tbuckley/cabot-search huggingface dataset:
Reply to Walter and Reyfman: Transcriptomic Analysis of Alveolar Immune Cells in Acute Respiratory Distress Syndrome: To Lump or to Split?
Authors: Eric D. Morrell, Pavan K. Bhatraju, Carmen Mikacenic, Frank Radella, Anne M. Manicone, Renee D. Stapleton, Mark W. Wurfel, Sina A. Gharib
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

5, 6). With increasing use of single-cell profiling, the breadth and potential clinical importance of AM heterogeneity have become even more apparent.Our group has used single-cell RNA sequencing to identify novel populations of alveolar macrophages expressing profibrotic genes in patients with pulmonary fibrosis (7).In addition, a single-cell approach was recently used to identify five transcriptionally distinct clusters of AMs within the inflamed lung (8).High-resolution studies aimed at splitting apart relevant populations of AMs in the injured lung can be limited by high cost and complex downstream analysis.In addition, it remains to be seen whether these novel approaches can support discovery of uniquely informative biomarkers or clinical phenotypes.However, it is important to consider how these splitting approaches may complement or improve on studies that analyze an immune cell population in the broadest terms.As an example, in the work by Morrell and colleagues, there were no differences in genome-wide expression profiles between patients with good versus poor clinical outcomes after adjustment for multiple testing (1).This may be because of the noise present in genomic datasets derived from critically ill patients, but it may also be driven in part by the limited resolution of the analysis; an overly broad view can make even complex systems look uniform.Should we lump or split immune cells when studying the injured lung?If the goal is to advance our understanding of the pathobiologic mechanisms of disease, then splitting using highresolution approaches offers particular promise.If the aim is to identify clinically informative disease phenotypes, then both approaches may prove useful and synergistic.However, when we choose the 10,000-foot view, we should remember and be informed by the complexity that lies below.
Association between a Polygenic Risk Score for Multiple Myeloma Risk and Overall Survival
Authors: Alyssa I. Clay-Gilmour, Michelle Hildebrandt, Yan Asmann, Elizabeth E. Brown, Jonathan N Hofmann, John Spinelli, Graham Giles, Parveen Bhatti, Wendy Cozen, Dennis P. Robinson, Daniel R O'Brien, S. Vincent Rajkumar, Shulan Tian, Sonja I Berndt, Stephen J Chanock, Mitchell Machiela, Aaron D. Norman, Jason P Sinnwell, Xifeng Wu, Rosalie Griffin Waller, Roger L Milne, Susan L Slager, Shaji K. Kumar, Nicola J Camp, Elad Ziv, Celine M. Vachon
Journal: Blood (2019)
Specific Guidelines Including Multidisciplinary Approach Is Critical of Management of Langerhans Cell Histiocytosis in Adults
Authors: Lorenzo Rizzo, Michelina Santopietro, Gianluca Sfaciotti, Marco Brunori, Luisa Cardarelli, Giovanna Palumbo, Daniela De Benedittis, Martina Di Palma, Maria Luisa Moleti, Anna Maria Testi, Tiziana Di Pippo, Fiorina Giona
Journal: Blood (2019)
Neoadjuvant stereotactic radiosurgery for intracerebral metastases of solid tumors (NepoMUC): a phase I dose escalation trial
Authors: Christian D. Diehl, Ehab Shiban, Christoph Straube, Jens Gempt, Jan J. Wilkens, Markus Oechsner, Carmen Kessel, Claus Zimmer, Benedict Wiestler, Bernhard Meyer, Stephanie E. Combs
Journal: Cancer Communications (2019)

