tbuckley/cabot-search huggingface dataset:
A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function
Authors: Enric Vilar, Raja M. Kaja Kamal, James Fotheringham, Amanda Busby, Jocelyn Berdeprado, Ewa Kislowska, David Wellsted, Bassam Alchi, James O. Burton, Andrew Davenport, Ken Farrington
Journal: Kidney International (2021)

Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.
Direct platelet adhesion potentiates group 2 innate lymphoid cell functions
Authors: Keisuke Orimo, Masato Tamari, Tomohiro Takeda, Terufumi Kubo, Beate Rückert, Kenichiro Motomura, Hiroki Sugiyama, Ayako Yamada, Kyoko Saito, Ken Arae, Motohiro Kuriyama, Mariko Hara, Michael B. Soyka, Masashi Ikutani, Sota Yamaguchi, Noriko Morimoto, Kazuhiko Nakabayashi, Kenichiro Hata, Akio Matsuda, Cezmi A. Akdis, Katsuko Sudo, Hirohisa Saito, Susumu Nakae, Jun Tamaoki, Etsuko Tagaya, Kenji Matsumoto, Hideaki Morita
Journal: Allergy (2021)

Abstract Background Platelets are thought to be involved in the pathophysiology of asthma, presumably through direct adhesion to inflammatory cells, including group 2 innate lymphoid cells (ILC2s). Here, we tried to elucidate the effects of platelet adhesion to ILC2s in vitro and in vivo, as well as the mechanisms involved. Methods Alternaria ‐induced ILC2‐dependent airway inflammation models using wild‐type and c ‐ mpl −/− mice were evaluated. Both purified CD41 + and CD41 − ILC2s were cultured with IL‐2 and IL‐33 to determine in vitro Type 2 (T2) cytokine production and cell proliferation. RNA‐seq data of flow‐cytometry‐sorted CD41 + and CD41 − ILC2s were used to isolate ILC2‐specific genes. Flow cytometry was performed to determine the expression of CD41 and adhesion‐related molecules on ILC2s in both mouse and human tissues. Results T2 inflammation and T2 cytokine production from ILC2s were significantly reduced in the c ‐ mpl −/− mice compared to wild‐type mice. Platelet‐adherent ILC2s underwent significant proliferation and showed enhanced T2 cytokine production when exposed to IL‐2 and IL‐33. The functions of ILC2‐specific genes were related to cell development and function. Upstream regulator analysis identified 15 molecules, that are thought to be involved in ILC2 activation. CD41 expression levels were higher in ILC2s from human PBMCs and mouse lung than in those from secondary lymphoid tissues, but they did not correlate with the P‐selectin glycoprotein ligand‐1 or CD24 expression level. Conclusion Platelets spontaneously adhere to ILC2s, probably in the peripheral blood and airways, thereby potentiating ILC2s to enhance their responses to IL‐33.
28115 Cost analysis of rosacea treatments in a dermatologic center in Bogotá, Colombia
Authors: David A. Castillo Molina, Diego M. Martinez Zúñiga, Jesús E. Jaimes Silva, Luisa Fernanda Camacho-Lázaro, María Juliana Sánchez Zapata, María José Centeno, Nelson J. Alvis-Zak, Gabriela Bula Galan, Jennipher A. Blanco Gómez, David E. Castillo Saavedra
Journal: Journal of the American Academy of Dermatology (2021)
26198 Evaluating patient outcomes in the BOLT 42-month trial using modified Response Evaluation Criteria in Solid Tumors methodology: Results from a preplanned analysis
Authors: Reinhard Dummer, Aaron S. Farberg, James Spencer, Felix Kiecker, Alexander Guminski, Kurt Gebauer, Carmen Loquai, Caroline Robert, Nicholas Squittieri, Michael Migden
Journal: Journal of the American Academy of Dermatology (2021)
A functional PVA aerogel-based membrane obtaining sutureability through modified electrospinning technology and achieving promising anti-adhesion effect after cardiac surgery
Authors: Dawei Jin, Shuofei Yang, Shuting Wu, Meng Yin, Haizhu Kuang
Journal: Bioactive Materials (2021)

