tbuckley/cabot-search huggingface dataset:
Persistent induction of goblet cell differentiation in the airways: Therapeutic approaches
Authors: Andrew T. Reid, Punnam Chander Veerati, Reinoud Gosens, Nathan W. Bartlett, Peter A. Wark, Chris L. Grainge, Stephen M. Stick, Anthony Kicic, Fatemeh Moheimani, Philip M. Hansbro, Darryl A. Knight
Journal: Pharmacology & Therapeutics (2017)
Use of Fetal Magnetic Resonance Image Analysis and Machine Learning to Predict the Need for Postnatal Cerebrospinal Fluid Diversion in Fetal Ventriculomegaly
Authors: Jared M. Pisapia, Hamed Akbari, Martin Rozycki, Hannah Goldstein, Spyridon Bakas, Saima Rathore, Julie S. Moldenhauer, Phillip B. Storm, Deborah M. Zarnow, Richard C. E. Anderson, Gregory G. Heuer, Christos Davatzikos
Journal: JAMA Pediatrics (2017)

Which children with fetal ventriculomegaly, or enlargement of the cerebral ventricles in utero, will develop hydrocephalus requiring treatment after birth is unclear.To determine whether extraction of multiple imaging features from fetal magnetic resonance imaging (MRI) and integration using machine learning techniques can predict which patients require postnatal cerebrospinal fluid (CSF) diversion after birth.This retrospective case-control study used an institutional database of 253 patients with fetal ventriculomegaly from January 1, 2008, through December 31, 2014, to generate a predictive model. Data were analyzed from January 1, 2008, through December 31, 2015. All 25 patients who required postnatal CSF diversion were selected and matched by gestational age with 25 patients with fetal ventriculomegaly who did not require CSF diversion (discovery cohort). The model was applied to a sample of 24 consecutive patients with fetal ventriculomegaly who underwent evaluation at a separate institution (replication cohort) from January 1, 1998, through December 31, 2007. Data were analyzed from January 1, 1998, through December 31, 2009.To generate the model, linear measurements, area, volume, and morphologic features were extracted from the fetal MRI, and a machine learning algorithm analyzed multiple features simultaneously to find the combination that was most predictive of the need for postnatal CSF diversion.Accuracy, sensitivity, and specificity of the model in correctly classifying patients requiring postnatal CSF diversion.A total of 74 patients (41 girls [55%] and 33 boys [45%]; mean [SD] gestational age, 27.0 [5.6] months) were included from both cohorts. In the discovery cohort, median time to CSF diversion was 6 days (interquartile range [IQR], 2-51 days), and patients with fetal ventriculomegaly who did not develop symptoms were followed up for a median of 29 months (IQR, 9-46 months). The model correctly classified patients who required CSF diversion with 82% accuracy, 80% sensitivity, and 84% specificity. In the replication cohort, the model achieved 91% accuracy, 75% sensitivity, and 95% specificity.Image analysis and machine learning can be applied to fetal MRI findings to predict the need for postnatal CSF diversion. The model provides prognostic information that may guide clinical management and select candidates for potential fetal surgical intervention.
Sucrose octasulfate dressing versus control dressing in patients with neuroischaemic diabetic foot ulcers (Explorer): an international, multicentre, double-blind, randomised, controlled trial
Authors: Michael Edmonds, José Luis Lázaro-Martínez, Jesus Manuel Alfayate-García, Jacques Martini, Jean-Michel Petit, Gerry Rayman, Ralf Lobmann, Luigi Uccioli, Anne Sauvadet, Serge Bohbot, Jean-Charles Kerihuel, Alberto Piaggesi
Journal: The Lancet Diabetes & Endocrinology (2017)
Type I interferons instigate fetal demise after Zika virus infection
Authors: Laura J. Yockey, Kellie A. Jurado, Nitin Arora, Alon Millet, Tasfia Rakib, Kristin M. Milano, Andrew K. Hastings, Erol Fikrig, Yong Kong, Tamas L. Horvath, Scott Weatherbee, Harvey J. Kliman, Carolyn B. Coyne, Akiko Iwasaki
Journal: Science Immunology (2018)

