tbuckley/cabot-search huggingface dataset:
Prevalence and Severity of Sesame Allergy in the United States
Authors: Christopher M. Warren, Avneet S. Chadha, Scott H. Sicherer, Jialing Jiang, Ruchi S. Gupta
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Sesame allergy is of growing concern in the United States. The US Food and Drug Administration recently issued a request for epidemiological data on the prevalence and severity of sesame allergies in the United States to inform possible regulatory action requiring sesame to be labeled as an allergen on packaged foods. <h3>Objective</h3> To provide current estimates of the prevalence, severity, distribution, and clinical characteristics of sesame allergy in the United States. <h3>Design, Setting, and Participants</h3> This cross-sectional study assessed findings of web- and telephone-based food allergy questionnaires. Study participants were first recruited from NORC (National Opinion Research Center) at the University of Chicago's probability-based AmeriSpeak panel, and additional participants were recruited through Survey Sampling International. Surveys were administered to a nationally representative sample of 51 819 US households from October 1, 2015, through September 31, 2016. Responses for 40 453 adults and 38 408 children were included in the analysis. Data were analyzed from January 1, 2017, through May 1, 2019. <h3>Exposures</h3> Demographic and allergic characteristics of participants. <h3>Main Outcomes and Measures</h3> Self-reported sesame allergy was the main outcome and was considered convincing if reported symptoms to sesame-allergic reactions were consistent with an IgE-mediated reaction. Diagnostic history of specific allergens and use of food allergy–related health care services were also primary outcomes. <h3>Results</h3> Using survey responses from 78 851 individuals, an estimated 0.49% (95% CI, 0.40%-0.58%) of the US population reported a current sesame allergy, whereas 0.23% (95% CI, 0.19%-0.28%) met symptom-report criteria for convincing IgE-mediated allergy. An additional 0.11% (95% CI, 0.08%-0.16%) had a sesame allergy reported as physician diagnosed but did not report reactions fulfilling survey-specified convincing reaction symptoms. Among individuals with convincing IgE-mediated sesame allergy, an estimated 23.6% (95% CI, 16.9%-32.0%) to 37.2% (95% CI, 29.2%-45.9%) had previously experienced a severe sesame-allergic reaction, depending on the definition used, and 81.6% (95% CI, 71.0%-88.9%) of patients with convincing sesame allergy had at least 1 additional convincing food allergy. Roughly one-third of patients with convincing sesame allergy (33.7%; 95% CI, 26.3%-42.0%) reported previous epinephrine use for sesame allergy treatment. <h3>Conclusions and Relevance</h3> These data indicate a substantial burden of sesame allergy and provide valuable context to physicians and policy makers in their efforts to evaluate and reduce the public health burden of sesame allergy. Moreover, the relatively low rates of physician diagnosis observed among individuals with convincing IgE-mediated sesame allergy seem to indicate the need for clear diagnosis and appropriate management.
Unilateral Absence of the Basal Ganglia on 123I-Ioflupane DaTScan
Authors: Yaser Baghdadi, Se Jin Anh, Allan Brook, Renee Moadel, Leonard M. Freeman
Journal: Clinical Nuclear Medicine (2019)

This 33-year-old man presented with hemorrhagic stroke manifesting with left hemiparesis and right ptosis. Angiography revealed no patent carotids. The anterior and middle cerebral arteries were filling collaterally through the posterior vertebrobasilar pathway. The presumptive diagnosis was moyamoya disease. The etiology of the bleeding was right basilar tip aneurysm that subsequently had partial coil placement. Months later, the neck of the aneurysm perforated and second coiling was performed. Later on follow-up, patient developed left hand tremor. A radionuclide DATscan revealed total absence of right-sided basal ganglia activity. A possible etiology was occlusion of the middle cerebral artery's lenticulostriate branches.
A pilot phase I/II study of combination chemotherapy with nafamostat mesilate and gemcitabine for unresectable pancreatic cancer
Authors: T. Uwagawa, T. Misawa, T. Iida, M. Matsumoto, T. Gocho, S. Hirohara, S. Sadaoka, K. Yanaga
Journal: Journal of Clinical Oncology (2009)

