tbuckley/cabot-search huggingface dataset:
Richard Higginson
Authors: Sarah Watson
Journal: BMJ (2021)

The hippocampal formation has been extensively studied for its special role in visual spatial learning and navigation. To ascertain the nature of the associations made, or computations performed, by hippocampus, it is important to delineate the functional contributions of its afferents. Therefore, single units were recorded in the lateral dorsal nucleus of the thalamus (LDN) as rats performed multiple trials on a radial maze. Many LDN neurons selectively discharged when an animal9s head was aligned along particular directions in space, irrespective of its location in the test room. These direction-sensitive cells were localized to the dorsal aspect of the caudal two-thirds of the LDN, the site of innervation by retinal recipient pretectal and intermediate/deep-layer superior colliculus cells (Thompson and Robertson, 1987b). The directional specificity and preference of LDN cells were disrupted if rats were placed on the maze in darkness. If the room light was then turned on, the original preference was restored. If the light was again turned off, directional firing was maintained briefly. Normal directional firing lasted about 2–3 min. After this time, the directional preference (but not specificity) appeared to “rotate” systematically in either the clockwise or counterclockwise direction. The duration of normal directional discharge patterns in darkness could be extended to 30 min by varying the behavior of the animal. LDN cells required visual input to initialize reliable directional firing. After the rat viewed the environment, directional specificity was maintained in the absence of visual cues. Maximal directional firing was achieved only when the rat viewed the entire test room, and not just the scene associated with the directional preference of the cell. Thus, contextual information seems important. Also, a significant correlation was found between directional specificity and errors made on the maze during acquisition of the task. It was concluded that the LDN may pass on to the hippocampal formation directional information that is not merely a reflection of current sensory input. As such, the LDN may serve an important integrative function for limbic spatial learning systems.
Social Interventions and Health Care Utilization for Child Asthma—What’s in a Name?
Authors: Kelly Kelleher, Mattina A. Davenport
Journal: JAMA Pediatrics (2021)

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Clinical Severity Prediction Scores in Low-Resource Settings and the Conundrum of Missing Data
Authors: B. Jason Brotherton, Faith Lelei, Kristina E. Rudd
Journal: JAMA Network Open (2021)

John P. Bonnewell, MD; Matthew P. Rubach, MD; Deng B. Madut, MD; Manuela Carugati, MD; Michael J. Maze, MB, ChB; Kajiru G. Kilonzo, MD; Furaha Lyamuya, MD; Annette Marandu, MD; Nathaniel H. Kalengo, MD; Bingileki F. Lwezaula, MD; Blandina T. Mmbaga, MD; Venance P. Maro, MD; John A. Crump, MD
I’d like to thank . . .
Authors: Abi Rimmer
Journal: BMJ (2021)

We report in this work the expression and characterization of class I molecules expressed as single-chain trimers consisting of an antigenic peptide-spacer-β<sub>2</sub>-microglobulin-spacer H chain. Our results indicate that these single-chain constructs assemble efficiently, maintain their covalent structure, and are unusually stable at the cell surface. Consequently, these constructs are at least 1000-fold less accessible to exogenous peptide than class I molecules loaded with endogenous peptides, and they are potent simulators of peptide-specific CTL and Abs. Our combined findings suggest that single-chain trimers may have applications as DNA vaccines against virus infection or tumors.
Error in Byline
Journal: JAMA Network Open (2021)