Pericardial barrier destruction, inflammatory cell infiltration, and fibrous tissue hyperplasia, trigger adhesions after cardiac surgery. There are few anti-adhesion materials that are both functional and sutureable for pericardial reconstruction. Besides, a few studies have reported on the mechanism of preventing pericardial adhesion. Herein, a functional barrier membrane with sutureability was developed via a modified electrospinning method. It was composed of poly(l-lactide-co-caprolactone) (PLCL) nanofibers, poly(vinyl alcohol) (PVA) aerogel, and melatonin, named PPMT. The PPMT had a special microstructure manifested as a staggered arrangement of nanofibers on the surface and a layered macroporous aerogel structure in a cross-section. Besides providing the porosity and hydrophilicity obtained from PVA, the structure also had suitable mechanical properties for stitching due to the addition of PLCL nanofibers. Furthermore, it inhibited the proliferation of fibroblasts by suppressing the activation of Fas and P53, and achieved anti-inflammatory effects by affecting the activity of inflammatory cells and reducing the release of pro-inflammatory factors, such as interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α). Finally, in vivo transplantation showed that it up-regulated the expression of matrix metalloproteinase-1 (MMP1) and tissue inhibitor of metalloproteinase-1 (TIMP1), and down-regulated the expression of Vinculin and transforming growth factor β (TGF-β) in the myocardium, thereby reducing the formation of adhesions. Collectively, these results demonstrate a great potential of PPMT membrane for practical application to anti-adhesion.
Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction
Authors: Richard Karlsson Linnér, Travis T. Mallard, Peter B. Barr, Sandra Sanchez-Roige, James W. Madole, Morgan N. Driver, Holly E. Poore, Ronald de Vlaming, Andrew D. Grotzinger, Jorim J. Tielbeek, Emma C. Johnson, Mengzhen Liu, Sara Brin Rosenthal, Trey Ideker, Hang Zhou, Rachel L. Kember, Joëlle A. Pasman, Karin J. H. Verweij, Dajiang J. Liu, Scott Vrieze, Bernice Porjesz, Victor Hesselbrock, Tatiana M. Foroud, Arpana Agrawal, Howard J. Edenberg, John I. Nurnberger Jr, Yunlong Liu, Samuel Kuperman, John Kramer, Jacquelyn L. Meyer, Chella Kamarajan, Ashwini K. Pandey, Laura Bierut, John Rice, Kathleen K. Bucholz, Marc A. Schuckit, Jay Tischfield, Andrew Brooks, Ronald P. Hart, Laura Almasy, Danielle M. Dick, Jessica E. Salvatore, Allison Goate, Manav Kapoor, Paul Slesinger, Denise M. Scott, Lance Bauer, Leah Wetherill, Xiaoling Xuei, Dongbing Lai, Sean J. O’Connor, Martin H. Plawecki, Spencer Lourens, Laura Acion, Grace Chan, David B. Chorlian, Jian Zhang, Sivan Kinreich, Gayathri Pandey, Michael J. Chao, Andrey P. Anokhin, Vivia V. McCutcheon, Scott Saccone, Fazil Aliev, Peter B. Barr, Hemin Chin, Abbas Parsian, Henry R. Kranzler, Joel Gelernter, Kathleen Mullan Harris, Elliot M. Tucker-Drob, Irwin D. Waldman, Abraham A. Palmer, K. Paige Harden, Philipp D. Koellinger, Danielle M. Dick
Journal: Nature Neuroscience (2021)
Do the benefits of being a smoker hint at the existence of PD-1/PD-L1 sensitizers for patients on single-agent immunotherapy?
Authors: Gintaras Zaleskis, Vita Pasukoniene, Dainius Characiejus, Vincas Urbonas
Journal: Journal for ImmunoTherapy of Cancer (2021)

Multiple studies demonstrate significantly better therapeutics outcomes in smokers as compared with never smokers when single-agent immunotherapy is applied. Non-smoker patients usually need a combination of chemoimmunotherapy to achieve comparable or slightly better therapeutic results. This effect is thought to be due to tobacco product-induced upregulation of PD-L1/PD-1 expression and tumor mutational burden score. Genomic transformation, however, cannot entirely explain the upregulation of PD-L1/PL-1 expression in cells following short-term exposure to cytotoxic compounds. Cytotoxic drugs, crude tobacco products, benzo(a)pyrene, nicotine, and multiple other toxic compounds were shown to exhibit rapid PD-L1/PD-1 upregulation. A significant immunomodulatory effect of nicotine via acetylcholine receptors is well documented. However, nicotine activity rapidly subsides when the drug is withdrawn. We hypothesize that smoking cessation might mitigate the benefits of monoimmunotherapy for some patients. Further studies of the nicotinic acetylcholine receptor stimulus of immunocytes are needed and might lead to characterization and clinical implementation of new immunotherapy sensitizer products.
Synergistic combination of cytotoxic chemotherapy and cyclin‐dependent kinase 4/6 inhibitors in biliary tract cancers
Authors: Mansi Arora, James M. Bogenberger, Amro M. Abdelrahman, Jennifer Yonkus, Roberto Alva‐Ruiz, Jennifer L. Leiting, Xianfeng Chen, Pedro Luiz Serrano Uson Junior, Chelsae R. Dumbauld, Alexander T. Baker, Scott I. Gamb, Jan B. Egan, Yumei Zhou, Bolni Marius Nagalo, Nathalie Meurice, Eeva‐Liisa Eskelinen, Marcela A. Salomao, Heidi E. Kosiorek, Esteban Braggio, Michael T. Barrett, Kenneth H. Buetow, Mohamad B. Sonbol, Aaron S. Mansfield, Lewis R. Roberts, Tanios S. Bekaii‐Saab, Daniel H. Ahn, Mark J. Truty, Mitesh J. Borad
Journal: Hepatology (2021)

