tbuckley/cabot-search huggingface dataset:
973. SEquence-Enabled Reassembly of β- Lactamase (SEER-LAC): A Sensitive Method for the Detection of Double-Stranded DNA
Authors: Aik T. Ooi, Cliff I. Stains, Indraneel Ghosh, David J. Segal
Journal: Molecular Therapy (2006)

This work describes the development of a new methodology for the detection of specific double-stranded DNA sequences. We previously showed that two inactive fragments of green fluorescent protein, each coupled to engineered zinc finger DNA-binding proteins, were able to reassemble an active reporter complex in the presence of a predefined DNA sequence [Stains et al., (2005) J. Am Chem. Soc. 127:10782]. This system, designated SEquence-Enabled Reassembly (SEER), was demonstrated in vitro to produce a DNA- concentration-dependent signal. Here we endow the SEER system with catalytic capability using the reporter enzyme TEM1 β- lactamase. This system could distinguish target from non-target DNA in less than 5 minutes, representing a more than 1,000-fold improvement over our previous SEER design. A single base pair substitution in the DNA binding sequence reduced the signal to nearly background levels. Substitution of a different custom zinc finger DNA-binding domain produced a signal only on the new cognate target. These results present SEER as a rapid and sensitive method for the detection of double-stranded DNA sequences. The results also suggest the use of SEER to activate prodrugs in cells as a strategy to achieve DNA sequence-dependant cell death.
Testosterone and estradiol are co-secreted episodically by the human testis.
Authors: S J Winters, P Troen
Journal: Journal of Clinical Investigation (1986)

In spite of a striking pulsatile pattern of luteinizing hormone (LH) secretion, testosterone (T) fluctuations in peripheral blood in normal adult men are irregular and of low amplitude. To determine whether T secretion by the human testis is episodic, T was measured in blood samples drawn at 15-min intervals for 4 h through a catheter placed in the testicular vein of six men with varicocele-associated infertility. Estradiol (E2) concentrations were also determined in each sample. Each subject released testosterone in well-defined pulses. Gonadal vein T levels ranged from 1 to 1,540 ng/ml. Mean (+/- SE) pulse amplitude was 176 +/- 42 ng/ml, with a frequency of 4.0 +/- 0.3 pulses per 4 h. Testicular vein E2 levels ranged from 0.01 to 6.8 ng/ml. E2 secretory episodes were generally coincident with T pulses, and their amplitudes were highly positively correlated (r = 0.90, P less than 0.01). These results indicate that T secretion by the adult human testis is pulsatile, and suggest a functional relationship between intermittent LH secretion and normal testicular steroidogenesis in men. The failure to appreciate these fluctuations as hormone pulses in peripheral blood may relate to their absolute amplitude and frequency. The concordance between E2 and T pulses suggests that the Leydig cell, under LH control, is the source of most of the E2 secreted by the adult human testis.
Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery
Authors: Francesco Rubino, Ricardo V Cohen, Geltrude Mingrone, Carel W le Roux, Jeffrey I Mechanick, David E Arterburn, Josep Vidal, George Alberti, Stephanie A Amiel, Rachel L Batterham, Stefan Bornstein, Ghassan Chamseddine, Stefano Del Prato, John B Dixon, Robert H Eckel, David Hopkins, Barbara M McGowan, An Pan, Ameet Patel, François Pattou, Philip R Schauer, Paul Z Zimmet, David E Cummings
Journal: The Lancet Diabetes & Endocrinology (2020)
Evolution of Sequence-Diverse Disordered Regions in a Protein Family: Order within the Chaos
Authors: Thomas Shafee, Antony Bacic, Kim Johnson
Journal: Molecular Biology and Evolution (2020)

Approaches for studying the evolution of globular proteins are now well established yet are unsuitable for disordered sequences. Our understanding of the evolution of proteins containing disordered regions therefore lags that of globular proteins, limiting our capacity to estimate their evolutionary history, classify paralogs, and identify potential sequence-function relationships. Here, we overcome these limitations by using new analytical approaches that project representations of sequence space to dissect the evolution of proteins with both ordered and disordered regions, and the correlated changes between these. We use the fasciclin-like arabinogalactan proteins (FLAs) as a model family, since they contain a variable number of globular fasciclin domains as well as several distinct types of disordered regions: proline (Pro)-rich arabinogalactan (AG) regions and longer Pro-depleted regions. Sequence space projections of fasciclin domains from 2019 FLAs from 78 species identified distinct clusters corresponding to different types of fasciclin domains. Clusters can be similarly identified in the seemingly random Pro-rich AG and Pro-depleted disordered regions. Sequence features of the globular and disordered regions clearly correlate with one another, implying coevolution of these distinct regions, as well as with the N-linked and O-linked glycosylation motifs. We reconstruct the overall evolutionary history of the FLAs, annotated with the changing domain architectures, glycosylation motifs, number and length of AG regions, and disordered region sequence features. Mapping these features onto the functionally characterized FLAs therefore enables their sequence-function relationships to be interrogated. These findings will inform research on the abundant disordered regions in protein families from all kingdoms of life.
Gut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice
Authors: Juneyoung Lee, John d’Aigle, Louise Atadja, Victoria Quaicoe, Pedram Honarpisheh, Bhanu P. Ganesh, Ahmad Hassan, Joerg Graf, Joseph Petrosino, Nagireddy Putluri, Liang Zhu, David J. Durgan, Robert M. Bryan, Louise D. McCullough, Venugopal Reddy Venna
Journal: Circulation Research (2020)

