tbuckley/cabot-search huggingface dataset:
DIPG-23. SINGLE CASE REPORT OF LOW DOSE RADIOTHERAPY AND CHEMOTHERAPY IN THE TREATMENT OF DIPG
Authors: Chen Kan Tseng, I-Jun Chou
Journal: Neuro-Oncology (2020)

Abstract A 3 year-old girl, was noted to have progressive gait problem since Nov. 2017 and brought to hospital for checkup. Brain MRI on Jan. 2018 showed T2 hyperintensity infiltrative pontine lesion, favoring diffuse infiltrative pontine glioma and mild obstructive hydrocephalus, received VP-shunting on Jan. 15, 2018. Due to the refusal of surgical biopsy for tissue proof, we started the radiotherapy from Jan. 24, 2018, using Rapidarc technique with 6MV photon energy to treat the brain stem lesion, ended on Feb. 24, 2018 with total dose of 25.5Gy in 17 fractions as our usual practice. Following the completion of radiotherapy, we started the adjuvant chemotherapy using 1-week on, 1-week off regimen of temozolomide using dosage of 75 mg/sq-m/day, and this patient’s general condition returned back to nearly normal. Serial follow-up images of brain MRI on 04/30/2018, 08/01/2018, 11/30/2018, 02/26/2019, 05/30/2019, 08/28/2019 showed slow progression of the pontine lesion, without the development of contrast enhanced new lesion. She maintained the functional independent until Sep. 2019, she was noted to have symptoms of ataxic gait, esotropia and choking on drinking liquid. We started the retreatment of radiotherapy from Oct.7, 2019, using same technique, ended on Nov. 5, 2019 with total dose of 30Gy in 20 fractions. The symptoms improved partially after the treatment, with residual weakness over left extremity. We are still treating the patient with adjuvant temozolomide, and she has survived most of time functionally independent in these 2 years.
CTNI-22. RETROSPECTIVE ANALYSIS OF THE COMBINED TREATMENT OF VINCRISTINE, ACNU, CARBOPLATIN AND INTERFERON-β PLUS RADIOTHERAPY (VAC-FERON-R)IN PATIENTS WITH DIFFUSE ASTROCYTOMA
Authors: Yoshiki Arakawa, Yasuhide Makino, Takeshi Kawauchi, Masaharu Tanji, Yohei Mineharu, Yonehiro Kanemura, Susumu Miyamoto
Journal: Neuro-Oncology (2020)

Abstract OBJECTIVE Diffuse astrocytomas are classified as WHO grade II and its median overall survival (mOS) is 10 to 11 years. The efficacy of chemoradiation in the high-risk feature has been reported. The prognosis is associated with IDH and TERT promoter (TERTp) mutations. Here, we retrospectively analyzed the patients with diffuse astrocytoma treated with vincristine, ACNU, carboplatin and interferon-β plus radiotherapy (VAC-feron-R)in our institute. PATIENTS AND METHODS Between December 2003 to January 2016, 44 patients were diagnosed as diffuse astrocytoma with integrated diagnosis of histological and molecular analysis. The average age was 43.1 years (22–71 years). They received VAC-feron-R as initial treatment in our institute. We analyzed the IDH1/2 and the TERTp mutation using Sangar sequencing and determined the 1p/19q codeletion by the fluorescence in situ hybridization or the multiplex ligation-dependent probe amplification. RESULTS Median follow-up period was 76.5 months, mPFS was 126 months, mOS did not reach, and 10-year survival rate was 60%.IDH status was determined in 29 patients, 9 mutant and 20 wild types. There was no significant difference in PFS and OS between the two groups. TERTp status was determined in 18 patients with IDH wild type, 6 mutant and 12 wild types. mPFS of patients with TERTp wild type did not reach, but that with TERTp mutant type was 34.5 months (p = 0.0356). CONCLUSION Compared with previous clinical studies, VAC-feron-R showed a favorable clinical outcome in diffuse astrocytoma. The impact of TERTp status on prognosis was identified but not IDH status in this cohort.
Covid-19 vaccines: delivering protective immunity
Authors: Herb F Sewell, Raymond M Agius, Denise Kendrick, Marcia Stewart
Journal: BMJ (2020)

