tbuckley/cabot-search huggingface dataset:
The impact of GOLD (Geriatric Oncology Liaison Development) service in oncology patients with significant co-morbidities and/or borderline performance status.
Authors: Matthaios Kapiris, Janine Mansi, Eleni Karapanagiotou
Journal: Journal of Clinical Oncology (2019)

90 Background: ASCO guidelines suggest patients &gt; 65 should have a formal geriatric assessment [1]. We set up a new service in a London Cancer Centre. Cancer patients &gt; 65 were reviewed in a one-stop GOLD clinic. Their focus was to provide a holistic approach to improve the oncology management. Nevertheless, not all cancer patients are fit to receive SACT. The aim of this study was to retrospectively review this group of patients. Methods: From October 2016 to April 2018, 596 patients were reviewed by GOLD. We analysed data for 298 (50%), including GOLD interventions and oncology management. In this cohort, 73% were between70-84 years (median 78). While most patients had SACT, 36 (12.4%) were deemed unfit by the oncology teams and had best supportive care only. These patients had a median age of 78.7 (64-93) and 20 (55.5%) were between 70-84. We also collected data on palliative care referral. Results: The main referrers were GI (10, 28%) and Urology (9, 25%). The rest included haematology (7, 19.4%), lung (5, 13.9%), gynaecology (3, 8.3%), melanoma and H&amp;N (1, 2.8%) each. Referrals came mainly from the oncology teams (22, 61.1%). The remainder were identified from screening due to age (10, 27.8%) or following inpatient admission/Acute Oncology attendance (4, 11.1%). Co-morbidities and borderline performance status for systemic treatment were the two most common reasons for GOLD reviews (47.2% each), 8.3% involved polypharmacy and 2 (5.5%) cases involved social issues. Medication changes were advised for 52.8%. 41.6% did not have any changes to their management. One patient (2.8%) was referred to AHP and one (2.8%) to community palliative care. Fifteen (41.7%) had been referred to the Palliative Care team at the time of their review by GOLD. Conclusions: Despite multi-professional input, there are patients who remain unfit for SACT. It remains unclear whether a one-stop GOLD review added to the management of this group. Further evaluation is required to correctly identify patients who do not require multiple reviews. [1] Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Chemotherapy: ASCO Guideline for Geriatric Oncology Hurria et al.
Long-term and late effects (LLEs), anxiety, and depression among long-term survivors of pediatric, adolescent, and young adult (P-AYA) cancer.
Authors: Linda A. Jacobs, Abigail N. Blauch, Donna A. Pucci, Steven C Palmer
Journal: Journal of Clinical Oncology (2019)