The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown. To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy. Aged male mice (18-20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2-3 months) or aged biome (18-20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers (Bifidobacterium longum, Clostridium symbiosum, Faecalibacterium prausnitzii, and Lactobacillus fermentum) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.
Divergent T follicular helper cell requirement for IgA and IgE production to peanut during allergic sensitization
Authors: Biyan Zhang, Elise Liu, Jake A. Gertie, Julie Joseph, Lan Xu, Elisha Y. Pinker, Daniel A. Waizman, Jason Catanzaro, Kedir Hussen Hamza, Katharina Lahl, Uthaman Gowthaman, Stephanie C. Eisenbarth
Journal: Science Immunology (2020)

Generation of peanut-specific gut immunoglobulin A antibodies is independent of T follicular helper cells.
Toward Circuit Mechanisms of Pathophysiology in Depression
Authors: Timothy Spellman, Conor Liston
Journal: American Journal of Psychiatry (2020)

The search for more effective treatments for depression is a long-standing primary objective in both psychiatry and translational neuroscience. From initial models centered on neurochemical deficits, such as the monoamine hypothesis, research toward this goal has shifted toward a focus on network and circuit models to explain how key nodes in the limbic system and beyond interact to produce persistent shifts in affective states. To build these models, researchers have turned to two complementary approaches: neuroimaging studies in human patients (and their healthy counterparts) and neurophysiology studies in animal models, facilitated in large part by optogenetic and chemogenetic techniques. As the authors discuss, functional neuroimaging studies in humans have included largely task-oriented experiments, which have identified brain regions differentially activated during processing of affective stimuli, and resting-state functional MRI experiments, which have identified brain-wide networks altered in depressive states. Future work in this area will build on a multisite approach, assembling large data sets across diverse populations, and will also leverage the statistical power afforded by longitudinal imaging studies in patient samples. Translational studies in rodents have used optogenetic and chemogenetic tools to identify not just nodes but also connections within the networks of the limbic system that are both critical and permissive for the expression of motivated behavior and affective phenotypes. Future studies in this area will exploit mesoscale imaging and multisite electrophysiology recordings to construct network models with cell-type specificity and high statistical power, identifying candidate circuit and molecular pathways for therapeutic intervention.
A Manual of Clinical Diagnosis by Means of Laboratory Methods for Students, Hospital Physicians and Practitioners.
Journal: JAMA (1918)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
661 USE OF EARLY-TIPS FOR HIGH-RISK VARICEAL BLEEDING. RESULTS OF A POST-RCT SURVEILLANCE STUDY
Authors: M. Di Pascoli, J.C. García-Pagan, K. Caca, W. Laleman, C. Bureau, B. Appenrodt, A. Luca, A. Zipprich, J.G. Abraldes, F. Nevens, J.P. Vinel, J. Bosch
Journal: Journal of Hepatology (2012)
Schistocytosis is not always microangiopathic hemolytic anemia
Authors: Thomas Lofaro, Barbara J. Bain
Journal: American Journal of Hematology (2020)

Rapid diagnosis and treatment of TTP is important and the index of suspicion must be high. However it is important to be aware of other causes of schistocytosis. The dyserythropoiesis of a myelodysplastic syndrome (MDS) can lead to the presence of schistocytes and we are aware of another patient with MDS in whom plasma exchange for suspected TTP was carried out before bone marrow examination revealed the correct diagnosis. Severe megaloblastic anemia can also have marked schistocytosis so that TTP is suspected. The authors declare no conflicts of interest.
Abstract #4721: Overcoming PTEN-loss mediated trastuzumab resistance by targeting Src family kinase
Authors: Siyuan Zhang, Wen-Chien Huang, Hua Guo, Zhaoxi Ding, Aysegul Sahin, Francisco Esteva, Dihua Yu
Journal: Cancer Research (2009)

