tbuckley/cabot-search huggingface dataset:
Covid-19: NHS will keep offering vaccinations to those who refuse, says minister
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The NHS will continue to contact and hold one-to-one meetings with doctors and other staff who haven't taken up the offer of a covid-19 vaccine to tackle any hesitancy, the vaccines minister said this week.Nadhim Zahawi told the Women and Equalities House of Commons Committee on 10 March that, although uptake among health staff had been "incredibly high"-with over 90% of those offered so far taking up the vaccine-the NHS was not resting on its laurels."If you are looking after a vulnerable person, then it is your professional duty if offered the jab to take the jab," he said.Zahawi acknowledged that uptake had been lower among some groups of the general public, such as black and ethnic minority communities, which he said the government was tackling through a range of measures including a media campaign in many different languages, new community champions, and outreach with healthcare providers and faith leaders.
<sup>68</sup>Ga-PSMA expression changes on PET/CT for response assessment during taxane-based chemotherapy in metastatic prostate cancer patients.
Authors: Qaid Shagera, Carlos Artigas, Patrick Flamen
Journal: Journal of Clinical Oncology (2021)

35 Background: Imaging-based response to systemic therapies in metastatic prostate cancer is still challenging. The aim of this study was to retrospectively investigate the association between Prostate-Specific Membrane Antigen (PSMA) expression changes on 68 Ga PSMA PET/CT and the response to treatment following the start of taxane-based chemotherapies (docetaxel or cabazitaxel) in both metastatic hormonosensitive (mHSPC) and castration-resistant prostate cancer (mCRPC) patients. Methods: We retrospectively reviewed all 68 Ga-PSMA-11 PET/CT scans performed at our institution from November 2014 to June 2020. We included mHSPC and mCRPC patients with a baseline 68 Ga-PSMA PET/CT performed &lt; 2 months before, and a second 68 Ga-PSMA PET/CT performed &lt; 3 months after docetaxel or cabazitaxel (with no modification in therapy between scans). The biological data was used to distinguish PSA-non-responders (increasing PSA or decreasing PSA by &lt; 50% from pretherapy level) and PSA-responders (decreasing PSA &gt; 50% following the start of therapy or the peak thereafter). The PSMA PET/CT response was assessed visually by two independent nuclear medicine physicians blinded to clinical data and patient outcomes. Patients were classified as PSMA-non-responders (≥1 new PSMA-expressing metastases, majority of PSMA-expressing metastases increasing in intensity, or stable PSMA-expression of the disease) or PSMA-responders (complete disappearance of pathologic PSMA uptake, or majority of PSMA-expressing metastases decreasing in intensity). Majority of lesions was defined as &gt; 50% of registered lesions. Descriptive statistics and measures of associations (two-sided Fisher’s exact test and Phi coefficient) were calculated. Results: A total of 37 patients were included (8 mHSPC and 29 mCRPC), 21 patients under docetaxel and 16 cabazitaxel. All patients received at least 3 cycles [median 6 (range 3-10)]. The mean time (±standard deviation) between the first 68 Ga-PSMA PET/CT and the start of therapy was 22±16 days. The mean time between the the last cycleand the second 68 Ga-PSMA PET/CT was 36±27 days. PSA-response and PSMA-response were concordant in 95% of cases with 18 patients PSA/PSMA-non-responders and 17 PSA/PSMA-responders (Phi = 0.90, p = 0.0001). Two discordant patients presented with PSMA-response but PSA-non-response. No isolated PSMA flare was observed, as PSA-response was always associated with a decrease in PSMA-expression on the second PET/CT. Conclusions: This retrospective study suggests PSMA expression changes on PET/CT at least after 3 cycles of chemotherapy (docetaxel or cabazitaxel) are strongly associated with PSA response. No flare phenomenon was found at this evaluation. Prospective studies are needed to better define the potential role of PSMA-PET/CT in response assessment.
Intraprostatic calcification and biochemical recurrence in men treated with Cs-131 prostate brachytherapy.
Authors: Michael D Schad, Joshua L Rodríguez-López, Ankur Patel, Christopher J Houser, Zachary D Horne, Ronald M Benoit, Ryan P Smith, Sushil Beriwal
Journal: Journal of Clinical Oncology (2021)

