tbuckley/cabot-search huggingface dataset:
Neonatal imitation in context: Sensorimotor development in the perinatal period
Authors: Nazim Keven, Kathleen A. Akins
Journal: Behavioral and Brain Sciences (2016)

More than 35 years ago, Meltzoff and Moore (1977) published their famous article, "Imitation of facial and manual gestures by human neonates." Their central conclusion, that neonates can imitate, was and continues to be controversial. Here, we focus on an often-neglected aspect of this debate, namely, neonatal spontaneous behaviors themselves. We present a case study of a paradigmatic orofacial "gesture," namely tongue protrusion and retraction (TP/R). Against the background of new research on mammalian aerodigestive development, we ask: How does the human aerodigestive system develop, and what role does TP/R play in the neonate's emerging system of aerodigestion? We show that mammalian aerodigestion develops in two phases: (1) from the onset of isolated orofacial movements in utero to the postnatal mastery of suckling at 4 months after birth; and (2) thereafter, from preparation to the mastery of mastication and deglutition of solid foods. Like other orofacial stereotypies, TP/R emerges in the first phase and vanishes prior to the second. Based upon recent advances in activity-driven early neural development, we suggest a sequence of three developmental events in which TP/R might participate: the acquisition of tongue control, the integration of the central pattern generator (CPG) for TP/R with other aerodigestive CPGs, and the formation of connections within the cortical maps of S1 and M1. If correct, orofacial stereotypies are crucial to the maturation of aerodigestion in the neonatal period but also unlikely to co-occur with imitative behavior.
Clinical Significance of PD-L1 Protein Expression in Surgically Resected Primary Lung Adenocarcinoma
Authors: Kazuki Takada, Tatsuro Okamoto, Fumihiro Shoji, Mototsugu Shimokawa, Takaki Akamine, Shinkichi Takamori, Masakazu Katsura, Yuzo Suzuki, Takatoshi Fujishita, Gouji Toyokawa, Yosuke Morodomi, Shinji Okano, Yoshinao Oda, Yoshihiko Maehara
Journal: Journal of Thoracic Oncology (2016)
Signaling by TNFα promotes cell death induced by IAP antagonists
Authors: Alireza Alavi, Anne Renee van der Vuurst de Vries, Christopher Benetatos, Pamela Holland, Stephen Condon, John Silke, David Vaux, Mark McKinlay, Srinivas Chunduru
Journal: Cancer Research (2008)

2333  IAP antagonists were originally designed to function as Smac mimetics to promote caspase-9 and caspase-3 activation by neutralizing XIAP. However, recently we and others have shown that IAP antagonists are potent binders of cIAP-1 and cIAP-2, and promote tumor cell apoptosis by activating caspase-8 in a TNFα dependent manner. In sensitive tumor cell lines, IAP antagonists antagonize and induce degradation of both cIAP-1 and cIAP-2 resulting in accumulation of NF-κB-inducing kinase (NIK), activation of the non-canonical NF-κB pathway, stimulation of autocrine TNFα production and induction of apoptosis. IAP antagonist single agent activity across a range of tumor cell lines may be dependent on whether cells can produce TNFα. Cell lines resistant to single agent IAP antagonists show dramatic synergy in the presence of small amounts of TNFα. Moreover, IAP antagonists also cooperate with other biologic and chemotherapeutic agents to induce tumor cell death. The mechanisms of cooperativity between IAP antagonists and other agents will be presented. These findings may have significant clinical ramifications for the use of these compounds to treat cancer.
Genomic profiling of metastatic prostate cancer through analysis of circulating tumor DNA (ctDNA).
Authors: Theodore Stewart Gourdin, Michael B. Lilly
Journal: Journal of Clinical Oncology (2016)

