tbuckley/cabot-search huggingface dataset:
Monitoring Adherence to Inhaled Medications—Reply
Authors: Mark Hew, Helen K. Reddel
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Developmental differences in health-related quality of life (HRQL) in adolescent and young adult (AYA) survivors of childhood cancer.
Authors: Kerri Becktell, Rachel Phelan, Debra Schmidt, Lynnette Anderson, Julie Nichols, Pippa Simpson, Kristin Bingen
Journal: Journal of Clinical Oncology (2019)

e21524 Background: AYAs experience many distinct periods of developmental transition within this life stage. AYA survivors of childhood cancer are at risk for chronic physical and psychosocial health conditions due to treatment-related exposures. Few studies have evaluated HRQL differences that may exist among developmental subgroups of AYA cancer survivors. This study examined HRQL differences across AYA developmental subgroups (early teens 12-14 years; late teens 15-17; emerging adults 18-24; young adults 25-39) of long term childhood cancer survivors. Methods: Cancer survivors ages 12-39 years who were seen in a long term follow up clinic at time of survey completion (as part of larger HRQL study) and completed therapy ≥2 years ago were included. HRQL was assessed using PedsQL (&lt; 18) and FACT-G (&gt; 18) measures. Demographic and treatment data were obtained from EMR. Analyses compared HRQL measure scores among AYA age subgroups and investigated predictors of HRQL outcomes. Results: A total of 155 patients were included in analysis. Mean age at survey completion was 17.9 [range 12-33] years. PedsQL school functioning was significantly lower for 15-17 year-old compared to 12-14 year-old survivors (M = 77.60, p = 0.01). There were no differences between 18-24 and 25-39 year-old survivors on the FACT-G. PedsQL school functioning was significantly lower for survivors (&lt; 18) compared to normative data (p = 0.004). FACT-G scores for survivors were significantly higher compared to population norms in all domains (p≤0.001) except emotional well-being. Regression CART analysis indicated survivors who were ≤15 years-old and had not relapsed and survivors who were &gt; 15 years old and had ≥2 late effects had lower PedsQL scores. Survivors who were ≥21 years-old had lower FACT-G scores compared to &lt; 21 years. Survivors who were &lt; 21 years-old, &gt; 7 years-old at diagnosis, and &gt; 6 years from end of treatment had lower FACT-G scores. Conclusions: Adolescent survivors may be at risk for school problems years after cancer treatment. Young adult survivors may be at greater risk of poor HRQL. This study highlights potential developmental differences in HRQL predictors and outcomes in long term AYA cancer survivors.
Polymerase δ deficiency causes syndromic immunodeficiency with replicative stress
Authors: Cecilia Domínguez Conde, Özlem Yüce Petronczki, Safa Baris, Katharina L. Willmann, Enrico Girardi, Elisabeth Salzer, Stefan Weitzer, Rico Chandra Ardy, Ana Krolo, Hanna Ijspeert, Ayca Kiykim, Elif Karakoc-Aydiner, Elisabeth Förster-Waldl, Leo Kager, Winfried F. Pickl, Giulio Superti-Furga, Javier Martínez, Joanna I. Loizou, Ahmet Ozen, Mirjam van der Burg, Kaan Boztug
Journal: Journal of Clinical Investigation (2019)

