tbuckley/cabot-search huggingface dataset:
Effect of age and frailty on the efficacy and tolerability of once‐weekly selinexor, bortezomib, and dexamethasone in previously treated multiple myeloma
Authors: Holger W. Auner, Maria Gavriatopoulou, Sosana Delimpasi, Maryana Simonova, Ivan Spicka, Ludek Pour, Meletios A. Dimopoulos, Iryna Kriachok, Halyna Pylypenko, Xavier Leleu, Vadim Doronin, Ganna Usenko, Roman Hajek, Reuben Benjamin, Tuphan Kanti Dolai, Dinesh Kumar Sinha, Christopher P. Venner, Mamta Garg, Don Ambrose Stevens, Hang Quach, Sundar Jagannath, Phillipe Moreau, Moshe Levy, Ashraf Badros, Larry D. Anderson, Nizar J. Bahlis, Thierry Facon, Maria Victoria Mateos, Michele Cavo, Yi Chai, Melina Arazy, Jatin Shah, Sharon Shacham, Michael G. Kauffman, Paul G. Richardson, Sebastian Grosicki
Journal: American Journal of Hematology (2021)

Elderly and frail patients with multiple myeloma (MM) are more vulnerable to the toxicity of combination therapies, often resulting in treatment modifications and suboptimal outcomes. The phase 3 BOSTON study showed that once-weekly selinexor and bortezomib with low-dose dexamethasone (XVd) improved PFS and ORR compared with standard twice-weekly bortezomib and moderate-dose dexamethasone (Vd) in patients with previously treated MM. This is a retrospective subgroup analysis of the multicenter, prospective, randomized BOSTON trial. Post hoc analyses were performed to compare XVd versus Vd safety and efficacy according to age and frailty status (<65 and ≥65 years, nonfrail and frail). Patients ≥65 years with XVd had higher ORR (OR 1.77, p = .024), ≥VGPR (OR, 1.68, p = .027), PFS (HR 0.55, p = .002), and improved OS (HR 0.63, p = .030), compared with Vd. In frail patients, XVd was associated with a trend towards better PFS (HR 0.69, p = .08) and OS (HR 0.62, p = .062). Significant improvements were also observed in patients <65 (ORR and TTNT) and nonfrail patients (PFS, ORR, ≥VGPR, and TTNT). Patients treated with XVd had a lower incidence of grade ≥ 2 peripheral neuropathy in ≥65 year-old (22% vs. 37%; p = .0060) and frail patients (15% vs. 44%; p = .0002). Grade ≥3 TEAEs were not observed more often in older compared to younger patients, nor in frail compared to nonfrail patients. XVd is safe and effective in patients <65 and ≥65 and in nonfrail and frail patients with previously treated MM.
Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model
Authors: Kevin Clayton, Jean Christophe Delpech, Shawn Herron, Naotoshi Iwahara, Maria Ericsson, Takashi Saito, Takaomi C. Saido, Seiko Ikezu, Tsuneya Ikezu
Journal: Molecular Neurodegeneration (2021)