143 Background: Adult P-AYA cancer survivors report numerous LLEs, as well as potential decrements in psychological well-being. The relationship between LLEs and psychological well-being, however, has not been well described in this population. We examined this relationship and predictors of LLEs and well-being in a sample of adult survivors of P-AYA cancer. Methods: Survivors of P-AYA cancer &gt; 2 years from end of treatment completed the Hospital Anxiety and Depression Scale (HADS) and a measure of presence and severity of 11 common LLEs following a survivorship visit. LLEs included fatigue, pain, insomnia, numbness, joint or muscle pain, difficulties with concentration or memory, body image concerns, decreased sexual interest, and weight. Results: Participants (N = 237) were predominately white (89%), college educated (76%), single (63%), and had an annual income of &gt; $60,000 (69%). A plurality had diagnoses of leukemia (30%) or Hodgkin's lymphoma (29%) treated 17 years previously. Treatment included surgery (35%), chemotherapy (91%), XRT (59%), and BMT (17%). Anxiety (M = 6.02; SD = 3.07) and depression (M = 2.54; SD = 2.85) scores were generally low and below the cutpoint of 8 (all t &lt; -7.8; all p &lt; .001 ), although 21% and 9% screened positively for anxiety or depression, respectively. 91% of participants reported at least 1 LLE (M = 4.8, SD = 3.1), most commonly fatigue (73%), concentration (57%) and memory difficulties (53%), and body image problems (48%). Total number LLEs was associated with elevations in both anxiety and depression, as was severity for each individual LLE (all p &lt; 0.001). Only one LLE, difficulty with body image, produced large effects for both anxiety and depression. Low income status were associated with both LLEs and elevations in anxiety and depression (all p &lt; 0.01). Conclusions: Most P-AYA survivors report LLEs. Although anxiety and depression are modest, elevations occur in a substantial number of survivors. Presence of LLEs is associated with worse psychosocial outcomes, particularly difficulties with body image. Lower income individuals and those with body image concerns may be at particular risk of poorer psychosocial outcomes.
Characterizing the Anti-Apoptotic Dependencies of T-Cell Prolymphocytic Leukemia Identifies HDAC and JAK/STAT Pathway Inhibitors As Promising Combination Partners to Augment Bcl-2 Targeted Killing By Venetoclax
Authors: Charles Herbaux, Christoph Kornauth, Stéphanie Poulain, Olivier Tournilhac, Mary C Collins, Rebecca Valentin, Stephen Jun Fei Chong, Jehan Dupuis, Adrien Daniel, Micha Srour, Cecile Tomowiak, Kamel Laribi, Damien Roos-Weil, Cedric Rossi, Nicolas Vanlangendonck, Cecile Leyronnas, Fatiha Merabet, Jean Valère Malfuson, Mourad Tiab, Samuel Ng, Franck Morschhauser, Philipp Bernhard Staber, Matthew S. Davids
Journal: Blood (2019)
SAT0140 Hypersomnolence in fibromyalgia syndrome
Authors: M Rizzi, P Sarzi-Puttini, A Andreoli, B Panni, M Pecis, FG Vassallo, M Carrabba, M Sergi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate hypersomnolence in patients affected by fibromyalgia syndrome. <h3>Methods</h3> Thirty consecutive patients affected by fibromyalgia syndrome (FMS) (28 F) underwent a general sleep questionnaire, the Epsworth sleepiness scale (ESS), formal polysomnography, and lung function tests. <h3>Results</h3> Patients complaining of daytime hypersomnolence had a higher number of tender points (15 ± 2 vs 12 ± 1, p &lt; 0.01), a greater score of subjective pain (72 ± 15 vs 52 ± 13, p = 0.05) and more fatigue (p = 0.04), about twice as many arousals per hour and a lower sleep efficiency than patients who did not report this symptom. TLco was more impaired and the occurrence of PB higher. FMS patients who referred daytime somnolence slept significantly less efficiently than the FMS with no day time somnolence (p &lt; 0.05), had a lower proportion of stage 3 sleep (5 ± 2% vs 12 ± 3%; p &lt; 0.001), stage 4 (1 ± 0.5% vs 4 ± 1%; p &lt; 0.001), and twice as many arousals per hour of sleep (p &lt; 0.01). The respiratory pattern of FMS patients with hypersomnolence showed a higher occurrence of periodic breathing (p = 0.02). The short length of apneas and hypopneas did not affect the apnea/hypopnea index (5.1 ± 3 vs 7 ± 4; p = ns), but FMS patients with daytime hypersomnolence had a greater number of desaturations per hour of sleep (11 ± 6 vs 6 ± 5; p &lt; 0.05). Pulmonary volumes did not differ between the two groups. <h3>Conclusion</h3> The occurrence of daytime hypersomnolence in FMS patients, is linked to a greater severity of fibromyalgia symptoms and to a more severe polisomnographic alterations.
Supramolecular Nanofibers for Encapsulation and In Situ Differentiation of Neural Stem Cells
Authors: Hao Zhao, Jingwen Xu, Ke Peng, Xuancheng Fu, Endong Zhang, Fengting Lv, Libing Liu, Na Zhang, Yilin Wang, Shu Wang, Qi Gu
Journal: Advanced Healthcare Materials (2019)

