tbuckley/cabot-search huggingface dataset:
Using GC Content to Compare Recombination Patterns on the Sex Chromosomes and Autosomes of the Guppy,<i>Poecilia reticulata</i>, and Its Close Outgroup Species
Authors: Deborah Charlesworth, Yexin Zhang, Roberta Bergero, Chay Graham, Jim Gardner, Lengxob Yong
Journal: Molecular Biology and Evolution (2020)

Abstract Genetic and physical mapping of the guppy (Poecilia reticulata) have shown that recombination patterns differ greatly between males and females. Crossover events occur evenly across the chromosomes in females, but in male meiosis they are restricted to the tip furthest from the centromere of each chromosome, creating very high recombination rates per megabase, as in pseudoautosomal regions of mammalian sex chromosomes. We used GC content to indirectly infer recombination patterns on guppy chromosomes, based on evidence that recombination is associated with GC-biased gene conversion, so that genome regions with high recombination rates should be detectable by high GC content. We used intron sequences and third positions of codons to make comparisons between sequences that are matched, as far as possible, and are all probably under weak selection. Almost all guppy chromosomes, including the sex chromosome (LG12), have very high GC values near their assembly ends, suggesting high recombination rates due to strong crossover localization in male meiosis. Our test does not suggest that the guppy XY pair has stronger crossover localization than the autosomes, or than the homologous chromosome in the close relative, the platyfish (Xiphophorus maculatus). We therefore conclude that the guppy XY pair has not recently undergone an evolutionary change to a different recombination pattern, or reduced its crossover rate, but that the guppy evolved Y-linkage due to acquiring a male-determining factor that also conferred the male crossover pattern. We also identify the centromere ends of guppy chromosomes, which were not determined in the genome assembly.
Occult Hepatitis B Virus Infection in Immunized Infants Born to Untreated and Tenofovir-Treated Highly Viremic Mothers
Authors: Hong-Yuan Hsu, Huey-Ling Chen, Jia-Feng Wu, Yen-Hsuan Ni, Kai-Chi Chang, Cheng-Lun Chiang, Chien-Nan Lee, Lu-Lu Zhao, Ming-Wei Lai, Shu-Chi Mu, Wan-Hsin Wen, Lung-Huang Lin, Mei-Hwei Chang, Shyu MK, Hwa HL, Su YN, Shih JC, Chao KH, Chiu YC, Liu CJ, Su TH, Chen DS, Chen SM, Lin CC, Lin PY, Yang WR, Hu JJ, Yang CK, Chang YK, Chen KH, Lin HH, Lin YH, Chen HJ, Pan HS, Lau BH, Lee CL, Cheng PJ, Chang YL, Chiueh HY, Wang TH, Hsu JJ, Lo LM, Hsieh CL, Cheng SW, Tsai MS, She BQ, Peng FS, Lin YC, Chen CP, Huang JP, Yeung CY
Journal: Clinical Gastroenterology and Hepatology (2020)
Efficacy and safety of dupilumab for moderate‐to‐severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines
Authors: Ioana Agache, Yang Song, Margarita Posso, Pablo Alonso‐Coello, Claudio Rocha, Ivan Solà, Jessica Beltran, Cezmi A. Akdis, Mubeccel Akdis, Knut Brockow, Tomas Chivato, Stefano del Giacco, Thomas Eiwegger, Kilian Eyerich, Ana Giménez‐Arnau, Jan Gutermuth, Emma Guttman‐Yassky, Marcus Maurer, Graham Ogg, Peck Y. Ong, Liam O’Mahony, Jürgen Schwarze, Thomas Werfel, Carlos Canelo‐Aybar, Oscar Palomares, Marek Jutel
Journal: Allergy (2020)

