tbuckley/cabot-search huggingface dataset:
A BAFFling Association between Malaria Resistance and the Risk of Multiple Sclerosis
Authors: Thomas Korn, Mohamed Oukka
Journal: New England Journal of Medicine (2017)

B cells are increasingly recognized as a therapeutic target in autoimmune diseases. B-cell–depleting therapy with the use of rituximab, a monoclonal antibody to CD20, is approved for the treatment of rheumatoid arthritis and antineutrophil cytoplasmic antibody–associated vasculitis and is frequently used off-label to treat lupus nephritis.1 The rationale for targeting B cells in multiple sclerosis has remained controversial, particularly because major animal models of the disease do not involve B cells.2 Nevertheless, rituximab and its almost fully humanized successor, ocrelizumab, were tried in patients with multiple sclerosis and appear to be exceedingly potent in suppressing signs of inflammation in the . . .
P08.14 In situ detection of hypoxia inducible factor 2 alpha in malignant gliomas
Authors: J. J. Renfrow, R. E. Strowd, Y. Huang, D. Herpai, R. T. Mott, T. Wong, G. J. Lesser, W. Debinski
Journal: Neuro-Oncology (2017)

Introduction: Direct intratumoral measurements confirm that necrosis and hypoxia are fundamental features of the pathobiology of glioblastoma (GBM). Tumor cells adapt to hypoxia through up regulation of hypoxia inducible factors (HIFs), a conserved family of transcription factors. Of the HIFs, HIF-2 alpha (HIF-2α) appears to be expressed in GBM tumor cells (not neural progenitors) and drives adaptation to prolonged (>24 hour) hypoxia. Targeting HIFs is an attractive cancer treatment strategy given that tumor hypoxia is a constant environmental cue driving genetic instability, cell migration, angiogenesis, and chemoradiation resistance. GBM, a tumor uniformly characterized by an intratumoral hypoxic environment, is a prime candidate for HIF therapeutic targeting but specific drugs were not available. PT2385 is a novel, first-in-class, HIF-2α inhibitor which recently entered clinical trials for renal carcinoma. PT2385 is orally administered and is small, lipophilic with a brain:plasma ratio of 0.9 in rats. To establish HIF-2α as a therapeutic target in GBM, we investigated in situ expression of HIF-2α protein in tissue samples from the Wake Forest Brain Tumor Center of Excellence Brain Tumor Bank. Methods: 22 formalin-fixed, paraffin-embedded glioma samples (grade II-IV) were analyzed for HIF-2α expression using immunohistochemistry. After rehydration, endogenous peroxidase was blocked, epitopes were retrieved using a microwaved Tris EDTA pH 9.0 solution, non-specific epitopes were blocked, and HIF-2α antibody (Santa Cruz, sc-13596) was added. A horseradish peroxidase conjugated anti-mouse antibody was then added followed by detection chromagen. An inverted bright field microscope captured images and representative samples were digitally scanned. Localization and quantification of HIF-2α was independently verified by a neuropathologist. Results: There was no detectable HIF-2α expression in the four Grade II and two Grade III gliomas studied. Of the 16 GBMs (Grade IV), HIF-2α was expressed in 13 (81%). HIF-2α was highly expressed in seven specimens (>10% cells positive), intermediate in six specimens (<10% of cells positive), and minimal to none in three specimens. Staining was specific to both tumor cells and occasionally monocytic cells (based on morphology). It was noted that HIF-2α was frequently present in perivascular and perinecrotic regions. Conclusions: HIF-2α expression is found in the majority of GBM specimens, but is absent in low-grade gliomas. Immunohistochemistry demonstrated a range of HIF-2α abundance along with regional staining patterns, clustered in perivascular and perinecrotic niches. HIF-2α appears to correlate with increasing malignancy grade. This is the first in situ description of HIF-2α in gliomas and further studies are in progress for preclinical in vitro and in vivo testing of PT2385, a first-in-class HIF-2α targeted agent, in GBM.
Influenza Vaccination in the First Trimester of Pregnancy and Risk of Autism Spectrum Disorder—Reply
Authors: Ousseny Zerbo, Nicola P. Klein, Lisa A. Croen
Journal: JAMA Pediatrics (2017)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
β-alanine: performance effects, usage and side effects
Authors: Vincent Kelly
Journal: British Journal of Sports Medicine (2017)

β-alanine supplementation improves high-intensity exercise capacity. I investigated the influence of β-alanine supplementation combined with high intensity training on performance. I also examined the factors that potentially influence an athlete’s decision to use β-alanine including side effects and dosage compliance.