174 Background: We have performed genomic analysis of circulating tumor DNA (ctDNA) to identify actionable anomalies in 55 patients with metastatic prostate cancer. Methods: A publically-accessible assay (Guardant Health) was used to analyze 68 known cancer genes for anomalies (missense mutations, amplifications) by a digital PCR technique. The racial profile included Caucasian (27), African-American (27), Asian (1) patients. Most subjects (82%) had CRPC and had been treated with multiple forms of androgen deprivation and chemotherapy. Results: Genomic anomalies were found in 52/55 subjects. 127 missense mutations and 78 amplifications were identified in 35 genes. Missense mutations in each gene were overwhelmingly single (98/127). African-American patients each had an average of 3.9 genomic anomalies, whereas Caucasian patients each had an average of 2.7 anomalies (p = NS). Anomalies most commonly involved TP53 (43.2%), AR (43.4%), MYC (21.8%), BRAF (21.8%), and DNA repair genes (BRCA1, BRCA2, or ATM; 16.4%). Taxane-based chemotherapy was given to 24/55 subjects with mCRPC. These 24 patients were grouped by TP53 status (WT, n = 13; MUT, n = 11) and progression-free survival (PFS) was determined by PCWG2 criteria (PSA or imaging). Data for PFS vs time were presented as Kaplan-Meier plots and compared by the log rank test. Median PFS during taxane chemotherapy was approximately twice as long for subjects with MUT TP53, compared with that of subjects with WT TP53 (p = 0.013; HR = 2.5 [1.1-6.0]). Conclusions: 1. Genomic analysis on ctDNA from patients with metastatic prostate cancer is feasible and identifies anomalies in most patients. 2. Within the limits of the assay, ctDNA analysis provides similar findings to those identified by analysis of FFPE tissue (Robinson et al., Cell, 2015). 3. ctDNA analysis can identify missense mutations that are associated with an improved PFS from taxane-based chemotherapy. ctDNA analysis may help clinicians to judge the potential benefits of chemotherapy in subjects with mCRPC.
Correlation between efficacy and toxicity in pts with pretreated advanced melanoma treated within the Italian cohort of the ipilimumab expanded access programme (EAP).
Authors: Anna Maria Di Giacomo, Antonio M Grimaldi, Paolo Antonio Ascierto, Paola Queirolo, Michele Del Vecchio, Ruggero Ridolfi, Francesco De Rosa, Federica De Galitiis, Alessandro Testori, Francesco Cognetti, Maria Grazia Bernengo, Paola Savoia, Michele Guida, Sabino Strippoli, Luca Galli, Mario Mandala, Giorgio Parmiani, Gaetana Rinaldi, Massimo Aglietta, Vanna Chiarion-Sileni
Journal: Journal of Clinical Oncology (2013)

9065 Background: Ipilimumab was the first agent approved for the treatment of unresectable or metastatic melanoma that showed an overall survival benefit in randomised phase III trials. Early clinical studies explored the potential relationship between immune-related adverse events (irAEs) associated with ipilimumab and antitumor activity but no definitive conclusion has been reached. Here, we evaluated the possible correlation between efficacy of ipilimumab treatment and irAEs in patients (pts) enrolled in the EAP in Italy. Methods: Ipilimumab was available upon physician request for pts aged ≥16 years with unresectable stage III/stage IV melanoma who had either failed systemic therapy or were intolerant to ≥1 systemic treatment and for whom no other therapeutic option was available. Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for 4 doses. Tumour assessments were conducted at baseline and after completion of induction therapy using immune-related response criteria. Pts were monitored for adverse events (AEs), including immune-related AEs (irAEs), using Common Terminology Criteria for Adverse Events v.3.0. Results: In total, 855 Italian pts participated in the EAP from June 2010 to April 2012 across 55 centres. Among 833 evaluable pts, 278 pts (33.4%) reported an irAE and 555 (66.6%) did not. As of December 2012, the disease control rates among pts with or without irAEs were 35.3% and 33.9% respectively. We noted that there was a difference in the distribution of pts with or without irAEs among pts who experienced a fast progression, thus not being able to receive at least 3 cycles, and pts with slow progression. In fact, due to the mechanism of action of the drug and consequent delayed onset of irAEs, pts with irAEs among fast and slow progressors were 22% and 37% respectively. Therefore, median overall survival was evaluated by adjusting the 2 groups for this factor and results showed a comparable survival between pts who reported an irAE and pts who did not (10.0 vs 9.7 months respectively). Conclusions: This exploratory analysis of EAP data suggest that activity and efficacy of ipilimumab is not related with the occurrence of irAEs.
Corrado and colleagues reply to Van Brabandt and colleagues
Authors: Domenico Corrado, Cristina Basso, Maurizio Schiavon, Gaetano Thiene
Journal: BMJ (2016)

