tbuckley/cabot-search huggingface dataset:
Manipulation of Subcortical and Deep Cortical Activity in the Primate Brain Using Transcranial Focused Ultrasound Stimulation
Authors: Davide Folloni, Lennart Verhagen, Rogier B. Mars, Elsa Fouragnan, Charlotte Constans, Jean-François Aubry, Matthew F.S. Rushworth, Jérôme Sallet
Journal: Neuron (2019)

The causal role of an area within a neural network can be determined by interfering with its activity and measuring the impact. Many current reversible manipulation techniques have limitations preventing their application, particularly in deep areas of the primate brain. Here, we demonstrate that a focused transcranial ultrasound stimulation (TUS) protocol impacts activity even in deep brain areas: a subcortical brain structure, the amygdala (experiment 1), and a deep cortical region, the anterior cingulate cortex (ACC, experiment 2), in macaques. TUS neuromodulatory effects were measured by examining relationships between activity in each area and the rest of the brain using functional magnetic resonance imaging (fMRI). In control conditions without sonication, activity in a given area is related to activity in interconnected regions, but such relationships are reduced after sonication, specifically for the targeted areas. Dissociable and focal effects on neural activity could not be explained by auditory confounds.
Sodium Channels in Human Pain Disorders: Genetics and Pharmacogenomics
Authors: Sulayman D. Dib-Hajj, Stephen G. Waxman
Journal: Annual Review of Neuroscience (2019)

Acute pain is adaptive, but chronic pain is a global challenge. Many chronic pain syndromes are peripheral in origin and reflect hyperactivity of peripheral pain-signaling neurons. Current treatments are ineffective or only partially effective and in some cases can be addictive, underscoring the need for better therapies. Molecular genetic studies have now linked multiple human pain disorders to voltage-gated sodium channels, including disorders characterized by insensitivity or reduced sensitivity to pain and others characterized by exaggerated pain in response to normally innocuous stimuli. Here, we review recent developments that have enhanced our understanding of pathophysiological mechanisms in human pain and advances in targeting sodium channels in peripheral neurons for the treatment of pain using novel and existing sodium channel blockers.
Abstract 20542: The Interaction of Osr1 and Hh-Signaling is Important for Outflow Tract Development
Authors: Ke K Zhang, Menglan Xiang, Linglin Xie
Journal: Circulation (2017)

Introduction: Congenital heart defect (CHD) occurs in nearly 8 of 1000 live births, and approximately one third involves malformations of the cardiac outflow tract (OFT). Double outlet right ventri...
Cell-Type-Specific Interleukin 1 Receptor 1 Signaling in the Brain Regulates Distinct Neuroimmune Activities
Authors: Xiaoyu Liu, Daniel P. Nemeth, Daniel B. McKim, Ling Zhu, Damon J. DiSabato, Olimpia Berdysz, Gowthami Gorantla, Braedan Oliver, Kristina G. Witcher, Yufen Wang, Christina E. Negray, Rekha S. Vegesna, John F. Sheridan, Jonathan P. Godbout, Matthew J. Robson, Randy D. Blakely, Phillip G. Popovich, Staci D. Bilbo, Ning Quan
Journal: Immunity (2019)
Deubiquitinase OTUD7B Is Potential Prognostic Biomarker in Diffuse Large B-Cell Lymphoma
Authors: Qunling Zhang, Juan Gu, Kai Xue, Zuguang Xia, Cory Mavis, Francisco J. Hernandez-Ilizaliturri, Ye Guo, Xiaonan Hong, Junning Cao
Journal: Blood (2018)
Contraceptive use in Latin America and the Caribbean with a focus on long-acting reversible contraceptives: prevalence and inequalities in 23 countries
Authors: Rodolfo Gomez Ponce de Leon, Fernanda Ewerling, Suzanne Jacob Serruya, Mariangela F Silveira, Antonio Sanhueza, Ali Moazzam, Francisco Becerra-Posada, Carolina V N Coll, Franciele Hellwig, Cesar G Victora, Aluisio J D Barros
Journal: The Lancet Global Health (2019)

The rise in contraceptive use has largely been driven by short-acting methods of contraception, despite the high effectiveness of long-acting reversible contraceptives. Several countries in Latin America and the Caribbean have made important progress increasing the use of modern contraceptives, but important inequalities remain. We assessed the prevalence and demand for modern contraceptive use in Latin America and the Caribbean with data from national health surveys.
Comparative respiratory impedance in Thai children with obesity and asthma by using oscillomery
Authors: Patcharapa Nabthuedee, Tassalapa Daengsuwan
Journal: Journal of Allergy and Clinical Immunology (2019)