Polymerase δ is essential for eukaryotic genome duplication and synthesizes DNA at both the leading and lagging strands. The polymerase δ complex is a heterotetramer comprising the catalytic subunit POLD1 and the accessory subunits POLD2, POLD3, and POLD4. Beyond DNA replication, the polymerase δ complex has emerged as a central element in genome maintenance. The essentiality of polymerase δ has constrained the generation of polymerase δ–knockout cell lines or model organisms and, therefore, the understanding of the complexity of its activity and the function of its accessory subunits. To our knowledge, no germline biallelic mutations affecting this complex have been reported in humans. In patients from 2 independent pedigrees, we have identified what we believe to be a novel syndrome with reduced functionality of the polymerase δ complex caused by germline biallelic mutations in POLD1 or POLD2 as the underlying etiology of a previously unknown autosomal-recessive syndrome that combines replicative stress, neurodevelopmental abnormalities, and immunodeficiency. Patients' cells showed impaired cell-cycle progression and replication-associated DNA lesions that were reversible upon overexpression of polymerase δ. The mutations affected the stability and interactions within the polymerase δ complex or its intrinsic polymerase activity. We believe our discovery of human polymerase δ deficiency identifies the central role of this complex in the prevention of replication-related DNA lesions, with particular relevance to adaptive immunity.
p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus
Authors: Daniel Menendez, Joyce Snipe, Jacqui Marzec, Cynthia L. Innes, Fernando P. Polack, Mauricio T. Caballero, Shepherd H. Schurman, Steven R. Kleeberger, Michael A. Resnick
Journal: Journal of Clinical Investigation (2019)

The Toll-like receptor 8 (TLR8) has an important role in innate immune responses to RNA viral infections, including respiratory syncytial virus (RSV). We previously reported that TLR8 expression was increased directly by the tumor suppressor and transcription factor p53 via a single nucleotide polymorphism (SNP) (rs3761624) in the TLR8 promoter, thereby placing TLR8 in the p53/immune axis. Because this SNP is in linkage disequilibrium with other SNPs associated with several infectious diseases, we addressed the combined influence of p53 and the SNP on downstream inflammatory signaling in response to a TLR8 cognate ssRNA ligand. Using human primary lymphocytes, p53 induction by chemotherapeutic agents such as ionizing radiation caused SNP-dependent synergistic increases in IL-6 following incubation with an ssRNA ligand, as well as TLR8 RNA and protein expression along with p53 binding at the TLR-p53 SNP site. Because TLR8 is X-linked, the increases were generally reduced in heterozygous females. We found a corresponding association of the p53-responsive allele with RSV disease severity in infants hospitalized with RSV infection. We conclude that p53 can strongly influence TLR8-mediated immune responses and that knowledge of the p53-responsive SNP can inform diagnosis and prognosis of RSV disease and other diseases that might have a TLR8 component, including cancer.
Optimization of the method for analyzing endocytosis of fluorescently tagged molecules: Impact of incubation in the cell culture medium and cell surface wash with glycine-hydrochloric acid buffer
Authors: Noriyasu Kamei, Satoshi Yamamoto, Hiro Hashimoto, Megumi Nishii, Moe Miyaura, Kiho Tomada, Ikuhiko Nakase, Mariko Takeda-Morishita
Journal: Journal of Controlled Release (2019)
The Clinical Spectrum of <i>PTEN</i> Mutations
Authors: Lamis Yehia, Emma Keel, Charis Eng
Journal: Annual Review of Medicine (2019)