More than 25% of patients with solid cancers develop intracerebral metastases. Aside of surgery, radiation therapy (RT) is a mainstay in the treatment of intracerebral metastases. Postoperative fractionated stereotactic RT (FSRT) to the resection cavity of intracerebral metastases is a treatment of choice to reduce the risk of local recurrence. However, FSRT has to be delayed until a sufficient wound healing is attained; hence systemic therapy might be postponed. Neoadjuvant stereotactic radiosurgery (SRS) might offer advantages over adjuvant FSRT in terms of better target delineation and an earlier start of systemic chemotherapy. Here, we conducted a study to find the maximum tolerated dose (MTD) of neoadjuvant SRS for intracerebral metastases. This is a single-center, phase I dose escalation study on neoadjuvant SRS for intracerebral metastases that will be conducted at the Klinikum rechts der Isar Hospital, Technical University of Munich. The rule-based traditional 3 + 3 design for this trial with 3 dose levels and 4 different cohorts depending on lesion size will be applied. The primary endpoint is the MTD for which no dose-limiting toxicities (DLT) occur. The adverse events of each participant will be evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 continuously during the study until the first follow-up visit (4–6 weeks after surgery). Secondary endpoints include local control rate, survival, immunological tumor characteristics, quality of life (QoL), CTCAE grade of late clinical, neurological, and neurocognitive toxicities. In addition to the intracerebral metastasis which is treated with neoadjuvant SRS and resection up to four additional intracerebral metastases can be treated with definitive SRS. Depending on the occurrence of DLT up to 72 patients will be enrolled. The recruitment phase will last for 24 months. Neoadjuvant SRS for intracerebral metastases offers potential advantages over postoperative SRS to the resection cavity, such as better target volume definition with subsequent higher efficiency of eliminating tumor cells, and lower damage to surrounding healthy tissue, and much-needed systemic chemotherapy could be initiated more rapidly. Trial registration The local ethical review committee of Technical University of Munich (199/18S) approved this study on September 05, 2018. This trial was registered on German Clinical Trials Register (DRKS00016613; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016613) on January 29, 2019.
CSIG-22. REGULATION OF GLIOMA STEM CELL SELF-RENEWAL AND TUMORIGENESIS BY CARBOHYDRATE BINDING PROTEINS
Authors: Ahmad Sharanek, Idris Fatakdawala, Arezu Jahani-Asl
Journal: Neuro-Oncology (2019)

Abstract Glioma Stem Cells (GSC) are a population of malignant self-renewing stem cells in glioblastoma (GBM) tumors, the most common and aggressive primary brain tumor in the adult brain. GSC promote tumor growth and recurrence and acquire resistance to therapy. Strategies to target GSC in the tumor bulk are urgently needed in order to develop more effective therapeutic strategies for GBM. EGFRvIII/STAT3 signaling is a major oncogenic pathway in GBM. Here, we report our discovery that Galectin1, a family member of carbohydrate-binding proteins with affinity for b-galactosides, promotes GSC self-renewal and tumor growth in EGFRvIII-expressing subset of tumors. Analysis of RNA-Seq data shows that LGALS1, the gene encoding Galectin1, is highly expressed in human EGFRvIII-expressing GSC and its expression correlates with the expression of transcription factor STAT3. Importantly, STAT3 directly binds the promoter of LGALS1 to upregulate its expression and knockdown of STAT3 significantly attenuates LGALS1 mRNA levels. Genetic knockdown of LGALS1 impairs the ability of GSC to form spheres, as assayed in limiting dilution assay, suggesting that LGALS1-STAT3 signaling regulates glioma stem cell fate in EGFRvIII tumor subset. Strikingly, we employed genetic and pharmacological approaches in patient derived xenografts and found that LGALS1/Galectin1 impairs gliomas stem cell growth and tumorigenesis. Subcutaneous and stereotactic intracranial implantation of CRISPR knockout LGALS1 EGFRvIII-expressing GSC into SCID mice showed significantly reduced in vivo tumor xenografts growth and increased survival rate compared with controls. Treatment of GSC with OTX008, a specific inhibitor of galectin-1, significantly attenuates the self-renewal ability of these cells and impairs tumorigenesis. Together, our findings suggest that targeting LGALS1/Galectin1 in combination with current standards of care may provide an effective strategy for the future treatment of these deadly brain tumors.
