tbuckley/cabot-search huggingface dataset:
Tfh cells with NLRP3 inflammasome activation are essential for high-affinity antibody generation, germinal centre formation and autoimmunity
Authors: Zhenhuan Zhao, Bihua Xu, Shuang Wang, Mianjing Zhou, Yuefang Huang, Chaohuan Guo, Mengyuan Li, Jijun Zhao, Sun-Sang J Sung, Felicia Gaskin, Niansheng Yang, Shu Man Fu
Journal: Annals of the Rheumatic Diseases (2022)

NLRP3 inflammasome regulates T cell responses. This study examined the roles of NLRP3 inflammasome activation in the regulation of T follicular helper (Tfh) cells during humoral response to T dependent antigens and in systemic lupus erythematosus (SLE).NLRP3 inflammasome activation of Tfh cells was studied in B6, MRL/lpr and NZM2328 mice and in SLE patients and healthy controls using a fluorescence-labelled caspase-1 inhibitor probe. MCC950, a selective inhibitor of NLRP3, was used to investigate the relation between NLRP3 inflammasome activation and germinal centre (GC) reaction, Ab responses to immunisation, and autoantibody production.NLRP3 inflammasome activation in Tfh cells after immunisation was identified in B6 mice. MCC950 inhibited humoral responses to sheep red blood cell and NP-CGG with reduction of the GC reaction. B6 mice with lymphoid cell-specific deletion of NLRP3 or Casp1 mounted suboptimal humoral responses with impaired GC formation and defective affinity maturation. In MRL/lpr and NZM2328 mice, inhibition of NLRP3 activation suppressed NLRP3 activated Tfh cell expansion as well as attenuated lupus-like phenotypes. Tfh cells with activated NLRP3 inflammasome exhibited increased expression of molecules for Tfh cell function and differentiation, and had greater ability to activate B cells. In SLE patients, disease activity was positively correlated with an increase in the activated NLRP3+ Tfh population and this population was markedly reduced in response to therapy.The activation of NLRP3 inflammasome in Tfh cells is an integral part of responses to immunisation. The activated NLRP3+ Tfh population is essential for optimal humoral responses, GC formation and autoimmunity.
Outcome measures in the management of gluteal tendinopathy: a systematic review of their measurement properties
Authors: Anthony M Nasser, Angela M Fearon, Alison Grimaldi, Bill Vicenzino, Rebecca Mellor, Trevor Spencer, Adam Ivan Semciw
Journal: British Journal of Sports Medicine (2022)

Objective Evaluate properties of outcome measures for gluteal tendinopathy. Design Multistage scoping/systematic review. Data sources Cochrane, PubMed, Embase, Scopus, Web of Science, PEDro, CINAHL, SPORTDISCUS were searched (December 2021) to identify measures used to evaluate gluteal tendinopathy. Measures were mapped to the core health domains for tendinopathy. Medline, CINAHL, Embase and PubMed were searched (December 2021) for studies evaluating measurement properties of gluteal tendinopathy outcome measures captured in the initial search. Both reviews included studies that evaluated a treatment in participants with gluteal tendinopathy, diagnosed by a professional. Consensus-based-Standards for the Selection of Health Instruments methodology were followed—including bias assessment and synthesis of findings. Results Six studies reported on the Victorian Institute of Sport Assessment—Gluteal Tendinopathy (VISA-G). One study reported on the Hip Outcome Score (HOS)—activities of daily living (ADL) and Sport. The VISA-G had moderate-quality evidence of sufficient construct validity (known group) and responsiveness (pre–post intervention), low-quality evidence of sufficient reliability, measurement error, comprehensibility and insufficient construct validity (convergent), and very low-quality evidence of sufficient comprehensiveness, relevance and responsiveness (comparison with other outcome measures). Both the HOS(ADL) and HOS(Sport) had very low-quality evidence of sufficient reliability, relevance and insufficient construct validity and comprehensiveness. The HOS(ADL) had very low-quality evidence of sufficient comprehensibility and insufficient measurement error. The HOS(Sport) had very low quality evidence of inconsistent comprehensibility and sufficient measurement error. Conclusion Rigorously validated outcome measures for gluteal tendinopathy are lacking. The VISA-G is the preferred available option to capture the disability associated with gluteal tendinopathy.
