tbuckley/cabot-search huggingface dataset:
FOLFOX as adjuvant chemotherapy after curative resection of distant metastatic lesions in patients with colorectal cancer.
Authors: Joji Kitayama, Hiroaki Nozawa, Toshiaki Watanabe, Eiji Sunami
Journal: Journal of Clinical Oncology (2012)

e14142 Background: Although FOLFOX regimen is shown to be effective to suppress the recurrence of stage III colorectal cancer (CRC) who received curative resection, the prophylactic effect of has not fully been investigated in adjuvant setting of stage IV CRC cases, namely, after curative resection of distant metastases. Methods: This is a retrospective study including 116 CRC patients with synchronous metastases and 91 with metachronous metastases who received curative resection in our hospital between 2000 and 2009. Pathological parameters of primary CRC, postoperative chemotherapeutic regimen, relapse-free survival (RFS) were analyzed retrospectively. Results: After resection of CRC and synchronous metastases, 53 (84%) out of 63 patients without chemotherapy, and 38 (83%) out of 46 that received oral or intravenous 5-fluorouracil (5-FU) alone or with leucovorin (LV) developed recurrent tumors. By contrast, only single patient (17%) among 6 who underwent FOLFOX showed recurrence. With a median follow-up period of 775 days, the FOLFOX group exhibited a significantly improved RFS as compared to the 5-FU(+LV) or surgery alone group (p=0.03, p=0.007, respectively). The 5-year OS rates of the surgery alone, 5-FU(+LV), and FOLFOX group were 67%, 75%, and 100%. In CRC cases with metachronous metastases, on the other hand, the recurrence rate of the group without chemotherapy was 63%, and that of the 5-FU (+LV) group 55%. In 7 patients who underwent FOLFOX chemotherapy (5 cases of FOLFOX4 and 2 cases of mFOLFOX6, no antibody therapy) after metastasectomy, 71% (5 patients) relapsed afterward. Thus, the tumor-relapse rate after metastasectomy was similar among patients who received no postoperative chemotherapy. The median RFSs of the surgery alone, 5-FU(+LV), and FOLFOX groups were 323, 917, and 322 days, respectively. Conclusions: Adjuvant FOLFOX is certainly beneficial for stage IV CRC patients with synchronous metastasis who received curative resection. In contrast, the prophylactic effect of FOLFOX is not superior to other follow-up strategies in patients who received complete resection of metachronous metastases.
Validation of a health-related quality of life instrument for primary ciliary dyskinesia (QOL-PCD)
Authors: Laura Behan, Margaret W Leigh, Sharon D Dell, Audrey Dunn Galvin, Alexandra L Quittner, Jane S Lucas
Journal: Thorax (2017)

<h3>Background</h3> Quality of life (QOL)-primary ciliary dyskinesia (PCD) is the first disease-specific, health-related QOL instrument for PCD. Psychometric validation of QOL-PCD assesses the performance of this measure in adults, including its reliability, validity and responsiveness to change. <h3>Methods</h3> Seventy-two adults (mean (range) age: 33 years (18–79 years); mean (range) FEV<sub>1</sub>% predicted: 68 (26–115)) with PCD completed the 49-item QOL-PCD and generic QOL measures: Short-Form 36 Health Survey, Sino-Nasal Outcome Test 20 (SNOT-20) and St George Respiratory Questionnaire (SGRQ)-C. Thirty-five participants repeated QOL-PCD 10–14 days later to measure stability or reproducibility of the measure. <h3>Results</h3> Multitrait analysis was used to evaluate how the items loaded on 10 hypothesised scales: physical, emotional, role and social functioning, treatment burden, vitality, health perceptions, upper respiratory symptoms, lower respiratory symptoms and ears and hearing symptoms. This analysis of item-to-total correlations led to 9 items being dropped; the validated measure now comprises 40 items. Each scale had excellent internal consistency (Cronbach9s α: 0.74 to 0.94). Two-week test–retest demonstrated stability for all scales (intraclass coefficients 0.73 to 0.96). Significant correlations were obtained between QOL-PCD scores and age and FEV<sub>1</sub>. Strong relationships were also found between QOL-PCD scales and similar constructs on generic questionnaires, for example, lower respiratory symptoms and SGRQ-C (r=0.72, p&lt;0.001), while weak correlations were found between measures of different constructs. <h3>Conclusions</h3> QOL-PCD has demonstrated good internal consistency, test–retest reliability, convergent and divergent validity. QOL-PCD offers a promising tool for evaluating new therapies and for measuring symptoms, functioning and QOL during routine care.
STUDIES ON THE OXIDATION AND REDUCTION OF IMMUNOLOGICAL SUBSTANCES
Authors: James M. Neill, Tracy B. Mallory
Journal: The Journal of Experimental Medicine (1926)

