tbuckley/cabot-search huggingface dataset:
The Sources of Parent-Child Transmission of Risk for Suicide Attempt and Deaths by Suicide in Swedish National Samples
Authors: Kenneth S. Kendler, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist, Alexis C. Edwards
Journal: American Journal of Psychiatry (2020)

The authors aimed to clarify the sources of parent-child transmission for suicide attempt and death by suicide.Three sources of parent-child resemblance (genes plus rearing, genes only, and rearing only) were examined in parents and offspring from four family types from Swedish national samples: intact nuclear families, families with a not-lived-with biological father, families with a stepfather, and adoptees and their biological and adoptive parents. Parent-child resemblance was assessed primarily by tetrachoric correlation.For suicide attempt to suicide attempt transmission, best-estimate tetrachoric correlations for genes plus rearing, genes only, and rearing only were 0.23 (95% CI=0.23, 0.24), 0.13 (95% CI=0.11, 0.15), and 0.14 (95% CI=0.11, 0.16), respectively. Suicide attempt was more strongly transmitted to male offspring compared with female offspring. Parental psychiatric disorders accounted for 40% of the genetic transmission but had no impact on rearing effects. For suicide death to suicide death transmission, best estimates of tetrachoric correlations for genes plus rearing, genes only, and rearing only were 0.16 (95% CI=0.15, 0.18), 0.07 (95% CI=0.02, 0.12), and -0.05 (95% CI=-0.17, 0.07), respectively. Although the suicide attempt-suicide death genetic correlation was high (0.84), the hypothesis that they reflect behaviors only differing in severity on the same continuum of genetic liability could be rejected.The transmission of suicide attempt across generations is moderately strong and arises equally from genetic and rearing effects. Parental psychiatric illness explains almost half of the genetic transmission of suicide attempt but none of the rearing effect. Suicide death is modestly transmitted across generations, probably via genetic effects, although rearing may play a role. While suicide attempt and suicide death share a substantial proportion of their hereditary risk, they do not, from a genetic perspective, simply reflect milder and more severe forms of the same diathesis.
Covid-19: White House told CDC to stop recommending tests for asymptomatic contacts
Authors: Owen Dyer
Journal: BMJ (2020)

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Maternal Influenza A(H1N1) Immunization During Pregnancy and Risk for Autism Spectrum Disorder in Offspring
Authors: Jonas F. Ludvigsson, Henric Winell, Sven Sandin, Sven Cnattingius, Olof Stephansson, Björn Pasternak
Journal: Annals of Internal Medicine (2020)