Abstract This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate‐to‐severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD‐related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects &gt;12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD −30,72; 95% CI −34,65% to −26,79%) and EASI‐75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD −7.29; 95% CI −8.23 to −6.35) and anxiety/depression (MD −3.08; 95% CI −4.41 to −1.75) and improves quality of life (MD −4.80; 95% CI −5.55 to −4.06). The efficacy for adolescents is similar. Dupilumab‐related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab‐related serious AE is uncertain. The incremental cost‐effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long‐term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration : PROSPERO (CRD42020153645).
Improved survival for patients with invasive cancer after opening a comprehensive cancer center: comparisons to intramural and extramural benchmarks
Authors: Robert O. Dillman, Sherri D. Chico
Journal: Cancer Research (2005)

4198  We examined whether survival for patients improved after opening Hoag Cancer Center in 1991. Data from the Hoag Hospital tumor registry from the successive eras 1986-1991 and 1992-1999 were used for historical intramural comparisons. Patients were diagnosed and/or treated at Hoag Hospital within four months of diagnosis. SEER (National Surveillance Epidemiology and End Results program) data were used for contemporary extramural survival comparisons of patients with invasive cancer in the successive eras. The methodology used by SEER was used for the survival analysis; so survival data is reported as relative survival, the ratio of observed survival for cancer patients to the expected survival for the general population with adjustments for competing causes of mortality based on age, race, and gender. Relative 5-year survival rates for Hoag patients with invasive cancer increased from 63% during 1986-1991 (n=5487, median age 65.0 years) to 71% during 1992-1999 (n=10,548, median age 65.8 years), and were higher for 22/24 distinct tumor types in the more recent era (p=.00005, T-Test). Relative 5-year survival rates improved for each of the four most prevalent cancers: breast (89% to 95%), prostate (92% to 100%), lung (20% to 24%), and colon (66 to 72%) and rectal cancers (68% to 83%). Hoag survival for all patients with invasive cancer was higher than SEER figures in both eras: 63% vs 58% during 1986-1991, and increased to 71% vs 64% during 1992-1999. Survival for Hoag patients was the same or higher than SEER figures for only 50% (12/24) of malignancies during 1986-1991 but increased to 87% (21/24) during 1992-1999 (p=.013 Fisher’s exact test; p=.001, T-Test). Intramural comparisons for 1992-1999 to 1986-1991 revealed a higher percentage of patients diagnosed and treated at Hoag (84.0% vs 81.2%), a higher percentage with local disease at diagnosis (50.8% vs 45.3%), a lower percentage treated by surgery alone (31.0% vs 36.9%), and greater use of biological response modifiers (6.7% vs 1.7%) (all p
Transcatheter Valve-in-Valve Aortic Valve Replacement as an Alternative to Surgical Re-Replacement
Authors: Pierre Deharo, Arnaud Bisson, Julien Herbert, Thibaud Lacour, Christophe Saint Etienne, Alizée Porto, Alexis Theron, Frederic Collart, Thierry Bourguignon, Thomas Cuisset, Laurent Fauchier
Journal: Journal of the American College of Cardiology (2020)
Single-cell RNA-seq analysis reveals ploidy-dependent and cell-specific transcriptome changes in Arabidopsis female gametophytes
Authors: Qingxin Song, Atsumi Ando, Ning Jiang, Yoko Ikeda, Z. Jeffrey Chen
Journal: Genome biology (2020)

Polyploidy provides new genetic material that facilitates evolutionary novelty, species adaptation, and crop domestication. Polyploidy often leads to an increase in cell or organism size, which may affect transcript abundance or transcriptome size, but the relationship between polyploidy and transcriptome changes remains poorly understood. Plant cells often undergo endoreduplication, confounding the polyploid effect.
Survival in Crohn’s disease-associated small bowel adenocarcinoma
Authors: Paolo Giuffrida, Alessandro Vanoli, Antonio Di Sabatino
Journal: Gut (2020)