Krishna K. Patel, MD, MSc; Carole Decker, RN, PhD; Christina M. Pacheco, JD, MPH; Christine Fuss, RN; Ilham Boda, MD; Kensey L. Gosch, MS; Arthur I. McGhie, MD; Randall C. Thompson, MD; Brett W. Sperry, MD; Timothy M. Bateman, MD; John A. Spertus, MD, MPH
HuR-targeted agents: An insight into medicinal chemistry, biophysical, computational studies and pharmacological effects on cancer models
Authors: Giulia Assoni, Valeria La Pietra, Rosangela Digilio, Caterina Ciani, Nausicaa Valentina Licata, Mariachiara Micaelli, Elisa Facen, Weronika Tomaszewska, Linda Cerofolini, Anna Pérez-Ràfols, Marta Varela Rey, Marco Fragai, Ashwin Woodhoo, Luciana Marinelli, Daniela Arosio, Isabelle Bonomo, Alessandro Provenzani, Pierfausto Seneci
Journal: Advanced Drug Delivery Reviews (2021)
72P Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity
Authors: A. Diab, N. Abdel-Wahab, D.H. Johnson, Y. Hailemichael, W.C. Foo, S-E. Bentebibel, G.A. Lizee, S. Ekmekcioglu
Journal: Annals of Oncology (2021)
Association of Maternal Inflammation During Pregnancy With Birth Outcomes and Infant Growth Among Women With or Without HIV in India
Authors: Mehr Shafiq, Jyoti S. Mathad, Shilpa Naik, Mallika Alexander, Su Yadana, Mariana Araújo-Pereira, Vandana Kulkarni, Prasad Deshpande, Nathella Pavan Kumar, Subash Babu, Bruno B. Andrade, Cheng-Shiun Leu, Saltanat Khwaja, Ramesh Bhosale, Aarti Kinikar, Amita Gupta, Rupak Shivakoti
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The association of elevated levels of specific inflammatory markers during pregnancy with adverse birth outcomes and infant growth could indicate pathways for potential interventions. <h3>Objective</h3> To evaluate whether higher levels of certain inflammatory markers during pregnancy are associated with preterm birth (PTB), low birth weight (LBW), and infant growth deficits. <h3>Design, Setting, and Participants</h3> In this cohort study of pregnant women with or without HIV, 218 mother-infant pairs were followed up from pregnancy through 12 months post partum from June 27, 2016, to December 9, 2019. Pregnant women aged 18 to 40 years and between 13 and 34 weeks of gestation who were receiving antenatal care were enrolled in a cohort stratified by HIV status; sampling was based on convenience sampling from women receiving antenatal care at Byramjee Jeejeebhoy Government Medical College. <h3>Exposures</h3> Levels of multiple circulating inflammation markers during the third trimester of pregnancy. <h3>Main Outcomes and Measures</h3> The primary study outcome was PTB (&lt;37 weeks' gestation). Secondary outcomes were LBW (&lt;2500 g) and repeated measures (delivery; 6 weeks post partum; and 3, 6, and 12 months post partum using multivariable generalized linear models) of infant growth outcomes (length-for-age, weight-for-age, and weight-for-length<i>z</i>scores). <h3>Results</h3> The median age of the 218 women at enrollment was 23 years (IQR, 21-27 years). In multivariable models, higher pregnancy levels of interleukin 17A were associated with increased odds of both PTB (adjusted odds ratio [aOR], 2.62; 95% CI, 1.11-6.17) and LBW (aOR, 1.81; 95% CI, 1.04-3.15). Higher levels of interleukin 1β were associated with increased PTB (aOR, 1.47; 95% CI, 1.15-1.89) and infant growth deficits (lower length-for-age<i>z</i>score: adjusted β = −0.10; 95% CI, −0.18 to −0.01; lower weight-for-age<i>z</i>score: adjusted β = −0.07; 95% CI, −0.14 to 0.001). <h3>Conclusions and Relevance</h3> This study suggests that increased levels of certain systemic inflammatory markers, including interleukin 1β and interleukin 17A, during pregnancy were associated with adverse birth outcomes and infant growth deficits. Future studies should evaluate whether potential interventions to modulate specific inflammatory pathways during pregnancy could improve birth outcomes and infant growth.
4O Nivolumab (NIVO) + ipilimumab (IPI) versus chemotherapy (chemo) as first-line (1L) treatment for advanced NSCLC (aNSCLC) in CheckMate 227 part 1: Efficacy by KRAS, STK11, and KEAP1 mutation status
Authors: S.S. Ramalingam, D. Balli, T-E. Ciuleanu, A. Pluzanski, J-S. Lee, M. Schenker, R. Bernabe Caro, K.H. Lee, R. Bartolucci, C. Audigier-Valette, M.D. Hellmann, L.G. Paz-Ares, M. Reck, H. Borghaei, J.R. Brahmer, K. O’Byrne, P. Tran, T. Spires, W.J. Geese, S. Agrawal
Journal: Annals of Oncology (2021)
Reply to M. K. Bos et al
Authors: Jamie M. Sperger, Felix Y. Feng, Andrew J. Armstrong, Shuang G. Zhao, Joshua M. Lang
Journal: Journal of Clinical Oncology (2021)