There are concerns that influenza vaccine exposure during pregnancy may be associated with increased risk for autism spectrum disorder (ASD).To examine the risk for ASD in offspring of mothers who were vaccinated against influenza A(H1N1)pdm09 ("swine flu") during pregnancy.Population-based cohort study using nationwide registers.Seven health care regions in Sweden.Live births between October 2009 and September 2010, with follow-up through December 2016. In total, 39 726 infants were prenatally exposed to H1N1 vaccine (13 845 during the first trimester) and 29 293 infants were unexposed.Cox regression was used to estimate hazard ratios (HRs) for the primary outcome, ASD, before and after adjustment for potential confounders. The secondary outcome was autistic disorder (AD).Mean follow-up was 6.7 years in both unexposed and exposed children. During follow-up, 394 (1.0%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD. In adjusted analyses, prenatal exposure to H1N1 vaccination was not associated with a later diagnosis of ASD (adjusted HR [aHR], 0.95 [95% CI, 0.81 to 1.12]) or AD (aHR, 0.96 [CI, 0.80 to 1.16]). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (CI, -0.09% to 0.17%) for ASD and 0.02% (CI, -0.09% to 0.14%) for AD. Restricting the analysis to vaccination in the first trimester of pregnancy did not influence risk estimates (aHR, 0.92 [CI, 0.74 to 1.16] for ASD and 0.91 [CI, 0.70 to 1.18] for AD).Data on H1N1 influenza infection are lacking.This large cohort study found no association between maternal H1N1 vaccination during pregnancy and risk for ASD in the offspring.Swedish Research Council.
Humoral Immune Response to SARS-CoV-2 in Iceland
Authors: Daniel F Gudbjartsson, Gudmundur L Norddahl, Pall Melsted, Kristbjorg Gunnarsdottir, Hilma Holm, Elias Eythorsson, Asgeir O Arnthorsson, Dadi Helgason, Kristbjorg Bjarnadottir, Ragnar F Ingvarsson, Brynja Thorsteinsdottir, Steinunn Kristjansdottir, Kolbrun Birgisdottir, Anna M Kristinsdottir, Martin I Sigurdsson, Gudny A Arnadottir, Erna V Ivarsdottir, Margret Andresdottir, Frosti Jonsson, Arna B Agustsdottir, Jonas Berglund, Berglind Eiriksdottir, Run Fridriksdottir, Elisabet E Gardarsdottir, Magnus Gottfredsson, Olafia S Gretarsdottir, Steinunn Gudmundsdottir, Kjartan R Gudmundsson, Thora R Gunnarsdottir, Arnaldur Gylfason, Agnar Helgason, Brynjar O Jensson, Aslaug Jonasdottir, Hakon Jonsson, Thordur Kristjansson, Karl G Kristinsson, Droplaug N Magnusdottir, Olafur T Magnusson, Lovisa B Olafsdottir, Solvi Rognvaldsson, Louise le Roux, Gudrun Sigmundsdottir, Asgeir Sigurdsson, Gardar Sveinbjornsson, Kristin E Sveinsdottir, Maney Sveinsdottir, Emil A Thorarensen, Bjarni Thorbjornsson, Marianna Thordardottir, Jona Saemundsdottir, S Hjortur Kristjansson, Kamilla S Josefsdottir, Gisli Masson, Gudmundur Georgsson, Mar Kristjansson, Alma Moller, Runolfur Palsson, Thorolfur Gudnason, Unnur Thorsteinsdottir, Ingileif Jonsdottir, Patrick Sulem, Kari Stefansson
Journal: New England Journal of Medicine (2020)

Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed.Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR.Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.
Consensus definitions for glomerular lesions by light and electron microscopy: recommendations from a working group of the Renal Pathology Society
Authors: Mark Haas, Surya V. Seshan, Laura Barisoni, Kerstin Amann, Ingeborg M. Bajema, Jan Ulrich Becker, Kensuke Joh, Danica Ljubanovic, Ian S.D. Roberts, Joris J. Roelofs, Sanjeev Sethi, Caihong Zeng, J. Charles Jennette
Journal: Kidney International (2020)
ACCF/AHA/SCAI 2013 Update of the Clinical Competence Statement on Coronary Artery Interventional Procedures
Authors: John G. Harold, Theodore A. Bass, Thomas M. Bashore, Ralph G. Brindis, John E. Brush, James A. Burke, Gregory J. Dehmer, Yuri A. Deychak, Hani Jneid, James G. Jollis, Joel S. Landzberg, Glenn N. Levine, James B. McClurken, John C. Messenger, Issam D. Moussa, J. Brent Muhlestein, Richard M. Pomerantz, Timothy A. Sanborn, Chittur A. Sivaram, Christopher J. White, Eric S. Williams, John G. Harold, Shalom Jacobovitz, William J. Oetgen, Charlene L. May, Dawn R. Phoubandith, Grace D. Ronan, Erin A. Barrett, Donna Arnett, Nancy Brown, Rose Marie Robertson, Gayle R. Whitman, Judy L. Bezanson, Theodore A. Bass, Norm Linsky, Joel Harder
Journal: Circulation (2013)

Supplemental Digital Content is available in the text.
Estimated Incidence of Electric Scooter Injuries in the US From 2014 to 2019
Authors: Kevin Xavier Farley, Matthew Aizpuru, Jacob M. Wilson, Charles A. Daly, John Xerogeanes, Michael B. Gottschalk, Eric R. Wagner
Journal: JAMA Network Open (2020)

