tbuckley/cabot-search huggingface dataset:
Cancer genetics-guided discovery of serum biomarker signatures for prostate cancer.
Authors: S. Gillessen, I. Cima, R. Schiess, P. Wild, M. Kälin, P. Schueffler, J. M. Buhmann, H. Moch, R. Aebersold, W. Krek
Journal: Journal of Clinical Oncology (2010)

4564 Background: The tumor suppressor gene PTEN is one of the most commonly inactivated genes in human cancer and is lost or mutated in several cancers including prostate cancer (PCa). It is expected that specific signaling pathway-activating mutations like PTEN-loss will produce changes in the surface and secreted proteomes of the affected tissue and should be detectable as biomarker signatures in the serum. Methods: We applied a novel two-stage strategy for the discovery of PCa biomarker signatures corresponding to cancer-causing PTEN loss. First, we used quantitative proteomic technologies to identify 785 glycoproteins from sera and prostate tissue of wild-type and prostate-specific PTEN-null mice. Second, following bioinformatic prioritization, we quantified 48 human orthologue candidate biomarkers in sera of patients with PCa or benign prostatic hyperplasia (BPH). The resulting candidate protein profiles were used to compute highly predictive regression models. Results: We identified a 5-protein signature that correctly predicted 71% of cases belonging to patients having aberrant or normal PTEN status (sensitivity=68%, specificity=85%, AUC=0.85). In addition we identified a 3-protein signature that correctly predicted patients having tumors with a Gleason score ≤ 7(3+4) or ≥ 7(4+3) (AUC 0.92). Finally we found a 4-protein signature that discriminated between BPH and PCa with a sensitivity=78% and specificity=63% (AUC=0.74), in combination with PSA with a sensitivity=90% and specificity=83% (AUC=0.84). Conclusions: The identification of the 5-protein signature reflecting tissue PTEN status may aid in selecting patients to treat with inhibitors of the PI3K pathway. Combination of our 4-protein signature and PSA has a higher diagnostic sensitivity and specificity than PSA alone and therefore may improve the effectiveness of PCa screening. The predictive 3-protein signature for Gleason score could facilitate decisions on individualized PCa treatment. Taken together our approach suggests a way for rational cancer biomarker discovery guided by human cancer genetics and based on integration of experimental mouse models, novel proteomics-based technologies and computational modeling. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ProteoMediX ProteoMediX ProteoMediX
Transcatheter Aortic Valve Replacement With Early- and New-Generation Devices in Bicuspid Aortic Valve Stenosis
Authors: Sung-Han Yoon, Thierry Lefèvre, Jung-Ming Ahn, Gidon Y. Perlman, Danny Dvir, Azeem Latib, Marco Barbanti, Florian Deuschl, Ole De Backer, Philipp Blanke, Thomas Modine, Gregor Pache, Franz-Josef Neumann, Philipp Ruile, Takahide Arai, Yohei Ohno, Hidehiro Kaneko, Edgar Tay, Niklas Schofer, Erik W. Holy, Ngai H.V. Luk, Gerald Yong, Qingsheng Lu, William K.F. Kong, Jimmy Hon, Hsien-Li Kao, Michael Lee, Wei-Hsian Yin, Duk-Woo Park, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Hyo-Soo Kim, Christian Butter, Omar K. Khalique, Ulrich Schaefer, Fabian Nietlispach, Susheel K. Kodali, Martin B. Leon, Jian Ye, Bernard Chevalier, Jonathon Leipsic, Victoria Delgado, Jeroen J. Bax, Corrado Tamburino, Antonio Colombo, Lars Søndergaard, John G. Webb, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2016)

