tbuckley/cabot-search huggingface dataset:
Conformational Transition‐Triggered Disassembly of Therapeutic Peptide Nanomedicine for Tumor Therapy
Authors: Guo‐Qiao Wang, Jia Yang, Da‐Yong Hou, Rui Zheng, Muhetaerjiang Mamuti, Min‐Jie Guo, Zhi Fan, Hong‐Wei An, Hao Wang
Journal: Advanced Healthcare Materials (2021)

Abstract Cationic therapeutic peptides have received widespread attention due to their excellent antibacterial and antitumor properties. However, most of these peptides have undesirable delivery efficiency and high hemolytic toxicity due to the positively charged α ‐helix structure containing many lysine and arginine, which may restrict its in vivo applications. Herein, a conformationally transformed therapeutic peptide Pep‐HCO 3 modified with bicarbonates on guanidine groups is designed. Such a design allows Pep‐HCO 3 ((nap‐RAGLQFPVGRLLRRLLRRLLR) nHCO 3 ) to self‐assemble into nanoparticles ( NP‐Pep ) due to disrupting helix folding and the formation of intermolecular hydrogen bonding between bicarbonates and guanidine groups. When pH is from 7.4 to 6.5 at the tumor sites, guanidine bicarbonate can be hydrolyzed to form CO 2 and guanidine groups, resulting in the disassembling of the NP‐Pep into monomers α ‐Pep with a positively charged α ‐helix structure. In vivo, NP‐Pep not only inhibits the tumor growth of xenografted mice with a twofold enhanced inhibition rate compared with α ‐Pep treatment group, but also significantly reduces the hemolytic toxicity by responding to the pH of tumor microenvironment. Therefore, the strategy of conformational transition‐triggered disassembly of nanoparticles allows efficient delivery of cationic therapeutic peptides and lowering the hemolytic toxicity, which may provide an avenue for developing high‐performance cationic peptide in vivo applications.
Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis
Authors: Javier Martínez, Virginia Hernández-Gea, Enrique Rodríguez-de-Santiago, Luis Téllez, Bogdan Procopet, Álvaro Giráldez, Lucio Amitrano, Candid Villanueva, Dominique Thabut, Luis Ibañez-Samaniego, Gilberto Silva-Junior, Joan Genescà, Christophe Bureau, Jonel Trebicka, Rafael Bañares, Aleksander Krag, Elba Llop, Wim Laleman, Jose María Palazon, Jose Castellote, Susana Rodrigues, Lise L. Gluud, Carlos Noronha-Ferreira, Nuria Cañete, Manuel Rodríguez, Arnulf Ferlitsch, Remy Schwarzer, Jose Luis Mundi, Henning Gronbaek, Manuel Hernández-Guerra, Romano Sassatelli, Alessandra Dell'Era, Marco Senzolo, Juan G. Abraldes, Manuel Romero-Gomez, Alexander Zipprich, Meritxell Casas, Helena Masnou, Massimo Primignani, Frederik Nevens, Jose Luis Calleja, Christian Jansen, Marie Angèle Robic, Irene Conejo, Maria Vega Catalina, Marika Rudler, Edilmar Alvarado, Valeria Perez-Campuzano, Maria Anna Guardascione, Petra Fischer, Jaime Bosch, Juan Carlos García-Pagán, Agustín Albillos
Journal: Journal of Hepatology (2021)
Coordination of escape and spatial navigation circuits orchestrates versatile flight from threats
Authors: Weisheng Wang, Peter J. Schuette, Jun Nagai, Brooke Christine Tobias, Fernando Midea Cuccovia V. Reis, Shiyu Ji, Miguel A.X. de Lima, Mimi Q. La-Vu, Sandra Maesta-Pereira, Meghmik Chakerian, Saskia J. Leonard, Lilly Lin, Amie L. Severino, Catherine M. Cahill, Newton S. Canteras, Baljit S. Khakh, Jonathan C. Kao, Avishek Adhikari
Journal: Neuron (2021)
COVID-19 Infection and Corrected QT Interval Prolongation—Collateral Damage From Our Newest Enemy
Authors: Susan P. Etheridge, S. Yukiko Asaki
Journal: JAMA Network Open (2021)

