tbuckley/cabot-search huggingface dataset:
Queen’s speech “lacks detail” on safe staffing, public health, social care reform, and covid inquiry
Authors: Matthew Limb
Journal: BMJ (2021)

The UK government is facing criticism over gaps in commitments made in the Queen’s speech to improve public health, which included pledges to boost NHS funding, tackle obesity, and “lead the world” in life sciences.

The legislative programme announced on 11 May drew broad support for some health measures but also alarm over what was omitted or only thinly sketched out.1

Leading analysts and professional bodies were dismayed to hear no detailed spending sums to guarantee safe staffing, no new investment programme in public health, no long promised blueprint for social care reform, and no set date for a public inquiry into the handling of covid-19.

Doctors’ leaders and NHS trusts immediately called for sustained funding rises for the NHS and staff, on top of spending detailed in previous settlements, to enable full recovery from the pandemic.

Natasha Curry, deputy director of policy at the Nuffield Trust, echoed a widely …
Distinct immunological signatures discriminate severe COVID-19 from non-SARS-CoV-2-driven critical pneumonia
Authors: Stefanie Kreutmair, Susanne Unger, Nicolás Gonzalo Núñez, Florian Ingelfinger, Chiara Alberti, Donatella De Feo, Sinduya Krishnarajah, Manuel Kauffmann, Ekaterina Friebel, Sepideh Babaei, Benjamin Gaborit, Mirjam Lutz, Nicole Puertas Jurado, Nisar P. Malek, Siri Goepel, Peter Rosenberger, Helene A. Häberle, Ikram Ayoub, Sally Al-Hajj, Jakob Nilsson, Manfred Claassen, Roland Liblau, Guillaume Martin-Blondel, Michael Bitzer, Antoine Roquilly, Burkhard Becher
Journal: Immunity (2021)
自己免疫性肝炎患者におけるプレドニソ(LO)NE投与量と寛解のチャンス【JST・京大機械翻訳】
Authors: Pape Simon, J G Gevers Tom, Belias Michail, F Mustafajev Ilyas, Vrolijk Jan Maarten, van Hoek Bart, Bouma Gerd, M J van Nieuwkerk Carin, Hartl Johannes, Schramm Christoph, W Lohse Ansgar, Taubert Richard, Jaeckel Elmar, P Manns Michael, Papp Maria, Stickel Felix, A Heneghan Michael, P H Drenth Joost
Journal: Clinical Gastroenterology and Hepatology (2019)
Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in <i>BRCA1</i>, <i>BRCA2</i>, or <i>PALB2</i>
Authors: Kim A. Reiss, Rosemarie Mick, Mark H. O'Hara, Ursina Teitelbaum, Thomas B. Karasic, Charles Schneider, Stacy Cowden, Traci Southwell, Janae Romeo, Natallia Izgur, Zain M. Hannan, Rashmi Tondon, Katherine Nathanson, Robert H. Vonderheide, Max M. Wattenberg, Gregory Beatty, Susan M. Domchek
Journal: Journal of Clinical Oncology (2021)

