tbuckley/cabot-search huggingface dataset:
Erythema Gyratum Repens
Authors: Nicolas Votquenne, Bertrand Richert
Journal: JAMA Dermatology (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
How a Scorpion Toxin Selectively Captures a Prey Sodium Channel: The Molecular and Evolutionary Basis Uncovered
Authors: Shunyi Zhu, Bin Gao, Steve Peigneur, Jan Tytgat
Journal: Molecular Biology and Evolution (2020)

The growing resistance of insects to chemical pesticides is reducing the effectiveness of conventional methods for pest control and thus, the development of novel insecticidal agents is imperative. Scorpion toxins specific for insect voltage-gated sodium channels (Navs) have been considered as one of the most promising insecticide alternatives due to their host specificity, rapidly evoked toxicity, biodegradability, and the lack of resistance. However, they have not been developed for uses in agriculture and public health, mainly because of a limited understanding of their molecular and evolutionary basis controlling their phylogenetic selectivity. Here, we show that the traditionally defined insect-selective scorpion toxin LqhIT2 specifically captures a prey Nav through a conserved trapping apparatus comprising a three-residue-formed cavity and a structurally adjacent leucine. The former serves as a detector to recognize and bind a highly exposed channel residue conserved in insects and spiders, two major prey items for scorpions; and the latter subsequently seizes the "moving" voltage sensor via hydrophobic interactions to reduce activation energy for channel opening, demonstrating its action in an enzyme-like manner. Based on the established toxin-channel interaction model in combination with toxicity assay, we enlarged the toxic spectrum of LqhIT2 to spiders and certain other arthropods. Furthermore, we found that genetic background-dependent cavity shapes determine the species selectivity of LqhIT2-related toxins. We expect that the discovery of the trapping apparatus will improve our understanding of the evolution and design principle of Nav-targeted toxins from a diversity of arthropod predators and accelerate their uses in pest control.
Regional BCG vaccination policy in former East- and West Germany may impact on both severity of SARS-CoV-2 and incidence of childhood leukemia
Authors: Julia Hauer, Ute Fischer, Franziska Auer, Arndt Borkhardt
Journal: Leukemia (2020)

We read with great interest the recent thorough study from Miller et al. [1], who reported a beneficial impact of early Bacillus Calmette–Guerin (BCG) vaccination, and linked morbidity and mortality due to SARS-CoV-2 with BCG vaccination policy. They found that countries without policies of universal BCG vaccination (like Italy, the Netherlands, or the United States) have been more severely affected compared with countries with universal and long-standing BCG policies. Since senior citizens are particularly sensitive to COVID-19, newborn vaccination programs implemented in the 1940s and 1950s should be the most beneficial. Thus, we were impressed by the linear correlation between the year of the establishment of universal BCG vaccination and the mortality rate presented by Miller et al. [1]. In our view, this is a convincing argument for the hypothesis that the earlier the vaccination policy was established, the larger the segment of the elderly population being protected.
Primed circulating monocytes are a source of IL-1β in patients with cirrhosis and ascites
Authors: Sven Stengel, Arndt Steube, Nilay Köse-Vogel, Tatiana Kirchberger-Tolstik, Sachin Deshmukh, Tony Bruns
Journal: Gut (2020)

We read with great interest the study of Monteiro and colleagues1 reporting the diagnostic significance and the prognostic relevance of elevated serum concentrations of interleukin (IL)-1α in compensated cirrhosis and IL-1β in recompensated cirrhosis. While we do agree that systemic inflammation is a major driver for the progression of liver disease and acute-on-chronic liver failure, caution is advised when interpreting serum IL-1β concentrations as evidence for underlying inflammasome activation causing complications of cirrhosis. Studies1–4 have been inconsistent about stage-dependent concentrations of circulating IL-1β in cirrhosis and acute-on-chronic liver failure (ACLF). Although some of these discrepancies can be attributed to differences in patients, cohort sizes, causes and severity of liver damage, the short serum half-life of cleaved IL-1β, and the sensitivity and specificity of the assays used, one major factor presumably affecting serum concentration is the cellular source of IL-1β and its mode of release.