Zika virus (ZIKV) infection during pregnancy is associated with adverse fetal outcomes, including microcephaly, growth restriction, and fetal demise. Type I interferons (IFNs) are essential for host resistance against ZIKV, and IFN-α/β receptor (IFNAR)-deficient mice are highly susceptible to ZIKV infection. Severe fetal growth restriction with placental damage and fetal resorption is observed after ZIKV infection of type I IFN receptor knockout (Ifnar1-/-) dams mated with wild-type sires, resulting in fetuses with functional type I IFN signaling. The role of type I IFNs in limiting or mediating ZIKV disease within this congenital infection model remains unknown. In this study, we challenged Ifnar1-/- dams mated with Ifnar1+/- sires with ZIKV. This breeding scheme enabled us to examine pregnant dams that carry a mixture of fetuses that express (Ifnar1+/-) or do not express IFNAR (Ifnar1-/-) within the same uterus. Virus replicated to a higher titer in the placenta of Ifnar1-/- than within the Ifnar1+/- concepti. Yet, rather unexpectedly, we found that only Ifnar1+/- fetuses were resorbed after ZIKV infection during early pregnancy, whereas their Ifnar1-/- littermates continue to develop. Analyses of the fetus and placenta revealed that, after ZIKV infection, IFNAR signaling in the conceptus inhibits development of the placental labyrinth, resulting in abnormal architecture of the maternal-fetal barrier. Exposure of midgestation human chorionic villous explants to type I IFN, but not type III IFNs, altered placental morphology and induced cytoskeletal rearrangements within the villous core. Our results implicate type I IFNs as a possible mediator of pregnancy complications, including spontaneous abortions and growth restriction, in the context of congenital viral infections.
Empleo de prótesis autoexpandibles en el tratamiento de las dehiscencias postquirúrgicas esofágicas
Authors: M López Álvarez, I Couto Worner, B González Conde, A Guerrero Montañés, MM Blanco Rodríguez, MT Vázquez Rey, E Valdivielso Cortázar, L Yánez González-Dopeso, L Madarnás Alonso, PA Alonso Aguirre
Journal: Endoscopy (2017)

las dehiscencias de suturas en anastomosis quirúrgicas esofágicas y gástricas son una complicación con una elevada morbimortalidad. A pesar de la ausencia de tratamiento estandarizado, las prótesis se han posicionado como un tratamiento efectivo.
Risk Factors for Occurrence and Outcome of Acute Graft Versus Host Disease in Allogeneic Hematopoietic Stem Cell Transplant: Analysis of 7 Year Health Care Utilization Project Data
Authors: Nauman Saleem Siddiqui, Mohammad Saud Khan, Zubair Khan, Hermann Simo, Jamal Mohamad Saleh, Kellie Sprague
Journal: Blood (2017)
Love’s Muse
Authors: Valerie Wohlfeld
Journal: JAMA (2018)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Proton-pump inhibitors and increased gastric cancer risk: time-related biases
Authors: Samy Suissa, Alain Suissa
Journal: Gut (2018)

We read with interest the cohort study by Cheung et al 1 reporting that use of proton-pump inhibitors (PPIs) after Helicobacter pylori eradication is associated with an increased risk of gastric cancer (GC). We believe that the significantly elevated HR of GC with PPI use (HR 2.44; 95% CI 1.42 to 4.20) is a consequence of two time-related biases. Immortal time bias was introduced by misclassifying exposure,2–4 while latency bias was introduced by not incorporating latency in the exposure definition, a major issue for potential carcinogenic drug effects.5 6

Immortal time in a cohort study refers to a period of follow-up time when the outcome could not occur.3 It arises in this study from the definition of frequency of PPI use, ‘calculated by dividing the total treatment duration by the duration of follow-up’, namely the average use over the entire follow-up. Exposure to PPIs was then categorised ‘into non-regular use (<weekly use; reference group) and regular use (at least weekly use)’.1 Thus, the PPI ‘non-users’ included authentic non-users of PPIs and the non-regular PPI users (less than weekly use), together making up the reference group against which the risk …
Therapy-Educated Mesenchymal Stem Cells Enrich for Tumor-Initiating Cells
Authors: Michael Timaner, Nitzan Letko-Khait, Ruslana Kotsofruk, Madeleine Benguigui, Ofrat Beyar-Katz, Chen Rachman-Tzemah, Ziv Raviv, Tomer Bronshtein, Marcelle Machluf, Yuval Shaked
Journal: Cancer Research (2018)

