tbuckley/cabot-search huggingface dataset:
Vasopressin Increases Urinary Acidification via V1a Receptors in Collecting Duct Intercalated Cells
Authors: Torsten Giesecke, Nina Himmerkus, Jens Leipziger, Markus Bleich, Taka-aki Koshimizu, Michael Fähling, Alina Smorodchenko, Julia Shpak, Carolin Knappe, Julian Isermann, Niklas Ayasse, Katsumasa Kawahara, Jan Schmoranzer, Niclas Gimber, Alexander Paliege, Sebastian Bachmann, Kerim Mutig
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Use of vasopressin V1a receptor (V1aR) agonists and antagonists may be instrumental for corrections of acid-base homeostasis, but the distribution and function of this receptor in the kidney remain to be characterized in detail. The authors investigated whether V1aR stimulation facilitates urinary acidification via intercalated cells. Using a new specific antibody they localized V1aR to the basolateral membrane of type A intercalated cells (A-ICs). In contrast, type B intercalated cells exhibited intracellular but not plasma membrane–bound V1aR signal. Using in vivo and ex vivo models, the authors also showed that selective stimulation of V1aR induces activation of vacuolar H + -ATPase in A-ICs, luminal H + secretion, and urinary acidification. These new details regarding renal vasopressin signaling may have clinical implications for patients with distal renal tubular acidosis. Background Antagonists of the V1a vasopressin receptor (V1aR) are emerging as a strategy for slowing progression of CKD. Physiologically, V1aR signaling has been linked with acid-base homeostasis, but more detailed information is needed about renal V1aR distribution and function. Methods We used a new anti-V1aR antibody and high-resolution microscopy to investigate Va1R distribution in rodent and human kidneys. To investigate whether V1aR activation promotes urinary H + secretion, we used a V1aR agonist or antagonist to evaluate V1aR function in vasopressin-deficient Brattleboro rats, bladder-catheterized mice, isolated collecting ducts, and cultured inner medullary collecting duct (IMCD) cells. Results Localization of V1aR in rodent and human kidneys produced a basolateral signal in type A intercalated cells (A-ICs) and a perinuclear to subapical signal in type B intercalated cells of connecting tubules and collecting ducts. Treating vasopressin-deficient Brattleboro rats with a V1aR agonist decreased urinary pH and tripled net acid excretion; we observed a similar response in C57BL/6J mice. In contrast, V1aR antagonist did not affect urinary pH in normal or acid-loaded mice. In ex vivo settings, basolateral treatment of isolated perfused medullary collecting ducts with the V1aR agonist or vasopressin increased intracellular calcium levels in ICs and decreased luminal pH, suggesting V1aR-dependent calcium release and stimulation of proton-secreting proteins. Basolateral treatment of IMCD cells with the V1aR agonist increased apical abundance of vacuolar H + -ATPase in A-ICs. Conclusions Our results show that activation of V1aR contributes to urinary acidification via H + secretion by A-ICs, which may have clinical implications for pharmacologic targeting of V1aR.
<i>Notes from the Field:</i>Verona Integron-Encoded Metallo-β-Lactamase–Producing Carbapenem-Resistant<i>Pseudomonas aeruginosa</i>Infections in U.S. Residents Associated with Invasive Medical Procedures in Mexico, 2015–2018
Authors: Ian Kracalik, Cal Ham, Amanda R. Smith, Maureen Vowles, Kelly Kauber, Melba Zambrano, Gretchen Rodriguez, Kelley Garner, Kaitlyn Chorbi, P. Maureen Cassidy, Shannon McBee, Rhett Stoney, Allison C. Brown, Kathleen Moser, Margarita E. Villarino, Maroya Spalding Walters
Journal: MMWR Morbidity and Mortality Weekly Report (2019)
A NEW PREPARATION METHOD FOR IMPROVING GASTRIC MUCOSAL VISIBILITY AND CLEANLINESS DURING MAGNETICALLY ASSISTED CAPSULE ENDOSCOPY: A PROSPECTIVE STUDY
Authors: P Schmiedt, M Szalai, L Oczella, K Zsobrak, B Dorottya Lovasz, Z Dubravcsik, L Madacsy
Journal: Endoscopy (2019)

