tbuckley/cabot-search huggingface dataset:
Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression
Authors: Urmo Võsa, Annique Claringbould, Harm-Jan Westra, Marc Jan Bonder, Patrick Deelen, Biao Zeng, Holger Kirsten, Ashis Saha, Roman Kreuzhuber, Seyhan Yazar, Harm Brugge, Roy Oelen, Dylan H. de Vries, Monique G. P. van der Wijst, Silva Kasela, Natalia Pervjakova, Isabel Alves, Marie-Julie Favé, Mawussé Agbessi, Mark W. Christiansen, Rick Jansen, Ilkka Seppälä, Lin Tong, Alexander Teumer, Katharina Schramm, Gibran Hemani, Joost Verlouw, Hanieh Yaghootkar, Reyhan Sönmez Flitman, Andrew Brown, Viktorija Kukushkina, Anette Kalnapenkis, Sina Rüeger, Eleonora Porcu, Jaanika Kronberg, Johannes Kettunen, Bernett Lee, Futao Zhang, Ting Qi, Jose Alquicira Hernandez, Wibowo Arindrarto, Frank Beutner, Peter A. C. ’t Hoen, Joyce van Meurs, Jenny van Dongen, Maarten van Iterson, Morris A. Swertz, Marc Jan Bonder, Julia Dmitrieva, Mahmoud Elansary, Benjamin P. Fairfax, Michel Georges, Bastiaan T. Heijmans, Alex W. Hewitt, Mika Kähönen, Yungil Kim, Julian C. Knight, Peter Kovacs, Knut Krohn, Shuang Li, Markus Loeffler, Urko M. Marigorta, Hailang Mei, Yukihide Momozawa, Martina Müller-Nurasyid, Matthias Nauck, Michel G. Nivard, Brenda W. J. H. Penninx, Jonathan K. Pritchard, Olli T. Raitakari, Olaf Rotzschke, Eline P. Slagboom, Coen D. A. Stehouwer, Michael Stumvoll, Patrick Sullivan, Peter A. C. ’t Hoen, Joachim Thiery, Anke Tönjes, Jenny van Dongen, Maarten van Iterson, Jan H. Veldink, Uwe Völker, Robert Warmerdam, Cisca Wijmenga, Morris Swertz, Anand Andiappan, Grant W. Montgomery, Samuli Ripatti, Markus Perola, Zoltan Kutalik, Emmanouil Dermitzakis, Sven Bergmann, Timothy Frayling, Joyce van Meurs, Holger Prokisch, Habibul Ahsan, Brandon L. Pierce, Terho Lehtimäki, Dorret I. Boomsma, Bruce M. Psaty, Sina A. Gharib, Philip Awadalla, Lili Milani, Willem H. Ouwehand, Kate Downes, Oliver Stegle, Alexis Battle, Peter M. Visscher, Jian Yang, Markus Scholz, Joseph Powell, Greg Gibson, Tõnu Esko, Lude Franke
Journal: Nature Genetics (2021)
In suspected COVID-19, RT-PCR with nasal plus throat swabs has 97% sensitivity vs. nasopharyngeal swabs
Authors: Dennis G. Maki
Journal: Annals of Internal Medicine (2021)

Tsang NN, So HC, Ng KY, et al. Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis. Lancet Infect Dis. 2021. [Epub ahead of print.] 33857405.
Teprasiran, a Small Interfering RNA, for the Prevention of Acute Kidney Injury in High-Risk Patients Undergoing Cardiac Surgery: A Randomized Clinical Study
Authors: Matthias Thielmann, David Corteville, Gabor Szabo, Madhav Swaminathan, Andre Lamy, Lukas J. Lehner, Craig D. Brown, Nicolas Noiseux, Mohamed G. Atta, Elizabeth C. Squiers, Shai Erlich, Daniel Rothenstein, Bruce Molitoris, C. David Mazer
Journal: Circulation (2021)