A novel sphincterotome facilitates endoscopic sphincterotomy in patients with Roux-en-Y gastrectomy
Authors: Yuki Tanisaka, Masafumi Mizuide, Akashi Fujita, Tomoya Ogawa, Hiromune Katsuda, Kazuya Miyaguchi, Shomei Ryozawa
Journal: Endoscopy (2022)

Endoscopic retrograde cholangiopancreatography (ERCP) using a short-type single-balloon enteroscope (short SBE) (SIF-H290; Olympus Medical Systems, Tokyo, Japan), with a working length of 152 cm and a working channel diameter of 3.2 mm, has been reported to be effective in patients with surgically altered anatomy (SAA) [1] [2] [3]. However, endoscopic sphincterotomy (ES) in such patients is challenging, as the appearance of the papilla is inverted and the position is frequently tangential, which makes visualizing the correct incision direction difficult. Despite the effectiveness of reported devices, they do not always achieve the correct incision direction [4] [5].
Free will without consciousness?
Authors: Liad Mudrik, Inbal Gur Arie, Yoni Amir, Yarden Shir, Pamela Hieronymi, Uri Maoz, Timothy O'Connor, Aaron Schurger, Manuel Vargas, Tillmann Vierkant, Walter Sinnott-Armstrong, Adina Roskies
Journal: Trends in Cognitive Sciences (2022)

Findings demonstrating decision-related neural activity preceding volitional actions have dominated the discussion about how science can inform the free will debate. These discussions have largely ignored studies suggesting that decisions might be influenced or biased by various unconscious processes. If these effects are indeed real, do they render subjects' decisions less free or even unfree? Here, we argue that, while unconscious influences on decision-making do not threaten the existence of free will in general, they provide important information about limitations on freedom in specific circumstances. We demonstrate that aspects of this long-lasting controversy are empirically testable and provide insight into their bearing on degrees of freedom, laying the groundwork for future scientific-philosophical approaches.
Size Exclusion of Radioactive Polymers (SERP) informs on the biodegradation of trimethyl chitosan and biodegradable polymer nanoparticles in vitro and in vivo
Authors: Amrita Dikpati, Nicolas Gaudreault, Valérie Chénard, Philippe Grenier, Élodie Boisselier, Nicolas Bertrand
Journal: Journal of Controlled Release (2022)
TCTAP C-030 Best of Both Worlds - Debulking With DK Crush in Complex Bifurcation
Authors: Wan Faizal Bin Wan Rahimi Shah, Mohamed Nazrul Mohamed Nazeeb, Afif Ashari, Faten Aqilah Aris, Yee Sin Tey, Wei Liang Lee, Amin Ariff Nuruddin
Journal: Journal of the American College of Cardiology (2022)
Late Balloon Valvuloplasty for Transcatheter Heart Valve Dysfunction
Authors: Mariama Akodad, Philipp Blanke, Ming-Yu A Chuang, Jade Duchscherer, Stephanie L Sellers, Andrew G Chatfield, Gaurav G Gulsin, Sandra Lauck, Jonathon A Leipsic, David Meier, Rob R Moss, Anson Cheung, Janarthanan Sathananthan, David A Wood, Jian Ye, John G Webb
