tbuckley/cabot-search huggingface dataset:
Recent research in infectious disease
Journal: Journal of Infection (2005)

Recent research in infectious disease *Antiviral therapy is effective in patients with HCV and non-organ-specific autoantibodies ST.LOUIS (MD Consult)-The presence of non-organspecific autoantibodies (NOSAs) in patients with hepatitis C virus (HCV) infection does not interfere with the response to combined antiviral therapy, according to the February 15 Clinical Infectious Diseases.Dr Paolo Muratori and colleagues of Alma Mater Studiorum-University of Bologna in Italy studied 143 treatment-naı ¨ve adults with HCV.All patients were treated with combined interferon and ribavirin.Blood samples were obtained at baseline to measure levels of NOSAs, specifically antinuclear antibody antismooth muscle antibody and antiliver/kidney microsomal antibody type 1.NOSAs were present in 37 patients (25%).The proportion of patients with a good long-term response (i.e.persistently normal transaminase levels and undetectable HCV RNA levels 6 months after the end of treatment) was similar in the NOSApositive and NOSA-negative patients (48.6 and 56.6%, respectively).However, among NOSA-positive patients, those with HCV genotype 1 (HCV-1) were significantly less likely to have a good long-term response than those with another HCV genotype (30 vs 93.3%).Multivariate analyses indicated that the detection of HCV-1 and elevated serum g-glutamyl transpeptidase levels were significant and negative predictors of treatment response.Thus, NOSA positivity should not be a contraindication to combined antiviral therapy in patients with HCV infection.However, NOSA-positive patients with the HCV-1 genotype appear to be much less likely to have a good long-term response.
Time required to achieve therapeutic anticoagulation with warfarin prior to cardioversion for atrial fibrillation Radmira S. Greenstein, Julie Merz, William Fay, Robert L. Baker, Chi-Wo Chan, Steven P. Chough, Christian Sticherling, Hiroshi Tada, Kristina Wasmer, Hakan Oral, Frank Pelosi, Jr., Adam Strickberger, Fred Morady, Bradley P. Knight. University of Michigan, Ann Arbor, MI
Journal: Journal of the American College of Cardiology (2001)
Cancer Tales
Authors: M. Desai
Journal: BMJ (2003)

Written by Nell Dunn Directed by Trevor Walker Greenwood Theatre, Weston Street, London SE1, 16 May Performed as part of the Art of Dying symposium at King's College London www.kcl.ac.uk/depsta/humanities/art\_of\_dying Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> When Nell Dunn's father died from cancer, she found it difficult to handle. She did not know how to help him or cope with his death. She lived in denial for years. That was 25 years ago. Now, at the age of 67, she feels that she needs to learn from that experience and be "more friendly with death." She says: "I want it to be part of ordinary life." Dunn decided to learn from others and write Cancer Tales . She got in touch with friends whose lives had been affected by cancer, friends of friends, and oncologists and their patients, and decided to tell their … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
У 2014 році Інституту гастроентерології НАМН України — 50 років!
Authors: . .
Journal: GASTROENTEROLOGY (2013)

До 1964 року поширеність хронічних захворювань органів травлення вже займала 4-те місце серед інших захворювань. У зв’язку з великою соціальною значущістю гастроентерології як основної галузі медичної науки і практики Постановою Ради Міністрів Української РСР від 19 грудня 1964 року і наказом Міністерства охорони здоров’я УРСР № 40 від 19 січня 1965 року створений Дніпропетровський інститут гастроентерології, що почав свою діяльність 16 березня 1965 року.
Atrial tachycardia in dogs with rapid ventricular pacing induced heart failure is due to either a focal or reentrant mechanism Jayakumar Sahadevan, James Golebiewski, Celeen Khrestian, Kyung Ryu, Albert L. Waldo, Bruce S. Stambler. Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH
Journal: Journal of the American College of Cardiology (2001)
Selection for Cell Yield Does Not Reduce Overflow Metabolism in <i>Escherichia coli</i>
Authors: Iraes Rabbers, Willi Gottstein, Adam M Feist, Bas Teusink, Frank J Bruggeman, Herwig Bachmann
Journal: Molecular Biology and Evolution (2021)

