tbuckley/cabot-search huggingface dataset:
Discovering Genes Essential to the Hypothalamic Regulation of Human Reproduction Using a Human Disease Model: Adjusting to Life in the “-Omics” Era
Authors: M. I. Stamou, K. H. Cox, William F. Crowley
Journal: Endocrine Reviews (2015)

Abstract The neuroendocrine regulation of reproduction is an intricate process requiring the exquisite coordination of an assortment of cellular networks, all converging on the GnRH neurons. These neurons have a complex life history, migrating mainly from the olfactory placode into the hypothalamus, where GnRH is secreted and acts as the master regulator of the hypothalamic-pituitary-gonadal axis. Much of what we know about the biology of the GnRH neurons has been aided by discoveries made using the human disease model of isolated GnRH deficiency (IGD), a family of rare Mendelian disorders that share a common failure of secretion and/or action of GnRH causing hypogonadotropic hypogonadism. Over the last 30 years, research groups around the world have been investigating the genetic basis of IGD using different strategies based on complex cases that harbor structural abnormalities or single pleiotropic genes, endogamous pedigrees, candidate gene approaches as well as pathway gene analyses. Although such traditional approaches, based on well-validated tools, have been critical to establish the field, new strategies, such as next-generation sequencing, are now providing speed and robustness, but also revealing a surprising number of variants in known IGD genes in both patients and healthy controls. Thus, before the field moves forward with new genetic tools and continues discovery efforts, we must reassess what we know about IGD genetics and prepare to hold our work to a different standard. The purpose of this review is to: 1) look back at the strategies used to discover the “known” genes implicated in the rare forms of IGD; 2) examine the strengths and weaknesses of the methodologies used to validate genetic variation; 3)substantiate the role of known genes in the pathophysiology of the disease; and 4) project forward as we embark upon a widening use of these new and powerful technologies for gene discovery. (Endocrine Reviews 36: 603–621, 2015)
Free Papers
Authors: G. Emmanuel, S. Carranza, S. Vettichira, M. Paradis, T. Lie, P. Kessler, V. B. Schini-Kerth, Y. Koh, B. M. Hybertson, E. K. Jepson, M. J. Kim, I. Lee, C. M. Lim, S. D. Lee, W. S. Kim, D. S. Kim, W. D. Kim, J. E. Repine, T. Takeda, T. Yukioka, H. Matsuda, S. Shimazaki, D. Kammermeier, J. Birkmann, L. Blinzler, W. M. Gallmeier, D. Heuser, M. Jourdain, J. Mangalaboyi, O. Carrette, A. Toumoys, F. Fourrier, J. Mizon, C. Chopin, S. L. Peake, J. K. Carter, R. G. Russ, J. Pierides, J. P. Leppard, K. Porter, H. F. Galley, N. R. Webster, S. J. Wigmore, T. S. Walsh, P. Hopton, A. Lee, J. A. Ross, P. A. Majcherczyk, J. Pugin, M. P. Glauser, D. Heumann, G. Zanetti, I. de Werra, A. Sablotzki, I. Welters, T. Menges, G. Görlach, N. Lehmann, G. Hempelmann, E. Giannitsis, I. Tettenborn, U. Stierle, K. Dalhoff, A. Sheikhzadeh, K. W. Diederich, V. Gant, C. Maciver, D. F. Treacher, M. Lamy, L. G. Thijs, B. Eisele, H. -O. Keinecke, H. P. Schuster, F. R. Matthias, W. Oettinger, U. Hartenauer, F. Fourrier, U. Delvos, S. A. Stott, D. W. Noble, W. Schobersberger, G. Hoffmann, J. Fandrey, G. J. Bellingan, H. Caldwell, I. Dransfield, S. M. Howie, C. Haslett, L. Liaudet, F. Feihl, M. Markert, C. Perret, M. A. Williams, C. Rhoades, S. A. White, J. Miller, S. Withington, A. C. Newland, S. M. Kelsey, A. Froon, M. Bonten, C. Gaillard, J. Greve, P. de Leeuw, M. Drent, E. Stobberingh, W. Buurman, O. Fourcade, M. -F. Simon, F. Leballe, R. Ashraf, L. Sarda, B. Cathala, H. Chap, P. Reper, R. Danckaert, R. Jeunen, T. Bruyns, J. De Hemptinne, A. Vanderkelen
Journal: Intensive Care Medicine (1996)
HSP90-CDC37 functions as a chaperone for the oncogenic FGFR3-TACC3 fusion
Authors: Tao Li, Farideh Mehraein-Ghomi, M Elizabeth Forbes, Sanjeev V Namjoshi, E Ashley Ballard, Qianqian Song, Ping-Chieh Chou, Xuya Wang, Brittany C Parker Kerrigan, Frederick F Lang, Glenn Lesser, Waldemar Debinski, Xuejun Yang, Wei Zhang
Journal: Molecular Therapy (2022)