Bos et al 1 raise three concerns regarding the results published in our article 2 : (1) tumor cell purity using the VERSA chips for circulating tumor cell (CTC) enrichment, (2) interference from WBCs to detect tumorspecific transcripts, and (3) contribution of CTC enumeration to the gene expression results.With regard to purity, we have published the CTC capture technology that achieved .70% purity 3 as well as RNA and DNA extraction with single-cell resolution 4 that was seamlessly integrated into the VERSA platform. 57][8] The historic alternative to CTCs has been tissue biopsies for bulk molecular profiling, which also does not achieve perfect purity.However, our entire understanding of cancer genomics and transcriptomics is based on studies like these from the The Cancer Genome Atlas program and others. 9A 100% tumor purity is neither a biological requirement nor is it technically feasible for any molecular studies, whether in solid organ biopsy or blood.The VERSA CTC purity is comparable with landmark metastatic biopsy studies in prostate cancer.Bos et al 1 suggest that single-cell sequencing may address their concerns.We agree that single-cell
Abstract 13150: Racial/Ethnic Disparities of the Impact of the COVID-19 Pandemic Out-of-Hospital Cardiac Arrest (OHCA) in Texas
Authors: Summer Chavez, Ryan Huebinger, Kevin Schulz, Hei Kit Chan, Micah Panczyk, Normandy W Villa, Renee Johnson, Robert Greenberg, Veer D Vithalani, Bentley Bobrow
Journal: Circulation (2021)

Introduction: Prior research shows a greater disease burden, lower BCPR rates, and worse outcomes in Black and Hispanic patients after OHCA. The CDC has declared that the COVID-19 pandemic has disproportionately affected many racial and ethnic minority groups. However, the influence of the COVID-19 pandemic on OHCA incidence and outcomes in different races and ethnicities is unknown. Purpose: To describe racial/ethnic disparities in OHCA incidence, processes of care and outcomes in Texas during the COVID-19 pandemic. Methods: We used data from the Texas Cardiac Arrest Registry to Enhance Survival (CARES) comparing adult OHCA from the pre-pandemic period (March 11 - December 31, 2019) to the pandemic period (March 11- December 31, 2020). The racial and ethnic categories were White, Black, Hispanic or Other. Outcomes were rates of BCPR, AED use, sustained ROSC, prehospital termination of resuscitation (TOR), survival to hospital admission, survival to discharge and good neurological outcomes. We fit a mixed effect logistic regression model, with EMS agency designated as the random intercept to obtain aORs. We adjusted for the pandemic and other covariates. Results: A total of 8,070 OHCAs were included. The proportion of cardiac arrests increased for Blacks (903 to 1, 113, 24.9% to 25.5%) and Hispanics (935 to 1,221, 25.8% to 27.5%) and decreased for Whites (1 595 to 1,869, 44.0% to 42.1%) and Other (194 to 220, 5.4% to 5.0%) patients. Compared to Whites, Black (aOR = 0.73, 95% CI 0.65-0.82) and Hispanic patients (aOR = 0.78, 95% CI 0.68-0.87) were less likely to receive BCPR. Compared to Whites, Blacks were less likely to have sustained ROSC (aOR = 0.81, 95% CI 0.70-0.93%), with lower rates of survival to hospital admission (aOR = 0.87, 95% CI 0.75-1.0), and worse neurological outcomes (aOR = 0.45, 95% 0.28-0.73). Hispanics were less likely to have prehospital TOR compared to Whites (aOR = 0.86, 95% CI = 0.75-0.99). The Utstein bystander survival rate was worse for Blacks (aOR = 0.72, 95% CI 0.54-0.97) and Hispanics (aOR = 0.71, 95% 0.53-0.95) compared to Whites. Conclusion: Racial and ethnic disparities persisted during the COVID-19 pandemic in Texas.
Abstract 10975: National Study of In-Hospital Cardiac Arrest in the Emergency Department, 2010-2018
Authors: Tsung-Chien Lu, Chia-Hsin Ko, CHIH-HUNG WANG, Cheng-Chung Fang, Chien-Hua Huang, Wen-Jone Chen, Chu-Lin Tsai
Journal: Circulation (2021)