PTEN is a tumor suppressor gene that classically dampens the PI3K/AKT/mTOR growth-promoting signaling cascade. PTEN dysfunction causes dysregulation of this and other pathways, resulting in overgrowth. Cowden syndrome, a hereditary cancer predisposition and overgrowth disorder, was the first Mendelian condition associated with germline PTEN mutations. Since then, significant advances by the research and medical communities have elucidated how clinical phenotypic manifestations result from the underlying germline PTEN mutations. With time, it became evident that PTEN mutations can result in a broad phenotypic spectrum, causing seemingly disparate disorders from cancer to autism. Hence, the umbrella term of PTEN hamartoma tumor syndrome (PHTS) was coined. Timely diagnosis and understanding the natural history of PHTS are vital because early recognition enables gene-informed management, particularly as related to high-risk cancer surveillance and addressing the neurodevelopmental symptoms.
Resuming Anticoagulation After Cerebral Intraparenchymal Hemorrhage
Authors: Audrey C. Leasure, Kevin N. Sheth
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Lobe specificity of iron binding to transferrin modulates murine erythropoiesis and iron homeostasis
Authors: Nermi L. Parrow, Yihang Li, Maria Feola, Amaliris Guerra, Carla Casu, Princy Prasad, Luke Mammen, Faris Ali, Edvinas Vaicikauskas, Stefano Rivella, Yelena Z. Ginzburg, Robert E. Fleming
Journal: Blood (2019)
BCOR and BCORL1 mutations in Myelodysplastic Syndromes (MDS): Clonal Architecture and Impact on Outcomes
Authors: Nour Abuhadra, Karam Al-Issa, Aaron T. Gerds, Sudipto Mukherjee, Bhumika Patel, Michael J. Clemente, Vera Adema, Cassandra M. Hirsch, Anjali S. Advani, Mai Aly, Przychodzen P Bartlomiej, Hetty E. Carraway, Jaroslaw P Maciejewski, Mikkael A. Sekeres, Aziz Nazha
Journal: Blood (2016)
Genomic Landscape and Immune Microenvironment Features of Preinvasive and Early Invasive Lung Adenocarcinoma
Authors: Chao Zhang, Jianjun Zhang, Fang-Ping Xu, Yin-Guang Wang, Zhi Xie, Jian Su, Song Dong, Qiang Nie, Yang Shao, Qing Zhou, Jin-Ji Yang, Xue-Ning Yang, Xu-Chao Zhang, Zhi Li, Yi-Long Wu, Wen-Zhao Zhong
Journal: Journal of Thoracic Oncology (2019)

Understanding the genomic landscape and immune microenvironment features of preinvasive and early invasive lung adenocarcinoma may provide critical insight and facilitate development of novel strategies for early detection and intervention.A total of 80 tumor tissue samples and 30 paired histologically normal lung tissue samples from 30 patients with adenocarcinoma in situ (AIS) (n = 8), minimally invasive adenocarcinoma (MIA) (n = 8), and invasive adenocarcinoma (IAC) (n = 14) were subjected to multiregion whole exome sequencing and immunohistochemistry staining for CD8 and programmed death ligand 1 (PD-L1).All tumors, including AIS, exhibited evidence of genomic intratumor heterogeneity. Canonical cancer gene mutations in EGFR, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), NRAS, and BRAF were exclusively trunk mutations detected in all regions within each tumor, whereas genes associated with cell mobility, gap junction, and metastasis were all subclonal mutations. EGFR mutation represented the most common driver alterations across AIS, MIA, and IAC, whereas tumor protein p53 gene (TP53) was identified in MIA and IAC but not in AIS. There was no difference in PD-L1 expression among AIS, MIA, and IAC, but the CD8 positivity rate was higher in IAC. Tumors positive for both PD-L1 and CD8 had a larger proportion of subclonal mutations.Mutations in EGFR, ERBB2, NRAS, and BRAF are early clonal genomic events during carcinogenesis of lung adenocarcinoma, whereas TP53 and cell mobility, gap junction, and metastasis-related genes may be late events associated with subclonal diversification and neoplastic progression. Genomic intratumor heterogeneity and immunoediting are common and early phenomena that may have occurred before the acquisition of invasion.
Nodular Regenerative Hyperplasia Associated With Primary Liver Malignancies
Authors: Daniel Penrice, Douglas A. Simonetto
Journal: Hepatology (2019)

1Department of Internal MedicineMayo ClinicRochesterMN 2Division of Gastroenterology and HepatologyMayo ClinicRochesterMN * Address Correspondence and Reprint Requests to: Douglas A Simonetto, M.D. Division of Gastroenterology and Hepatology, Mayo Clinic 200 First Street Southwest Rochester, MN 55905 E‐mail: [email protected] Tel.: +1‐507‐284‐1649
Cross-cultural validation of a medical leadership competencies survey in Latin-American physicians: A multinational study.
Authors: Max S. Mano, Rafaela Gomes, Carlos H. Barrios, Gustavo Nader Marta, Cynthia Villarreal-Garza, Antonio Luiz Frasson, Cinthya Sternberg, Renan Clara, Sergio D. Simon, Gustavo Werutsky, Fadil Çitaku
Journal: Journal of Clinical Oncology (2019)