Geoffrey A. Rubin, MD; Amar D. Desai, BS; Zilan Chai, MS; Aijin Wang, MS; Qixuan Chen, PhD; Amy S. Wang, BS; Cameron Kemal, MD; Haajra Baksh, MBBS; Angelo Biviano, MD; Jose M. Dizon, MD; Hirad Yarmohammadi, MD, MPH; Frederick Ehlert, MD; Deepak Saluja, MD; David A. Rubin, MD; John P. Morrow, MD; Uma Mahesh R. Avula, MD; Jeremy P. Berman, MD; Alexander Kushnir, MD, PhD; Mark P. Abrams, MD; Jessica A. Hennessey, MD, PhD; Pierre Elias, MD; Timothy J. Poterucha, MD; Nir Uriel, MD, MS; Christine J. Kubin, PharmD; Elijah LaSota, BS; Jason Zucker, MD; Magdalena E. Sobieszczyk, MD, MPH; Allan Schwartz, MD; Hasan Garan, MD; Marc P. Waase, MD, PhD; Elaine Y. Wan, MD
Immunometabolic responses according to physical fitness status and lifelong exercise during aging: New roads for exercise immunology
Authors: Camila S. Padilha, Caique Figueiredo, Luciele Guerra Minuzzi, Patricia Chimin, Rafael Deminice, Karsten Krüger, José Cesar Rosa-Neto, Fabio Santos Lira
Journal: Ageing Research Reviews (2021)
Role of Cardiac CT in Pre-Procedure Planning for Transcatheter Mitral Valve Replacement
Authors: Yin Ge, Sumit Gupta, Emilio Fentanes, Ayaz Aghayev, Michael Steigner, Piotr Sobieszczyk, Tsuyoshi Kaneko, Marcelo F Di Carli, Deepak L Bhatt, Pinak Shah, Ron Blankstein
Journal: JACC. Cardiovascular imaging (2021)
Persistent variations of blood DNA methylation associated with treatment exposures and risk for cardiometabolic outcomes in long-term survivors of childhood cancer in the St. Jude Lifetime Cohort
Authors: Nan Song, Chia-Wei Hsu, Haitao Pan, Yinan Zheng, Lifang Hou, Jin-ah Sim, Zhenghong Li, Heather Mulder, John Easton, Emily Walker, Geoffrey Neale, Carmen L. Wilson, Kirsten K. Ness, Kevin R. Krull, Deo Kumar Srivastava, Yutaka Yasui, Jinghui Zhang, Melissa M. Hudson, Leslie L. Robison, I-Chan Huang, Zhaoming Wang
Journal: Genome Medicine (2021)

It is well-established that cancer treatment substantially increases the risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify the DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions.
Effects of a multi-faceted education and support programme on anxiety symptoms among people with systemic sclerosis and anxiety during COVID-19 (SPIN-CHAT): a two-arm parallel, partially nested, randomised, controlled trial
Authors: Brett D Thombs, Linda Kwakkenbos, Brooke Levis, Angelica Bourgeault, Richard S Henry, Alexander W Levis, Sami Harb, Lydia Tao, Marie-Eve Carrier, Laura Bustamante, Delaney Duchek, Laura Dyas, Ghassan El-Baalbaki, Kelsey Ellis, Danielle B Rice, Amanda Wurz, Julia Nordlund, Maria Gagarine, Kimberly A Turner, Nora Østbø, Nicole Culos-Reed, Shannon Hebblethwaite, Scott Patten, Susan J Bartlett, John Varga, Luc Mouthon, Sarah Markham, Michael S Martin, Andrea Benedetti
Journal: The Lancet Rheumatology (2021)
A Single-arm, Multicenter, Phase 2 Study of Lenvatinib Plus Everolimus in Patients with Advanced Non-Clear Cell Renal Cell Carcinoma
Authors: Thomas E. Hutson, M. Dror Michaelson, Timothy M. Kuzel, Neeraj Agarwal, Ana M. Molina, James J. Hsieh, Ulka N. Vaishampayan, Ran Xie, Urmi Bapat, Weifei Ye, Rohit K. Jain, Mayer N. Fishman
Journal: European Urology (2021)