We read with interest Van Brabandt and colleagues’ review questioning the utility of pre-participation screening in preventing sudden cardiac death (SCD) in sports activity.1 The paper is not a balanced “pro and cons” analysis; rather, it seems to be a direct attack on the Italian screening programme and on the researchers who provided scientific evidence that cardiovascular evaluation of athletes is a lifesaving strategy based on more than 30 years’ experience in the Veneto region, northeast Italy.2 3 4 5 6

The paper was signed by laypersons with no experience in the field of sports cardiology, who provided a personal viewpoint and omitted the “real world” opinion of thousands of international physicians daily involved in athlete evaluation who favoured the need for pre-participation screening.7

The authors started by mistakenly reporting that Italy’s screening of competitive athletes has been mandatory since 1979. Instead, screening has been in place by law in Italy since 1982,8 which would be the correct starting point for evaluating its impact on mortality. This initial inaccuracy jeopardises the entire analysis.

The inaccuracy is confirmed by the authors’ statement that the usefulness of ECG screening is confined to detecting athletes with Wolff-Parkinson-White syndrome, when in fact the main strength is …
P-059 Phase I trial of FOLFOXIRI in combination with Panitumumab as first-line treatment of RAS wild-type metastatic colorectal cancer (JACCRO CC-14)
Authors: A. Tsuji, M. Nakamura, M. Ogawa, H. Satake, T. Kotake, Y. Hatachi, A. Takagane, Y. Okita, K. Nakamura, T. Onikubo, M. Takeuchi, M. Fujii, T. Nakajima
Journal: Annals of Oncology (2016)
Trends in Long‐Term Outcomes Among Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis With Renal Disease
Authors: Rennie L. Rhee, Susan L. Hogan, Caroline J. Poulton, Julie Anne G. McGregor, J. Richard Landis, Ronald J. Falk, Peter A. Merkel
Journal: Arthritis & Rheumatology (2016)

Objective It is still not clear how advances in the management of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) have impacted long‐term outcomes. We undertook this study to examine changes over 25 years in long‐term clinical outcomes, including the impact of renal function at diagnosis (a potential marker of time to disease detection) and the duration of cyclophosphamide use in AAV patients with renal involvement. Methods We included ANCA‐positive patients with biopsy‐proven AAV diagnosed between 1985 and 2009 who were followed up in the Glomerular Disease Collaborative Network inception cohort. Outcomes included the composite outcome of end‐stage renal disease (ESRD) or death as well as relapse. Cox proportional hazards or competing risks regression models were adjusted for potential baseline confounders. Results Data from 554 patients were included in the analysis. There was a decreasing 5‐year risk of ESRD or death over time ( P &lt; 0.001 by log rank test for trend). After adjustment for baseline characteristics, the risk of relapse was similar across the time periods ( P = 0.45 by test for trend). Serum creatinine level at baseline was the only significant predictor of an increased risk of ESRD or death (hazard ratio 1.11 per 1 mg/dl of serum creatinine [95% confidence interval 1.04–1.18], P = 0.002). Conclusion In patients with renal disease secondary to AAV, over 25 years the risk of ESRD or death has decreased but the risk of relapse has not changed. A higher serum creatinine level at diagnosis is associated with a higher risk of ESRD or death, suggesting that earlier disease detection is potentially an important measure to improve outcomes in AAV.
Red Scaly Eruption in an Otherwise Healthy 2-Month-Old Boy
Authors: Shane M. Swink, Leslie Castelo-Soccio
Journal: JAMA Pediatrics (2016)

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 Pediatrics 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 Pediatrics journal
Book: Essential Evidence-Based Medicine
Authors: Kristina Fišter
Journal: BMJ (2005)

Almost every textbook about evidence based medicine (EBM) starts with its definition, and that is usually when I roll my eyes and quickly turn the page. Of course, I always go back and read the piece, because I love EBM. But why is it that we still need to define it? It is now about 20 years old and by most relevant medical professionals acknowledged as the way to practise and advance in today's medicine. It is today's medicine.​medicine.