10517 Background: Despite the growing complexity in the healthcare sector, physicians rarely receive formal training in leadership skills. In a previous survey, Citaku et el identified a set of leadership competencies (LC) which were evaluated by North-American (NA) and European (EU) leaders involved with medical education. We aim 1) To apply this same survey to a population of Latin-American (LA) physicians from the oncology community and related areas who hold leadership positions of various levels; 2) To compare the results with those of the previous survey and 3) To perform subgroup analyses within the LA cohort. Methods: The survey was sent to close to 8.000 members of contributing medical societies from LA countries. In addition to the 63 questions with 5 possible responses, we also collected data on type of institution (private vs public), country of practice, main specialty, gender, age, years of experience in oncology and years of experience in leadership position. Results: We collected a total of 217 responses on a web-based tool. LA leaders placed the highest value on task-management competencies(91,37% of `important` or `very important` responses vs 87,0% for NA/EU; p &lt; .0001), followed by self-management(87,45% vs 87,55%; p = NS), social responsibility(86,83% vs 87,48% ; p = NS), innovation(86,69% vs 85,31% ; p = NS) and leading others(83,31% vs 84,71% ; p = NS). Social responsibility, which was first in importance in the NA/EU survey, was only third in the LA survey. Subgroup analyses revealed significant interactions which will be fully presented. Conclusions: We successfully applied the survey to a population of LA medical leaders from the oncology community and related areas. LC valued by LA leaders somewhat differ from those valued by their NA/EU counterparts, implying that cultural aspects might influence the perception of desired/required LC. We also detected significant variations in the responses within the LA population. Our data might indicate that current physician leadership training programs should be tailored to suit specific needs and cultural aspects of each region. Further validation of this survey in other clusters of world culture is warranted.
Preoperative detection of circulating tumor cells in patients with colorectal carcinoma: Correlation with clinicopathologic variables and recurrence.
Authors: Hideyasu Sakihama, Nozomi Kobayashi, Tohru Funakoshi, Tatsushi Shimokuni, Shigenori Homma, Norihiko Takahashi, Akihiko Kataoka, Michitaka Ozaki, Toshiya Kamiyama, Akinobu Taketomi
Journal: Journal of Clinical Oncology (2012)

10578 Background: The role of circulating tumor cells (CTC) in the management of colorectal cancer patients has not fully established. The aims of this study are to investigate the relationship between the presence of CTC with clinicopathological variables and recurrence by magnetic activated cell sorting (MACS) system. Methods: Peripheral blood samples were collected from 80 patients. Enrichment of CTC was performed by direct immunomagnetic labeling of EpCAM positive cells in peripheral blood. Subsequently, double immunofluorescence for cytokeratin and CD45 was performed to detect CTC. Peripheral blood samples from twenty healthy volunteers were used as controls. Results: Preoperative positive rate of CTC was 35% while specificity was 100%. No CTC was found in peripheral blood from healthy volunteers. No correlation was found between the presence of CTC and location of tumors, grade of differentiation, vessel invasion, lymph node metastasis or TNM stages. On the other hand, the depth of invasion (0% in Tis, 11.1% in T1, 18.2% in T2 and 34.7% in T3+T4, P=0.05) and tumor recurrence (28.2% for initial operation and 88.9% for reoperative surgery for tumor recurrence, P&lt;0.001) closely correlated with the presence of CTC. Preoperative positive rate of CTC among patients who have recurred postoperatively was 75%. Conclusions: Our results indicate that detections of CTCs correlate with the depth of invasion and tumor recurrence. Preoperative presence of CTCs might be a strong predictor for tumor recurrence.
Phase I trial of neoadjuvant chemoradiotherapy with capecitabine and weekly irinotecan followed by laparoscopic mesorectal excision
Authors: L. Ugidos, C. Conill, S. Delgado, A. Gines, R. Gallego, J. R. Ayuso, R. Miquel, A. M. Lacy, A. Castells, J. Maurel
Journal: Journal of Clinical Oncology (2007)