Biliary tract cancers (BTCs) are uncommon, but highly lethal, gastrointestinal malignancies. Gemcitabine/cisplatin is a standard-of-care systemic therapy, but has a modest impact on survival and harbors toxicities, including myelosuppression, nephropathy, neuropathy, and ototoxicity. Whereas BTCs are characterized by aberrations activating the cyclinD1/cyclin-dependent kinase (CDK)4/6/CDK inhibitor 2a/retinoblastoma pathway, clinical use of CDK4/6 inhibitors as monotherapy is limited by lack of validated biomarkers, diffident preclinical efficacy, and development of acquired drug resistance. Emerging studies have explored therapeutic strategies to enhance the antitumor efficacy of CDK4/6 inhibitors by the combination with chemotherapy regimens, but their mechanism of action remains elusive.Here, we report in vitro and in vivo synergy in BTC models, showing enhanced efficacy, reduced toxicity, and better survival with a combination comprising gemcitabine/cisplatin and CDK4/6 inhibitors. Furthermore, we demonstrated that abemaciclib monotherapy had only modest efficacy attributable to autophagy-induced resistance. Notably, triplet therapy was able to potentiate efficacy through elimination of the autophagic flux. Correspondingly, abemaciclib potentiated ribonucleotide reductase catalytic subunit M1 reduction, resulting in sensitization to gemcitabine.As such, these data provide robust preclinical mechanistic evidence of synergy between gemcitabine/cisplatin and CDK4/6 inhibitors and delineate a path forward for translation of these findings to preliminary clinical studies in advanced BTC patients.
Lesional Mechanism of Alpha Thalassemias : Towards a Common Mechanism Alpha Thal / Beta Thal
Authors: Serge Pissard, Flavia Guillem, Elisa Domingues-Hamdi, Michaël Dussiot, Thunwarat Suriyun, Olivier Hermine, Veronique Baudin creuza, Genevieve Courtois
Journal: Blood (2017)
Clinicopathological and Molecular Characteristics of Early-Onset Stage III Colon Adenocarcinoma: An Analysis of the ACCENT Database
Authors: Zhaohui Jin, Jesse G Dixon, Jack M Fiskum, Hiral D Parekh, Frank A Sinicrope, Greg Yothers, Carmen J Allegra, Norman Wolmark, Daniel Haller, Hans-Joachim Schmoll, Aimery de Gramont, Rachel Kerr, Julien Taieb, Eric Van Cutsem, Christopher Tweleves, Michael O’Connell, Leonard B Saltz, Sotaro Sadahiro, Charles D Blanke, Naohiro Tomita, Jean-Francois Seitz, Charles Erlichman, Takayuki Yoshino, Takeharu Yamanaka, Silvia Marsoni, Thierry Andre, Amit Mahipal, Richard M Goldberg, Thomas J George, Qian Shi
Journal: JNCI Journal of the National Cancer Institute (2021)

