tbuckley/cabot-search huggingface dataset:
P-188 Safety and efficacy of first-line gemcitabine plus nab-paclitaxel for elderly metastatic pancreatic cancer patients
Authors: I. Pecora, C. Vivaldi, G. Rovesti, S. Catanese, F. Salani, A. Casadei Gardini, V. Massa, L. Bernardini, M. Riggi, K. Andrikou, I. Rapposelli, V. Formica, S. Cesario, M. Caccese, M. Lencioni, E. Vasile, A. Falcone, L. Fornaro
Journal: Annals of Oncology (2020)
Lester Grinspoon: psychiatrist who laid the intellectual foundation for marijuana reform
Authors: Bob Roehr
Journal: BMJ (2020)

grinspoon080720.f1 Photo caption: Lester Grinspoon (R) as best man at Carl Sagan’s (L) 1981 wedding to Ann Druyan

Credit: Peter Grinspoon

Even though it was the swinging ’60s, Lester Grinspoon was a bit taken aback when his good friend and fellow Harvard assistant professor Carl Sagan offered him a joint. “You’ll love it,” said the astrophysicist. But Grinspoon demurred, arguing the establishment line that it was bad for your health.

That encounter set Grinspoon off on a journey to prove his point. His rigorous research rediscovered the history of marijuana’s use as medicine over thousands of years, but little evidence that it was harmful, certainly not when compared with popular drugs such as tobacco and alcohol.

“The greatest potential for social harm lies in the scarring of so many young people and the reactive, institutional damages that are direct products of present marijuana laws,” Grinspoon wrote in Marihuana Reconsidered , published in 1971.

One reviewer wrote, “I can only express my admiration for the manner in which Grinspoon has extracted, analysed, and synthesised the most relevant literature to present the reader with a coherent, logical case.” Those words came from a pillar of the establishment, former commissioner of the US Food and Drug Administration (FDA), James L Goddard, who was writing in the New York Times . The headline said of the article was “The best dope so far.”1

Hippies and more straitlaced proponents of marijuana embraced the book as an intellectual cornerstone for the decades-long movement to decriminalise its use and document its benefits as both medicine and recreation.

The US president at the time, Richard Nixon, was not a fan. “Every one of the bastards that are out for legalising marijuana is Jewish, this clown is far on the left,” he told the White House staff in secret recordings later made …
Serum antibody response in critically ill patients with COVID-19
Authors: Alban Longchamp, Justine Longchamp, Antony Croxatto, Gilbert Greub, Bienvenido Sanchez, Julie Delaloye, Livia Whiting, Séverin Jeanneret, Alix T. Coste, Alexis Dumoulin, Stéphane Emonet, Raymond Friolet
Journal: Intensive Care Medicine (2020)
10 minute consultation: Persistent crying in babies
Authors: A R Gatrad, Aziz Sheikh
Journal: BMJ (2004)

A young mother presents with her 12 week old son, complaining that he “cries all the time.” She also has a three year old daughter who was “never a problem.”

Elicit the mother's views--What does she think the problem might be? Take seriously any specific concerns she has. How experienced is she? For example, does she appreciate that the duration and frequency of crying can vary considerably between infants and at different times in the same infant? How is she coping? Is she depressed? Ask about what sources of support she has at home or among her wider circle of friends and relatives and whether she needs any additional help.

Nature of the crying--Excessive crying is defined medically as crying that lasts at least three hours a day, for three days a week, for at least three weeks. Is there …
Combining Systemic Therapy With Radiation: Head and Neck Cancer Treatments in an Era of Targeted Agents and Immunotherapy
Authors: Harish N. Vasudevan, Sue S. Yom
Journal: Journal of the National Comprehensive Cancer Network (2020)

