tbuckley/cabot-search huggingface dataset:
Foxo1 controls gut homeostasis and commensalism by regulating mucus secretion
Authors: Zuojia Chen, Jialie Luo, Jian Li, Girak Kim, Eric S. Chen, Sheng Xiao, Scott B. Snapper, Bin Bao, Dingding An, Richard S. Blumberg, Cheng-hui Lin, Sui Wang, Jiaxin Zhong, Kuai Liu, Qiyuan Li, Chuan Wu, Vijay K. Kuchroo
Journal: The Journal of Experimental Medicine (2021)

Mucus produced by goblet cells in the gastrointestinal tract forms a biological barrier that protects the intestine from invasion by commensals and pathogens. However, the host-derived regulatory network that controls mucus secretion and thereby changes gut microbiota has not been well studied. Here, we identify that Forkhead box protein O1 (Foxo1) regulates mucus secretion by goblet cells and determines intestinal homeostasis. Loss of Foxo1 in intestinal epithelial cells (IECs) results in defects in goblet cell autophagy and mucus secretion, leading to an impaired gut microenvironment and dysbiosis. Subsequently, due to changes in microbiota and disruption in microbiome metabolites of short-chain fatty acids, Foxo1 deficiency results in altered organization of tight junction proteins and enhanced susceptibility to intestinal inflammation. Our study demonstrates that Foxo1 is crucial for IECs to establish commensalism and maintain intestinal barrier integrity by regulating goblet cell function.
Radiomics in prostate cancer imaging for a personalized treatment approach - current aspects of methodology and a systematic review on validated studies
Authors: Simon K.B. Spohn, Alisa S. Bettermann, Fabian Bamberg, Matthias Benndorf, Michael Mix, Nils H. Nicolay, Tobias Fechter, Tobias Hölscher, Radu Grosu, Arturo Chiti, Anca L. Grosu, Constantinos Zamboglou
Journal: Theranostics (2021)

Prostate cancer (PCa) is one of the most frequently diagnosed malignancies of men in the world. Due to a variety of treatment options in different risk groups, proper diagnostic and risk stratification is pivotal in treatment of PCa. The development of precise medical imaging procedures simultaneously to improvements in big data analysis has led to the establishment of radiomics - a computer-based method of extracting and analyzing image features quantitatively. This approach bears the potential to assess and improve PCa detection, tissue characterization and clinical outcome prediction. This article gives an overview on the current aspects of methodology and systematically reviews available literature on radiomics in PCa patients, showing its potential for personalized therapy approaches. The qualitative synthesis includes all imaging modalities and focuses on validated studies, putting forward future directions.
Protease inhibitor-based direct-acting antivirals are associated with increased risk of aminotransferase elevations but not hepatic dysfunction or decompensation
Authors: Jessie Torgersen, Craig W. Newcomb, Dena M. Carbonari, Christopher T. Rentsch, Lesley S. Park, Alyssa Mezochow, Rajni L. Mehta, Lynn Buchwalder, Janet P. Tate, Norbert Bräu, Debika Bhattacharya, Joseph K. Lim, Tamar H. Taddei, Amy C. Justice, Vincent Lo Re
Journal: Journal of Hepatology (2021)
Post-infection cognitive impairments in a cohort of elderly patients with COVID-19
Authors: Yu-Hui Liu, Ye-Ran Wang, Qing-Hua Wang, Yang Chen, Xian Chen, Ying Li, Yuan Cen, Cheng Xu, Tian Hu, Xu-Dong Liu, Ling-Li Yang, Si-Jing Li, Xue-Fei Liu, Chun-Mei Liu, Jie Zhu, Wei Li, Li-Li Zhang, Juan Liu, Yan-Jiang Wang
Journal: Molecular Neurodegeneration (2021)

Abstract Background Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. Methods This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. Results Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p &lt; 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p &lt; 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p &lt; 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p &lt; 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p &lt; 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p &lt; 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p &lt; 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p &lt; 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p &lt; 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p &lt; 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. Conclusions Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.
Abstract 16466: Total Number of Pregnancies and Atrial Fibrillation Risk: The Women’s Health Study
Authors: Jorge A Wong, Kathryn M Rexrode, Roopinder K Sandhu, David Conen, Christine M Albert
Journal: Circulation (2015)

