tbuckley/cabot-search huggingface dataset:
Shared intentionality shapes humans' technical know-how
Authors: Henrike Moll, Ryan Nichols, Ellyn Pueschel
Journal: Behavioral and Brain Sciences (2020)

Abstract Osiurak and Reynaud argue that cumulative technological culture is made possible by a “non-social cognitive structure ” (sect. 1, para. 1) and they offer an account that aims “to escape from the social dimension” (sect. 1, para. 2) of human cognition. We challenge their position by arguing that human technical rationality is unintelligible outside of our species' uniquely social form of life, which is defined by shared intentionality (Kern &amp; Moll 2017, Philosophical Psychology 30 (3):319–37; Tomasello 2019a, Becoming human: A theory of ontogeny . Cambridge, MA: Belknap Press).
Metabolic effects of air pollution exposure and reversibility
Authors: Sanjay Rajagopalan, Bongsoo Park, Rengasamy Palanivel, Vinesh Vinayachandran, Jeffrey A. Deiuliis, Roopesh Singh Gangwar, Lopa Das, Jinhu Yin, Youngshim Choi, Sadeer Al-Kindi, Mukesh K. Jain, Kasper D. Hansen, Shyam Biswal
Journal: Journal of Clinical Investigation (2020)

Air pollution involving particulate matter smaller than 2.5 μm in size (PM2.5) is the world's leading environmental risk factor contributing to mortality through cardiometabolic pathways. In this study, we modeled early life exposure using chow-fed C57BL/6J male mice that were exposed to real-world inhaled, concentrated PM2.5 (~10 times ambient levels/~60–120 μg/m3) or filtered air over a 14-week period. We investigated the effects of PM2.5 on phenotype, the transcriptome, and chromatin accessibility and compared these with the effects of a prototypical high-fat diet (HFD) as well as cessation of exposure on phenotype reversibility. Exposure to PM2.5 impaired glucose and insulin tolerance and reduced energy expenditure and 18FDG-PET uptake in brown adipose tissue. Multiple differentially expressed gene clusters in pathways involving metabolism and circadian rhythm were noted in insulin-responsive tissues. Although the magnitude of transcriptional change detected with PM2.5 exposure was lower than that observed with a HFD, the degree of alteration in chromatin accessibility after PM2.5 exposure was significant. The novel chromatin remodeler SMARCA5 (SWI/SNF complex) was regulated in response to PM2.5 exposure, the cessation of which was associated with a reversal of insulin resistance and restoration of chromatin accessibility and nucleosome positioning near transcription start sites, as well as a reversal of exposure-induced changes in the transcriptome, including SMARCA5. These changes indicate pliable epigenetic control mechanisms following cessation of exposure.
Hereditary α tryptasemia is a valid genetic biomarker for severe mediator-related symptoms in mastocytosis
Authors: Georg Greiner, Bettina Sprinzl, Aleksandra Górska, Franz Ratzinger, Michael Gurbisz, Nadine Witzeneder, Klaus G. Schmetterer, Bettina Gisslinger, Goekhan Uyanik, Emir Hadzijusufovic, Harald Esterbauer, Karoline V. Gleixner, Maria T. Krauth, Michael Pfeilstöcker, Felix Keil, Heinz Gisslinger, Boguslaw Nedoszytko, Marek Niedoszytko, Wolfgang R. Sperr, Peter Valent, Gregor Hoermann
Journal: Blood (2020)
The social side of innovation
Authors: Bruce Rawlings, Cristine H Legare
Journal: Behavioral and Brain Sciences (2020)

Abstract Innovation is fundamental to cumulative culture, allowing progressive modification of existing technology. The authors define innovation as an asocial process, uninfluenced by social information. We argue that innovation is inherently social – innovation is frequently the product of modifying others' outputs, and successful innovations are acquired by others. Research should target examination of the cognitive underpinnings of socially-mediated innovations.
Design Bioethics: A Theoretical Framework and Argument for Innovation in Bioethics Research
Authors: Gabriela Pavarini, Robyn McMillan, Abigail Robinson, Ilina Singh
Journal: The American Journal of Bioethics (2021)

