tbuckley/cabot-search huggingface dataset:
Neural networks help zebrafish to step up as a model for efficient drug screening in glioblastoma
Authors: Roberto Ferrarese, Maria Stella Carro
Journal: Neuro-Oncology (2022)

In spite of the intensive search for a cure, glioblastoma (GBM) is still a deadly tumor with no effective treatment available. Therefore, there is an urgent need for new therapies. Most of the current research is based on orthotopic patient-derived xenograft (PDX) mouse models. Although certainly valuable for the characterization of tumor-associated mechanisms involving altered gene functions, these models are less suitable for large-scale drug screening and high-throughput studies. In fact, the maintenance of the mice from the injection of GBM cells to the animal sacrifice at the experimental endpoint, is quite expensive and time-consuming. Moreover, in large-scale drug screenings, there are also ethical concerns associated with the use of large numbers of higher vertebrates. In an attempt to overcome these hindrances, the zebrafish model has gained attention in the past years as an approachable model for cancer studies. This rapidly growing, low maintenance fish represents a worth-investigating opportunity to assess the efficacy of novel therapeutic drugs in large-scale, high-throughput screenings. Zebrafish has been widely used in developmental studies, while the applicability to the characterization of cancer-associated mechanisms has been less extensively investigated. Recent studies have shown that cancer traits described in mammals can be efficiently reproduced in zebrafish.1 Features of the zebrafish brain such as its gross anatomical organization, its cell populations, and its regulatory signaling pathways, are conserved and shared by all vertebrates. Additionally, the lack of a functional adaptive system in early-stage development favors a fast and efficient tumor engraftment. Zebrafish small size and unique transparent feature allow visualizing fluorescent proteins under the skin by direct live imaging of the fishes; light-sheet microscopy can also be applied for the detailed visualization of cell migration processes in live animals. Taken together, these features have made zebrafish a promising xenograft model for GBM studies, so far prevalently focused on proliferation and on migratory/invasive properties of GBM cells.2–5
Congress may resolve AMA-FTC clash
Authors: P. Gunby
Journal: JAMA (1982)

Physician advertising and contract practices seem unlikely to change immediately, and the American Medical Association's current ethical guidelines will require no dramatic changes, if a long-contested Federal Trade Commission (FTC) order becomes final next week. Still, the order—which bans a medical association from prohibiting truthful physician advertising or interfering with physicians' contractual arrangements—in effect establishes the FTC as the regulator of the delivery of health care, AMA officials say. It is scheduled to take effect May 18. For example, these officials point out, the FTC's powers to regulate what it considers "unfair trade practice" are broad enough to preempt state laws. Thus, appointed federal commissioners would be able to overrule elected state legislators, and "the learned professions can expect to be called upon to defend the last vestiges of their traditional self-regulatory activities." So far, according to published reports, physicians seem to be more reluctant than other professionals to advertise
From the Pacific Basin.
Authors: P Brooks
Journal: Annals of the Rheumatic Diseases (1990)

<h3>Abstract</h3> Hematopoietic differentiation has been considered as a multistep process which is metaphorically represented as linear trajectories with discrete steps from hematopoietic stem cells to mature cells. While the transcriptional state of cells at the beginning or at the end of these trajectories are relatively well described from bulk analysis, what happens in the intermediate states has remained elusive until the use of single cell approaches allowed to capture the dynamic changes of transcriptomic states. Applying Shannon entropy to measure cell-to-cell variability among cells at the same stage of differentiation, we observed a transient peak of gene expression variability in all the hematopoietic differentiation pathways. Strikingly, genes with the highest entropy variation in a given differentiation pathway matched genes known as pathway-specific, whereas genes with the highest expression variation were common to all pathways. Finally, we showed that the level of cell-to-cell variation is increased in the most immature compartment of hematopoiesis in myelodysplastic syndromes. These data suggest that differentiation may not be as deterministic and linear as previously thought, but could be better conceptualized as a dynamical stochastic process with a transient stage of cellular indetermination.
The biology of the immune response
Authors: H. N. Claman
Journal: JAMA (1987)