Journal: Journal of the American College of Cardiology (2022)
TCTAP C-102 Management and Retrieval of Undeflatable Non-Compliant Coronary Balloon During Percutaneous Coronary Intervention
Authors: Arvin Romero Yumul, Shaiful Azmi Yahaya, Kumara Gurupparan Ganesan, Jayakhanthan Kolanthaivelu, Faten Aqilah Aris, Mohamed Nazrul Mohamed Nazeeb, Khin Maung Zan Mohd Saad Jalaluddin, Chee Sin Khaw
Journal: Journal of the American College of Cardiology (2022)
Mitochondrial protease ClpP supplementation ameliorates diet-induced NASH in mice
Authors: Sung-E Choi, Yoonjung Hwang, Soo-Jin Lee, Hyunkyung Jung, Tae Hwan Shin, Youngho Son, Seokho Park, Seung Jin Han, Hae Jin Kim, Kwan Woo Lee, Gwang Lee, Jongsook Kim Kemper, Hyun Kyu Song, Yup Kang
Journal: Journal of Hepatology (2022)
Trends in Annual Surveillance Mammography Participation Among Breast Cancer Survivors From 2004 to 2016
Authors: Kathryn P. Lowry, Katherine A. Callaway, Janie M. Lee, Fang Zhang, Dennis Ross-Degnan, J. Frank Wharam, Karla Kerlikowske, Karen J. Wernli, Allison W. Kurian, Louise M. Henderson, Natasha K. Stout
Journal: Journal of the National Comprehensive Cancer Network (2022)

Annual mammography is recommended for breast cancer survivors; however, population-level temporal trends in surveillance mammography participation have not been described. Our objective was to characterize trends in annual surveillance mammography participation among women with a personal history of breast cancer over a 13-year period.We examined annual surveillance mammography participation from 2004 to 2016 in a nationwide sample of commercially insured women with prior breast cancer. Rates were stratified by age group (40-49 vs 50-64 years), visit with a surgical/oncology specialist or primary care provider within the prior year, and sociodemographic characteristics. Joinpoint models were used to estimate annual percentage changes (APCs) in participation during the study period.Among 141,672 women, mammography rates declined from 74.1% in 2004 to 67.1% in 2016. Rates were stable from 2004 to 2009 (APC, 0.1%; 95% CI, -0.5% to 0.8%) but declined 1.5% annually from 2009 to 2016 (95% CI, -1.9% to -1.1%). For women aged 40 to 49 years, rates declined 2.8% annually (95% CI, -3.4% to -2.1%) after 2009 versus 1.4% annually in women aged 50 to 64 years (95% CI, -1.9% to -1.0%). Similar trends were observed in women who had seen a surgeon/oncologist (APC, -1.7%; 95% CI, -2.1% to -1.4%) or a primary care provider (APC, -1.6%; 95% CI, -2.1% to -1.2%) in the prior year.Surveillance mammography participation among breast cancer survivors declined from 2009 to 2016, most notably among women aged 40 to 49 years. These findings highlight a need for focused efforts to improve adherence to surveillance and prevent delays in detection of breast cancer recurrence and second cancers.