The release of bioactive IL-1β from murine macrophages has first been described as a two-step activation dogma. While a first (priming) signal would be provided by pathogen-associated molecular patterns (PAMPs) or inflammatory cytokines in order to upregulate the inflammasome components, a second signal would …
Detection and discrimination of intracranial tumors using plasma cell-free DNA methylomes
Authors: Farshad Nassiri, Ankur Chakravarthy, Shengrui Feng, Shu Yi Shen, Romina Nejad, Jeffrey A. Zuccato, Mathew R. Voisin, Vikas Patil, Craig Horbinski, Kenneth Aldape, Gelareh Zadeh, Daniel D. De Carvalho
Journal: Nature Medicine (2020)
A proof of concept phase I/II pilot trial of LSD1 inhibition by tranylcypromine combined with ATRA in refractory/relapsed AML patients not eligible for intensive therapy
Authors: Maxi Wass, Stefanie Göllner, Birgit Besenbeck, Richard F. Schlenk, Petra Mundmann, Joachim R. Göthert, Richard Noppeney, Christoph Schliemann, Jan-Henrik Mikesch, Georg Lenz, Martin Dugas, Martin Wermke, Christoph Röllig, Martin Bornhäuser, Hubert Serve, Uwe Platzbecker, Kathrin I. Foerster, Jürgen Burhenne, Walter E. Haefeli, Lutz P. Müller, Mascha Binder, Caroline Pabst, Carsten Müller-Tidow
Journal: Leukemia (2020)
A challenge for predictive coding: Representational or experiential diversity?
Authors: Martina G. Vilas, Lucia Melloni
Journal: Behavioral and Brain Sciences (2020)

Abstract To become a unifying theory of brain function, predictive processing (PP) must accommodate its rich representational diversity. Gilead et al. claim such diversity requires a multi-process theory, and thus is out of reach for PP, which postulates a universal canonical computation. We contend this argument and instead propose that PP fails to account for the experiential level of representations.
Pamela Margaret Ashurst
Authors: Margaret Orr, Carry Selley
Journal: BMJ (2020)

Pamela Margaret Ashurst was a generous doctor who inspired generations of women therapists and pioneered short term and group psychotherapy in the NHS.

Born Pamela Lewis in Stourport-on-Severn, she fulfilled her father’s childhood ambition—thwarted by a bout of tuberculosis during grammar school entrance examinations—of becoming a doctor. The eldest of two daughters, she was the first member of the family to attend university, and among the youngest of 18 women in her year’s intake of 58 students at Bristol medical school.

Pamela met her future husband, Ron, on a badminton court in freshers’ week, and married between the two parts of her finals. She stayed to start postdoctoral research in gastroenterology, but found herself “more interested in the patient experience that by what happened in the lab,” she recalled. In the early 1960s Pamela was recruited by Sir Martin Roth, first president of the Royal College of Psychiatrists, to set up and chair a new working party of trainees, which became the Association of Psychiatrists in Training (APIT). She thought that Sir Martin had sought “an unassuming girl from the provinces” for the new venture.

While still a trainee, Pamela received a BMA award for a film she made about the care of people with …
Pre-Transplantation Predictors of Survival in Patients Undergoing Allogeneic Stem Cell Transplant for Myelofibrosis
Authors: Jeanne Palmer, Tania Jain, Katie L. Kunze, Daniel K. Partain, Nandita Khera, Lisa Sproat, Pierre Noel, James L. Slack, Vivek Roy, Jose F. Leis, William J. Hogan, Ayalew Tefferi, Veena D. S. Fauble, Mrinal M. Patnaik, Heidi Elizabeth Kosiorek, Ruben A Mesa
Journal: Blood (2017)
New Therapeutic Targets in Antineutrophil Cytoplasm Antibody–Associated Vasculitis
Authors: Maria Prendecki, Stephen P. McAdoo
Journal: Arthritis & Rheumatology (2020)

Antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare systemic autoimmune disease that is characterized by necrotizing inflammation of predominantly the small blood vessels and the presence of circulating ANCAs directed against myeloperoxidase or proteinase 3. Current treatment strategies for severe disease, supported by the findings of several well-coordinated randomized controlled trials, aim to induce remission with high-dose glucocorticoids and either rituximab or cyclophosphamide, followed by relapse prevention with a period of sustained low-dose treatment. This approach has dramatically improved outcomes in AAV; however, a significant proportion of patients develop serious treatment-related side effects or experience relapse. Recent advances in our understanding of the pathogenesis of AAV have led to the identification of novel therapeutic targets that may address these problems, including strategies directed at the aberrant adaptive autoimmune response (B and T cell-directed treatments) and those targeting innate immune elements (complement, monocytes, and neutrophils). It is anticipated that these novel treatments, used alone or in combination, will lead to more effective and less toxic treatment regimens for patients with AAV.
Abstract 10155: Applications of a Specialty Bicuspid Aortic Valve Program: Clinical Continuity and Translational Collaboration
Authors: Erin Crawford, Patrick M McCarthy, Jyothy Puthumana, Paul Fedak, Michael Markl, Menghan Liu, Adin-Cristian Andrei, Jane Kruse, Charles Davidson, S Chris Malaisrie
Journal: Circulation (2019)

Objective: Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality and is associated with both valvulopathy and aortopathy. Translational collaboration is necessary to close c...
The Battle to Sequence the Bread Wheat Genome: A Tale of the <i>Three Kingdoms</i>
Authors: Jiantao Guan, Diego F. Garcia, Yun Zhou, Rudi Appels, Aili Li, Long Mao
Journal: Genomics Proteomics & Bioinformatics (2020)

In the year 2018, the world witnessed the finale of the race to sequence the genome of the world's most widely grown crop, the common wheat. Wheat has been known to bear a notoriously large and complicated genome of a polyploidy nature. A decade competition to sequence the wheat genome initiated with a single consortium of multiple countries, taking a conventional strategy similar to that for sequencing Arabidopsis and rice, became ferocious over time as both sequencing technologies and genome assembling methodologies advanced. At different stages, multiple versions of genome sequences of the same variety (e.g., Chinese Spring) were produced by several groups with their special strategies. Finally, 16 years after the rice genome was finished and 9 years after that of maize, the wheat research community now possesses its own reference genome. Armed with these genomics tools, wheat will reestablish itself as a model for polyploid plants in studying the mechanisms of polyploidy evolution, domestication, genetic and epigenetic regulation of homoeolog expression, as well as defining its genetic diversity and breeding on the genome level. The enhanced resolution of the wheat genome should also help accelerate development of wheat cultivars that are more tolerant to biotic and/or abiotic stresses with better quality and higher yield.
Retrograde migration supplies resident memory T cells to lung-draining LN after influenza infection
Authors: J. Michael Stolley, Timothy S. Johnston, Andrew G. Soerens, Lalit K. Beura, Pamela C. Rosato, Vineet Joag, Sathi P. Wijeyesinghe, Ryan A. Langlois, Kevin C. Osum, Jason S. Mitchell, David Masopust
Journal: The Journal of Experimental Medicine (2020)

Numerous observations indicate that resident memory T cells (TRM) undergo unusually rapid attrition within the lung. Here we demonstrate that contraction of lung CD8+ T cell responses after influenza infection is contemporized with egress of CD69+/CD103+ CD8+ T cells to the draining mediastinal LN via the lymphatic vessels, which we term retrograde migration. Cells within the draining LN retained canonical markers of lung TRM, including CD103 and CD69, lacked Ly6C expression (also a feature of lung TRM), maintained granzyme B expression, and did not equilibrate among immunized parabiotic mice. Investigations of bystander infection or removal of the TCR from established memory cells revealed that the induction of the TRM phenotype was dependent on antigen recognition; however, maintenance was independent. Thus, local lung infection induces CD8+ T cells with a TRM phenotype that nevertheless undergo retrograde migration, yet remain durably committed to the residency program within the draining LN, where they provide longer-lived regional memory while chronicling previous upstream antigen experiences.
A dual MET/AXL small‐molecule inhibitor exerts efficacy against gastric carcinoma through killing cancer cells as well as modulating tumor microenvironment
Authors: Chenjing Zhu, Huashan Shi, Min Wu, Xiawei Wei
Journal: MedComm (2020)