The FGFR3-TACC3 (F3-T3) fusion gene was discovered as an oncogenic molecule in glioblastoma and bladder cancers, and has subsequently been found in many cancer types. Notably, F3-T3 was found to be highly expressed in both untreated and matched recurrence glioblastoma under the concurrent radiotherapy and temozolomide (TMZ) treatment, suggesting that targeting F3-T3 is a valid strategy for treatment. Here, we show that the F3-T3 protein is a client of heat shock protein 90 (HSP90), forming a ternary complex with the cell division cycle 37 (CDC37). Deprivation of HSP90 or CDC37 disrupts the formation of the ternary complex, which destabilizes glycosylated F3-T3, and thereby suppresses F3-T3 oncogenic activity. Gliomas harboring F3-T3 are resistant to TMZ chemotherapy. HSP90 inhibitors sensitized F3-T3 glioma cells to TMZ via the inhibition of F3-T3 activation and potentiated TMZ-induced DNA damage. These results demonstrate that F3-T3 oncogenic function is dependent on the HSP90 chaperone system and suggests a new clinical option for targeting this genetic aberration in cancer.
Heterogeneity of Type 1 Diabetes at Diagnosis Supports Existence of Age-Related Endotypes
Authors: Anna Parviainen, Taina Härkönen, Jorma Ilonen, Anna But, Mikael Knip
Journal: Diabetes Care (2022)

OBJECTIVE Previous findings suggest that there are age-related endotypes of type 1 diabetes with different underlying etiopathological mechanisms in those diagnosed at age &amp;lt;7 years compared with those diagnosed at age ≥13 years. We set out to explore whether variation in demographic, clinical, autoimmune, and genetic characteristics of children and adolescents with newly diagnosed type 1 diabetes support the existence of these proposed endotypes. RESEARCH DESIGN AND METHODS We used data from the Finnish Pediatric Diabetes Register to analyze characteristics of 6,015 children and adolescents diagnosed with type 1 diabetes between 2003 and 2019. We described and compared demographic data, clinical characteristics at diagnosis, autoantibody profiles, and HLA class II–associated disease risk between three groups formed based on age at diagnosis: &amp;lt;7, 7–12, and ≥13 years. RESULTS We found significant age-related differences in most of the characteristics analyzed. Children diagnosed at age &amp;lt;7 years were characterized by a higher prevalence of affected first-degree relatives, stronger HLA-conferred disease susceptibility, and higher number of autoantibodies at diagnosis, in particular a higher frequency of insulin autoantibodies, when compared with older children. Those diagnosed at age ≥13 years had a considerably higher male preponderance, higher frequency of glutamic acid decarboxylase autoantibodies, longer duration of symptoms before diagnosis, and more severe metabolic decompensation, reflected, for example, by a higher frequency of diabetic ketoacidosis. CONCLUSIONS Our findings suggest that the heterogeneity of type 1 diabetes is associated with the underlying disease process and support the existence of distinct endotypes of type 1 diabetes related to age at diagnosis.
Elicitation of potent SARS-CoV-2 neutralizing antibody responses through immunization with a versatile adenovirus-inspired multimerization platform
Authors: Christopher Chevillard, Axelle Amen, Solène Besson, Dalil Hannani, Isabelle Bally, Valentin Dettling, Evelyne Gout, Christophe J. Moreau, Marlyse Buisson, Salomé Gallet, Daphna Fenel, Emilie Vassal-Stermann, Guy Schoehn, Pascal Poignard, Marie-Claire Dagher, Pascal Fender
Journal: Molecular Therapy (2022)

