tbuckley/cabot-search huggingface dataset:
Simultaneous imaging of calcium and contraction in the beating heart of zebrafish larvae
Authors: Jussep Salgado-Almario, Manuel Vicente, Yillcer Molina, Antonio Martinez-Sielva, Pierre Vincent, Beatriz Domingo, Juan Llopis
Journal: Theranostics (2022)

In vivo models of cardiac function maintain the complex relationship of cardiomyocytes with other heart cells, as well as the paracrine and mechanoelectrical feedback mechanisms.We aimed at imaging calcium transients simultaneously with heart contraction in zebrafish larvae.Methods: To image calcium in beating hearts, we generated a zebrafish transgenic line expressing the FRET-based ratiometric biosensor Twitch-4.Since emission ratioing canceled out the motion artifacts, we did not use myosin inhibitors or tnnt2a morpholinos to uncouple contraction from changes in calcium levels.We wrote an analysis program to automatically calculate kinetic parameters of the calcium transients.In addition, the ventricular diameter was determined in the fluorescence images providing a real-time measurement of contraction correlated with calcium.Results: Expression of Twitch-4 did not affect the force of contraction, the size of the heart nor the heart rate in 3-and 5-days post-fertilization (dpf) larvae.Comparison of 3 and 5 dpf larvae showed that calcium levels and transient amplitude were larger at 5 dpf, but the fractional shortening did not change.To validate the model, we evaluated the effect of drugs with known effects on cardiomyocytes.Calcium levels and the force of contraction decreased by the L-type calcium channel blocker nifedipine, whereas they increased with the activator Bay-K 8644.Caffeine induced bradycardia, markedly decreased ventricular diastolic calcium levels, increased the size of the calcium transients, and caused an escape rhythm in some larvae. Conclusions:The Tg(myl7:Twitch-4) line provides a physiological approach to image systolic and diastolic calcium levels in the heart of zebrafish larvae.Since the heart is beating, calcium levels and contraction can be correlated.This line will be a useful tool to address pathophysiological mechanisms in diseases like heart failure and arrhythmia, in cardiotoxicity studies and for drug screening.
Book Review An Atlas of the Commoner Skin Diseases . Second edition. By Henry C. G. Semon, D.M. (Oxon.), F.R.C.P. (London). 4°, cloth, 273 pp., with 120 colored plates. Color photography under the direction of Arnold Moritz, M.B., B.C. (Cantab.). Baltimore: Williams and Wilkins Company, 1940. $12.00.
Journal: New England Journal of Medicine (1941)
Hepatic interferon regulatory factor 8 expression suppresses hepatocellular carcinoma progression and enhances the response to anti–programmed cell death protein‐1 therapy
Authors: Hongxi Wu, Yan Li, Guangjiang Shi, Shijia Du, Xiaobin Wang, Wanli Ye, Zixuan Zhang, Ya Chu, Shuqian Ma, Dajia Wang, Yuan Li, Zhen Chen, Lutz Birnbaumer, Zhuo Wang, Yong Yang
Journal: Hepatology (2022)

Abstract Background and Aims Therapeutic blockade of the programmed cell death protein‐1 (PD‐1) immune checkpoint pathways has resulted in significant reactivation of T cell–mediated antitumor immunity and is a promising clinical anticancer treatment modality in several tumor types, but the durable response rate remains relatively low (15%–20%) in most patients with HCC for unknown reasons. Evidence reveals that the interferon signaling pathway plays a critical role in modulating the efficacy and sensitivity of anti–PD‐1 therapy against multiple tumor types, but the mechanisms are unclear. Approach and Results Using Kaplan‐Meier survival analysis based on HCC databases, we found that deceased expression of interferon regulatory factor (IRF) 8 in HCC, among all the nine IRF members that regulate interferon signals, was associated with poor prognosis of patients with HCC. Moreover, gene set enrichment analysis identified the interferon‐gamma and PD‐1 signaling signatures as the top suppressed pathways in patients with IRF8‐low HCC. Contrarily, overexpression of IRF8 in HCC cells significantly enhanced antitumor effects in immune‐competent mice, modulating infiltration of tumor‐associated macrophages (TAMs) and T cell exhaustion in tumor microenvironment. We further demonstrated that IRF8 regulated recruitment of TAMs by inhibiting the expression of chemokine (C‐C motif) ligand 20 (CCL20). Mechanically, IRF8‐mediated repression of c‐fos transcription resulted in decreased expression of CCL20, rather than directly bound to CCL20 promoter region. Importantly, adeno‐associated virus 8–mediated hepatic IRF8 rescue significantly suppressed HCC progression and enhanced the response to anti–PD‐1 therapy. Conclusions This work identified IRF8 as an important prognostic biomarker in patients with HCC that predicted the response and sensitivity to anti–PD‐1 therapy and uncovered it as a therapeutic target for enhancing the efficacy of immune therapy.
Preferences for colorectal cancer screening of physicians and individuals at average risk in the United States: A discrete choice experiment.
Authors: Sebastian Heidenreich, Lila J Finney Rutten, Lesley-Ann Miller-Wilson, Cecilia Moreno-Jimenez, Gin Nie Chua, Deborah Fisher
Journal: Journal of Clinical Oncology (2022)

60 Background: Several colorectal cancer (CRC) screening options are considered in guidelines for individuals at average-risk (IAR). These options differ in aspects such as invasiveness, recommended frequency, and precision that need to be compared and weighed. This study elicited and compared the relative importance that physicians and IAR place on these screening aspects. Methods: Primary care physicians [PCPs] and gastroenterologists [GIs] who recommended/performed ≥1 screening one month prior to study and adult IAR completed a discrete choice experiment (DCE). Participants repeatedly chose between screening tests described by type of test, frequency, true-positive (TP), true-negative (TN), and adenoma TP (physicians only). The instrument was tested in qualitative (physicians: n=6; IAR: n=6) and quantitative pilots (physicians: n=100; IAR: n=202). A mixed logit model was used to estimate relative attribute importance (RAI) and predicted choice probabilities for colonoscopy, multi-target stool DNA (mt-sDNA), fecal immunochemical test (FIT), and methylated septin 9 (mSEPT9) blood test. Generalizability to the population was confirmed. Results: 1,249 IAR and 400 physicians participated. IAR were 46% male and the mean age was 58.9. Physicians were 79% male and their mean age was 53.4. Preferences were most affected by TP rates (IAR RAI=58%; physicians RAI=42%). Physicians also placed high importance (RAI=41%) on adenoma TP rates. TN rates (IAR RAI=33%; physician RAI=9%), frequency (IAR RAI=6%; physician RAI=2%) and type (IAR RAI=4%; physician RAI=6%) were less important. Despite both IAR and physicians placing most importance on precision, preferences for screening modalities differed. On average, physicians preferred colonoscopy, while IAR preferred mt-sDNA over colonoscopy (p&lt;0.001). Both preferred mt-sDNA and colonoscopy over FIT (p&lt;0.001), with a mSEPT9 blood test being least preferred (p&lt;0.001). Preferences of IAR were heterogeneous with individuals who underwent colonoscopy or sigmoidoscopy screening preferring colonoscopy and the rest preferring mt-sDNA (p&lt;0.001). Conclusions: While both GI and PCPs overwhelmingly preferred colonoscopy, preferences of IAR were heterogenous, with mt-sDNA being preferred on average other modalities. Offering choices in addition to colonoscopy could improve screening uptake. [Table: see text]
Prophylactic Scopolamine Butylbromide and Death Rattle in Patients at the End of Life—Reply
Authors: Harriette J. van Esch, Lia van Zuylen, Carin C. D. van der Rijt
Journal: JAMA (2022)

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
Rural-Urban Disparities in Outcomes of Myocardial Infarction, Heart Failure, and Stroke in the United States
Authors: Eméfah C. Loccoh, Karen E. Joynt Maddox, Yun Wang, Dhruv S. Kazi, Robert W. Yeh, Rishi K. Wadhera
Journal: Journal of the American College of Cardiology (2022)
Monitoring for side effects of NSAIDs
Authors: G. K. Graham
Journal: JAMA (1991)

<h3>In Reply. —</h3> Drs Bentkover, Boselli, and Lambird raise several issues concerning our article; the principal ones concern our construction of the LDL-HDL index, our analytic perspective, and the costs of side effects. We address these in turn. Dr Bentkover correctly observes that the LDL-HDL index reported in Table 1 (p 3028) does not appear well calibrated; it finds gemfibrozil ( —16) to be almost equivalent to cholestyramine resin ( —14), yet the two long-term trials for these agents indicate substantially different reductions in CHD risk (34% vs 19%). Dr Boselli also faults our first index, arguing that Gordon's<sup>1</sup>observations indicate that elevations of HDL cholesterol levels and diminutions of LDL cholesterol levels have equivalent effects on CHD risk. Neither author notes that we report on a second index in our sensitivity analysis. This index is better calibrated with the long-term trials (gemfibrozil, —15.5; cholestyramine resin, —10.9) and equates the effects
RETRACTED ARTICLE: Decreased expression of the long noncoding RNA LINC00261 indicate poor prognosis in gastric cancer and suppress gastric cancer metastasis by affecting the epithelial–mesenchymal transition
Authors: Yu Fan, Yan-fen Wang, Hua-fang Su, Na Fang, Chen Zou, Wen-feng Li, Zheng-hua Fei
Journal: Journal of Hematology & Oncology (2016)

Recent evidence indicates that long noncoding RNAs (lncRNAs) play pivotal roles in the regulation of cellular processes and are found to be dysregulated in a variety of cancers. LINC00261 is an lncRNA that is aberrantly expressed in gastric cancer (GC). The clinical role of LINC00261 in GC and molecular mechanisms remains to be found. Real-time polymerase chain reaction (PCR) was used to examine LINC00261 expression in GC cell lines/tissues compared with normal epithelial cells/adjacent non-tumorous tissues. Gain and loss of function approaches were used to investigate the biological role of LINC00261 in GC cells. The effects of LINC00261 on cell viability were evaluated by MTT and colony formation assays. Wound healing assay, cell migration and invasion assays, and nude mice were used to examine the effects of LINC00261 on tumor cell metastasis in vitro and in vivo. Protein levels of LINC00261 targets were determined by western blot and immunohistochemistry. LINC00261 was downregulated in GC cell lines and cancerous tissues, as compared with normal gastric epithelial cells and adjacent noncancerous tissue samples. Low LINC00261 expression was correlated with deeper tumor invasion (P < 0.001), higher tumor stage (P = 0.013), and lymphatic metastasis (P = 0.006). Univariate and multivariate analyses indicated that low LINC00261 expression predicted poor prognosis. Ectopic expression of LINC00261 impaired cell migration and invasion, leading to the inhibition of metastasis in vitro and in vivo. Knockdown of LINC00261 expression promoted cell migration and invasion in vitro. Overexpression of LINC00261 was found to play a key role in epithelial–mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin, and Vimentin expression. Low expression of the lncRNA LINC00261 occurs in GC and is associated with poor prognosis. LINC00261 suppresses GC metastasis by regulating EMT. Thus, LINC00261 plays an important role in the progression and metastasis of GC.
Corrigendum to: Antibiotic Treatment Regimes as a Driver of the Global Population Dynamics of a Major Gonorrhea Lineage
Authors: Magnus N Osnes, Lucy van Dorp, Ola B Brynildsrud, Kristian Alfsnes, Thamarai Schneiders, Kate E Templeton, Koji Yahara, Francois Balloux, Dominique A Caugant, Vegard Eldholm
Journal: Molecular Biology and Evolution (2022)
Acute Otitis Media.
Authors: W. H. Daly
Journal: JAMA (1897)

Pittsburg, Pa., March 5, 1897. <h3>To the Editor:</h3> —The instructive report of a case of acute otitis media in theJournalof Feb. 27, 1897, by Dr. B. Merrill Hopkinson of Baltimore, Md., in which he figured and suffered as a patient, leads me to give to the readers of theJournalsome instructions that I have for many years carefully enjoined upon patients and the profession who use the nasal douche in any form, viz.,<i>to blow one side of the nose only at a time</i>after using the douche or after snuffing fluids up into the nares. It is a physical law that fluids will pass always in the direction of the least resistance. Hence, if one naris is left open as must be done to blow it in this manner, it is quite impossible to blow fluids into the Eustachian tube and thereby set up an acute
THE NEURONS.
Authors: LEWELLYS F. BARKER
Journal: JAMA (1906)

(<i>Concluded from Page 935</i>.) The next questions to be decided are, (1) Do the minute fibers ending in the terminal buttons form anastomoses with one another? and (2) Do neurofibrils pass from the terminal buttons into the adjacent cell body or dendrite to form connections with the neurofibrils lying in the protoplasm there? I am unable to find them in the preparations I have been studying, nor can Ramón y Cajal, von Lenhossék, Retzius, van Gehuchten or Mahaim in theirs. Held<sup>12</sup>thinks that he sees such communications, and Max Wolff is inclined to a similar view. Further study is needed to decide this point. Ramón y Cajal is so convinced of the separateness of the terminal buttons from the adjacent nerve-cell protoplasm that he unhesitatingly assures us that not only is the neuron conception valid, but even the contact doctrine is better supported now than ever before, and Sherrington
IMbrave150: Exploratory efficacy and safety in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab beyond radiological progression until loss of clinical benefit in a global phase III study.
Authors: Han Chong Toh, Peter R. Galle, Andrew X. Zhu, Alan Nicholas, Vincent Gaillard, Michel Ducreux, Ann-Lii Cheng, Richard S. Finn
Journal: Journal of Clinical Oncology (2022)

470 Background: First-line atezolizumab (atezo) + bevacizumab (bev) has been approved in &gt; 80 countries based on significantly longer survival vs sorafenib (sor) in systemic treatment (tx)–naive patients (pts) with unresectable HCC in IMbrave150 (NCT03434379; Finn NEJM 2020). This clinically meaningful tx benefit was maintained with an additional 12 months of follow-up (Finn ASCO GI 2021). We report the efficacy and safety in pts who received atezo beyond radiological progression until loss of clinical benefit. Methods: Pts were randomized 2:1 to receive atezo 1,200 mg IV + bev 15 mg/kg IV q3w or sor 400 mg bid until unacceptable toxicity or loss of clinical benefit per investigator (INV). In the presence of clinical benefit, pts with progressive disease (PD) per INV RECIST 1.1 (not at a critical anatomical site) could continue study tx. Pts from the atezo + bev arm who had PD and continued atezo were included. Results: Of the 336 pts who received atezo + bev, 236 had PD, of whom 130 continued atezo (± bev), 60 had other tx, and 46 received no tx on or after first PD. Of the pts who continued atezo, 78% were Barcelona Clinic Liver Cancer (BCLC) stage C and 80% Child-Pugh A5 vs pts receiving other tx (85% BCLC stage C, 72% Child-Pugh A5). Sor (13% and 53%) and lenvatinib (14% and 35%) were the most common other txs received post PD among pts who continued atezo or received other tx, respectively. At clinical cutoff (August 31, 2020), the median number of cycles of atezo received post PD was 5 (range, 1-33) and 41 (32%) pts received ≥ 10 cycles. 60 of 130 (46%) pts who continued atezo died vs 180 of 336 (54%) receiving atezo + bev in the ITT population. See Table for efficacy data from baseline (BL) and PD. Grade (Gr) 3/4 and tx-related Gr 3/4 AEs occurred in 30 (23%) and 21 (16%) pts who continued atezo, respectively. There were 6 (5%) Gr 5 AEs, none tx-related. Conclusions: Atezo + bev is the standard of care for pts with unresectable HCC. In IMbrave150, pts with maintained clinical benefit continuing atezo after PD may have further benefited from staying on tx, although interpretation is limited by selection bias (prespecified criteria excluding pts with loss of clinical benefit). These data suggest that tx with atezo until loss of clinical benefit may contribute to post-PD outcomes. Beyond this exploratory analysis in select pts, the value of tx with atezo beyond formal progression will be assessed prospectively in IMbrave251 (NCT04770896). Clinical trial information: NCT03434379. [Table: see text]
Impacts of a high-fat diet on the metabolic profile and the phenotype of atrial myocardium in mice
Authors: Nadine Suffee, Elodie Baptista, Jérôme Piquereau, Maharajah Ponnaiah, Nicolas Doisne, Farid Ichou, Marie Lhomme, Camille Pichard, Vincent Galand, Nathalie Mougenot, Gilles Dilanian, Laurence Lucats, Elise Balse, Mathias Mericskay, Wilfried Le Goff, Stéphane N Hatem
Journal: Cardiovascular Research (2021)

Obesity, diabetes, and metabolic syndromes are risk factors of atrial fibrillation (AF). We tested the hypothesis that metabolic disorders have a direct impact on the atria favouring the formation of the substrate of AF.Untargeted metabolomic and lipidomic analysis was used to investigate the consequences of a prolonged high-fat diet (HFD) on mouse atria. Atrial properties were characterized by measuring mitochondria respiration in saponin-permeabilized trabeculae, by recording action potential (AP) with glass microelectrodes in trabeculae and ionic currents in myocytes using the perforated configuration of patch clamp technique and by several immuno-histological and biochemical approaches. After 16 weeks of HFD, obesogenic mice showed a vulnerability to AF. The atrial myocardium acquired an adipogenic and inflammatory phenotypes. Metabolomic and lipidomic analysis revealed a profound transformation of atrial energy metabolism with a predominance of long-chain lipid accumulation and beta-oxidation activation in the obese mice. Mitochondria respiration showed an increased use of palmitoyl-CoA as energy substrate. APs were short duration and sensitive to the K-ATP-dependent channel inhibitor, whereas K-ATP current was enhanced in isolated atrial myocytes of obese mouse.HFD transforms energy metabolism, causes fat accumulation, and induces electrical remodelling of the atrial myocardium of mice that become vulnerable to AF.
What's new in the other general journals
Authors: Kristina Fister
Journal: BMJ (2006)

The choice of antibiotics for treating cholera is primarily determined by the patterns of bacterial resistance and antibiotic toxicity. Tetracycline and its derivatives have for decades been the antibiotics of choice for treating cholera in adults, but they should be avoided in children and pregnant women. Erythromycin has often been used as an alternative, but, unlike tetracycline, it is not effective in a single dose. Azithromycin, a derivative of erythromycin, has less gastrointestinal toxicity than erythromycin and has been shown effective for treating cholera in children with a single dose. Credit: N ENGL J MED A recent equivalence trial of a single dose of azithromycin versus a single dose of ciprofloxacin, which had previously been shown to be effective for treating severe cholera in adults, showed that azithromycin was effective, but ciprofloxacin was not. The trial included almost 200 adult men with severe cholera who were treated in one hospital in Bangladesh in a period of a year and a half. Watery stools stopped within two days of giving azithromycin in more than 70% of patients. Ciprofloxacin was clinically effective in less than a third of people randomised to receive this drug. Similarly, azithromycin eliminated Vibrio cholerae from stool within two days from the start of treatment in almost 80% of people, compared with ciprofloxacin's 10%. The authors say that a single dose of ciprofloxacin may be too low a threshold for V cholerae , 01 strain. N Engl J Med 2006;254: 2452–62 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Maori people, New Zealand's large indigenous minority, have previously been reported to have disadvantaged health status compared with the rest of the population. It is notoriously hard to distinguish, however, whether differences in the quality of care between ethnic groups result from discrimination by the system and staff or from other variations, such as access, appropriateness of treatment, or patients' choice. A recent … [1]: {openurl}?query=rft.jtitle%253DNew%2BEngland%2BJournal%2Bof%2BMedicine%26rft.stitle%253DNEJM%26rft.issn%253D0028-4793%26rft.aulast%253DSaha%26rft.auinit1%253DD.%26rft.volume%253D354%26rft.issue%253D23%26rft.spage%253D2452%26rft.epage%253D2462%26rft.atitle%253DSingle-dose%2Bazithromycin%2Bfor%2Bthe%2Btreatment%2Bof%2Bcholera%2Bin%2Badults.%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa054493%26rft_id%253Dinfo%253Apmid%252F16760445%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa054493&link_type=DOI [3]: /lookup/external-ref?access_num=16760445&link_type=MED&atom=%2Fbmj%2F332%2F7555%2F1442.atom [4]: /lookup/external-ref?access_num=000238100800007&link_type=ISI
Β-Catenin-Tcf/Lef Signaling Promotes Steady State and Emergency Granulopoiesis through G-CSF Receptor Upregulation
Authors: Petr Danek, Miroslava Kardosova, Lucie Janeckova, Vladimir Korinek, Touati Benoukraf, Daniel G. Tenen, Meritxell Alberich-Jorda
Journal: Blood (2019)
BOOK REVIEW
Authors: DEBORAH C. MARCELLUS
Journal: JNCI Journal of the National Cancer Institute (1994)

BOOK REVIEW High-Dose Cancer Therapy: Pharmacology, Hematopoietins, Stem Cells James O. Armitage , Karen H. Antman , eds . Baltimore, Md. : Williams & Wilkins Publ. , 1992 . 816 pp., illus. $160. ISBN 0-683-00254-6 DEBORAH C. MARCELLUS DEBORAH C. MARCELLUS Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 21, 2 November 1994, Page 1641, https://doi.org/10.1093/jnci/86.21.1641 Published: 02 November 1994