Empirical research in bioethics has developed rapidly over the past decade, but has largely eschewed the use of technology-driven methodologies. We propose "design bioethics" as an area of conjoined theoretical and methodological innovation in the field, working across bioethics, health sciences and human-centred technological design. We demonstrate the potential of digital tools, particularly purpose-built digital games, to align with theoretical frameworks in bioethics for empirical research, integrating context, narrative and embodiment in moral decision-making. Purpose-built digital tools can engender situated engagement with bioethical questions; can achieve such engagement at scale; and can access groups traditionally under-represented in bioethics research and theory. If developed and used with appropriate rigor, tools motivated by "design bioethics" could offer unique insights into new and familiar normative and empirical issues in the field.
Abstract 16142: Increased TGFβ1 Signaling, Fibrosis and Circulating Cell Infiltration of Female Graft Veins Contribute to Sex Differences in Murine Arteriovenous Fistulas
Authors: Chuanqi Cai, Chenglei Zhao, Sreenivasulu Kilari, Amit Sharma, Binxia Yang, Singh Avishek, Simeon Michael, Avanish Misra, Li Yiqing, Rajiv Kumar, Sanjay Misra
Journal: Circulation (2019)

Introduction: Arteriovenous fistula (AVF) maturation and patency rates are decreased in women as a result of poorly defined processes. To illustrate the sexual diversities among female and male fis...
Re: Lisa Moris, Marcus G. Cumberbatch, Thomas Van den Broeck, et al. Benefits and Risks of Primary Treatments for High-risk Localized and Locally Advanced Prostate Cancer: An International Multidisciplinary Systematic Review. Eur Urol 2020;77:614–27
Authors: Francesco Montorsi, Andrea Salonia, Alberto Briganti
Journal: European Urology (2020)
Covid-19: Inadequate health and safety regulatory planning in the UK
Authors: Andrew Watterson
Journal: BMJ (2020)

OBJECTIVES--To assess the prevalence of lower genital tract symptoms and the association between reported symptoms and past and present signs of sexually transmitted diseases (STD) in young women. DESIGN--All women belonging to the 19-, 21-, 23- and 25-year age cohorts and living in the catchment area of the community health centre, were invited by mail to take part in a population-based study. The participants answered a structured questionnaire and a gynaecologic examination was performed. Samples for wet smear, cervical Pap smear, HPV DNA determination and Chlamydia trachomatis culture were taken at the gynaecologic examination. The presence of genital warts was noted. A blood sample was analysed for antibodies against C trachomatis and HSV-2. SETTING--The community health care centre was located in Umeå, a city in Northern Sweden. RESULTS--Of the 886 women who were eligible, 611 (70%) participated in the investigation. One out of four women reported symptoms from the lower genital tract. The most commonly reported symptoms were itching, followed by discharge, and soreness. The most commonly reported STD was C trachomatis (15%). The most prevalent present STD was HPV infection (20%) whereas C trachomatis infection could be isolated from 2.7% of the women. Antibodies against C trachomatis and HSV-2 were present among 22% and 6% of the women, respectively. There was a significant correlation between the women9s complaint of vaginal discharge and previous C trachomatis infection, lack of lactobacilli and presence of leucocytosis in wet smear. CONCLUSIONS--We have in a population-based study of young healthy women found that one out of four women had some kind of lower genital tract complaint. Itching was the most commonly reported symptom and was associated with pseudohyphae and acetowhite patches. Reported vaginal discharge and soreness were associated with the history of a past C trachomatis infection and signs of a disturbed vaginal flora.
Emerging evidence of myocardial injury in COVID-19: A path through the smoke
Authors: Gregorio Tersalvi, Giacomo Veronese, Dario Winterton
Journal: Theranostics (2020)

Although Coronavirus Disease 2019 (COVID-19) presents primarily as a respiratory condition, a growing body of evidence shows it is a systemic disease. Recently, many authors have described myocardial damage in COVID-19, suggesting various pathophysiological mechanisms. In this issue, Cao et al. demonstrate the prognostic value of cardiac troponin I in patients with COVID-19, showing how even minor elevations in this molecule carry a great impact on patient mortality. In a situation such as the worldwide COVID-19 pandemic, where healthcare resources are placed under enormous stress, readily available tests such as this play an important role in helping clinicians identify patients at greater risk of developing severe forms of the disease, and should be included in the initial triage panel.
Repression of the B cell identity factor Pax5 is not required for plasma cell development
Authors: Grace J. Liu, Markus Jaritz, Miriam Wöhner, Benedikt Agerer, Andreas Bergthaler, Stephen G. Malin, Meinrad Busslinger
Journal: The Journal of Experimental Medicine (2020)

