tbuckley/cabot-search huggingface dataset:
Reward-Based Learning Drives Rapid Sensory Signals in Medial Prefrontal Cortex and Dorsal Hippocampus Necessary for Goal-Directed Behavior
Authors: Pierre Le Merre, Vahid Esmaeili, Eloïse Charrière, Katia Galan, Paul-A. Salin, Carl C.H. Petersen, Sylvain Crochet
Journal: Neuron (2017)

The neural circuits underlying learning and execution of goal-directed behaviors remain to be determined. Here, through electrophysiological recordings, we investigated fast sensory processing across multiple cortical areas as mice learned to lick a reward spout in response to a brief deflection of a single whisker. Sensory-evoked signals were absent from medial prefrontal cortex and dorsal hippocampus in naive mice, but developed with task learning and correlated with behavioral performance in mice trained in the detection task. The sensory responses in medial prefrontal cortex and dorsal hippocampus occurred with short latencies of less than 50 ms after whisker deflection. Pharmacological and optogenetic inactivation of medial prefrontal cortex or dorsal hippocampus impaired behavioral performance. Neuronal activity in medial prefrontal cortex and dorsal hippocampus thus appears to contribute directly to task performance, perhaps providing top-down control of learned, context-dependent transformation of sensory input into goal-directed motor output.
Long-Term Clinical Outcomes after Early Initiation of RRT in Critically Ill Patients with AKI
Authors: Melanie Meersch, Mira Küllmar, Christoph Schmidt, Joachim Gerss, Toni Weinhage, Andreas Margraf, Thomas Ermert, John A. Kellum, Alexander Zarbock
Journal: Journal of the American Society of Nephrology (2017)

Whether earlier initiation of RRT in critically ill patients with AKI can improve outcomes remains debated. We examined follow-up data from a large clinical trial to prospectively investigate the long-term outcomes associated with the timing of RRT initiation in such patients. We extended the follow-up of patients in the Early Versus Delayed Initiation of RRT in Critically Ill Patients with AKI (ELAIN) Trial from 90 days to 1 year after randomization for 230 (99.6%) patients. The primary outcome was a composite of major adverse kidney events (persistent renal dysfunction, dialysis dependence, and mortality) at 1 year. Secondary outcomes included inflammatory markers. Overall, 72 of 111 (64.9%) and 106 of 119 (89.1%) patients met the primary outcome in the early (stage 2 AKI) and delayed (stage 3 AKI) initiation groups, respectively (odds ratio [OR] with early initiation, 0.23; 95% confidence interval [95% CI], 0.11 to 0.45; P &lt; 0.001). The early initiation group had a 1-year all-cause mortality rate (56 of 111 [50.2%]) significantly lower than that of the delayed initiation group (83 of 119 [69.8%]; absolute difference, −19.6%; 95% CI, −32.0% to −7.2%; P &lt;0.01). After 1 year, 16 of 55 (29.1%) and 23 of 36 (63.9%) surviving patients in the early and delayed groups, respectively, failed to recover renal function (absolute difference, −34.8%; 95% CI, −54.6% to −15.0%; P =0.001). In conclusion, early initiation of RRT in these critically ill patients with AKI significantly reduced the occurrence of major adverse kidney events, reduced mortality, and enhanced renal recovery at 1 year.
Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease
Authors: Pim van der Harst, Niek Verweij
Journal: Circulation Research (2017)

Coronary artery disease (CAD) is a complex phenotype driven by genetic and environmental factors. Ninety-seven genetic risk loci have been identified to date, but the identification of additional susceptibility loci might be important to enhance our understanding of the genetic architecture of CAD.To expand the number of genome-wide significant loci, catalog functional insights, and enhance our understanding of the genetic architecture of CAD.We performed a genome-wide association study in 34 541 CAD cases and 261 984 controls of UK Biobank resource followed by replication in 88 192 cases and 162 544 controls from CARDIoGRAMplusC4D. We identified 75 loci that replicated and were genome-wide significant (P<5×10-8) in meta-analysis, 13 of which had not been reported previously. Next, to further identify novel loci, we identified all promising (P<0.0001) loci in the CARDIoGRAMplusC4D data and performed reciprocal replication and meta-analyses with UK Biobank. This led to the identification of 21 additional novel loci reaching genome-wide significance (P<5×10-8) in meta-analysis. Finally, we performed a genome-wide meta-analysis of all available data revealing 30 additional novel loci (P<5×10-8) without further replication. The increase in sample size by UK Biobank raised the number of reconstituted gene sets from 4.2% to 13.9% of all gene sets to be involved in CAD. For the 64 novel loci, 155 candidate causal genes were prioritized, many without an obvious connection to CAD. Fine mapping of the 161 CAD loci generated lists of credible sets of single causal variants and genes for functional follow-up. Genetic risk variants of CAD were linked to development of atrial fibrillation, heart failure, and death.We identified 64 novel genetic risk loci for CAD and performed fine mapping of all 161 risk loci to obtain a credible set of causal variants. The large expansion of reconstituted gene sets argues in favor of an expanded omnigenic model view on the genetic architecture of CAD.
Speed, Safety, and Industry Funding — From PDUFA I to PDUFA VI
Authors: Jonathan J Darrow, Jerry Avorn, Aaron S Kesselheim
Journal: New England Journal of Medicine (2017)