Few studies have evaluated the clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve stenosis (AS). Particularly, limited data exist comparing the results of TAVR with new-generation devices versus early-generation devices. This study sought to evaluate the clinical outcomes of TAVR for bicuspid AS with early- and new-generation devices. The Bicuspid TAVR Registry is an international multicenter study enrolling consecutive patients with bicuspid AS undergoing TAVR between April 2005 and May 2015. Of 301 patients, 199 patients (71.1%) were treated with early-generation devices (Sapien XT [Edwards Lifesciences Corporation, Irvine, California]: n = 87; CoreValve [Medtronic, Minneapolis, Minnesota]: n = 112) and 102 with new-generation devices (Sapien 3 [Edwards Lifesciences Corporation]: n = 91; Lotus [Boston Scientific Corporation, Marlborough, Massachusetts]: n = 11). The mean Society of Thoracic Surgeons score was 4.7 ± 5.2 without significant differences between groups (4.6 ± 5.1 vs. 4.9 ± 5.4; p = 0.57). Overall, all-cause mortality rates were 4.3% at 30 days and 14.4% at 1 year. Moderate or severe paravalvular leak was absent and significantly less frequent with new-generation compared to early-generation devices (0.0% vs. 8.5%; p = 0.002), which resulted in a higher device success rate (92.2% vs. 80.9%; p = 0.01). There were no differences between early- and new-generation devices in stroke (2.5% vs. 2.0%; p > 0.99), life-threatening bleeding (3.5% vs. 2.9%; p > 0.99), major vascular complication (4.5% vs. 2.9%; p = 0.76), stage 2 to 3 acute kidney injury (2.5% vs. 2.9%; p > 0.99), early safety endpoints (15.1% vs. 10.8%; p = 0.30), and 30-day all-cause mortality (4.5% vs. 3.9%; p > 0.99). The clinical outcomes of TAVR in patients with bicuspid AS were favorable. New-generation devices were associated with less paravalvular leak and, hence, a higher device success rate than early-generation devices. (The Bicuspid Aortic Stenosis Following Transcatheter Aortic Valve Replacement Registry [Bicuspid TAVR]; NCT02394184)
Association Between Cesarean Birth and Risk of Obesity in Offspring in Childhood, Adolescence, and Early Adulthood
Authors: Changzheng Yuan, Audrey J. Gaskins, Arianna I. Blaine, Cuilin Zhang, Matthew W. Gillman, Stacey A. Missmer, Alison E. Field, Jorge E. Chavarro
Journal: JAMA Pediatrics (2016)

<h3>Importance</h3> Cesarean birth has been associated with higher risk of obesity in offspring, but previous studies have focused primarily on childhood obesity and have been hampered by limited control for confounders. <h3>Objective</h3> To investigate the association between cesarean birth and risk of obesity in offspring. <h3>Design, Setting, and Participants</h3> A prospective cohort study was conducted from September 1, 1996, to December 31, 2012, among participants of the Growing Up Today Study, including 22 068 offspring born to 15 271 women, followed up via questionnaire from ages 9 to 14 through ages 20 to 28 years. Data analysis was conducted from October 10, 2015, to June 14, 2016. <h3>Exposure</h3> Birth by cesarean delivery. <h3>Main Outcomes and Measures</h3> Risk of obesity based on International Obesity Task Force or World Health Organization body mass index cutoffs, depending on age. Secondary outcomes included risks of obesity associated with changes in mode of delivery and differences in risk between siblings whose modes of birth were discordant. <h3>Results</h3> Of the 22 068 offspring (20 950 white; 9359 male and 12 709 female), 4921 individuals (22.3%) were born by cesarean delivery. The cumulative risk of obesity through the end of follow-up was 13% among all participants. The adjusted risk ratio for obesity among offspring delivered via cesarean birth vs those delivered via vaginal birth was 1.15 (95% CI, 1.06-1.26;<i>P</i> = .002). This association was stronger among women without known indications for cesarean delivery (adjusted risk ratio, 1.30; 95% CI, 1.09-1.54;<i>P</i> = .004). Offspring delivered via vaginal birth among women who had undergone a previous cesarean delivery had a 31% (95% CI, 17%-47%) lower risk of obesity compared with those born to women with repeated cesarean deliveries. In within-family analysis, individuals born by cesarean delivery had 64% (8%-148%) higher odds of obesity than did their siblings born via vaginal delivery. <h3>Conclusions and Relevance</h3> Cesarean birth was associated with offspring obesity after accounting for major confounding factors. Although additional research is needed to clarify the mechanisms underlying this association, clinicians and patients should weigh this risk when considering cesarean delivery in the absence of a clear indication.
House dust mite sublingual tablet is effective and safe in patients with allergic rhinitis
Authors: Y. Okamoto, S. Fujieda, M. Okano, Y. Yoshida, S. Kakudo, K. Masuyama
Journal: Allergy (2016)