Abstract Background Recent studies suggest that microglia contribute to tau pathology progression in Alzheimer’s disease. Amyloid plaque accumulation transforms microglia, the primary innate immune cells in the brain, into neurodegenerative microglia (MGnD), which exhibit enhanced phagocytosis of plaques, apoptotic neurons and dystrophic neurites containing aggregated and phosphorylated tau (p-tau). It remains unclear how microglia promote disease progression while actively phagocytosing pathological proteins, therefore ameliorating pathology. Methods Adeno-associated virus expressing P301L tau mutant (AAV-P301L-tau) was stereotaxically injected into the medial entorhinal cortex (MEC) in C57BL/6 (WT) and humanized APP mutant knock-in homozygote ( App NL-G-F ) mice at 5 months of age. Mice were fed either chow containing a colony stimulating factor-1 receptor inhibitor (PLX5622) or control chow from 4 to 6 months of age to test the effect of microglia depletion. Animals were tested at 6 months of age for immunofluorescence, biochemistry, and FACS of microglia. In order to monitor microglial extracellular vesicle secretion in vivo, a novel lentiviral EV reporter system was engineered to express mEmerald-CD9 (mE-CD9) specifically in microglia, which was injected into the same region of MEC. Results Expressing P301L tau mutant in the MEC induced tau propagation to the granule cell layer of the hippocampal dentate gyrus, which was significantly exacerbated in App NL-G-F mice compared to WT control mice. Administration of PLX5622 depleted nearly all microglia in mouse brains and dramatically reduced propagation of p-tau in WT and to a greater extent in App NL-G-F mice, although it increased plaque burden and plaque-associated p-tau + dystrophic neurites. Plaque-associated MGnD microglia strongly expressed an EV marker, tumor susceptibility gene 101, indicative of heightened synthesis of EVs. Intracortical injection of mE-CD9 lentivirus successfully induced microglia-specific expression of mE-CD9 + EV particles, which were significantly enhanced in Mac2 + MGnD microglia compared to Mac2 − homeostatic microglia. Finally, consecutive intracortical injection of mE-CD9 lentivirus and AAV-P301L-tau into App NL-G-F mice revealed encapsulation of p-tau in microglia-specific mE-CD9 + EVs as determined by super-resolution microscopy and immuno-electron microscopy. Discussion Our findings suggest that MGnD microglia hyper-secrete p-tau + EVs while compacting Aβ plaques and clearing NP tau, which we propose as a novel mechanistic link between amyloid plaque deposition and exacerbation of tau propagation in App NL-G-F mice.
Fetal body MRI and its application to fetal and neonatal treatment: an illustrative review
Authors: Joseph R Davidson, Alena Uus, Jacqueline Matthew, Alexia M Egloff, Maria Deprez, Iain Yardley, Paolo De Coppi, Anna David, Jim Carmichael, Mary A Rutherford
Journal: The Lancet Child & Adolescent Health (2021)
Signal transduction in primary cilia – analyzing and manipulating GPCR and second messenger signaling
Authors: Dagmar Wachten, David U. Mick
Journal: Pharmacology & Therapeutics (2021)

The primary cilium projects from the surface of most vertebrate cells, where it senses extracellular signals to regulate diverse cellular processes during tissue development and homeostasis. Dysfunction of primary cilia underlies the pathogenesis of severe diseases, commonly referred to as ciliopathies. Primary cilia contain a unique protein repertoire that is distinct from the cell body and the plasma membrane, enabling the spatially controlled transduction of extracellular cues. G-protein coupled receptors (GPCRs) are key in sensing environmental stimuli that are transmitted via second messenger signaling into a cellular response. Here, we will give an overview of the role of GPCR signaling in primary cilia, and how ciliary GPCR signaling can be targeted by pharmacology, chemogenetics, and optogenetics.
P30.02 Assessing SIADH (Syndrome of Inapproriate Antidiuretic Hormone Secretion) Management and Outcome Among Lung Cancer Patients: The Assert Trial
Authors: R. Berardi, M.C. Garassino, M. Tiseo, S. Palazzo, V. Montesarchio, G. Tonini, L. Cavanna, D. Ferrari, L. Palermo, E. Rijavec, G. Altavilla, A. Morabito, G. Pinotti, R. Buosi, F. Cognetti, M. Scartozzi, S. Gori, M. Torniai, V. De Marino
Journal: Journal of Thoracic Oncology (2021)
Association of Children’s Mode of School Instruction with Child and Parent Experiences and Well-Being During the COVID-19 Pandemic — COVID Experiences Survey, United States, October 8–November 13, 2020
Authors: Jorge V. Verlenden, Sanjana Pampati, Catherine N. Rasberry, Nicole Liddon, Marci Hertz, Greta Kilmer, Melissa Heim Viox, Sarah Lee, Neha K. Cramer, Lisa C. Barrios, Kathleen A. Ethier
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In March 2020, efforts to slow transmission of SARS-CoV-2, the virus that causes COVID-19, resulted in widespread closures of school buildings, shifts to virtual educational models, modifications to school-based services, and disruptions in the educational experiences of school-aged children.Changes in modes of instruction have presented psychosocial stressors to children and parents that can increase risks to mental health and well-being and might exacerbate educational and health disparities (1,2).CDC examined differences in child and parent experiences and indicators of well-being according to children's mode of school instruction (i.e., in-person only [in-person], virtual-only [virtual], or combined virtual and inperson [combined]) using data from the COVID Experiences nationwide survey.During October 8-November 13, 2020, parents or legal guardians (parents) of children aged 5-12 years were surveyed using the NORC at the University of Chicago AmeriSpeak panel,* a probability-based panel designed to be representative of the U.S. household population.Among 1,290 respondents with a child enrolled in public or private school, 45.7% reported that their child received virtual instruction, 30.9% in-person instruction, and 23.4% combined instruction.For 11 of 17 stress and well-being indicators concerning child mental health and physical activity and parental emotional distress, findings were worse for parents of children receiving virtual or combined instruction than were those for parents of children receiving in-person instruction.Children not receiving in-person instruction and their parents might * The AmeriSpeak panel includes approximately 40,000 households recruited using random sampling from an address-based sample with mail, e-mail, Internet, telephone, and in-person follow-up.https://amerispeak.norc.org/Documents/Research/AmeriSpeak%20Technical%20Overview%202019%20 02%2018.pdfexperience increased risk for negative mental, emotional, or physical health outcomes and might need additional support to mitigate pandemic effects.Community-wide actions to reduce COVID-19 incidence and support mitigation strategies in schools are critically important to support students' return to in-person learning.
CLO21-018: Clinical Characteristics of Breast Cancer Patients Treated With Trastuzumab-anns, a Trastuzumab Biosimilar, in a Real-World Setting
Authors: Ran Jin, Neil Accortt, Darcie Sandschafer, Tatiana Lawrence, Reshma Mahtani
Journal: Journal of the National Comprehensive Cancer Network (2021)