Non-clear cell renal cell carcinoma (nccRCC) accounts for ≤20% of RCC cases. Lenvatinib (a multitargeted tyrosine kinase inhibitor) in combination with everolimus (an mTOR inhibitor) is approved for the treatment of advanced RCC after one prior antiangiogenic therapy.To determine the safety and efficacy of lenvatinib plus everolimus as a first-line treatment for patients with advanced nccRCC.This open-label, single-arm, multicenter, phase 2 study enrolled patients with unresectable advanced or metastatic nccRCC and no prior anticancer therapy for advanced disease.Lenvatinib (18 mg) plus everolimus (5 mg) orally once daily.The primary endpoint was the objective response rate (ORR) as assessed by investigators according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety assessments. The 95% confidence intervals (CIs) for ORRs were calculated using the two-sided Clopper-Pearson method. Median PFS and median OS were estimated using the Kaplan-Meier product-limit method and their 95% CIs were estimated via a generalized Brookmeyer and Crowley method.The study (start date: February 20, 2017) enrolled 31 patients with nccRCC (papillary, n = 20; chromophobe, n = 9; unclassified, n = 2). At the data cutoff date (July 17, 2019), the best overall response was a partial response (eight patients: papillary, n = 3; chromophobe, n = 4; unclassified, n = 1) for an overall ORR of 26% (95% CI 12-45). Median PFS was 9.2 mo (95% CI 5.5-not estimable), and median OS was 15.6 mo (95% CI 9.2-not estimable). The most common treatment-emergent adverse events were fatigue (71%), diarrhea (58%), decreased appetite (55%), nausea (55%), and vomiting (52%). Limitations include the small sample size and single-arm design.Lenvatinib plus everolimus showed promising anticancer activity in patients with advanced nccRCC with an ORR of 26% and is worthy of further study. The safety profile was consistent with the established profile of the study-drug combination.We examined the combination of lenvatinib plus everolimus as the first therapy for 31 patients who had advanced nccRCC. We found that this treatment seemed effective, because most patients had a decrease in tumor size and manageable treatment-related side effects.This trial is registered at ClinicalTrials.Gov as NCT02915783.
Distinct cellular immune profiles in the airways and blood of critically ill patients with COVID-19
Authors: Anno Saris, Tom D Y Reijnders, Esther J Nossent, Alex R Schuurman, Jan Verhoeff, Saskia van Asten, Hetty Bontkes, Siebe Blok, Janwillem Duitman, Harm-Jan Bogaard, Leo Heunks, Rene Lutter, Tom van der Poll, Juan J Garcia Vallejo
Journal: Thorax (2021)