The FDA Reauthorization Act of 2017 includes the sixth version of the Prescription Drug User Fee Act. User fees have accelerated drug approvals in the context of inadequate funding of the FDA, and industry now pays 75% of the costs of the scientific review of drugs.
Performance of a Prostate Cancer Genomic Classifier in Predicting Metastasis in Men with Prostate-specific Antigen Persistence Postprostatectomy
Authors: Daniel E. Spratt, Darlene L.Y. Dai, Robert B. Den, Patricia Troncoso, Kasra Yousefi, Ashley E. Ross, Edward M. Schaeffer, Zaid Haddad, Elai Davicioni, Rohit Mehra, Todd M. Morgan, Walter Rayford, Firas Abdollah, Edouard Trabulsi, Mary Achim, Elsa Li Ning Tapia, Mireya Guerrero, Robert Jeffrey Karnes, Adam P. Dicker, Mark A. Hurwitz, Paul L. Nguyen, Felix F.Y. Feng, Stephen J. Freedland, John W. Davis
Journal: European Urology (2017)
Scoring hypoechogenic areas in one parotid and one submandibular gland increases feasibility of ultrasound in primary Sjögren’s syndrome
Authors: Esther Mossel, Suzanne Arends, Jolien F van Nimwegen, Konstantina Delli, Alja J Stel, Frans G M Kroese, Fred K L Spijkervet, Arjan Vissink, Hendrika Bootsma
Journal: Annals of the Rheumatic Diseases (2017)

Objective To assess whether ultrasonographic scoring of (i) both parotid and submandibular salivary glands and (ii) all individual components of the Hocevar scoring system, is needed for classifying patients as primary Sjögren’s syndrome (pSS). Methods Ultrasound examination of the major salivary glands (sUS) was performed in 204 consecutive patients clinically suspected (n=171) or diagnosed (n=33) with pSS. Parenchymal echogenicity, homogeneity, hypoechogenic areas, hyperechogenic reflections and salivary gland posterior border were scored in left and right parotid and submandibular glands. Logistic regression analyses were performed to assess which glands and sUS components contributed significantly to classification as pSS or non-pSS according to the 2016 American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) criteria. Results 116 (57%) patients were classified as pSS, the remaining as non-pSS. Instead of scoring both sides (area under the curve; AUC=0.856, Nagelkerke R 2 =0.526), multivariate analysis showed that sUS scoring of only right (AUC=0.850; R 2 =0.518) or left (AUC=0.852; R 2 =0.511) parotid and submandibular glands is sufficient to predict ACR-EULAR classification. Moreover, all individual components of the Hocevar scoring system significantly predicted classification. Multivariate analysis showed that parenchymal echogenicity and hypoechogenic areas contributed independently to ACR-EULAR classification (AUC=0.857; R 2 =0.539). Scoring these components in one parotid and one submandibular gland highly predicted ACR-EULAR classification (AUC=0.855; R 2 =0.539). Scoring only hypoechogenic areas on one side showed almost similar results (AUC=0.846; R 2 =0.498). Conclusion sUS examination of parotid and submandibular glands on one side is sufficient to predict classification of patients according to the ACR-EULAR criteria. To further increase feasibility of sUS in outpatient clinics worldwide, only hypoechogenic areas can be scored.
Downregulating Neuropilin-2 Triggers a Novel Mechanism Enabling EGFR-Dependent Resistance to Oncogene-Targeted Therapies
Authors: Sabrina Rizzolio, Chiara Battistini, Gabriella Cagnoni, Maria Apicella, Viviana Vella, Silvia Giordano, Luca Tamagnone
Journal: Cancer Research (2017)