The decline in lung function is observed among asthma and obesity. Measurement of obstructive airway by spirometry is suggested to confirm the diagnosis and monitor treatment outcomes in asthma. Nevertheless, spirometry is hard to complete in preschooler. Impulse oscillometry (IOS) is a new and easier technique to measure airway resistance. We aim to evaluate IOS parameter in Thai asthmatic patients and Thai obese children. Forty-two asthmatic children and thirteen obese children (without ashtma), aged 5-15 years old, were enrolled in our study. They all consent/assent to performed IOS measurement (Jeaker, Germany) to determine airway obstruction. Among fifty-five volunteers, male were predominant (25/42 in asthmatic group and 11/13 in obese group). Mean age of asthmatic patients was 9.25±3.02 and obese children was 10.08±3.15. zBMI in asthmatic patients was 0.11±0.02 and obese children was 0.21±0.05. The airway resistance at 5 Hz(R5) were similar in both asthmatic and obese group (0.84±0.26 vs 0.84±0.31, p=0.971). The airway reactance to 5 Hz(X5) were increased in obese children (-0.12±0.1 vs -0.21±0.11, p=0.008). R20 and X20 measurement were not different in both groups [(0.59±0.13 vs 0.54±0.2, p=0.385) and (-0.03±0.08 vs -0.03±0.18,p=0.889)]. IOS in our study did not demonstrate airway resistance in Thai children with asthma. Though, this parameter may be advantage in obese children.
Central Nervous System Relapse in Patients with Extranodal NK/T-Cell Lymphoma, Nasal Type
Authors: Hyehyun Jeong, Jung Yong Hong, Dok Hyun Yoon, Shin Kim, Jung Sun Park, Sang Wook Lee, Chan Sik Park, Jin-Sook Ryu, Jooryung Huh, Cheolwon Suh
Journal: Blood (2018)
Eomes+T-betlow CD8+ T Cells Are Functionally Impaired and Are Associated with Poor Clinical Outcome in Patients with Acute Myeloid Leukemia
Authors: Bei Jia, Chenchen Zhao, Kevin L. Rakszawski, David F. Claxton, W. Christopher Ehmann, Witold B. Rybka, Shin Mineishi, Ming Wang, Hiroko Shike, Michael G. Bayerl, Jeffrey M. Sivik, Todd D. Schell, Joseph J. Drabick, Raymond J. Hohl, Hong Zheng
Journal: Cancer Research (2019)

Acute myeloid leukemia (AML) is a devastating blood cancer with poor prognosis. Immunotherapy targeting inhibitory pathways to unleash the antileukemia T-cell response is a promising strategy for the treatment of leukemia, but we must first understand the underlying molecular mechanisms. Eomesodermin (Eomes) and T-bet are both T-box transcription factors that regulate CD8+ T-cell responses in a context-specific manner. Here, we examined the role of these transcription factors in CD8+ T-cell immunity in AML patients. We report that the frequency of Eomes+T-betlow CD8+ T cells increased in newly diagnosed AML. This cell subset produced fewer cytokines and displayed reduced killing capacity, whereas depletion of Eomes by siRNA reversed these functional defects. Furthermore, Eomes bound the promoter of T-cell immunoglobulin and ITIM domain (TIGIT) and positively regulated the expression of this inhibitory receptor on patient-derived T cells. A high frequency of Eomes+T-betlow CD8+ T cells was associated with poor response to induction chemotherapy and shorter overall survival in AML patients. These findings have significant clinical implications as they not only identify a predictive and prognostic biomarker for AML, but they also provide an important target for effective leukemia therapeutics. SIGNIFICANCE: These findings reveal that a high frequency of Eomes+T-betlow CD8+ T cells predicts poor clinical outcome in AML and that targeting Eomes may provide a therapeutic benefit against AML.
Effect of Trimetazidine Dihydrochloride Therapy on Exercise Capacity in Patients With Nonobstructive Hypertrophic Cardiomyopathy
Authors: Caroline J. Coats, Menelaos Pavlou, Oliver T. Watkinson, Alexandros Protonotarios, Linda Moss, Rebecca Hyland, Khadija Rantell, Antonis A. Pantazis, Maite Tome, William J. McKenna, Michael P. Frenneaux, Rumana Omar, Perry M. Elliott
Journal: JAMA Cardiology (2019)