The aim was to consider factors that influence how the findings of β-alanine research relate to practice. Others have examined the efficacy of β-alanine1; however, its influence on repeated-sprint performance when combined with a structured training programme was unknown. Also I wanted to know if β-alanine would assist team sport athletes who are required to sprint repeatedly.

The current practices and level of knowledge relating to the benefits of supplementing with β-alanine among elite athletes are …
Self-efficacy through survivorship: Results from the LIVESTRONG Cancer Navigation Study.
Authors: Bree Hemingway, Sarah R. Arvey, Ruth Rechis, Linda Squiers, Emily Eargle, Katherine Treiman
Journal: Journal of Clinical Oncology (2015)

9577 Background: With more than 13.7 million cancer survivors in the U.S., two-thirds of whom will live beyond five years post-treatment, creating programs to support survivors can be challenging as their needs evolve through each stage of survivorship. LIVESTRONG Cancer Navigation (LCN) offers services designed to address survivors’ needs at all stages of the cancer experience. Survivors experience new challenges and concerns when they transition from treatment to post-treatment care. We present the results of a LCN research study to describe how clients’ self-efficacy (SE) and needs vary depending on their stage of survivorship. Methods: In 2012, researchers studied LCN to determine how well the program enables cancer survivors to manage their health and practical concerns. Participants (n = 1388) completed surveys at intake, two, and six weeks post-intake to measure quality of life outcomes including cancer-related concerns, SE and distress. The SE score is based on three items that assess the individual’s confidence related to: emotional support; communication with their doctor; and making themselves feel better. Participants’ needs were documented at intake and those who completed two or more surveys (63%) were included in the analytical sample (n = 874) and were categorized into three groups: in treatment (60.9%), < 5 years post-treatment (24%) and 5+ years post-treatment (4.5%). Results: At all three time points, SE was lowest among individuals who finished treatment 5+ years ago. Significant differences in the mean number of needs were also found between participants at different stages of survivorship (p< .003). Participants in treatment reported the most needs (6.6), followed by participants 5+ years post-treatment (6.3). Participants 5+ years post-treatment reported significantly higher cancer concern score than participants who had completed treatment < 5 years ago. Additional outcomes will be shared. Conclusions: Findings suggest that SE decreases post-treatment. Understanding the various challenges and type of support survivors need at all stages of survivorship can inform service design in clinical and community-based settings that can continue to support clients into survivorship.
Foxo3a Is Essential for the Quiescence and Self-Renewal of Hematopoietic Stem Cells.
Authors: Kana Miyamoto, Atsushi Hirao, Kiyomi Y. Araki, Fumio Arai, Kazuhito Naka, Keiyo Takubo, Sahoko Matsuoka, Satoshi Yamazaki, Keisuke Ito, Masako Ohmura, Kentaro Hosokawa, Mine Harada, Noboru Motoyama, Toshio Suda
Journal: Blood (2006)
Phase I study of vorinostat (suberoylanilide hydroxamic acid) in combination with temozolomide (TMZ) in patients with malignant gliomas (NABTC 04–03)
Authors: P. Y. Wen, V. Puduvalli, J. Kuhn, J. Reid, T. Cloughesy, W. A. Yung, S. M. Chang, H. I. Robbins, R. McGovern, M. Ames, M. D. Prados
Journal: Journal of Clinical Oncology (2007)