Abstract Neuropilins are a class of cell surface proteins implicated in cell migration and angiogenesis, with aberrant expression in human tumors. Here, we show that the expression of Neuropilin-2 (NRP2) controls EGFR protein levels, thereby impinging on intracellular signaling, viability, and response to targeted therapies of oncogene-addicted cells. Notably, increased NRP2 expression in EGFR-addicted tumor cells led to downregulation of EGFR protein and tumor cell growth inhibition. NRP2 also blunted upregulation of an EGFR "rescue" pathway induced by targeted therapy in Met-addicted carcinoma cells. Cancer cells acquiring resistance to MET oncogene-targeted drugs invariably underwent NRP2 loss, a step required for EGFR upregulation. Mechanistic investigations revealed that NRP2 loss activated NFkB and upregulated the EGFR-associated protein KIAA1199/CEMIP, which is known to oppose the degradation of activated EGFR kinase. Notably, KIAA1199 silencing in oncogene-addicted tumor cells improved therapeutic responses and counteracted acquired drug resistance. Our findings define NRP2 as the pivotal switch of a novel broad-acting and actionable pathway controlling EGFR signaling, and driving resistance to therapies targeting oncogene-addiction. Significance: These important findings identify the cell surface molecule Nrp2 as the pivotal switch of a novel, actionable pathway driving EGFR upregulation and resistance to oncogene- targeted therapies. Cancer Res; 78(4); 1058–68. ©2017 AACR.
A notificação obrigatoria dos laboratorios na Alemanha : um inquérito sobre atitudes, práticas e necesidades
Authors: A P Zucs, J Benzler, G Krause
Journal: Eurosurveillance (2005)

Em 2000, a nova lei alema sobre o controle de doencas infecciosas sustituiu a notificacao agregada de casos pela declaracao individual. Este processo foi facilitado pela introduccao simultanea de um sistema de transferencia electronica de dados no sistema de saude publica. Os laboratorios notificadores nao tinham sido conectados electronicamente a essa rede. Foi realizado um inquerito em 2003, por meio de um questionario mandado por correio a 537 laboratorios alemaos de microbiologia medica, com o objectivo de conhecer os seus habitos de declaracao, as suas preferencias em quanto aos formatos de declaracao electronica e equipamentos correspondentes de software. Quase 90% dos que responderam indicaram um prazo de declaracao que nao era superior a 24 horas, e 45% continuam preenchendo manualmente os formularios de declaracao. 74% dos laboratorios mostraram-se favoraveis a notificacao electronica. 33% dentre eles nao usam qualquer software microbiologico especifico. O resto (67%) mencionou 62 produtos differentes. Nesse sentido, poderia ser util de implementar projetos piloto em colaboracao com fabricantes de software seleccionados, para levar a cabo um formato electronico estandardizado de notificacao de doencas infecciosas na Alemanha.
Unexpected Detection of Urethral Stone on 18F-NaF PET/CT
Authors: Fuqiang Shao, Li Chen, Yu Wang, Shumao Zhang, Yue Chen
Journal: Clinical Nuclear Medicine (2017)

A 48-year-old man was referred for an F-NaF PET/CT to examine his lower back pain. The images did not identify any osseous lesion. Unexpectedly, the images showed elevated activity in a urethral stone. The patient received urinary surgery for stone removal.
Recent advances in pre-exposure prophylaxis for HIV
Authors: Monica Desai, Nigel Field, Robert Grant, Sheena McCormack
Journal: BMJ (2017)