237 Background: Vigneault et al. reported that baseline intraprostatic calcification (IC) was associated with a higher risk of biochemical recurrence (BCR) in men treated with I-125 prostate brachytherapy (PB). Cs-131 has different physical properties than I-125. We assessed whether baseline IC was associated with BCR in men treated with Cs-131 PB. Methods: We retrospectively reviewed the records of all low-risk (LR), favorable intermediate-risk (FIR), and unfavorable IR (UIR) prostate cancer patients treated with Cs-131 PB +/- external beam radiotherapy (EBRT) from 2/2011 to 7/2018 at our institution. Patients who received hormone therapy or those with &lt; 24 months follow-up were excluded. Baseline IC status (defined as 1 or more ICs ≥ 5 mm) and characteristics were determined on post-PB CT scans. Baseline patient characteristics were compared via χ 2 , Mann–Whitney U, or Student’s t-test. Predictors of BCR (Phoenix definition) were analyzed via Cox proportional hazards model and Kaplan–Meier survival curves were generated. Results: Two hundred and sixteen LR, FIR, and UIR prostate cancer patients treated with Cs-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1–111.4 months). 76 patients (35.2%) had baseline IC and 140 patients (64.8%) did not. Baseline disease characteristics did not differ significantly between patients with vs. without ICs. In patients with baseline IC, the median number of ICs was 1 (range 1–3), median length of largest IC was 9.1 mm (range 5.0–33.1), and median peak density of largest IC was 884 Hounsfield units (range 283–1744). ICs were most commonly present in the midgland (88.2%) and central (97.4%) regions. On univariate Cox analysis of all baseline disease, treatment, and IC characteristics, only initial PSA (p = 0.016) and NCCN risk group (p = 0.047) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with vs. without baseline IC was 97.7% vs. 93.8% (p = 0.40), respectively. Conclusions: In a cohort of LR and IR prostate cancer patients treated with Cs-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.
Ketone therapy for heart failure: current evidence for clinical use
Authors: Shingo Takahara, Shubham Soni, Zaid H Maayah, Mourad Ferdaoussi, Jason R B Dyck
Journal: Cardiovascular Research (2021)

During conditions that result in depleted circulating glucose levels, ketone bodies synthesized in the liver are necessary fuel substrates for the brain. In other organs, such as the heart, the reliance on ketones for generating energy in the absence of glucose is less important as the heart can utilize alternative fuel sources, such as fatty acids. However, during pathophysiological conditions, such as heart failure, cardiac defects in metabolic processes that normally allow for sufficient energy production from fatty acids and carbohydrates contribute to a decline in contractile function. As such, it has been proposed that the failing heart relies more on ketone bodies as an energy source than previously appreciated. Furthermore, it has been shown that ketone bodies function as signaling molecules that can suppress systemic and cardiac inflammation. Thus, it is possible that intentionally elevating circulating ketones may be beneficial as an adjunct treatment for heart failure. Although many approaches can be used for 'ketone therapy', each of these has their own advantages and disadvantages in the treatment of heart failure. Thus, we summarize current preclinical and clinical studies involving various types of ketone therapy in cardiac disease and discuss the advantages and disadvantages of each modality as possible treatments for heart failure.
seqQscorer: automated quality control of next-generation sequencing data using machine learning
Authors: Steffen Albrecht, Maximilian Sprang, Miguel A. Andrade-Navarro, Jean-Fred Fontaine
Journal: Genome biology (2021)

Controlling quality of next-generation sequencing (NGS) data files is a necessary but complex task. To address this problem, we statistically characterize common NGS quality features and develop a novel quality control procedure involving tree-based and deep learning classification algorithms. Predictive models, validated on internal and external functional genomics datasets, are to some extent generalizable to data from unseen species. The derived statistical guidelines and predictive models represent a valuable resource for users of NGS data to better understand quality issues and perform automatic quality control. Our guidelines and software are available at https://github.com/salbrec/seqQscorer .
How the lessons of previous epidemics helped successful countries fight covid-19
Authors: Alvin Qijia Chua, Bandar Al Knawy, Ben Grant, Helena Legido-Quigley, Wui-Chiang Lee, Gabriel M Leung, Mun-Keat Looi, Sebastian Maurer-Stroh
Journal: BMJ (2021)

Covid-19 caught the West by surprise, but the legacy of Ebola, MERS, and SARS meant that several Asian and African nations had systems in place to mitigate the severity of the pandemic. Experts explain what Hong Kong, Liberia, Saudi Arabia, Singapore, and Taiwan learnt and how they have made a difference.
Calpastatin prevents Angiotensin II–mediated podocyte injury through maintenance of autophagy
Authors: Imane Bensaada, Blaise Robin, Joëlle Perez, Yann Salemkour, Anna Chipont, Marine Camus, Mathilde Lemoine, Lea Guyonnet, Hélène Lazareth, Emmanuel Letavernier, Carole Hénique, Pierre-Louis Tharaux, Olivia Lenoir
Journal: Kidney International (2021)