Virus-like particles (VLPs) are highly suited platforms for protein-based vaccines. In the present work, we adapted a previously designed non-infectious adenovirus-inspired 60-mer dodecahedric VLP (ADDomer) to display a multimeric array of large antigens through a SpyTag/SpyCatcher system. To validate the platform as a potential COVID-19 vaccine approach, we decorated the newly designed VLP with the glycosylated receptor binding domain (RBD) of SARS-CoV-2. Cryoelectron microscopy structure revealed that up to 60 copies of this antigenic domain could be bound on a single ADDomer particle, with the symmetrical arrangements of a dodecahedron. Mouse immunization with the RBD decorated VLPs already showed a significant specific humoral response following prime vaccination, greatly reinforced by a single boost. Neutralization assays with SARS-CoV-2 spike pseudo-typed virus demonstrated the elicitation of strong neutralization titers, superior to those of COVID-19 convalescent patients. Notably, the presence of pre-existing immunity against the adenoviral-derived particles did not hamper the immune response against the antigen displayed on its surface. This plug and play vaccine platform represents a promising new highly versatile tool to combat emergent pathogens.
SARS‐CoV‐2 Omicron variant: A next phase of the COVID‐19 pandemic and a call to arms for system sciences and precision medicine
Authors: Ebrahim Mostafavi, Ankit Kumar Dubey, Laura Teodori, Seeram Ramakrishna, Ajeet Kaushik
Journal: MedComm (2022)

Since early 2020, coronavirus diseases 2019 (COVID-19) infection pandemic/endemic is constantly surprising health experts because of continuous variations in the structures of severe acute respiratory coronavirus 2 (SARS-CoV-2) in the form of newly emerged variants. Such mutations have exhibited high mortality and severity due to the newly emerged more infectious sites of SARS-CoV-2, making viral infection more transmissible, infectious, and severe. Recently, SARS-CoV-2 mutated to another variant, namely, Omicron (B.1.1.529), which is many times more transmissible and infectious than existed deadly Delta variants of the virus. This severity is closely correlated to a larger number of mutations observed in the receptor-binding domain of the spike protein of the Omicron-SARS-CoV-2. Considering severity, Omicron has been declared as variant of concerns by the World Health Organization and within days from its emergence, Omicron infection has spread globally, increased hospitalization, exhibited more severity for the young generation, invaded defense mechanism of natural immunity, not responsive to the available vaccines. Such circumstances resonated with the efficiency of available strategies established to manage COVID-19 intelligently and successfully. To explore these aspects, this perspective article carefully and critically summarizes the Omicron's origin, structure, pathogenesis, impact health along with health systems, and experts' recommendations to manage it successfully.
Cranberry Circus! The How-To Book for Home Health Care
Journal: JAMA (1997)

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
Symposium on Infections and Immunosuppression in Subhuman Primates
Journal: JNCI Journal of the National Cancer Institute (1969)

Symposium on Infections and Immunosuppression in Subhuman Primates Get access JNCI: Journal of the National Cancer Institute, Volume 43, Issue 3, September 1969, Page 747, https://doi.org/10.1093/jnci/43.3.747-a Published: 01 September 1969
一项使用两种方法检查称为网状编织图案上层皮肤层的研究
Authors: H. Goto, A. Tada, A. Ibe, Y. Kitajima
Journal: British Journal of Dermatology (2020)