PURPOSE Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline BRCA1 or BRCA2 pathogenic variant (PV). This investigator-initiated, single-arm phase II study assessed the role of the PARPi rucaparib as maintenance therapy in advanced PC with germline or somatic PV in BRCA1, BRCA2, or PALB2. PATIENTS AND METHODS Eligible patients had advanced PC; germline (g) or somatic (s) PVs in BRCA1, BRCA2, or PALB2, and received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was discontinued and patients received rucaparib 600 mg orally twice a day until progression. The primary end point was the progression-free survival (PFS) rate at 6 months (PFS6). Secondary end points included safety, ORR, disease control rate, duration of response, and overall survival. RESULTS Of 46 enrolled patients, 42 were evaluable (27 g BRCA2, seven g BRCA1, six g PALB2, and two s BRCA2). PFS6 was 59.5% (95% CI, 44.6 to 74.4), median PFS was 13.1 months (95% CI, 4.4 to 21.8), and median overall survival was 23.5 months (95% CI, 20 to 27). The PFS at 12 months was 54.8%. ORR of the 36 patients with measurable disease was 41.7% (3 complete responses; 12 partial responses; 95% CI, 25.5 to 59.2), and disease control rate was 66.7% (95% CI, 49.0 to 81.4). Median duration of response was 17.3 months (95% CI, 8.8 to 25.8). Responses occurred in patients with gBRCA2 (41%, 11 out of 27), gPALB2 (50%, 3 out of 6), and sBRCA2 (50%, 1 out of 2). No new safety signals were noted. CONCLUSION Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced PC with a PV in BRCA1, BRCA2, or PALB2. The finding of efficacy in patients with g PALB2 and s BRCA2 PVs expands the population likely to benefit from PARPi beyond g BRCA1/ 2 PV carriers.
Abstract P127: Associations Between Acculturation, Nutrient Intake, And Diet Quality Among Non-hispanic Black Adults In The United States
Authors: Oluwafikayo S Adeyemi, Alexandra M Roehll, Edson Flores, Chelsea R Singleton
Journal: Circulation (2021)

Introduction: Consuming a nutrient poor diet can negatively affect the health status of an individual. Recent increases in African immigration into the U.S. has called for more research on the health and health behaviors of this growing population. Little is known about how acculturation (as measured by place of birth and length of time in the country) affects nutrient intake and diet quality among Non-Hispanic Blacks in the U.S. We aim to address this gap in knowledge by studying the association between acculturation, nutrient intake, and diet quality among a large sample of Non-Hispanic Black adults. Hypothesis: We hypothesize that foreign-born (FB) Blacks who immigrated to the U.S. less than 10 years ago are more likely to meet national recommendations for diet and nutrient intake compared to FB Blacks who immigrated more than 10 years ago and U.S. born Blacks. Methods: We analyzed cross-sectional data from the 2005-2016 cycles of the National Health and Nutrition Examination Survey (NHANES). The analytical sample comprised 7,073 Non-Hispanic Blacks who we categorized into three groups: FB Blacks less than 10 years (3.35%), FB Blacks greater than 10 years (7.42%), and U.S. born Blacks (89.23%). We analyzed each participant’s 24-hour recall data to determine if they met 2015-2020 Dietary Guidelines for Americans (DGA) recommendations for intake of specific nutrients (e.g., saturated fat, fiber, sugar, cholesterol, sodium, etc.). We used logistic regression to assess differences across the three groups in regards to odds of meeting DGA recommendations for nutrient intake. Results: Compared to U.S. born blacks and FB Blacks (≥10 years), FB Blacks (&lt;10 years) had significantly higher odds of meeting DGA recommendations for most nutrients after adjusting for all covariates (e.g., age, gender, education level, poverty level, etc.). Specifically, FB Blacks (&lt;10 years) had significantly higher odds of meeting recommendations for saturated fat (OR: 2.7; 95% CI: 1.6-4.6), cholesterol (OR: 1.7; 95% CI: 1.2-2.5) and sodium intake (OR: 2.2; 95% CI: 1.2-4.3) compared to U.S. born Blacks. FB Blacks (≥ 10 years) had significantly higher odds of meeting recommendations for total fat and dietary fiber compared to U.S. born Blacks. Conclusion: FB Blacks (&lt;10 years) had higher odds of meeting DGA guidelines for nutrient intake compared FB Blacks (≥10 years) and U.S. born Blacks. These findings further highlight the importance of acculturation and its impact on dietary intake among immigrant populations. Future studies should evaluate how acculturation influences overall health status and chronic disease risk across the African diaspora in the U.S.
Abstract 16866: Artificial Neural Networks as Prediction Tools: Predicting Permanent Pacemaker Implantation (PPMI) in Patients Undergoing Transcatheter Aortic Valve Replacement (TAVR) Utilizing a Shallow Feed-Forward Neural Network
Authors: Anshul Parulkar, Wasiq Sheikh, Malik B Ahmed, Sachit Singal, Fabio V Lima, Esseim Sharma, Sanchita S Parulkar, Antony F Chu
Journal: Circulation (2020)