<h3>CHARACTERISTICS OF THE IMMUNE SYSTEM</h3> THE IMMUNE system is composed of a large and complex set of elements that are widely distributed. It seems to be designed to protect against foreign pathogens while not responding adversely to self-components. Thus, it must distinguish "self" from "not self." This distinction is made by an elaborate, specific-recognition system that, ultimately, inheres in T and B lymphocytes —the only immunologically specific components of the immune mechanism. The immune system also has nonspecific effector mechanisms that (usually) amplify the specific functions. These nonspecific features include mononuclear phagocytes, polymorphonuclear leukocytes, and the complement system. The immune system has several interesting characteristics. <h3>Specificity</h3> Immune reactions distinguish between non—cross-reacting antigens. Specificity is mediated through the antigen-specific receptors on the surfaces of T and B lymphocytes and through antibodies. <h3>Memory</h3> The immunologic response to an antigenic stimulus usually leaves the immune system changed. Ordinarily, a second administration of antigen
Tracheostomy
Authors: R. Bannister, R. A. Beaver
Journal: BMJ (1969)

all the micro-organisms commonly respon- sible for such lesions.We find it surprising that no mention is made in his paper of the genus of anaerobic Gram-negative bacilli, the Bacteroides fusiformis, various species of which have been reported in cerebral abscesses, particularly those occurring in association with chronic infections of the middle ear, respiratory sinuses, and respiratory tract, and in cyanotic congenital heart disease.' 2 The particular importance of the Bacteroides organisms isolated from these abscesses is that they are usually resistant to penicillin.During the past five years in this hospital of approximately 50 patients with cerebral abscesses 11 patients yielded Bacteraides on culture, and of these 10 were Bacteroides fragilis-a species which is highly resistant to penicillin' 4 Treatment of infec- tions due to penicillin-resistant Bacteroides with penicillin in high dosage has usually been unsuccessful ' We therefore suggest that in cerebral abscesses arising from chronic foci or associated with congenital cyanotic heart disease it would be desirable to employ in addition to penicillin an antibiotic such as chloramphenicol, erythromycin, or lincomycin to deal with these penicillin-resistant bacteria.''-We are, etc.,
Records of the Lock Hospital
Authors: H. Lee
Journal: BMJ (1862)

GENERAL calomel fumigation may be used in cases where the administration of mercury by other methods is inadmissible.On account of the small amounit of calomel required, it may be used, some- times with the greatest benefit, even where other modes of fumig,ation, requiring larger quantities of miercury, cannot be borne.Two remarkable cases, illustrating this fact, are at present under my observationu.*Calom-el appears, indeed, to have been formerly used for the purposes of general fumigation, as well as other preparations of mercury.But it was used in the samne quantities as those other preparations, and was, therefore, open to some of the saine objec- tions as they.M. Rapou published in Paris, in 1824, two vol- umes on Fumigations as employed in various dis- eases.The imercurial preparations which he recom- mended were cinnabar, Lalonette's mercurial powder (which consisted of a mixture of mercury and clay),
Miscellanea Medica
Journal: JAMA (1999)

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
Trench Fever
Authors: A. Hurst
Journal: BMJ (1942)

<h3>SUMMARY</h3> The transmembrane Hsp40 DNAJB12 and cytosolic Hsp70 cooperate on the ER’s cytoplasmic face to facilitate the triage of nascent polytopic membrane proteins for folding versus degradation. N1303K is the second most common mutation in the ion channel CFTR, but unlike F508del-CFTR, biogenic and functional defects in N1303K-CFTR are resistant to correction bolding modulators. N1303K is reported to arrest CFTR folding at a late stage after partial assembly of its N-terminal domains. N1303K-CFTR intermediates are clients of JB12-Hsp70 complexes, maintained in a detergent soluble-state, and have a relatively long 3-hour half-life. ERAD-resistant pools of N1303K-CFTR are concentrated in ER-tubules that associate with autophagy initiation sites containing WIPI1, FlP200, and LC3. Destabilization of N1303K-CFTR or depletion of JB12 prevents entry of N1303K-CFTR into the membranes of ER-connected phagophores and autolysosomes. Whereas, the stabilization of intermediates with the modulator VX-809 promotes the association of N1303K-CFTR with autophagy initiation machinery. N1303K-CFTR is excluded from the ER-exits site, and its passage from the ER to autolysosomes does not require ER-phagy receptors. DNAJB12 operates in biosynthetically active ER-microdomains to triage in a conformation-specific manner membrane protein intermediates for secretion versus degradation via ERAD or selective-ER associated autophagy.
Drug Eruptions
Authors: G. H. Percival
Journal: BMJ (1951)

The term "drug eruption," or dermatitis medica- mentosa, refers to any eruption attributable to the action of a drug which reaches the skin by way of the blood stream, irrespective of the method by which it has been administered.The term does not apply to any local reaction which may occur as a result of direct contact of the drug with the skin from the outside, but it does include eruptions attributable to drugs which have been absorbed through the skin into the blood stream, whether or not this process is accompanied by a local reaction at the point of entrance.
PLASTIC SURGERY.
Authors: A. C. POST
Journal: JAMA (1884)