皮肤由几层组成,其中最外层是角质层。正常角质层 (SC) 本身分为两层,上层是网状编织 (B‐W) 图案层,下层是较低的致密层。角化桥粒是在角质层中发现的细胞,在健康的皮肤中,它们的数量从下层致密层到上层网状编织层不断减少(细胞降解),并且其分布(布局)发生变化。这可以通过观察在胶带(胶带粘贴)上采集的皮肤细胞样本中的桥粒芯蛋白 1 (Dsg1) 水平看出,因为 Dsg1 的水平代表角化桥粒的数量。在某些皮肤病中,例如寻常型鱼鳞病和 X 连锁鱼鳞病中,没有网状编织图案层,或者不完整。 在这项研究中,利用重建的人表皮(RHE,一种由皮肤细胞发育而成的皮肤模型)以及通过胶带粘贴从女性志愿者身上获得的皮肤细胞,探索了网状编织图案上层的功能。 科学家们使用了水包油型乳剂,制备了乳霜 A,并成功地在重建的人表皮中生成了网状编织图案上层,从而促进了角化桥粒的降解。这可能是有用的工具,可用于体外(指在实验室而不是在人体中)研究网状编织层的生理意义。 研究人员使用女性志愿者的细胞发现,最外层角质层中 Dsg1 的降解(代表网状编织图案层的形成)与健康皮肤水屏障功能(健康皮肤屏障的标志)和 SC 柔软度相关,而后者差异很大。测量通过胶带粘贴从人体皮肤上获得的角质层中 Dsg1 的含量,可以研究外用刺激剂(例如乳霜/软膏)对网状编织层完整性的影响,而无需活检。 本摘要涉及研究:通过重建人体表皮和胶带粘贴人脸颊皮肤进行的研究显示角质层中的网状编织结构是维持人体皮肤生理特性的重要因素
Intestinal peptidases.
Authors: T J Peters
Journal: Gut (1970)

Progress report Intestinal peptidasesCurrent interest in the intestinal peptidases is centred round two main topics: (1) their role in the digestion of dietary protein and (2) investigation of Fraser's hypothesis that coeliac disease is due to a congenital deficiency of the peptidase(s) which normally digest gluten.This report will consider these topics and also briefly review recent studies on a lysosomal peptidase concerned with the digestion of dietary folate. Role of Peptidases in Protein DigestionAlthough it has been accepted for many years that proteins are completely hydrolysed to their constituent amino acidsl-5 it is only relatively recently that the intestinal epithelial cells (enterocytes) have been acknowledged as playing a direct role in this process.Previously it had been considered that the peptidases were secreted by these cells into the lumen as 'erepsin'6-8 although Ugolev and his colleagues have claimed that the entire process of protein digestion occurs at the brush border9.Their hypothesis has recently received support by the demonstration of binding of pancreatic proteases to the brush border.10'11Following the isolation, by Crane and his colleagues, of intact brush borders'2, and the localization of disaccharidase activity to this organelle, it has become generally accepted that the final stages of polysaccharide digestion occurs at the brush border.Studies on the subcellular localization of peptidases were soon undertaken and indicated that these enzymes, too, were localized to the brush border.It thus appeared that the final stages of protein digestion, like that of polysaccharide digestion, occurred at the brush border.These early studies on the subcellular localization of peptidases within the enterocyte used the artificial substrate L leucyl-,B naphthylamide.However, the enzymes responsible for the hydrolysis of leucine-containing dipeptides have now been clearly separated from the enzymes which hydrolyse leucyl-,P naphthylamide in several tissues, including intestinal mucosa.18-21This criticism may apply to certain other studies using artificial chromogenic substrates.22-25 This observation helps to resolve the apparent conflict between the histo- chemical localization of leucine amino-peptidase (leucyl-,B naphthylami- dase) to the brush border and the biochemical studies which indicated that only 5 to 10 % of dipeptidase activity was localized to isolated brush borders.The major proportion of the true peptidase activity was found in the cytosol.26-30Joseffson and his colleagues have, however, sounded a note of caution in the interpretation of these subcellular fractionation experiments.3'They have noted that dipeptidase activity is rapidly released from isolated intestinal mucosa and commented that this invalidates subcellular fractiona-on August 19,
Peroral endoscopic myotomy, septotomy, and restoration of esophageal lumen with over-the-scope clips: closing the circle of esophageal diverticula management
Authors: Eduardo Albéniz, Fermín Estremera-Arévalo, Marta Gómez Alonso, Pedro J. Rosón, Francisco J. Gallego Rojo, Juan Vila, Sheyla Montori
Journal: Endoscopy (2022)

Peroral endoscopic myotomy (POEM) is an option for esophageal diverticula treatment based on septum myotomy. However, a significant number of patients continue to be symptomatic owing to the pouch persistence [1] [2] [3] [4].
New and Nonofficial Remedies
Journal: JAMA (1923)

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
THE BACKBONE OF MEDICAL JOURNALISM
Journal: JAMA (1965)