Background: Acute kidney injury (AKI) affects up to 30% of patients undergoing cardiac surgery, leading to increased in-hospital and long-term morbidity and mortality. Teprasiran is a novel small interfering RNA that temporarily inhibits p53-mediated cell death that underlies AKI. Methods: This prospective, multicenter, double-blind, randomized, controlled phase 2 trial evaluated the efficacy and safety of a single 10 mg/kg dose of teprasiran versus placebo (1:1), in reducing the incidence, severity, and duration of AKI after cardiac surgery in high-risk patients. The primary end point was the proportion of patients who developed AKI determined by serum creatinine by postoperative day 5. Other end points included AKI severity and duration using various prespecified criteria. To inform future clinical development, a composite end point of major adverse kidney events at day 90, including death, renal replacement therapy, and ≥25% reduction of estimated glomerular filtration rate was assessed. Both serum creatinine and serum cystatin-C were used for estimated glomerular filtration rate assessments. Results: A total of 360 patients were randomly assigned in 41 centers; 341 dosed patients were 73±7.5 years of age (mean±SD), 72% were men, and median European System for Cardiac Operative Risk Evaluation score was 2.6%. Demographics and surgical parameters were similar between groups. AKI incidence was 37% for teprasiran- versus 50% for placebo-treated patients, a 12.8% absolute risk reduction, P =0.02; odds ratio, 0.58 (95% CI, 0.37–0.92). AKI severity and duration were also improved with teprasiran: 2.5% of teprasiran- versus 6.7% of placebo-treated patients had grade 3 AKI; 7% teprasiran- versus 13% placebo-treated patients had AKI lasting for 5 days. No significant difference was observed for the major adverse kidney events at day 90 composite in the overall population. No safety issues were identified with teprasiran treatment. Conclusions: The incidence, severity, and duration of early AKI in high-risk patients undergoing cardiac surgery were significantly reduced after teprasiran administration. A phase 3 study with a major adverse kidney event at day 90 primary outcome that has recently completed enrollment was designed on the basis of these findings (NCT03510897). Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02610283.
Fungal diseases: Oral dysbiosis in susceptible hosts
Authors: Cristina Cunha Villar, Anna Dongari‐Bagtzoglou
Journal: Periodontology 2000 (2021)

Abstract The oral cavity is colonized by a large number of microorganisms that are referred to collectively as the oral microbiota. These indigenous microorganisms have evolved in symbiotic relationships with the oral mucosal immune system and are involved in maintaining homeostasis in the oral cavity. Although Candida species are commonly found in the healthy oral cavity without causing infection, these fungi can become pathogenic. Recents advances indicate that the development of oral candidiasis is driven both by Candida albicans overgrowth in a dysbiotic microbiome and by disturbances in the host's immune system. Perturbation of the oral microbiota triggered by host‐extrinsic (ie, medications), host‐intrinsic (ie, host genetics), and microbiome‐intrinsic (ie, microbial interactions) factors may increase the risk of oral candidiasis. In this review, we provide an overview of the oral mycobiome, with a particular focus on the interactions of Candida albicans with some of the most common oral bacteria and the oral mucosal immune system. Also, we present a summary of our current knowledge of the host‐intrinsic and host‐extrinsic factors that can predispose to oral candidiasis.
Gastric adenocarcinoma of fundic gland type with two closely located lesions endoscopically resected en masse
Authors: Tomohiko Mannami, Takehiro Tanaka, Nobukiyo Fujiwara
Journal: Endoscopy (2021)

A 73-year-old man with type 2 diabetes mellitus, but otherwise healthy, underwent esophagogastroduodenoscopy screening. The examination revealed red streaks and no atrophic mucosal areas. Therefore, Helicobacter pylori infection was not suspected. Two small lesions < 2 mm in diameter and located < 1 cm apart were observed in the fornix. Both lesions were similar: whitish and flat with poorly defined borders ([Fig. 1]). A biopsy from the anterior-sided lesion was diagnosed as gastric adenocarcinoma of the fundic gland type.
HIF in the heart: development, metabolism, ischemia, and atherosclerosis
Authors: Andrew Kekūpaʻa Knutson, Allison L. Williams, William A. Boisvert, Ralph V. Shohet
Journal: Journal of Clinical Investigation (2021)