Stromal cells residing in the tumor microenvironment contribute to the development of therapy resistance. Here we show that chemotherapy-educated mesenchymal stem cells (MSC) promote therapy resistance via cross-talk with tumor-initiating cells (TIC), a resistant tumor cell subset that initiates tumorigenesis and metastasis. In response to gemcitabine chemotherapy, MSCs colonized pancreatic adenocarcinomas in large numbers and resided in close proximity to TICs. Furthermore, gemcitabine-educated MSCs promoted the enrichment of TICs in vitro and enhance tumor growth in vivo These effects were dependent on the secretion of CXCL10 by gemcitabine-educated MSCs and subsequent activation of the CXCL10-CXCR3 axis in TICs. In an orthotopic pancreatic tumor model, targeting TICs using nanovesicles (called nanoghosts) derived from MSC membranes and loaded with a CXCR3 antagonist enhanced therapy outcome and delayed tumor regrowth when administered in combination with gemcitabine. Overall, our results establish a mechanism through which MSCs promote chemoresistance, and propose a novel drug delivery system to target TICs and overcome this resistance.Significance: These results establish a mechanism by which mesenchyme stem cells in the tumor microenvironment promote chemoresistance, and they propose a novel drug delivery system to overcome this challenge. Cancer Res; 78(5); 1253-65. ©2018 AACR.
Early B cell changes predict autoimmunity following combination immune checkpoint blockade
Authors: Rituparna Das, Noffar Bar, Michelle Ferreira, Aaron M. Newman, Lin Zhang, Jithendra Kini Bailur, Antonella Bacchiocchi, Harriet Kluger, Wei Wei, Ruth Halaban, Mario Sznol, Madhav V. Dhodapkar, Kavita M. Dhodapkar
Journal: Journal of Clinical Investigation (2018)

Combination checkpoint blockade (CCB) targeting inhibitory CTLA4 and PD1 receptors holds promise for cancer therapy. Immune-related adverse events (IRAEs) remain a major obstacle for the optimal application of CCB in cancer. Here, we analyzed B cell changes in patients with melanoma following treatment with either anti-CTLA4 or anti-PD1, or in combination. CCB therapy led to changes in circulating B cells that were detectable after the first cycle of therapy and characterized by a decline in circulating B cells and an increase in CD21lo B cells and plasmablasts. PD1 expression was higher in the CD21lo B cells, and B cell receptor sequencing of these cells demonstrated greater clonality and a higher frequency of clones compared with CD21hi cells. CCB induced proliferation in the CD21lo compartment, and single-cell RNA sequencing identified B cell activation in cells with genomic profiles of CD21lo B cells in vivo. Increased clonality of circulating B cells following CCB occurred in some patients. Treatment-induced changes in B cells preceded and correlated with both the frequency and timing of IRAEs. Patients with early B cell changes experienced higher rates of grade 3 or higher IRAEs 6 months after CCB. Thus, early changes in B cells following CCB may identify patients who are at increased risk of IRAEs, and preemptive strategies targeting B cells may reduce toxicities in these patients.
MASL1 Is a Critical Modifier of Hepcidin Expression Via Smad1/5/8 Phosphorylation in the Bone Morphogenetic Protein (BMP) Signaling Pathway
Authors: Chutima Kumkhaek, Christian LaChance, Wulin Aerbajinai, Jianqiong Zhu, Griffin P. Rodgers
Journal: Blood (2016)
The Hidden Costs of Medical Education and the Impact on Oncology Workforce Diversity
Authors: Neha Vapiwala, Karen M. Winkfield
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
Favism and Glucose-6-Phosphate Dehydrogenase Deficiency
Authors: Lucio Luzzatto, Paolo Arese
Journal: New England Journal of Medicine (2018)

When persons with G6PD deficiency eat fava beans, acute hemolytic anemia may develop. It is caused by the generation of free radicals from the metabolism of glucosides in the beans. The free radicals damage red cells, resulting in intravascular and extravascular lysis.
Efficacy, Safety, and Pharmacokinetics of Axitinib in Nasopharyngeal Carcinoma: A Preclinical and Phase II Correlative Study
Authors: Edwin P. Hui, Brigette B. Y. Ma, Herbert H. F. Loong, Frankie Mo, Leung Li, Ann D. King, Ki Wang, Anil T. Ahuja, Charles M. L. Chan, Connie W. C. Hui, Chi H. Wong, Anthony T. C. Chan
Journal: Clinical Cancer Research (2018)

Purpose: We hypothesized that axitinib is active with an improved safety profile in nasopharyngeal carcinoma (NPC).Experimental Design: We evaluated axitinib in preclinical models of NPC and studied its efficacy in a phase II clinical trial in recurrent or metastatic NPC patients who progressed after at least one line of prior platinum-based chemotherapy. We excluded patients with local recurrence or vascular invasion. Axitinib was started at 5 mg twice daily in continuous 4-week cycles. Primary endpoint was clinical benefit rate (CBR), defined as the percentage of patients achieving complete response, partial response, or stable disease by RECIST criteria for more than 3 months.Results: We recruited 40 patients, who received a median of 3 lines of prior chemotherapy. Axitinib was administered for a mean of 5.6 cycles, with 16 patients (40%) receiving ≥6 cycles. Of 37 patients evaluable for response, CBR was 78.4% (95% CI, 65.6%-91.2%) at 3 months and 43.2% (30.4%-56.1%) at 6 months. Grade 3/4 toxicities were uncommon, including hypertension (8%), diarrhea (5%), weight loss (5%), and pain (5%). All hemorrhagic events were grade 1 (15%) or grade 2 (3%). Elevated diastolic blood pressure during the first 3 months of axitinib treatment was significantly associated with improved overall survival (HR, 0.29; 95% CI, 0.13-0.64, P = 0.0012). Patient-reported fatigue symptom was associated with hypothyroidism (P = 0.039). Axitinib PK parameters (Cmax and AUC(0-t)) were significantly correlated with tumor response, toxicity, and serum thyroid-stimulating hormone changes.Conclusions: Axitinib achieved durable disease control with a favorable safety profile in heavily pretreated NPC patients. Clin Cancer Res; 24(5); 1030-7. ©2018 AACR.
The Gateway from Near into Remote Oceania: New Insights from Genome-Wide Data
Authors: Irina Pugach, Ana T Duggan, D Andrew Merriwether, Françoise R Friedlaender, Jonathan S Friedlaender, Mark Stoneking
Journal: Molecular Biology and Evolution (2017)