Abstract The receptor tyrosine kinases MET and AXL have been implicated in tumorigenesis and aggressiveness of multiple malignancies. We performed this study to evaluate the antitumor impact of LY2801653, a dual MET and AXL inhibitor on gastric cancer and to elucidate the underlying mechanisms. In the present study, tissue microarrays containing gastric cancer tissues were stained with MET and AXL antibodies, which showed the prognostic values of MET and AXL. Administration of LY2801653 inhibited cell proliferation, migration, epithelial‐mesenchymal transition, induced apoptosis, and cell cycle arrest. Xenograft mouse models showed suppressed cell proliferation of tumors in high MET and AXL expression cells. LY2801653 also inhibited the growth of MET and AXL‐independent cells at higher but clinically relevant doses through decreased angiogenesis and M2 macrophages in the tumor microenvironment. In conclusion, our study provides evidence for MET and AXL as prognostic biomarkers and potential therapeutic targets in gastric cancer. The dual MET/AXL inhibitor LY2801653 represents a promising therapeutic strategy for the treatment of patients with gastric carcinoma.
Corrigendum to: IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era
Authors: Bui Quang Minh, Heiko A Schmidt, Olga Chernomor, Dominik Schrempf, Michael D Woodhams, Arndt von Haeseler, Robert Lanfear
Journal: Molecular Biology and Evolution (2020)
Gut microbiota contributes towards immunomodulation against cancer: New frontiers in precision cancer therapeutics
Authors: Kentaro Inamura
Journal: Seminars in Cancer Biology (2020)

The microbiota influences human health and the development of diverse diseases, including cancer. Microbes can influence tumor initiation and development in either a positive or negative manner. In addition, the composition of the gut microbiota affects the efficacy and toxicity of cancer therapeutics as well as therapeutic resistance. The striking impact of microbiota on oncogenesis and cancer therapy provides compelling evidence to support the notion that manipulating microbial networks represents a promising strategy for treating and preventing cancer. Specific microbes or the microbial ecosystem can be modified via a multiplicity of processes, and therapeutic methods and approaches have been evolving. Microbial manipulation can be applied as an adjunct to traditional cancer therapies such as chemotherapy and immunotherapy. Furthermore, this approach displays great promise as a stand-alone therapy following the failure of standard therapy. Moreover, such strategies may also benefit patients by avoiding the emergence of toxic side effects that result in treatment discontinuation. A better understanding of the host–microbial ecosystem in patients with cancer, together with the development of methodologies for manipulating the microbiome, will help expand the frontiers of precision cancer therapeutics, thereby improving patient care. This review discusses the roles of the microbiota in oncogenesis and cancer therapy, with a focus on efforts to harness the microbiota to fight cancer.
Atrial Dysfunction Assessed by Cardiac Magnetic Resonance as an Early Marker of Fabry Cardiomyopathy
Authors: Andrea Bernardini, Antonia Camporeale, Maurizio Pieroni, Federico Pieruzzi, Stefano Figliozzi, Paola Lusardi, Marco Spada, Renzo Mignani, Alessandro Burlina, Francesca Carubbi, Yuri Battaglia, Francesca Graziani, Silvia Pica, Lara Tondi, Kelvin Chow, Sara Boveri, Iacopo Olivotto, Massimo Lombardi
Journal: JACC. Cardiovascular imaging (2020)
Sars‐CoV‐2 infection: the same virus can cause different cutaneous manifestations: reply from authors
Authors: C. Galván‐Casas, A. Catalá, G. Carretero Hernández, I.  Garcia‐Doval
Journal: British Journal of Dermatology (2020)