Optimal mucosal visibility is essential during gastrointestinal endoscopy and it is even more important during magnetically assisted capsule endoscopy (MACE) as cleaning the mucosa during the procedure is not possible. Better pre-procedural preparation may improve the sensitivity and specificity of the MACE investigation. The aim of the current study was to compare the cleanliness of the stomach with or without our new gastric preparation protocol.
Exome-Based Rare-Variant Analyses in CKD
Authors: Sophia Cameron-Christie, Charles J. Wolock, Emily Groopman, Slavé Petrovski, Sitharthan Kamalakaran, Gundula Povysil, Dimitrios Vitsios, Mengqi Zhang, Jan Fleckner, Ruth E. March, Sahar Gelfman, Maddalena Marasa, Yifu Li, Simone Sanna-Cherchi, Krzysztof Kiryluk, Andrew S. Allen, Bengt C. Fellström, Carolina Haefliger, Adam Platt, David B. Goldstein, Ali G. Gharavi
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Studies have identified common CKD-associated gene variants, but the contribution of rare variants has not been systematically examined. The authors use exome sequencing and rare-variant collapsing analyses to compare rare genetic variants in 3150 cases (representing broad clinical CKD subtypes) with 9563 controls. For five known CKD-associated genes, they detected a significant enrichment of rare variants in PKD1 , PKD2 , COL4A5 , and found suggestive evidence for rare COL4A3 and COL4A4 variants. They also found evidence for four other genes not previously implicated in CKD. By demonstrating that rare-variant collapsing analyses can validate known genes and identify candidate genes and modifiers for nephropathy, these findings provide a rationale for larger-scale investigation of the rare variants’ contribution to disease risk across major clinical CKD categories. Background Studies have identified many common genetic associations that influence renal function and all-cause CKD, but these explain only a small fraction of variance in these traits. The contribution of rare variants has not been systematically examined. Methods We performed exome sequencing of 3150 individuals, who collectively encompassed diverse CKD subtypes, and 9563 controls. To detect causal genes and evaluate the contribution of rare variants we used collapsing analysis, in which we compared the proportion of cases and controls carrying rare variants per gene. Results The analyses captured five established monogenic causes of CKD: variants in PKD1 , PKD2 , and COL4A5 achieved study-wide significance, and we observed suggestive case enrichment for COL4A4 and COL4A3 . Beyond known disease-associated genes, collapsing analyses incorporating regional variant intolerance identified suggestive dominant signals in CPT2 and several other candidate genes. Biallelic mutations in CPT2 cause carnitine palmitoyltransferase II deficiency, sometimes associated with rhabdomyolysis and acute renal injury. Genetic modifier analysis among cases with APOL1 risk genotypes identified a suggestive signal in AHDC1 , implicated in Xia–Gibbs syndrome, which involves intellectual disability and other features. On the basis of the observed distribution of rare variants, we estimate that a two- to three-fold larger cohort would provide 80% power to implicate new genes for all-cause CKD. Conclusions This study demonstrates that rare-variant collapsing analyses can validate known genes and identify candidate genes and modifiers for kidney disease. In so doing, these findings provide a motivation for larger-scale investigation of rare-variant risk contributions across major clinical CKD categories.
Polychromic Reporter Mice Reveal Unappreciated Innate Lymphoid Cell Progenitor Heterogeneity and Elusive ILC3 Progenitors in Bone Marrow
Authors: Jennifer A. Walker, Paula A. Clark, Alastair Crisp, Jillian L. Barlow, Aydan Szeto, Ana C.F. Ferreira, Batika M.J. Rana, Helen E. Jolin, Noe Rodriguez-Rodriguez, Meera Sivasubramaniam, Richard Pannell, James Cruickshank, Maria Daly, Liora Haim-Vilmovsky, Sarah A. Teichmann, Andrew N.J. McKenzie
Journal: Immunity (2019)

Innate lymphoid cells (ILCs) play strategic roles in tissue homeostasis and immunity. ILCs arise from lymphoid progenitors undergoing lineage restriction and the development of specialized ILC subsets. We generated "5x polychromILC" transcription factor reporter mice to delineate ILC precursor states by revealing the multifaceted expression of key ILC-associated transcription factors (Id2, Bcl11b, Gata3, RORγt, and RORα) during ILC development in the bone marrow. This approach allowed previously unattained enrichment of rare progenitor subsets and revealed hitherto unappreciated ILC precursor heterogeneity. In vivo and in vitro assays identified precursors with potential to generate all ILC subsets and natural killer (NK) cells, and also permitted discrimination of elusive ILC3 bone marrow antecedents. Single-cell gene expression analysis identified a discrete ILC2-committed population and delineated transition states between early progenitors and a highly heterogeneous ILC1, ILC3, and NK precursor cell cluster. This diversity might facilitate greater lineage potential upon progenitor recruitment to peripheral tissues.
INTER-OBSERVER AGREEMENT IN BROTZ CLEANING SCALES FOR CAPSULE ENDOSCOPY
Authors: M Sousa, R Pinho, A Ponte, A Rodrigues, J Silva, C Gomes, J Carvalho
Journal: Endoscopy (2019)