Figure 1



Dan Mayer

Cambridge University Press, £24.99, pp 392, with CD ISBN 0 521 54027 5

Rating: ★★★★




Dan Mayer's book starts with statistics. His premise seems to be that there is no way around the fact that medical students and doctors need to learn more of it—because there is no critical appraisal of medical research without it. There are no shortcuts. You need to put your studying cap on and dive into the scary world of numbers, odds, and areas under curve, not to mention all sorts of measurements, biases, analyses... and what you finally start to grasp is never enough. The narrative but concrete tone in which this book is written will give you as good a chance as any to find your way in this strange environment.

The accompanying CD Rom opens yet another whole new world. Once you figure out how to browse it, you stumble across carefully prepared exercises and workbooks. But when you discover the TemplateFor-MedicalStats, all doubts that buying this book was money well spent will vanish. Unfortunately, the CD contains no link to the BMJ Publishing Group's Clinical Evidence. There is one, but it is at the end of the book, the last entry in the bibliography (www.clinicalevidence.com), which amounts to borderline-tolerable inappreciation of the BMJ's massive contribution to the daily practice of EBM.

The author, Dan Mayer, is a professor of emergency medicine and the theme leader of the four-year evidence based healthcare course at Albany Medical College, New York. Mayer's writing possesses qualities of the best of teachers—patience and simplicity. The result is that we finally have a reasonably comprehensive, highly accurate, and easy to read textbook about EBM, suitable for all lifelong learners of medicine. Modestly titled “Essential,” it contains much more than the essentials. It contains—and conveys—true understanding.
Case 43-1966
Authors: John P. Merrill, Martin H. Flax
Journal: New England Journal of Medicine (1966)

Presentation of CaseA twenty-three-year-old man entered the hospital because of edema, hypertension and azotemia.Eight months previously, because of gradually increasing uremia that necessitated repeated peritoneal dialysis, he had undergone bilateral nephrectomy, with the insertion of a renal transplant donated by his fifty-seven-year-old father. The examination of the kidneys confirmed the preoperative diagnosis of chronic glomerulonephritis. After an initial dose of 300 mg., azathioprine (Imuran) was administered in relatively small doses of 25 to 50 mg. daily because of an unusual sensitivity to its effects on the platelets and white cells. Prednisone was given in a daily dose of . . .
Custom Gene Capture and Next-Generation Sequencing to Resolve Discordant ALK Status by FISH and IHC in Lung Adenocarcinoma
Authors: Jin Sung Jang, Xiaoke Wang, Peter T. Vedell, Ji Wen, Jinghui Zhang, David W. Ellison, Jared M. Evans, Sarah H. Johnson, Ping Yang, William R. Sukov, Andre M. Oliveira, George Vasmatzis, Zhifu Sun, Jin Jen, Eunhee S. Yi
Journal: Journal of Thoracic Oncology (2016)
Значення кишкової метаплазії та дисплазії у морфологічній діагностиці хворих на хронічний рефлюкс-гастрит
Authors: Yu.M. Stepanov, О.М. Kovalenko, N.Yu. Oshmyanska
Journal: GASTROENTEROLOGY (2017)

У роботі за допомогою сучасних гістологічних, гістохімічних і морфометричних методів дослідження проаналізовано біоптати 120 хворих на хронічний рефлюкс-гастрит. Під час гістологічного дослідження слизової оболонки шлунка атрофічні процеси спостерігалися у 73,3 % випадків, при цьо­му у 46,7 % до атрофії приєднувалися більш глибокі ураження: кишкова метаплазія та гіперплазія, а у 15 % випадків — дисплазія шлункових залоз. Авторами запропоновано використання інтегрального показника «кишкова метаплазія + дисплазія» як додаткового критерію оцінки тяжкості передракових змін слизової оболонки шлунка у хворих на хронічний рефлюкс-гастрит, вірогідно пов’язаного з гіперплазією шлункових залоз, інфекцією H.руlori, підвищенням рівня нітритів і тенденцією до збільшення рівня нітратів і гастрину.
European Association of Urology Guidelines for Clear Cell Renal Cancers That Are Resistant to Vascular Endothelial Growth Factor Receptor–Targeted Therapy
Authors: Thomas Powles, Michael Staehler, Börje Ljungberg, Karim Bensalah, Steven E. Canfield, Saeed Dabestani, Rachel H. Giles, Fabian Hofmann, Milan Hora, Markus A. Kuczyk, Thomas Lam, Lorenzo Marconi, Axel S. Merseburger, Alessandro Volpe, Axel Bex
Journal: European Urology (2016)
Harnessing Negative B Cell Selection to Overcome Drug-Resistance in Acute Lymphoblastic Leukemia
Authors: Zhengshan Chen, Seyedmehdi Shojaee, Huimin Geng, Jae-Woong Lee, Maike Buchner, Lars Klemm, Clifford A. Lowell, Elisabeth Paietta, Cheryl L. Willman, William L. Carroll, Ari Melnick, Jae U. Jung, Hassan Jumaa, John E. Coligan, Silvia Bolland, Tak W. Mak, Markus Muschen
Journal: Blood (2014)
Infant Protection Against Influenza Through Maternal Immunization
Authors: Flor M. Munoz
Journal: JAMA Pediatrics (2016)