B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the IghPax5/+ mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young IghPax5/+ mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in IghPax5/+ plasma cells. While IgM and IgA secretion by IghPax5/+ plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells.
Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study
Authors: Noa Biran, Andrew Ip, Jaeil Ahn, Ronaldo C Go, Shuqi Wang, Shivam Mathura, Brittany A Sinclaire, Urszula Bednarz, Michael Marafelias, Eric Hansen, David S Siegel, Andre H Goy, Andrew L Pecora, Ihor S Sawczuk, Lauren S Koniaris, Micky Simwenyi, Daniel W Varga, Lisa K Tank, Aaron A Stein, Valerie Allusson, George S Lin, William F Oser, Roman A Tuma, Joseph Reichman, Louis Brusco, Kim L Carpenter, Eric J Costanzo, Vincent Vivona, Stuart L Goldberg
Journal: The Lancet Rheumatology (2020)
Cancer Disparities and Health Equity: A Policy Statement From the American Society of Clinical Oncology
Authors: Manali I. Patel, Ana Maria Lopez, William Blackstock, Katherine Reeder-Hayes, E. Allyn Moushey, Jonathan Phillips, William Tap
Journal: Journal of Clinical Oncology (2020)

ASCO strives, through research, education, and promotion of the highest quality of patient care, to create a world where cancer is prevented and every survivor is healthy. In this pursuit, cancer health equity remains the guiding institutional principle that applies to all its activities across the cancer care continuum. In 2009, ASCO committed to addressing differences in cancer outcomes in its original policy statement on cancer disparities. Over the past decade, despite novel diagnostics and therapeutics, together with changes in the cancer care delivery system such as passage of the Affordable Care Act, cancer disparities persist. Our understanding of the populations experiencing disparate outcomes has likewise expanded to include the intersections of race/ethnicity, geography, sexual orientation and gender identity, sociodemographic factors, and others. This updated statement is intended to guide ASCO's future activities and strategies to achieve its mission of conquering cancer for all populations. ASCO acknowledges that much work remains to be done, by all cancer stakeholders at the systems level, to overcome historical momentum and existing social structures responsible for disparate cancer outcomes. This updated statement affirms ASCO's commitment to moving beyond descriptions of differences in cancer outcomes toward achievement of cancer health equity, with a focus on improving equitable access to care, improving clinical research, addressing structural barriers, and increasing awareness that results in measurable and timely action toward achieving cancer health equity for all.
Purifying Selection against Pathogenic Mitochondrial DNA in Human T Cells
Authors: Melissa A. Walker, Caleb A. Lareau, Leif S. Ludwig, Amel Karaa, Vijay G. Sankaran, Aviv Regev, Vamsi K. Mootha
Journal: New England Journal of Medicine (2020)

Many mitochondrial diseases are caused by mutations in mitochondrial DNA (mtDNA). Patients' cells contain a mixture of mutant and nonmutant mtDNA (a phenomenon called heteroplasmy). The proportion of mutant mtDNA varies across patients and among tissues within a patient. We simultaneously assayed single-cell heteroplasmy and cell state in thousands of blood cells obtained from three unrelated patients who had A3243G-associated mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes. We observed a broad range of heteroplasmy across all cell types but also found markedly reduced heteroplasmy in T cells, a finding consistent with purifying selection within this lineage. We observed this pattern in six additional patients who had heteroplasmic A3243G without strokelike episodes. (Funded by the Marriott Foundation and others.).
Abstract 43: Clinical implications of real-world data on plasma circulating tumor DNA in gynecologic cancer patients
Authors: Lindsey Michelle Charo, Ramez N. Eskander, Ryosuke Okamura, Sandip Patel, Mina Nikanjam, Richard Layman, David E. Piccioni, Shamei Kato, Michael McHale, Razelle Kurzrock
Journal: Clinical Cancer Research (2020)