The "spontaneous deterioration" of streptolysin has been studied by the methods already used in investigations of the oxidation-reduction of blood pigments and of the lysins of other bacteria. From the results of this study, it may be concluded that the commonly observed "spontaneous deterioration" of streptolysin consists in the conversion of the originally active lysin to a hemolytically inactive oxidation product. This process is a reversible one, and the activity of the lysin is restored by reduction.
Cholera toxin inhibits IL-12 production and CD8α+ dendritic cell differentiation by cAMP-mediated inhibition of IRF8 function
Authors: Andrea la Sala, Jianping He, Leopoldo Laricchia-Robbio, Stefania Gorini, Akiko Iwasaki, Michael Braun, George S. Yap, Alan Sher, Keiko Ozato, Brian Kelsall
Journal: The Journal of Experimental Medicine (2009)
PRKD2 Serine-Threonine Kinase, an Essential Effector of Gabp Transcription Factor, Is Required for Development of Chronic Myelogenous Leukemia
Authors: Zhong-Fa Yang, Haojian Zhang, Leyuan Ma, Cong Peng, Yaoyu Chen, Michael Green, Shaoguang Li, Alan G. Rosmarin
Journal: Blood (2012)
Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection
Authors: Joseph F. Perez-Rogers, Joseph Gerrein, Christina Anderlind, Gang Liu, Sherry Zhang, Yuriy Alekseyev, Kate Porta Smith, Duncan Whitney, W. Evan Johnson, David A. Elashoff, Steven M. Dubinett, Jerome Brody, Avrum Spira, Marc E. Lenburg
Journal: JNCI Journal of the National Cancer Institute (2017)

Background: We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Methods: Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. Results: We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up (P < .001). Using bronchial gene expression data from the AEGIS-1 patients, we found statistically significant concordant cancer-associated gene expression alterations between the two airway sites (P < .001). Differentially expressed genes in the nose were enriched for genes associated with the regulation of apoptosis and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. Conclusions: These results support that the airway epithelial field of lung cancer–associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection.
Earlier menarche is linked to increased risk of gestational diabetes, study finds
Authors: Jacqui Wise
Journal: BMJ (2017)

Girls who start their periods at a young age could be at increased risk of developing gestational diabetes mellitus, a study in the American Journal of Epidemiology has found.1

The researchers collected data from 4749 women with an average age of 25 who were participating in the Australian Longitudinal Study on Women’s Health. At …
The Language of Biosimilars: Clarification, Definitions, and Regulatory Aspects
Authors: Paul Declerck, Romano Danesi, Danielle Petersel, Ira Jacobs
Journal: Drugs (2017)

Biologic therapies have revolutionized treatment of a number of diseases. Patents and exclusivity for a number of biologics are expiring. This has created the opportunity for the development and approval of biosimilars. Biosimilars are biologic products developed using a step-wise approach to result in a biologic that demonstrates no clinically meaningful differences in terms of quality attributes, efficacy, safety, and immunogenicity compared with an existing licensed, originator biologic. As more biosimilars receive regulatory approval and reach the market, it is increasingly important for healthcare providers to understand the terminology about biosimilars. To help support healthcare providers, the aim of this manuscript is to (i) support understanding of the language of biosimilars, (ii) review the regulatory and manufacturing processes employed in developing a biosimilar, and (iii) provide information for clinical decisions about the use of biosimilars. Because biologics are large, structurally complex proteins, biosimilars cannot be considered generic equivalents to the originator. Biosimilars are developed and evaluated using rigorous processes involving detailed analytical and functional studies, nonclinical assessments, and clinical trials. Clinical studies evaluating the potential biosimilar are designed differently than those for approval of a novel biologic since the aim is merely to confirm similar efficacy and safety and not to demonstrate clinical benefit per se. Extrapolation of data may be used to grant approval of biosimilars in indications not directly evaluated in clinical studies using the biosimilar.
Diagnosis of Zika virus infection on a nanotechnology platform
Authors: Bo Zhang, Benjamin A Pinsky, Jeyarama S Ananta, Su Zhao, Shylaja Arulkumar, Hao Wan, Malaya K Sahoo, Janaki Abeynayake, Jesse J Waggoner, Clay Hopes, Meijie Tang, Hongjie Dai
Journal: Nature Medicine (2017)
Abstract 152: Intrinsic Vascular Tone may be Necessary for Successful Resuscitation from Experimental Cardiac Arrest
Authors: Andrew Ramadeen, Gerhard Dashi, Xudong Hu, Albert K Tsui, Lily Zou, Ehtesham Baig, Gregory M Hare, Paul Dorian
Journal: Circulation Research (2013)