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
Varicose veins.
Authors: W B Campbell
Journal: BMJ (1990)

Pulmonary hypertension due to chronic hypoxia Treat the lung not the pressure Pulmonary vasoconstriction in response to hypoxia is a basic reflex that occurs in all mammals studied.It has long been thought to have two main physiological functions.In the fetus it is responsible for closing off the pulmonary circulation to prevent blood from shunting through the unventilated lung.After birth it ensures that perfusion is constantly matched to ventilation.The problem comes when the lung is faced with global hypoxia due either to high altitude or to chronic hypoxic lung disease.Then the reflex seems malign and causes pulmonary hypertension.Not surprisingly, hypoxic vasconstriction is virtually absent in those animals that live constantly at high altitude.Bar headed geese, for example, fly over the Himalayas to nest in Tibet.These birds and also mammals that live at high altitude seem to suffer very little from their inability to control the flow of blood to the underventilated lung-so is the reflex of any benefit to adult animals or man?Patients with chronic hypoxic lung disease (usually chronic bronchitis and emphysema but also chronic asthma and restrictive diseases such as fibrosing alveolitis and kyphoscoliosis) are all at risk of pulmonary hypertension, and its development is associated with a poor prognosis.'Some authors have claimed that the pulmonary hypertension in these patients is coincidental to their poor prognosis and poor exercise tolerance rather than their cause.They base this assertion on the observation that the resting pulmonary artery pressure is often not high in patients with severe lung disease.A mean pressure of only 30 mm Hg is typical-whereas in primary pulmonary hypertension it may often reach systemic values.In such patients, however, the pulmonary pressure may rise much higher on exercise, owing to the low compliance of the constricted pulmonary circulation, or at night, owing to worsening hypoxia.Furthermore, the low oxygen content of the arterial blood means that adequate oxygen delivery to the tissues depends on a high cardiac output, and these patients
JAMA reference directories
Journal: JAMA (1979)

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
Spatial transcriptomics of dorsal root ganglia identifies molecular signatures of human nociceptors
Authors: Diana Tavares-Ferreira, Stephanie Shiers, Pradipta R. Ray, Andi Wangzhou, Vivekanand Jeevakumar, Ishwarya Sankaranarayanan, Anna M. Cervantes, Jeffrey C. Reese, Alexander Chamessian, Bryan A. Copits, Patrick M. Dougherty, Robert W. Gereau, Michael D. Burton, Gregory Dussor, Theodore J. Price
Journal: Science Translational Medicine (2022)

Nociceptors are specialized sensory neurons that detect damaging or potentially damaging stimuli and are found in the dorsal root ganglia (DRG) and trigeminal ganglia. These neurons are critical for the generation of neuronal signals that ultimately create the perception of pain. Nociceptors are also primary targets for treating acute and chronic pain. Single-cell transcriptomics on mouse nociceptors has transformed our understanding of pain mechanisms. We sought to generate equivalent information for human nociceptors with the goal of identifying transcriptomic signatures of nociceptors, identifying species differences and potential drug targets. We used spatial transcriptomics to molecularly characterize transcriptomes of single DRG neurons from eight organ donors. We identified 12 clusters of human sensory neurons, 5 of which are C nociceptors, as well as 1 C low-threshold mechanoreceptors (LTMRs), 1 Aβ nociceptor, 2 Aδ, 2 Aβ, and 1 proprioceptor subtypes. By focusing on expression profiles for ion channels, G protein-coupled receptors (GPCRs), and other pharmacological targets, we provided a rich map of potential drug targets in the human DRG with direct comparison to mouse sensory neuron transcriptomes. We also compared human DRG neuronal subtypes to nonhuman primates showing conserved patterns of gene expression among many cell types but divergence among specific nociceptor subsets. Last, we identified sex differences in human DRG subpopulation transcriptomes, including a marked increase in calcitonin-related polypeptide alpha (CALCA) expression in female pruritogen receptor-enriched nociceptors. This comprehensive spatial characterization of human nociceptors might open the door to development of better treatments for acute and chronic pain disorders.
Norwegian Scabies
Authors: G. C. Wells
Journal: BMJ (1952)