Knowledge of the pathophysiology of COVID-19 is almost exclusively derived from studies that examined the immune response in blood. We here aimed to analyse the pulmonary immune response during severe COVID-19 and to compare this with blood responses.This was an observational study in patients with COVID-19 admitted to the intensive care unit (ICU). Mononuclear cells were purified from bronchoalveolar lavage fluid (BALF) and blood, and analysed by spectral flow cytometry; inflammatory mediators were measured in BALF and plasma.Paired blood and BALF samples were obtained from 17 patients, four of whom died in the ICU. Macrophages and T cells were the most abundant cells in BALF, with a high percentage of T cells expressing the ƴδ T cell receptor. In the lungs, both CD4 and CD8 T cells were predominantly effector memory cells (87·3% and 83·8%, respectively), and these cells expressed higher levels of the exhaustion marker programmad death-1 than in peripheral blood. Prolonged ICU stay (>14 days) was associated with a reduced proportion of activated T cells in peripheral blood and even more so in BALF. T cell activation in blood, but not in BALF, was higher in fatal COVID-19 cases. Increased levels of inflammatory mediators were more pronounced in BALF than in plasma.The bronchoalveolar immune response in COVID-19 has a unique local profile that strongly differs from the immune profile in peripheral blood. Fully elucidating COVID-19 pathophysiology will require investigation of the pulmonary immune response.
Natural killer cell receptors regulate responses of HLA-E–restricted T cells
Authors: Lucy C. Sullivan, Thi H.O. Nguyen, Christopher M. Harpur, Sanda Stankovic, Abbie R. Kanagarajah, Marios Koutsakos, Philippa M. Saunders, Zhangying Cai, James A. Gray, Jacqueline M.L. Widjaja, Jie Lin, Gabriella Pietra, Maria Cristina Mingari, Lorenzo Moretta, Jerome Samir, Fabio Luciani, Glen P. Westall, Karl J. Malmberg, Katherine Kedzierska, Andrew G. Brooks
Journal: Science Immunology (2021)

CMV-specific, HLA-E–restricted T cell responses to both cognate and self-antigen are fine-tuned by the expression of NK cell receptors.
For-Profit Enterprise in Health Care
Authors: Bradford H. Gray, Walter J. McNerney
Journal: New England Journal of Medicine (1986)

Health care is undergoing a major and often troubling transition. The once dominant structure of community not-for-profit hospitals and their independent, largely solo-practitioner medical staffs has undergone many organizational transformations. Multi-institutional systems have proliferated. Solo medical practitioners have become the exception, and a wave of physician entrepreneurship, often involving economic arrangements with health care institutions, has provoked concern about conflict of interest and fiduciary responsibility. New types of entities, ranging from ambulatory care centers to preferred provider organizations, have been created. Old boundaries are blurring as organizations increasingly provide different levels of care, become involved in both financing and providing . . .
Effectiveness of treatments for acute and subacute mechanical non-specific low back pain: a systematic review with network meta-analysis
Authors: Silvia Gianola, Silvia Bargeri, Gabriele Del Castillo, Davide Corbetta, Andrea Turolla, Anita Andreano, Lorenzo Moja, Greta Castellini
Journal: British Journal of Sports Medicine (2021)

Objective To assess the effectiveness of interventions for acute and subacute non-specific low back pain (NS-LBP) based on pain and disability outcomes. Design A systematic review of the literature with network meta-analysis. Data sources Medline, Embase and CENTRAL databases were searched from inception until 17 October 2020. Eligibility criteria for selecting studies Randomised clinical trials (RCTs) involving adults with NS-LBP who experienced pain for less than 6 weeks (acute) or between 6 and 12 weeks (subacute). Results Forty-six RCTs (n=8765) were included; risk of bias was low in 9 trials (19.6%), unclear in 20 (43.5%), and high in 17 (36.9%). At immediate-term follow-up, for pain decrease, the most efficacious treatments against an inert therapy were: exercise (standardised mean difference (SMD) −1.40; 95% confidence interval (CI) −2.41 to –0.40), heat wrap (SMD −1.38; 95% CI −2.60 to –0.17), opioids (SMD −0.86; 95% CI −1.62 to –0.10), manual therapy (SMD −0.72; 95% CI −1.40 to –0.04) and non-steroidal anti-inflammatory drugs (NSAIDs) (SMD −0.53; 95% CI −0.97 to –0.09). Similar findings were confirmed for disability reduction in non-pharmacological and pharmacological networks, including muscle relaxants (SMD -0.24; 95% CI -0.43 to -0.04). Mild or moderate adverse events were reported in the opioids (65.7%), NSAIDs (54.3%) and steroids (46.9%) trial arms. Conclusion With uncertainty of evidence, NS-LBP should be managed with non-pharmacological treatments which seem to mitigate pain and disability at immediate-term. Among pharmacological interventions, NSAIDs and muscle relaxants appear to offer the best harm–benefit balance.
Association of Plasmodium falciparum kelch13 R561H genotypes with delayed parasite clearance in Rwanda: an open-label, single-arm, multicentre, therapeutic efficacy study
Authors: Aline Uwimana, Noella Umulisa, Meera Venkatesan, Samaly S Svigel, Zhiyong Zhou, Tharcisse Munyaneza, Rafiki M Habimana, Anicet Rucogoza, Leah F Moriarty, Ryan Sandford, Emily Piercefield, Ira Goldman, Bryan Ezema, Eldin Talundzic, M Andreína Pacheco, Ananias A Escalante, Daniel Ngamije, Jean-Louis N Mangala, Michee Kabera, Kaendi Munguti, Monique Murindahabi, William Brieger, Clarisse Musanabaganwa, Leon Mutesa, Venkatachalam Udhayakumar, Aimable Mbituyumuremyi, Eric S Halsey, Naomi W Lucchi
Journal: The Lancet Infectious Diseases (2021)
Abstract 14845: Diuretic Efficiency is Higher for Black Subjects Enrolled in Acute Decompensated Heart Failure Trials
Authors: Alanna A Morris, Aditi Nayak, Yi-An Ko, Michael Felker, Margaret M Redfield, Jeffrey M Testani, Javed Butler
Journal: Circulation (2019)