e15600 Background: To improve chemoresistance of gemcitabine (GEM) caused by GEM-induced nuclear factor kappa B (NF- κB) activation, we have conducted combination chemotherapy of GEM with NF-κB inhibitor, nafamostat mesilate (NAM) which is commercially approved as an effective therapeutic agent for disseminated intravascular coagulation, systemic response syndrome, or pancreatitis in Japan for patients with unresectable pancreatic cancer patients through phase 1/2 study. Methods: Study treatment consists of GEM 1,000 mg/m2 on d 8, 15 and 22 plus NAM 2.4∼4.8 mg/kg on d 8, 15 and 22. NAM was administered intra-arterially by continuous regional infusion for 24 hours via an infusion port system one hour before administration of GEM. Overall survival, response rate (RECIST), serum CA19–9 and clinical benefit response (body weight, pain alleviation) were assessed. Results: Between Feb 2007 and Oct 2008, 20 patients with unresectable pancreatic cancer were included in this study. Pts characteristics: male/female: 18/2, median age 63.5 (range 38–79) yrs, median Karnofsky PS 80% (range 70–90%), stage III/IV: 8/12, serum CA19–9 4,662 U/ml (range 88–32,100), baseline visual analogue scale 0–1/2–4/5–7/8–10; 9/4/7/0, baseline analgesic consumption (morphine-equivalent, mg/day) 0/10–100/100&gt;; 10/7/3. The combination of NAM with GEM is well tolerated and MTD has not been reached. The recommended dose was GEM 1,000 mg/m2; NAM 4.8 mg/kg. Overall survival was 8.0 (range 4.7–17) months. CR/PR/NC/PD/not evaluated; 0/3/14/2/1. Serum CA19–9 reduction rate; 89%. Three pts. could become off and 1pt. could reduce oral morphine sulfate, and 5 pts. gained weight. Conclusions: The GEM/NAM regimen is safe, and the clinical data, including overall survival and clinical benefit response, suggest that the initial clinical outcome of this trial has been encouraging. An expanded cohort of the combination chemotherapy is underway. No significant financial relationships to disclose.
Correlation between serum tumor markers, tissue proliferative activity, and clinicopathologic factors in patients with locally advanced esophageal squamous cell carcinoma.
Authors: Somkiat Sunpaweravong, Patrapim Sunpaweravong, Puttisak Puttawibul, Pleumjit Boonyaphiphat, Anupong Nitiruangjaras
Journal: Journal of Clinical Oncology (2012)

e14639 Background: Squamous cell carcinoma antigen (SCCA) and CYFRA 21-1 have been reported as useful tumor markers for esophageal squamous cell carcinoma (ESCC), but no information has yet been reported about the relationship between these serum tumor markers and tissue proliferative activity (Ki-67). The aim of this study was to compare SCCA, CYFRA 21-1 and Ki-67 with clinicopathological factors and survival in locally advanced ESCC patients. Methods: Pre-treatment SCCA and CYFRA 21-1 serum levels were measured by enzyme-linked immunoassays while the expression of tissue Ki-67 activity was calculated by immunohistochemical nuclear staining on paraffin-embedded tumor samples of locally advanced ESCC patients. The association between these biomarkers, clinicopathological factors, and overall survival were analyzed by Cox proportional hazards model. Results: 166 locally advanced ESCC patients from our institution (2002-6) were evaluated. Their median age was 62 years (39-90), M:F 144:22, location of tumor (upper:middle:lower 31:83:53) and histological grade (well:moderate:poor 50:73:43). 43% had received surgery, 22% chemoradiation and 35% best supportive care. Follow-up times ranged from 2 months to 38 months, and the median survival was 11.0 months. Elevated SCCA (&gt;1.5 ng/mL) and CYFRA 21-1 (&gt;3.5 ng/mL) before treatment were found in 79.1% and 50.4% of the patients, respectively, while 42.6% had both serum markers elevated. The SCCA and CYFRA 21-1 levels were not correlated (p=0.128) to each other, nor either to age, sex, T, N, M, location, grade or Ki-67. High Ki-67 expression levels were significantly correlated with T4 (p=0.010), M1 (p=0.010) and poor grade (p=0.015) but not to age, sex, N or location. Levels of SCCA, CYFRA 21-1 and Ki-67, alone or in any combination, were not correlated to survival of patients. Conclusions: This study suggests that the evaluation of SCCA and CYFRA 21-1 are of no particular correlation to clinicopathological factors and survival in locally advanced ESCC, but Ki-67 is correlated with T, M and grade.
The Dynamics of Frailty Among Older Adults
Authors: Steven M. Albert
Journal: JAMA Network Open (2019)