Introduction: Survival rates from out-of-hospital cardiac arrest are often &lt;10% despite performance of good quality CPR. We assessed the hypothesis that the effect of CPR on cardiac and brain perfusion may be dependent on factors other than thoracic compression force and ventilation. Methods: Eighty healthy Yorkshire pigs (29±3 kg) were anesthetized and underwent 2-4 minutes of untreated ventricular fibrillation (VF), followed by guideline based CPR, then defibrillation. “Survivors” were pigs in sinus rhythm with aortic systolic pressure ≥30 mmHg 30 minutes after defibrillation; all others were “non-survivors”. Hemodynamic, ventilatory and defibrillation parameters were measured and tested for association with survival. Results: Thirty four pigs survived (43%). During baseline and untreated VF, hemodynamic and blood gas parameters were not different between survivors and non-survivors. During CPR, compressions generated adequate left ventricular pressures in both groups (99±21 mmHg vs. 106±28 mmHg, survivors vs. non-survivors, P=ns). Compressions produced 28% higher peak aortic pressures in survivors than non-survivors (respectively 73±21 mmHg vs. 57±17 mmHg, P&lt;0.005). During the decompression phase, nadir aortic pressures were 41% higher in survivors than non-survivors (respectively 24±7 mmHg vs. 17±5 mmHg, P&lt;0.0001). Controlled manual bag ventilation during CPR resulted in significantly higher minute ventilation being delivered to survivors compared to non-survivors (4.8±2.3 L/min vs. 3.9±1.4 L/min, P&lt;0.05). Coronary perfusion pressure, carotid blood flow, cerebral O 2 tension, and end tidal CO 2 were also higher in survivors. Conclusions: Guideline based CPR in a uniform population of pigs undergoing a structured cardiac arrest and resuscitation protocol does not produce consistent results. Intravascular pressures, intrathoracic pressure and critical organ flow correlate with survival. During cardiac arrest, more emphasis may need to be placed on vascular support rather than powerful compressions.
Metabolic Rewiring Drives Resistance to Arsenic Trioxide in Acute Promyelocytic Leukemia
Authors: Nithya Balasundaram, Saravanan Ganesan, Hamenth Kumar Palani, Ansu Abu Alex, Sachin David, Anu Korula, Biju George, Christine Chomienne, Poonkuzhali Balasubramanian, Vikram Mathews
Journal: Blood (2016)
Dysregulated Aid/Apobec Family Proteins Promote Genomic Instability in Multiple Myeloma
Authors: Srikanth Talluri, Mehmet Kemal Samur, Leutz Buon, Stekla A Megan, Purushothama Nanjappa, Rao Prabhala, Masood A. Shammas, Nikhil C. Munshi
Journal: Blood (2016)
Abstract PR02: Humanized mouse melanoma model using patient-derived xenografts
Authors: Clemens Krepler, Michela Perego, Mizuho Kalabis, Marilda Beqiri, Denitsa Hristova, Min Xiao, Nicholas J. Petrelli, Rajasekharan Somasundaram, Meenhard Herlyn
Journal: Clinical Cancer Research (2016)