The addition of chemotherapy to radiation therapy (RT) has been established for decades to improve outcomes in patients with head and neck cancer (HNC). Concurrent chemoradiation increases both local control and overall survival but at the cost of significant toxicity, motivating extensive investigations to optimize the balance of clinical efficacy and adverse effects. This review discusses the rationale and seminal studies underlying the concurrent chemoradiation treatment paradigm in HNC, and describes attempts to better tailor systemic therapy beyond standard-of-care cisplatin, such as the use of alternate cytotoxic agents and nonstandard dosing regimens. Modern efforts to incorporate targeted therapies and immunotherapy are then summarized, particularly for patients unable to receive standard cytotoxic chemotherapy. Finally, mechanisms through which RT and systemic therapy cooperate to improve the therapeutic ratio are discussed, with a focus on the interaction between immunotherapy and RT, a rapidly emerging treatment paradigm. With increasing application of novel diagnostic and therapeutic approaches, determining the optimal concurrent systemic program to maximize RT efficacy will continue to evolve. Identification of patient- and tumor-specific factors will offer a unique opportunity to implement personalized oncologic care.
3D Brain Organoids: Studying Brain Development and Disease Outside the Embryo
Authors: Silvia Velasco, Bruna Paulsen, Paola Arlotta
Journal: Annual Review of Neuroscience (2020)

Scientists have been fascinated by the human brain for centuries, yet knowledge of the cellular and molecular events that build the human brain during embryogenesis and of how abnormalities in this process lead to neurological disease remains very superficial. In particular, the lack of experimental models for a process that largely occurs during human in utero development, and is therefore poorly accessible for study, has hindered progress in mechanistic understanding. Advances in stem cell–derived models of human organogenesis, in the form of three-dimensional organoid cultures, and transformative new analytic technologies have opened new experimental pathways for investigation of aspects of development, evolution, and pathology of the human brain. Here, we consider the biology of brain organoids, compared and contrasted with the endogenous human brain, and highlight experimental strategies to use organoids to pioneer new understanding of human brain pathology.
Oxidative stress markers in bus drivers
Authors: Pavel Rossner, Vlasta Svecova, Alena Milcova, Zdena Lnenickova, Ivo Solansky, Radim Sram
Journal: Cancer Research (2007)