Introduction: Despite increasing TAVR volumes after a series of recent favorable clinical trials, adverse outcomes remain frequent, including new or worsened conduction disease requiring PPMI, life-threatening bleeding, paravalvular leak, and stroke. PPMI carries a reported incidence ranging from 8.8-14.6% and is of particular concern given the increased risk of mortality and rehospitalization. New techniques in signal processing may inform novel statistical approaches to better predict PPMI from a set of clinical variables. Artificial neural networks (ANN) comprise a family of algorithms that utilize non-linear activation functions to enable improved prediction of PPMI in TAVR patients. Objective: To examine the predictive utility of a feed-forward neural network in classifying PPM implantation in patients undergoing TAVR. Methods: Pre and post-operative data from a single institution were collected for all patients undergoing TAVR without prior pacemaker implantation from January 2016 to December 2019. Data was imported into Matlab, partitioned into training, validation, and test sets, and processed in a two-layer feed-forward neural network with sigmoid hidden and softmax output neurons. Performance data included confusion matrices and receiver operating characteristic (ROC) curves. Results: The total sample size for the cohort was 513 patients with a PPMI incidence of 8.6%. The training set contained 40 variables and 359 patients, while the validation and test sets contained 77 patients each. The final optimized model showed cross-entropy of 0.25 with 6 iterations and an area under ROC curve of 0.73. Overall model accuracy was 92.7% in the validation set and 88.3% in the test set. Conclusions: In summary, we show that feed-forward neural networks can be useful in processing multiple interdependent variables to aid clinical prediction. Our network demonstrated modest discriminatory ability in predicting the need for PPMI after TAVR.
Successful use of two guidewires with different properties using a double-lumen catheter for postoperative biliary stricture
Authors: Mamoru Takenaka, Tomohiro Yamazaki, Yasuo Otsuka, Rei Ishikawa, Masatoshi Kudo
Journal: Endoscopy (2021)

The drainage of nonphysiological postoperative biliary stricture is often challenging as the severe degree of stenosis and bending make insertion of a guidewire and catheter difficult [1] [2] [3] [4].
Diverse immune response of DNA damage repair-deficient tumors
Authors: Tao Qing, Tomi Jun, Katherine E. Lindblad, Amaia Lujambio, Michal Marczyk, Lajos Pusztai, Kuan-lin Huang
Journal: Cell Reports Medicine (2021)