Introduction: Little is known about in-hospital cardiac arrest (IHCA) in the U.S. emergency department (ED). This study aimed to describe the incidence and mortality of ED-based IHCA visits and to investigate factors associated with higher incidence and poor outcome of IHCA. Hypothesis: We hypothesized that ED-based IHCA contributes to a stable proportion of ED visits and remains a higher mortality rate after the event. Methods: Data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) during 2010 to 2018. Adult ED visits with IHCA were identified using the cardiopulmonary resuscitation code, excluding those with out-of-hospital cardiac arrest. Analysis used descriptive statistics and multivariable logistic regression accounting for NHAMCS's complex survey design. Results: Over the 9-year study period, there was an estimated 1,114,000 ED visits with IHCA and the proportion of IHCA visits in the entire ED population (1.8 per 1,000 ED visits) appeared stable. The mean age of the IHCA visits was 60 years, and 65% were men. Older age, male sex, arrival by ambulance, and being uninsured independently predicted a higher incidence of ED-based IHCA. About 51% of ED-based IHCA died in the ED, and the trend remained stable. Arrival by ambulance, nighttime or weekend arrival, and being in the non-Northeast location were independently associated with a higher mortality rate after IHCA. Conclusions: The high burden of ED visits with IHCA persisted and the outcome remained poor. Some patients were disproportionately affected and certain contextual factors were associated with a poorer outcome.
Pulmonary Innate Lymphoid Cell Responses during Rhinovirus-induced Asthma Exacerbations<i>In Vivo</i>: A Clinical Trial
Authors: Jaideep Dhariwal, Aoife Cameron, Ernie Wong, Malte Paulsen, Maria-Belen Trujillo-Torralbo, Ajerico del Rosario, Eteri Bakhsoliani, Tatiana Kebadze, Mark Almond, Hugo Farne, Leila Gogsadze, Julia Aniscenko, Batika M. J. Rana, Trevor T. Hansel, David J. Jackson, Onn Min Kon, Michael R. Edwards, Roberto Solari, David J. Cousins, Ross P. Walton, Sebastian L. Johnston, Sebastian L. Johnston, Roberto Solari, Michael R. Edwards, Paul Lavender, Ross P. Walton, Hannah Gould, David Cousins, Antoon J. van Oosterhout, Jaideep Dhariwal, Aoife Cameron, Nathan W. Bartlett, Patrick Mallia, David J. Jackson, Maria-Belen Trujillo-Torralbo, Jerico del Rosario, Janet L. Smith, Matthew J. Edwards, Karen Affleck, Nil Turan Jurdzinski, Veronique Birault, Peter McErlean, Yu-Chang Wu, Nadine Upton, Ismael Ranz Jimenez
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Type 2 innate lymphoid cells (ILC2s) are significant sources of type 2 cytokines, which are implicated in the pathogenesis of asthma and asthma exacerbations. The role of ILC2s in virus-induced asthma exacerbations is not well characterized. Objectives: To characterize pulmonary ILC responses following experimental rhinovirus challenge in patients with moderate asthma and healthy subjects. Methods: Patients with moderate asthma and healthy subjects were inoculated with rhinovirus-16 and underwent bronchoscopy at baseline and at Day 3, and Day 8 after inoculation. Pulmonary ILC1s and ILC2s were quantified in bronchoalveolar lavage using flow cytometry. The ratio of bronchoalveolar lavage ILC2:ILC1 was assessed to determine their relative contributions to the clinical and immune response to rhinovirus challenge. Measurements and Main Results: At baseline, ILC2s were significantly higher in patients with asthma than in healthy subjects. At Day 8, ILC2s significantly increased from baseline in both groups, which was significantly higher in patients with asthma than in healthy subjects (all comparisons P < 0.05). In healthy subjects, ILC1s increased from baseline at Day 3 (P = 0.001), while in patients with asthma, ILC1s increased from baseline at Day 8 (P = 0.042). Patients with asthma had significantly higher ILC2:ILC1 ratios at baseline (P = 0.024) and Day 8 (P = 0.005). Increased ILC2:ILC1 ratio in patients with asthma correlated with clinical exacerbation severity and type 2 cytokines in nasal mucosal lining fluid. Conclusions: An ILC2-predominant inflammatory profile in patients with asthma was associated with increased severity and duration of rhinovirus infection compared with healthy subjects, supporting the potential role of ILC2s in the pathogenesis of virus-induced asthma exacerbations.
Reprogramming <i>Mycobacterium Tuberculosis</i> CRISPR System for Gene Editing and Genome-Wide RNA Interference Screening
Authors: Khaista Rahman, Muhammad Jamal, Xi Chen, Wei Zhou, Bin Yang, Yanyan Zou, Weize Xu, Yingying Lei, Chengchao Wu, Xiaojian Cao, Rohit Tyagi, Muhammad Ahsan Naeem, Da Lin, Zeshan Habib, Nan Peng, Zhen F. Fu, Gang Cao
Journal: Genomics Proteomics & Bioinformatics (2021)