Overflow metabolism is ubiquitous in nature, and it is often considered inefficient because it leads to a relatively low biomass yield per consumed carbon. This metabolic strategy has been described as advantageous because it supports high growth rates during nutrient competition. Here, we experimentally evolved bacteria without nutrient competition by repeatedly growing and mixing millions of parallel batch cultures of Escherichia coli. Each culture originated from a water-in-oil emulsion droplet seeded with a single cell. Unexpectedly we found that overflow metabolism (acetate production) did not change. Instead, the numerical cell yield during the consumption of the accumulated acetate increased as a consequence of a reduction in cell size. Our experiments and a mathematical model show that fast growth and overflow metabolism, followed by the consumption of the overflow metabolite, can lead to a higher numerical cell yield and therefore a higher fitness compared with full respiration of the substrate. This provides an evolutionary scenario where overflow metabolism can be favorable even in the absence of nutrient competition.
Abstract 170: Differential Regulation of miRNA and mRNA Expression in the Myocardium of Nrf2 Knockout Mice
Authors: Justin M Quiles, Madhusudhanan Narasimhan, Gobinath Shanmugam, Brett Milash, John R Hoidal, Namakkal Soorappan Rajasekaran
Journal: Circulation Research (2017)

Background: Preclinical studies indicate that disruption of the transcription factor nuclear factor, erythroid 2 like 2 (Nrf2) leads to pathological oxidative stress in several tissues. However, the transcriptional role of Nrf2 in the heart, a highly aerobic organ sensitive to redox disturbances and aberrant microRNA (miRNA) activity, remains elusive. Here, we tested the hypothesis that Nrf2 ablation disrupts cardiac miRNA abundance leading to impaired transcriptional regulation of the myocardial defense system. Methods: Age-matched wild-type (WT) and Nrf2 knockout (Nrf2 -/- ) mice (n=3-6/group) were used in this study. Independent next-generation sequencing experiments were conducted to evaluate differential expression of mRNA and miRNA in the heart. Real-time qPCR was used to validate RNA sequencing (RNAseq) data. Results: RNAseq for mRNA uncovered 152 differentially expressed genes (DEGs) in Nrf2 -/- hearts, of which 129 were downregulated relative to WT. Novel DEGs previously unreported as Nrf2 targets were detected and Gene Ontology analysis revealed the enrichment (p&lt;0.05) of several biological processes distinct from canonical Nrf2 function including; wound healing, protein folding, cytokine response, cell migration and adhesion. In line with previous reports, altered regulation of apoptosis, stress response and oxidative metabolism was also implicated in Nrf2 -/- DEG signatures. Next, small RNAseq detected a total of 27 miRNAs (11 up and 16 downregulated) altered in Nrf2 -/- mice. Validation by qPCR revealed a significant (p&lt;0.05) decrease in miR-10b-5p, miR-674-3p, miR-3535, and miR-378c while miR-30b-5p, miR-208a-5p, miR-350-3p, miR-582-5p, and miR-1249-3p were increased. In silico integration of RNAseq data discovered complementarity between 39 repressed mRNAs and 4 upregulated miRNAs; miR-30b-5p, miR-208a-5p, miR-350-3p, and miR-582-5p. These miRNAs may cooperatively regulate expression in Nrf2 -/- hearts as 22 DEGs matched with 2 or more miRNAs. Conclusion: Our results highlight novel mRNA targets and indicate that Nrf2 regulates a subset of cardiac miRNAs. Biological changes distinct from canonical Nrf2 function suggest that regulatory cross-talk with miRNAs contribute to unique roles for Nrf2 in the myocardium.
Biomaterial-assisted biotherapy: A brief review of biomaterials used in drug delivery, vaccine development, gene therapy, and stem cell therapy
Authors: Xuejiao Han, Aqu Alu, Hongmei Liu, Yi Shi, Xiawei Wei, Lulu Cai, Yuquan Wei
Journal: Bioactive Materials (2022)

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications, as demonstrated in preclinical and clinical studies. However, the broad applications of biotherapy have been limited by critical challenges, including the lack of safe and efficient delivery systems and serious side effects. Due to the unique potentials of biomaterials, such as good biocompatibility and bioactive properties, biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy. The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions, enabling a sustained and localized release of drugs at the target sites. Furthermore, the biomaterials can provide a niche with specific extracellular conditions for the proliferation, differentiation, attachment, and migration of stem cells, leading to tissue regeneration. In this review, the state-of-the-art studies on the applications of biomaterials in biotherapy, including drug delivery, vaccine development, gene therapy, and stem cell therapy, have been summarized. The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.
Planning in the brain
Authors: Marcelo G. Mattar, Máté Lengyel
Journal: Neuron (2022)