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 Pediatrics 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 Pediatrics journal
RPL23 Links Oncogenic RAS Signaling to p53-Mediated Tumor Suppression
Authors: Xuan Meng, Nicole R. Tackmann, Shijie Liu, Jing Yang, Jiahong Dong, Congying Wu, Adrienne D. Cox, Yanping Zhang
Journal: Cancer Research (2016)

Abstract The ribosomal protein (RP)–MDM2 interaction is a p53 response pathway critical for preventing oncogenic c-MYC–induced tumorigenesis. To investigate whether the RP-MDM2-p53 pathway is a broad antioncogenic mechanism, we crossed mice bearing an MDM2C305F mutation, which disrupts RPL11 binding to MDM2, with mice expressing an oncogenic HrasG12V transgene. Interestingly, the MDM2C305F-mutant mice, which are hypersensitive to c-MYC–induced tumorigenesis, are not hypersensitive to oncogenic HrasG12V-induced tumorigenesis. Unlike c-MYC, which induces expression of RPL11, RAS overexpression leads to an increase in RPL23 mRNA and protein whereas RPL11 expression remains unchanged. The induction of RPL23 involves both MEK and PI3K signaling pathways and requires mTOR function. Increased expression of RPL23, which maintains binding to MDM2C305F mutant, correlates with increased p53 expression in MDM2C305F cells. Furthermore, RAS overexpression can induce p53 in the absence of p19ARF, and the induction can be abolished by downregulation of RPL23. Thus, although the RPL11–MDM2–p53 pathway coordinates with the p19ARF–MDM2–p53 pathway against oncogenic c-MYC–induced tumorigenesis, the RPL23–MDM2–p53 pathway coordinates with the p19ARF–MDM2–p53 pathway against oncogenic RAS-induced tumorigenesis. Cancer Res; 76(17); 5030–9. ©2016 AACR.
Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come
Authors: Phatsapong Yingchoncharoen, Danuta S. Kalinowski, Des R. Richardson
Journal: Pharmacological Reviews (2016)

Cancer is a leading cause of death in many countries around the world. However, the efficacy of current standard treatments for a variety of cancers is suboptimal. First, most cancer treatments lack specificity, meaning that these treatments affect both cancer cells and their normal counterparts. Second, many anticancer agents are highly toxic, and thus, limit their use in treatment. Third, a number of cytotoxic chemotherapeutics are highly hydrophobic, which limits their utility in cancer therapy. Finally, many chemotherapeutic agents exhibit short half-lives that curtail their efficacy. As a result of these deficiencies, many current treatments lead to side effects, noncompliance, and patient inconvenience due to difficulties in administration. However, the application of nanotechnology has led to the development of effective nanosized drug delivery systems known commonly as nanoparticles. Among these delivery systems, lipid-based nanoparticles, particularly liposomes, have shown to be quite effective at exhibiting the ability to: 1) improve the selectivity of cancer chemotherapeutic agents; 2) lower the cytotoxicity of anticancer drugs to normal tissues, and thus, reduce their toxic side effects; 3) increase the solubility of hydrophobic drugs; and 4) offer a prolonged and controlled release of agents. This review will discuss the current state of lipid-based nanoparticle research, including the development of liposomes for cancer therapy, different strategies for tumor targeting, liposomal formulation of various anticancer drugs that are commercially available, recent progress in liposome technology for the treatment of cancer, and the next generation of lipid-based nanoparticles.