Abstract Melanoma patients develop resistance to both chemo- and targeted-therapy drugs. Promising pre-clinical and clinical results with immune checkpoint inhibitors using antibodies directed against CTLA4 and PD1 have re-energized the field of immune-based therapies in melanoma. However, similar to chemo- or targeted-therapies only subsets of melanoma patients respond to immune checkpoint blockade. Currently available immunodeficient mouse xenograft and transgenic mouse melanoma models have a number of short comings and are unable to address the basis of drug resistance and immune non-responsiveness frequently observed in melanoma patients treated either with chemo- and targeted-therapy drugs or immune checkpoint inhibitors. Thus there is an urgent need to establish a mouse model with an immune microenvironment that can address the above issues encountered in melanoma patients. For this, our laboratory has developed a humanized mouse melanoma model using patient-derived xenograft (PDX). Immunodeficient (NOD/Shi-SCID/IL-2Rgnull [NOG; Taconic]/ NOD.Cg-Prkdcscid IL2rgtm1Wjl/SzJ [NSG; Jackson Laboratory]) mice were reconstituted with human CD34+ cells and after 12 weeks, mature human CD45+ cells are observed in mouse peripheral blood and in the lymphoid organs. Humanized mice with optimum number of mature human CD45+ cells in peripheral blood were challenged with HLA-matched melanoma PDX and the immune response to melanoma associated antigens were monitored. Lymphoid cells derived from humanized mice that are challenged with human leukocyte antigen (HLA) matched melanoma cells in vivo showed enhanced cytokine expression to in vitro stimulation with peptides derived from melanoma antigens. In addition, cytotoxic T-cells were able to functionally lyse tumor cells in vitro, infiltrate and restrict in vivo tumor growth. We are currently refining our model to establish an autologous mouse melanoma model. Our innovative humanized mouse melanoma model will enable one to understand the causes of therapy resistance and immune non-responsiveness in patients. This abstract is also being presented as Poster B33. Citation Format: Clemens Krepler, Michela Perego, Mizuho Kalabis, Marilda Beqiri, Denitsa Hristova, Min Xiao, Nicholas J. Petrelli, Rajasekharan Somasundaram, Meenhard Herlyn. Humanized mouse melanoma model using patient-derived xenografts. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr PR02.
The Optimal Timing for Stem Cell Collection After Induction Therapy for Patients with Multiple Myeloma
Authors: Aziz Nazha, Dan T. Vogl, Una O'Doherty, Patricia Mangan, Kathleen Cunningham, Selina Luger, David L. Porter, Stephen J. Schuster, Marie Gardler, Mary Sell, Don L. Siegel, Edward A Stadtmauer
Journal: Blood (2010)
FDA Drug Approval: Elotuzumab in Combination with Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma
Authors: Nicole J. Gormley, Chia-Wen Ko, Albert Deisseroth, Lei Nie, Edvardas Kaminskas, Natasha Kormanik, Kirsten B. Goldberg, Ann T. Farrell, Richard Pazdur
Journal: Clinical Cancer Research (2017)

On November 30, 2015, the FDA approved elotuzumab (Empliciti; Bristol-Myers Squibb) in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who received one to three prior therapies. FDA approval was based primarily on the results of a phase III, randomized, open-label, multicenter trial, CA204004, which evaluated elotuzumab in combination with lenalidomide and dexamethasone (E-Ld) compared with lenalidomide and dexamethasone (Ld) alone in patients with relapsed or refractory multiple myeloma. Coprimary endpoints were progression-free survival (PFS) and overall response rate (ORR). The key secondary endpoint was overall survival, but these data were not mature at the time of clinical database cutoff. The trial demonstrated a statistically significant improvement in PFS, with an estimated HR of 0.70 for E-Ld over Ld [95% confidence interval (CI), 0.57-0.85; P = 0.0004). Estimated median PFS was 19.4 months in the E-Ld arm and 14.9 months in the Ld arm. ORR was 75.8% in the E-Ld arm compared with 65.5% in the Ld arm. Serious adverse reactions were reported in 65% of patients in the E-Ld arm compared with 57% in the Ld arm. The FDA approved elotuzumab with the following warnings and precautions: infusion reactions, infections, second primary malignancies, hepatotoxicity, and interference with the determination of complete response. Clin Cancer Res; 23(22); 6759-63. ©2017 AACR.
Vancomycin Resistant Enterococcus (VRE) Bloodstream Infections (BSI) in Patients with Hematological Malignancies: Is the Sick Getting Sicker?.
Authors: Erik R. Dubberke, James Holland, Peter Georgantopolis, Kristan Augustin, John F. Dipersio, Linda Mundy, Hanna J. Khoury
Journal: Blood (2005)
Entomological Studies: Studies on Insects of Medical Importance in South Africa
Journal: JAMA (1935)