Abstract Design and fabrication of fibrous materials by natural biological macromolecules in light of biomimetics to achieve spatially cellular arrangements are highly desirable in tissue engineering. Herein, chromatin‐inspired supramolecular fibers formed through the interfacial polyelectrolyte complexation (IPC) process by DNA and histone proteins for encapsulation and in situ differentiation of murine brain‐derived neural stem cells (NSCs) are reported. High cell viability of encapsulated NSCs demonstrates the excellent biocompatibility of fibers as 3D scaffolds. Moreover, a cell‐adhesive peptide (K 6 ‐PEG‐RGD) is introduced into fibers by electrostatic interaction to improve NSCs encapsulation efficiency and prevent them from migrating out of fibers for enhanced spatially cellular arrangement. In situ differentiation of NSCs into oligodendrocytes within fibers is revealed by immunocytochemical staining assay. Due to the robust abilities to encapsulate and in situ differentiate NSCs, these chromatin‐inspired supramolecular fibers show great potential in neural system‐related tissue.
Single Chain Variable Fragment Linker Length Regulates CAR Biology and T Cell Efficacy
Authors: Nathan Singh, Noelle V. Frey, Boris Engels, David M. Barrett, Olga Shestova, Pranali Ravikumar, Amy Shyu, Steven Highfill, Linlin Zhao, Liaomin Peng, Brian Granda, Melissa Ramones, Xeuqing Maggie Lu, David A Christian, Jessica Perazzelli, Simon F Lacey, Nathan Roy, Janis K Burkhardt, Florent Colomb, Mohamed Abdel-Mohsen, Regina M Young, Jennifer Brogdon, Stephan Grupp, Carl H June, Shannon L. Maude, Saar I. Gill, Marco Ruella
Journal: Blood (2019)
From the “coding metaphor” to a theory of representation
Authors: Jonathan Birch, Joulia Smortchkova
Journal: Behavioral and Brain Sciences (2019)

Abstract Brette highlights a conceptual problem in contemporary neuroscience: Loose talk of “coding” sometimes leads to a conflation of the distinction between representing and merely detecting a property. The solution is to replace casual talk of “coding” with an explicit, demanding set of conditions for neural representation. Various theories of this general type can be found in the philosophical literature.
Effects of immune architecture on response to adjuvant capecitabine in triple negative breast cancer (FinXX trial)
Authors: D.A. Hinerfeld, S. Chumsri, K. Asleh, H.A. Brauer, J. Kachergus, S. Lauttia, H. Lindman, T. Nielsen, H. Joensuu, A. Thompson
Journal: Annals of Oncology (2019)
Histone Lysine Methylation Dynamics Control<i>EGFR</i>DNA Copy-Number Amplification
Authors: Thomas L. Clarke, Ran Tang, Damayanti Chakraborty, Capucine Van Rechem, Fei Ji, Sweta Mishra, Anqi Ma, H. Ümit Kaniskan, Jian Jin, Michael S. Lawrence, Ruslan I. Sadreyev, Johnathan R. Whetstine
Journal: Cancer Discovery (2019)