Background House dust mite (HDM) is the major indoor allergen for allergic diseases such as allergic rhinitis (AR) and asthma. Although sublingual immunotherapy is a curative treatment for HDM-induced AR, data from large-scale studies are limited. We evaluated the efficacy and safety of HDM tablets in adolescent and adult patients (aged 12–64 years) with HDM-induced AR with or without intermittent asthma. Methods In a double-blind trial in Japan, 968 subjects were randomized 1 : 1 : 1 to 300 index of reactivity (IR), 500 IR, or placebo groups. The primary endpoint was the Average Adjusted Symptom Score (AASS) in the last eight weeks of the 52-week treatment. Secondary endpoints included individual nasal and ocular symptom scores, rescue medication use, and the Japanese Rhinoconjunctivitis Quality of Life Questionnaire (JRQLQ) scores. Results The AASS in the last eight weeks of treatment significantly improved in both the 300 IR and the 500 IR groups compared to that in the placebo group (P < 0.001). In the 300 IR group, the onset of action occurred at week 8–10. All four nasal symptoms significantly improved in both active treatment groups; rescue medication use and JRQLQ outcome improved in the 300 IR group. Most adverse events (AEs) were mild, and 16 serious AEs (SAEs) were reported; however, none of them were drug-related. Conclusions One-year treatment with 300 IR and 500 IR HDM tablets was effective without major safety concerns. The recommended therapeutic dose for AR is 300 IR.
Anencephalic Infants as Sources for Organs: Gravity and the Steepness and Slipperiness of Slopes
Authors: Michelle Oberman
Journal: JAMA (1989)

To the Editor.—  Shewmon et al 1 help focus the debate on the medical, ethical, and legal factors at stake in using anencephalic infants as organ sources. They discuss the difficulty of diagnosing anencephaly, and correctly suggest that if such infants are considered to be alive, their organs cannot be harvested. This dilemma warrants an inquiry into whether a diagnosis of anencephaly can be strictly limited to infants born without brains and whether one lacking a  is brain dead. However, their argument against using these infants as donors is not based on diagnostic ambiguity, but rather on a laundry list of nonmedical problems that they fear may result should donations be sanctioned.  For the most part, their arguments against using these infants as donors are variations of the slippery slope doctrine. For example, they assert that the small number of usable organs may result in the intentional production of
The role of mTOR inhibitors in targeting a putative cancer stem cell-like population in esophageal cancer.
Authors: Da Wang, Roland Chiu, John Theodorus Plukker, Robert P. Coppes
Journal: Journal of Clinical Oncology (2016)