This cross-sectional study uses data from the US Consumer Product Safety Commission’s National Electronic Injury Surveillance System to assess trends in the prevalence of electric scooter injuries in the US from 2014 to 2019.
Personalized medicine for allergy treatment: Allergen immunotherapy still a unique and unmatched model
Authors: Cristoforo Incorvaia, Mona Al‐Ahmad, Ignacio J. Ansotegui, Stefania Arasi, Claus Bachert, Catherine Bos, Jean Bousquet, Andrzéj Bozek, Davide Caimmi, Moises A. Calderón, Thomas Casale, Adnan Custovic, Frédéric De Blay, Pascal Demoly, Philippe Devillier, Alain Didier, Alessandro Fiocchi, Adam T. Fox, Philippe Gevaert, Maximiliano Gomez, Enrico Heffler, Natalia Ilina, Carla Irani, Marek Jutel, Efstrathios Karagiannis, Ludger Klimek, Piotr Kuna, Robin O'Hehir, Oxana Kurbacheva, Paolo M. Matricardi, Mario Morais‐Almeida, Ralph Mosges, Natalija Novak, Yoshitaka Okamoto, Petr Panzner, Nikolaos G. Papadopoulos, Hae‐Sim Park, Giovanni Passalacqua, Ruby Pawankar, Oliver Pfaar, Peter Schmid‐Grendelmeier, Silvia Scurati, Miguel Tortajada‐Girbés, Carmen Vidal, J. Christian Virchow, Ulrich Wahn, Margitta Worm, Petra Zieglmayer, Giorgio W. Canonica
Journal: Allergy (2020)

The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.
A Single Autologous Stem Cell Transplant (ASCT) Followed By Two Years of Post-Transplant Therapy Is Safe in Older Recently Diagnosed Multiple Myeloma (MM) Patients. Preliminary Results from the Prospective Phase II Trial (NCT01849783)
Authors: Kalyan Nadiminti, Lindsay Dozeman, Annick Tricot, Allyson Schultz, Sheila Ouverson, Fenghuang Zhan, Margarida Silverman, Guido J. Tricot, Yogesh Jethava
Journal: Blood (2017)
Abstract 3689: Mutation spectrum of MEF cells transformed by overexpression of novel activating KRAS mutation candidates in lung adenocarcinoma
Authors: Jiro Abe, Nobuhiro Tanuma, Miyuki Nomura, Shin Ito, Isao Kasugai, Ikuro Sato, Keiichi Tamai, Mai Mochizuki, Kazunori Yamaguchi, Hiroshi Shima, Yoshinori Okada, Jun Yasuda
Journal: Cancer Research (2020)

Abstract Lung adenocarcinoma (LUAC) is a unique lung cancer subtype that is responsive to several therapeutic agents. The KRAS gene is the second most frequently mutated gene in LUAC and the majority of KRAS mutations are one of three classical activating mutations (G12, G13, and Q61). Recently, we have characterized other types of “minor” KRAS mutation (A66T, A66V, and G75E) identified among LUAC patients and found these three mutants had tumor-forming activity in mouse embryonic fibroblasts in an allograft model. RNA-Seq analysis revealed that mouse embryonic fibroblasts overexpressing these three minor KRAS mutations have distinct expression profiles compared with overexpression of the wild type but similar expression profiles compared with overexpression of the classical KRAS mutants, G12V. In this study, we have searched candidate somatic genetic alterations in the RNA-seq data and will discuss the impact of the mutations in KRAS carcinogenesis. Citation Format: Jiro Abe, Nobuhiro Tanuma, Miyuki Nomura, Shin Ito, Isao Kasugai, Ikuro Sato, Keiichi Tamai, Mai Mochizuki, Kazunori Yamaguchi, Hiroshi Shima, Yoshinori Okada, Jun Yasuda. Mutation spectrum of MEF cells transformed by overexpression of novel activating KRAS mutation candidates in lung adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3689.
Artificial intelligence manages congenital cataract with individualized prediction and telehealth computing
Authors: Erping Long, Jingjing Chen, Xiaohang Wu, Zhenzhen Liu, Liming Wang, Jiewei Jiang, Wangting Li, Yi Zhu, Chuan Chen, Zhuoling Lin, Jing Li, Xiaoyan Li, Hui Chen, Chong Guo, Lanqin Zhao, Daoyao Nie, Xinhua Liu, Xin Liu, Zhe Dong, Bo Yun, Wenbin Wei, Fan Xu, Jian Lv, Min Li, Shiqi Ling, Lei Zhong, Junhong Chen, Qishan Zheng, Li Zhang, Yi Xiang, Gang Tan, Kai Huang, Yifan Xiang, Duoru Lin, Xulin Zhang, Meimei Dongye, Dongni Wang, Weirong Chen, Xiyang Liu, Haotian Lin, Yizhi Liu
Journal: npj Digital Medicine (2020)