Introduction: African-Americans (AA) are more likely to have HF hospitalization than other race/ethnic groups. Diuretic efficiency (DE), a measure of the efficiency with which the kidneys produce u...
Cytokine Storm
Authors: Philip A Mudd, Jeremy C Crawford, Paul G Thomas
Journal: New England Journal of Medicine (2021)

To the Editor: In their review article on cytokine storm, Fajgenbaum and June (Dec.3 issue) 1 include a discussion of signaling by mitogenactivated protein kinase (MAPK), nuclear factor κB, and mammalian target of rapamycin.We feel compelled to point out one major omission that has a clear therapeutic effect for cytokine storm in general and for therapies for coronavirus disease 2019 (Covid-19) in particular: the p38 MAPK-MAPKAPK2 pathway.3][4] Covid-19 infection has been shown to lead to phosphorylation and activation of p38 MAPK. 5 Therefore, small-molecule inhibitors of p38 MAPK (e.g., losmapimod) and of the p38 MAPK-MAPKAPK2 signaling complex (e.g., ATI-450) are currently in clinical trials as anti-Covid-19 therapeutics (ClinicalTrials.govnumbers, NCT04511819 and NCT04481685, respectively).These two drugs are expected to show efficacy that extends beyond that seen with single monotherapies directed at individual cytokines alone.
Perspectives on outpatient administration of CAR-T cell therapy in aggressive B-cell lymphoma and acute lymphoblastic leukemia
Authors: G Doug Myers, Michael R Verneris, Andre Goy, Richard T Maziarz
Journal: Journal for ImmunoTherapy of Cancer (2021)

Chimeric antigen receptor (CAR) T-cell therapies that specifically target the CD19 antigen have emerged as a highly effective treatment option in patients with refractory B-cell hematological malignancies. Safety and efficacy outcomes from the pivotal prospective clinical trials of axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel and the retrospective, postmarketing, real-world analyses have confirmed high response rates and durable remissions in patients who had failed multiple lines of therapy and had no meaningful treatment options. Although initially administered in the inpatient setting, there has been a growing interest in delivering CAR-T cell therapy in the outpatient setting; however, this has not been adopted as standard clinical practice for multiple reasons, including logistic and reimbursement issues. CAR-T cell therapy requires a multidisciplinary approach and coordination, particularly if given in an outpatient setting. The ability to monitor patients closely is necessary and proper protocols must be established to respond to clinical changes to ensure efficient, effective and rapid evaluation either in the clinic or emergency department for management decisions regarding fever, sepsis, cytokine release syndrome and neurological events, specifically immune effector cell-associated neurotoxicity syndrome. This review presents the authors' institutional experience with the preparation and delivery of outpatient CD19-directed CAR-T cell therapy.
A novel and highly effective mitochondrial uncoupling drug in T-cell leukemia
Authors: Victoria da Silva-Diz, Bin Cao, Olga Lancho, Eric Chiles, Amer Alasadi, Maya Aleksandrova, Shirley Luo, Amartya Singh, Hanlin Tao, David Augeri, Sonia Minuzzo, Stefano Indraccolo, Hossein Khiabanian, Xiaoyang Su, Shengkan Jin, Daniel Herranz
Journal: Blood (2021)
The changing epidemiology of Plasmodium vivax: Insights from conventional and novel surveillance tools
Authors: Sarah Auburn, Qin Cheng, Jutta Marfurt, Ric N. Price
Journal: PLoS Medicine (2021)