ERYTHROBLASTS J3RITISH(c) Total Nucleated-Cell Count.-Suspensiondiluted 1/10 in three pipettes, each of which was used to fill a separate counting chamber.Number of cells counted in the three chambers 67, 65, and 73 respectively.Mean number of cells counted = 68.Dilution factor = 1/25 .-Totalnucleated cell count=1,700/c.mm.Coefficient of variation of this count: 1002 4.62 4.72J / n + nc + np Whcre n the number of cells counted.nc = the number of counting chambers used.np = the number of pip_ttes used. 1 2002Jr462,4.7 = 7.96% .Standard Deviation = 136 Calculations:(i) The percentage of P. + M. of total nucleated cells:(i.e., a x b) = 51 x 35.1 = 17.9 100 = 1 5. 1.The standard deviation of this product is obtained from the formula:where a is the mean percentage of erythroblasts which are P. + M. and aa is its standard deviation, and b is the mean percentage of total nucleated cells which are erythroblasts and crb its standard deviation.i.e., a -0/(l 72 X 11.72) + (10.72 x 35.12) + (11.72 X 512) 100 = 7.2 (ii) The number of P.+M./c.mm.(i.e., (a1 x c) 17.9 x 1700 = 304. 1O00The standard deviation of this figure \/ ( ( 100) X 136 ) +(( f)Xx 1700)+ (1362x (10)2) 124We wish to thank Professor Bartlett and Miss N. Goodman for their help with the statistical aspects of this study; Mr. A.Duval for deriving the formula for the standard error of the product of two independent variables; and Dr. L. G. Lajtha for giving us a full account of his methods.
Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study
Authors: Kristina Ibañez, James Polke, R Tanner Hagelstrom, Egor Dolzhenko, Dorota Pasko, Ellen Rachel Amy Thomas, Louise C Daugherty, Dalia Kasperaviciute, Katherine R Smith, Zandra C Deans, Sue Hill, Tom Fowler, Richard H Scott, John Hardy, Patrick F Chinnery, Henry Houlden, Augusto Rendon, Mark J Caulfield, Michael A Eberle, Ryan J Taft, Arianna Tucci, Ellen M McDonagh, Antonio Rueda, Dimitris Polychronopoulos, Georgia Chan, Heather Angus-Leppan, Kailash P Bhatia, James E Davison, Richard Festenstein, Pietro Fratta, Paola Giunti, Robin Howard, Laxmi Venkata, Matilde Laurá, Meriel McEntagart, Lara Menzies, Huw Morris, Mary M Reilly, Robert Robinson, Elisabeth Rosser, Francesca Faravelli, Anette Schrag, Jonathan M Schott, Thomas T Warner, Nicholas W Wood, David Bourn, Kelly Eggleton, Robyn Labrum, Philip Twiss, Stephen Abbs, Liana Santos, Ghareesa Almheiri, Isabella Sheikh, Jana Vandrovcova, Christine Patch, Ana Lisa Taylor Tavares, Zerin Hyder, Anna Need, Helen Brittain, Emma Baple, Loukas Moutsianas, Viraj Deshpande, Denise L Perry, Subramanian S. Ajay, Aditi Chawla, Vani Rajan, Kathryn Oprych, Patrick F Chinnery, Angela Douglas, Gill Wilson, Sian Ellard, I Karen Temple, Andrew Mumford, Dom McMullan, Kikkeri Naresh, Frances A Flinter, Jenny C Taylor, Lynn Greenhalgh, William Newman, Paul Brennan, John A Sayer, F Lucy Raymond, Lyn S Chitty, John C. Ambrose, Prabhu Arumugam, Marta Bleda, Freya Boardman-Pretty, Jeanne M. Boissiere, Christopher R. Boustred, Clare E.H. Craig, Anna de Burca, Andrew Devereau, Greg Elgar, Rebecca E. Foulger, Pedro Furió-Tarí, Joanne Hackett, Dina Halai, Angela Hamblin, Shirley Henderson, James Holman, Tim J.P. Hubbard, Rob Jackson, Louise J. Jones, Melis Kayikci, Lea Lahnstein, Kay Lawson, Sarah E.A. Leigh, Ivonne U.S. Leong, Javier F. Lopez, Fiona Maleady-Crowe, Joanne Mason, Michael Mueller, Nirupa Murugaesu, Chris A. Odhams, Daniel Perez-Gil, Dimitris Polychronopoulos, John Pullinger, Tahrima Rahim, Pablo Riesgo-Ferreiro, Tim Rogers, Mina Ryten, Kevin Savage, Kushmita Sawant, Afshan Siddiq, Alexander Sieghart, Damian Smedley, Alona Sosinsky, William Spooner, Helen E. Stevens, Alexander Stuckey, Razvan Sultana, Simon R. Thompson, Carolyn Tregidgo, Emma Walsh, Sarah A. Watters, Matthew J. Welland, Eleanor Williams, Katarzyna Witkowska, Suzanne M. Wood, Magdalena Zarowiecki
Journal: The Lancet Neurology (2022)