A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.
Abstract 604: Combination of the Aurora A inhibitor TAS-119 and adavosertib results in synergistic c-Jun-mediated cell death in head and neck and lung cancers
Authors: Jong Woo Lee, Cindy Yang, Barbara Burtness
Journal: Cancer Research (2020)

Abstract Head and neck squamous cell carcinomas (HNSCC) account for more than 800,000 cases annually worldwide. Human papillomavirus (HPV)-negative HNSCC mainly harbor disruptive mutations in TP53 and/or CDKN2A tumor suppressor genes, which are associated with refractoriness to treatment as well as poor prognosis and survival. Synthetic lethal approaches hold promise for such patients. Cancers with TP53/CDKN2A mutations lose the G1/S checkpoint, and foster a dependence on the G2/M checkpoint as the primary mechanism to repair the resulting accumulation of genomic instability, thus creating a vulnerability that can potentially be exploited with synthetic lethal targeted therapy. We have previously demonstrated in HPV-negative HNSCC patients that elevation in expression of Aurora kinase A (AURKA), a crucial mitotic regulator, is correlated with worse outcome. Combined inhibition of AURKA and WEE1, a G2/M checkpoint kinase, resulted in a synergistic anti-tumor effect in HNSCC in vitro and in vivo. Upon these findings, we confirmed synergy in testing the more specific AURKA inhibitor, TAS-119 in HNSCC and lung cancers harboring TP53 mutations, and explored mechanisms of cell death. TAS119 and adavosertib combination treatment synergistically suppressed cell viability, clonogenic cell survival, anchorage-independent cell growth in soft agar and oncosphere formation relative to vehicle and single-agent treatment in HNSCC FaDu and CAL27 cells, and lung cancer NCI-H520 and NCI-H358 cells bearing TP53/CDKN2A mutations. Of note, this synergistic anti-tumor effect was not seen in normal human tracheobronchial epithelial cells, predicting a favorable therapeutic index. Furthermore, combination treatment accelerated an accumulation of mitotic catastrophe with mitotic arrest, and led to apoptotic cell death. Mechanistically, combination TAS-119 and adavosertib in HNSCC cells drastically augmented DNA damage and phosphorylation of c-Jun (Ser 63) as demonstrated by kinase array and western blotting, indicating an activation of c-Jun-mediated pro-apoptotic genes. In vivo, this combination demonstrated a synergistic suppressive effect on tumor growth in FaDu xenografts compared with either vehicle or single-agent treatment. Taken together, these results support the promise of further clinical evaluation of AURKA inhibitor in combination with WEE1 inhibitor as a novel and effective treatment for HNSCC and lung cancer patients with TP53/CDKN2A mutations. Citation Format: Jong Woo Lee, Cindy Yang, Barbara Burtness. Combination of the Aurora A inhibitor TAS-119 and adavosertib results in synergistic c-Jun-mediated cell death in head and neck and lung cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 604.
Abstract 1388: Loss of TGFβ signaling increases alternative end-joining and could sensitize high-grade serous ovarian cancer to PARP inhibitors
Authors: Ines Guix, Qi Liu, Luis Palomero, Jade Moore, Miquel Angel Pujana, Mary Helen Barcellos-Hoff
Journal: Cancer Research (2020)