Renewed efforts to eliminate malaria have had greater impact on Plasmodium fAU : Pleasenotethatasp alciparum than Plasmodium vivax, a reflection of the fundamental differences in the biology of the parasite, its transmission dynamics, and ability to form dormant liver stages.• The main burden of P. vivax malaria is in young children residing in remote communities with poor access to healthcare services.• The decline in P. vivax malaria has led to an increasing proportion of the parasite reservoir occurring in asymptomatic and low-density P. vivax infections and heterogeneous patterns of parasite transmission.• Genetic tools to study the spatial and temporal patterns of P. vivax transmission in different endemicities and ultrasensitive PCR (uPCR)-based techniques are expanding our knowledge of the magnitude and biology of low-density P. vivax infections.• Serology offers alternative ways of detecting recent P. vivax infections and monitoring of the impact of public health interventions at very low endemicity.
The methodological quality of individual participant data meta-analysis on intervention effects: systematic review
Authors: Huan Wang, Yancong Chen, Yali Lin, Julius Abesig, Irene XY Wu, Wilson Tam
Journal: BMJ (2021)

Abstract Objective To assess the methodological quality of individual participant data (IPD) meta-analysis and to identify areas for improvement. Design Systematic review. Data sources Medline, Embase, and Cochrane Database of Systematic Reviews. Eligibility criteria for selecting studies Systematic reviews with IPD meta-analyses of randomised controlled trials on intervention effects published in English. Results 323 IPD meta-analyses covering 21 clinical areas and published between 1991 and 2019 were included: 270 (84%) were non-Cochrane reviews and 269 (84%) were published in journals with a high impact factor (top quarter). The IPD meta-analyses showed low compliance in using a satisfactory technique to assess the risk of bias of the included randomised controlled trials (43%, 95% confidence interval 38% to 48%), accounting for risk of bias when interpreting results (40%, 34% to 45%), providing a list of excluded studies with justifications (32%, 27% to 37%), establishing an a priori protocol (31%, 26% to 36%), prespecifying methods for assessing both the overall effects (44%, 39% to 50%) and the participant-intervention interactions (31%, 26% to 36%), assessing and considering the potential of publication bias (31%, 26% to 36%), and conducting a comprehensive literature search (19%, 15% to 23%). Up to 126 (39%) IPD meta-analyses failed to obtain IPD from 90% or more of eligible participants or trials, among which only 60 (48%) provided reasons and 21 (17%) undertook certain strategies to account for the unavailable IPD. Conclusions The methodological quality of IPD meta-analyses is unsatisfactory. Future IPD meta-analyses need to establish an a priori protocol with prespecified data syntheses plan, comprehensively search the literature, critically appraise included randomised controlled trials with appropriate technique, account for risk of bias during data analyses and interpretation, and account for unavailable IPD.
Implant Surface Texture and Breast Cancer Recurrence—Reply
Authors: Kyeong-Tae Lee, Sa Ik Bang
Journal: JAMA Surgery (2021)

In Reply We deeply appreciate valuable comments provided by de Andrade Urban et al, Bijlard and Mureau, and Maarse and Teunis in response to our study.1 Thankfully, they addressed several critical points that had not been fully considered during preparation of our original study.