<h3>Abstract</h3> Although pre-exposure prophylaxis (PrEP)—the use of antiretroviral drugs by non-infected people to prevent the acquisition of HIV—is a promising preventive option, important public health questions remain. Daily oral emtricitabine (FTC)-tenofovir disoproxil fumarate (TDF) is highly efficacious in preventing the acquisition of HIV in people at risk as a result of a range of different types of sexual exposure. There is good evidence of efficacy in women and men, and when men who have sex with men use event based dosing. Studies have been conducted in several countries and epidemics. Because adherence to this treatment varies greatly there are questions about its public health benefit. Oral FTC-TDF is extremely safe, with minimal impact on kidney, bone, or pregnancy outcomes, and there is no evidence that its effectiveness has been reduced by risk compensation during open label and programmatic follow-up. It is too early to assess the impact of this treatment on the incidence of sexually transmitted infections (STIs) at a population level. Many challenges remain. Access to pre-exposure prophylaxis is limited and disparities exist, including those governed by race and sex. Different pricing and access models need to be explored to avoid further widening inequalities. The optimal combination prevention program needs to be defined, and this will depend on local epidemiology, service provision, and cost effectiveness. This review updates the evidence base for pre-exposure prophylaxis regarding its effectiveness, safety, and risk compensation.
Considerations Concerning Disease Redefinition
Authors: Zu-Yao Yang, Hong Fan, Jin-Ling Tang
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Sustainability of cancer screening in China: a multicentre assessment from the perspective of service suppliers and demanders
Authors: Ju-Fang Shi, A-Yan Mao, Zong-Xiang Sun, Pei Dong, Hui-Yao Huang, Wu-Qi Qiu, Hai-Ke Lei, Guo-Xiang Liu, De-Bin Wang, Ya-Na Bai, Xiao-Jie Sun, Xian-Zhen Liao, Jian-Song Ren, Lan-Wei Guo, Le Wang, Jiang Li, Li Lan, Qi Zhou, Bing-Bing Song, Li Yang, Ling-Bin Du, Jin-Yi Zhou, Lin Zhu, Jia-Lin Wang, Ling Mai, Yu-Qin Liu, Yun-Yong Liu, Yong-Zhen Zhang, Shou-Ling Wu, Kai Zhang, Jie He, Min Dai
Journal: The Lancet (2017)
Contemporary Sarcoma Diagnosis, Genetics, and Genomics
Authors: Inga-Marie Schaefer, Gregory M. Cote, Jason L. Hornick
Journal: Journal of Clinical Oncology (2017)

Sarcomas include diverse mesenchymal neoplasms with widely varied prognosis, clinical behavior, and treatment. Owing to their rarity and histologic overlap, accurate diagnosis of sarcomas can be challenging. Our approach has evolved dramatically in the past few decades, where novel insights into the molecular pathogenetic basis for sarcomas has dramatically (re)shaped contemporary diagnosis, building on a largely morphology- and clinical presentation–based strategy. Examples include the introduction of novel immunohistochemical markers that serve as surrogates for molecular genetic alterations and identification of characteristic molecular alterations. Accordingly, cytogenetic and molecular genetic analyses, such as conventional karyotyping, fluorescence in situ hybridization, reverse transcription–polymerase chain reaction, and targeted sequencing, have increasingly been incorporated into the routine diagnostic work-up of these neoplasms. For those sarcomas with complex cytogenetic changes that lack specific alterations, additional testing is often directed toward identifying lines of differentiation and excluding pathognomonic (cyto-)genetic alterations. Although some gene rearrangements are diagnostic of particular sarcoma types, certain fusion partners, most notably EWSR1, are not tumor specific (and may, in fact, also be found in benign tumors). Correlation with clinical, radiologic, morphologic, and immunohistochemical findings is particularly important in tumors with such rearrangements to establish the correct diagnosis, acknowledging the inherent limitations of diagnostic tests. The recognition of sarcomas occurring in cancer predisposition syndromes is critical, with implications not only for the index patient but also potentially for family members, including the need for genetic counseling and sometimes particular types of surveillance. Together, contemporary sarcoma evaluation involves combining the initial morphologic evaluation with diagnostically relevant cytogenetic, molecular, and immunohistochemical testing methods.
Measuring Loop Gain via Home Sleep Testing in Patients with Obstructive Sleep Apnea
Authors: Jeremy E. Orr, Scott A. Sands, Bradley A. Edwards, Pamela N. Deyoung, Naomi Deacon, Rachel Jen, Yanru Li, Robert L. Owens, Atul Malhotra
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