Direct targeting of FOXP3 in Tregs with AZD8701, a novel antisense oligonucleotide to relieve immunosuppression in cancer
Authors: Alexey Revenko, Larissa S Carnevalli, Charles Sinclair, Ben Johnson, Alison Peter, Molly Taylor, Lisa Hettrick, Melissa Chapman, Stephanie Klein, Anisha Solanki, Danielle Gattis, Andrew Watt, Adina M Hughes, Lukasz Magiera, Gozde Kar, Lucy Ireland, Deanna A Mele, Vasu Sah, Maneesh Singh, Josephine Walton, Maelle Mairesse, Matthew King, Mark Edbrooke, Paul Lyne, Simon T Barry, Stephen Fawell, Frederick W Goldberg, A Robert MacLeod
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background The Regulatory T cell (Treg) lineage is defined by the transcription factor FOXP3, which controls immune-suppressive gene expression profiles. Tregs are often recruited in high frequencies to the tumor microenvironment where they can suppress antitumor immunity. We hypothesized that pharmacological inhibition of FOXP3 by systemically delivered, unformulated constrained ethyl-modified antisense oligonucleotides could modulate the activity of Tregs and augment antitumor immunity providing therapeutic benefit in cancer models and potentially in man. Methods We have identified murine Foxp3 antisense oligonucleotides (ASOs) and clinical candidate human FOXP3 ASO AZD8701. Pharmacology and biological effects of FOXP3 inhibitors on Treg function and antitumor immunity were tested in cultured Tregs and mouse syngeneic tumor models. Experiments were controlled by vehicle and non-targeting control ASO groups as well as by use of multiple independent FOXP3 ASOs. Statistical significance of biological effects was evaluated by one or two-way analysis of variance with multiple comparisons. Results AZD8701 demonstrated a dose-dependent knockdown of FOXP3 in primary Tregs, reduction of suppressive function and efficient target downregulation in humanized mice at clinically relevant doses. Surrogate murine FOXP3 ASO, which efficiently downregulated Foxp3 messenger RNA and protein levels in primary Tregs, reduced Treg suppressive function in immune suppression assays in vitro. FOXP3 ASO promoted more than 70% reduction in FOXP3 levels in Tregs in vitro and in vivo, strongly modulated Treg effector molecules (eg, ICOS, CTLA-4, CD25 and 4-1BB), and augmented CD8 + T cell activation and produced antitumor activity in syngeneic tumor models. The combination of FOXP3 ASOs with immune checkpoint blockade further enhanced antitumor efficacy. Conclusions Antisense inhibitors of FOXP3 offer a promising novel cancer immunotherapy approach. AZD8701 is being developed clinically as a first-in-class FOXP3 inhibitor for the treatment of cancer currently in Ph1a/b clinical trial ( NCT04504669 ).
Automated virtual reality therapy to treat agoraphobic avoidance and distress in patients with psychosis (gameChange): a multicentre, parallel-group, single-blind, randomised, controlled trial in England with mediation and moderation analyses
Authors: Daniel Freeman, Sinéad Lambe, Thomas Kabir, Ariane Petit, Laina Rosebrock, Ly-Mee Yu, Robert Dudley, Kate Chapman, Anthony Morrison, Eileen O'Regan, Charlotte Aynsworth, Julia Jones, Elizabeth Murphy, Rosie Powling, Ushma Galal, Jenna Grabey, Aitor Rovira, Jennifer Martin, Chris Hollis, David M Clark, Felicity Waite, James Altunkaya, Humma Andleeb, Aislinn Bergin, Emily Bold, Jessica Bond, Kate Bransby-Adams, Susan Brown, Cindy Chan, Nisha Chauhan, Michael Craven, Jason Freeman, John Geddes, Andrew Goodsell, Lucy Jenner, Alex Kenny, José Leal, Joanna Mitchell, Heather Peel, Maryam Pervez, Eloise Prouten, Eva Roberts, Dan Robotham, Harry Walker, Jonathan West
Journal: The Lancet Psychiatry (2022)

Automated delivery of psychological therapy using immersive technologies such as virtual reality (VR) might greatly increase the availability of effective help for patients. We aimed to evaluate the efficacy of an automated VR cognitive therapy (gameChange) to treat avoidance and distress in patients with psychosis, and to analyse how and in whom it might work.