Recent breakthroughs in artificial intelligence (AI) have enabled machines to plan in tasks previously thought to be uniquely human. Meanwhile, the planning algorithms implemented by the brain itself remain largely unknown. Here, we review neural and behavioral data in sequential decision-making tasks that elucidate the ways in which the brain does—and does not—plan. To systematically review available biological data, we create a taxonomy of planning algorithms by summarizing the relevant design choices for such algorithms in AI. Across species, recording techniques, and task paradigms, we find converging evidence that the brain represents future states consistent with a class of planning algorithms within our taxonomy—focused, depth-limited, and serial. However, we argue that current data are insufficient for addressing more detailed algorithmic questions. We propose a new approach leveraging AI advances to drive experiments that can adjudicate between competing candidate algorithms.
COMPLETE EXCISION OF PATELLA.
Journal: JAMA (1895)

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
Refractory neutrophilic asthma and ciliary genes
Authors: Vamsi P. Guntur, Laurie A. Manka, Camille M. Moore, Elizabeth Wynn, Eszter K. Vladar, Rafeul Alam, Tuyet-Hang Pham, Tasha E. Fingerlin, Richard J. Martin
Journal: Journal of Allergy and Clinical Immunology (2022)
Early myocardial BMIPP uptake is enhanced relative to perfusion in a canine model of reperfused, viable myocardium Kazuya Takehana, Mirta Ruiz, Laurent M. Riou, Toshiji Iwasaka, Denny D. Watson, George A. Beller, David K. Glover. University of Virginia, Charlottesville, VA, Kansai Medical University, Osaka, Japan
Journal: Journal of the American College of Cardiology (2001)
Биологическая терапия болезни Крона в Украине
Authors: A.E. Dorofeyev, O.A. Rassokhina, A.Yu. Butova
Journal: GASTROENTEROLOGY (2014)

В статье дана оценка современного состояния проблемы болезни Крона (БК) в Украине и мире. Проведен сравнительный анализ эффективности применения стандартной, а также биологической терапии в лечении БК по данным проспективных рандомизированных исследований. Приведены собственные данные об эффективности биологической терапии у 47 пациентов с воспалительными заболеваниями кишечника, а также клинический пример использования антагонистов фактора некроза опухоли α. Применение препаратов биологической терапии является высокоэффективным у пациентов с БК при неэффективности стандартной терапии, может продлить периоды стабильной клинической и эндоскопической ремиссии, отсрочить развитие осложнений и необходимость оперативных вмешательств, что позволит повысить качество жизни пациентов с БК.
Polygenic Prediction of Type 2 Diabetes in Africa
Authors: Tinashe Chikowore, Kenneth Ekoru, Marijana Vujkovi, Dipender Gill, Fraser Pirie, Elizabeth Young, Manjinder S. Sandhu, Mark McCarthy, Charles Rotimi, Adebowale Adeyemo, Ayesha Motala, Segun Fatumo
Journal: Diabetes Care (2022)

OBJECTIVE Polygenic prediction of type 2 diabetes (T2D) in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of T2D from Africa and the poor transferability of European-derived polygenic risk scores (PRSs) in diverse ethnicities. We set out to evaluate if African American, European, or multiethnic-derived PRSs would improve polygenic prediction in continental Africans. RESEARCH DESIGN AND METHODS Using the PRSice software, ethnic-specific PRSs were computed with weights from the T2D GWAS multiancestry meta-analysis of 228,499 case and 1,178,783 control subjects. The South African Zulu study (n = 1,602 case and 981 control subjects) was used as the target data set. Validation and assessment of the best predictive PRS association with age at diagnosis were conducted in the Africa America Diabetes Mellitus (AADM) study (n = 2,148 case and 2,161 control subjects). RESULTS The discriminatory ability of the African American and multiethnic PRSs was similar. However, the African American–derived PRS was more transferable in all the countries represented in the AADM cohort and predictive of T2D in the country combined analysis compared with the European and multiethnic-derived scores. Notably, participants in the 10th decile of this PRS had a 3.63-fold greater risk (odds ratio 3.63; 95% CI 2.19–4.03; P = 2.79 × 10−17) per risk allele of developing diabetes and were diagnosed 2.6 years earlier than those in the first decile. CONCLUSIONS African American–derived PRS enhances polygenic prediction of T2D in continental Africans. Improved representation of non-European populations (including Africans) in GWAS promises to provide better tools for precision medicine interventions in T2D.
Clinicopathologic correlates and prognostic relevance of the immune checkpoint CD73 (NT5E) in resected biliary cancers (BC).
Authors: Massimiliano Salati, Francesco Caputo, Andrea Spallanzani, Fabio Gelsomino, Beatrice Ricco', Gabriele Luppi, Luca Reggiani Bonetti, Anna Barbato, Luigi Ferrante, Roberta Biondi, Antonella Iuliano, Gennaro Gambardella, Maria Salatiello, Antonino Iaccarino, Pasquale Pisapia, Giancarlo Troncone, Massimo Dominici, Brunella Franco, Pietro Carotenuto
Journal: Journal of Clinical Oncology (2022)