2039 Background: Vorinostat (V) is an oral inhibitor of histone deacetylase. In preclinical studies it inhibits growth of glioblastoma (GBM) cell lines and has supra-additive activity when combined with TMZ. Methods: The North American Brain Tumor Consortium (NABTC) is conducting a phase I study of V in combination with TMZ in patients with malignant gliomas (MG). Eligibility criteria are histologically proven GBM and anaplastic gliomas (AG) who have received radiotherapy and have not progressed on temozolomide, &gt; 18 yrs old, life expectancy &gt; 8 weeks, KPS &gt; 60, adequate bone marrow reserve and organ function. There was no limitation to the type of antiepileptic drugs that could be used. All patients received TMZ at a dose of 150 mg/m 2 /day on days 1–5 days every 28 days. Variable doses of V were administered with food on days 1–14 every 28 days. Dose-limiting toxicities (DLT), determined during the first 4 weeks of therapy, were defined as any grade 4 hematologic toxicity except for grade 3 thrombocytopenia, and any grade 3 non-hematologic toxicities. Escalation was performed in standard groups of 3. The maximum tolerated dose (MTD) was defined as the dose at which DLTs occurred in no more than 1/6 patients. PKs were determined on cycle 1 for TMZ, V and its metabolites. Results: To date, 19 eligible patients have been enrolled (15 GBM; 4 AG). Patients’ characteristics are 11 male, 8 female; median age 54 yrs (36–78); median KPS 90 (70–100). DLTs were encountered at 300 mg bid of vorinostat (1 grade 3 thrombocytopenia; 1 grade 3 fatigue in 3 patients), 200 mg tid (1 grade 3 nausea, 1 grade 4 thrombocytopenia in 3 patients) and 200 mg twice daily (grade 3 fatigue in 2/6 patients). No DLTs were encountered in 6 patients receiving 300 mg daily. TMZ PKs included [n=16: Cmax 5.2 (± 1.55) μg/ml; AUC 20.1 (±4.66) μg x hr/ml; t 1/2 1.9 (±0.32)/hr]. Vorinostat PKs (300mg dose level) were [n=4; Cmax 267 (±174) ng/ml; AUC 0–8 603 (±197) ng x hr/ml]. The t 1/2 for V and its glucuronide metabolite were identical (1.6 hrs) vs. 5.6 hrs for the acid metabolite. Conclusions: The MTD of vorinostat in combination with TMZ is 300 mg daily on days 1–14 every 28 days. Final PK results, and toxicities from an additional 10 patients enrolled at the MTD will be presented. [Table: see text]
P04.16 Multiparametric magnetic resonance imaging revealed tumor niches in glioblastoma patients
Authors: C. Li, J. Yan, N. R. Boonzaier, Y. Huang, J. Yuan, S. J. Price
Journal: Neuro-Oncology (2017)

Purpose: Heterogeneity poses challenge to personalised treatment of glioblastoma (GBM). Different habitats within GBM may have diverse treatment response. Magnetic resonance imaging (MRI) is crucial for targeted surgery. However, conventional imaging methods fail to target intratumor habitats. Finding validated imaging method to address GBM regional heterogeneity is crucial. Methods: Patients 112 patients (mean age 59.41 years, range 22–76, 84 males) with newly diagnosed supratentorial GBM were recruited. All patients received surgery and diagnosis was confirmed by pathology. Survival data of 79 patients were available for study. Exclusion criteria include history of cranial surgery/radiotherapy/chemotherapy. The study was approved by local Institutional Review Board. Imaging processing: Anatomical, spectroscopy (MRS), dynamic susceptibility contrast (DSC) and diffusion tensor imaging (DTI) were acquired preoperatively with a 3T MRI scanner. All images were co-registered to T2W images. DTI, DSC and MRS data were processed as previously described. Imaging markers, i.e., apparent diffusion coefficient (ADC), relative cerebral blood volume (rCBV) and a series of metabolites were calculated. Data analysis: Region of interest (ROI) was manually delineated on the contrast-enhanced (CE) T1W and FLAIR images. ADC and rCBV values were obtained from each pixel within CE. Thresholds of 0.25 and 0.75 were used for both rCBV and ADC maps to generate four overlapping ADC-rCBV ROIs, which were low-ADC-high-rCBV (LH), low-ADC-low-rCBV (LL), high-ADC-high-rCBV (HH) and high-ADC-low-rCBV (HL) ROIs. The volumetric and metabolic analysis of all ROIs were performed. Results of volume and metabolites were correlated with patient survival. Results: LH, HH, LL, and HL all displayed higher Choline/N-acetylaspartate ratio than normal appearing white matter (p<0.001, p<0.001, p<0.001, p<0.01). HL, mainly locating in the necrosis on T1 contrast images, showed higher lactate level than LH, HH, LL (p<0.001, p<0.001, p<0.001) and higher macromolecule/lipid level than LH and HH (p<0.05, p<0.05). LL showed similar metabolic pattern with HL but may display enhancement on T1 contrast images. The volumes of LL and LH were inversely correlated (p<0.001). The proportional volume of LH in CE were positively correlated with non-enhancing tumor volume in FLAIR (p<0.01). Kaplan-Meier and multivariate survival analysis showed an increased volume ratio of LH/LL in CE was associated with worse progress free survival (p<0.05). Conclusion: Difference in cellularity and vascularity can create diverse tumor microenvironment. The LH, LL, HL and HH regions may represent the proliferative, hypoxic, necrotic and invasive tumor niches respectively. This approach shows potential in targeting intratumor niches. In next step we will take multiple biopsies and validate this approach at histological and genomic levels.
Maternal pertussis immunisation: clinical gains and epidemiological legacy
Authors: Ana I Bento, Aaron A King, Pejman Rohani
Journal: Eurosurveillance (2017)