Colon cancer (CC) incidence in young adults (age 20-49 years), termed early-onset CC (EO-CC), is increasing.Individual patient data on 35 713 subjects with stage III colon cancer from 25 randomized studies in the Adjuvant Colon Cancer ENdpoint database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and outcome data were summarized by age group. Overall survival, disease-free survival, time to recurrence, and survival after recurrence were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for sex, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness, and molecular markers. All statistical tests were 2-sided.Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III EO-CC had similar sex, race, performance status, risk group, tumor sidedness, and T stage compared with patients with late-onset CC (age 50 years and older). EO-CC patients were less likely to be overweight (30.2% vs 36.2%) and more commonly had 12 or more lymph nodes resected (69.5% vs 58.7%). EO-CC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%) and less likely to have BRAFV600E (5.6% vs 14.0%), suggesting a higher rate of Lynch syndrome in EO-CC. Patients with EO-CC had statistically significantly better overall survival (hazard ratio [HR] = 0.81, 95% confidence interval [CI] = 0.74 to 0.89; P < .001), disease-free survival (HR = 0.91, 95% CI = 0.84 to 0.98; P = .01), and survival after recurrence (HR = 0.88, 95% CI = 0.80 to 0.97; P = .008) in the analysis without molecular markers; however, age at onset of CC lost its prognostic value when outcome was adjusted for molecular markers.Tumor biology was found to be a more important prognostic factor than age of onset among stage III colon cancer patients in the Adjuvant Colon Cancer ENdpoint database.
27571 Dupilumab provides clinically meaningful responses in adults with moderate-to-severe atopic dermatitis (AD): Results from LIBERTY AD CHRONOS study
Authors: Jonathan I. Silverberg, Eric L. Simpson, Marjolein de Bruin&, None ;Weller, Peter Foley, Yoko Kataoka, Zhen Chen, Brad Shumel, Ana B. Rossi, Debra Sierka, Jingdong Chao
Journal: Journal of the American Academy of Dermatology (2021)
27505 Bimekizumab short-term and longer-term anxiety, depression, and suicidal ideation/behavior in patients with moderate to severe plaque psoriasis: Analysis of pooled data from eight phase 2/3 clinical trials
Authors: Bruce Strober, Kim A. Papp, Andrew Blauvelt, Mark Lebwohl, Jashin J. Wu, Delphine Deherder, Cynthia Madden, Krista Wixted, Maggie Wang, Matthias Augustin
Journal: Journal of the American Academy of Dermatology (2021)
Endoscopy International Open – recently published
Authors: Kenji Takashima, Yasuhiro Oono, Motohiro Kojima, Hiroaki Ikematsu, Tetsuo Akimoto, Tomonori Yano
Journal: Endoscopy (2019)

Comment on: Lumen apposing metal stents are superior to plastic stents in pancreatic walled-off necrosis: a large international multicenter studyEndosc Int Open 2019; 07(03): E347-E354DOI: 10.1055/a-0828-7630 Comment on: CO2 vs. air insufflation in endoscopic ultrasonography: a prospective studyEndosc Int Open 2019; 07(03): E317-E321DOI: 10.1055/a-0809-4912 Comment on: Clinicopathological features and endoscopic characteristics of inverted sessile serrated adenomas/polypsEndosc Int Open 2019; 07(03): E330-E336DOI: 10.1055/a-0820-2179
Non-contact physiological monitoring of post-operative patients in the intensive care unit
Authors: João Jorge, Mauricio Villarroel, Hamish Tomlinson, Oliver Gibson, Julie L. Darbyshire, Jody Ede, Mirae Harford, John Duncan Young, Lionel Tarassenko, Peter Watkinson
Journal: npj Digital Medicine (2022)