Early in the covid-19 pandemic it was unclear whether and how individuals and populations would develop protective and enduring immunity against SARS-CoV-2, either after infection or vaccination.Initial focus was on defining virus neutralising antibodies from B cells after infection.Early reports indicated that such antibodies decline substantially over less than six months, raising questions about how long protective immunity might last following infection.T cells are also known to be important in protecting against many viral infections through processes known as cellular immunity.Defining the roles of T cells in covid-19 became a central focus for investigation.
Abstract 13175: Social Jet Lag in Eating Patterns as a Marker of Meal Timing Variability is Associated With Elevated Cardiometabolic Risk in the AHA Go Red for Women Strategically Focused Research Network
Authors: Nour Makarem, Dorothy D Sears, Marie-Pierre St-Onge, Faris M Zuraikat, Linda Gallo, Gregory A Talavera, Sheila Castaneda, Huaqing Xi, Brooke A Aggarwal
Journal: Circulation (2020)

Introduction: Social jet lag, typically defined as the difference in sleep timing on work vs. free days, is related to elevated cardiovascular disease (CVD) risk, via circadian disruption. Irregular meal timing may also lead to circadian disruption, but the role of social jet lag in eating patterns in CVD risk has not been examined. Hypothesis: Social jet lag in eating patterns, a measure of meal timing variability, will be associated with elevated cardiometabolic risk in women. Methods: Women from the AHA Go Red for Women SFRN at Columbia (n=116, mean age: 33 y, 45% Hispanic) completed a 1-wk food record using the web-based NIH Automated Self-Administered 24-h Dietary Assessment Tool. Social jet lag in eating patterns was evaluated using the difference between weekday vs. weekend: 1) nightly fasting duration (NFD), 2) time of first meal, and 3) time of last meal. Standard deviation (SD) of % kcal consumed after 5PM and 8PM was used to capture variability in nighttime eating. Cardiovascular health (CVH) was assessed with the AHA Life Simple 7 (LS7) score. Linear regression models adjusted for age, socioeconomic status, and sleep were used to examine associations with CVH, BMI, waist circumference (WC), systolic blood pressure (SBP), diastolic BP (DBP), and fasting glucose. Results: The average time of first meal and NFD on weekdays vs. weekends was 8:54AM vs. 10:11AM and 12.5 h vs. 13.7 h, respectively; average time of last meal was similar (8:27PM). Each 1-h increase in the difference between first meal time on weekdays vs. weekends was associated with higher BMI (β=0.81, p=0.018), WC (β=0.67, p=0.029), DBP (β=1.34, p=0.049), and SBP (β=1.45, p=0.062). Each 1-h increase in the difference between weekday vs. weekend NFD was associated with higher BMI (β=0.55, p=0.045), fasting glucose (β=2.46, p=0.028), and SBP (β=1.17, p=0.058) and lower LS7 score (β=-0.24, p=0.014). Greater variability in nighttime eating (higher %kcal after 5PM and 8PM SD) was associated with higher WC (β=0.014, p=0.020 and β=0.030, p=0.040). Conclusions: Greater meal timing variability was related to poorer CVH and higher BMI, WC, BP, and fasting glucose. Results suggest that stabilizing meal timing patterns should be considered for lowering CVD risk and warrant confirmation in a larger sample.
CTIM-20. PHASE I STUDY OF IBRUTINIB WITH RADIATION AND TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Yasmeen Rauf, David Peereboom, Jaleh Fallah, Cathy Schilero, Pamela Lackner, Glen Stevens, Manmeet Ahluwalia
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Glioblastoma is a devastating disease that is notoriously resistant to current therapies, leading to dismal patient outcomes and a median survival of just 14.6 months. A major problem in glioblastoma treatment is the inability to effectively target the cell population that gives rise to recurrence. These cells, known as glioma stem cells (GSCs) or tumor propagating cells are endowed with a large capacity for self-renewal to propagate the tumor. GSCs are resistant to radiation. Ibrutinib is a first-in-class, potent, orally administered, covalently binding Inhibitor of Bruton’s Tyrosine Kinase (BTK). Ibrutinib is a small-molecule tyrosine kinase. It also inhibits BMX. Bone marrow X-linked (BMX) nonreceptor tyrosine kinase activates STAT3 signaling to maintain self-renewal and tumorigenic potential of GSCs. Hence a combination of ibrutinib with radiation and or temozolomide in patients with newly diagnosed Glioblastoma is warranted. METHODS This is a two arm study. Arm 1 is for patients with unmethylated MGMT Glioblastoma. Every patient gets ibrutinib and 60 Gy radiation over 6 weeks. Patients will undergo a 4-week break and Ibrutinib treatment will then continue until disease progression, intolerable toxicity or death. Arm 2 is for patients with MGMT methylated glioblastoma. Every patient will receive Ibrutinib and 60 Gy radiation and daily Temozolomide at 75 mg/m2 for 6 weeks. Patients will undergo a 4-week break then receive daily ibrutinib and adjuvant Temozolomide. The temozolomide will continue until disease progression, intolerable toxicity or death or maximum of 6 cycles. Ibrutinib treatment will continue until disease progression, intolerable toxicity or death. RESULTS The maximum tolerated dose (MTD) of Ibrutinib with radiation (2 Gy x 30) in patients in each arm will be reported. The safety of Ibrutinib with radiation and with radiation and temozolomide will be reported. The Progression free survival and overall survival in each arm will be reported. CONCLUSION This is an ongoing clinical trial. Results will be reported once study is complete.
Gaps in the total management of cancer
Authors: Shubha Maudgal, Y. K. Sapru
Journal: Cancer Research (2004)