DEAR EDITOR, Dr Drago et al. are right to point out that our paper did not provide data on enanthems. 1,2As the data collection form did not include the description of mucous membranes, they might have not been explored in many patients.We have reported and included in the supplementary material a few cases that were noticed by their doctors and were the first descriptions of enanthem in COVID-19.Given the low number of cases and their non-systematic acquisition, we avoided any analysis of these data.We disagree with the suggestion of collecting data for a study and later asking for consent.All the included patients gave informed consent before incorporating their data in the study.We feel that the limitations of this strategy are already highlighted in the discussion of the paper and do not seriously bias the results of the study.Regarding serologic testing, we agree that it could have been useful, but it was not available at the time that the study was done, and diagnosis was made using Polymerase Chain Reaction.We also agree on the discussed hypotheses about coinfection or reactivation and the need for further studies to test them.
Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?
Authors: Alice Huertas, David Montani, Laurent Savale, Jérémie Pichon, Ly Tu, Florence Parent, Christophe Guignabert, Marc Humbert
Journal: European Respiratory Journal (2020)

<b>Endothelial cell dysfunction and impaired microcirculatory function contribute markedly to life-threatening complications of COVID-19, such as venous thromboembolic disease and multiple organ involvement</b>https://bit.ly/3cZMjKV
A single-cell landscape of high-grade serous ovarian cancer
Authors: Benjamin Izar, Itay Tirosh, Elizabeth H. Stover, Isaac Wakiro, Michael S. Cuoco, Idan Alter, Christopher Rodman, Rachel Leeson, Mei-Ju Su, Parin Shah, Marcin Iwanicki, Sarah R. Walker, Abhay Kanodia, Johannes C. Melms, Shaolin Mei, Jia-Ren Lin, Caroline B. M. Porter, Michal Slyper, Julia Waldman, Livnat Jerby-Arnon, Orr Ashenberg, Titus J. Brinker, Caitlin Mills, Meri Rogava, Sébastien Vigneau, Peter K. Sorger, Levi A. Garraway, Panagiotis A. Konstantinopoulos, Joyce F. Liu, Ursula Matulonis, Bruce E. Johnson, Orit Rozenblatt-Rosen, Asaf Rotem, Aviv Regev
Journal: Nature Medicine (2020)
Direct Readout of Neural Stem Cell Transgenesis with an Integration-Coupled Gene Expression Switch
Authors: Takuma Kumamoto, Franck Maurinot, Raphaëlle Barry-Martinet, Célia Vaslin, Sandrine Vandormael-Pournin, Mickaël Le, Marion Lerat, Dragos Niculescu, Michel Cohen-Tannoudji, Alexandra Rebsam, Karine Loulier, Stéphane Nedelec, Samuel Tozer, Jean Livet
Journal: Neuron (2020)

Stable genomic integration of exogenous transgenes is essential in neurodevelopmental and stem cell studies. Despite tools driving increasingly efficient genomic insertion with DNA vectors, transgenesis remains fundamentally hindered by the impossibility of distinguishing integrated from episomal transgenes. Here, we introduce an integration-coupled On genetic switch, iOn, which triggers gene expression upon incorporation into the host genome through transposition, thus enabling rapid and accurate identification of integration events following transfection with naked plasmids. In vitro, iOn permits rapid drug-free stable transgenesis of mouse and human pluripotent stem cells with multiple vectors. In vivo, we demonstrate faithful cell lineage tracing, assessment of regulatory elements, and mosaic analysis of gene function in somatic transgenesis experiments that reveal neural progenitor potentialities and interaction. These results establish iOn as a universally applicable strategy to accelerate and simplify genetic engineering in cultured systems and model organisms by conditioning transgene activation to genomic integration.
Judge rules that baby should be removed from ventilator and given palliative care
Authors: Clare Dyer
Journal: BMJ (2020)

An eight week old baby should no longer be kept alive on a ventilator and should be given palliative care to spare him the risk of a “painful, agonising death,” a High Court judge has declared.1

There are no further treatment options for the baby, who was referred to in court as Z, said Mr Justice Hayden. The judge was satisfied that intensive care was futile and that it had “come to place an insupportable burden” on the child.

Hayden granted Sheffield Teaching Hospitals NHS Foundation Trust a declaration that it would be in the best interests of the baby to leave intensive care and to have palliative care only. The trust had hoped to reach agreement with the child’s Muslim parents and avoid a court application. But because of …