473 Background: CD73, an ecto-5’-nucleotidase (NT5E), creates an immunosuppressive tumour-promoting microenvironment by converting ATP to adenosine. The expression of CD73 has been linked to poorer patients (pts) outcome across several cancer types and the targeted inhibition of this immunoinhibitory protein has been recently advanced to clinical development. However, the clinicopathologic role of CD73 as well as its potential implications are largely unexplored in BC. Methods: The expression of CD73 was assessed by immunohistochemistry on both tumour (tCD73) and stromal tissue (sCD73) of a clinically-annotated cohort of radically-resected BC and scored for staining intensity as follows: +1, +2 and +3. RNAseq was performed on RNA isolated from surgical specimens. Differences between groups were evaluated using the Chi-square test. Survival functions were estimated by the Kaplan-Meier method and comparisons were made using the log-rank test. The Cox proportional hazards model was used to assess the impact of covariates on survival outcomes. Results: CD73 immunohistochimichal expression was evaluated on resected specimens of 70 BC pts. 43 pts (61%) were tCD73-positive, while 44 pts (62%) were sCD73-positive. Among the former group, the intensity score was 1+ in 19 pts (44%), 2+ in 16 pts (37%), 3+ in 10 pts (23%), while in the latter group was 1+ in 22 pts (50%), 2+ in 10 pts (22%) and 3+ in 12 pts (27%). CD73 positivity was associated with older age (&gt; 70 years, p = 0.01), gallbladder subsite (p = 0.03), and nodal involvement (p = 0.04). Patients with tCD73-positive BC experienced a significantly shorter relapse-free survival (8,4 vs 39,4 months; p = 0.016) and overall survival (60,7 vs 13,7 months; p = 0.017). Notably, high tCD73 expressors (score 3+) displayed the poorest prognosis (12,03 months; p = 0.023). When evaluated on univariate and multivariate analysis, tCD73 positivity was an independent prognostic factor for both relapse-free survival (p = 0.038) and overall survival (p = 0.023), together with ECOG PS and pTNM stage. Whole-transcriptome sequencing is ongoing to correlate CD73 expression with cancer-related pathways. Conclusions: In this study, we provided a clinicopathologic characterization of CD73 expression in resected BC, demonstrating that tCD73 is an independent negative prognostic biomarker in this disease. Although these findings are in need of a validation in larger dataset, they foster novel combination of anti-CD73 agents with conventional therapy in the poorer-prognosis subset of CD73-positive BC.
Association of Cigarette Sales With Comprehensive Menthol Flavor Ban in Massachusetts
Authors: Samuel Asare, Anuja Majmundar, J. Lee Westmaas, Priti Bandi, Zheng Xue, Ahmedin Jemal, Nigar Nargis
Journal: JAMA Internal Medicine (2022)

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Hedgehog signaling is controlled by Rac1 activity
Authors: Chao Tang, Ximei Wu, Qianlei Ren, Minli Yao, Shouying Xu, Ziyi Yan
Journal: Theranostics (2022)