Abstract Acquired chromosomal DNA copy gains are a feature of many tumors; however, the mechanisms that underpin oncogene amplification are poorly understood. Recent studies have begun to uncover the importance of epigenetic states and histone lysine methyltransferases (KMT) and demethylases (KDM) in regulating transient site-specific DNA copy-number gains (TSSG). In this study, we reveal a critical interplay between a myriad of lysine methyltransferases and demethylases in modulating H3K4/9/27 methylation balance to control extrachromosomal amplification of the EGFR oncogene. This study further establishes that cellular signals (hypoxia and EGF) are able to directly promote EGFR amplification through modulation of the enzymes controlling EGFR copy gains. Moreover, we demonstrate that chemical inhibitors targeting specific KMTs and KDMs are able to promote or block extrachromosomal EGFR amplification, which identifies potential therapeutic strategies for controlling EGFR copy-number heterogeneity in cancer, and, in turn, drug response. Significance: This study identifies a network of epigenetic factors and cellular signals that directly control EGFR DNA amplification. We demonstrate that chemical inhibitors targeting enzymes controlling this amplification can be used to rheostat EGFR copy number, which uncovers therapeutic opportunities for controlling EGFR DNA amplification heterogeneity and the associated drug response. This article is highlighted in the In This Issue feature, p. 161
Efficacy and Safety of Ibrutinib in Combination with Rituximab As Frontline Treatment for Indolent Clinical Forms of Mantle Cell Lymphoma (MCL): Preliminary Results of Geltamo IMCL-2015 Phase II Trial
Authors: Eva Gine, Maria de Fatima De La Cruz, Carlos Grande, Javier Lopez Jimenez, Alejandro Martín, Maria Jose Terol, Eva González-Barca, Adolfo de la Fuente, Ana Marin Niebla, Maria Casanova, Ana Muntañola Prat, Tomás José González-López, Marta Aymerich, Lucia Palacios, Xavier Setoain, Montserrat Cortés-Romera, Amanda Rotger, Alejandro Medina, Ramón García-Sanz, Elias Campo, Armando Lopez-Guillermo
Journal: Blood (2019)
Multicenter phase II study of trastuzumab with S-1 alone in elderly patients with HER-2 positive advanced gastric cancer (JACCRO GC-06).
Authors: Toshiki Masuishi, Tomono Kawase, Kazuhiro Nishikawa, Chikara Kunisaki, Satoshi Matsusaka, Yoshihiko Segawa, Masato Nakamura, Kinro Sasaki, Narutoshi Nagao, Akihito Tsuji, Yasuhiro Yuasa, Shinya Asami, Masahiro Takeuchi, Hiroshi Furukawa, Masashi Fujii, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2015)

106 Background: S-1 plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. In patients with HER2-positive AGC, ToGA trial showed survival benefit with the addition of trastuzumab to capecitabine plus cisplatin or fluorouracil plus cisplatin and HERBIS-1 trial demonstrated promising antitumor activity with the addition of trastuzumab to SP. However, cisplatin has several important drawbacks, including nausea, vomiting, and renal toxicity. And these disadvantages of cisplatin are noticeable in elderly patients. We evaluated the efficacy and safety of trastuzumab combined with S-1 alone in elderly patients with HER-2 positive AGC. Methods: Patients, 65 years or older, with HER2-positive AGC received S-1 (80–120mg per day) orally on days 1–28 of a 42-day cycle and trastuzumab (course 1, 8 mg/kg; course 2 onward, 6 mg /kg) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary endpoints were overall survival (OS), progression free survival (PFS), time to treatment failure (TTF) and adverse events. The sample size was 40 to 60 patients estimated on the basis of threshold RR=20%, expected RR=35%, alpha=0.1 (one-sided) and power=80 to 90%. Results: A total of 51 patients were enrolled. One patient was ineligible, therefore in the full analysis set of 50 patients (actual statistical power = 87.5%), the median age was 71 years (range=65-85), male: female was 37:13 and ECOG PS was 0/1/2= 33/14/3. The confirmed RR (CR/PR/SD/PD=3/17/23/7) was 40.0% (80% confidence interval (CI); 31.1-48.9%, 95% CI; 26.4-53.6%), and the null hypothesis was rejected. The disease control rate was 86.0% (95% CI; 76.4-95.6%). Median OS, PFS, and TTF were immature. Major grade 3 or 4 adverse events included neutropenia (10.0%), anemia (24.0%), diarrhea (10.0%) and anorexia (12.0%). There was one treatment-related death. Conclusions: The primary end point was met. Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects in elderly patients with HER2-positive AGC. Clinical trial information: UMIN000007368.
Detection of new endemic focus of tick-borne encephalitis virus (TBEV), Hampshire/Dorset border, England, September 2019
Authors: Maya Holding, Stuart D Dowall, Jolyon M Medlock, Daniel P Carter, Liz McGinley, Mollie Curran-French, Steven T Pullan, John Chamberlain, Kayleigh M Hansford, Matthew Baylis, Richard Vipond, Roger Hewson
Journal: Eurosurveillance (2019)