To the Editor:Nonanatomical traits contribute to obstructive sleep apnea (OSA) in certain individuals (1) and can predict response to therapies beyond continuous positive airway pressure (CPAP) (2, 3).Unstable ventilatory control (high loop gain) is one such trait that is useful for personalizing treatment (4).Measuring loop gain has traditionally required the use of specialized equipment and laborintensive techniques (5); however, recently developed methods can determine loop gain from polysomnography (PSG) using a modelfitting technique (6).Because clinical testing for OSA is shifting to home sleep testing (HST), our aim in this study was to determine whether we could estimate loop gain using this limited dataset, which might facilitate personalized OSA treatment in clinical practice.Subjects with untreated OSA (apnea-hypopnea index [AHI] > 5/h) who underwent both PSG and HST within a 3-month period were included in the study.The research was approved by the institutional review board (#141272 and #150465), and the subjects provided written informed consent.The exclusion criteria were use of sedatives, hypnotics, or narcotics, ongoing OSA treatment, and/or prior airway surgery.In-laboratory attended PSG was performed in the standard fashion with the subjects supine.HST was performed with a type III device (ApneaLink Plus/Air; ResMed).Results were scored using American Academy of Sleep Medicine Chicago criteria (3% desaturation) by a technologist blinded to outcomes.
Phase II, randomized, placebo-controlled study of BYL719 or buparlisib (BKM120) with letrozole for neoadjuvant treatment of postmenopausal women with HR+/HER2−, <i>PIK3CA</i> mutant or wild-type, breast cancer (BC).
Authors: Ingrid A. Mayer, Peter A. Fasching, Michael Gnant, Mario Campone, Lars Blumenstein, Anuradha Dutta, Caroline Germa, Rachel Li, Carlos L. Arteaga
Journal: Journal of Clinical Oncology (2014)

TPS655^ Background: The PI3K/AKT/mTOR pathway is frequently activated in BC, with mutations in PIK3CA particularly common in hormone receptor-positive (HR+) tumors. In preclinical studies of HR+ BC, BYL719 (an α-specific PI3K inhibitor) and buparlisib (a pan-PI3K inhibitor) have shown synergistic effects in vitro and near-complete tumor regression in vivo, respectively, when used in combination with hormone therapy. Methods: This is a Phase II, randomized, double-blind, placebo-controlled trial of BYL719 (300 mg QD) or buparlisib (100 mg QD) combined with letrozole (2.5 mg QD) for the neoadjuvant treatment of postmenopausal women with HR+/HER2– BC (NCT01923168). Key inclusion criteria are stage T1c–T3, any N, M0, operable BC; measurable disease; HR+, HER2– BC; known PIK3CA status (mutant or wild type) and Ki-67 level, determined centrally; Eastern Cooperative Oncology Group performance status ≤1; and adequate bone marrow and organ function. Key exclusion criteria are locally recurrent/metastatic disease and prior systemic therapy or radiotherapy for current BC. Patients will be assigned to 1 of 2 cohorts (PIK3CA mutant or wild type) and randomized to 1 of 3 arms (letrozole + BYL719, buparlisib, or placebo), stratified by Ki-67 level (<14% vs ≥14%) and lymph node status (+ve or –ve). Patients will be treated for 24 weeks, until surgery. The primary endpoint is pathologic complete response (pCR; defined as ypT0/Tis, ypN0) after 24 weeks’ treatment. The secondary endpoints are objective response rate (complete + partial, per RECIST 1.1), safety, rate of breast-conserving surgery, correlation between pCR and Ki-67 changes from baseline to Day 15 and to surgery, response (defined as central preoperative endocrine prognostic index score of 0), and pharmacokinetic profiles of all drugs used in the combination treatments. For each cohort, pCR rates will be summarized by treatment arm. The activity signal with either combination will be established if pre-defined proof-of-concept criteria are met. Approximately 360 patients will be randomized. Global recruitment is ongoing. Clinical trial information: NCT01923168.
Core-binding factor β and Runx transcription factors promote adaptive natural killer cell responses
Authors: Moritz Rapp, Colleen M. Lau, Nicholas M. Adams, Orr-El Weizman, Timothy E. O’Sullivan, Clair D. Geary, Joseph C. Sun
Journal: Science Immunology (2017)

Runx1 and Runx3 play nonredundant roles in promoting the clonal expansion of NK cells during viral infection.
Controversies Regarding Use of Myeloid Growth Factors in Leukemia
Authors: Jacqueline N. Poston, Pamela S. Becker
Journal: Journal of the National Comprehensive Cancer Network (2017)

This review focuses on the data supporting the use of myeloid growth factors (MGFs) in patients being treated for acute myeloid leukemia, acute lymphoblastic leukemia, chronic myeloid leukemia, and hairy cell leukemia, for which neutropenia is a common complication of treatment. However, due to the lack of randomized trial data or conflicting results of clinical studies, comprehensive guidelines have been difficult to formulate. Moreover, to date, these diagnoses have not been addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MGFs. However, in most cases, the general principles have been included in the applicable NCCN Guidelines for each individual cancer site.