Tumors with DNA damage repair (DDR) deficiency accumulate genomic alterations that may serve as neoantigens and increase sensitivity to immune checkpoint inhibitor. However, over half of DDR-deficient tumors are refractory to immunotherapy, and it remains unclear which mutations may promote immunogenicity in which cancer types. We integrate deleterious somatic and germline mutations and methylation data of DDR genes in 10,080 cancers representing 32 cancer types and evaluate the associations of these alterations with tumor neoantigens and immune infiltrates. Our analyses identify DDR pathway mutations that are associated with higher neoantigen loads, adaptive immune markers, and survival outcomes of immune checkpoint inhibitor-treated animal models and patients. Different immune phenotypes are associated with distinct types of DDR deficiency, depending on the cancer type context. The comprehensive catalog of immune response-associated DDR deficiency may explain variations in immunotherapy outcomes across DDR-deficient cancers and facilitate the development of genomic biomarkers for immunotherapy.
Covid-19: Fever, chills, and aches more common when AstraZeneca and Pfizer vaccines are mixed, early data show
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Covid-19: Fever, chills, and aches more common when AstraZeneca and Pfizer vaccines are mixed, early data show Gareth IacobucciMixing doses of the Oxford AstraZeneca and the Pfizer BioNTech covid-19 vaccine leads to more frequent mild to moderate reactions compared with standard dosing schedules, researchers have reported.Researchers running the University of Oxford led Com-COV study-which is investigating the reactogenicity and immunogenicity from mixing doses of the two vaccines-reported their preliminary results in a peer reviewed research letter in the Lancet. 1 1 Heterologous prime-boost covid-19 vaccination: initial reactogenicity data.May 2021.www.
Mutant SETBP1 enhances NRAS-driven MAPK pathway activation to promote aggressive leukemia
Authors: Sarah A. Carratt, Theodore P. Braun, Cody Coblentz, Zachary Schonrock, Rowan Callahan, Brittany M. Curtiss, Lauren Maloney, Amy C. Foley, Julia E. Maxson
Journal: Leukemia (2021)
Abstract P094: Food Insecurity And Elevated Blood Pressure In The Eastern Caribbean
Authors: Carol R Oladele, Josefa Martinez, Marcella Nunez-Smith
Journal: Circulation (2021)

Background: Food insecurity (FI), an economic or social condition of limited or uncertain access to adequate food, has emerged as a contributing factor in the development and poor management of chronic diseases. The Caribbean region faces serious challenges from FI that threaten the sustainability of food systems and health of populations. Increased FI has led to greater consumption of unhealthy, cheap, and calorie dense foods that are associated with elevated blood pressure. The demonstrated challenges with FI, increased prevalence of elevated blood pressure, and dearth of evidence in part of the region make it imperative to understand the relationship between FI and elevated blood pressure. Methods: We used baseline data (2013-2018) from the Eastern Caribbean Health Outcomes Research Network Cohort Study (ECS), a population-based cohort of 2,961 community-dwelling individuals 40 years or older residing in Barbados, Puerto Rico, Trinidad and Tobago, or U.S. Virgin Islands. Participants with complete FI and blood pressure data were included. Household FI within the past 90 days was measured using the 9-item Latin American and Caribbean Food Security Scale. Responses were summed for participants to create a score (0-8) and create four categories: 0 no FI, 1-6 -mild FI, and 7-8 severe FI. The outcome, elevated blood pressure, was defined as self-report of hypertension diagnosis or systolic blood =&gt;140 mm Hg or diastolic pressure =&gt;90 mm Hg. Chi-square tests, analysis of variance, and multivariable logistic regression was used for analyses. We hypothesized that FI was greater among women compared to men, those with lower versus higher educational attainment, and that FI was associated with elevated blood pressure. Results: A total of 2942 participants were included in analyses. Mean age of participants was 57, 65 percent were women, and 36 percent had less than a high school education. Results showed that 27 percent of participants experienced FI, women, younger persons, and those with lower educational attainment were more likely to experience low, moderate or severe FI. Forty-one percent of those with low FI had elevated blood pressure compared to 40 percent among those with moderate, and 40 percent with severe FI. Logistic model results showed that mild (OR=1.04, CI=0.74-1.47), moderate (OR=1.01, CI=0.60-1.7), and severe FI (OR=1.38, CI=0.64-2.95) was not associated with elevated blood pressure after adjusting for demographic and clinical covariates. Post-hoc analysis showed that that moderate/severe FI was associated elevated blood pressure among women (OR=1.50, CI=1.02-2.20). Conclusions: Findings for FI and elevated blood pressure among women is consistent with prior research conducted in other contexts. Findings have implications for safety net programs and targeted efforts to reduce FI overall and among women.
Updated Standardized Definitions for Efficacy End Points (STEEP) in Adjuvant Breast Cancer Clinical Trials: STEEP Version 2.0
Authors: Sara M. Tolaney, Elizabeth Garrett-Mayer, Julia White, Victoria S. Blinder, Jared C. Foster, Laleh Amiri-Kordestani, E. Shelley Hwang, Judith M. Bliss, Eileen Rakovitch, Jane Perlmutter, Patricia A. Spears, Elizabeth Frank, Nadine M. Tung, Anthony D. Elias, David Cameron, Neelima Denduluri, Ana F. Best, Angelo DiLeo, Lawrence Baizer, Lynn Pearson Butler, Elena Schwartz, Eric P. Winer, Larissa A. Korde
Journal: Journal of Clinical Oncology (2021)