The heart forms early in development and delivers oxygenated blood to the rest of the embryo. After birth, the heart requires kilograms of ATP each day to support contractility for the circulation. Cardiac metabolism is omnivorous, utilizing multiple substrates and metabolic pathways to produce this energy. Cardiac development, metabolic tuning, and the response to ischemia are all regulated in part by the hypoxia-inducible factors (HIFs), central components of essential signaling pathways that respond to hypoxia. Here we review the actions of HIF1, HIF2, and HIF3 in the heart, from their roles in development and metabolism to their activity in regeneration and preconditioning strategies. We also discuss recent work on the role of HIFs in atherosclerosis, the precipitating cause of myocardial ischemia and the leading cause of death in the developed world.
Novel Mouse Models of Bladder Cancer Identify a Prognostic Signature Associated with Risk of Disease Progression
Authors: Soonbum Park, Lijie Rong, Tomasz B. Owczarek, Matteo Di Bernardo, Rivka L. Shoulson, Chee-Wai Chua, Jaime Y. Kim, Amir Lankarani, Prithi Chakrapani, Talal Syed, James M. McKiernan, David B. Solit, Michael M. Shen, Hikmat A. Al-Ahmadie, Cory Abate-Shen
Journal: Cancer Research (2021)

Abstract To study the progression of bladder cancer from non–muscle-invasive to muscle-invasive disease, we have developed a novel toolkit that uses complementary approaches to achieve gene recombination in specific cell populations in the bladder urothelium in vivo, thereby allowing us to generate a new series of genetically engineered mouse models (GEMM) of bladder cancer. One method is based on the delivery of adenoviruses that express Cre recombinase in selected cell types in the urothelium, and a second uses transgenic drivers in which activation of inducible Cre alleles can be limited to the bladder urothelium by intravesicular delivery of tamoxifen. Using both approaches, targeted deletion of the Pten and p53 tumor suppressor genes specifically in basal urothelial cells gave rise to muscle-invasive bladder tumors. Furthermore, preinvasive lesions arising in basal cells displayed upregulation of molecular pathways related to bladder tumorigenesis, including proinflammatory pathways. Cross-species analyses comparing a mouse gene signature of early bladder cancer with a human signature of bladder cancer progression identified a conserved 28-gene signature of early bladder cancer that is associated with poor prognosis for human bladder cancer and that outperforms comparable gene signatures. These findings demonstrate the relevance of these GEMMs for studying the biology of human bladder cancer and introduce a prognostic gene signature that may help to stratify patients at risk for progression to potentially lethal muscle-invasive disease. Significance: Analyses of bladder cancer progression in a new series of genetically engineered mouse models has identified a gene signature of poor prognosis in human bladder cancer.
포스터 발표 : HBe항원 음성 만성 B형 간염 환자에서 혈청 HBV DNA치와 ALT치의 상관성
Authors: 나일환, 이상용, 허정, 김광하, 강대환, 송근암, 조몽, 양웅석
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 만성 B형 간염 바이러스 감염자에서 상당수의 환자에서는 HBe항원이 소실되는 혈청전환 후 비증폭 방법에 의한 검사법(hybridization assay)으로 HBV DNA가 검출되지 않아도 간 내 염증이 지속되는 경우가 있다. 최근 보다 예민한 정량 PCR법이 개발됨으로서 미량의 혈청 HBV DNA도 측정 가능하게 되었다. 본 연구에서는 HBe항원 음성 만성 B형 간염 바이러스 감염자에서 혈청 HBV DNA치와 ALT치의 상관관계를 조사하였다. 대상과 방법: 혈청 생화학 검사와 혈청 HBV DNA 정량검사가 동시에 시행된 HBe항원 음성 만성 B형 간염 바이러스 감염자 82명을 대상으로 하였다. 대상군의 평균 연령은 45세였으며, 남녀비는 각각 61명, 21명이었다. 만성 간염은 ALT치를 기준으로 ALT/UNL의 1-2배에 해당하는 I군과 ALT/UNL의 2배이상으로 상승된 II군으로 분류하였다. HBV DNA 정량은 민감도가 200 copies/mL인 Cobas amplicor HBV Monitor(TM)법으로 측정하였다. 영상 소견과 조직 소견으로 만성 간염과 간경변으로 구분하였다. 결과: 혈청 HBV DNA치는 II군의 경우 중앙값 1.0×106 copies/mL로 I군의 경우 중앙값 5.6×104 copies/mL보다 유의하게 높았다(p＝0.000). 간경변 환자(중앙값 2.0×05 copies/mL)는 만성 간염 환자(중앙값 4.7×105 copies/mL)보다 HBV DNA치가 낮았으나 통계적 유의성은 없었다(p＞0.05). 전체 환자에서 ALT치와 HBV DNA양과는 유의한 양의 상관관계가 있었으나(r＝0.416, p＝0.000), 각 군별로는 유의한 상관관계가 없었다(p＞0.05). 결론: HBe항원 음성 만성 B형 간염 바이러스 감염자에서 ALT치를 기준으로 두 군으로 나누었을 때, ALT/UNL의 2배이상으로 상승된 군이 ALT/UNL의 1∼2배에 해당하는 군보다 혈청 HBV DNA치가 유의하게 높았다.
Ward based management of dementia symptoms: check the patient can hear you
Authors: Ted Leverton
Journal: BMJ (2021)