Hypertrophic cardiomyopathy causes limiting symptoms in patients, mediated partly through inefficient myocardial energy use. There is conflicting evidence for therapy with inhibitors of myocardial fatty acid metabolism in patients with nonobstructive hypertrophic cardiomyopathy.
Abstract 17678: Earlier Stage I Operation in Neonates With Hypoplastic Left Heart Syndrome is Not Associated With Worse Short-term Outcomes
Authors: Ann L McCarthy, Madeline E Winters, Elizabeth Bixler, Jennifer M Lynch, John J Newland, David R Busch, Tiffany Ko, Rui Xiao, Susan C Nicolson, Lisa M Montenegro, Christopher E Mascio, Stephanie Fuller, William J Gaynor, Thomas L Spray, Daniel J Licht, Maryam Y Naim
Journal: Circulation (2015)

Introduction: We have previously reported that earlier stage I palliation (S1P) is protective against White Matter Injury (WMI) for term infants with hypoplastic left heart syndrome (HLHS). The present study compares clinical outcomes from the acute hospitalization between neonates who had early (≤ 4 days) versus late surgery (&gt; 4 days). Hypothesis: Earlier S1P intervention is associated with greater post-operative complications rates. Methods: A retrospective chart review was performed on all neonates with HLHS or variants who underwent S1P at a single institution between 10/2008 - 03/2013. Excluded were a preterm (&lt;37 weeks gestation), left-ventricle physiology, prior operations and international referral. Anthropometric data, pre- post- and intra-operative factors, post-operative complications, and both intensive care unit (ICU) and hospital length of stay were evaluated for differences between early vs. late surgery. Analysis was performed excluding patients who had either early, or late surgery for non-elective diagnoses. Results: A total of 145 infants, 114 (73 with early surgery, 41 late) met inclusion criteria. The mean day of surgery was 4.2 days (early 2.7±0.1 days, late 6.9±3.7 days). There were no significant differences between the groups’ post-operative complications or operative factors (see Table 1). In addition exclusion of patients with non-elective change to their surgical date did not change results significantly. Neonates who had earlier surgery had significantly longer post-operative ICU stay (median 9 days vs. median 13 days, p = 0.02). Conclusion: Early surgery for neonates with HLHS was not associated with either protection against or greater risk for post-operative complications. Neonates who have earlier surgery have a longer initial post-operative ICU stay, but total ICU and hospital stay was not different than that for infants with surgery after day four.
“Dorsal–Ventral” Genes Are Part of an Ancient Axial Patterning System: Evidence from Trichoplax adhaerens (Placozoa)
Authors: Timothy Q DuBuc, Joseph F Ryan, Mark Q Martindale
Journal: Molecular Biology and Evolution (2019)

Placozoa are a morphologically simplistic group of marine animals found globally in tropical and subtropical environments. They consist of two named species, Trichoplax adhaerens and more recently Hoilungia hongkongensis, both with roughly six morphologically distinct cell types. With a sequenced genome, a limited number of cell types, and a simple flattened morphology, Trichoplax is an ideal model organism from which to explore the biology of an animal with a cellular complexity analagous to that of the earliest animals. Using a new approach for identification of gene expression patterns, this research looks at the relationship of Chordin/TgfΒ signaling and the axial patterning system of Placozoa. Our results suggest that placozoans have an oral-aboral axis similar to cnidarians and that the parahoxozoan ancestor (common ancestor of Placozoa and Cnidaria) was likely radially symmetric.
Differentiating Lung Involvement in Adult T-Cell Leukemia Lymphoma (ATLL) Versus HTLV Infection: Results from a Large Single-Center Cohort with Implications for Staging and Response Criteria
Authors: Ana Acuna-Villaorduna, Jesus D Gonzalez-Lugo, B. Hilda Ye, Urvi A Shah, Gurbakhash Kaur, Nishi Shah, Ioannis Mantzaris, Aditi Shastri, Ira Braunschweig, Noah Kornblum, Olga Derman, Amit Verma, Benjamin Zalta, Murali Janakiram
Journal: Blood (2018)
Identification of Gene Regulatory Networks Governing Stemness Properties of Human HSC and LSC
Authors: Stanley W.K. Ng, Stephanie Zhi-Juan Xie, Elvin Wagenblast, Naoya Takayama, Liqing Jin, Nathan Mbong, Alex Murison, Schoof E Erwin, Amanda Mitchell, Peter Van Galen, Mathieu Lupien, Mark D. Minden, Jean C.Y. Wang, Peter W. Zandstra, John E. Dick
Journal: Blood (2018)
Safety and efficacy of high-intensity focused ultrasound in pancreatic cancer.
Authors: Jin Il Kim, DaeYoung Cheung
Journal: Journal of Clinical Oncology (2019)