Introduction: Parity has been associated with an increased risk of cardiovascular disease (CVD), which is thought to be mediated by obesity and insulin resistance. However, the relationship between parity and atrial fibrillation (AF) remains unclear. Methods: We examined 34,636 female health professionals aged ≥45 years and free of AF or CVD at baseline within the Women’s Health Study. Women were prospectively followed for development of new-onset AF, which was confirmed by medical record review. Cox proportional hazards models were used to evaluate the relationship between total number of pregnancies ≥6 months in duration (0-1 [referent], 2-3, 4-5, 6) and incident AF risk. Results: During a median follow-up of 19.2 years, 1467 women developed incident AF. Median baseline age was 52.9 [IQR 48.9, 58.8] years. In multivariable analyses (Table), after adjustment for multiple confounders, including measures of socioeconomic status, hazard ratios (HR) and 95% confidence intervals (95%CI) for incident AF across categories of increasing total number of pregnancies were 1.0, 1.12 (0.94 - 1.33), 1.26 (1.04 - 1.53), and 1.37 (1.06 - 1.76). Further adjustment for time-updated changes in body mass index (BMI), hypertension, diabetes, hypercholesterolemia and other variables did not have a significant impact on these associations. Adjustment for CVD events occurring during follow-up did not significantly alter these results (fully adjusted HRs and 95%CIs across pregnancy categories: 1.0, 1.11 (0.93 - 1.32), 1.25 (1.03 - 1.52), 1.35 (1.05- 1.74); p for linear trend=0.005). Conclusions: In this large prospective cohort, number of prior pregnancies was directly associated with subsequent AF risk among women over age 45. This risk was not mediated by non-fatal CVD events, obesity, and/or diabetes. Repeated exposure to metabolic, physiological and/or hormonal changes during pregnancy may predispose to AF in later life and requires further investigation.
Cost-Sharing and Out-of-Pocket Cost for Women Who Received MRI for Breast Cancer Screening
Authors: I-Wen Pan, Kevin C Oeffinger, Ya-Chen Tina Shih
Journal: JNCI Journal of the National Cancer Institute (2021)

Abstract Background The financial protection of the prevention provision of the Affordable Care Act (ACA) doesn’t apply to breast MRI but only to mammography for breast cancer screening. The purpose of the study is to examine the financial burden among women who received breast magnetic resonance imaging (MRI) for screening. Methods This observational study used the Marketscan database. Women who underwent breast MRI between 2009 and 2017 and had screening mammography within 6 months of the MRI were included. We compared the time trend of the proportion of zero cost-share for women undergoing screening mammography and that for MRI. We quantified out-of-pocket (OOP) costs as the sum of copayment, coinsurance, and deductible and defined zero cost-share as having no OOP cost. We conducted multivariable logistic regression and 2-part model to examine factors associated with zero cost-share and OOP costs of MRI, respectively. Results During the study period, 16 341 women had a screening breast MRI. The proportion of screening MRI claims with zero cost-share decreased from 43.1% (2009) to 26.2% (2017). The adjusted mean OOP cost for women in high-deductible plans was more than twice the cost for their counterparts ($549 vs $251; 2-sided P &amp;lt; .001). Women who resided in the South in the post–Affordable Care Act era were less likely to have zero cost-share and paid higher OOP costs for screening MRI. Conclusions Many women are subject to high financial burden when receiving MRI for breast cancer screening. Those enrolled in high-deductible plans and who reside in the South are especially vulnerable financially.
Abstract 17009: Coronary Multi-stenting Negatively Affects Functional Recovery After Coronary Artery Bypass Grafting for Ischemic Cardiomyopathy
Authors: Shin Yajima, Koichi Toda, Daisuke Yoshioka, Shigeru Miyagawa, Yasushi Yoshikawa, Hiroki Hata, Shunsuke Saito, Tetsuya Saito, Keitaro Domae, Noriyuki Kashiyama, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2017)