Richard Ofori-Asenso, MSc, PhD; Ken L. Chin, MClinPharm, PhD; Mohsen Mazidi, MSc, PhD; Ella Zomer, PhD; Jenni Ilomaki, MPharm, PhD; Andrew R. Zullo, PharmD, ScM, PhD; Danijela Gasevic, MD, PhD; Zanfina Ademi, MPharm, MPH, PhD; Maarit J. Korhonen, PhD; Dina LoGiudice, MBBS, PhD; J. Simon Bell, PhD; Danny Liew, MBBS(Hons), FRACP, PhD
Theranostic profiling of Ewing sarcoma (ES) and desmoplastic small round cell tumors (DSRCT).
Authors: Wenhsiang Wen, Sting Chen, Anatole Ghazalpour, Brian Rhees, Matthew Jerome McGinniss, Zoran Gatalica
Journal: Journal of Clinical Oncology (2012)

e20507 Background: Ewing Sarcoma (ES)/PNET and Desmoplastic Small Round Cell Tumor (DSRCT) are sarcomas with distinct chromosomal translocations involving the EWS gene (predominately EWS-FLI1 and EWS-WT1; respectively). Their diagnosis and treatment has been difficult due to the rarity, diverse clinical presentation, overlapping histologic features and genetic complexity (Taylor BS et al, 2011). Therefore, novel approaches in clinical management are warranted. Methods: Seventeen cases (9 ES and 8 DSRCT) were analyzed using a commercial molecular profiling service (CarisTargetNow, Caris Life Sciences, Phoenix, AZ). The whole genome transcriptome analysis (29285 transcripts) was performed using HumanHT-12 beadChip (Illuminia Inc, San Diego, CA) and comparison to pooled soft tissue reference sample. Additionally, a select number of chemotherapy-predictive (theranostic) biomarkers were evaluated using immunohistochemistry, FISH, and DNA sequencing. Results: We observed 160 commonly up and 357 commonly down regulated genes between ES and DSRCT in transcriptome analysis. Cell cycle signaling, DNA replication and E2F mediated pathway genes were most commonly up regulated. In addition, higher expression of SOX-2, a recently identified cancer stem cell marker (Riggi et al, 2010), were observed in DSRCT than in ES, suggesting EWS-WT1 translocation might result in reprogramming of DSRCT to express cancer stem cells. Above threshold expression of TOP2A and TOPO1was observed in approximately 50% of all cases. Additional theranostic biomarkers (ERCC1, TS, SPARC and MGMT) showed significant inter-individual variations. No KRAS mutations or EGFR gene amplification were observed in any case. Conclusions: 1. Our transcriptome analyses might provide future therapeutic targets in cell cycle regulation, DNA replication, receptor TKI pathways and stem cell reprogramming. 2. Using multimodality test approaches, we confirmed and refined the benefits in both tumor types of individualized therapeutic assessment including predicted susceptibilities to anthracycline, irinotecan, platinum analogs, fluorouracil, and temozolomide.
Profiling of receptor tyrosine kinases (RTK) activation in metastatic breast cancer lesions <i>via</i> proximity mediated microarray immunoassay
Authors: P. Kim, L. Liu, X. Liu, G. Harvie, L. Zhang, R. Kirkland, K. Magonova, B. Ybarrondo, S. Singh
Journal: Journal of Clinical Oncology (2009)

e22095 Background: The changes in the tumor receptor expression status between primary site and metastatic lesions are known to occur at a significant frequency (∼15–20%). Methods for profiling RTK activation patterns on metastatic tumors may provide valuable insight into the shifting disease pathogenesis allowing better selection of therapy combination for individual patient. Methods: A novel technology capable of specifically detecting phosphorylation events in ErbB family RTKs has been developed. It utilizes the formation of a unique immuno-complex requiring the co-localization of two detector enzyme-conjugated-antibodies once target proteins are captured on the microarray-surface. The channeling events between two detector enzymes (Glucose Oxidase &amp; Horse Radish Peroxidase) in proximity enabled the profiling of the RTK with extreme sensitivity. The analytical specificity is greatly enhanced given the requirement for simultaneous binding of three different antibodies. We used 29 frozen breast cancer tissues (stage II to IV) as a model system for metastatic fine needle aspirate (mFNA) RTK profiling. Results: Out of 29 mFNA-samples, 27% (8/29) showed highly activated HER2, and 2 samples (6%) showed intermediate level of HER2-activation. Two of the 8 samples with high level HER2-activation showed significant level of HER1-activation as well. A similar level of HER1-activation was also found in one of the samples with intermediate HER2-activation. Among 19 activated-HER2-negative samples, 3 showed moderate level of HER1-activation. Conclusion: The multiplexed-proximity mediated immuno-microarray was utilized to detect the phosphorylation of HER1/HER2 in limited amount of mFNA-tissue-samples. We were able to detect activated HER1-RTKs in number of mFNA samples regardless of their HER2-IHC status. Having the ability to profile tumors at different metastatic sites with an expanded pathway panel could provide information on their differential metastatic potentials; hence minimally invasive single-passage-mFNA samples may be utilized to tailor therapy selection/adjustment and monitoring the disease progression. [Table: see text]
Response to: ‘Ultrasonographic salivary gland evaluation in systemic sclerosis: is sicca syndrome secondary to an authentic overlap syndrome or another specific fibrotic manifestation of the disease?’ by Coiffier<i>et al</i>
Authors: Marion Couderc, Jean-Jacques Dubost
Journal: Annals of the Rheumatic Diseases (2019)