43 Background: Despite modern advances in the treatment of esophageal cancer (EC), using neoadjuvant chemoradiotherapy (CRT) and esophagectomy, most patients face poor outcome. Growing evidence indicates that cancer stem cells (CSCs) might contribute to the poor prospects. CSCs are usually resistant to CRT and ultimately can generate a new tumor. The mammalian target of rapamycin (mTOR) pathway is associated with cancer stemness. However, its role in EC CSC-like populations needs to be elucidated. Here, we investigate the role of mTOR pathway on the stemness of a putative CSC-like population. Methods: Previously, we identified a putative CSC-like population (CD44+/CD24-) in EC cell lines and in tumor biopsy from EC patients. qPCR was used to measure the expression of mTOR in CD44+/CD24- CSC-like population of OE21 squamous cell carcinoma and OE33 adenocarcinoma cell lines compared to controls, that consisted of solid tumors generated from the same cell lines obtained from xenografts. mTOR inhibitors rapamycin and torin-1 were used to see their effect on CD44+/CD24- expression and sphere formation. Results: mTOR expression was 2-fold up-regulated in the OE33 CD44+/CD24- CSC-like population compared to control. Furthermore, in OE21 this up-regulation was 1.9-fold. Surprisingly, inhibiting the mTOR pathway with rapamycin enhanced OE33 CD44+/CD24- expression compared to its control (p = 0.01). In pilot experiments this effect was dose dependent and cells treated with rapamycin formed more spheres than control. Rapamycin did not alter the expression of CD44+/CD24- in OE21. Inhibiting the mTOR pathway with Torin-1 enhanced OE21 CD44+/CD24- expression by 1.2-fold compared to control (N = 2). In another pilot experiment Torin-1 treated cells were able to form more spheres compared to control. Torin-1 did not have an effect on the expression of CD44+/CD24- in OE33. Conclusions: These findings indicate that inhibiting the mTOR pathway may enhance CSC-like properties in EC. Additional research needs to be done to further support this hypothesis and elucidate the mechanism in this process. Furthermore, the effect of mTOR pathway inducers in EC needs to be explored.
Timing Is Everything: What Is the Optimal Duration After Chemoradiation for Surgery for Rectal Cancer?
Authors: Karyn A. Goodman
Journal: Journal of Clinical Oncology (2016)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. A 47-year-old woman was referred for management of a newly diagnosed rectal cancer. She presented with a 2-month history of rectal bleeding and change in bowel habits. She underwent a colonoscopy that demonstrated a 5-cm fungating, friable, and partially obstructing mass in the distal rectum, approximately 5 cm from the anal verge. The tumor was palpable on digital rectal examination on the anterior wall of rectum. The biopsy demonstrated a moderately differentiated invasive adenocarcinoma, microsatellite stable. A staging work-up, including a computed tomography scan of the chest, abdomen, and pelvis, demonstrated rectal wall thickening in the midrectum and small lymph nodes in the left perirectal fat. There was a nonspecific 3-mm right lower lobe pulmonary nodule. Rectal magnetic resonance imaging demonstrated a 3-cm mass arising from mid-distal rectum with minimal extension beyond muscularis propria into the mesorectal fat, but without invasion of mesorectal fascia ( Fig 1 ). There were at least three small mesorectal lymph nodes present; the largest rounded node measured up to 5 mm, and no additional pelvic lymphadenopathy was identified. Her carcinoembryonic antigen was 1.1, and all other laboratory studies were within normal limits. She was seen in the Colorectal Multidisciplinary Conference for a discussion of her treatment options.
Outbreak of Zika in Singapore sparks warnings in neighbouring countries
Authors: Owen Dyer
Journal: BMJ (2016)

Zika virus disease has a foothold in Singapore—a major travel hub—and the outbreak is spreading beyond its initial epicentre, a large building site hosting many foreign workers.

Twenty eight new cases were confirmed on 30 August; at least five of them were contracted outside the district where the men worked. The total number of confirmed cases since the outbreak was announced at the weekend stands at 82.1

Most of the cases were found through general practitioners: the health ministry was first alerted to Zika’s arrival by a phone call from three GPs at a local clinic who had identified a cluster of mild …
Association of pharmacogenetic variations in <i>ABCG2</i> with cisplatin toxicity in patients with head and neck squamous cell carcinoma.
Authors: B. Lee, R. Slack, J. J. Hwang, K. Steadman, W. Harter, B. J. Davidson, K. A. Newkirk, P. G. Shields, R. Goldman, J. F. Deeken
Journal: Journal of Clinical Oncology (2011)