"CLO21-018: Clinical Characteristics of Breast Cancer Patients Treated With Trastuzumab-anns, a Trastuzumab Biosimilar, in a Real-World Setting" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Antibody response to a single dose of SARS-CoV-2 mRNA vaccine in patients with rheumatic and musculoskeletal diseases
Authors: Brian J Boyarsky, Jake A Ruddy, Caoilfhionn M Connolly, Michael T Ou, William A Werbel, Jacqueline M Garonzik-Wang, Dorry L Segev, Julie J Paik
Journal: Annals of the Rheumatic Diseases (2021)

The immune response to SARS-CoV-2 messenger RNA (mRNA) vaccines in patients with rheumatic and musculoskeletal diseases (RMD) is undefined because these individuals were largely excluded from phase I–III studies. To better understand the immune response to vaccination in this patient population, we studied the antibody response in patients with RMD who completed the first dose of SARS-CoV-2 mRNA vaccination.

Participants with RMD across the USA were recruited to participate in this prospective cohort via social media. Those with prior SARS-CoV-2 were excluded. We collected demographics, RMD diagnoses and immunomodulatory regimens and tested for SARS-CoV-2 antibodies at baseline and prior to the second vaccine dose. Antibody testing was conducted on the semiquantitative Roche Elecsys anti-SARS-CoV-2 S enzyme immunoassay (EIA) which tests for antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein.1 We evaluated the association between demographic/clinical characteristics and positive antibody response using Fisher’s exact test and Wilcoxon rank-sum test.