The strong predictive value of proteinuria in chronic glomerulopathies is firmly established as well as the pathogenic role of angiotensin II promoting progression of glomerular disease with an altered glomerular filtration barrier, podocyte injury and scarring of glomeruli. Here we found that chronic angiotensin II-induced hypertension inhibited autophagy flux in mouse glomeruli. Deletion of Atg5 (a gene encoding a protein involved autophagy) specifically in the podocyte resulted in accelerated angiotensin II-induced podocytopathy, accentuated albuminuria and glomerulosclerosis. This indicates that autophagy is a key protective mechanism in the podocyte in this condition. Angiotensin-II induced calpain activity in podocytes inhibits autophagy flux. Podocytes from mice with transgenic expression of the endogenous calpain inhibitor calpastatin displayed higher podocyte autophagy at baseline that was resistant to angiotensin II-dependent inhibition. Also, sustained autophagy with calpastatin limited podocyte damage and albuminuria. These findings suggest that hypertension has pathogenic effects on the glomerular structure and function, in part through activation of calpains leading to blockade of podocyte autophagy. These findings uncover an original mechanism whereby angiotensin II-mediated hypertension inhibits autophagy via calcium-induced recruitment of calpain with pathogenic consequences in case of imbalance by calpastatin activity. Thus, preventing a calpain-mediated decrease in autophagy may be a promising new therapeutic strategy for nephropathies associated with high renin-angiotensin system activity.
Large-scale Identification of Clonal Hematopoiesis and Mutations Recurrent in Blood Cancers
Authors: Julie E. Feusier, Sasi Arunachalam, Tsewang Tashi, Monika J. Baker, Chad VanSant-Webb, Amber Ferdig, Bryan E. Welm, Juan L. Rodriguez-Flores, Christopher Ours, Lynn B. Jorde, Josef T. Prchal, Clinton C. Mason
Journal: Blood Cancer Discovery (2021)

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by detectable hematopoietic-associated gene mutations in a person without evidence of hematologic malignancy. We sought to identify additional cancer-presenting mutations useable for CHIP detection by performing a data mining analysis of 48 somatic mutation studies reporting mutations at diagnoses of 7,430 adult and pediatric patients with hematologic malignancies. Following extraction of 20,141 protein-altering mutations, we identified 434 significantly recurrent mutation hotspots, 364 of which occurred at loci confidently assessable for CHIP. We then performed an additional large-scale analysis of whole exome sequencing data from 4,538 persons belonging to three non-cancer cohorts for clonal mutations. We found the combined cohort prevalence of CHIP with mutations identical to those reported at blood cancer mutation hotspots to be 1.8%, and that some of these CHIP mutations occurred in children. Our findings may help to improve CHIP detection and pre-cancer surveillance for both children and adults.
Ethnicity, household composition and COVID-19 mortality: a national linked data study
Authors: Vahé Nafilyan, Nazrul Islam, Daniel Ayoubkhani, Clare Gilles, Srinivasa Vittal Katikireddi, Rohini Mathur, Annabel Summerfield, Karen Tingay, Miqdad Asaria, Ann John, Peter Goldblatt, Amitava Banerjee, Myer Glickman, Kamlesh Khunti
Journal: Journal of the Royal Society of Medicine (2021)

Objective To estimate the proportion of ethnic inequalities explained by living in a multi-generational household. Design Causal mediation analysis. Setting Retrospective data from the 2011 Census linked to Hospital Episode Statistics (2017-2019) and death registration data (up to 30 November 2020). Participants Adults aged 65 years or over living in private households in England from 2 March 2020 until 30 November 2020 (n=10,078,568). Main outcome measures Hazard ratios were estimated for COVID-19 death for people living in a multi-generational household compared with people living with another older adult, adjusting for geographic factors, socioeconomic characteristics and pre-pandemic health. Results Living in a multi-generational household was associated with an increased risk of COVID-19 death. After adjusting for confounding factors, the hazard ratios for living in a multi-generational household with dependent children were 1.17 (95% confidence interval [CI] 1.06–1.30) and 1.21 (95% CI 1.06–1.38) for elderly men and women. The hazard ratios for living in a multi-generational household without dependent children were 1.07 (95% CI 1.01–1.13) for elderly men and 1.17 (95% CI 1.07–1.25) for elderly women. Living in a multi-generational household explained about 11% of the elevated risk of COVID-19 death among elderly women from South Asian background, but very little for South Asian men or people in other ethnic minority groups. Conclusion Elderly adults living with younger people are at increased risk of COVID-19 mortality, and this is a contributing factor to the excess risk experienced by older South Asian women compared to White women. Relevant public health interventions should be directed at communities where such multi-generational households are highly prevalent.
Novel somatic mutations in UBA1 as a cause of VEXAS syndrome
Authors: James A. Poulter, Jason C. Collins, Catherine Cargo, Ruth M. De Tute, Paul Evans, Daniela Ospina Cardona, David T. Bowen, Joanna R. Cunnington, Elaine Baguley, Mark Quinn, Michael Green, Dennis McGonagle, David B. Beck, Achim Werner, Sinisa Savic
Journal: Blood (2021)
Abstract 10566: Impact of Atrial Fibrillation Ablation With Cryoballoon Catheter on Cardiac Sympathetic Nervous System in Patients With and Without Heart Failure
Authors: Masato Kawasaki, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Atsushi Kikuchi, Tsutomu Kawai, Masahiro Seo, Makoto Abe, Jun Nakamura, Kyouko Yamamoto, Masatsugu Kawahira, Kiyomi Kayama, Kazuya Tanabe, Masatake Fukunami
Journal: Circulation (2018)