Introduction: The impact of functional recovery of the impaired left ventricle after coronary artery bypass grafting (CABG) on the prognosis has not been fully understood. Therefore, we investigate...
Injection‐Free Delivery of MSC‐Derived Extracellular Vesicles for Myocardial Infarction Therapeutics
Authors: Junnan Tang, Xiaolin Cui, Zenglei Zhang, Yanyan Xu, Jiacheng Guo, Bram G Soliman, Yongzheng Lu, Zhen Qin, Qiguang Wang, Hu Zhang, Khoon S Lim, Tim B F Woodfield, Jinying Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract As emerging therapeutic factors, extracellular vesicles (EVs) offer significant potential for myocardial infarction (MI) treatment. Current delivery approaches for EVs involve either intra‐myocardial or intravenous injection, where both have inherent limitations for downstream clinical applications such as secondary tissue injury and low delivery efficiency. Herein, an injection‐free approach for delivering EVs onto the heart surface to treat MI is proposed. By spraying a mixture of EVs, gelatin methacryloyl (GelMA) precursors, and photoinitiators followed by visible light irradiation for 30 s, EVs are physically entrapped within the GelMA hydrogel network covering the surface of the heart, resulting in an enhanced retention rate. Moreover, EVs are gradually released from the hydrogel network through a combination of diffusion and/or enzymatic degradation of the hydrogel, and they are effectively taken up by the sprayed tissue area. More importantly, the released EVs further migrate deep into myocardium tissue, which exerts an improved therapeutic effect. In an MI‐induced mice model, the group treated with EVs‐laden GelMA hydrogels shows significant recovery in cardiac function after 4 weeks. The work demonstrates a new strategy for delivering EVs into cardiac tissues for MI treatment in a localized manner with high retention.
Comparison of antibiotics included in national essential medicines lists of 138 countries using the WHO Access, Watch, Reserve (AWaRe) classification: a cross-sectional study
Authors: Itunuoluwa Adekoya, Darshanand Maraj, Liane Steiner, Hannah Yaphe, Lorenzo Moja, Nicola Magrini, Graham Cooke, Mark Loeb, Nav Persaud
Journal: The Lancet Infectious Diseases (2021)
Is it really necessary to achieve R0 resection in duodenal superficial lesions? If yes, does it justify surgery?
Authors: Pierre H. Deprez
Journal: Endoscopy (2021)

Superficial duodenal lesions include several types of tumor, namely nonampullary duodenal adenomas, which range in size from a few millimeters to several centimeters and rarely have extensive circumferential extension into the papilla, adenocarcinomas, and subepithelial lesions (SELs; mainly neuroendocrine tumors and stromal tumors). Multiple other lesions are described in the duodenum but they do not require follow-up or resection (Brunner’s hyperplasia, gastric heterotopy, lipoma, or submucosal cysts). The first step in management is therefore to make a precise endoscopic differential diagnosis, possibly assisted by echo endoscopy with a diagnostic fine-needle biopsy in cases of SELs.
Human γδ T cell sensing of AMPK-dependent metabolic tumor reprogramming through TCR recognition of EphA2
Authors: Christelle Harly, Stephen Paul Joyce, Charlotte Domblides, Thomas Bachelet, Vincent Pitard, Charlotte Mannat, Angela Pappalardo, Lionel Couzi, Sonia Netzer, Layal Massara, Emilie Obre, Omar Hawchar, Lydia Lartigue, Stéphane Claverol, Carla Cano, Jean-François Moreau, Isabelle Mahouche, Isabelle Soubeyran, Rodrigue Rossignol, Benoit Viollet, Carrie R. Willcox, Fiyaz Mohammed, Benjamin E. Willcox, Benjamin Faustin, Julie Déchanet-Merville
Journal: Science Immunology (2021)