The diagnostic yield of capsule endoscopy (CE) depends on the adequate visualization of the mucosa. As with colonoscopy, cleaning scales should be described in the report in order to better interpret results. In 2008, Brotz et al proposed and validated 3 different cleansing scales. The aim of this study was to evaluate the inter-observer variability of this cleaning scales.
Dozens of US states sue 20 generic drug companies over “industry wide conspiracy” to drive up prices
Authors: Owen Dyer
Journal: BMJ (2019)

Generic drug makers conspired to avoid competition and drive up the prices of more than a hundred common drugs, sometimes by more than 1000%, according to a major lawsuit filed by 43 US states and Puerto Rico.1

The “industry wide conspiracy” is the principal reason the promise of generics delivering affordable drugs to US patients has never materialised, according to Connecticut attorney general William Tong, who is leading the suit.

“We have hard evidence that shows the generic drug industry perpetrated a multi-billion dollar fraud on the American people,” he said, announcing the suit’s filing in a Connecticut federal court. “We have emails, text messages, telephone records, and former company insiders that we believe will prove a conspiracy to fix prices and divide market share for huge numbers of generic drugs.”

“These are drugs that people in this country rely on every day,” …
ANALYSIS OF BILIARY CANNULATION ALGORITHM IN HIGH-VOLUME HUNGARIAN ERCP CENTERS BASED ON PROSPECTIVELY COLLECTED REGISTRY DATA
Authors: D Pécsi, S Gódi, P Hegyi, I Altorjay, T Bakucz, L Czakó, G Kovács, Á Orbán-Szilágyi, F Pakodi, Á Patai, Z Szepes, T Gyökeres, Á Vincze
Journal: Endoscopy (2019)

Selective biliary duct cannulation (BDC) was analysed in our current practice based on the data from five tertiary centers according to the recent evidence-based ESGE algorithm of biliary access.
Mental health symptoms and disorders in elite athletes: a systematic review on cultural influencers and barriers to athletes seeking treatment
Authors: João Mauricio Castaldelli-Maia, João Guilherme de Mello e Gallinaro, Rodrigo Scialfa Falcão, Vincent Gouttebarge, Mary E Hitchcock, Brian Hainline, Claudia L Reardon, Todd Stull
Journal: British Journal of Sports Medicine (2019)

Objective To summarise the literature on the barriers to athletes seeking mental health treatment and cultural influencers of mental health in elite athletes. Design Systematic review Data sources PubMed, Cochrane, Scopus, SportDiscus (Ebsco), and PsycINFO (ProQuest) up to November 2018. Eligibility criteria for selecting studies Qualitative and quantitative original studies of elite athletes (those who competed at the professional, Olympic, or collegiate/university levels), published in any language. Results Stigma, low mental health literacy, negative past experiences with mental health treatment-seeking, busy schedules, and hypermasculinity are barriers to elite athletes seeking mental health treatment. Cultural influencers of mental health in elite athletes include: (1) the lack of acceptance of women as athletes; (2) lower acceptability of mental health symptoms and disorders among non-white athletes; (3) non-disclosure of religious beliefs; and (4) higher dependence on economic benefits. Coaches have an important role in supporting elite athletes in obtaining treatment for mental illness. Brief anti-stigma interventions in elite athletes decrease stigma and improve literary about mental health. Conclusion There is a need for various actors to provide more effective strategies to overcome the stigma that surrounds mental illness, increase mental health literacy in the athlete/coach community, and address athlete-specific barriers to seeking treatment for mental illness. In this systematic review, we identified strategies that, if implemented, can overcome the cultural factors that may otherwise limit athletes seeking treatment. Coaches are critical for promoting a culture within elite athletes’ environments that encourages athletes to seek treatment.
Open access: remember the limitations of abstracts and the role of professional endorsement
Authors: Erika F J Frey
Journal: BMJ (2019)

Further to e-patient Dave’s plea to think of the patients in open access publishing,1 some other important points have been overlooked.