Background: Catheter ablation of atrial fibrillation (AF) might influence the cardiac sympathetic nervous system (CSNS). We sought to investigate the impact of AF ablation with cryoballoon catheter...
Extract and molecular‐based early infant sensitization and associated factors—A PreventADALL study
Authors: Sandra G. Tedner, Cilla Söderhäll, Jon R. Konradsen, Karen E. S. Bains, Magnus P. Borres, Kai‐Håkon Carlsen, Karin C. L. Carlsen, Martin Färdig, Sabina W. Gerdin, Hrefna K. Gudmundsdóttir, Guttorm Haugen, Gunilla Hedlin, Christine M. Jonassen, Ina Kreyberg, Caroline‐Aleksi O. Mägi, Live S. Nordhagen, Eva M. Rehbinder, Knut Rudi, Håvard O. Skjerven, Anne C. Staff, Riyas Vettukattil, Marianne van Hage, Björn Nordlund, Anna Asarnoj
Journal: Allergy (2021)

More knowledge about sensitization patterns in early infancy, including impact of molecular allergology, is needed to help predict future allergy development more accurately.We aimed to determine the prevalence and patterns of allergic sensitization at 3 months of age, and explore possible associated factors.From the Scandinavian antenatally recruited PreventADALL mother-child cohort, we included 1110 3-month infants with available serum. Sensitization was defined as s-IgE of ≥0.1 kUA /L by Phadiatop Infant® (ThermoFisher Scientific) including birch, cat, grass, dog, milk, egg, peanut and wheat. Further ImmunoCAP analyses to ovomucoid, casein, Ara h 1-3, omega-5-gliadin were performed in food extract s-IgE-positive children. Maternal sensitization was defined as s-IgE ≥ 0.35 kUA /L to Phadiatop® (inhalant allergen mix) and/or Fx5 (food allergen mix) at 18-week pregnancy.Overall 79 (7.3%) infants had specific sensitization, many with low s-IgE-levels (IQR 0.16-0.81 kUA /L), with 78 being sensitized to food extract allergens; 41 to egg, 27 to milk, 10 to peanut, and 25 to wheat. A total of 62/78 were further analysed, 18 (29%) had s-IgE to ovomucoid, casein, Ara h 1-3 and/or omega-5-gliadin. Eight infants (0.7%) were sensitized to inhalant allergens. Maternal sensitization to food allergens was associated with infant sensitization, odds ratio 3.64 (95% CI 1.53-8.68).Already at 3 months of age, 7% were sensitized to food, mostly without detectable s-IgE to food allergen molecules, and <1% to inhalant allergens. Maternal food sensitization was associated with infants' sensitization.
Addressing the mental health impact of COVID-19 through population health
Authors: Matt Boden, Lindsey Zimmerman, Kathryn J. Azevedo, Josef I. Ruzek, Sasha Gala, Hoda S. Abdel Magid, Nichole Cohen, Robyn Walser, Naina D. Mahtani, Katherine J. Hoggatt, Carmen P. McLean
Journal: Clinical Psychology Review (2021)
Stable oxime-crosslinked hyaluronan-based hydrogel as a biomimetic vitreous substitute
Authors: Alexander E.G. Baker, Hong Cui, Brian G. Ballios, Sonja Ing, Peng Yan, Joe Wolfer, Thomas Wright, Mickael Dang, Nicola Y. Gan, Michael J. Cooke, Arturo Ortín-Martínez, Valerie A. Wallace, Derek van der Kooy, Robert Devenyi, Molly S. Shoichet
Journal: Biomaterials (2021)
Erythrocyte membrane-camouflaged nanoworms with on-demand antibiotic release for eradicating biofilms using near-infrared irradiation
Authors: Luoxiao Ran, Bitao Lu, Haoyu Qiu, Guofang Zhou, Jing Jiang, Enling Hu, Fangyin Dai, Guangqian Lan
Journal: Bioactive Materials (2021)