Human γδ T cells contribute to tissue homeostasis and participate in epithelial stress surveillance through mechanisms that are not well understood. Here, we identified ephrin type-A receptor 2 (EphA2) as a stress antigen recognized by a human Vγ9Vδ1 TCR. EphA2 is recognized coordinately by ephrin A to enable γδ TCR activation. We identified a putative TCR binding site on the ligand-binding domain of EphA2 that was distinct from the ephrin A binding site. Expression of EphA2 was up-regulated upon AMP-activated protein kinase (AMPK)-dependent metabolic reprogramming of cancer cells, and coexpression of EphA2 and active AMPK in tumors was associated with higher CD3 T cell infiltration in human colorectal cancer tissue. These results highlight the potential of the human γδ TCR to cooperate with a co-receptor to recognize non-MHC-encoded proteins as signals of cellular dysregulation, potentially allowing γδ T cells to sense metabolic energy changes associated with either viral infection or cancer.
Mental health, substance use, experiences of violence, and access to health care among transgender and non-binary people during the COVID-19 lockdown in Argentina
Authors: Pablo D. Radusky, Nadir Cardozo, Mariana Duarte, Solange Fabian, Emilia Frontini, Omar Sued, Ines Aristegui
Journal: International Journal of Transgender Health (2021)

Background: Lockdown measures are effective to control COVID-19 spread; however, concerns have increased regarding its impact on transgender and non-binary people.Aims: This study describes self-reported changes in mental health, substance use, experiences of violence, and access to health care and basic services among transgender and non-binary population from Argentina after two months of implementation of the lockdown.Methods: An online national survey was responded by 182 participants (72 transfeminine [TF], 66 transmasculine [TM], 44 non-binary [NB] people) between May and June 2020. The questionnaire was informed by the results of focus groups, reviewed by activists, and disseminated through social media. Descriptive statistics were used to summarize data.Results: The COVID-19 pandemic and the lockdown have had a general negative impact on the participants. TF participants reported a greater proportion of negative changes in the socioeconomic aspect, such as reduction in income and barriers to access basic services (housing, food, hygiene products and financial assistance). TM and NB participants reported higher proportions of adverse psychological impact, with high frequencies of intense negative emotions and suicidal ideation. A general reduction in substance use was observed in the three groups. The most frequent source of violence in the three groups was from a family member, especially among NB participants. Half of the TF and TM individuals reported difficulties to access or continue their hormone therapy. TM and NB participants reported considerable barriers to access mental health care.Conclusion: The COVID-19 pandemic and the prolonged lockdown have had a negative impact on the transgender and NB population, aggravating their preexisting situation of vulnerability and exclusion. Furthermore, this impact affected each subgroup differently in a particular and specific way.
<i>Pseudomonas aeruginosa</i> and chronic lung allograft dysfunction: does evading an iceberg prevent the ship from sinking?
Authors: Robin Vos, Anke Van Herck
Journal: European Respiratory Journal (2021)

<b>Respiratory tract colonisation with <i>Pseudomonas aeruginosa</i> may represent a treatable trait to avert subsequent development of chronic lung allograft dysfunction in lung transplant recipients</b>https://bit.ly/35rCVhW
Tobacco industry capitalises on the COVID-19 pandemic
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2021)

The COVID-19 pandemic does not seem to have done much damage to the tobacco industry. "Beyond disruption to supply chains, analysts believe the short-term impact of COVID-19 on the tobacco industry will be relatively limited", states British American Tobacco (BAT) on their website. They add that "it is likely that key cigarette volumes were only slightly lower than expected in 2020". Having started the year by worrying about reduced consumption and stock shortages occasioned by factory closures, by the end of 2020 the major tobacco firms were raising their sales and profit targets.
Pannexin 1 channels facilitate communication between T cells to restrict the severity of airway inflammation
Authors: Christopher B. Medina, Yu-Hsin Chiu, Marta E. Stremska, Christopher D. Lucas, Ivan Poon, Kenneth S. Tung, Michael R. Elliott, Bimal Desai, Ulrike M. Lorenz, Douglas A. Bayliss, Kodi S. Ravichandran
Journal: Immunity (2021)