The Standardized Definitions for Efficacy End Points (STEEP) criteria, established in 2007, provide standardized definitions of adjuvant breast cancer clinical trial end points. Given the evolution of breast cancer clinical trials and improvements in outcomes, a panel of experts reviewed the STEEP criteria to determine whether modifications are needed.We conducted systematic searches of ClinicalTrials.gov for adjuvant systemic and local-regional therapy trials for breast cancer to investigate if the primary end points reported met STEEP criteria. On the basis of common STEEP deviations, we performed a series of simulations to evaluate the effect of excluding non-breast cancer deaths and new nonbreast primary cancers from the invasive disease-free survival end point.Among 11 phase III breast cancer trials with primary efficacy end points, three had primary end points that followed STEEP criteria, four used STEEP definitions but not the corresponding end point names, and four used end points that were not included in the original STEEP manuscript. Simulation modeling demonstrated that inclusion of second nonbreast primary cancer can increase the probability of incorrect inferences, can decrease power to detect clinically relevant efficacy effects, and may mask differences in recurrence rates, especially when recurrence rates are low.We recommend an additional end point, invasive breast cancer-free survival, which includes all invasive disease-free survival events except second nonbreast primary cancers. This end point should be considered for trials in which the toxicities of agents are well-known and where the risk of second primary cancer is small. Additionally, we provide end point recommendations for local therapy trials, low-risk populations, noninferiority trials, and trials incorporating patient-reported outcomes.
Nursing practice is associated with high risk for hepatitis C virus infection
Authors: Pooja Pundhir, Lillian Ruth Roach, Jalen R. Bartek, Rebecca P. Trask, Marcel Yibirin, Eduardo Yepez Guevara, Bruno P. Granwehr, Crystal R. Swalwell, Harrys A. Torres
Journal: Clinical Microbiology and Infection (2021)
Abstract 16551: Transcatheter Closure of Patent Ductus Arteriosus in Premature Infants - How Young is Too Young?
Authors: Abhishek Chakraborty, Ranjit Philip, Ronak Naik, Huma Abdulmajeed, Mimily Harsono, Rush Waller, Shyam Sathanandam
Journal: Circulation (2020)

Background: Transcatheter patent ductus arteriosus (PDA) closure (TCPC), has been shown to be feasible and safe for infants as small as 700 grams or even smaller. Hypothesis: The corrected gestational age of the infant may be a better representation of tissue maturity than the weight of the infant. This study was aimed to explore the outcomes of TCPC based not just on weight, but also on the age of the infant. Methods: This was a retrospective study including infants born at gestational age &lt; 28 weeks who underwent TCPC between Jan-2012 and May-2020 and weighed &lt; 3 kg at the time of the procedure. The study period was divided into four-time blocks. Success and complication rates were compared for those who underwent the procedure at &lt; 28 days to those infants that underwent TCPC &gt;28 days of age. Results: In study period, TCPC was attempted on 241 infants that satisfied the inclusion criteria, with a 99.1% success rate. There was no difference in success rates based on the age at TCPC (99.3% vs. 99% for procedural age &lt; 28 days vs. &gt;28 days respectively; P=0.82). Overall, 140 infants underwent TCPC at &lt; 28 days of age, 29 of whom were &lt; 14 days, and 54 infants underwent TCPC between 15 and 21 days of age. The median age at TCPC progressively decreased from 60 days of life (14-211 days) between January 2012 and December 2014 to 18 days (8-38 days) between August 2019 and May 2020 (P &lt; 0.00001). Similarly, the weight at TCPC decreased over the same time periods (median 1985 grams vs. 900 grams; P &lt; 0.00001). Procedure-related complication rates were similar for those &lt; 28 days vs. &gt;28 days of age at the time of TCPC (2.8% vs. 4.9% respectively; P=0.42). Conclusions: It is feasible and safe to perform TCPC after the first week of life for infants born &lt; 28 weeks’ gestation. As experience grows, more infants are referred to earlier after birth which translates to performing TCPC on smaller infants. The benefits of early TCPC have to be determined in order for this therapy to be advocated routinely for all premature infants.
Abstract 2773: Prognostic value of <i>KRASP53PIK3CA</i> in non-small cell lung cancer patients
Authors: Yiping Han
Journal: Cancer Research (2019)