339 Background: The aim of this study was to evaluate safety and efficacy of high-intensity focused ultrasound (HIFU) for advanced pancreatic cancer. Methods: Patients with pancreatic cancer TNM stage III or IV were included. Magnetic resonance imaging was performed 2 weeks before and after the HIFU. The ablating tumor volume was calculated by ratio of the non-perfused necrotic area of the planned area on contrast-enhanced T1-weighted image on post-HIFU magnetic resonance imaging. The ablation results were stratified into 4 ranges: 100% to 90% unenhanced area of targeting area, 90% to 50%, within 50%, and no change. Results: High-intensity focused ultrasound treatment was performed without severe adverse event in 52 patients, 53 times (male/female = 28/24; mean age, 62.7 ± 12.1; TNM stage 3/stage 4 = 21/31). Average size of the pancreatic cancer lesion was 4.5 ± 1.6 cm (1.4 - 9.5 cm). After HIFU treatment, ablating tumor volume was as follows: 90% to 100% in 41 lesions, 90% to 50% in 11, and within 50% in 3. Overall median survival (S1) from initial pancreatic cancer diagnosis was 13.1 months. Overall survival (S2) rates at 6, 12, and 18 months from HIFU were 53.1%, 31.6%, and 23.5%, respectively, with a median survival of 7.4 months. Conclusions: High-intensity focused ultrasound is safe and effective, which induced excellent local tumor control in most patients with advanced pancreatic cancer.
Recent advances and perspectives of metabolomics-based investigations in Parkinson’s disease
Authors: Yaping Shao, Weidong Le
Journal: Molecular Neurodegeneration (2019)

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease of the central nervous system (CNS), which affects mostly older adults. In recent years, the incidence of PD has been dramatically increasing with the aging population expanding. Due to the lack of effective biomarkers, the accurate diagnosis and precise treatment of PD are currently compromised. Notably, metabolites have been considered as the most direct reflection of the physiological and pathological conditions in individuals and represent attractive candidates to provide deep insights into disease phenotypes. By profiling the metabolites in biofluids (cerebrospinal fluid, blood, urine), feces and brain tissues, metabolomics has become a powerful and promising tool to identify novel biomarkers and provide valuable insights into the etiopathogenesis of neurological diseases. In this review, we will summarize the recent advancements of major analytical platforms implemented in metabolomics studies, dedicated to the improvement and extension of metabolome coverage for in-depth biological research. Based on the current metabolomics studies in both clinical populations and experimental PD models, this review will present new findings in metabolomics biomarkers research and abnormal metabolic pathways in PD, and will discuss the correlation between metabolomic changes and clinical conditions of PD. A better understanding of the biological underpinning of PD pathogenesis might offer novel diagnostic, prognostic, and therapeutic approaches to this devastating disease.
Abstract A016: KDM4B promotes castration-resistant prostate cancer by regulating alternative splicing of the androgen receptor
Authors: Zhi-Ping Liu
Journal: Cancer Research (2018)

Abstract Emergence of constitutively active androgen receptor variant AR-V7 is associated with poor survival of castration-resistant prostate cancer (CRPC). AR-V7 can be generated by the inclusion of cryptic exon CE3 via alternative splicing, but the mechanism of AR-V7 activation remains elusive. Here, we show that histone lysine demethylase KDM4B promotes CRPC via generation of AR-V7. Genetic inactivation of KDM4B in CRPC cells suppressed xenograft growth and abolished tumor AR-V7 expression. Pharmacologic inhibition of KDM4B inhibited tumor growth and sensitized CRPC cells to current antiandrogen therapy. Mechanistically, KDM4B promotes AR-V7 as a trans-acting splicing factor and couples the spliceosome to the chromatin. Our study defines KDM4B-regulated alternative splicing as a pivotal mechanism for generating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRPC. Citation Format: Zhi-Ping Liu. KDM4B promotes castration-resistant prostate cancer by regulating alternative splicing of the androgen receptor [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr A016.
Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial
Authors: M. Moore, J. Trill, C. Simpson, F. Webley, M. Radford, L. Stanton, T. Maishman, A. Galanopoulou, A. Flower, C. Eyles, M. Willcox, A.D. Hay, E. van der Werf, S. Gibbons, G. Lewith, P. Little, G. Griffiths
Journal: Clinical Microbiology and Infection (2019)