We read with great interest the recent work by Axelrad et al 1 dealing with small bowel cancer-related death rate in patients with inflammatory bowel disease. The authors concluded that small bowel cancer mortality is higher in Crohn’s disease (CrD) patients than in sporadic cases. However, the latter data are not in keeping with all studies published so far showing a similar death rate between patients with CrD-associated small bowel adenocarcinoma (CrD-SBA) and those with sporadic SBA (table 1). In particular, Palascak-Juif et al 2 demonstrated a slightly, but not significantly, higher survival rate, in CrD-SBAs (54% at 2 years and 35% at 5 years) than in sporadic SBAs (37% …
Mitochondria as a promising target for developing novel agents for treating Alzheimer's disease
Authors: Elena F. Shevtsova, Andrey V. Maltsev, Darya V. Vinogradova, Pavel N. Shevtsov, Sergey O. Bachurin
Journal: Medicinal Research Reviews (2020)

The mitochondria-targeting drugs can be conventionally divided into the following groups: those compensating for the energy deficit involved in neurodegeneration, including stimulants of mitochondrial bioenergetics and activators of mitochondrial biogenesis; and neuroprotectors, that are compounds increasing the resistance of mitochondria to opening of mitochondrial permeability transition (MPT) pores. Although compensating for the energy deficit and inhibition of MPT are obvious targets for drugs used in the very early stages of Alzheimer-like pathology, but their use as the monotherapy for patients with severe symptoms is unlikely to be sufficiently effective. It would be optimal to combine targets that would provide the cognitive-stimulating, the neuroprotective effects and the ability to affect specific disease-forming mechanisms. In the design of such drugs, assessment of their potential mitochondrial-targeted effects is of particular importance. The possibility of targeted drug design for simultaneous action on mitochondrial and neurotransmitter's receptors targets is, in particularly, based on the known interplay of various cellular pathways and the presence of common structural components. Of particular interest is directed search for multitarget drugs that would act simultaneously on mitochondrial calcium-dependent functions, the targets (receptors, enzymes, etc.) facilitating neurotransmission, and the molecular targets related to the action of so-called disease-modifying factors, in particular, the formation and overcoming of the toxicity of β-amyloid or hyperphosphorylated tau protein. The examples of such approaches realized on the level of preclinical and clinical trials are presented below.
Dual-targeting nanovesicles enhance specificity to dynamic tumor cells in vitro and in vivo via manipulation of αvβ3-ligand binding
Authors: Yang Song, Xiangfu Guo, Jijun Fu, Bing He, Xueqing Wang, Wenbing Dai, Hua Zhang, Qiang Zhang
Journal: Acta Pharmaceutica Sinica B (2020)

The dynamic or flowing tumor cells just as leukemia cells and circulating tumor cells face a microenvironment difference from the solid tumors, and the related targeting nanomedicines are rarely reported. The existence of fluidic shear stress in blood circulation seems not favorable for the binding of ligand modified nanodrugs with their target receptor. Namely, the binding feature is very essential in this case. Herein, we utilized HSPC, PEG-DSPE, cholesterol and two αvβ3 ligands (RGDm7 and DT4) with different binding rates to build dual-targeting nanovesicles, in an effort to achieve a "fast-binding/slow-unbinding" function. It was demonstrated that the dual-targeting nanovesicles actualized efficient cellular uptake and antitumor effect in vitro both for static and dynamic tumor cells. Besides, the potency of the dual-targeting vesicles for flowing tumor cells was better than that for static tumor cells. Then, a tumor metastasis mice model and a leukemia mice model were established to detect the killing ability of the drug-loaded dual-targeting vesicles to dynamic tumor cells in vivo. The therapy efficacy of the dual-targeting system was higher than other controls including single-targeting ones. Generally, it seems possible to strengthen drug-targeting to dynamic tumor cells via the control of ligand-receptor interaction.
Impact of the SARS-CoV-2 epidemic on tuberculosis treatment outcome in Northern Italy
Authors: Paola Magro, Beatrice Formenti, Valentina Marchese, Maurizio Gulletta, Lina Rachele Tomasoni, Silvio Caligaris, Francesco Castelli, Alberto Matteelli
Journal: European Respiratory Journal (2020)