841  Exposure to ambient air pollution is associated with many diseases. Oxidative stress is believed to be the major source of particulate matter (PM)-mediated adverse health effects. PM in ambient air arises from industry, local heating, and vehicle emissions and poses a serious problem mainly in large cities. Among other compounds PM contains carcinogenic polycyclic aromatic hydrocarbons (cPAHs). In the present study we analyzed the level of oxidative stress among 50 bus drivers from Prague, Czech Republic, and 50 matching controls. Samples from the same individuals were collected in two seasons with different levels of air pollution: in winter 2005 and in summer 2006. We assessed simultaneously the levels of 15-F2t-isoprostane (15-F2t-IsoP) and 8-oxodeoxyguanosine (8-oxodG) in urine and protein carbonyl groups in blood plasma. For the analysis of all markers we used ELISA techniques. In samples collected in winter 2005 we observed significantly increased levels of oxidative stress in bus drivers. The median levels (min, max) of individual markers in bus drivers vs. controls were as follows: 8-oxodG: 7.79 (2.64-12.34) vs. 6.12 (0.70-11.38) nmol/mmol creatinine (p  Acknowledgements:The study was supported by the Czech Ministry of Environment grant VaV-SL/5/160/05.
LBA-2 A two arm randomized prospective superiority phase II multicentric clinical trial to evaluate the efficacy of capecitabine-irinotecan (CAPIRI) versus irinotecan in advanced gall bladder cancer progressing on first line chemotherapy
Authors: A. Ramaswamy, A. Sharma, P. Bhargava, P. Jadhav, S. Mandavkar, M. Goel, S. Patkar, S. Ankathi, A. Baheti, V. Ostwal
Journal: Annals of Oncology (2020)
FRI0163 Initial assessment of wegener’s granulomatosis – an audit of rheumatological practice
Authors: JS McLaren, RA Luqmani
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Accurate initial assessment of organ involvement in Wegener's granulomatosis (WG) is essential to determine immediate and future management. Renal and pulmonary involvement are associated with a worse outcome. <h3>Objectives</h3> We audited the initial assessment of patients referred to the Rheumatic Diseases Unit (RDU) who were subsequently confirmed to have WG. As there are no published gold standards on what should be assessed, the following essential items were chosen following consensus discussion: blood pressure (BP), urinalysis (and microscopy if haematuria present) and serum creatinine for renal involvement and chest radiograph (CXR) for pulmonary involvement. Tissue biopsy from symptomatic sites was important to establish evidence of granulomata or inflammation (ear, nose and throat (ENT)), vasculitis (cutaneous/ENT) or focal segmental glomerulonephritis (renal). <h3>Methods</h3> All patients with WG referred to the RDU over 8 years until Sept 2000 were identified by search of the computer database. Patients with incomplete medical records and re-referrals were excluded. 35 patients were identified and their medical records and CXRs were reviewed to establish if basic investigations had been performed and if so, their results. <h3>Results</h3> Demographics: 19 F:16 M. Mean age 53, range 13–85. 83% of patients were referred by either general practitioners, general physicians or ENT surgeons. Features at presentation (%): ENT (94), arthralgia (66), cutaneous (51), renal (40), ocular (29), pulmonary (20) and neurological (17). The results are presented in the table. In 29% (10/35) of patients at least one test was not performed. 11% (4/35) of patients had hypertension (diastolic BP &gt; 99) and in none were recommendations made for BP to be rechecked or treatment to be commenced. 6% (2/35) of patients with microscopic haematuria did not have urine microscopy or a renal biopsy performed (one patient also had an elevated creatinine). 9 patients had an abnormal CXR: 1 had evidence of previous tuberculosis, 4 had active pulmonary disease and 4 had further investigation to exclude infection. <h3>Conclusion</h3> 71% of patients referred to a tertiary rheumatology centre and later confirmed to have WG received adequate basic investigation at presentation. Patients found to be hypertensive should have their BP repeated and those with haematuria should have urine microscopy performed. These results indicate that we should be more vigilant in performing basic tests in patients with suspected WG and in this regard our data have been presented to our department by means of an audio visual presentation and written information. The audit will be repeated in 2005 to reassess the recording of basic investigations in patients with WG.
The JAK-STAT pathway regulates CD38 on myeloma cells in the bone marrow microenvironment: therapeutic implications
Authors: Daisuke Ogiya, Jiye Liu, Hiroto Ohguchi, Keiji Kurata, Mehmet K. Samur, Yu-Tzu Tai, Sophia Adamia, Kiyoshi Ando, Teru Hideshima, Kenneth C. Anderson
Journal: Blood (2020)
SAT0078 Experiences with a viscosupplementation (hyalgan) clinic
Authors: C Rao, N Kumar, S Young-Min, NJ Marshall, PN Platt, ID Griffiths
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Osteoarthritis (OA) is the commonest condition to affect human joints. It is a major cause of pain, disability and handicap, and a difficult condition to treat. Pharmacological treatment has been limited to the use of analgesics, non-steroidal anti-inflammatory drugs and the controversial use of intra-articular steroid injections. None of these options provide a truly effective treatment. Viscosupplementation has only recently become available in the UK. Hyaluronon in synovial fluid has multiple functions in joint homeostasis. It is reduced in concentration and molecular weight in OA. Therefore viscosupplementation would not only remove pathological synovial fluid (by prior joint aspiration) but also restore the molecular weight and concentration of hyaluronan.<sup>1</sup> <h3>Objectives</h3> We wished to evaluate viscosupplementation for OA of the knee, and to ascertain which patient groups would derive the most benefit from Hyalgan. <h3>Methods</h3> We have an ongoing dedicated visco-supplementation clinic. Patients are assessed to ensure suitability and are also advised about weight reduction (if appropriate) and quadriceps exercises. They attend weekly for the course of 5 injections. The patients are asked to complete a WOMAC Questionnaire pre-course and at 6 weeks, 3 and 6 months after treatment. This is a health status instrument for measuring clinically important patient relevant outcomes to anti-rheumatic drug therapy in patients with osteoarthritis of the hip or knee.<sup>2</sup> No ethical approval was required. <h3>Results</h3> Comparing pre-course WOMAC scores with all time intervals a statistically significant difference at 6 weeks (paired T test p = 0.0081) was found. Patients were sub-divided into 2 groups according to WOMAC scores, 1600. (Maximum score 2400, indicating maximum severity). These groups were also compared. Results to reach statistical significance were WOMAC changes at 6 weeks and 6 months in the &gt;1600 group, compared to pre-course where p = 0.0053 and p = 0.023 respectively (unpaired T test). <h3>Conclusion</h3> From our study patients reported an improved WOMAC at 6 weeks. Those with score &gt;1600, pre-course do better than those with scores inconclusive but do appear to offer some benefit to patients.<sup>3</sup> As with intra-articular steroid injections in this condition, it is difficult to predict who will benefit.<sup>4</sup> Our work would suggest that patients with higher initial scores on WOMAC questionnaire may respond better. <h3>References</h3> Marshall KW. Intra-articular hyaluronan therapy. Curr Opin Rheumatol. 2000;12(5):468–74 Bellamy N, <i>et al</i>. Validation study of WOMAC. J Rheumatol. 1988;15:1833–40 Wen DY. Intra-articular hyaluronic acid for knee osteoarthritis. Am Fam Physician 2000;62(3):565–70 Jones A, Doherty M. Intra-articular corticosteroids are effective in osteoarthritis but there are no clinical predictors of response. Ann Rheum Dis. 1996;55(11):829–32
Preliminary Experience of Imatinib after Nilotinib in the First Line Treatment of Chronic Myeloid Leukemia
Authors: Ester Pungolino, Mariella D'adda, Alessandra Perego, Ester Maria Orlandi, Mauro Turrini, Lorenza Maria Borin, Alessandra Iurlo, Salvatore Artale, Maria Luisa Latargia, Michela Anghilieri, Simona Malato, Alessandra Trojani, Francesco Spina, Carraro Maria Cristina, Maria Luisa Pioltelli, Chiara Elena, Cristina Bucelli, Pierangelo Spedini, Giuseppe Rossi, Enrica Morra, Roberto Cairoli
Journal: Blood (2017)
The pro-cell death Bcl-2 family member, BNIP3 is mutated in breast tumors and this mutation increases resistance to hypoxia-induced cell death in breast cancer cell lines
Authors: Nicolle A. Bristow, Elizabeth S. Henson, Niki Vegh-Yarema, David D. Eisenstat, Spencer B. Gibson
Journal: Cancer Research (2006)