Abstract Molecular characterization of individual cancers is increasingly important in dictating prognostic factors and directing therapy. Next-generation sequencing of blood-derived circulating tumor DNA (ctDNA) offers less invasive, more convenient collection and a more real-time representation of a tumor and its molecular heterogeneity than tissue-based analysis. However, little is known about the clinical implications of ctDNA assessment in gynecologic cancer. We report the clinicopathologic and genomic information for 105 gynecologic cancer patients with ctDNA analysis, including 78 patients with tissue-based sequencing, who were enrolled in Profile Related Evidence Determining Individualized Cancer Therapy (PREDICT, NCT02478931). Tumors in our cohort included ovarian (47.6%), uterine (35.2%), cervical (12.4%), vulvar or vaginal (2.9%), and gynecologic cancer of unknown primary (1.9%). The majority of patients (74.3%) had at least one characterized alteration on ctDNA analysis. The most common alterations were in the following genes: TP53 (N=59, 56.2% of patients), PIK3CA (N=26, 24.8%), KRAS (N=14, 13.3%), BRAF (N=10, 9.5%), ERBB2 (N=8, 7.6%), and MYC (N=8, 7.6%). Higher total percentage of ctDNA was associated with worse overall survival (HR 2.18, p=0.008), and therapy matched to ctDNA genomic alterations (N = 33 patients) independently predicted improved overall survival (HR 0.34, p=0.007) as compared to unmatched therapy (N = 28 patients). Tissue and ctDNA genomic results showed high concordance unaffected by temporal or spatial factors. This study provides evidence for the utility of ctDNA in determining outcome and individualizing cancer therapy in patients with gynecologic cancer. Citation Format: Lindsey Michelle Charo, Ramez N. Eskander, Ryosuke Okamura, Sandip Patel, Mina Nikanjam, Richard Layman, David E. Piccioni, Shamei Kato, Michael McHale, Razelle Kurzrock. Clinical implications of real-world data on plasma circulating tumor DNA in gynecologic cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 43.
Effect of High Add Power, Medium Add Power, or Single-Vision Contact Lenses on Myopia Progression in Children
Authors: Jeffrey J. Walline, Maria K. Walker, Donald O. Mutti, Lisa A. Jones-Jordan, Loraine T. Sinnott, Amber Gaume Giannoni, Katherine M. Bickle, Krystal L. Schulle, Alex Nixon, Gilbert E. Pierce, David A. Berntsen
Journal: JAMA (2020)

<h3>Importance</h3> Slowing myopia progression could decrease the risk of sight-threatening complications. <h3>Objective</h3> To determine whether soft multifocal contact lenses slow myopia progression in children, and whether high add power (+2.50 D) slows myopia progression more than medium (+1.50 D) add power lenses. <h3>Design, Setting, and Participants</h3> A double-masked randomized clinical trial that took place at 2 optometry schools located in Columbus, Ohio, and Houston, Texas. A total of 294 consecutive eligible children aged 7 to 11 years with −0.75 D to −5.00 D of spherical component myopia and less than 1.00 D astigmatism were enrolled between September 22, 2014, and June 20, 2016. Follow-up was completed June 24, 2019. <h3>Interventions</h3> Participants were randomly assigned to wear high add power (n = 98), medium add power (n = 98), or single-vision (n = 98) contact lenses. <h3>Main Outcomes and Measures</h3> The primary outcome was the 3-year change in cycloplegic spherical equivalent autorefraction, as measured by the mean of 10 autorefraction readings. There were 11 secondary end points, 4 of which were analyzed for this study, including 3-year eye growth. <h3>Results</h3> Among 294 randomized participants, 292 (99%) were included in the analyses (mean [SD] age, 10.3 [1.2] years; 177 [60.2%] were female; mean [SD] spherical equivalent refractive error, −2.39 [1.00] D). Adjusted 3-year myopia progression was −0.60 D for high add power, −0.89 D for medium add power, and −1.05 D for single-vision contact lenses. The difference in progression was 0.46 D (95% CI, 0.29-0.63) for high add power vs single vision, 0.30 D (95% CI, 0.13-0.47) for high add vs medium add power, and 0.16 D (95% CI, −0.01 to 0.33) for medium add power vs single vision. Of the 4 secondary end points, there were no statistically significant differences between the groups for 3 of the end points. Adjusted mean eye growth was 0.42 mm for high add power, 0.58 mm for medium add power, and 0.66 mm for single vision. The difference in eye growth was −0.23 mm (95% CI, −0.30 to −0.17) for high add power vs single vision, −0.16 mm (95% CI, −0.23 to −0.09) for high add vs medium add power, and −0.07 mm (95% CI, −0.14 to −0.01) for medium add power vs single vision. <h3>Conclusions and Relevance</h3> Among children with myopia, treatment with high add power multifocal contact lenses significantly reduced the rate of myopia progression over 3 years compared with medium add power multifocal and single-vision contact lenses. However, further research is needed to understand the clinical importance of the observed differences. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02255474
Rapid printing of bio-inspired 3D tissue constructs for skin regeneration
Authors: Feifei Zhou, Yi Hong, Renjie Liang, Xianzhu Zhang, Youguo Liao, Deming Jiang, Jiayan Zhang, Zixuan Sheng, Chang Xie, Zhi Peng, Xinhao Zhuang, Varitsara Bunpetch, Yiwei Zou, Wenwen Huang, Qin Zhang, Enateri Vera Alakpa, Shufang Zhang, Hongwei Ouyang
Journal: Biomaterials (2020)
Risk of New Bloodstream Infections and Mortality Among People Who Inject Drugs With Infective Endocarditis
Authors: Charlie Tan, Esfandiar Shojaei, Joshua Wiener, Meera Shah, Sharon Koivu, Michael Silverman
Journal: JAMA Network Open (2020)