Response to: 'Ultrasonographic salivary gland evaluation in systemic sclerosis: is sicca syndrome secondary to an authentic overlap syndrome or another specific fibrotic manifestation of the disease?' by Coiffier et alWe would like to thank Coiffier and colleagues for their attention to our paper. 1 2 Dryness in systemic sclerosis (SSc) may result from salivary gland fibrosis secondary to the disease or Sjögren's syndrome associated with SSc, especially in patients with anticentromere antibodies, or both mechanisms.Ultrasound of the major salivary glands is a simple, rapid and non-invasive assessment tool.Correlated to biopsy, it could provide pathophysiological evidence in favour of either of these hypotheses.We look forward to the study proposed by the authors.
Leukocyte Elastase Release during Blood Coagulation
Authors: Edward F. Plow
Journal: Journal of Clinical Investigation (1982)

Immunological detection of elastase, an enzyme present within leukocyte granules, has been used as a marker for polymorphonuclear leukocyte activation. Polymorphonuclear leukocytes contained 4.6 μg/107 cells, whereas erythrocytes, mononuclear cells, and platelets contained <1% of this level. In plasma that was separated from blood cells after 1 h at 22°C, the mean level of elastase-related antigen in seven normal donors was 25±6 ng/ml. This level was unaltered by immediate separation of the plasma from the cells, by inclusion of protease inhibitors, or by anticoagulation of the plasma with either EDTA or acidcitrate-dextrose (the level in heparinized plasma was approximately threefold higher). In serum, the level of elastase-related antigen was 288±125 ng/ml, representing an 11.5-fold increase above plasma levels. The antigen detected in serum was immunochemically indistinguishable from the leukocyte enzyme. Release of elastase was observed when isolated polymorphonuclear leukocytes were added to nonanticoagulated platelet-rich or platelet-poor plasma, recalcified plasma, or to serum. Addition of a chelating agent to serum prevented elastase release, but calcium or magnesium did not induce release in the absence of plasma. Coagulation induced by addition of thrombin to plasma also failed to induce release. In whole blood or in anticoagulated plasma reconstituted with polymorphonuclear leukocytes and then recalcified, initial release of elastase occurred concomitantly with or slightly after clotting and reached maximal levels within 20-40 min after clot formation. The data indicates that early events in coagulation or other pathways that occur in parallel with coagulation induce leukocyte release. The release of elastase, a major fibrinolytic protease of leukocytes, from the cells provides a mechanism for this enzyme or other granule proteases to participate in physiological events.
Unlocking stress and forecasting its consequences with digital technology
Authors: Sarah M. Goodday, Stephen Friend
Journal: npj Digital Medicine (2019)

Chronic stress is a major underlying origin of the top leading causes of death, globally. Yet, the mechanistic explanation of the association between stress and disease is poorly understood. This stems from the inability to adequately measure stress in its naturally occurring state and the extreme heterogeneity by inter and intraindividual characteristics. The growth and availability of digital technologies involving wearable devices and mobile phone apps afford the opportunity to dramatically improve measurement of the biological stress response in real time. In parallel, the advancement and capabilities of artificial intelligence (AI) and machine learning could discern heterogeneous, multidimensional information from individual signs of stress, and possibly inform how these signs forecast the downstream consequences of stress in the form of end-organ damage. The marriage of these tools could dramatically enhance the field of stress research contributing to impactful and empowering interventions for individuals bridging knowledge to practice, and intervention to real-world use. Here we discuss this potential, anticipated challenges, and emerging opportunities.
Is autologous graft versus host disease (AutoGVHD) really reactivation of Epstein-Barr virus (EBV)?
Authors: J. D. Bitran, A. Ragam, J. Rowan, L. Klein, C. Majcher, M. Hurd
Journal: Journal of Clinical Oncology (2007)