4078  BNIP3 (Bcl-2/adenovirus E1B 19 kDa Interacting Protein) is a pro-cell death member of the Bcl-2 family of proteins. It has been shown that BNIP3 expression is increased in hypoxic regions of breast tumors. This increased expression is paradoxical since BNIP3 induces cell death, yet these tumor cells remain viable. One possible explanation is the presence of mutations in the BNIP3 gene leading to the inactivation of the BNIP3 protein. We have previously found that BNIP3 is over-expressed in brain glioblastoma multiforme (GBM) tumors and is mutated in 17% of these tumors inactivating its cell death function. Therefore, we are investigating whether mutations in the BNIP3 gene are present in breast tumors and whether these mutations block hypoxia-induced cell death. To determine whether BNIP3 is mutated in breast tumors, RNA is isolated from frozen high grade breast tumor sections from the Manitoba Breast Tumor Bank. Reverse-transcriptase PCR is performed and the resultant cDNA sequenced. Of the 17 tumors sequenced to date, four mutations have been found, including two nonsense mutations (single nucleotide insertions) and two missense mutations. These mutations were confirmed using a single nucleotide primer extension assay. Immuno-fluorescent staining for BNIP3 expression in breast tumors revealed BNIP3 expression in tumors where the BNIP3 gene is mutated. We also determined that the ovarian cancer cell line SkOv3 has a mutation in BNIP3 resulting in a truncated protein. To determine if the mutations detected in breast tumors affect BNIP3 protein function, the breast cancer cell line MCF-7 and the human embryonic cell line HEK293 were transfected with expression constructs containing wild type or mutant BNIP3 cDNA. The expression of mutant BNIP3 renders these cells more resistant to hypoxia-induced cell death compared to cells expressing empty vector or wild type BNIP3. Since BNIP3 induces cell death by localizing with the mitochondria, we evaluated the ability of mutant BNIP3 to localize to the mitochondria. We demonstrated that mutant BNIP3 localizes to the mitochondria. Ongoing studies will demonstrate whether breast cancer cells expressing mutant BNIP3 injected into nude mice form tumors faster than cells expressing empty vector. Overall, our results indicate that BNIP3 is mutated in breast tumors and these mutations render breast cancer cells resistant to hypoxia-induced cell death.
P-351 RNA sequencing for personalized therapy prescription in colon cancer
Authors: E. Poddubkaya, M. Sorokin, M. Baranova, D. Lantsov, A. Glusker, L. Kogoniya, E. Markarova, M. Suntsova, A. Garazha, A. Buzdin, M. Sekacheva
Journal: Annals of Oncology (2020)
P-67 Short-term outcomes of capecitabine plus oxaliplatin versus S-1 plus oxaliplatin as adjuvant chemotherapies for advanced gastric cancer after laparoscopic gastrectomy and D2 resection: A prospective, multicenter randomized, controlled clinical trial
Authors: Y. Yan, L. Lu, X. Wang, D. Wang, Q. Huang, Q. Zhao, T. Liu, W. Fu
Journal: Annals of Oncology (2020)
P-69 Efficacy and safety of S-1 following gemcitabine with cisplatin for biliary tract cancer
Authors: H. Inoue, K. Yamazaki, H. Shirasu, T. Kawakami, A. Todaka, T. Tsushima, S. Hamauchi, T. Yokota, N. Machida, A. Fukutomi, Y. Onozawa, H. Yasui
Journal: Annals of Oncology (2020)
P-12 A descriptive analysis of patient characteristics from Russian internet postings focused on CRC (iPatient study)
Authors: Y. Khomitskaya, A. Paleeva, A. Ivankov, E. Shulepina, N. Korovkina, O. Trifonova, N. Saburkina, A. Grishin, A. Krotkevich
Journal: Annals of Oncology (2020)
Crude extracts of and pure boswellic acid acetates isolated from Boswellia carterri Birdw inhibit cell growth and induce apoptosis in prostate cancer cells by inhibition of 5-lipoxygenase
Authors: Min Lu, Lijuan Xia, Huiming Hua, Yongkui Jing
Journal: Cancer Research (2005)