Prolonged non-contact camera-based monitoring in critically ill patients presents unique challenges, but may facilitate safe recovery. A study was designed to evaluate the feasibility of introducing a non-contact video camera monitoring system into an acute clinical setting. We assessed the accuracy and robustness of the video camera-derived estimates of the vital signs against the electronically-recorded reference values in both day and night environments. We demonstrated non-contact monitoring of heart rate and respiratory rate for extended periods of time in 15 post-operative patients. Across day and night, heart rate was estimated for up to 53.2% (103.0 h) of the total valid camera data with a mean absolute error (MAE) of 2.5 beats/min in comparison to two reference sensors. We obtained respiratory rate estimates for 63.1% (119.8 h) of the total valid camera data with a MAE of 2.4 breaths/min against the reference value computed from the chest impedance pneumogram. Non-contact estimates detected relevant changes in the vital-sign values between routine clinical observations. Pivotal respiratory events in a post-operative patient could be identified from the analysis of video-derived respiratory information. Continuous vital-sign monitoring supported by non-contact video camera estimates could be used to track early signs of physiological deterioration during post-operative care.
Immunogenicity of mRNA-1273 COVID vaccine after 6 months surveillance in health care workers; a third dose is necessary
Authors: Marie Tré-Hardy, Roberto Cupaiolo, Alain Wilmet, Thomas Antoine-Moussiaux, Andrea Della Vecchia, Alexandra Horeanga, Emmanuelle Papleux, Marc Vekemans, Ingrid Beukinga, Laurent Blairon
Journal: Journal of Infection (2021)
Colchicine in Patients With Chronic Coronary Disease in Relation to Prior Acute Coronary Syndrome
Authors: Tjerk S.J. Opstal, Aernoud T.L. Fiolet, Amber van Broekhoven, Arend Mosterd, John W. Eikelboom, Stefan M. Nidorf, Peter L. Thompson, Michiel Duyvendak, J.W. Martijn van Eck, Eugène A. van Beek, Frank den Hartog, Charley A. Budgeon, Willem A. Bax, Jan G.P. Tijssen, Saloua El Messaoudi, Jan H. Cornel, S.M. Nidorf, X.F. Xu, M.A. Ireland, D. Latchem, A. Whelan, R. Hendriks, P. Salkani, I.W. Tan, A.G. Thompson, A.M. Morton, B.E. Hockings, P.L. Thompson, B. King, J.H. Cornel, H. Bakker-Lohmeijer, A. Mosterd, P. Bunschoten, S.H.K. The, S. van der Kooi, T. Lenderink, R.G.J.L. Lardinois, P.A.M. Hoogslag, A. de Vos, A. Jerzewski, S. Jansen, P.R. Nierop, M. van der Knaap, H.P. Swart, R. Kingma, J. Schaap, L.B. Blom, A.F.M. Kuijper, E. Bayraktar-Verver, M.W.J. van Hessen, W.C.T.C. Engelen, J.W.M. van Eck, N. van der Ven-Elzebroek, J.M.C. van Hal, I.M.J. Drost, F.R. den Hartog, D. van Wijk, E. van Beek, C. van der Horst, G.L. Bartels, M. Hendriks, C. de Nooijer, C. Welten, E. Ronner, A. Dijkshoorn, F.J. Prins, R.N.A. Rutten, D.P.W. Beele, I. Hendriks, A. van der Sluis, E.A. Badings, I.C.D. Westendorp, A. Melein, Tj.J. Römer, P. Bruines, R. van de Wal, I. Leenders - van Lieshout, M.E.W. Hemels, K. Meinen-Werner, M.R. de Groot, G. Post, M.W.C. Mulder, S. Stuij, E. van Nes, P. Luyten, J. Plomp, S.V. Veldmeijer, M.J. Asselman, P.A. Scholtus
Journal: Journal of the American College of Cardiology (2021)
Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure
Authors: Ingrid W. Zhang, Anna Curto, Cristina López-Vicario, Mireia Casulleras, Marta Duran-Güell, Roger Flores-Costa, Benoit Colsch, Ferran Aguilar, Ana M. Aransay, Juan José Lozano, María Hernández-Tejero, David Toapanta, Javier Fernández, Vicente Arroyo, Joan Clària
Journal: Journal of Hepatology (2021)

Patients with acute-on-chronic liver failure (ACLF) present a systemic hyperinflammatory response associated with increased circulating levels of small-molecule metabolites. To investigate whether these alterations reflect inadequate cell energy output, we assessed mitochondrial morphology and central metabolic pathways with emphasis on the tricarboxylic acid (TCA) cycle in peripheral leukocytes from patients with acutely decompensated (AD) cirrhosis, with and without ACLF.The study included samples from patients with AD cirrhosis (108 without and 128 with ACLF) and 41 healthy individuals. Leukocyte mitochondrial ultrastructure was visualized by transmission electron microscopy and cytosolic and mitochondrial metabolic fluxes were determined by assessing NADH/FADH2 production from various substrates. Plasma GDF15 and FGF21 were determined by Luminex and acylcarnitines by LC-MS/MS. Gene expression was analyzed by RNA-sequencing and PCR-based glucose metabolism profiler array.Mitochondrial ultrastructure in patients with advanced cirrhosis was distinguished by cristae rarefication and swelling. The number of mitochondria per leukocyte was higher in patients, accompanied by a reduction in their size. Increased FGF21 and C6:0- and C8:0-carnitine predicted mortality whereas GDF15 strongly correlated with a gene set signature related to leukocyte activation. Metabolic flux analyses revealed increased energy production in mononuclear leukocytes from patients with preferential involvement of extra-mitochondrial pathways, supported by upregulated expression of genes encoding enzymes of the glycolytic and pentose phosphate pathways. In patients with ACLF, mitochondrial function analysis uncovered break-points in the TCA cycle at the isocitrate dehydrogenase and succinate dehydrogenase level, which were bridged by anaplerotic reactions involving glutaminolysis and nucleoside metabolism.Our findings provide evidence at the cellular, organelle and biochemical levels that severe mitochondrial dysfunction governs immunometabolism in leukocytes from patients with AD cirrhosis and ACLF.Patients at advanced stages of liver disease have dismal prognosis due to vital organ failures and the lack of treatment options. In this study, we report that the functioning of mitochondria, which are known as the cell powerhouse, is severely impaired in leukocytes of these patients, probably as a consequence of intense inflammation. Mitochondrial dysfunction is therefore a hallmark of advanced liver disease.