<b>It is important to recognise the impact of COVID-19 on TB care to mitigate its consequences. TB services have an urgent need to identify novel strategies to ensure the continuum of TB care at the time of the coronavirus pandemic.</b> https://bit.ly/2OIKnwL
Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP–PRODIGE 15): a randomised, phase 3 study
Authors: Diane Goéré, Olivier Glehen, François Quenet, Jean-Marc Guilloit, Jean-Marc Bereder, Gérard Lorimier, Emilie Thibaudeau, Laurent Ghouti, Amandine Pinto, Jean-Jacques Tuech, Reza Kianmanesh, Michel Carretier, Frédéric Marchal, Catherine Arvieux, Cécile Brigand, Pierre Meeus, Patrick Rat, Sylvaine Durand-Fontanier, Pascale Mariani, Zaher Lakkis, Valeria Loi, Nicolas Pirro, Charles Sabbagh, Matthieu Texier, Dominique Elias, M Ducreux, D Malka, V Boige, E Benhamou
Journal: The Lancet Oncology (2020)
GYS1 induces glycogen accumulation and promotes tumor progression via the NF-κB pathway in Clear Cell Renal Carcinoma
Authors: Shi-Lu Chen, Qun-Sheng Huang, Yu-Hua Huang, Xia Yang, Ming-Ming Yang, Yang-Fan He, Yun Cao, Xin-Yuan Guan, Jing-Ping Yun
Journal: Theranostics (2020)

Metabolism reprogramming is a hallmark of many cancer types. We focused on clear cell renal carcinoma (ccRCC) which is characterized by its clear and glycogen-enriched cytoplasm with unknown reasons. The aim of this study was to identify the clinical significance, biological function, and molecular regulation of glycogen synthase 1 (GYS1) in ccRCC glycogen accumulation and tumor progression.
Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial
Authors: Susumu Sakamoto, Kensuke Kataoka, Yasuhiro Kondoh, Motoyasu Kato, Masaki Okamoto, Hiroshi Mukae, Masashi Bando, Takafumi Suda, Kazuhiro Yatera, Yoshinori Tanino, Tomoo Kishaba, Noboru Hattori, Yoshio Taguchi, Takefumi Saito, Yasuhiko Nishioka, Kazuyoshi Kuwano, Kazuma Kishi, Naohiko Inase, Shinichi Sasaki, Hajime Takizawa, Takeshi Johkoh, Fumikazu Sakai, Sakae Homma
Journal: European Respiratory Journal (2020)

Background A randomised controlled trial in Japan showed that inhaled N-acetylcysteine monotherapy stabilised serial decline in forced vital capacity (FVC) in some patients with early idiopathic pulmonary fibrosis (IPF). However, the efficacy and tolerability of combination therapy with an antifibrotic agent and inhaled N-acetylcysteine are unknown. Methods This 48-week, randomised, open-label, multicentre phase 3 trial compared the efficacy and tolerability of combination therapy with pirfenidone plus inhaled N-acetylcysteine 352.4 mg twice daily with the results for pirfenidone alone in patients with IPF. The primary end-point was annual rate of decline in FVC. Exploratory efficacy measurements included serial change in diffusing capacity of the lung for carbon monoxide ( D LCO ) and 6-min walk distance (6MWD), progression-free survival (PFS), incidence of acute exacerbation, and tolerability. Results 81 patients were randomly assigned in a 1:1 ratio to receive pirfenidone plus inhaled N-acetylcysteine (n=41) or pirfenidone (n=40). The 48-week rate of change in FVC was −300 mL and −123 mL, respectively (difference −178 mL, 95% CI −324–−31 mL; p=0.018). Serial change in D LCO , 6MWD, PFS and incidence of acute exacerbation did not significantly differ between the two groups. The incidence of adverse events (n=19 (55.9%) for pirfenidone plus N-acetylcysteine; n=18 (50%) for pirfenidone alone) was similar between groups. Conclusions Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF.
Molecular Profiling Reveals a Common Metabolic Signature of Tissue Fibrosis
Authors: Ji Zhang, Eric S. Muise, Seongah Han, Peter S. Kutchukian, Philippe Costet, Yonghua Zhu, Yanqing Kan, Haihong Zhou, Vinit Shah, Yongcheng Huang, Ashmita Saigal, Taro E. Akiyama, Xiao-Lan Shen, Tian-Quan Cai, Kashmira Shah, Ester Carballo-Jane, Emanuel Zycband, Lan Yi, Ye Tian, Ying Chen, Jason Imbriglio, Elizabeth Smith, Kristine Devito, James Conway, Li-Jun Ma, Maarten Hoek, Iyassu K. Sebhat, Andrea M. Peier, Saswata Talukdar, David G. McLaren, Stephen F. Previs, Kristian K. Jensen, Shirly Pinto
Journal: Cell Reports Medicine (2020)