14556 Background: To establish the feasibility and efficacy of capecitabine with weekly irinotecan (CAPIRI) and concurrent radiotherapy (RT) in patients with locally advanced and resectable metastatic rectal cancer, followed by LAME. Methods: Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (us), spiral abdominal and pelvic CT and chest X-ray. Patients received weekly irinotecan 50 mg/m2 (days 1,8,15,22,29) and two doses of capecitabine (days 1 through 5 for 5 weeks); dose level; (DL) I 250 mg/m2 bid; DL II 375 mg/m2 bid; DL III 500 mg/m2 bid, according to phase I methodology. Conformal radiotherapy was administered up to a total dose of 45 Gy/1.8 Gy per fraction. LAME was planned 5–7 weeks after CRT. Results: From January 2003 to March 2006, 22 patients (three with potentially resectable metastatic disease) were included. Median age was 62 (range 48 to 78). 6 pts were usT3N0 and 16 pts usT3–4N1. Seven patients were treated at DL I, six at DL II and nine at DL III. Grade 3 or 4 adverse events were observed in all levels; DL I asthenia (1p); DL II diarrhea (2p) and DL III asthenia and neutropenia (1p), diarrhea (1p) and hyperbilirrubinaemia (1p). All patients except one who refused treatment after 1 week therapy (DL I), completed CRT and underwent surgical resection (R0 81%, R2 19%). Abdominoperineal resection was done in two cases (9%). Conversion rate to open surgery was 5%. Median hospital stay was 7.9 days. The overall postoperative morbidity was 4.7%. Median excised nodes were 11 (range 4–21). Pathological complete response was observed in two patients (9%), both of them in DL III. With a median follow-up of 25 months (range 9–46), disease free survival and overall survival was 67% and 95% respectively. Conclusions: Preoperative CRT with CAPIRI is feasible, but severe adverse events were found in all levels despite the use of lower dose of capecitabine than previously published. LAME after CAPIRI had short oncologic outcomes comparable with open mesorectal excision. No significant financial relationships to disclose.
A randomized phase II non-comparative study of Ispinesib given weekly or every three weeks in metastatic colorectal cancer. A California Cancer Consortium Study (CCC-P)
Authors: A. B. El-Khoueiry, S. Iqbal, D. A. Singh, S. D’Andre, R. K. Ramanathan, S. Shibata, D. Y. Yang, H. J. Lenz, T. Synold, D. R. Gandara
Journal: Journal of Clinical Oncology (2006)

3595 Background: Ispinesib(SB-715992) is a polycyclic, nitrogen-containing heterocycle that inhibits the mitotic kinesin spindle protein (KSP). KSP is essential for mitotic spindle assembly and function during mitosis, and is a rational target of anti-cancer therapy. This phase II study used two different dosing schedules; the primary objective was to determine the response rate (RR) and the secondary objectives were to determine time to tumor progression (TTP), progression free survival (PFS), overall survival (OS) and toxicity. Methods: Patients (pts) were randomized to receive (Arm A) ispinesib 7 mg/m 2 every week for 3 weeks, every 28 days or (Arm B) 18 mg/m 2 every 21 days. Response was assessed every 6 weeks. Chemotherapy was administered until disease progression or intolerance. Results: A total of 64 pts were accrued. The median number of cycles was 2 for both arms. Five pts had stable disease and 48 had progressive disease. PFS was 49 days in Arm A (44 to 51) and 37 days in Arm B (35 to 42 days). The most common grade 3/4 toxicities in arms A and B respectively included neutropenia (3 and 20), nausea and vomiting (3 and 1), neurologic (1 and 2). Of these, only 1 pt had febrile neutropenia and 1 pt had peripheral sensory neuropathy. The toxicity data is not available on 2 patients. Eleven pts are not evaluable for response yet. Conclusions: Ispinesib did not demonstrate significant activity in heavily pretreated patients with advanced/metastatic colorectal cancer at the dose and schedule employed in this trial. Correlative studies are in progress. Supported by NO1 CM17101 [Table: see text] No significant financial relationships to disclose.