3069  Gummy exudates of Boswellia carterri Birdw and Boswellia serrata have been traditionally used as anti-arthritic and anti-cancer mediations. Boswellic acid and its acetates isolated from these gummy exudates were found to be inhibitors of topoisomerases and to be non-redox, non-competitive specific inhibitors of 5-lipoxygenase (5-LOX). 5S-hydroxy-6,8,11,14-eicosatetraenoic acid, the product of 5-LOX activity, has been found to be both mitogenic and antiapoptotic in prostate cancer cells. The growth inhibitory effect of boswellic acid acetates (BAA), Boswellin (a crude methanol extract), and BEF (a chloroform extract) were used to test their ability to inhibit cell growth and to induce apoptosis in prostate cancer cells. The cell growth inhibitory effects were measured by an MTT assay and apoptosis was measured by a TUNEL assay in three prostate cancer cell lines, LNCaP, DU-145 and PC-3. BAA, Boswellin, and BEF had similar effects in the three prostate cancer cell lines tested. The IC50s of BAA, Boswellin, and BEF in LNCaP cells were 7.5, 8.0 and 12.5 ug/ml, respectively. To standardize the Boswellin and BEF based on BAA content using HPLC, only 3% and 64% of BAA was detected in Boswellin and BEF, respectively. These findings suggest that BAA was not the sole active component against prostate cancer growth in Boswellin and BEF. Using immunocytochemical and immunoblotting techniques, it was found that 5-LOX protein was highly expressed in all of the three prostate cancer cell lines. MK886, a 5-LOX inhibitor, enhanced BAA- and BEF-induced cell growth inhibition and apoptosis significantly. These data suggest that crude extracts Boswellia carterri Birdw and Boswellia serrata alone or in combination with a 5-LOX inhibitor may have therapeutic potential in the treatment of prostate cancer. (This work was supported by NIH R21AT001539).
O-6 The novel regimen of tremelimumab in combination with durvalumab provides a favorable safety profile and clinical activity for patients with advanced hepatocellular carcinoma
Authors: R. Kelley, M. Kudo, W. Harris, M. Ikeda, T. Okusaka, Y. Kang, S. Qin, D. Tai, H. Lim, T. Yau, W. Yong, A. Cheng, A. Gasbarrini, F. de Braud, J. Bruix, M. Borad, N. Standifer, P. He, A. Negro, G. Vlahovic, B. Sangro, G. Abou-Alfa
Journal: Annals of Oncology (2020)
Antiemetics: ASCO Guideline Update
Authors: Paul J. Hesketh, Mark G. Kris, Ethan Basch, Kari Bohlke, Sally Y. Barbour, Rebecca Anne Clark-Snow, Michael A. Danso, Kristopher Dennis, L. Lee Dupuis, Stacie B. Dusetzina, Cathy Eng, Petra C. Feyer, Karin Jordan, Kimberly Noonan, Dee Sparacio, Gary H. Lyman
Journal: Journal of Clinical Oncology (2020)