Background: The HER2-targeted therapy, trastuzumab, significantly improves disease free survival. However, less than 35% of HER2 positive patients respond to trastuzumab as a single agent. Trastuzumab resistance has become a devastating problem and there is an imposing need for new rationally designed regimens to overcome trastuzumab resistance. We have previously shown that PTEN loss confers trastuzumab resistance in HER2-overexpressing breast cancer. Recently, we found that the non-receptor tyrosine kinase Src is hyper-activated in trastuzumab-resistant PTEN-loss cells. Since Src is well-known to play important roles in tumor development, we hypothesized that this aberrant activation of Src may contribute to trastuzumab resistance and blocking Src activation with Src inhibitor will re-sensitize PTEN-loss tumors to trastuzumab. Experimental Design: We used in vitro breast cancer cell line models and in vivo orthotopic mouse model to test our hypothesis. In the in vitro study, multiple cancer cells with/without PTEN knockdown were treated with Src inhibitor AZD0530, trastuzumab, or combined treatments. The response of cells to trastuzumab treatment was evaluated by MTS proliferation, apoptosis assay, and soft agar colony formation assay. Changes in cell signaling pathways were evaluated by western blot. In the in vivo study, mammary gland xenograft tumors were established in ICR/SCID mouse. Mice were treated with vehicle control, AZD0530, trastuzumab, or AZD0530 plus trastuzumab for 4 weeks. Tumor volume were monitored and the changes of tumor cell proliferation, apoptosis, and cell signaling events were further studied by immunohistochemistry on collected tumors. Results: We established stable multiple pairs of PTEN-loss cells by PTEN shRNA. The PTEN knockdown cells have an elevated level of the Src activation compared with PTEN wild type cells. Inhibition of Src activation by AZD0530 sensitized PTEN-deficient breast cancer cells to trastuzumab treatment in vitro. Compared with single treatment, combined treatment led to a significantly more effective inhibition of cell proliferation and induced apoptosis. In a mouse mammary gland xenograft model, combination therapy with trastuzumab and AZD0530 dramatically inhibited PTEN-deficient tumor growth. Conclusions: Since the Src inhibitor AZD0530 is currently under Phase II clinical trial, combining trastuzumab with this Src inhibitors is a clinically applicable strategy and a promising combinatory targeted anti-cancer therapy to overcome PTEN-loss mediated trastuzumab resistance.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4721.
COVID-19: Should sexual practices be discouraged during the pandemic?
Authors: ZhiQiang Yin
Journal: Journal of the American Academy of Dermatology (2020)

To the Editor: Patrì et al1Patrì A. Gallo L. Guarino M. Fabbrocini G. Sexual transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A new possible route of infection?.J Am Acad Dermatol. 2020; 82: e227Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar recently reported that sexual transmission might be a new possible route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and they strongly suggested that physicians, especially dermatologists, dissuade people from having sex during the pandemic outbreak of COVID-19. Saliva and feces may both carry SARS-CoV-2. Glandular cells of oral mucosa and rectal epithelia express angiotensin converting enzyme II (ACE2). SARS-CoV-2 enters cells by binding with ACE2. Fan et al2Fan C. Li K. Ding Y.H. Lu W.L. Wang J.Q. ACE2 expression in kidney and testis may cause kidney and testis damage after 2019-nCoV infection.medRxiv. 2020; https://doi.org/10.1101/2020.02.12.20022418Crossref Google Scholar reported high messenger RNA expression level of ACE2 in the urinary tract, prostate, testis, endometrium, and ovary, which indicates that these human tissues could be a potential target of SARS-CoV-2. However the question of viable SARS-CoV-2 in semen or testis remains unanswered. Sex and reproduction are primal human drives and calling on physicians to dissuade people from having sex during the pandemic may be a bit radical. Until more data are available, it may be best to focus on general guidelines regarding social distancing. Sexual transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): A new possible route of infection?Journal of the American Academy of DermatologyVol. 82Issue 6PreviewTo the Editor: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease (COVID-19), first identified in Wuhan, China, in December 2019, and that has now actually spread worldwide. The human-to-human transmission routes hitherto recognized include direct transmission, through cough, sneeze, droplet inhalation, and contact transmission, comprising contact with oral, nasal, and eye mucous membranes. Full-Text PDF
PTH-070 Correlation of the recorded image quality index (RIQI) score with existing colonoscopy key performance indicators
Authors: Kate Edwards, James Berrill, Joanna Hurley, Bee Lee, Neil Hawkes
Journal: Endoscopy (2018)