1407  The incidence of cancer in a number of countries is related to faulty life-styles. In India 70% of all cancers are related to use of tobacco, smoked or chewed. A huge amount of money and the best talent in advertising is engaged in the propagation of this faulty life-style. Not even 1% of resources available for cancer control are allocated to educating people and fostering awareness. For the total management of cancer this needs to be corrected. Early diagnosis of cancer in majority of the cases can result in better management of cancer and even cure in 60-80% of patients. In India, cure rates are very poor because the disease is detected only in the advanced stages. Despite this, very little is being invested in cancer screening. In the check-ups conducted by CPAA of 150,000 healthy individuals we found incidence of cancer to the tune of 0.3%; incase of high risk individuals i.e. smokers or blood relations of cancer patients this figure goes up to 3%. Many lives can be saved through the investment into screening for cancer in healthy individuals. Communication gap between the treating clinician, the patients and their relatives is a major inadequacy in the management of a cancer patient in India. It results in development of confusion, depression and avoidable fears in the minds of cancer patients and their family members. If the treating clinician could spare time to answer questions of the cancer patients on his disease, prognosis, side-effects of treatment and other related issues, the patient would be psychologically more positive and at peace about his disease. Need for sensitivity on issues other than malignancy and tumor is most essential. Prostheses after radical mastectomy is a typical case where for the patient the issue is as important as the malignancy itself while for the clinician it may have low priority and could be given lesser attention. Emphasis on quality of life (QOL) issues is very important in the total management of cancer patients. Over the last decade clinicians have accepted that while survival and disease free state are both critical factors for cancer patients, overall QOL is of primary importance. Oncologists often concentrate all their expertise on the scientific application of medical knowledge and forget that emotional and psychological support is also essential. Relief of pain is an ethical imperative and clinicians must maximize their knowledge, skills and diligence to attend to this task, which currently remains under treated in many cases mainly due to inadequate assessment. Surveys indicate that 30-60% of cancer patients experience pain during active therapy and more than 70% with advanced disease. Assessment of pain must be an on going and dynamic process to include accurate characterization of the pain and the syndrome as well as the evaluation of the impact of pain and the role it plays in the overall suffering of the patient.
Patient Consumerism, Healing Relationships, and Rebuilding Trust in Health Care
Authors: Dhruv Khullar, Gwen Darien, Debra L. Ness
Journal: JAMA (2020)

This Viewpoint discusses barriers to building trust between physicians and patients and offers recommendations to increase that trust, including minimizing emphasis on patient consumerism, promoting authentic partnerships, and accelerating select payment and delivery system reforms.
Hyocholic acid species improve glucose homeostasis through a distinct TGR5 and FXR signaling mechanism
Authors: Xiaojiao Zheng, Tianlu Chen, Runqiu Jiang, Aihua Zhao, Qing Wu, Junliang Kuang, Dongnan Sun, Zhenxing Ren, Mengci Li, Mingliang Zhao, Shouli Wang, Yuqian Bao, Huating Li, Cheng Hu, Bing Dong, Defa Li, Jiayu Wu, Jialin Xia, Xuemei Wang, Ke Lan, Cynthia Rajani, Guoxiang Xie, Aiping Lu, Weiping Jia, Changtao Jiang, Wei Jia
Journal: Cell Metabolism (2020)
Imaging Atherosclerosis in Great Apes
Authors: Randall C. Thompson, Elaine C. Thompson, Navneet Narula, L. Samuel Wann, Ian Kwong, M. Linda Sutherland, James D. Sutherland, Jagat Narula, Adel H. Allam, Christine A.M. France, David E. Michalik, Darrin Lunde, Caleb E. Finch, Gregory S. Thomas, David R. Hunt, Bruno Frohlich
Journal: JACC. Cardiovascular imaging (2020)
Unbiased Phosphoproteomics Reveals a Therapeutically Relevant Connection between Pre-mRNA Splicing and Proteasome Inhibition in Multiple Myeloma
Authors: Hector H Huang, Christine Yt Lam, Alexis Thornton, Margarette Mariano, Ian Ferguson, Byron C Hann, Angela Brooks, Arun P. Wiita
Journal: Blood (2017)
Abstract 16002: Chronotropic Incompetence Limits Exercise Capacity in Patients Taking Beta-Blockers
Authors: Maciej Tysarowski, Krzysztof Smarz, Beata Zaborska, Ewa Pilichowska-Paszkiet, Malgorzata Sikora-Frac, Andrzej Budaj, Tomasz Jaxa-Chamiec
Journal: Circulation (2020)