Essentials, 7-14 August

Good news! Unlike so many papers from specialists treating dementia, Nguyen and colleagues mentioned the need to assess hearing impairment.1 Albeit as an aside on the fourth page.

In the case described, the 81 year old patient is likely to have lost one or both her hearing aids (if they have not been removed and set aside on the ward, as often happens). In …
Aberrant gut-microbiota-immune-brain axis development in premature neonates with brain damage
Authors: David Seki, Margareta Mayer, Bela Hausmann, Petra Pjevac, Vito Giordano, Katharina Goeral, Lukas Unterasinger, Katrin Klebermaß-Schrehof, Kim De Paepe, Tom Van de Wiele, Andreas Spittler, Gregor Kasprian, Benedikt Warth, Angelika Berger, David Berry, Lukas Wisgrill
Journal: Cell Host & Microbe (2021)
Cardiovascular disease related circulating biomarkers and cancer incidence and mortality: is there an association?
Authors: Manol Jovani, Elizabeth E Liu, Samantha M Paniagua, Emily S Lau, Shawn X Li, Katherine S Takvorian, Bernard E Kreger, Greta Lee Splansky, Rudolf A de Boer, Amit D Joshi, Shih Jen Hwang, Chen Yao, Tianxiao Huan, Paul Courchesne, Martin G Larson, Daniel Levy, Andrew T Chan, Jennifer E Ho
Journal: Cardiovascular Research (2021)

