tbuckley/cabot-search huggingface dataset:
Minimal Residual Disease in Myeloma: Application for Clinical Care and New Drug Registration
Authors: Kenneth C. Anderson, Daniel Auclair, Stacey J. Adam, Amit Agarwal, Melissa Anderson, Hervé Avet-Loiseau, Mark Bustoros, Jessica Chapman, Dana E. Connors, Ajeeta Dash, Alessandra Di Bacco, Ling Du, Thierry Facon, Juan Flores-Montero, Francesca Gay, Irene M. Ghobrial, Nicole J. Gormley, Ira Gupta, Howard Higley, Jens Hillengass, Bindu Kanapuru, Dickran Kazandjian, Gary J. Kelloff, Ilan R. Kirsch, Brandon Kremer, Ola Landgren, Elizabeth Lightbody, Oliver C. Lomas, Sagar Lonial, María-Victoria Mateos, Rocio Montes de Oca, Lata Mukundan, Nikhil C. Munshi, Elizabeth K. O'Donnell, Alberto Orfao, Bruno Paiva, Reshma Patel, Trevor J. Pugh, Karthik Ramasamy, Jill Ray, Mikhail Roshal, Jeremy A. Ross, Caroline C. Sigman, Katie L. Thoren, Suzanne Trudel, Gary Ulaner, Nancy Valente, Brendan M. Weiss, Elena Zamagni, Shaji K. Kumar
Journal: Clinical Cancer Research (2021)

The development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow-based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy-based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid-based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.
Agricultural Pesticides and Shingles Risk in a Prospective Cohort of Licensed Pesticide Applicators
Authors: Christine G. Parks, Jonathan N. Hofmann, Laura E. Beane Freeman, Dale P. Sandler
Journal: Environmental Health Perspectives (2021)

Some pesticides are immunotoxic and have been associated with an increased risk of immune-mediated diseases. The risk of shingles, the clinical reactivation of varicella-zoster virus, increases with aging and immunosuppression; little is known about its associations with pesticides.We examined the use of agricultural pesticides in relation to incident shingles in a prospective cohort of licensed pesticide applicators.The study sample included 12,820 (97% male) farmers (enrolled in 1993-1997 in North Carolina and Iowa), who were followed for a median of 12 y (interquartile range: 11-13). Shingles was self-reported at enrollment and at follow-up. We evaluated ever-use of 48 agricultural pesticides reported at study enrollment in relation to shingles risk and considered exposure-response for intensity-weighted lifetime days (IWLDs) of use. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models, adjusting for state, and allowing estimates to vary by median attained age (60 y).Incident shingles was reported by 590 participants. Associations were positive (HRs>1.2) for ever- vs. never-use of eight insecticides, three fumigants, two fungicides, and five herbicides, and exposure-response trends were seen across increasing quartiles (Q3 and Q4>Q1) or tertiles (T3 and T2>T1) of IWLDs for four insecticides [permethrin (crops), coumaphos, malathion, and lindane], two fumigants (carbon tetrachloride/carbon disulfide and methyl bromide), and three herbicides [alachlor, trifluralin (<60 years of age) and 2,4-dichlorophenoxyacetic acid]. Shingles was not associated with total years or days per year mixed or applied any pesticides, but in older participants, shingles was associated with a history of a high pesticide exposure event [HR=1.89 (95% CI: 1.45, 2.45)].Several specific pesticides were associated with increased risk of shingles in farmers, especially at higher levels of cumulative use. These novel findings, if replicated in other populations, could have broader implications for the potential effects of pesticides on vaccine efficacy and susceptibility to other infections. https://doi.org/10.1289/EHP7797.
The newly discovered role of endocytosis in artemisinin resistance
Authors: Hannah Michaela Behrens, Sabine Schmidt, Tobias Spielmann
Journal: Medicinal Research Reviews (2021)

Abstract Artemisinin and its derivatives (ART) are the cornerstone of malaria treatment as part of artemisinin combination therapy (ACT). However, reduced susceptibility to artemisinin as well as its partner drugs threatens the usefulness of ACTs. Single point mutations in the parasite protein Kelch13 (K13) are necessary and sufficient for the reduced sensitivity of malaria parasites to ART but several alternative mechanisms for this resistance have been proposed. Recent work found that K13 is involved in the endocytosis of host cell cytosol and indicated that this is the process responsible for resistance in parasites with mutated K13. These studies also identified a series of further proteins that act together with K13 in the same pathway, including previously suspected resistance proteins such as UBP1 and AP‐2μ. Here, we give a brief overview of artemisinin resistance, present the recent evidence of the role of endocytosis in ART resistance and discuss previous hypotheses in light of this new evidence. We also give an outlook on how the new insights might affect future research.
The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration
Authors: Xiaoxi Lv, Chang Liu, Shanshan Liu, Yunxuan Li, Wanyu Wang, Ke Li, Fang Hua, Bing Cui, Xiaowei Zhang, Jiaojiao Yu, Jinmei Yu, ZhuoWei Hu
Journal: Acta Pharmaceutica Sinica B (2021)