We studied 123 participants who received their first SARS-CoV-2 vaccination dose between 8 January 2021 and 12 February 2021; 52% underwent BNT162b2, and 48% underwent mRNA-1273 (table 1). The most common reported RMD diagnoses were inflammatory arthritis (28%), systemic lupus erythematosus (SLE) (20%), Sjogren’s syndrome (13%) and overlap connective tissue diseases(29%). Whereas …
Nationwide Survey of Pediatric Hypodiploid Acute Lymphoblastic Leukemia in Japan
Authors: Sae Ishimaru, Yasuhiro Okamoto, Chihaya Imai, Hirotoshi Sakaguchi, Tomohiko Taki, Daisuke Hasegawa, Yuko Cho, Harumi Kakuda, Hideki Sano, Atushi Manabe, Toshihiko Imamura, Motohiro Kato, Yuki Arakawa, Hidemi Shimonodan, Atsushi Sato, So-ichi Suenobu, Takeshi Inukai, Arata Watanabe, Yoshifumi Kawano, Atsushi Kikuta, Keizo Horibe, Akira Ohara, Katsuyoshi Koh
Journal: Blood (2017)
P01.21 ANSELMA: Antiangiogenic Second Line Lung Cancer Meta-Analysis on Individual Patient Data in Non-Small Cell Lung Cancer, Again Relevant in ICI Era
Authors: J. Remon, B. Lacas, R. Herbst, M. Reck, E. Garon, G. Scagliotti, R. Ramlau, N. Hanna, J. Vansteenkiste, K. Yoh, H. Groen, J. Heymach, S. Mandrekar, I. Okamoto, J. Neal, R. Heist, J. Pignon, B. Besse
Journal: Journal of Thoracic Oncology (2021)
P86.16 Rationale of a Phase II Trial of Nivolumab Combined with Anlotinib in Advanced NSCLC Previously Treated with Immunotherapy
Authors: B. Han, B. Zhang, C. Shi, Z. Gao, H. Zhong, L. Xiong, A. Gu, W. Wang, T. Chu, W. Zhang, H. Wang, X. Zhang, R. Zhong
Journal: Journal of Thoracic Oncology (2021)
Narrative Ethics in Response to Unbearable Suffering—the Dutch Slippery Slope Is Nonexistent
Authors: Barend W. Florijn, Ad A. Kaptein
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine 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 Internal Medicine journal
Response to: ‘Correspondence on ‘Statistical review: frequently given comments’’ by Waki<i>et al</i>
Authors: Stian Lydersen
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Aim</h3> To objectively evaluate the effect of Holmich protocol-based exercise therapy on long-standing adductor-related groin pain (LSAGP). <h3>Methods</h3> We reproduced the Holmich protocol of exercise therapy and objectively evaluated its effect on 17 male athletes (mean age, 25.07±4.96 years) suffering from LSAGP, of whom 14 participants completed the 10 weeks treatment period. The study was designed as a single-blinded, before-and-after clinical trial. Main outcome measures included pain, functional ability, hip range of motion (ROM), hip abductor and adductor muscle strength, and successful return to sports activity. <h3>Results</h3> Eleven athletes (78.57%) returned to their sports activities&nbsp;in a mean time of 14.2 weeks (range, 10-20 weeks). Visual analogue scale&nbsp;pain score, hip abductor and adductor muscles strength, and function scores improved significantly. Although hip abduction ROM did not show any significant changes (p = 0.609), the extent of progress in the hip internal rotation ROM was significant (p = 0.001). The ratio of hip adduction to abduction strength did not change significantly (p = 0.309 for the isometric and p = 0.957 for the eccentric ratio). <h3>Conclusions</h3> Exercise therapy according to the Holmich programme may be an effective treatment for LSAGP. However, more emphasis should be paid to the hip adductor muscles’ eccentric strength. <h3>Trial registration number</h3> IRCT2016080829269N1.
Abstract 1505: Tumor associated antigen uptake tracking following immuno-radiotherapy
Authors: Esben Christensen, Lars Ringgaard, Anja Brus, Andreas Kjaer, Anders E. Hansen, Thomas L. Andresen
Journal: Cancer Research (2019)

Abstract Immuno-radiotherapy is a promising strategy for generation of immunologic cancer recognition, rejection and induction of anti-cancer memory. Radiotherapy (RT) causes single or double strand DNA breaks in a dose dependent manner leading to immunogenic cell death of cancer cells and induction of type 1 interferons. Furthermore, RT increases MHCI expression on cancer cells and infiltration of cytotoxic T cells. Combined, these effects make RT a potent primer of anti-cancer immune responses. The most promising approaches in anti-cancer immunotherapy is to augment the adaptive immune response through danger associated molecular patterns signaling, including toll-like receptor (TLR) agonists. Optimally, these interventions should be given when tumor-associated antigen (TAA) uptake and presentation peaks. Previous studies on TAA uptake have mostly focused on in vitro or ex vivo assays to mimic the in vivo mechanisms. In the present study, we investigate the in vivokinetics of TAA uptake and trafficking using stably transfected mCherry-transfected B16F10 melanoma. B16F10 transfected with mCherry, a pH-stable fluorescent protein, allows tracking by e.g. flow cytometry in both cancer cells and phagocytosing populations. In vivo trafficking of mCherry fluorescence was investigated in mice treated with RT alone or in combination with TLR7 agonists given locally or systemically. Following treatment, TAA-uptake, -trafficking, and activation of relevant immune populations was evaluated in tumors or tumor draining lymph nodes (tdLNs). Increased TAA uptake was observed in MHCII high populations compared to MHCII low across all phagocytosing populations in tumors. The highest uptake (MFI of mCherry) was found in patrolling monocytes (CD11b+CD11c-Ly6c-CX3CR1high) and tumor-associated macrophages (CD11b+CD11c+CD64+). Interestingly, we exclusively found increased mCherry signal in resident cDC1s in tdLNs after treatment. RT led to a diminished population of migratory CD103+ cDC1s in tumors and we did not observe any increase in mCherry+ CD103+ cDC1s in tdLNs. We did not observe any mCherry signal in spleens - indicating that no cancer-specific immune response are mounted from the spleen. The results also indicate that TAA antigen is trafficked to tdLNs primarily by monocytes or by lymphatic drainage. Citation Format: Esben Christensen, Lars Ringgaard, Anja Brus, Andreas Kjaer, Anders E. Hansen, Thomas L. Andresen. Tumor associated antigen uptake tracking following immuno-radiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1505.
The cardiovascular safety of oral alitretinoin: a population‐based cohort study involving 19 513 patients exposed to oral alitretinoin*
Authors: F. Poizeau, F. Balusson, A.P. Jonville‐Béra, E. Nowak, M.D. Drici, P.Y. Scarabin, C. Droitcourt, A. Dupuy, E. Oger
Journal: British Journal of Dermatology (2021)