Abstract Aims Recent studies suggest an association between cardiovascular disease (CVD) and cancer incidence/mortality, but the pathophysiological mechanisms underlying these associations are unclear. We aimed to examine biomarkers previously associated with CVD and study their association with incident cancer and cancer-related death in a prospective cohort study. Methods and results We used a proteomic platform to measure 71 cardiovascular biomarkers among 5032 participants in the Framingham Heart Study who were free of cancer at baseline. We used multivariable-adjusted Cox models to examine the association of circulating protein biomarkers with risk of cancer incidence and mortality. To account for multiple testing, we set a 2-sided false discovery rate &amp;lt;0.05. Growth differentiation factor-15 (also known as macrophage inhibitory cytokine-1) was associated with increased risk of incident cancer [hazards ratio (HR) per 1 standard deviation increment 1.31, 95% CI 1.17–1.47], incident gastrointestinal cancer (HR 1.85, 95% CI 1.37–2.50), incident colorectal cancer (HR 1.94, 95% CI 1.29–2.91), and cancer-related death (HR 2.15, 95% CI 1.72–2.70). Stromal cell-derived factor-1 showed an inverse association with cancer-related death (HR 0.75, 95% CI 0.65–0.86). Fibroblast growth factor-23 showed an association with colorectal cancer (HR 1.55, 95% CI 1.20–2.00), and granulin was associated with haematologic cancer (HR 1.61, 95% CI 1.30–1.99). Other circulating biomarkers of inflammation, immune activation, metabolism, and fibrosis showed suggestive associations with future cancer diagnosis. Conclusion We observed several significant associations between circulating CVD biomarkers and cancer, supporting the idea that shared biological pathways underlie both diseases. Further investigations of specific mechanisms that lead to both CVD and cancer are warranted.
Effect of Vaccination on Transmission of SARS-CoV-2
Authors: Anoop S V Shah, Ciara Gribben, Jennifer Bishop, Peter Hanlon, David Caldwell, Rachael Wood, Martin Reid, Jim McMenamin, David Goldberg, Diane Stockton, Sharon Hutchinson, Chris Robertson, Paul M McKeigue, Helen M Colhoun, David A McAllister
Journal: New England Journal of Medicine (2021)

Effect of Vaccination on Transmission of SARS-CoV-2 In this report from Scotland, vaccination of health care workers for SARS-CoV-2 was associated with a decrease in household transmission.
Mechanotopography‐Driven Design of Dispersible Nanofiber‐Laden Hydrogel as a 3D Cell Culture Platform for Investigating Tissue Fibrosis
Authors: Suntae Kim, Cholong Choi, Chaenyung Cha
Journal: Advanced Healthcare Materials (2021)

Fibrosis is one of the most frequent occurrences during one's lifetime, identified by various physiological changes including, most notably, excessive deposition of extracellular matrix (ECM). Despite its physiological importance, it is still a significant challenge to conduct a systematic investigation of tissue fibrosis, mainly due to the lack of in vitro 3D tissue model that can accurately portray the characteristic features of fibrotic events. Herein, a hybrid hydrogel system incorporating dispersible nanofibers is developed to emulate highly collagenous deposits formed within a fibrotic tissue leading to altered mechanotopographical properties. Micrometer-length, aqueous-stable nanofibers consisting of crosslinked gelatin network embedded with graphene oxide (GO) or reduced graphene (rGO) are infused into hydrogel, resulting in controllable mechanotopographical properties while maintaining permeability sufficiently enough for various cellular activities. Ultimately, the ability to induce fibrotic behavior of fibroblasts cultured in these mechanotopography-controlled, nanofiber-laden hydrogels is investigated in detail.
Improve care pathways for covid now to do better when the next variant or pandemic hits
Authors: Daniel K Goyal
Journal: BMJ (2021)

How did we let it get to this stage? Abbasi asks.1 The answers are not forthcoming. A brash and, despite its numerous failures, emboldened government finally get the release it needs: attempted herd immunity.