To update the guideline to include new anticancer agents, antiemetics, and antiemetic regimens and to provide recommendations on the use of dexamethasone as a prophylactic antiemetic in patients receiving checkpoint inhibitors (CPIs).ASCO convened an Expert Panel and updated the systematic review to include randomized controlled trials (RCTs) and meta-analyses of RCTs published between June 1, 2016, and January 24, 2020. To address the dexamethasone and CPI question, we conducted a systematic review of RCTs that evaluated the addition of a CPI to chemotherapy.The systematic reviews included 3 publications from the updated search and 10 publications on CPIs. Two phase III trials in adult patients with non-small-cell lung cancers evaluating a platinum-based doublet with or without the programmed death 1 (PD-1) inhibitor pembrolizumab recommended that all patients receive dexamethasone as a component of the prophylactic antiemetic regimen. In both studies, superior outcomes were noted in the PD-1 inhibitor-containing arms. Other important findings address olanzapine in adults and fosaprepitant in pediatric patients.Recommendations for adults are unchanged with the exception of the option of adding olanzapine in the setting of hematopoietic stem cell transplantation. Dosing information now includes the option of a 5-mg dose of olanzapine in adults and intravenous formulations of aprepitant and netupitant-palonosetron. The option of fosaprepitant is added to pediatric recommendations. There is no clinical evidence to warrant omission of dexamethasone from guideline-compliant prophylactic antiemetic regimens when CPIs are administered to adults in combination with chemotherapy. CPIs administered alone or in combination with another CPI do not require the routine use of a prophylactic antiemetic.Additional information is available at www.asco.org/supportive-care-guidelines.
Immunogenomic Landscape of Hematological Malignancies
Authors: Olli Dufva, Petri Pölönen, Oscar Brück, Mikko A.I. Keränen, Jay Klievink, Juha Mehtonen, Jani Huuhtanen, Ashwini Kumar, Disha Malani, Sanna Siitonen, Matti Kankainen, Bishwa Ghimire, Jenni Lahtela, Pirkko Mattila, Markus Vähä-Koskela, Krister Wennerberg, Kirsi Granberg, Suvi-Katri Leivonen, Leo Meriranta, Caroline Heckman, Sirpa Leppä, Matti Nykter, Olli Lohi, Merja Heinäniemi, Satu Mustjoki
Journal: Cancer Cell (2020)