17526 Background: AutoGVHD is a rare complication following autologous bone marrow transplantation(ABMT). It has been described as an autoimmune syndrome initiated by auto-effector T cells that recognize self-major histocompatibility complex class II antigens. AutoGVHD can be induced with immunosuppresives such as cyclosporine and alemtuzumab. Methods: We wish to report two patients among 17 patients who underwent ABMT this year of what was intially thought to be AutoGVHD but in both instances was really reactivation of EBV. Results: A 70 year old white man underwent ABMT for relapsed AML M2 in second CR. The conditioning regimen was cyclophosphamide and busulfan (BuCy). His hospital was uneventful and the prophylatic antibiotics used were ciprofloxacin, fluconazole, and valacyclovir. Neutropenic fever occured on day +11 and prophylatic antibiotics were discontinued and replaced with intravenous vancomycin, piperacillin&amp;tazobactam, and caspofugin. Engraftment occured on day +15 and the patient was discharged on day + 20 on oral valacyclovir and fluconazole. An AutoGVHD rash occurred on day+29. The second patient was a 67 year old white with a stage IIIA E mantle cell lynphoma who underwent ABMT in first CR with the BEAM+rituximab regimen. His hospital course was uneventful; he received the identical prophylatic antibiotic regimen. Engraftment occured on day +12 and he was discharged on valacyclovir and fluconazole. On day +14 he developed an AutoGVHD rash. The first patient underwent a skin biopsy which showed a spongiotic dermatitis with intraepithelial vesicular formation and dermal perivascular lymphocytes. The immunostains of the lymphocytes showed a predominance of CD4 T cells. Immunostains for CMV, EBV, HSV1 and 2 were nonreactive. Serum antibodies to the Early EBV antigen and EBV capsid (IgG) and EBV nuclear (IgG) were elevated. Serologies for Human Herpes Virus 6, 7, and 8 were negative. The second patient had elevated antibodies to the Early EBV antigen, EBV capsid antigen, and the EBV nuclear antigen. He had elevated antibodies to Human Herpes Virus 6. Conclusions: These two patient suggests that what clinically is thought to be AutoGVHD may indeed be reactivation of EBV. The incidence of reactivation of EVB in ABMT needs to be studied prospectively. No significant financial relationships to disclose.
NY-ESO-1 as a predictive and prognostic marker in NSCLC.
Authors: Tom John, Prudence Russell, Stephen Barnett, Zoe Wainer, Shane White, Paul Mitchell, Marzena Walkiewicz, Paul C Boutros, Maud HW Starmans, Yao-Tseng Chen, Gavin Wright, Simon Knight, Jonathan S. Cebon
Journal: Journal of Clinical Oncology (2012)

e17539 Background: Cancer-testis antigens (CTAgs) have previously been shown to be markers of poor prognosis and to be associated with chemoresistance in short interference RNA screens. In contradistinction, we recently reported the CTAg NY-ESO-1 predicted improved responses to neoadjuvant chemotherapy in pathological stage IIIA NSCLC. Despite this, no significant survival benefit was seen in NY-ESO-1 positive (NY-ESO-1+) patients. Given that tissues available for staining in the neoadjuvant setting were limited, we investigated a retrospective cohort of patients who underwent curative surgery for pathological N2 disease. As some of these patients were operated on prior to the broad acceptance of adjuvant chemotherapy (ACT), half did not receive chemotherapy. We investigated NY-ESO-1 as a prognostic and/or predictive marker in these patients. Methods: Formalin fixed paraffin embedded tissues were reviewed and stained using standard methods for a panel of CTAgs including NY-ESO-1 by immunohistochemistry. Tumors were categorized as NY-ESO-1+ or NY-ESO-1-. Isolated DNA was subjected to mutation profiling using Sequenom’s MassArray platform. Molecular markers were correlated with clinicopathological features and survival. Results: NY-ESO-1 stained 26/104 (25%) samples, including 15 cases that received ACT and 11 that did not. NY-ESO-1+ tumors were enriched for squamous cell carcinomas over adenocarcinomas (12/29 vs. 8/57; p = 0.01). They also lacked EGFR mutants and were enriched for KRAS mutants amongst adenocarcinomas relative to NY-ESO-1- tumors (5/8 vs. 9/49; p=0.02). NY-ESO-1+ patients who did not receive ACT had significantly worse outcome than NY-ESO-1- patients who did not receive ACT (HR 2.66 1.2-5.86, p=0.01). Median survival favored NY-ESO-1+ patients who received chemotherapy (37.7 months) compared to NY-ESO-1- patients regardless of chemotherapy (28.2 ACT vs 15.7 No ACT; p= 0.25) and NY-ESO-1+ patients who did not receive ACT (7.75). Conclusions: In this dataset, NY-ESO-1 was poorly prognostic but also predictive for more favorable outcomes with chemotherapy. These data support our previous observation of increased responses to chemotherapy in NY-ESO-1+ N2 patients and warrant further study.