The increase in the number of resistant bacteria caused by the abuse of antibiotics and the emergence of biofilms significantly reduce the effectiveness of antibiotics. Bacterial infections are detrimental to our life and health. To reduce the abuse of antibiotics and treat biofilm-related bacterial infections, a biomimetic nano-antibacterial system, RBCM-NW-G namely, that controls the release of antibiotics through near infrared was prepared. The hollow porous structure and the high surface activity of nanoworms are used to realize antibiotic loading, and then, biomimetics are applied with red blood cell membranes (RBCM). RBCM-NW-G, which retains the performance of RBCM, shows enhanced permeability and retention effects. Fluorescence imaging in mice showed the effective accumulation of RBCM-NW-G at the site of infection. In addition, the biomimetic nanoparticles showed a longer blood circulation time and good biocompatibility. Anti-biofilm test results showed damage to biofilms due to a photothermal effect and a highly efficient antibacterial performance under the synergy of the photothermal effect, silver iron, and antibiotics. Finally, by constructing a mouse infection model, the great potential of RBCM-NW-G in the treatment of in vivo infections was confirmed.
A Burned-Out CD8+ T-cell Subset Expands in the Tumor Microenvironment and Curbs Cancer Immunotherapy
Authors: Miguel F. Sanmamed, Xinxin Nie, Shruti S. Desai, Franz Villaroel-Espindola, Ti Badri, Dejian Zhao, Anthony W. Kim, Lan Ji, Tianxiang Zhang, Edward Quinlan, Xiaoxiao Cheng, Xue Han, Matthew D. Vesely, Ala F. Nassar, Jingwei Sun, Yu Zhang, Tae Kon Kim, Jun Wang, Ignacio Melero, Roy S. Herbst, Kurt A. Schalper, Lieping Chen
Journal: Cancer Discovery (2021)

Abstract Specific mechanisms by which tumor-infiltrating lymphocytes (TIL) become dysfunctional remain poorly understood. Here, we employed a two-pronged approach using single-cell mass cytometry and tissue imaging technologies to dissect TILs from 25 patients with resectable and 35 patients with advanced non–small cell lung cancer (NSCLC). We identified a burned-out CD8+ TIL subset (Ebo) that specifically accumulated within the tumor microenvironment (TME) but not in adjacent nontumoral tissues. Ebo showed the highest expression of proliferation and activation markers but produced the lowest amount of IFNγ and were the most apoptotic CD8+ TIL subset. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-1/B7-H1 pathway-dependent manner. Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in patients with NSCLC. Our study identifies a dysfunctional TIL subset, with distinct features from previously described exhausted T cells, and implies strategies to overcome immunotherapy resistance. Significance: We identified a highly proliferative, overactivated, and apoptotic dysfunctional CD8+ tumor-infiltrating subpopulation that is functionally distinct from previously described exhausted T cells. This population is expanded in lung cancer tissues in a PD-1/B7-H1-dependent manner, and its abundance is associated with resistance to cancer immunotherapy, thus becoming a potential tissue biomarker. This article is highlighted in the In This Issue feature, p. 1601
A first-in-human phase 0 clinical study of RNA interference–based spherical nucleic acids in patients with recurrent glioblastoma
Authors: Priya Kumthekar, Caroline H. Ko, Tatjana Paunesku, Karan Dixit, Adam M. Sonabend, Orin Bloch, Matthew Tate, Margaret Schwartz, Laura Zuckerman, Ray Lezon, Rimas V. Lukas, Borko Jovanovic, Kathleen McCortney, Howard Colman, Si Chen, Barry Lai, Olga Antipova, Junjing Deng, Luxi Li, Serena Tommasini-Ghelfi, Lisa A. Hurley, Dusten Unruh, Nitya V. Sharma, Manoj Kandpal, Fotini M. Kouri, Ramana V. Davuluri, Daniel J. Brat, Miguel Muzzio, Mitchell Glass, Vinod Vijayakumar, Jeremy Heidel, Francis J. Giles, Ann K. Adams, C. David James, Gayle E. Woloschak, Craig Horbinski, Alexander H. Stegh
Journal: Science Translational Medicine (2021)

RNA interference–based spherical nucleic acid nanoconjugates are a potentially safe and brain-penetrant approach for glioblastoma treatment.