The increase in whooping cough (pertussis) incidence in many countries with high routine vaccination coverage is alarming, with incidence in the US reaching almost 50,000 reported cases per year, reflecting incidence levels not seen since the 1950s. While the potential explanations for this resurgence remain debated, we face an urgent need to protect newborns, especially during the time window between birth and the first routine vaccination dose. Maternal immunisation has been proposed as an effective strategy for protecting neonates, who are at higher risk of severe pertussis disease and mortality. However, if maternally derived antibodies adversely affect the immunogenicity of the routine schedule, through blunting effects, we may observe a gradual degradation of herd immunity. 'Wasted' vaccines would result in an accumulation of susceptible children in the population, specifically leading to an overall increase in incidence in older age groups. In this Perspective, we discuss potential long-term epidemiological effects of maternal immunisation, as determined by possible immune interference outcomes.
P09.19 Glioblastoma Multiforme in an adult after Complete Remission of Acute Lymphoblastic Lymphoma
Authors: D. Kang, J. Lee
Journal: Neuro-Oncology (2017)

Introduction: Concurrent chemo-radiotherapy has been well known prophylactic methods to increase long-term survival rate for ALL patients. There are several case reports of brain tumor with a patient having complete remission of ALL history. Meningioma and sarcoma are possibly occurred in patients who got therapeutic irradiation, and it could be simply recurred lymphoma in the central nervous system. Radiation-induced glioblastoma multiforme have been reported very rarely. Materials and Methods: A 36-year old man with the complete remission of Acute Lymphoblastic Lymphoma(ALL) who have received chemotherapy, radiotherapy, and intrathecal methotrexate 25 years ago presented with decreased mentality and left hemiparesis grade 3 after a sudden generalized tonic-clonic seizure for about a minute. Gadolinium-enhanced magnetic resonance imaging showed 5.5 cm x 3.6 cm heterogeneous enhancing mass with vaguely outlined infiltrative lesions in right frontal and parietal lobe and extension across the corpus callosum. Secondary to the mass effect, right ventricle is compressed and there is a shift towards left. Stereotactic brain biopsy was performed. Histopathology studies confirmed the diagnosis of glioblastoma multiforme(GM). Results: From the histopathologic result, total resection of tumor is highly recommended, but patient’s parents refuse to get surgical treatment. Alternatively we suggest non-invasive theraphy, concurrent chemo-radiotheraphy(CCRT). The patient underwent concurrent 100mg temozolomide for 42 days and 60 Gy of radiation. After 2 months of diagnosis, follow up MRI study showed tumor size reduction to 3.4 cm x 2.8 cm, and his mentality, left hemiparesis improved to alert, and grade 4. He will go through 3 more cylcles of temozolomide and follow up image studies will be performed. Conclusions: There are several case reports of GM occurrence after therapeutic irradiation or intrathecal injection of methotrexate in ALL patients, and we experienced patient who has same disease entity. Since there is years of latency period between GM development and complete remission of ALL, long term period of regular follow up is recommended for the complete remission of ALL patients in order to early detection of GM occurrence.
Evaluation of Bacteria-Mediated Potential "Bystander" Hemolysis of PNH RED CELLS In Vitro: NO Evidence of Significant Complement Classical or Lectin Pathway-Mediated Hemolysis Induced by Microorganisms
Authors: Xuan Yuan, Guangwei Yang, Jane A Thanassi, Manuel D Galvan, Steven D Podos, Mingjun Huang, Robert A. Brodsky
Journal: Blood (2016)
Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses
Authors: Kapil Bahl, Joe J. Senn, Olga Yuzhakov, Alex Bulychev, Luis A. Brito, Kimberly J. Hassett, Michael E. Laska, Mike Smith, Örn Almarsson, James Thompson, Amilcar (Mick) Ribeiro, Mike Watson, Tal Zaks, Giuseppe Ciaramella
Journal: Molecular Therapy (2017)

Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles.
Pathogenetic Role of Impaired Telomere Repair in Myelodysplastic Syndrome.
Authors: P.K. Epling-Burnette, Alan F List, Justine Clark, Ji-Hyun Lee, Kristen A. Jonathan, William Fulp, Xiaohong Li, Weipeng Zheng, Jeffrey S. Painter, JianXiang Zou, Rami S. Komrokji, Sheng Wei, Jong Park, Amber Schmidt, Chiharu Sugimori, Ashley Cole, Dana E Rollison
Journal: Blood (2009)
P17.01 Subgroup stratification of adult diffuse gliomas - an adaptation of the updated WHO classification in a resource constrained environment
Authors: U. A S, V. Santosh, A. Arivazhagan, V. Lokesh
Journal: Neuro-Oncology (2017)

Introduction: Updated WHO classification recommends addition of molecular parameters to histological diagnosis. In a resource constrained setting, gene sequencing and fluorescent in-situ hybridization is not feasible for all the patients. We assessed utility of immunohistochemistry for IDH1/R132H and ATRX, to stratify adult diffuse gliomas into subgroups and analyzed the outcomes. Materials/Methods: Subgroup stratification of histopathologically confirmed 58 grades III/IV gliomas based on results of IHC testing for IDH1/R132H and ATRX proteins performed as per the standard protocol, was done to look for long term outcomes following maximal safe resection, adjuvant radiation and Temozolomide (as per Stupp regime). IDH1 positive/ ATRX retained gliomas were stratified as group 1 (G1), IDH positive/ATRX lost as G2 and IDH negative as G3. Outcomes and survival was analysed by Kaplan- Meier analysis using SPSS 21.v. Results: Median age of the cohort of 58 patients (male: 39, female: 19) was 40 years. Histologically, Glioblastoma (GB), anaplastic astrocytoma (AA) and anaplastic Oligodendroglioma (AOD) was seen in 23:17:18 patients. 48% were tested positive for IDH1, 62% had retained ATRX protein, stratifying patients into three subgroups (G1:14, G2:14, G3:30). The G3 group contained both AA & GB cases. At median follow up of 18 months, OS of the entire cohort was 76%, higher in AOD compared to AA and GB (p=0.01). There was significant difference in survival among the groups, longer in G1, compared to G2 & G3 (log rank p= 0.002). The AAs within G3 showed no survival difference with their counterparts in G2. Age </= 40 years was prognostic for survival in G3. Thus, IDH negative tumours in G3 with AA histology and patients younger than 40 years demonstrating no significant survival difference when compared to their counterparts in G2, call for further testing with IDH gene sequencing for appropriate group stratification. Conclusion: Subgroup stratification of adult diffuse gliomas based on IHC demonstrates that IDH positivity was the most favorable prognostic factor. Anaplastic astrocytoma constituted the subgroup G2. In a resource constrained environment, IHC alone may guide appropriate management decision for majority of adult diffuse gliomas, gene sequencing reserved for IDH negative- anaplastic gliomas & patients younger than 40 years.