Fibrosis, or the accumulation of extracellular matrix, is a common feature of many chronic diseases. To interrogate core molecular pathways underlying fibrosis, we cross-examine human primary cells from various tissues treated with TGF-β, as well as kidney and liver fibrosis models. Transcriptome analyses reveal that genes involved in fatty acid oxidation are significantly perturbed. Furthermore, mitochondrial dysfunction and acylcarnitine accumulation are found in fibrotic tissues. Substantial downregulation of the PGC1α gene is evident in both in vitro and in vivo fibrosis models, suggesting a common node of metabolic signature for tissue fibrosis. In order to identify suppressors of fibrosis, we carry out a compound library phenotypic screen and identify AMPK and PPAR as highly enriched targets. We further show that pharmacological treatment of MK-8722 (AMPK activator) and MK-4074 (ACC inhibitor) reduce fibrosis in vivo. Altogether, our work demonstrate that metabolic defect is integral to TGF-β signaling and fibrosis.
β-Glucan–induced reprogramming of human macrophages inhibits NLRP3 inflammasome activation in cryopyrinopathies
Authors: Giorgio Camilli, Mathieu Bohm, Alícia Corbellini Piffer, Rachel Lavenir, David L. Williams, Benedicte Neven, Gilles Grateau, Sophie Georgin-Lavialle, Jessica Quintin
Journal: Journal of Clinical Investigation (2020)

Exposure of mononuclear phagocytes to β-glucan, a naturally occurring polysaccharide, contributes to the induction of innate immune memory, which is associated with long-term epigenetic, metabolic, and functional reprogramming. Although previous studies have shown that innate immune memory induced by β-glucan confers protection against secondary infections, its impact on autoinflammatory diseases, associated with inflammasome activation and IL-1β secretion, remains poorly understood. In particular, whether β-glucan-induced long-term reprogramming affects inflammasome activation in human macrophages in the context of these diseases has not been explored. We found that NLRP3 inflammasome-mediated caspase-1 activation and subsequent IL-1β production were reduced in β-glucan-reprogrammed macrophages. β-Glucan acted upstream of the NLRP3 inflammasome by preventing potassium (K+) efflux, mitochondrial ROS (mtROS) generation, and, ultimately, apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization and speck formation. Importantly, β-glucan-induced memory in macrophages resulted in a remarkable attenuation of IL-1β secretion and caspase-1 activation in patients with an NLRP3-associated autoinflammatory disease, cryopyrin-associated periodic syndromes (CAPS). Our findings demonstrate that β-glucan-induced innate immune memory represses IL-1β-mediated inflammation and support its potential clinical use in NLRP3-driven diseases.
BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner
Authors: Valerie A.C.M. Koeken, L. Charlotte J. de Bree, Vera P. Mourits, Simone J.C.F.M. Moorlag, Jona Walk, Branko Cirovic, Rob J.W. Arts, Martin Jaeger, Helga Dijkstra, Heidi Lemmers, Leo A.B. Joosten, Christine S. Benn, Reinout van Crevel, Mihai G. Netea
Journal: Journal of Clinical Investigation (2020)