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Pharmacological Inhibition of NF-KB Underpins the Strong Synergy Between LC-1 and Fludarabine in Chronic Lymphocytic Leukaemia Cells
Authors: Saman Hewamana, Thet Thet Lin, Chris Fegan, Steven Knapper, Alan Burnett, Paul Brennan, Clare Rowntree, Chris Pepper
Journal: Blood (2008)
In Utero Exposure to Maternal Hyperglycemia Increases Childhood Cardiometabolic Risk in Offspring
Authors: Wing Hung Tam, Ronald Ching Wan Ma, Risa Ozaki, Albert Martin Li, Michael Ho Ming Chan, Lai Yuk Yuen, Terence Tzu Hsi Lao, Xilin Yang, Chung Shun Ho, Gregory Emanuele Tutino, Juliana Chung Ngor Chan
Journal: Diabetes Care (2017)

The objective of this study was to evaluate the effect of maternal hyperglycemia during pregnancy on cardiometabolic risk in offspring during early childhood.A total of 970 mothers who had joined the Hyperglycemia and Adverse Pregnancy Outcome study were reevaluated, together with their child born during the study period, 7 years after delivery.Offspring born to mothers diagnosed with gestational diabetes mellitus (GDM), as defined by the World Health Organization 2013 GDM criteria, had higher rates of abnormal glucose tolerance (4.7% vs. 1.7%; P = 0.04), higher rates of overweight or obesity, greater BMI, higher blood pressure (BP), lower oral disposition index, and a trend toward reduced β-cell function compared with those born to mothers without GDM. For each SD increase in maternal fasting, 1-h, and 2-h glucose levels on oral glucose tolerance tests (OGTTs) between 24 and 32 weeks of the index pregnancy, the risk of abnormal glucose tolerance in the offspring showed a corresponding increase (adjusted odds ratio [OR] 1.85-2.00). The associations were independent of BMI before pregnancy, childhood obesity, or being born large for gestational age. The area under the curve for glucose levels during the five-point OGTT increased to a similar extent in boys and girls with each SD increase in maternal 1-h and 2-h plasma glucose on OGTTs during pregnancy. All three maternal glucose levels were also associated with increased adjusted ORs for childhood overweight or obesity and adiposity among girls, but not boys.Maternal hyperglycemia in pregnancy is independently associated with offsprings' risk of abnormal glucose tolerance, obesity, and higher BP at 7 years of age. Its effect on childhood adiposity was apparent only in girls, not boys.
Brexit raises concern over UK role in EU rare disease initiative
Authors: Rory Watson
Journal: BMJ (2017)

The UK’s participation in a new pan-European programme to diagnose and treat complex diseases of rare or low prevalence may be at risk after Brexit, experts have said.

Launched on 1 March, the European Reference Networks (ERNs) link more than 900 medical teams in centres of excellence across the continent to enable doctors and other healthcare professionals to collaborate and share information on rare diseases. The first wave focuses on 24 disease areas, ranging from bone disorders and haematological diseases …
Long-Term Outcomes of Salvage Stereotactic Ablative Radiotherapy for Isolated Lung Recurrence of Non–Small Cell Lung Cancer: A Phase II Clinical Trial
Authors: Bing Sun, Eric D. Brooks, Ritsuko Komaki, Zhongxing Liao, Melenda Jeter, Mary McAleer, Peter A. Balter, James D. Welsh, Michael O’Reilly, Daniel Gomez, Stephen M. Hahn, Boris Sepesi, David C. Rice, John V. Heymach, Joe Y. Chang
Journal: Journal of Thoracic Oncology (2017)
Control of Multidrug Resistant Pseudomonas Aeruginosa through Hospital Construction Design and Extensive Environmental and Clinical Surveillance in an Allogeneic Transplantat Unit
Authors: Annelene Kossow, Frank Kipp, Gerda Silling, Andreas H Groll, Claudia Rössig, Heribert Jürgens, Alexander Mellmann, Helge Karch, Wolfgang E Berdel, Matthias Stelljes
Journal: Blood (2014)