The Journalis not an island, entire of itself. Decisions to publish, or not to publish, are the final prerogative of its editor, but they are reached by a process which is often tortuous and contrived. There is no device or schema by which these judgments are achieved. Variable and capricious as they may often appear to be, especially to authors, behind every critical decision lies a "third-party" view. This issue introduces our third parties on page 192. They are the spinal vertebrae of scientific medicine, supporting well-presented communication and annihilating editorial or writer prejudice. Sometimes they give the inside view essential to sensitive focus; on other occasions they range their telescopic lenses from a distance, pulling things into true perspective. Not infrequently a manuscript requires examination from several focal planes so that it may be adjusted to yield a sharp image. The consultant performs a service to author as
Autoimmune hepatitis
Authors: Ansgar W. Lohse, Giorgina Mieli-Vergani
Journal: Journal of Hepatology (2010)

Autoimmune hepatitis was one of the first liver diseases for which an effective treatment was developed and the benefit proven by randomized controlled trials. Nonetheless, both the diagnosis and the treatment of autoimmune hepatitis remain full of challenges. The clinical spectrum is very wide, ranging from subclinical non-progressive disease to fulminant hepatic failure. Diagnostic criteria based on elevation of IgG, demonstration of characteristic autoantibodies, and histological features of hepatitis in the absence of viral disease are very helpful. However, in some patients, diagnosis remains a clinical challenge. Adequately dosed steroids are the mainstay of remission induction treatment, while remission maintenance is best achieved by azathioprine. Therapeutic alternatives are required in a small group of patients responding insufficiently to these drugs or intolerant to their side effects.
Dietary fibre.
Authors: J H Cummings
Journal: Gut (1973)

Progress report Dietary fibreAlthough an important component of animal feeds, fibre has for long been considered an insignificant part of our diet.Recent advances in our knowledge of its chemistry', coupled with some epidemiological2'3'4 observations have led to the suggestion that it plays an essential role in the gut and in maintain- ing man's health.A relative lack of fibre in the diet of the 'Western' world has been linked with the increasing incidence of several common diseases5'6'7, and has provoked comment on the radio, television, and in the press8.Fibre is not an inert, unpalatable substance which passes unchanged through the gut, but a group of compounds with physical, chemical, and metabolic properties which significantly alter gastrointestinal function. DefinitionDietary fibre has been defined as that part of plant material taken in our diet which is resistant to digestion by the secretions of the human gastrointestinal tract9.It comprises a heterogeneous group of carbohydrate compounds including cellulose and the hemicelluloses and a non-carbohydrate substance lignin.These substances form the structure of plants being present in the cell walls of all parts including the leaf, stem, root, and seed.McCance and Lawrence'0 called this fraction of the diet the 'unavailable carbohydrate', although it is not strictly unavailable or entirely carbohydrate.The term 'dietary fibre' is not synonymous with 'crude fibre', which is a time-honoured and internationally accepted term used to define the fibre content of foodstuffs".Crude fibre, as defined by the association of Official Analytical Chemists12 is the residue of a feeding material after treatment with boiling sulphuric acid, sodium hydroxide, water, alcohol, and ether.It is a measure of the cellulose and lignin content mainly.The basis of this method was originally described by Hennenburg and Stohmann13 in 1860 and came to be known as the Weende method after the town in Germany where it originated.However, it has been recognized for many years that this method underestimates the total amount of fibre in food by up to 50% 4,15.The difference between crude fibre and dietary fibre arises because during the Weende procedure the water-and alkali-soluble hemicelluloses are extracted and therefore not measured.Trowell has suggested that it is dietary fibre and not crude fibre that protects against disease. IntakeIn Britain crude fibre intake is between 4 and 8 g/day7"16 whilst in the UnitedStates intakes of about 8 to 11 g/day are reported17.True dietary fibre intakes are, however, very difficult to estimate as current tables of the composition of food either do not give fibre content'8 or use the crude fibre value'9'20 which gives only a relative idea of the total fibre content.Dietary fibre intakes 69 on August 2,
Vascular cognitive impairment
Authors: John T O'Brien, Timo Erkinjuntti, Barry Reisberg, Gustavo Roman, Tohru Sawada, Leonardo Pantoni, John V Bowler, Clive Ballard, Charles DeCarli, Philip B Gorelick, Kenneth Rockwood, Alistair Burns, Serge Gauthier, Steven T DeKosky
Journal: The Lancet Neurology (2003)