Abstract We explored the relationship of KRAS, PIK3CA, and TP53 mutations with the clinical features and survival prognosis in 50 non-small cell lung cancer (NSCLC) patients. The most common concurrent single gene mutation was TP53, followed by KRAS and PIK3CA. Coexisting mutations were found in 17 patients. KRAS, PIK3CA, and TP53 mutations were related to Ca19-9 expression, invasive growth, vacuolar signs, and margin lobulation in chest CT imaging. The incidence of distant metastasis (bone and adrenal) with KRAS and TP53 mutations was greater than that of local metastasis (pleura). Patients the wild-type gene had longer progression-free survival than those with KRAS, TP53, KRAS/TP53, or PIK3CA/TP53 mutations. Patients with KRAS/TP53 or PIK3CA/TP53 mutations had shorter progression free survival than those with a single KRAS or TP53 mutation. KRAS, PIK3CA, and TP53 mutations were associated with distant metastases and poor prognosis. NSCLC patients should receive routine KRAS, PIK3CA, and TP53 gene sequencing to determine mutations for the analysis of clinical characteristics and prognosis. Note: This abstract was not presented at the meeting. Citation Format: Yiping Han. Prognostic value of KRASP53PIK3CA in non-small cell lung cancer patients [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 2773.
The Worldwide Invasion of<i>Drosophila suzukii</i>Is Accompanied by a Large Increase of Transposable Element Load and a Small Number of Putatively Adaptive Insertions
Authors: Vincent Mérel, Patricia Gibert, Inessa Buch, Valentina Rodriguez Rada, Arnaud Estoup, Mathieu Gautier, Marie Fablet, Matthieu Boulesteix, Cristina Vieira
Journal: Molecular Biology and Evolution (2021)

Transposable elements (TEs) are ubiquitous and mobile repeated sequences. They are major determinants of host fitness. Here, we characterized the TE content of the spotted wing fly Drosophila suzukii. Using a recently improved genome assembly, we reconstructed TE sequences de novo and found that TEs occupy 47% of the genome and are mostly located in gene-poor regions. The majority of TE insertions segregate at low frequencies, indicating a recent and probably ongoing TE activity. To explore TE dynamics in the context of biological invasions, we studied the variation of TE abundance in genomic data from 16 invasive and six native populations of D. suzukii. We found a large increase of the TE load in invasive populations correlated with a reduced Watterson estimate of genetic diversity θw^ a proxy of effective population size. We did not find any correlation between TE contents and bioclimatic variables, indicating a minor effect of environmentally induced TE activity. A genome-wide association study revealed that ca. 2,000 genomic regions are associated with TE abundance. We did not find, however, any evidence in such regions of an enrichment for genes known to interact with TE activity (e.g., transcription factor encoding genes or genes of the piRNA pathway). Finally, the study of TE insertion frequencies revealed 15 putatively adaptive TE insertions, six of them being likely associated with the recent invasion history of the species.