Allergic airway inflammation is driven by type-2 CD4+ T cell inflammatory responses. We uncover an immunoregulatory role for the nucleotide release channel, Panx1, in T cell crosstalk during airway disease. Inverse correlations between Panx1 and asthmatics and our mouse models revealed the necessity, specificity, and sufficiency of Panx1 in T cells to restrict inflammation. Global Panx1−/− mice experienced exacerbated airway inflammation, and T-cell-specific deletion phenocopied Panx1−/− mice. A transgenic designed to re-express Panx1 in T cells reversed disease severity in global Panx1−/− mice. Panx1 activation occurred in pro-inflammatory T effector (Teff) and inhibitory T regulatory (Treg) cells and mediated the extracellular-nucleotide-based Treg-Teff crosstalk required for suppression of Teff cell proliferation. Mechanistic studies identified a Salt-inducible kinase-dependent phosphorylation of Panx1 serine 205 important for channel activation. A genetically targeted mouse expressing non-phosphorylatable Panx1S205A phenocopied the exacerbated inflammation in Panx1−/− mice. These data identify Panx1-dependent Treg:Teff cell communication in restricting airway disease.
Multi-omic profiling of plasma reveals molecular alterations in children with COVID-19
Authors: Chong Wang, Xufang Li, Wanshan Ning, Sitang Gong, Fengxia Yang, Chunxiao Fang, Yu Gong, Di Wu, Muhan Huang, Yujie Gou, Shanshan Fu, Yujie Ren, Ruyi Yang, Yang Qiu, Yu Xue, Yi Xu, Xi Zhou
Journal: Theranostics (2021)

Children usually develop less severe symptoms responding to Coronavirus Disease 2019 (COVID-19) than adults. However, little is known about the molecular alterations and pathogenesis of COVID-19 in children.
Missing Self–Induced Microvascular Rejection of Kidney Allografts: A Population-Based Study
Authors: Jasper Callemeyn, Aleksandar Senev, Maarten Coemans, Evelyne Lerut, Ben Sprangers, Dirk Kuypers, Alice Koenig, Olivier Thaunat, Marie-Paule Emonds, Maarten Naesens
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Microvascular inflammation (MVI) of the kidney transplant is an important determinant of allograft outcome. Although MVI is considered a cardinal manifestation of antibody-mediated rejection, it is often encountered in the absence of circulating donor-specific antibodies, which raises uncertainty about the underlying cause. The authors used genotyping of killer cell Ig-like receptors of recipients and high-resolution HLA genotyping to assess the presence of missing self, a nonhumoral natural killer cell stimulus, in a large cohort of kidney transplantations. They found that missing self specifically increases the risk of MVI after transplantation, and could explain one fifth of patients without detectable antibodies. This study suggests systematic evaluation of missing self improves our understanding of MVI, and might be relevant for improved diagnostic classification and patient risk stratification. Background Circulating anti-HLA donor-specific antibodies (HLA-DSA) are often absent in kidney transplant recipients with microvascular inflammation (MVI). Missing self, the inability of donor endothelial cells to provide HLA I–mediated signals to inhibitory killer cell Ig-like receptors (KIRs) on recipient natural killer cells, can cause endothelial damage in vitro , and has been associated with HLA-DSA–negative MVI. However, missing self’s clinical importance as a nonhumoral trigger of allograft rejection remains unclear. Methods In a population-based study of 924 consecutive kidney transplantations between March 2004 and February 2013, we performed high-resolution donor and recipient HLA typing and recipient KIR genotyping. Missing self was defined as the absence of A3/A11, Bw4, C1, or C2 donor genotype, with the presence of the corresponding educated recipient inhibitory KIR gene. Results We identified missing self in 399 of 924 transplantations. Co-occurrence of missing self types had an additive effect in increasing MVI risk, with a threshold at two concurrent types (hazard ratio [HR], 1.78; 95% confidence interval [95% CI], 1.26 to 2.53), independent of HLA-DSA (HR, 5.65; 95% CI, 4.01 to 7.96). Missing self and lesions of cellular rejection were not associated. No HLA-DSAs were detectable in 146 of 222 recipients with MVI; 28 of the 146 had at least two missing self types. Missing self associated with transplant glomerulopathy after MVI (HR, 2.51; 95% CI, 1.12 to 5.62), although allograft survival was better than with HLA-DSA–associated MVI. Conclusion Missing self specifically and cumulatively increases MVI risk after kidney transplantation, independent of HLA-DSA. Systematic evaluation of missing self improves understanding of HLA-DSA–negative MVI and might be relevant for improved diagnostic classification and patient risk stratification.