Researchers know that knowledge dissemination is pivotal. As they want their research to have reach and real life impacts, they prioritise publishing fees. Essentially, if it isn’t published and disseminated, it didn’t happen.

In my discipline (e-health literacy), I …
Treatment and monitoring of Philadelphia chromosome-positive leukemia patients: recent advances and remaining challenges
Authors: Simona Soverini, Renato Bassan, Thomas Lion
Journal: Journal of Hematology & Oncology (2019)

The Philadelphia (Ph) chromosome, resulting from the t(9;22)(q34;q11) translocation, can be found in chronic myeloid leukemia (CML) as well as in a subset of acute lymphoblastic leukemias (ALL). The deregulated BCR-ABL1 tyrosine kinase encoded by the fusion gene resulting from the translocation is considered the pathogenetic driver and can be therapeutically targeted. In both CML and Ph-positive (Ph+) ALL, tyrosine kinase inhibitors (TKIs) have significantly improved outcomes. In the TKI era, testing for BCR-ABL1 transcript levels by real-time quantitative polymerase chain reaction (RQ-PCR) has become the gold standard to monitor patient response, anticipate relapse, and guide therapeutic decisions. In CML, key molecular response milestones have been defined that draw the ideal trajectory towards optimal long-term outcomes. Treatment discontinuation (treatment-free remission, TFR) has proven feasible in a proportion of patients, and clinical efforts are now focused on how to increase this proportion and how to best select TFR candidates. In Ph+ ALL, results of trials with second- and third-generation TKIs are challenging the role of intensive chemotherapy and even that of allogeneic stem cell transplantation. Additional weapons are offered by the recently introduced monoclonal antibodies. In patients harboring mutations in the BCR-ABL1 kinase domain, prompt therapeutic reassessment and individualization based on mutation status are important to regain response and prevent disease progression. Next-generation sequencing is likely to become a precious tool for mutation testing because of the greater sensitivity and the possibility to discriminate between compound and polyclonal mutations. In this review, we discuss the latest advances in treatment and monitoring of CML and Ph+ ALL and the issues that still need to be addressed to make the best use of the therapeutic armamentarium and molecular testing technologies currently at our disposal.
Biomarker guidance allows a more personalized allocation of patients for remote patient management in heart failure: results from the TIM‐HF2 trial
Authors: Martin Möckel, Kerstin Koehler, Stefan D. Anker, Jörn Vollert, Volker Moeller, Magdalena Koehler, Stefan Gehrig, Jan C. Wiemer, Stephan von Haehling, Friedrich Koehler
Journal: European Journal of Heart Failure (2019)
Metastatic Extramammary Paget Disease of the Perianal Region
Authors: Anitha Mandava, Veeraiah Koppula, Rohit Yalamanchili, Zakir Ali
Journal: Clinical Nuclear Medicine (2019)

Abstract A 72-year-old man with history of itching for 8 months presented with an ill-defined, ulcerated, eczematous, thickened cutaneous lesion in the left perianal region. 18 F-FDG PET/CT was performed, and neoplastic skin thickening with FDG uptake was seen at the left gluteal cleft. Hypermetabolic inguinal, retroperitoneal, and mediastinal lymph nodes, liver, and bone metastases were seen. Histopathology and immunohistochemistry of the perianal growth and left inguinal lymph node were positive for cytokeratin7 and gross cystic disease fluid protein and negative for cytokeratin 20 and CDX2, confirming the diagnosis of primary extramammary Paget disease with metastases.
HOW LONG TIME SHOULD AN ESOPHAGOGASTRODUODENOSCOPY BE DONE?
Authors: KM Sohn
Journal: Endoscopy (2019)

Esophagogastroduodenoscopy (EGD) is commonly used to detect upper gastrointestinal (GI) neoplasms. However, it is not clear how the time of EGD affects the detection of cancer or premalignant lesions that increase the risk for GI cancer. We investigate whether differences in endoscopy exam time of cancer affect cancer detection rates.
Programme assurance qualité en endoscopie: audit clinique prospectif de plus de 400 coloscopies
Authors: A guignard, V Nardon, MI Gheorghiu, J Bottlaender, L Plastaras, G Breysacher, M Bolliet, A Topolscki, I Amaritei, D Gospei, B Denis
Journal: Endoscopy (2019)

La coloscopie a toutes les caractéristiques pour relever d'un programme d'amélioration de la qualité. La plupart des sociétés savantes recommandent l'adoption d'une démarche qualité avec enregistrement systématique de certains indicateurs. Un référentiel qualité coloscopie SFED-SNFGE-SYNMAD devrait être publié en 2018. Le but de ce travail était d'évaluer la qualité des coloscopies réalisées dans notre unité d'endoscopie dans le but de l'améliorer.
Antidepressant withdrawal guidance must be updated to reflect evidence
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Recommendations on antidepressant withdrawal need to be updated urgently to reflect the scientific evidence, said a group of experts writing in The BMJ .1

It was a concern that the evidence base contradicted the official position of the UK National Institute on Health and Clinical Excellence on antidepressant withdrawal, they said, and they warned that if doctors were following these recommendations many people may have had their withdrawal symptoms misdiagnosed as a relapse or a failure to respond to treatment.

As a result, patients who were trying to come off antidepressants may have had them reinstated or switched, or …
Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes
Authors: Lionel Spielmann, Benoit Nespola, François Séverac, Emmanuel Andres, Romain Kessler, Aurélien Guffroy, Vincent Poindron, Thierry Martin, Bernard Geny, Jean Sibilia, Alain Meyer
Journal: Annals of the Rheumatic Diseases (2019)

Objective To refine the spectrum of anti-Ku-associated disease, a condition that is equivocally described by current diagnostic criteria for connective tissue diseases. Methods Among 42 consecutive patients harbouring anti-Ku antibodies, subgroups with similar phenotypes and prognosis were delineated without an a priori diagnosis using hierarchical clustering analysis of the cumulative clinico-biological features recorded during the follow-up. Features present at baseline that most efficiently predicted the outcomes were then identified using a sensitivity–specificity sum maximisation approach. Results Clinico-biological features were clustered into three groups. Glomerulonephritis and ILD, the two fatal complications in this cohort, were unequally distributed between the three clusters that additionally differed on six clinico-biological features. Among features present at baseline, elevated serum level of creatine kinase (CK) and anti-dsDNA antibodies were generally mutually exclusive and most efficiently predicted the cluster belonging at last follow-up. Anti-Ku patients with elevated CK had a 22-fold higher risk of ILD while anti-Ku patients with anti-dsDNA antibodies had a 13-fold higher risk of glomerulonephritis Conclusion “Anti-Ku with elevated CK” syndrome and “anti-Ku with anti-dsDNA” syndrome represent two distinct entities that are important to recognise in order to best tailor patient care.
SUBMUCOSAL TUNNELLING ENDOSCOPIC SEPTUM DIVISION (Z-POEM) FOR ZENKER'S DIVERTICULUM: A NEW EMERGING TECHNIQUE COMPARED TO CONVENTIONAL ENDOSCOPIC SEPTOTOMY
Authors: P Desai, M Kabrawala, S Nandwani, R Mehta, C Patel, P Kalra, R Prajapati, N Patel
Journal: Endoscopy (2019)

Zenker's diverticulum (ZD) is an acquired protrusion of the esophageal wall. A wide variety of different treatment techniques have been published. Historically ZD managed by surgery and for last few years endoscopic septum division is done. We compared the clinical success of Z-POEMfor ZD with conventional.
FACTORS ASSOCIATED WITH SEDATION USE IN DIAGNOSTIC AND SCREENING PATIENTS ≥50 YEARS OF AGE: OBSERVATIONS FROM THE EUROPEAN COLONOSCOPY QUALITY INVESTIGATION (ECQI) QUESTIONNAIRE
Authors: E Toth, A Agrawal, P Amaro, L Brink, W Fischbach, M Hünger, R Jover, U Kinnunen, A Koulaouzidis, A Ono, Á Patai, S Pecere, L Petruzziello, JF Riemann, B Amlani, C Spada
Journal: Endoscopy (2019)

To assess the factors associated with sedation use in diagnostic and screening patients ≥50 years of age using questionnaire responses from across Europe.
ENDOSCOPIC SUBMUCOSAL LASER ABLATION FOR THE TREATMENT OF TYPE 2 DIABETES – PRELIMINARY FIRST IN HUMAN STUDY RESULTS
Authors: M Benes, I Marcovitch, M Mraz, A Herschkovitz, M Haluzik
Journal: Endoscopy (2019)

Duodenal Glycemic Control (DGC) is an endoscopic procedure under direct vision which uses a disposable catheter (DiaGone) without an Implant. DiaGone utilizes precisely controlled laser technology to target the duodenal submucosa in order to modulate the GI neurohormonal axis, hence improving glucose metabolism.