The presence of tick-borne encephalitis virus (TBEV) was detected in a questing tick pool in southern England in September 2019. Hitherto, TBEV had only been detected in a limited area in eastern England. This southern English viral genome sequence is distinct from TBEV-UK, being most similar to TBEV-NL. The new location of TBEV presence highlights that the diagnosis of tick-borne encephalitis should be considered in encephalitic patients in areas of the United Kingdom outside eastern England.
Targeting glycosylation of PD-1 to enhance CAR-T cell cytotoxicity
Authors: Xiaojuan Shi, Daiqun Zhang, Feng Li, Zhen Zhang, Shumin Wang, Yujing Xuan, Yu Ping, Yi Zhang
Journal: Journal of Hematology & Oncology (2019)

Abstract Asparagine-linked ( N -linked) glycosylation is ubiquitous and can stabilize immune inhibitory PD-1 protein. Reducing N -linked glycosylation of PD-1 may decrease PD-1 expression and relieve its inhibitory effects on CAR-T cells. Considering that the codon of Asparagine is aac or aat, we wondered if the adenine base editor (ABE), which induces a·t to g·c conversion at specific site, could be used to reduce PD-1 suppression by changing the glycosylated residue in CAR-T cells. Our results showed ABE editing altered the coding sequence of N74 residue of PDCD1 and downregulated PD-1 expression in CAR-T cells. Further analysis showed ABE-edited CAR-T cells had enhanced cytotoxic functions in vitro and in vivo. Our study suggested that the single base editors can be used to augment CAR-T cell therapy.
The Burden of Clinically Significant Bleeding, Thrombocytopenia and Platelet Transfusions in Myelodysplastic Syndromes
Authors: Kathleen Pao Lynn Cheok, Rakchha Chhetri, Li Yan A Wee, Arabelle Salvi, Simon McRae, David John Roxby, Deepak Singhal, Devendra K Hiwase
Journal: Blood (2019)
Phase I/II, Open-Label, Adaptive Study of Oral Bruton Tyrosine Kinase Inhibitor PRN1008 in Patients with Relapsed/Refractory Primary or Secondary Immune Thrombocytopenia
Authors: David J. Kuter, Ralph V. Boccia, Eun-Ju Lee, Merlin Efraim, Nikolay Tzvetkov, Jiri Mayer, Marek Trněný, Milan Kostal, Roman Hajek, Vickie McDonald, Olga Bandman, Regan Burns, Ann Neale, Dolca Thomas, Nichola Cooper
Journal: Blood (2019)
Cell-free Mycobacterium tuberculosis DNA test in pleural effusion for tuberculous pleurisy: a diagnostic accuracy study
Authors: X. Yang, N. Che, H. Duan, Z. Liu, K. Li, H. Li, C. Guo, Q. Liang, Y. Yang, Y. Wang, J. Song, W. Du, C. Zhang, Y. Wang, Y. Zhang, H. Wang, X. Chen
Journal: Clinical Microbiology and Infection (2019)
Associations of caregiver-oncologist discordance in prognostic understanding with caregiver-reported therapeutic alliance and anxiety.
Authors: Kah Poh Loh, Huiwen Xu, Ronald M. Epstein, Supriya Gupta Mohile, Holly Gwen Prigerson, Sandy Plumb, Susan Ladwig, Melisa L. Wong, Sindhuja M Kadambi, Colin McHugh, Amy W. An, Kelly Marie Trevino, Fahad Saeed, Paul Duberstein
Journal: Journal of Clinical Oncology (2019)