Rationale:The nuclear translocation of transcriptional factor Gli is indispensable for Hedgehog (Hh) signaling activation, whose deregulation causes cancer progressions; however, the mechanisms governing Gli nuclear translocation are poorly understood.Here, we report that the Gli translocation in response to Hh requires Rac1 activation.Methods: C3H10T1/2 cell line and mouse embryonic fibroblasts were used to explore the molecular mechanisms underlying Rac1 activity in regulation of Hh signaling transduction.Transgenic mouse strains and human medulloblastoma (MB) tissue samples were utilized to examine the role of Rac1 in Hh-directed limb bud development and MB progression.Results: We show that upon the binding of Hh to receptor Patched1 (Ptch1), receptor Smoothened (Smo) dissociates from Ptch1 and binds to Vav2, resulting in the increased phosphorylation levels of Vav2 at Y172, which further activates Rac1.The role of Rac1 is dependent on the regulation of phosphorylation levels of KIF3A at S689 and T694, which in turn affects IFT88 stability and subsequently dampens SuFu-Gli complex formation, leading to the release of Gli from the complex and the consequent translocation of Gli into the nucleus.Moreover, Vav2 phospho-Y172 levels are up-regulated in GFAP-Cre;SmoM2 +/-mouse cerebellum and human Shh type MB tissues, whereas deficiency of Rac1 in mouse embryonic limb bud ectoderm (Prx1-Cre;Rac1 f/f ) impedes Hh activation by disruption of Gli nuclear translocation.Conclusion: Together, our results uncover the Rac1 activation and the subsequent Gli translocation as a hitherto uncharacterized mechanism controlling Hh signaling and may provide targets for therapeutic intervention of this signaling pathway.
Biomarker-oriented study of pembrolizumab in combination with chemotherapy in chemotherapy-naïve advanced pancreatic cancer: A phase 2 trial-in-progress.
Authors: Jeesun Yoon, Jin Won Kim, Ji-Won Kim, Tae-Yong Kim, Ah-Rong Nam, Ju-Hee Bang, Jae-Min Kim, Kyoung Seok Oh, Do-Youn Oh
Journal: Journal of Clinical Oncology (2022)

TPS639 Background: Pancreatic cancer (PC) is well-known as a strongly immunosuppressive tumor. The tumor microenvironment of PC play a fundamental part in maintaining a non-immunogenic and immuno-suppressive environment through the production of inhibitory cytokines and complex interaction between tumor cells, regulatory T cells, and myeloid-derived suppressor cells (Li KY et al. 2020). However, through integrated genomics and immunophenotyping, the immune-rich type had a relatively good prognosis in advanced PC (Wartenberg M et al. 2018). Based on this, various attempts have been made to apply immune checkpoint inhibitor (ICI) to PC. Disappointingly, ICI monotherapy is ineffective in most advanced PCs, and a strategy of combining ICI with ICI, chemotherapy or targeted therapy has been recently tried. However, the mechanism of immune modulation induced by ICI in combination with chemotherapy in PC is still not well-known, so biomarker studies are needed to understand the role of immunotherapy in advanced PC. Also based on this, it is expected to develop an effective ICI treatment strategy in PC. This study is a non-randomized, parallel assignment phase 2 trial aimed to explore dynamic modulation of the immune system caused by co-administration of pembrolizumab and cytotoxic chemotherapy in patients with advanced PC. Methods: Eligible patients have recurred or metastatic pancreatic cancer. Patients who have received chemotherapy for advanced PC are excluded, except for previous adjuvant chemotherapy. Patients who have received ICI are excluded. There are 2 chemotherapy cohorts (FOLFIRINOX, n=41; Gemcitabine/Nab-paclitaxel, n=36). Patients enrolled in the FOLFIRINOX cohort will receive pembrolizumab 200mg intravenously once every 3 weeks, plus FOLFIRINOX chemotherapy every 2 weeks. In Gemcitabine/Nab-paclitaxel cohort, patients will receive gemcitabine 1000mg/m2 plus nab-paclitaxel 125mg/m2 day 1, 8, 15 of a 4-week cycle, plus pembrolizumab 200mg intravenously once every 3 weeks. The primary endpoint is objective response rate, with key secondary endpoints including progression-free survival, duration of response, disease control rate, overall survival, safety, and patient-reported outcome. For evaluating metabolic response, 18 F-FDG PET-CT scan will be conducted before treatment and at the first response evaluation. Tumor tissue biopsies are performed three times in total: screening, the first response evaluation, and disease progression. Blood samples are being collected every cycles for translational biomarker studies. Clinical trial information: NCT04447092.
Lack of compensatory activity of brain natriuretic peptide (BNP) in patients with left ventricular remodeling Atsushi Hirayama, Tomohito Otani, Kazunori Kashiwase, Yuya Mizuno, Hiroyoshi Yamamoto, Kazuhisa Kodama. Osaka Police Hospital, Osaka, Japan
Journal: Journal of the American College of Cardiology (2001)