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.
The Initial and Followed Results of Endovascular Interventional Therapy for Central Venous Stenosis or Occlusion with Hemodialysis Patients
Authors: Horita Yuki, Namura Masanobu, Ikeda Masatoshi, Terai Hidenobu, Inoki Isao, Kimura Ryusuke, Uchiyama Katsuharu, Tama Naoto, Takagi Toshimitsu
Journal: Circulation (2014)
Abrogation of HnRNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8+ T cell-mediated ferroptosis in castration-resistant prostate cancer
Authors: Xumin Zhou, Libin Zou, Hangyu Liao, Junqi Luo, Taowei Yang, Jun Wu, Wenbin Chen, Kaihui Wu, Shengren Cen, Daojun Lv, Fangpeng Shu, Yu Yang, Chun Li, Bingkun Li, Xiangming Mao
Journal: Acta Pharmaceutica Sinica B (2021)

Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
Tanycytic networks mediate energy balance by feeding lactate to glucose-insensitive POMC neurons
Authors: Tori Lhomme, Jerome Clasadonte, Monica Imbernon, Daniela Fernandois, Florent Sauve, Emilie Caron, Natalia da Silva Lima, Violeta Heras, Ines Martinez-Corral, Helge Mueller-Fielitz, Sowmyalakshmi Rasika, Markus Schwaninger, Ruben Nogueiras, Vincent Prevot
Journal: Journal of Clinical Investigation (2021)

Hypothalamic glucose sensing enables an organism to match energy expenditure and food intake to circulating levels of glucose, the main energy source of the brain. Here, we established that tanycytes of the arcuate nucleus of the hypothalamus, specialized glia that line the wall of the third ventricle, convert brain glucose supplies into lactate that they transmit through monocarboxylate transporters to arcuate proopiomelanocortin neurons, which integrate this signal to drive their activity and to adapt the metabolic response to meet physiological demands. Furthermore, this transmission required the formation of extensive connexin-43 gap junction–mediated metabolic networks by arcuate tanycytes. Selective suppression of either tanycytic monocarboxylate transporters or gap junctions resulted in altered feeding behavior and energy metabolism. Tanycytic intercellular communication and lactate production are thus integral to the mechanism by which hypothalamic neurons that regulate energy and glucose homeostasis efficiently perceive alterations in systemic glucose levels as a function of the physiological state of the organism.
Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis (vol 41, pg 228, 2009)
Authors: Yaran Wen, Yang Liu, Yiming Xu, Yiwei Zhao, Rui Hua, Kaibo Wang, Miao Sun, Yuanhong Li, Sen Yang, Xue-Jun Zhang, Roland Kruse, Sven Cichon, Regina C Betz, Markus M Noethen, Maurice Am van Steensel, Michel van Geel, Peter M Steijlen, Daniel Hohl, Marcel Huber, Giles S Dunnill, Cameron Kennedy, Andrew Messenger, Colin S Munro, Alessandro Terrinoni, Alain Hovnanian, Christine Bodemer, Yves de Prost, Amy S Paller, Alan D Irvine, Rod Sinclair, Jack Green, Dandan Shang, Qing Liu, Yang Luo, Li Jiang, Hong-Duo Chen, Wilson H-Y Lo, WH Irwin McLean, Chun-Di He, Xue Zhang
Journal: Nature Genetics (2009)
Pulmonary-to-Systemic Arterial Shunt to Treat Children With Severe Pulmonary Hypertension
Authors: R. Mark Grady, Matthew W. Canter, Fei Wan, Anton A. Shmalts, Ryan D. Coleman, Maurice Beghetti, Rolf M.F. Berger, Maria J. del Cerro Marin, Scott E. Fletcher, Russel Hirsch, Tilman Humpl, D. Dunbar Ivy, Edward C. Kirkpatrick, Thomas J. Kulik, Marilyne Levy, Shahin Moledina, Delphine Yung, Pirooz Eghtesady, Damien Bonnet, S. Melissa Magness, Venus R. Anderson, Mary M. Mullen, Sergey V. Gorbachevsky, Sergey B. Zaets, Meindina G. Haarman, Isabelle Szezepanski
Journal: Journal of the American College of Cardiology (2021)
US life expectancy plunged in 2020, especially in Hispanic and African Americans
Authors: Owen Dyer
Journal: BMJ (2021)

Life expectancy in the United States fell by 1.5 years in 2020 as the covid pandemic battered the country, exposing stark disparities that saw black and Hispanic Americans die at far higher rates than white Americans.