Clarification of Disclosure
Journal: JAMA Network Open (2022)

Jennifer M. Hah, MD, MS; Eric Cramer, BS; Heather Hilmoe, BS ; Peter Schmidt, MD; Rebecca McCue, BS ; Jodie Trafton, PhD; Debra Clay, BSN, RN; Yasamin Sharifzadeh, BS; Gabriela Ruchelli, BS; Stuart Goodman, MD, PhD; James Huddleston, MD; William J. Maloney, MD; Frederick M. Dirbas, MD; Joseph Shrager, MD; John G. Costouros, MD; Catherine Curtin, MD; Sean C. Mackey, MD, PhD; Ian Carroll, MD, MS
TCTAP C-123 Embolic Shower to Coronary and Cerebral Arteries From a Cardiac Myxoma
Authors: Ghiath Sadek Baroudy, Fahmi Othman, Ahmed Mahfouz, Sherif Helmy, Ihsan Rafie, Abdulaziz Abdulla AL Khulaifi
Journal: Journal of the American College of Cardiology (2022)
Association of Abnormal Findings on Neonatal Cranial Ultrasound With Neurobehavior at Neonatal Intensive Care Unit Discharge in Infants Born Before 30 Weeks’ Gestation
Authors: Jennifer Helderman, T. Michael O’Shea, Lynne Dansereau, Jennifer Check, Julie A. Hofheimer, Lynne M. Smith, Elisabeth McGowan, Charles R. Neal, Brian S. Carter, Steven L. Pastyrnak, Bradford Betz, Joseph Junewick, Heather L. Borders, Sheri A. DellaGrotta, Barry M. Lester
Journal: JAMA Network Open (2022)

Cranial ultrasound (CUS) findings are routinely used to identify preterm infants at risk for impaired neurodevelopment, and neurobehavioral examinations provide information about early brain function. The associations of abnormal findings on early and late CUS with neurobehavior at neonatal intensive care unit (NICU) discharge have not been reported. To examine the associations between early and late CUS findings and infant neurobehavior at NICU discharge. This prospective cohort study included infants enrolled in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants Study between April 2014 and June 2016. Infants born before 30 weeks' gestational age were included. Exclusion criteria were maternal age younger than 18 years, maternal cognitive impairment, maternal inability to read or speak English or Spanish, maternal death, and major congenital anomalies. Overall, 704 infants were enrolled. The study was conducted at 9 university-affiliated NICUs in Providence, Rhode Island; Grand Rapids, Michigan; Kansas City, Missouri; Honolulu, Hawaii; Winston-Salem, North Carolina; and Torrance and Long Beach, California. Data were analyzed from September 2019 to September 2021. Early CUS was performed at 3 to 14 days after birth and late CUS at 36 weeks' postmenstrual age or NICU discharge. Abnormal findings were identified by consensus of standardized radiologists' readings. Neurobehavioral examination was performed using the NICU Network Neurobehavioral Scale (NNNS). Among the 704 infants enrolled, 675 had both CUS and NNNS data (135 [20.0%] Black; 368 [54.5%] minority race or ethnicity; 339 [50.2%] White; 376 [55.7%] male; mean [SD] postmenstrual age, 27.0 [1.9] weeks). After covariate adjustment, lower attention (adjusted mean difference, -0.346; 95% CI, -0.609 to -0.083), hypotonicity (mean difference, 0.358; 95% CI, 0.055 to 0.662), and poorer quality of movement (mean difference, -0.344; 95% CI, -0.572 to -0.116) were observed in infants with white matter damage (WMD). Lower attention (mean difference, -0.233; 95% CI, -0.423 to -0.044) and hypotonicity (mean difference, 0.240; 95% CI, 0.014 to 0.465) were observed in infants with early CUS lesions. In this cohort study of preterm infants, certain early CUS lesions were associated with hypotonicity and lower attention around term-equivalent age. WMD was associated with poor attention, hypotonicity, and poor quality of movement. Infants with these CUS lesions might benefit from targeted interventions to improve neurobehavioral outcomes during their NICU hospitalization.