BACKGROUNDInduction of innate immune memory, also termed trained immunity, by the antituberculosis vaccine bacillus Calmette-Guérin (BCG) contributes to protection against heterologous infections. However, the overall impact of BCG vaccination on the inflammatory status of an individual is not known; while induction of trained immunity may suggest increased inflammation, BCG vaccination has been epidemiologically associated with a reduced incidence of inflammatory and allergic diseases.METHODSWe investigated the impact of BCG (BCG-Bulgaria, InterVax) vaccination on systemic inflammation in a cohort of 303 healthy volunteers, as well as the effect of the inflammatory status on the response to vaccination. A targeted proteome platform was used to measure circulating inflammatory proteins before and after BCG vaccination, while ex vivo Mycobacterium tuberculosis- and Staphylococcus aureus-induced cytokine responses in peripheral blood mononuclear cells were used to assess trained immunity.RESULTSWhile BCG vaccination enhanced cytokine responses to restimulation, it reduced systemic inflammation. This effect was validated in 3 smaller cohorts, and was much stronger in men than in women. In addition, baseline circulating inflammatory markers were associated with ex vivo cytokine responses (trained immunity) after BCG vaccination.CONCLUSIONThe capacity of BCG to enhance microbial responsiveness while dampening systemic inflammation should be further explored for potential therapeutic applications.FUNDINGNetherlands Organization for Scientific Research, European Research Council, and the Danish National Research Foundation.
Correspondence regarding “Delamanid for rifampicin-resistant tuberculosis: a retrospective study from South Africa”
Authors: Erika Mohr-Holland, Anja Reuter, Jennifer Hughes, Johnny Daniels, Busisiwe Beko, Goodman Makhanda, Virginia De Avezedo, Yulene Kock, Helen Cox, Jennifer Furin, Laura Trivino Duran, Petros Isaakidis, Gabriella Ferlazzo
Journal: European Respiratory Journal (2020)

<b>Delamanid (Dlm) containing regimens to treat RR-TB are effective, but more data on Dlm use is needed. Dlm remains an important treatment option in programmatic settings with high rates of HIV co-infection and in persons with limited treatment options.</b>https://bit.ly/3cVLeUq
CircCDK14 protects against Osteoarthritis by sponging miR-125a-5p and promoting the expression of Smad2
Authors: Panyang Shen, Yute Yang, Gang Liu, Weijie Chen, Junxing Chen, Qingxin Wang, Hongliang Gao, Shunwu Fan, Shuying Shen, Xing Zhao
Journal: Theranostics (2020)

Rationale: Osteoarthritis (OA) is the most common joint disease worldwide. Previous studies have identified the imbalance between extracellular matrix (ECM) catabolism and anabolism in cartilage tissue as the main cause. To date, there is no cure for OA despite a few symptomatic treatments. This study aimed to investigate the role of CircCDK14, a novel circRNA factor, in the progression of OA, and to elucidate its underlying molecular mechanisms. Methods: The function of CircCDK14 in OA, as well as the interaction between CircCDK14 and its downstream target (miR-125a-5p) and mRNA target (Smad2), was evaluated by western blot (WB), immunofluorescence (IF), RNA immunoprecipitation (RIP), quantitative RT-PCR, luciferase assay and fluorescence in situ hybridization (FISH). Rabbit models were introduced to examine the function and mechanism of CircCDK14 in OA in vivo. Results: In our present study, we found that CircCDK14, while being down-regulated in the joint wearing position, regulated metabolism, inhibited apoptosis and promoted proliferation in the cartilage. Mechanically, the protective effect of CircCDK14 was mediated by miR-125a-5p sponging, which downregulated the Smad2 expression and led to the dysfunction of TGF-β signaling pathway. Intra-articular injection of adeno-associated virus-CircCDK14 also alleviated OA in the rabbit model. Conclusion: Our study revealed an important role of CircCDK14/miR-125a-5p/Smad2 axis in OA progression and provided a potential molecular therapeutic strategy for the treatment of OA.