Life expectancy at birth in all Americans fell from 78.8 years in 2019 to 77.3 last year, the US Centers for Disease Control and Prevention reported.1 Among white Americans it fell from 78.8 to 77.6 years, a drop of 1.2 years. Among Hispanic Americans it fell from 81.8 to 78.8 years, a decline of 3.0 years. Among black Americans it fell from 74.7 to 71.8 years, a decline of 2.9 years.

In 2019, white Americans lived an average of 4.1 years longer than black Americans. Last year that gap increased to 5.8 years.

Overall US life expectancy slid …
Central sensitisation: causes, therapies, and terminology – Authors' reply
Authors: Jo Nijs, Steven Z George, Daniel J Clauw, César Fernández-de-las-Peñas, Eva Kosek, Kelly Ickmans, Josué Fernández Carnero, Andrea Polli, Eleni Kapreli, Eva Huysmans, Antonio I Cuesta-Vargas, Ramakrishnan Mani, Mari Lundberg, Laurence Leysen, David Rice, Michele Sterling, Michele Curatolo
Journal: The Lancet Rheumatology (2021)
Comparison of Outcomes after Matched Sibling, Unrelated, or Haploidentical Allogeneic Hematopoietic Cell Transplantations (HCT). a Real World Experience of Gatmo (Grupo Argentino de Trasplante de Médula Ósea)
Authors: Jose Ignacio Ignacio Trucco, Mariano Berro, Maria Marta Rivas, Pablo Gabriel Longo, Juan Jose Garcia, Pablo Andres Garcia, Ana Basquiera, Gonzalo Ariel Ferini, Sebastian Yantorno, Jorge Milone, Silvina Palmer, German Stemmelin, Alejandro Requejo, Gregorio Jaimovich, Adriana Vitriu, Maria Cecilia Foncuberta, Juliana Martinez Rolon, Gustavo Kusminsky
Journal: Blood (2017)
Patient Perspectives on the Lived Experience of Acne and Its Treatment Among Adult Women With Acne
Authors: John S. Barbieri, Rachel Fulton, Rebecca Neergaard, Maria N. Nelson, Frances K. Barg, David J. Margolis
Journal: JAMA Dermatology (2021)

Acne often persists into adulthood in women. However, few studies have specifically explored the lived experience of acne in adult populations.To examine the lived experience of acne and its treatment among a cohort of adult women.A qualitative analysis was conducted from free listing and open-ended, semistructured interviews of patients at a large academic health care system (University of Pennsylvania Health System) and a private practice (Dermatologists of Southwest Ohio). Fifty women 18 to 40 years of age with moderate to severe acne participated in interviews conducted between August 30, 2019, and December 31, 2020.Free-listing data from interviews were used to calculate the Smith S, a measure of saliency for each list item. Semistructured interviews were examined to detect themes about patient perspectives regarding their acne and its treatment.Fifty participants (mean [SD] age, 28 [5.38] years; 24 [48%] White) described acne-related concerns about their appearance that affected their social, professional, and personal lives, with many altering their behavior because of their acne. Depression, anxiety, and social isolation were commonly reported. Participants described successful treatment as having completely clear skin over time or a manageable number of blemishes. Many participants described frustration with finding a dermatologist with whom they were comfortable and with identifying effective treatments for their acne.The results of this qualitative study suggest that women with acne have strong concerns about appearance and experience mental and emotional health consequences and disruption of their personal and professional lives. In addition, many patients describe challenges finding effective treatments and accessing care. Future trials to understand the optimal treatment approaches for women with acne are needed to improve outcomes in this population.
SNO 2020 diversity survey: defining demographics, racial biases, career success metrics and a path forward for the field of neuro-oncology
Authors: Ugonma N Chukwueke, Elizabeth Vera, Alvina Acquaye, Shawn L Hervey-Jumper, Yazmin Odia, Laura J Klesse, Erin Dunbar, Akanksha Sharma, Ekokobe Fonkem, Alissa A Thomas, Tamra E Werbowetski-Ogilvie, Sandra Camelo-Piragua, Na Tosha N Gatson, Macarena I de la Fuente, Terri S Armstrong, Alyx B Porter, Sadhana Jackson
Journal: Neuro-Oncology (2021)