TP53 Deficient/Mutant AMLs Are Resistant to Individual BH3 Mimetics: High Efficacy of Combined Inhibition of Bcl-2 and Mcl-1
Authors: Bing Z Carter, Po Yee Mak, Steven M. Kornblau, Wenjing Tao, Yuki Nishida, Vivian Ruvolo, Justin Cidado, Lisa Drew, Michael Andreeff
Journal: Blood (2019)
Autologous Hematopoietic Stem Cell Infusion for Myelosuppression after Bcma-CART Therapy in Relapsed Myeloma Patients
Authors: Quande Lin, Lu Han, Jian Zhou, Lina Liu, Yuzhang Liu, Fengkuan Yu, YangLi Zhang, Wenli Zuo, Keshu Zhou, Baijun Fang, Quanli Gao, Xudong Wei, Delong Liu, Yongping Song
Journal: Blood (2019)
ACTR-04. BIOMARK: A PHASE II STUDY OF BEVACIZUMAB BEYOND PROGRESSION FOR NEWLY DIAGNOSED GLIOBLASTOMA: SAFETY, EFFICACY AND PROSPECTIVE BIOMARKER ANALYSIS
Authors: Koichi Ichimura, Motoo Nagane, Mamoru Kato, Yoshitaka Narita, Tomokazu Aoki, Shota Tanaka, Akitake Mukasa, Toshihiko Wakabayashi, Takeo Uzuka, Hideo Nakamura, Yoshiki Arakawa, Satoshi Suehiro, Mitsutoshi Nakada, Mai Kitahara, Yuko Hibiya, Daichi Narushima, Ritsuko Onuki, Satoshi Morita, Ryo Nishikawa
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Clinical benefit of continuing bevacizumab beyond progression is unknown in glioblastomas. A biomarker analysis of the AVAglio trial suggested that proneural subtype of IDH-wildtype glioblastoma patients may receive an OS benefit from a first-line bevacizumab. This study explored biomarkers that may predict survival of glioblastoma patients treated with concurrent irradiation, temozolomide (TMZ) and bevacizumab (BEV) followed by BEV beyond progression (BBP). METHODS In the primary protocol, newly diagnosed GBM patients aged 20–75 received concurrent TMZ (75 mg/m2, D1-42), irradiation (2 Gy x 5 QW x6) and BEV (10 mg/kg Q2W x 3) followed by ≤12 4-week cycles of TMZ (150–200 mg/m2, D1-5) plus BEV (10 mg/kg, D1 and 15) and then 2 or 3-week cycles of BEV monotherapy (15 or 10 mg/kg). Upon PD/recurrence during the primary protocol, the patients were subjected to the secondary protocol with 2-3-week cycles of BEV monotherapy with or without other chemotherapeutic agents (BBP). The primary endpoint was 2-year survival rate in patients receiving BBP. Fresh-frozen tumor specimen were subjected to genome-wide methylation, copy number, expression and mutation analysis. A subset of the control cohort of the AVAglio study was used as BEV-negative control. RESULTS A total of 94 GBM patients were enrolled at 39 centers between June 2015 and January 2017. Efficacy analyses were based on the full analysis set (FAS) cohort (N=90), excluding non-GBM diagnosis by central review. The median time to PD/recurrence was 453 days in the FAS and 348 days in patients receiving BBP (N=27). The 2-year survival rate (90% CI) was 52.4% (43.3–60.8%) and 28.8% (15.4–43.7%), respectively. The 2-year survival rate in GBM patients receiving BBP was lower than expected (50%). That of proneural and mesenchymal IDH-wt GBM in the biomarker cohort (n=83) were 52.9% (31.7–70.3%) and 56.6% (41.6–69.1%), respectively. A full biomarker analysis will be presented.
Wintrobe’s Clinical Hematology
Authors: Paulette Mehta
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Association of Premature Natural and Surgical Menopause With Incident Cardiovascular Disease
Authors: Michael C. Honigberg, Seyedeh Maryam Zekavat, Krishna Aragam, Phoebe Finneran, Derek Klarin, Deepak L. Bhatt, James L. Januzzi, Nandita S. Scott, Pradeep Natarajan
Journal: JAMA (2019)

Recent guidelines endorse using history of menopause before age 40 years to refine atherosclerotic cardiovascular disease risk assessments among middle-aged women. Robust data on cardiovascular disease risk in this population are lacking.To examine the development of cardiovascular diseases and cardiovascular risk factors in women with natural and surgical menopause before age 40 years.Cohort study (UK Biobank), with adult residents of the United Kingdom recruited between 2006 and 2010. Of women who were 40 to 69 years old and postmenopausal at study enrollment, 144 260 were eligible for inclusion. Follow-up occurred through August 2016.Natural premature menopause (menopause before age 40 without oophorectomy) and surgical premature menopause (bilateral oophorectomy before age 40). Postmenopausal women without