5586 Background: Pharmacogenetic (PGx) research attempts to explain variations in the efficacy and toxicity of chemotherapy based on germline and tumor genetic variations. Standard treatment for locally advanced head and neck cancer (H&NC) is a combination of radiation and concurrent cisplatin (C, 100mg/m2q 21 days x 3). We investigated variations in genes involved in cisplatin disposition in patients with H&NC to better understand the PGx of C. Methods: Patients with Stage III-IVb H&NC treated with C and XRT with curative intent were identified. Efficacy was measured by overall survival (OS). Toxicity was assessed by level of myelosuppression and nephrotoxicity experienced during cycle 1 of C (absolute change, % change from baseline, and CTC grade). DNA was extracted from blood PBMC samples, and genetically tested for variants in ERCC1, ERCC2, ERCC4, ERCC6, XRCC1, GSTM1, GSTT1, MT2A, ABCG2, ATP7B,and SLC22A2. Analyses were done using log-rank, Kruskal-Wallis, and Jonkheere-Terpstra tests. Results: A total of 26 pts with stage III (n=7), IVa (n=18) and IVb (n=1) disease were included. Median age was 56 years, 88% were males, and the oropharynx was the predominant primary site (n=21). OS at 5 years was 58%. Mean decline in GFR, WBC, and ANC were 23%, 50%, and 45%, respectively. Grade 2/3 WBC and ANC toxicities occurred in 11 and 7 patients, respectively. The ABCG2 Q141K variant was associated with the grade of WBC count decline (p=0.05) and the percent decline from baseline in patients’ Absolute Neutrophil Count (p=0.026). There was a trend between the ABCG2Q141K variant and GFR decline (p=0.08). Genetic variations that were associated with OS were: ERCC1 Q504K (p=0.0002), ERCC2 D312N (p=0.04) and K751Q (p=0.03). Conclusions: This is the first report that genetic variation in the ABCG2drug transporter is associated with cisplatin toxicity. ABCG2 Q141K is a loss of function variant, and high ABCG2 expression in hematopoietic stem cells and in the proximal renal tubule may explain this finding. Confirming previous results, variations in ERCC1and ERCC2 were significantly associated with the efficacy of cisplatin therapy in this cohort. Confirmatory and prospective studies are ongoing.
Chronic spontaneous urticaria: Implications of subcutaneous inflammatory cell infiltration in an intractable clinical course
Authors: Eriko Itoh, Takeshi Nakahara, Maho Murata, Takamichi Ito, Daisuke Onozuka, Minao Furumura, Akihito Hagihara, Masutaka Furue
Journal: Journal of Allergy and Clinical Immunology (2016)
Incidence of Depression After Stroke, and Associated Risk Factors and Mortality Outcomes, in a Large Cohort of Danish Patients
Authors: Terese S. H. Jørgensen, Ida K. Wium-Andersen, Marie K. Wium-Andersen, Martin B. Jørgensen, Eva Prescott, Solvej Maartensson, Per Kragh-Andersen, Merete Osler
Journal: JAMA Psychiatry (2016)

More than 30 million people live with a stroke diagnosis worldwide. Depression after stroke is frequent, and greater knowledge of associated risk factors and outcomes is needed to understand the etiology and implications of this disabling complication.To examine whether the incidence of and risk factors for depression differ between patients with stroke and a reference population without stroke and to assess how depression influences mortality.Register-based cohort study in Denmark. Participants were all individuals 15 years or older with a first-time hospitalization for stroke between January 1, 2001, and December 31, 2011 (n = 157 243), and a reference population (n = 160 236) matched on age, sex, and municipality. The data were analyzed between January and March 2016.The incidence of depression and mortality outcomes of depression (defined by hospital discharge diagnoses or antidepressant medication use) were examined using Cox proportional hazards regression analyses.In total, 34 346 patients (25.4%) with stroke and 11 330 (7.8%) in the reference population experienced depression within 2 years after study entry. Compared with the reference population, patients with stroke had a higher incidence of depression during the first 3 months after hospitalization (hazard ratio for stroke vs the reference population, 8.99; 95% CI, 8.61-9.39), which declined during the second year of follow-up (hazard ratio for stroke vs the reference population, 1.93; 95% CI, 1.85-2.08). Significant risk factors for depression for patients with stroke and the reference population included older age, female sex, single cohabitation status, basic educational attainment, diabetes, high level of somatic comorbidity, history of depression, and stroke severity (in patients with stroke). The associations were strongest for the reference population. In both populations, depressed individuals, especially those with new onset, had increased all-cause mortality (hazard ratio for new-onset depression, 1.89 [95% CI, 1.83-1.95] for patients with stroke and 3.75 [95% CI, 3.51-4.00] for the reference population) after adjustment for confounders. Similar patterns were found for natural and unnatural causes of death. In most models, the depression-related relative mortality was approximately twice as high in the reference population vs the stroke population.Depression is common in patients with stroke during the first year after diagnosis, and those with prior depression or severe stroke are especially at risk. Because a large number of deaths can be attributable to depression after stroke, clinicians should be aware of this risk.
Protection of Patients From Physician Substance Misuse
Authors: Jeffrey Selzer
Journal: JAMA (2013)

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 Journals 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 2024 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