Neuro-oncology has grown tremendously since 2010, marked by increasing society membership, specialized clinical expertise, and new journals. Yet, modest improvement in racial/ethnic diversity amongst clinical trial participants, researchers, and clinicians led us to conduct a survey to identify opportunities to enhance diversity and inclusiveness amongst neuro-oncology professionals.In summer 2020, the Women and Diversity Committee of the Society for Neuro-Oncology (SNO) distributed an anonymous online survey to members and affiliates including the European Association of Neuro-Oncology (EANO), Asian Society for Neuro-Oncology (ASNO), Society for Neuro-Oncology Latin America (SNOLA) and Society for Neuro-Oncology Sub-Saharan Africa (SNOSSA). The survey captured personal and professional characteristics, biases, effective mentorship qualities, career service metrics, and suggested field/society changes. Results were analyzed by geography, profession, age, racial/ethnic, and sexual identity. Standard descriptive statistics characterized the study population.The 386 respondents were predominantly female (58%) with a median age range of 40-49 years (31%), White (65%), and SNO members (97%). Most worked in North America (77%) in a research profession (67%). A majority of White respondents reported never experiencing biases (64%), while the majority of non-White respondents reported unconscious biases/microaggressions, followed by a lack of/limited mentorship. Qualitative assessments showcased that personal/professional success metrics were linked to needed improvements in diversity and inclusion efforts within the neuro-oncology field.The prevalence of racial/ethnic biases and poor mentorship rates amongst underrepresented groups in neuro-oncology is high and potentially linked to the limited diverse representation amongst members and affiliates. These findings warrant a swift implementation of equity and inclusion practices within the neuro-oncology field.
Activation Levels of b-Catenin Signaling in Osteoblasts Define a Threshold for the Development of Myeloid Neoplasia of Variable Severity
Authors: Ioanna Mosialou, Alvaro Cuesta-Dominiguez, Govind Bhagat, Ellin Berman, Azra Raza, Stavroula Kousteni
Journal: Blood (2017)
Benefits of Electroconvulsive Therapy for Patients With Major Depressive Disorder
Authors: Bradley N. Gaynes
Journal: JAMA Network Open (2021)

In this issue of JAMA Network Open, Rönnqvist et al 1 report on a study of the association of electroconvulsive therapy (ECT) with suicide among patients hospitalized with major depressive disorder (MDD).Using population-level data obtained from 2 Swedish national registers (the Swedish National Quality Register for ECT and the Swedish National Inpatient Register), the authors focused on those with moderate or severe depression or severe depression with psychotic symptoms, and they stratified these groups by whether the patients had received ECT or not.Their main outcomes
DIPHTHERIA AND THE ANTITOXIN.
Journal: JAMA (1894)

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Characteristics of the delayed respiratory syncytial virus epidemic, 2020/2021, Rhône Loire, France
Authors: Jean-Sebastien Casalegno, Dominique Ploin, Aymeric Cantais, Elsa Masson, Emilie Bard, Martine Valette, Remi Fanget, Sandrine Couray Targe, Anne-Florence Myar-Dury, Muriel Doret-Dion, Mona Massoud, Gregory Queromes, Philippe Vanhems, Olivier Claris, Marine Butin, Sylvie Pillet, Florence Ader, Sylvie Bin, Alexandre Gaymard, Bruno Lina, Florence Morfin, Etienne Javouhey, Yves Gillet
Journal: Eurosurveillance (2021)

The Rhône-Loire metropolitan areas’ 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged &gt; 3 months to 5 years increased, and cases among adults &gt; 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.
Abstract 11955: Development of in vivo, Tissue-Engineered, Autologous, 3D Heart Valvular Tissue, Type SC Biovalve With Excellent Mechanical Properties, Valular Functions, and in vivo Performances
Authors: Yasuhide Nakayama, Yoshiaki Takewa, Takeshi Moriwaki, Hirohito Sumikura, Shinji Miyamoto, Keitaro Okamoto, Marina Funayama, Maya Furukoshi, Eisuke Tatsumi
Journal: Circulation (2015)

Background: Autologous pericardium is widely used for the reconstruction of intracardiac structures and pulmonary artery, and for aortic valve leaflets after fixation with glutaraldehyde for mechan...