of Growth Hormone–Producing Pituitary Neuroendocrine Tumours and Its Expression Shows No Association with Tumour Size or IGF1 Levels: a Clinicopathological Study of 109 Cases
Authors: Jiri Soukup, Tomáš Česák, Helena Hornychová, Květoslava Michalová, Ľudmila Michnová, David Netuka, Jan Čáp, Filip Gabalec
Journal: Endocrine Pathology (2020)
Effect of Aspiration Thrombectomy on Microvascular Obstruction in NSTEMI Patients
Authors: Holger Thiele, Suzanne de Waha, Uwe Zeymer, Steffen Desch, Bruno Scheller, Bernward Lauer, Tobias Geisler, Meinrad Gawaz, Oliver Gunkel, Leonhard Bruch, Norbert Klein, Dietrich Pfeiffer, Gerhard Schuler, Ingo Eitel
Journal: Journal of the American College of Cardiology (2014)