Abstract Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), which is still the leading cause of mortality from a single infectious disease worldwide. The development of novel anti-TB drugs and vaccines is severely hampered by the complicated and time-consuming genetic manipulation techniques for M. tuberculosis. Here, we harnessed an endogenous type III-A CRISPR/Cas10 system of M. tuberculosis for efficient gene editing and RNA interference (RNAi). This simple and easy method only needs to transform a single mini-CRISPR array plasmid, thus avoiding the introduction of exogenous protein and minimizing proteotoxicity. We demonstrated that M. tuberculosis genes can be efficiently and specifically knocked in/out by this system as confirmed by DNA high-throughput sequencing. This system was further applied to single- and multiple-gene RNAi. Moreover, we successfully performed genome-wide RNAi screening to identify M. tuberculosis genes regulating in vitro and intracellular growth. This system can be extensively used for exploring the functional genomics of M. tuberculosis and facilitate the development of novel anti-TB drugs and vaccines.
Barriers and facilitators for the inclusion of fertility care in reproductive health policies in Africa: a qualitative evidence synthesis
Authors: Anna Afferri, Haddijatou Allen, Andrew Booth, Susan Dierickx, Allan Pacey, Julie Balen
Journal: Human Reproduction Update (2021)

Infertility affects over 50 million couples worldwide and impacts people's social and emotional wellbeing. In low- and middle-income countries, particularly across Africa, the inclusion of fertility care into reproductive health (RH) policies remains fragmented or non-existent.This review aims to provide a framework for understanding the inclusion (or lack thereof) of fertility care in RH policies in African settings. It synthesizes the barriers and facilitators to such inclusion, with a view to uncovering the positioning of fertility care in broader health systems and on the agendas of key stakeholders such as health policymakers and practitioners.A qualitative evidence synthesis was performed, systematically searching papers and grey literature. Searches were conducted in MEDLINE, EMBASE, CINAHL, Web of Science and Scopus between February and April 2020. No date restrictions were applied. Language was limited to publications written in English and French. Two reviewers independently screened titles and abstracts, and extracted data, applying thematic coding. The quality of the included papers was evaluated using The Joanna Briggs Institute Checklist for Text and Opinion Papers.The search identified 744 papers, of which 20 were included. Findings were organized under four cross-cutting categories, namely: perceived importance of infertility; influence of policy context; resource availability and access; and perceived quality of care. Across these categories, key barriers to the inclusion of fertility care in RH policies were limited political commitment, under-recognition of the burden of infertility