The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI).A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016).An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded.We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.
Helen Salisbury: The informed patient
Authors: Helen Salisbury
Journal: BMJ (2019)

Shame, guilt, and apology abound in the GP consultation as people describe their failures to lose weight, give up smoking, or restrict their use of alcohol or other drugs. The language we use to talk about health status can compound these negative feelings.

“Good” and “bad” are used to describe levels of blood sugar, cholesterol, or blood pressure. It’s very easy for those words to be interpreted beyond their intended scope, so that the patient whose diabetes is difficult to control feels judged and found wanting.

But the apology I find the most surprising is when patients “admit” to having informed themselves …
IDO1 and Kynurenine Pathway Metabolites Activate PI3K-Akt Signaling in the Neoplastic Colon Epithelium to Promote Cancer Cell Proliferation and Inhibit Apoptosis
Authors: Kumar S. Bishnupuri, David M. Alvarado, Alexander N. Khouri, Mark Shabsovich, Baosheng Chen, Brian K. Dieckgraefe, Matthew A. Ciorba
Journal: Cancer Research (2019)

The tryptophan-metabolizing enzyme indoleamine 2,3 dioxygenase 1 (IDO1) is frequently overexpressed in epithelial-derived malignancies, where it plays a recognized role in promoting tumor immune tolerance. We previously demonstrated that the IDO1-kynurenine pathway (KP) also directly supports colorectal cancer growth by promoting activation of β-catenin and driving neoplastic growth in mice lacking intact adaptive immunity. In this study, we sought to delineate the specific role of epithelial IDO1 in colon tumorigenesis and define how IDO1 and KP metabolites interact with pivotal neoplastic signaling pathways of the colon epithelium. We generated a novel intestinal epithelial-specific IDO1 knockout mouse and utilized established colorectal cancer cell lines containing β-catenin-stabilizing mutations, human colorectal cancer samples, and human-derived epithelial organoids (colonoids and tumoroids). Mice with intestinal epithelial-specific knockout of IDO1 developed fewer and smaller tumors than wild-type littermates in a model of inflammation-driven colon tumorigenesis. Moreover, their tumors exhibited reduced nuclear β-catenin and neoplastic proliferation but increased apoptosis. Mechanistically, KP metabolites (except kynurenic acid) rapidly activated PI3K-Akt signaling in the neoplastic epithelium to promote nuclear translocation of β-catenin, cellular proliferation, and resistance to apoptosis. Together, these data define a novel cell-autonomous function and mechanism by which IDO1 activity promotes colorectal cancer progression. These findings may have implications for the rational design of new clinical trials that exploit a synergy of IDO1 inhibitors with conventional cancer therapies for which Akt activation provides resistance such as radiation.Significance: This study identifies a new mechanistic link between IDO1 activity and PI3K/AKT signaling, both of which are important pathways involved in cancer growth and resistance to cancer therapy.
Burden and Risk of Neurological and Cognitive Impairment in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE): Final Results of the Cross-Sectional Analysis
Authors: Nancy S. Green, Deogratias Munube, Paul Bangirana, Robert Opoka, Edward Kayongo, Ezekiel Mupere, Linda Rosset Buluma, Bridget Kebirungi, Rogers Sekibira, Sarah Kiguli, Michael Kawooya, Samson Kamya Lubowa, Mitchell S.V. Elkind, Gen Li, Philip LaRussa, Richard Idro
Journal: Blood (2018)
Abstract 15849: Use of Machine Learning to Determine Stroke Severity of Patients Diagnosed With Stroke in Integrated Claims-Medical Records Dataset
Authors: Emily Kogan, Kathryn Twyman, Jesse Heap, Dejan Milentijevic, Jennifer H Lin, Mark J Alberts
Journal: Circulation (2017)

Introduction: The National Institutes of Health Stroke Scale (NIHSS) scores are often recorded in a form of free text in the neurologist’s diagnosis reports and this information is not readily avai...