Introduction: Chronotropic incompetence in patients taking beta-blockers is associated with poor prognosis; however, its impact on exercise capacity (EC) remains unclear. Hypothesis: We assessed the hypothesis that chronotropic incompetence is associated with decreased exercise capacity in patients taking beta-blockers. Methods: We retrospectively analyzed data from consecutive patients taking beta-blockers referred for cardiopulmonary exercise testing. EC was expressed as peak oxygen uptake (VO 2 peak; mL/kg/min). Chronotropic incompetence was defined as chronotropic index (CI) ≤ 62%. CI was calculated as [(HR at peak-resting HR) / (maximum predicted HR-resting HR)] х 100%. Results: Among 140 patients all taking beta-blockers (age 61 ± 9.7 years; 73% males), there were 113 (80.7%) patients with chronotropic incompetence. EC was lower in the group with chronotropic incompetence than the group without it, VO 2 peak 18.3 ± 5.7 vs. 24.0 ± 5.3 mL/kg/min, p &lt; 0.001. In multivariate analysis ( Table ), EC correlated positively with CI (β = 0.14, p &lt; 0.001) and male gender (β = 5.12, p &lt; 0.001), and negatively with age (β = –0.17, p &lt; 0.001) and presence of heart failure (β = –3.35, p &lt; 0.001). Beta-blocker dose was not associated with EC. Partial correlation attributable to CI (partial R 2 = 24.7%) accounted for more than one-third of the variance in EC explained by the model (adjusted R 2 = 59.8%). Conclusions: In patients taking beta-blockers, the presence of chronotropic incompetence was associated with lower EC, regardless of the beta-blocker dose. CI accounted for more than one-third of EC variance explained by our model.
EPCO-08. TUMOR-IMMUNE INTERACTIONS ARE DYNAMIC AND INFLUENCE THE EVOLUTIONARY TRAJECTORY OF ADULT DIFFUSE GLIOMA
Authors: Frederick Varn, Kevin Johnson, Floris Barthel, Hoon Kim, Taylor Wade, Disha Lodha, Shoaib Ajaib, Nazia Ahmed, Luciano Garofano, Fulvio D’Angelo, Lucy Stead, Houtan Noushmehr, Antonio Iavarone, Roel Verhaak
Journal: Neuro-Oncology (2020)

Abstract Diffuse glioma is an aggressive brain cancer that is characterized by a poor prognosis and a universal resistance to therapy. The evolutionary processes behind this resistance remain unclear. Previous studies by the Glioma Longitudinal Analysis (GLASS) Consortium have indicated that therapy-induced selective pressures shape the genetic evolution of glioma in a stochastic manner. However, single cell studies have revealed that malignant glioma cells are highly plastic, and capable of changing their cell state in response to diverse challenges in their microenvironment. The tumor immune response has been implicated as a major driver of these malignant cell state transitions, and is known to be affected by the administration of therapy, but the extent to which tumor genetics, therapy, and the different components of the immune response interact to influence a glioma’s evolutionary trajectory are poorly understood. To further investigate these factors, we collected DNA and RNA sequencing data on pre- and post-treatment tumor pairs from over 150 glioma patients that have received chemotherapy, radiotherapy, and/or immune checkpoint blockade agents. By integrating mutation, copy number, and in silico deconvolution analyses of bulk transcriptome data across the three molecular subtypes of diffuse glioma, we show that longitudinal increases in chromosomal instability and gene fusions associate with decreased immune infiltrate and altered cell states at recurrence. We additionally find that specific molecular alterations and malignant cell states associate with unique inflammatory and immunosuppressive programs in tumor-associated macrophages and microglia. Lastly, we show that the abundance of T cells in the tumor microenvironment does not associate with changes in neoantigen depletion and the acquisition of antigen presentation machinery defects, suggesting minimal immunoediting activity over time. Collectively, our results indicate that the administration of therapy can alter the dynamics of tumor-immune interactions in glioma, resulting in new steady-states at recurrence that can be subsequently targeted.
LGG-19. SPINAL LOW-GRADE GLIOMAS IN CANADIAN CHILDREN: A MULTI-CENTRE RETROSPECTIVE REVIEW
Authors: Hallie Coltin, Savvy Benipal, S Rod Rassekh, Liana Figueiredo Nobre, Julie Bennett, Uri Tabori, Bev Wilson, Vivek Mehta, Wendy Beaudoin, Shayna Zelcer, Sylvia Cheng, Juliette Hukin, Cynthia Hawkins, Eric Bouffet, Donna Johnston
Journal: Neuro-Oncology (2020)