premature menopause served as the reference group.The primary outcome was a composite of incident coronary artery disease, heart failure, aortic stenosis, mitral regurgitation, atrial fibrillation, ischemic stroke, peripheral artery disease, and venous thromboembolism. Secondary outcomes included individual components of the primary outcome, incident hypertension, hyperlipidemia, and type 2 diabetes.Of 144 260 postmenopausal women included (mean [SD] age at enrollment, 59.9 [5.4] years), 4904 (3.4%) had natural premature menopause and 644 (0.4%) had surgical premature menopause. Participants were followed up for a median of 7 years (interquartile range, 6.3-7.7). The primary outcome occurred in 5415 women (3.9%) with no premature menopause (incidence, 5.70/1000 woman-years), 292 women (6.0%) with natural premature menopause (incidence, 8.78/1000 woman-years) (difference vs no premature menopause, +3.08/1000 woman-years [95% CI, 2.06-4.10]; P < .001), and 49 women (7.6%) with surgical premature menopause (incidence, 11.27/1000 woman-years) (difference vs no premature menopause, +5.57/1000 woman-years [95% CI, 2.41-8.73]; P < .001). For the primary outcome, natural and surgical premature menopause were associated with hazard ratios of 1.36 (95% CI, 1.19-1.56; P < .001) and 1.87 (95% CI, 1.36-2.58; P < .001), respectively, after adjustment for conventional cardiovascular disease risk factors and use of menopausal hormone therapy.Natural and surgical premature menopause (before age 40 years) were associated with a small but statistically significant increased risk for a composite of cardiovascular diseases among postmenopausal women. Further research is needed to understand the mechanisms underlying these associations.
RTHP-18. PROSPECTIVE PHASE II RANDOMIZED TRIAL COMPARING PROTON THERAPY VS. PHOTON IMRT FOR NEWLY DIAGNOSED GBM: SECONDARY ANALYSIS COMPARISON OF GENDER AND NEUTROPHIL-LYMPHOCYTE RATIO (NLR) IN GBM OUTCOMES
Authors: James Randall, Karine Al Feghali, Jeffrey Wefel, David Grosshans, Seyedeh Dibaj, Denai Milton, Sarah McAvoy, Jing Li, Susan McGovern, Mary McAleer, Amol Ghia, Arnold Paulino, Erik Sulman, Marta Penas-Prado, Jihong Wang, John DeGroot, Amy Heimberger, Terri Armstrong, Mark Gilbert, Anita Mahajan, Paul Brown, Caroline Chung
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND While glioblastoma (GBM) is more prevalent in males, studies show that females with GBM tend to have longer overall survival (OS) than males. Pretreatment neutrophil to lymphocyte ratio (NLR) has also proven to be prognostic in GBM, with lower NLR having favorable outcomes. This secondary analysis of a prospective randomized trial of proton vs. photon intensity modulated radiotherapy aims to explore the interaction of gender and NLR on GBM outcomes. METHODS Analysis was performed on the full patient population. Kaplan-Meier methods estimated OS with censoring at last follow-up for those who were alive. Univariate (UVA) and multivariate (MVA)Cox proportional hazards models assessed predictors of OS. RESULTS Of 90 patients, 77 were included (43 males; 34 females) with median age of 52 years (range: 26–82 years). Median OS was longer for females than males (30.7 vs 18.2 months, p=0.004). On UVA, patients with NLR below median value (NLR= 3.1) tended to have longer OS than those above median, though not meeting statistical significance (23.1 vs. 17.9 months, p=0.051). Difference in OS was statistically significant in females (OS 36.4 months NLR &gt;median vs. 16.7 months NLR&lt; median, p=0.002), but not in males (OS 17.8 months NLR &gt;median vs. 19.1 NLR&lt; median, p=0.95). MVA analysis was consistent, with female gender predicting reduced hazard ratio (HR) (0.28, p=0.034) and females with below median NLR showing a reduced HR over those with above median (0.28, p=0.005). Again, males did not benefit (HR 0.90, p=0.77). CONCLUSION Consistent with prior publications, females and all patients with lower pre-treatment NLR with newly diagnosed GBM had longer OS. However, combining these two factors revealed that the benefits from lower pre-treatment NLR were conferred only in females with no impact on males. This different impact of NLR between genders may suggest innate immune differences in gender during response to malignancy.