A widely accepted two-wave scenario of human settlement of Oceania involves the first out-of-Africa migration circa 50,000 years ago (ya), and the more recent Austronesian expansion, which reached the Bismarck Archipelago by 3,450 ya. Whereas earlier genetic studies provided evidence for extensive sex-biased admixture between the incoming and the indigenous populations, some archaeological, linguistic, and genetic evidence indicates a more complicated picture of settlement. To study regional variation in Oceania in more detail, we have compiled a genome-wide data set of 823 individuals from 72 populations (including 50 populations from Oceania) and over 620,000 autosomal single nucleotide polymorphisms (SNPs). We show that the initial dispersal of people from the Bismarck Archipelago into Remote Oceania occurred in a “leapfrog” fashion, completely by-passing the main chain of the Solomon Islands, and that the colonization of the Solomon Islands proceeded in a bidirectional manner. Our results also support a divergence between western and eastern Solomons, in agreement with the sharp linguistic divide known as the Tryon–Hackman line. We also report substantial post-Austronesian gene flow across the Solomons. In particular, Santa Cruz (in Remote Oceania) exhibits extraordinarily high levels of Papuan ancestry that cannot be explained by a simple bottleneck/founder event scenario. Finally, we use simulations to show that discrepancies between different methods for dating admixture likely reflect different sensitivities of the methods to multiple admixture events from the same (or similar) sources. Overall, this study points to the importance of fine-scale sampling to understand the complexities of human population history.
Cytokine release syndrome after radiation therapy: case report and review of the literature
Authors: Christopher A. Barker, Samuel K. Kim, Sadna Budhu, Konstantina Matsoukas, Anthony F. Daniyan, Sandra P. D’Angelo
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> Cytokine release syndrome (CRS) has been reported after immunologic manipulations, most often through therapeutic monoclonal antibodies. To our knowledge, CRS after radiation therapy (RT) for cancer has not been reported before. The development of unusual clinical signs and symptoms after RT led us to investigate the possibility of CRS after RT and review the medical literature on this topic. <h3>Case presentation</h3> A 65&nbsp;year-old man with untreated chronic lymphocytic leukemia and recurrent, metastatic Merkel cell carcinoma undergoing anti-programmed death 1 (PD1) immunotherapy was referred for palliative RT to sites of progressing metastases. Within hours of each weekly dose of RT, he experienced fever, tachycardia, hypotension, rash, dyspnea, and rigors. Based on clinical suspicion for CRS, blood cytokine measurements were performed 1 h after the second and third dose of RT and demonstrated tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels approximately ten-fold higher than normal. These were near normal immediately prior to the third dose of RT, and resolved to normal levels 3&nbsp;weeks after RT. He experienced rapid regression of irradiated tumors, with development of new sites of metastases soon thereafter. A literature review revealed no clinical cases of CRS after RT for cancer. <h3>Conclusions</h3> RT during anti-PD1 immunotherapy in a patient with underlying immune dysfunction appeared to be the putative mediator of an immune process which yielded significant increases in pro-inflammatory cytokines, and produced the clinical symptoms meeting the definition of grade 3 CRS. This case demonstrates the capability of RT to elicit immune-related adverse events.
Fibrotic Venous Remodeling and Nonmaturation of Arteriovenous Fistulas
Authors: Laisel Martinez, Juan C. Duque, Marwan Tabbara, Angela Paez, Guillermo Selman, Diana R. Hernandez, Chad A. Sundberg, Jason Chieh Sheng Tey, Yan-Ting Shiu, Alfred K. Cheung, Michael Allon, Omaida C. Velazquez, Loay H. Salman, Roberto I. Vazquez-Padron
Journal: Journal of the American Society of Nephrology (2018)

The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; P =0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population’s median value (OR, 2.63; 95% CI, 1.07 to 6.46; P =0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; P =0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.