Abstract Defective DNA damage repair (DDR) is an important therapeutic target in high-grade serous ovarian cancer (HGSOC). This is exemplified by the efficacy of platinum analogues in this disease, as well as the advent of PARP inhibitors that exhibit synthetic lethality when applied to BRCA-mutated tumors. We recently found that loss of transforming growth factor β (TGFβ) signaling in head and neck squamous cell carcinoma causes dysregulation of BRCA1 and hence defective homologous recombination, which pushes cells to rely on error-prone alternative end-joining (alt-EJ) for DDR (Liu et al. Clin Ca Res 2018). To examine this link in ovarian cancer, here we interrogated the transcriptomes from 562 HGSOC patients from The Cancer Genome Atlas Consortium (TCGA) using a 50-gene signature of chronic TGFβ signaling and a 30-gene signature of alt-EJ competency. Our study unveiled a highly significant (p&amp;lt;0.00001) inverse correlation between TGFβ and alt-EJ in HGSOC. Alt-EJ is error prone, thus we examined the fraction of the genome altered as a function of TGFβ/alt-EJ; the TGFβ/alt-EJ pathway index score was negatively associated with the fraction of genome altered (Pearson correlation coefficient: -0.3288887; P-value = 2.9e-15), with tumors with low TGFβ/high alt-EJ exhibiting more genomic alterations. Alt-EJ increases tumor cell sensitivity to radiation and chemotherapy. Patients with low TGFβ/high alt-EJ profile were associated with an overall survival advantage (p=0.02) and a disease-free survival advantage (p=0.03). Consistent with this, patients with low TGFβ/high alt-EJ profile showed a significantly better response to primary treatment with cisplatin (p=0.038). These data support combinations of TGFβ inhibitors that could boost response to chemotherapy in HGSOC. Because PARP enzymes are key to alt-EJ, which sensitizes cells to PARP inhibition (ibid), these data suggest a novel means to identify patients that will likely be responsive to PARP inhibitors independently of BRCA mutational status. Citation Format: Ines Guix, Qi Liu, Luis Palomero, Jade Moore, Miquel Angel Pujana, Mary Helen Barcellos-Hoff. Loss of TGFβ signaling increases alternative end-joining and could sensitize high-grade serous ovarian cancer to PARP inhibitors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1388.
Embryo-Like Features in Developing <i>Bacillus subtilis</i> Biofilms
Authors: Momir Futo, Luka Opašić, Sara Koska, Nina Čorak, Tin Široki, Vaishnavi Ravikumar, Annika Thorsell, Maša Lenuzzi, Domagoj Kifer, Mirjana Domazet-Lošo, Kristian Vlahoviček, Ivan Mijakovic, Tomislav Domazet-Lošo
Journal: Molecular Biology and Evolution (2020)

Correspondence between evolution and development has been discussed for more than two centuries. Recent work reveals that phylogeny-ontogeny correlations are indeed present in developmental transcriptomes of eukaryotic clades with complex multicellularity. Nevertheless, it has been largely ignored that the pervasive presence of phylogeny-ontogeny correlations is a hallmark of development in eukaryotes. This perspective opens a possibility to look for similar parallelisms in biological settings where developmental logic and multicellular complexity are more obscure. For instance, it has been increasingly recognized that multicellular behavior underlies biofilm formation in bacteria. However, it remains unclear whether bacterial biofilm growth shares some basic principles with development in complex eukaryotes. Here we show that the ontogeny of growing Bacillus subtilis biofilms recapitulates phylogeny at the expression level. Using time-resolved transcriptome and proteome profiles, we found that biofilm ontogeny correlates with the evolutionary measures, in a way that evolutionary younger and more diverged genes were increasingly expressed toward later timepoints of biofilm growth. Molecular and morphological signatures also revealed that biofilm growth is highly regulated and organized into discrete ontogenetic stages, analogous to those of eukaryotic embryos. Together, this suggests that biofilm formation in Bacillus is a bona fide developmental process comparable to organismal development in animals, plants, and fungi. Given that most cells on Earth reside in the form of biofilms and that biofilms represent the oldest known fossils, we anticipate that the widely adopted vision of the first life as a single-cell and free-living organism needs rethinking.