and high costs associated with ART. Conversely, facilitators comprised specialized training on infertility for healthcare providers, standard procedures for ART safety and guidelines and North-South/South-South collaborations.The inclusion of fertility care in African RH policies depends upon factors that include the recognition of infertility as a disease, strong political engagement and proactivity and affordability of ART through opportunities for partnership with the private sector, which ease costs on the public health system. Further qualitative and quantitative research, including context-specific analysis and in-depth comparative approaches across diverse African countries, will help to delineate differential impacts of local and global factors on fertility care to address this neglected RH issue.
149P KEYNOTE-629: Efficacy of pembrolizumab (Pembro) per immune-related RECIST (irRECIST) in locally advanced (LA) and recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC)
Authors: E. Munoz Couselo, B.G.M. Hughes, Å. Bratland, R. Gutzmer, O. Roshdy, R. González Mendoza, J. Schachter, A.M. Arance Fernandez, F. Grange, N. Meyer, A.J. Joshi, S. Billan, J.J. Grob, P. Zhang, B. Gumuscu, R. Swaby, L. Mortier
Journal: Annals of Oncology (2021)
A national infrastructure plan for the NHS, social care, and public health is needed to build resilience for the future
Authors: Chris Ham
Journal: BMJ (2021)

A national infrastructure plan for the NHS, social care, and public health is needed to build resilience for the future The time has come to recognise that spare capacity is not a sign of inefficiency, but rather necessary to ensure that public services are prepared for future threats, argues Chris Ham Chris Ham co-chair 1An important and urgent lesson from covid-19 is the need for properly resourced public services able to deal with crises on the scale of the pandemic.Covid will not be the last national emergency of the 20 first century and if any good can come out of the challenges it has created it would be a willingness to prepare more effectively in the future.A national infrastructure plan for the NHS, social care, and public health is overdue to build up capacity in essential public services.
Ten-Day Decitabine with Venetoclax (DEC10-VEN) in Acute Myeloid Leukemia and Myelodysplastic Syndrome: Updated Results of a Phase II Trial
Authors: Abhishek Maiti, Courtney D. DiNardo, Caitlin R. Rausch, Naveen Pemmaraju, Guillermo Garcia-Manero, Maro Ohanian, Naval Daver, Ghayas C. Issa, Gautam Borthakur, Farhad Ravandi, Yesid Alvarado, Tapan M. Kadia, Nicholas J. Short, Elias J. Jabbour, Guillermo Montalban-Bravo, Nitin Jain, Steven M. Kornblau, Lucia Masarova, William G. Wierda, Koji Sasaki, Koichi Takahashi, Musa Yilmaz, Jan A. Burger, Zeev E. Estrov, Srdan Verstovsek, Michael Andreeff, Prithviraj Bose, Alessandra Ferrajoli, Philip A. Thompson, Kathryn Montalbano, Kenneth Vaughan, Carol A. Bivins, Sherry A. Pierce, Wei Qiao, Jing Ning, John Welch, Hagop Kantarjian, Marina Konopleva
Journal: Blood (2021)