People who inject drugs (PWID) who are being treated for infective endocarditis remain at risk of new bloodstream infections (BSIs) due to ongoing intravenous drug use (IVDU).To characterize new BSIs in PWID receiving treatment for infective endocarditis, to determine the clinical factors associated with their development, and to determine whether new BSIs and treatment setting are associated with mortality.This retrospective cohort study was performed at 3 tertiary care hospitals in London, Ontario, Canada, from April 1, 2007, to March 31, 2018. Participants included a consecutive sample of all PWID 18 years or older admitted with infective endocarditis. Data were analyzed from April 1, 2007, to June 29, 2018.New BSIs and factors associated with their development, treatment setting of infective endocarditis episodes (ie, inpatient vs outpatient), and 90-day mortality.The analysis identified 420 unique episodes of infective endocarditis in 309 PWID (mean [SD] patient age, 35.7 [9.7] years; 213 episodes [50.7%] involving male patients), with 82 (19.5%) complicated by new BSIs. There were 138 independent new BSIs, of which 68 (49.3%) were polymicrobial and 266 were unique isolates. Aerobic gram-negative bacilli (143 of 266 [53.8%]) and Candida species (75 of 266 [28.2%]) were the most common microorganisms. Ongoing inpatient IVDU was documented by a physician in 194 infective endocarditis episodes (46.2%), and 127 of these (65.5%) were confirmed by urine toxicology results. Multivariable time-dependent Cox regression demonstrated that previous infective endocarditis (hazard ratio [HR], 1.89; 95% CI, 1.20-2.98), inpatient treatment (HR, 4.49; 95% CI, 2.30-8.76), and physician-documented inpatient IVDU (HR, 5.07; 95% CI, 2.68-9.60) were associated with a significantly higher rate of new BSIs, whereas inpatient addiction treatment was associated with a significantly lower rate (HR, 0.53; 95% CI, 0.32-0.88). New BSIs were not significantly associated with 90-day mortality (HR, 1.76; 95% CI, 0.78-4.02); significant factors associated with mortality included inpatient infective endocarditis treatment (HR, 3.39; 95% CI, 1.53-7.53), intensive care unit admission (HR, 9.51; 95% CI, 4.91-18.42), and methicillin-resistant Staphylococcus aureus infective endocarditis (HR, 1.77; 95% CI, 1.03-3.03), whereas right-sided infective endocarditis was associated with a significantly lower mortality rate (HR, 0.41; 95% CI, 0.25-0.67).In this study, new BSIs were common in PWID receiving parenteral treatment for infective endocarditis. Discharging patients to outpatient treatment was not associated with an increase in new BSI incidence or mortality; carefully selected PWID may therefore be considered for such treatment.
Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients
Authors: Yannouck F. van Lier, Mark Davids, Nienke J. E. Haverkate, Pieter F. de Groot, Marjolein L. Donker, Ellen Meijer, Floor C. J. I. Heubel-Moenen, Erfan Nur, Sacha S. Zeerleder, Max Nieuwdorp, Bianca Blom, Mette D. Hazenberg
Journal: Science Translational Medicine (2020)

Donor fecal microbiota transplantation restores gut microbial diversity and reduces graft-versus-host disease in hematopoietic cell transplant recipients.