Background Oral alitretinoin is a retinoid used for severe chronic hand eczema. Although caution is recommended for patients with uncontrolled dyslipidaemia or cardiovascular risk factors, the actual atherothrombotic risk has not been investigated thus far. Objectives To detect any excess of atherothrombotic events among patients exposed to alitretinoin, during treatment or in the 2 years following initiation. Methods Using the French Health Insurance database, we compared the number of patients who had an atherothrombotic event (coronary artery disease, ischaemic stroke or peripheral artery disease requiring revascularization) in the population exposed to oral alitretinoin vs. the general population of the same age, sex and baseline cardiovascular risk, using standardized morbidity ratios (SMRs). Results Between 2009 and 2017, 19 513 patients were exposed to oral alitretinoin in France. Sixty-four (0·3%) patients had an atherothrombotic event while on alitretinoin. Patients receiving alitretinoin experienced no more atherothrombotic events than the general population: patients without cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·65 [95% confidence interval (CI) 0·26–1·34] during alitretinoin treatment, and 1·21 (95% CI 0·90–1·59) in the 2 years following initiation; patients with cardiovascular risk factors or previous atherothrombotic events had a SMR of 0·82 (95% CI 0·60–1·08) during alitretinoin treatment and 0·95 (95% CI 0·82–1·09) in the 2 years following initiation. Taken separately, SMRs for each outcome did not increase either. Conclusions These data from an exhaustive nationwide population-based study do not support an increase in the incidence of atherothrombotic events with alitretinoin use, regardless of the baseline cardiovascular risk of the patient.
P02.01 Evaluation of PFS for Pulmonary Adenocarcinoma Patient Treated With EGFR Tyrosine Kinase Inhibitors Using Deep Learning Based on CT Image
Authors: J. Xiong, X. Li, R. Hou, T. Shen, J. Wu, Y. Zhu, X. Fu, J. Zhao
Journal: Journal of Thoracic Oncology (2021)
Gut microbial communities from patients with anorexia nervosa do not influence body weight in recipient germ-free mice
Authors: Elaine M. Glenny, Farnaz Fouladi, Stephanie A. Thomas, Emily C. Bulik-Sullivan, Quyen Tang, Zorka Djukic, Yesel S. Trillo-Ordonez, Anthony A. Fodor, Lisa M. Tarantino, Cynthia M. Bulik, Ian M. Carroll
Journal: Gut Microbes (2021)

Anorexia nervosa (AN) is a psychiatric disorder that presents with profound weight dysregulation, metabolic disturbances, and an abnormal composition of gut microbial communities. As the intestinal microbiota can influence host metabolism, the impact of enteric microbial communities from patients with AN on host weight and adiposity was investigated. Germ-free (GF) mice were colonized with fecal microbiotas from either patients with AN (n = 4) prior to inpatient treatment (AN T1, n = 50 recipient mice), the same 4 patients following clinical renourishment (AN T2, n = 53 recipient mice), or age- and sex-matched non-AN controls (n = 4 human donors; non-AN, n = 50 recipient mice). Biological and fecal microbiota data were analyzed with linear mixed-effects models. Body weight did not differ significantly between AN recipient mice (T1 and T2) and non-AN recipient mice following 4 weeks of colonization. Enteric microbiotas from recipient mice colonized with AN T1 and AN T2 fecal microbiotas were more similar to each other compared with enteric microbiotas from non-AN recipient mice. Specific bacterial families in the Actinobacteria, Bacteroidetes, and Firmicutes phyla were significantly associated with body weight, fat mass, and cecum weight irrespective of the donor group. These data suggest that body weight, fat mass, and cecum weight of colonized GF mice are associated with human fecal microbes and independent of donor AN status, although additional analyses with larger cohorts are warranted.