Like most “calculated” decisions made by our political elite, the unilateral costs of lives saved versus economic wellbeing falter in the face of reality. Beyond what …
Decomposing normal and abnormal features of medical images for content-based image retrieval of glioma imaging
Authors: Kazuma Kobayashi, Ryuichiro Hataya, Yusuke Kurose, Mototaka Miyake, Masamichi Takahashi, Akiko Nakagawa, Tatsuya Harada, Ryuji Hamamoto
Journal: Medical Image Analysis (2021)

In medical imaging, the characteristics purely derived from a disease should reflect the extent to which abnormal findings deviate from the normal features. Indeed, physicians often need corresponding images without abnormal findings of interest or, conversely, images that contain similar abnormal findings regardless of normal anatomical context. This is called comparative diagnostic reading of medical images, which is essential for a correct diagnosis. To support comparative diagnostic reading, content-based image retrieval (CBIR) that can selectively utilize normal and abnormal features in medical images as two separable semantic components will be useful. In this study, we propose a neural network architecture to decompose the semantic components of medical images into two latent codes: normal anatomy code and abnormal anatomy code. The normal anatomy code represents counterfactual normal anatomies that should have existed if the sample is healthy, whereas the abnormal anatomy code attributes to abnormal changes that reflect deviation from the normal baseline. By calculating the similarity based on either normal or abnormal anatomy codes or the combination of the two codes, our algorithm can retrieve images according to the selected semantic component from a dataset consisting of brain magnetic resonance images of gliomas. Moreover, it can utilize a synthetic query vector combining normal and abnormal anatomy codes from two different query images. To evaluate whether the retrieved images are acquired according to the targeted semantic component, the overlap of the ground-truth labels is calculated as metrics of the semantic consistency. Our algorithm provides a flexible CBIR framework by handling the decomposed features with qualitatively and quantitatively remarkable results.
Deep learning to identify a gene signature associated with molecular subtypes that predicts prognosis in colorectal cancer.
Authors: Du Cai, Wei Wang, Min-Er Zhong, Dejun Fan, Xuanhui Liu, Cheng-Hang Li, Ze-Ping Huang, Qiqi Zhu, Min-Yi Lv, Chuling Hu, Xin Duan, Xiaojian Wu, Feng Gao
Journal: Journal of Clinical Oncology (2021)

e15520 Background: Identifying robust prognostic risk groups of colorectal cancer (CRC) will significantly improve patients’ outcomes. However, CRC has been demonstrated to be molecularly heterogeneous which affected clinical decision-making. Recently, a comprehensive study proposed four consensus molecular subtypes (CMSs) of CRC with a comprehensive biological and clinical characterization, but a cost-effective clinical assay for prognosis is lacking. To fill this gap, we present a supervised framework using deep learning to identify CMS associated gene signature for prognosis. Methods: A total of 1,729 CRC patients with complete follow-up data were included in this study. We first applied a supervised deep learning-based framework in the training cohort ( n = 624) to extract the CMS-associated deep features and then identified a gene panel highly correlated to these deep features. Subsequently, the prognostic power of this gene signature was evaluated on 6 independent CRC datasets. Results: We identified a 21-gene signature associated CMS subtypes and a trained risk model significantly predicted patients’ disease-free survival (DFS) on six independent CRC datasets ( n = 1,729): Training cohort ( n = 624, HR = 2.53, 95% CI: 1.53-4.18, P &lt; 0.001), Validation 1 cohort ( n = 557, HR = 1.77, 95%CI: 1.27 – 2.47, P &lt; 0.001) and Validation 2 cohort merged by other four datasets ( n = 548, HR = 2.10, 95%CI: 1.50 – 2.93, P &lt; 0.001). Especially, this 21-gene signature can also stratify stage 2 and 3 patients into distinct survival groups: Training cohort ( n = 338, HR = 2.14, 95%CI: 1.18-3.85, P &lt; 0.01), Validation 1 cohort ( n = 457, HR = 1.63, 95%CI: 1.12 – 2.37, P &lt; 0.01) and Validation 2 cohort ( n = 437, HR = 1.73, 95%CI: 1.37 – 2.82, P &lt; 0.001), outperformed Oncotype DX on the same cohorts. Conclusions: To summarize, using our DL-based framework, we successfully developed a CMS-associated gene signature for robust prognostic prediction in CRC. Compared with genome-wide expression profile-based CMS classification system, the 21-gene panel can be easily deployed in clinical practice to facilitate decision making.