15 Background: Discordance in prognostic understanding between caregivers of adults with cancer and the patient’s oncologist is common. However, the relationship between caregiver-oncologist discordance and caregiver bereavement outcomes is unknown. We evaluated the associations of caregiver-oncologist discordance in beliefs about the patient’s curability and life expectancy with caregiver-reported therapeutic alliance and anxiety. Methods: This is a secondary analysis of a multicenter study that assessed the effect of a communication intervention among patients with advanced cancer and their caregivers. Prior to intervention exposure, caregivers and oncologists were asked about their belief in the patient’s chances for cure and living ≥2 years: 100%, about 90%, about 75%, about 50/50, about 25%, about 10%, and 0%. Discordance was defined as a difference by 2 response levels on each prognostic understanding item. Outcomes at 7 months after patient death included caregiver-reported therapeutic alliance [modified 5-item Human Connection (THC) scale] and anxiety (Generalized Anxiety Disorder-7). We used multivariable linear regression models to assess the independent associations of discordance with therapeutic alliance and anxiety. Results: We included 97 caregivers (mean age 63, range 22-83). Approximately 40% of caregiver-oncologist dyads had discordant beliefs about curability (caregivers were more optimistic in 100% of dyads) and 63% had discordant beliefs about life expectancy (caregivers were more optimistic in 94% of dyads). On multivariate analysis, discordance in beliefs about prognostic estimates was associated with lower THC score (b = -6.94, SE 3.17, p = 0.03). Discordance in beliefs about curability was associated with lower anxiety levels (b = -1.79, SE 0.90, p = 0.05). Conclusions: Caregiver-oncologist discordance may decrease caregiver-reported therapeutic alliance and anxiety, both of which may shape how caregivers interact with the healthcare system. A better understanding the role of caregivers’ prognostic understanding will guide interventions to improve caregiver-oncologist therapeutic alliance and caregiver anxiety. Clinical trial information: NCT01485627.
18F-FDG Imaging of a Case of Disseminated Nocardiosis
Authors: Margot Playe, Margot Einfalt, Sinn Rithy Toch, Antoine Froissart, Gérald Bodardel
Journal: Clinical Nuclear Medicine (2019)

Nocardiosis is an uncommon infection caused by ubiquitous environmental aerobic gram-positive filamentous bacteria, present in soil and water. Skin and lungs are usually the main targets of localized infections. Rarely, disseminated forms can occur in immunocompromised individuals. A 63-year-old man with a history of late-onset asthma and nasal and sinus polyposis treated with oral low-dose corticosteroid regimen presented with fever, headache, myalgia, skin erythematous plaques, and pustules. Brain MRI revealed multiple abscesses and pachymeningitis. F-FDG PET/CT was performed to assess the extent of the infection. Cutaneous samples and sputum culture isolated Nocardia brasiliensis, confirming diagnosis of disseminated nocardiosis.
Additional Lumpectomy and Irradiation for In-Breast Recurrence of Cancer—When Less Is More
Authors: Kiri Cook, Maggie DiNome
Journal: JAMA Oncology (2019)

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Corrigendum to “Toll-like receptor 3 downregulation is an escape mechanism from apoptosis during hepatocarcinogenesis” [J Hepatol 71 (2019) 763–772]
Authors: Marc Bonnin, Nadim Fares, Barbara Testoni, Yann Estornes, Kathrin Weber, Béatrice Vanbervliet, Lydie Lefrançois, Amandine Garcia, Alain Kfoury, Floriane Pez, Isabelle Coste, Pierre Saintigny, Alain Viari, Kévin Lang, Baptiste Guey, Virginie Petrilli, Valérie Hervieu, Brigitte Bancel, Birke Bartosch, David Durantel, Toufic Renno, Philippe Merle, Serge Lebecque
Journal: Journal of Hepatology (2019)