<h3>Introduction</h3> The RIQI score (scale 0–10) has been validated as a measure of the quality of image recording during endoscopic examination. A high RIQI score (9–10) provides good clinical utility of the images to support clinical decision-making e.g. in MDTs. Taking high quality images requires good tip control to hold the correct focal length and time spent cleaning the mucosa. We aimed to assess the correlation between median RIQI scores and existing colonoscopy key performance indicators (KPIs) including the Caecal Intubation Rate (CIR), Polyp Detection Rate (PDR) and median colonoscopic withdrawal time (WDT). <h3>Methods</h3> 80 datasets of clinical images were reviewed by 3 assessors yielding a median RIQI score from 30 observations for 8 independently practising colonoscopists. This was correlated against annual KPI data for each colonoscopist – including CIR (%), PDR (%) and median WDT (mins). Pearson Rank correlation was performed. <h3>Results</h3> Median RIQI scores for the 8 colonoscopists ranged from 2 to 10 (&lt;5= poor; 6–8=moderate, 9–10=high image quality). Unadjusted CIR ranged from 81.6% to 95.0%; PDR from 24.2% to 64.5% and median WDT from 7 to 19 min. Median RIQI scores had a moderate to good positive correlation with existing KPIs – correlation values: CIR r=0.59; PDR r=0.53; WDT=0.54. <h3>Conclusions</h3> The RIQI score is a novel KPI assessing the recording of image quality. This is a surrogate marker of both tip control and ability to identify, wash and assess lesions. We have demonstrated that the RIQI score shows positive correlation with other commonly used KPIs in colonoscopy and further work is anticipated in exploring its role in upper GI endoscopy aligned to the BSG Quality Standards.<sup>1</sup> <h3>Reference</h3> 1. Beg S, Ragunath K, Wyman A, et al. Quality standards in upper gastrointestinal endoscopy: a position statement of the British Society of Gastroenterology (BSG) and Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS). <i>Gut</i> 2017 Sep 13:gutjnl-2017.
Stem cell-derived HCV infection systems illustrate the bright future of human hepatocyte research
Authors: Ype P de Jong, T Jake Liang
Journal: Gut (2020)

Most cells in the body can produce the cytokine interferon (IFN) in response to viral infections. IFN produced by virus-infected cell signals in both autocrine and paracrine fashion through the janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway to activate interferon stimulated genes (ISG). There are over 400 ISG with numerous antiviral functions. Depending on the virus and the cell type, subsets of ISG are induced that help clear the infection. Thus, the IFN-ISG pathways are complex networks that form the first response to viral infections.1

For many decades, chronic hepatitis C virus (HCV) infection was the leading cause of advanced liver disease in many nations around the world. Exposure to HCV leads to spontaneous clearance in 20%–30% of individuals, while the majority develop chronic infection that can lead to advanced liver disease. On exposure to HCV, human livers respond by producing a number of ISG. Based on several observations, ISGs have long been postulated to play a key role in HCV clearance. Since the early 1990s high doses of recombinant IFNα became the first effective treatment for HCV infection. For over two decades, various formulations of IFNα remained …
Complications of Orbital Emphysema in a COVID-19 Patient
Authors: Dylan V. Stevens, Ann Q. Tran, Eleanore Kim
Journal: Ophthalmology (2020)

A 74-year-old man presented with a 10-day history of fever, cough, and progressive dyspnea. The patient was diagnosed with severe pneumonia related to COVID-19, after a positive polymerase chain reaction test and radiographic imaging (Fig A). The hospital course was complicated by respiratory failure requiring orotracheal intubation. Refractory hypoxia prompted increased levels of positive end-expiratory pressure (up to 18 cm H2O) and prone positioning. Upon supination, subcutaneous emphysema extended from the chest to the face, unilaterally in the conjunctiva (Fig B), and bilaterally around the eyelids (Fig C). Complete ophthalmologic examination did not reveal any evidence of orbital compartment syndrome or vascular occlusion. (Magnified version of Fig A-C is available online at www.aaojournal.org).
A Dominant-Negative GFI1B Mutation in Gray Platelet Syndrome
Authors: Bert A. Van der Reijden, Davide Monteferrario, Nikhita Bolar, Anna Marneth, Konnie Hebeda, Saskia Bergevoet, Hans Veenstra, Britta Laros-van Gorkum, Marius MacKenzie, Cyrus Khandanpour, Lacramioara Botezatu, Erik Fransen, Guy Van Camp, Anthonie Duijnhouwer, Simone Salemink, Brigith Willemsen, Gerwin Huls, Franks Preijers, Waander L. van Heerde, Joop H. Jansen, Marlies Kempers, Bart Loeys, Lut Van Laer
Journal: Blood (2013)
Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units
Authors: Lara S. Shekerdemian, Nabihah R. Mahmood, Katie K. Wolfe, Becky J. Riggs, Catherine E. Ross, Christine A. McKiernan, Sabrina M. Heidemann, Lawrence C. Kleinman, Anita I. Sen, Mark W. Hall, Margaret A. Priestley, John K. McGuire, Konstantinos Boukas, Matthew P. Sharron, Jeffrey P. Burns
Journal: JAMA Pediatrics (2020)

The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs).