tbuckley/cabot-search huggingface dataset:
Association Between Maternal Fluoride Exposure and Child IQ
Authors: Chad P. Gehani, Howard Pollick, Richard A. Stevenson
Journal: JAMA Pediatrics (2019)

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 Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Pediatrics journal
Improved Medical Photography
Authors: Lauren Muraco
Journal: JAMA Dermatology (2020)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Immunohistochemical score of phospho-AKT and its correlation to primary melanoma survival
Authors: Braslav Jovanovic, Suzanne Egyhazi, Johan Hansson
Journal: Cancer Research (2007)

5310  BACKGROUND: AKT is a downstream protein of NRAS and it has been shown to be activated when NRAS is mutated. Up to 30% of all melanomas have activating mutations in NRAS gene, a contrast to BRAF mutations that have been reported in up to 60%.  Immunohistochemical score (previously known as Immuno-Reactive score - IRS) is a semiquantitative method that uses arbitrary scale in order to approximate quality and quantity of the stained section of the slide.  The aim of the study was to identify the frequency of pAKT samples as well as to judge the validity of IRS system in primary melanomas.  METHODS: A cohort of 57 melanoma patients was used in the study. Thirty-nine (68%) were male while eighteen (32%) were female. Median Clark level was III with mean thickness of 1.3 mm. The majority of samples, 74%, were superficial spreading melanomas. Forty-four percent of patients were still alive. Genomic DNA was extracted from dissected paraffin-embedded sections with subsequent analysis of exons 1 and 2 of the NRAS gene as well as BRAF exon 15. Mutation analysis was performed by polymerase chain reaction, single strand confirmation polymorphism and nucleotide sequence analysis. Immunohistochemistry (IHC) was performed on formalin-fixed paraffin-embedded sections using a rabbit anti-phospho-AKT (Ser473) antibody (Cell Signaling Technology) according to the protocol. Staining percentage was based on estimated number of stained cells in each tissue sample. Quantity score was calculated in the following manner: 0 (0-5% percent of stained area); 1 (6-25%); 2 (26-50%); 3 (51-75%) and 4 (76-100%). Intensity score was rated as: 0 - no staining; 1 - mild staining; 2 - moderate staining and 3 - strong staining. IRS was calculated by multiplying quantity score with intensity score. Three observers analyzed all sections.  RESULTS: Mutation frequency was 5% for NRAS exon 1, 21% for NRAS exon 2 and 39% for BRAF exon 15. Average cytoplasmic IRS for the whole group was 5.0 with almost identical IRS for the wildtype (for both genes) NRAS exon 2 and BRAF exon 15 mutated groups (4.5; 5.0 and 4.3, respectively). The group that harbored mutations in NRAS exon 1 had IRS of 11. Nuclear pAKT IRS was almost 2 times lower when compared to cytoplasmic IRS with the same trend for all other subgroups, with only exception for the NRAS exon 1 that showed almost 4 times difference (overall - 2.1; wildtype - 2.1, NRAS exon 1 - 2.7; NRAS exon 2 - 3.3 and BRAF exon 15 - 1.6). Twenty-six patients had nuclear IRS equal to zero while twenty-three had an IRS score greater than 0. Longer survival was observed in the group that had IRS greater than zero (Wilcoxon-Gehan exact life table test showed a significant difference, p=0.022). A univariate Cox proportional regression analysis also showed significant probability value (p=0.048).  CONCLUSION: pAKT nuclear IRS score might show to be a useful surrogate prognostic marker in primary melanomas, but larger studies are warrant.
SETDB1 Mediated H3K9 Methylation Suppresses MLL-Fusion Target Expression and Leukemic Transformation
Authors: Andrew G. Muntean, James Ropa, Nirmalya SAHA, Hsiang-Yu Hu, Justin Serio, Lili Zhao, Venkatesha Basrur, Alexei Nesvizhskii, Ivan Maillard
Journal: Blood (2019)
Severe fever with thrombocytopenia syndrome virus targets B cells in lethal human infections
Authors: Tadaki Suzuki, Yuko Sato, Kaori Sano, Takeshi Arashiro, Harutaka Katano, Noriko Nakajima, Masayuki Shimojima, Michiyo Kataoka, Kenta Takahashi, Yuji Wada, Shigeru Morikawa, Shuetsu Fukushi, Tomoki Yoshikawa, Masayuki Saijo, Hideki Hasegawa
Journal: Journal of Clinical Investigation (2020)

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne banyangvirus and is associated with high fatality. Despite increasing incidence of SFTS and serious public health concerns in East Asia, the pathogenesis of lethal SFTS virus (SFTSV) infection in humans is not fully understood. Numbers of postmortem examinations to determine target cells of the viral infection have so far been limited. Here we showed that B cells differentiating into plasmablasts and macrophages in secondary lymphoid organs were targets for SFTSV at the end stage of lethal infection, and the majority of SFTSV-infected cells were B cell–lineage lymphocytes. In affected individuals, B cell–lineage lymphocytes with SFTSV infection were widely distributed in both lymphoid and nonlymphoid organs, and infiltration of these cells into the capillaries of the organs could be observed occasionally. Moreover, a human plasmablastic lymphoma cell line, PBL-1, was susceptible to SFTSV propagation and had a similar immunophenotype to that of target cells of SFTSV in fatal SFTS. PBL-1 can therefore provide a potential in vitro model for human SFTSV infection. These results extend our understanding of the pathogenesis of human lethal SFTSV infection and can facilitate the development of SFTSV countermeasures.
RhoA Targeting Suppresses Cold-Induced Platelet Lesion and Allows Refrigerated Storage of Functional Human Platelets to Fourteen Days
Authors: Shailaja N Hegde, Huzoor Akbar, Shawnagay Nestheide, Ashley M Wellendorf, Breanna Bohan, James F Johnson, Yi Zheng, Jose A Cancelas
Journal: Blood (2019)
Abstract 14232: A Mobile-Responders Smartphone Application Improves Out-Of-Hospital Cardiac Arrest Survival: The First Year “Greater Paris Fire Brigade” Experience
Authors: Clement Derkenne, Florian Roquet, Daniel Jost, Stephane Travers, Bernard Prunet, Dardel Paul, Alexandre Mignon
Journal: Circulation (2019)

Introduction: Out of Hospital Cardiac Arrest (OHCA) is still associated with very poor survival. Optimization of the first link of the chain of survival is a key objective to improve outcome. Hypot...
Magnitude of and Characteristics Associated With the Treatment of Calcium Channel Blocker–Induced Lower-Extremity Edema With Loop Diuretics
Authors: Scott Martin Vouri, Xinyi Jiang, Todd M. Manini, Laurence M. Solberg, Carl Pepine, Daniel C. Malone, Almut G. Winterstein
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Calcium channel blockers, specifically dihydropyridine calcium channel blockers (DH CCBs, eg, amlodipine), may cause lower-extremity edema. Anecdotal reports suggest this may result in a prescribing cascade, where DH CCB–induced edema is treated with loop diuretics. <h3>Objective</h3> To assess the magnitude and characteristics of the DH CCB prescribing cascade. <h3>Design, Setting, and Participants</h3> This cohort study used a prescription sequence symmetry analysis to assess loop diuretic initiation before and after the initiation of DH CCBs among patients aged 20 years or older without heart failure. Data from a private insurance claims database from 2005 to 2017 was analyzed. Use of loop diuretics associated with initiation of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and other commonly used medications was used as negative controls. Data were analyzed from March 2019 through October 2019. <h3>Exposures</h3> Initiation of DH CCB or negative control medications. <h3>Main Outcomes and Measures</h3> The temporality of loop diuretic initiation relative to DH CCB or negative control initiation. Secular trend-adjusted sequence ratios (aSRs) with 95% CIs were calculated using data from 360 days before and after initiation of DH CCBs. <h3>Results</h3> Among 1 206 093 DH CCB initiators, 55 818 patients (4.6%) (33 100 [59.3%] aged &lt;65 years; 32 916 [59.0%] women) had a new loop diuretic prescription 360 days before or after DH CCB initiation, resulting in an aSR of 1.87 (95% CI, 1.84-1.90). An estimated 1.44% of DH CCB initiators experienced the prescribing cascade. The aSR was disproportionately higher among DH CCB initiators who were prescribed high doses (aSR, 2.20; 95% CI, 2.13-2.27), initiated amlodipine (aSR, 1.89; 95% CI, 1.86-1.93), were men (aSR, 1.96; 95% CI, 1.91-2.01), and used fewer antihypertensive classes (aSR, 2.55; 95% CI, 2.47-2.64). The evaluation of ACE inhibitors or ARBs as negative controls suggested hypertension progression may have tempered the incidence of the prescribing cascade (aSR for ACE inhibitors and ARBs, 1.27; 95% CI, 1.24-1.29). <h3>Conclusions and Relevance</h3> This study found an excessive use of loop diuretics following initiation of DH CCBs that cannot be completely explained by secular trends or hypertension progression. The prescribing cascade was more pronounced among those initially prescribed a high dose of DH CCBs.
Гастроинтестинальные проявления системных васкулитов: спектр клинических симптомов, диагностика и лечение
Authors: I.Yu. Golovach, Ye.D. Yehudina
Journal: GASTROENTEROLOGY (2019)

Системные васкулиты представляют собой гетерогенную группу заболеваний, которые характеризуются воспалением стенок кровеносных сосудов и классифицируются в зависимости от типа и размера вовлеченных в патологический процесс сосудов. Гастроинтестинальная система может быть вовлечена в патологический процесс при первичных и вторичных васкулитах. Поражение желудочно-кишечного тракта (ЖКТ) чаще всего встречается при IgA-васкулите, АНЦА-ассоциированных васкулитах, узелковом полиартериите и синдроме Бехчета. Исходами воспалительного поражения сосудов являются аневризмы или окклюзии в брыжеечных, печеночных или селезеночных сосудах с развитием воспаления, эрозий и/или язв, которые могут привести к перфорации, кровотечению и непроходимости желудка и кишечника и быть важной причиной заболеваемости и смертности у пациентов с васкулитами. Клинические признаки поражения ЖКТ при системных васкулитах обычно неспецифичны, к ним относятся лихорадка, боль в животе, тошнота, рвота, диарея и кровотечение. Диагностика базируется главным образом на визуализации при помощи катетерной ангиографии, компьютерной томографической и/или магнитно-резонансной ангиографии, эндоскопии с проведением гистопатологического исследования. Лечение поражения ЖКТ зависит от типа васкулита и обычно включает применение высоких доз глюкокортикоидов, иммунодепрессантов, таких как циклофосфамид, азатиоприн или микофенолата мофетил, и биологических препаратов. В данном обзоре литературы представлены данные о патофизиологии, клинических данных, диагностике, лечении и исходе поражения ЖКТ при различных типах системных васкулитов.
Abstract 14326: SnapShot Freeze (SSF) Image Reconstruction Improves Image Quality and Reduces Motion Scores of Images From Computed Tomography Scanners
Authors: Nicholas S Kim, Rine Nakanishi, Christopher Dailing, Rachael O’Rourke, Daniele Andreini, Gianluca Pontone, Edoardo Conte, Matthew Budoff
Journal: Circulation (2018)

Introduction: Recent advancement in post-processing methods in coronary computed tomographic angiography (CCTA) include motion correction algorithms, such as SnapShot Freeze (SSF), which improve te...
Selective Intratumoral Drug Release and Simultaneous Inhibition of Oxidative Stress by a Highly Reductive Nanosystem and Its Application as an Anti-tumor Agent
Authors: Chunqi Zhu, Lihua Luo, Xindong Jiang, Mengshi Jiang, Zhenyu Luo, Xiang Li, Weigen Qiu, Zhaolei Jin, Tianxiang Shen, Chunlong Li, Qingpo Li, Yunqing Qiu, Jian You
Journal: Theranostics (2020)

Excessive oxidative stress is always associated with the serious side effects of chemotherapy. In the current study, we developed a vitamin E based strongly reductive nanosystem to increase the loading efficiency of docetaxel (DTX, DTX-VNS), reduce its side toxicity and enhance the antitumor effect. Methods: We used Förster Resonance Energy Transfer (FRET) to reveal the in vivo and in vitro fate of DTX-VNS over time. All FRET images were observed using the Maestro imaging system (CRI, Inc., Woburn, MA) and Fluo-View software (Olympus LX83-FV3000). Results: Through FRET analyzing, we found that our nanosystem showed a selective rapider release of drugs in tumors compared to normal organs due to the higher levels of ROS in tumor cells than normal cells, and the accumulation of DTX at tumor sites in the DTX-VNS group was also notably more than that in the Taxotere group after 24 h injection. Meanwhile, DTX-VNS had a prominently stronger anti-tumor effect in various models than Taxotere, and had a synergistic effect of immunotherapy. Conclusions: Our work presented a useful reference for clinical exploration of the in vivo behavior of nanocarriers (DTX-VNS), inhibition oxidative stress and selective release of drugs at tumor sites, thus reducing the side effects and enhancing the anti-tumor effects.
Platelets from Calreticulin mutated essential thrombocythemia patients are less reactive than JAK2 V617F mutated platelets
Authors: Hagit Hauschner, Melanie Bokstad Horev, Modi Misgav, Meital Nagar, Uri Seligsohn, Nurit Rosenberg, Maya Koren‐Michowitz
Journal: American Journal of Hematology (2019)

Both JAK2V617F and calreticulin (CALR) mutated essential thrombocythemia (ET) patients have different clinical characteristics, with lower thrombosis risk in patients with CALR mutations. To elucidate the mechanism for this lower risk we studied platelet function in ET patients with either JAK2V617F or a CALR mutation. Platelet activation state was similar in ET and healthy controls at baseline using P-selectin and PAC1 flow cytometry analysis. However, CALR mutated platelets were significantly less activated following ADP stimulation, compared to control or JAK2 mutated platelets (P < .001). In live-cell imaging of platelet attachment to immobilized fibrinogen by Interference Reflection Microscopy (IRM), the number of attached CALR mutated platelets was lower compared to control and JAK2 mutated platelets, with lower fractions of platelets achieving the fully spread state (90%, 78% and 54% of adherent cells for control, JAK2 and CALR mutated subjects, respectively). Compared to controls, ET patients, regardless of the mutation type, had increased numbers of immature platelets (IP) and leukocyte platelet aggregates (LPA), as well as plasma sP-selectin. These were all correlated with the platelet count and not to the state of platelet activation. We also found that intracellular free Ca2+ was increased in resting ET compared to control platelets. Note, CALR had a more dispersed localization in activated ET platelets compared to healthy controls, and mutated CALR interact physically with TpoR in CALR mutated platelets. We hypothesize that defects in platelet activation and spreading in CALR mutated patients can explain, at least in part, the lower thrombotic tendency in CALR mutated ET patients.
The other side of the coin: Semantic dementia as a lesion model for understanding recollection and familiarity
Authors: Cherie Strikwerda-Brown, Muireann Irish
Journal: Behavioral and Brain Sciences (2019)

Abstract The syndrome of semantic dementia represents the “other side of the coin” to Alzheimer's disease, offering convergent evidence to help refine Bastin et al.’s integrative memory model. By considering the integrative memory model through the lens of semantic dementia, we propose a number of important extensions to the framework, to help clarify the complex neurocognitive mechanisms underlying recollection and familiarity.
Neoantigen-specific immunity in low mutation burden colorectal cancers of the consensus molecular subtype 4
Authors: Jitske van den Bulk, Els M. E. Verdegaal, Dina Ruano, Marieke E. Ijsselsteijn, Marten Visser, Ruud van der Breggen, Thomas Duhen, Manon van der Ploeg, Natasja L. de Vries, Jan Oosting, Koen C. M. J. Peeters, Andrew D. Weinberg, Arantza Farina-Sarasqueta, Sjoerd H. van der Burg, Noel F. C. C. de Miranda
Journal: Genome Medicine (2019)

Abstract Background The efficacy of checkpoint blockade immunotherapies in colorectal cancer is currently restricted to a minority of patients diagnosed with mismatch repair-deficient tumors having high mutation burden. However, this observation does not exclude the existence of neoantigen-specific T cells in colorectal cancers with low mutation burden and the exploitation of their anti-cancer potential for immunotherapy. Therefore, we investigated whether autologous neoantigen-specific T cell responses could also be observed in patients diagnosed with mismatch repair-proficient colorectal cancers. Methods Whole-exome and transcriptome sequencing were performed on cancer and normal tissues from seven colorectal cancer patients diagnosed with mismatch repair-proficient tumors to detect putative neoantigens. Corresponding neo-epitopes were synthesized and tested for recognition by in vitro expanded T cells that were isolated from tumor tissues (tumor-infiltrating lymphocytes) and from peripheral mononuclear blood cells stimulated with tumor material. Results Neoantigen-specific T cell reactivity was detected to several neo-epitopes in the tumor-infiltrating lymphocytes of three patients while their respective cancers expressed 15, 21, and 30 non-synonymous variants. Cell sorting of tumor-infiltrating lymphocytes based on the co-expression of CD39 and CD103 pinpointed the presence of neoantigen-specific T cells in the CD39 + CD103 + T cell subset. Strikingly, the tumors containing neoantigen-reactive TIL were classified as consensus molecular subtype 4 (CMS4), which is associated with TGF-β pathway activation and worse clinical outcome. Conclusions We have detected neoantigen-targeted reactivity by autologous T cells in mismatch repair-proficient colorectal cancers of the CMS4 subtype. These findings warrant the development of specific immunotherapeutic strategies that selectively boost the activity of neoantigen-specific T cells and target the TGF-β pathway to reinforce T cell reactivity in this patient group.
Abstract 133: Cardiovascular Protective Effect of Thyroxine and Nano- Thyroxine Against Ischemic Insults
Authors: Shaker A Mousa, Abeer Sallam, Noureldien Darwish
Journal: Circulation (2019)

Introduction: Cardioprotection is a key purpose for therapeutic interventions in cardiology that aim to reduce infarct size, and thus prevent progression toward heart failure, after acute ischemic and cardiac arrest. Triiodothyronine/thyroxine (T3) therapy has been used to reverse myocardial stunning. Hyperthyroidism prevents the stunning with high dependence on the mitochondrial sodium-calcium exchanger and mitochondrial K+ channels. Hypothesis: This study aimed to investigate the positive protective role of T3 and PRO-AL 616 (Nano-T3) and PRO-AL 617 (Nano-T3 with Phosphocreatine, Pcr) in hypoxia-mediated cardiac cell insults, as well as its influences on vascularization and neuronal protection. Methods: The effects of T3 and Nano-T3 + Pcr on angiogenesis were studied in a CAM model. Their cardioprotective effect under hypoxia was studied using isolated neonatal cardiomyocytes treated with PBS (control), T3 (3 uM), Pcr (30 uM) and T3 + Pcr. Mitochondrial function and sarcomere integrity were studied using an ATP- bioluminescence assay, and cardiac Troponin T levels using flow cytometry, respectively. The effect of Nano-T3 on induced neuronal cells under hypoxia was also studied. Finally, Nano-T3-Cy7 were injected into mice tail veins to monitor their biodistribution in real time. Results: Nano-T3 activate the cell surface receptor αvβ3 and is distributed into the cytoplasm, but not the nucleus. Nano-T3 enhanced angiogenesis in the CAM model (~3 fold) versus T3. Under hypoxia, cardiac ATP improvement was achieved with T3+Pcr ( p &lt;0.001) while maintaining normal Troponin T levels. ( Figure 1 ). Nano-T3 produced a significant upregulation of the neural protection markers, PAX6 and DLX2 by ~ 50%. In vivo, the Cy7 signal intensity was detected primarily in mice brains, and hearts, within minutes of administration. Conclusion: Nano-T3 + Pcr represents a potentially new therapeutic for the control of tissue damage in cardiac ischemia and resuscitation.