Consolidation with Carfilzomib, Lenalidomide and Dexamethasone (KRd) Following ASCT Results in High Rates of Minimal Residual Disease Negativity and Improves Bone Metabolism, in the Absence of Bisphosphonates, Among Newly Diagnosed Patients with Multiple Myeloma
Authors: Maria Gavriatopoulou, Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Panagiotis Malandrakis, Evangelos Eleutherakis-Papaiakovou, Athanasios Papatheodorou, Nikolaos Kanellias, Magdalini Migkou, Despina Fotiou, Ioanna Dialoupi, Maria Roussou, Nikoletta-Aikaterini Kokkali, Eftathios Kastritis, Meletios A. Dimopoulos
Journal: Blood (2019)
Molecular Subtyping to Predict Risk of Venous Thromboembolism in Patients with Advanced Lung Adenocarcinoma: A Cohort Study
Authors: Lorenzo Gervaso, Shyam K Poudel, Joanna Roopkumar, Chandana A Reddy, Nathan A Pennell, Vamsidhar Velcheti, Keith R McCrae, Alok A Khorana
Journal: Blood (2019)
Genome-wide association analysis of 19,629 individuals identifies variants influencing regional brain volumes and refines their genetic co-architecture with cognitive and mental health traits
Authors: Bingxin Zhao, Tianyou Luo, Tengfei Li, Yun Li, Jingwen Zhang, Yue Shan, Xifeng Wang, Liuqing Yang, Fan Zhou, Ziliang Zhu, Hongtu Zhu
Journal: Nature Genetics (2019)
Medical Management of Opioid-Induced Constipation
Authors: Vijaya L. Rao, Dejan Micic, Andrew M. Davis
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors 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
NIMG-13. GLYCINE IS A METABOLIC BIOMARKER OF MALIGNANCY IN GLIOMAS: IN VIVO MAGNETIC RESONANCE SPECTROSCOPY STUDY
Authors: Changho Choi, Vivek Tiwari, Elena Daoud, Kimmo Hatanpaa, Song Zhang, Jack Raisanen, Cheryl Lewis, Michael Levy, Elizabeth Maher, Edward Pan, Toral Patel, Bruce Mickey
Journal: Neuro-Oncology (2019)

Abstract Malignant tumors reprogram cellular metabolism, resulting in altered concentration of some metabolites. We measured glycine (GLY) and 2-hydroxyglutarate (2HG) in 37 adult subjects with gliomas noninvasively using proton magnetic resonance spectroscopy and examined their association with immunochemical analyses of tumor biopsies and overall patient survival. MRS data were acquired using optimized point-resolved spectroscopy (PRESS TE 97ms) at 3T and the millimolar concentrations of metabolites were estimated with reference to water. The GLY concentration was positively correlated with MIB-1 proliferation index (p=1.7×10−7). The GLY estimation was inversely correlated with expression of glycine decarboxylase (GLDC) (p=0.02), without showing significant correlation with expression of serine hydroxymethyltransferase 2 (SHMT2). There was a strong association between elevated GLY and breakdown of blood-brain barrier, as indicated by higher GLY in post-gadolinium enhancing tumors than in non-enhancing tumors (p=10−6). In contrast, 2HG did not show significant correlation with MIB-1 index or post-gadolinium enhancement. In Kaplan-Meier survival analysis, patients with GLY level above 2.5 mM were significantly associated with poor survival (log-rank p value 0.003; median survival 8.8 months), compared to those with GLY level below 2.5 mM. The hazard ratio of the high-GLY tumors with respect to the low-GLY tumors was 6.7. 2HG level lower than a detection threshold (1 mM), which may represent IDH wildtype tumors, was associated with poor survival (p=0.01). In addition, we performed Kaplan-Meier analysis for the GLY-to-2HG ratio. 2HG estimates less than 1 mM were put as unity. Tumors with GLY/2HG &gt; 2 showed strong association with poor survival (p=5.2×10−9; medial survival 5.4 months), with a 12-fold higher hazard rate compared to those with GLY/2HG &lt; 2. Together, our data suggest that GLY-mediated one-carbon metabolism may underlie rapid cell proliferation in malignant gliomas and that elevation of GLY provides a noninvasive imaging biomarker predictive of cell proliferation and patient outcome.
INPP4B is a Biomarker of Poor Prognosis in AML Which is Associated with EVI1 Overexpression and a LSC Signature
Authors: Irakli Dzneladze, John F Woolley, Youqi Han, Mark Sharobim, Ayesha Rashid, Michael D Jain, Mark D. Minden, Leonardo Salmena
Journal: Blood (2016)