Abstract PURPOSE Primary spinal low-grade gliomas (LGGs) are rare, can be difficult to treat, and can result in significant morbidity. The management of pediatric spinal LGGs remains controversial. METHODS A national multi-centre retrospective review of spinal LGGs diagnosed in children less than 18 years of age between 1990–2015 was undertaken to examine the clinical features, pathological subtypes, and treatment outcomes. RESULTS Forty-three patients from five institutions were included. The median age of diagnosis was 5.2 years. All patients were symptomatic at diagnosis. Forty-four percent of patients were diagnosed at least 6 months after symptoms developed. Two patients had metastatic disease at diagnosis. The most common histology was pilocytic astrocytoma (48.8%). Molecular information was available for 15/43 patients: 6 patients had BRAF fusions and 4 patients had BRAF V600E mutations. Gross-total resection was achievable in only 6 patients. Twenty-seven patients were treated with surgery-only and the others received chemotherapy and/or focal radiation. Eleven patients were irradiated. No patients were registered in clinical trials for first-line therapy. Twenty-three patients experienced relapse or progression. Patients were followed for a median of 8.3 years (range, 0.5–20.4 years). Five-year progression-free survival (PFS) and overall survival (OS) rates were 48.3% (95% CI, 32.3% to 62.5%) and 89.7% (95% CI, 74.6% to 96.1%) respectively. CONCLUSION There is significant heterogeneity in surgical outcomes and treatment modalities of pediatric spinal LGGs. The PFS and OS rates remain suboptimal, likely due to tumor location. The low clinical trial enrollment rate highlights the paucity of available trials for spinal LGGs.
Cathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome
Authors: Carmela Morrone, Natalia F. Smirnova, Aicha Jeridi, Nikolaus Kneidinger, Christine Hollauer, Jonas Christian Schupp, Naftali Kaminski, Dieter Jenne, Oliver Eickelberg, Ali Önder Yildirim
Journal: European Respiratory Journal (2020)

Bronchiolitis obliterans syndrome (BOS) is a major complication after lung transplantation (LTx). BOS is characterised by massive peribronchial fibrosis, leading to air trapping-induced pulmonary dysfunction. Cathepsin B, a lysosomal cysteine protease, has been shown to enforce fibrotic pathways in several diseases. However, the relevance of cathepsin B in BOS progression has not yet been addressed. The aim of the study was to elucidate the function of cathepsin B in BOS pathogenesis. We determined cathepsin B levels in bronchoalveolar lavage fluid (BALF) and lung tissue from healthy donors (HD) and BOS LTx patients. Cathepsin B activity was assessed via a fluorescence resonance energy transfer-based assay and protein expression was determined using Western blotting, ELISA and immunostaining. To investigate the impact of cathepsin B in the pathophysiology of BOS, we used an in vivo orthotopic left LTx mouse model. Mechanistic studies were performed in vitro using macrophage and fibroblast cell lines. We found a significant increase of cathepsin B activity in BALF and lung tissue from BOS patients, as well as in our murine model of lymphocytic bronchiolitis. Moreover, cathepsin B activity was associated with increased biosynthesis of collagen and had a negative effect on lung function. We observed that cathepsin B was mainly expressed in macrophages that infiltrated areas characterised by a massive accumulation of collagen deposition. Mechanistically, macrophage-derived cathepsin B contributed to transforming growth factor-β1-dependent activation of fibroblasts, and its inhibition reversed the phenotype. Infiltrating macrophages release active cathepsin B, thereby promoting fibroblast activation and subsequent collagen deposition, which drive BOS. Cathepsin B represents a promising therapeutic target to prevent the progression of BOS.
Abstract 15450: Present Day Outcomes of Continuous Home Milrinone Infusion Therapy in Advanced Heart Failure With Reduced Ejection Fraction: A Single-Center Experience
Authors: Pakpoom Tantrachoti, Wasawat Vutthikraivit, Pavida Pachariyanon, Sofia Prieto, Nandini Nair
Journal: Circulation (2019)

Introduction: Home intravenous (IV) milrinone has been recommended as a bridge to decision or as palliative therapy in patients with advanced heart failure (HF). Initial studies showed improved HF ...