Postmortem Assessment of Olfactory Tissue Degeneration and Microvasculopathy in Patients With COVID-19
Authors: Cheng-Ying Ho, Mohammad Salimian, Julia Hegert, Jennifer O’Brien, Sun Gyeong Choi, Heather Ames, Meaghan Morris, John C. Papadimitriou, Joseph Mininni, Peter Niehaus, Allen Burke, Leyla Canbeldek, Jonathan Jacobs, Autumn LaRocque, Kavi Patel, Kathryn Rice, Ling Li, Robert Johnson, Alexandra LeFevre, Thomas Blanchard, Ciara M. Shaver, Ann Moyer, Cinthia Drachenberg
Journal: JAMA Neurology (2022)

Loss of smell is an early and common presentation of COVID-19 infection. Although it has been speculated that viral infection of olfactory neurons may be the culprit, it is unclear whether viral infection causes injuries in the olfactory bulb region.To characterize the olfactory pathology associated with COVID-19 infection in a postmortem study.This multicenter postmortem cohort study was conducted from April 7, 2020, to September 11, 2021. Deceased patients with COVID-19 and control individuals were included in the cohort. One infant with congenital anomalies was excluded. Olfactory bulb and tract tissue was collected from deceased patients with COVID-19 and appropriate controls. Histopathology, electron microscopy, droplet digital polymerase chain reaction, and immunofluorescence/immunohistochemistry studies were performed. Data analysis was conducted from February 7 to October 19, 2021.(1) Severity of degeneration, (2) losses of olfactory axons, and (3) severity of microvasculopathy in olfactory tissue.Olfactory tissue from 23 deceased patients with COVID-19 (median [IQR] age, 62 [49-69] years; 14 men [60.9%]) and 14 control individuals (median [IQR] age, 53.5 [33.25-65] years; 7 men [50%]) was included in the analysis. The mean (SD) axon pathology score (range, 1-3) was 1.921 (0.569) in patients with COVID-19 and 1.198 (0.208) in controls (P < .001), whereas axon density was 2.973 (0.963) × 104/mm2 in patients with COVID-19 and 3.867 (0.670) × 104/mm2 in controls (P = .002). Concomitant endothelial injury of the microvasculature was also noted in olfactory tissue. The mean (SD) microvasculopathy score (range, 1-3) was 1.907 (0.490) in patients with COVID-19 and 1.405 (0.233) in control individuals (P < .001). Both the axon and microvascular pathology was worse in patients with COVID-19 with smell alterations than those with intact smell (mean [SD] axon pathology score, 2.260 [0.457] vs 1.63 [0.426]; P = .002; mean [SD] microvasculopathy score, 2.154 [0.528] vs 1.694 [0.329]; P = .02) but was not associated with clinical severity, timing of infection, or presence of virus.This study found that COVID-19 infection is associated with axon injuries and microvasculopathy in olfactory tissue. The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 infection may be severe and permanent.
GPR177 in A-fiber sensory neurons drives diabetic neuropathic pain via WNT-mediated TRPV1 activation
Authors: Ya-Kai Xie, Hao Luo, Shan-Xin Zhang, Xiao-Ying Chen, Ran Guo, Xiao-Yun Qiu, Shuai Liu, Hui Wu, Wen-Bo Chen, Xing-Hua Zhen, Qiang Ma, Jin-Lan Tian, Shun Li, Xinzhong Chen, Qingjian Han, Shumin Duan, Chengyong Shen, Fan Yang, Zhen-Zhong Xu
Journal: Science Translational Medicine (2022)

Diabetic neuropathic pain (DNP) is a common and devastating complication in patients with diabetes. The mechanisms mediating DNP are not completely elucidated, and effective treatments are lacking. A-fiber sensory neurons have been shown to mediate the development of mechanical allodynia in neuropathic pain, yet the molecular basis underlying the contribution of A-fiber neurons is still unclear. Here, we report that the orphan G protein-coupled receptor 177 (GPR177) in A-fiber neurons drives DNP via WNT5a-mediated activation of transient receptor potential vanilloid receptor-1 (TRPV1) ion channel. GPR177 is mainly expressed in large-diameter A-fiber dorsal root ganglion (DRG) neurons and required for the development of DNP in mice. Mechanistically, we found that GPR177 mediated the secretion of WNT5a from A-fiber DRG neurons into cerebrospinal fluid (CSF), which was necessary for the maintenance of DNP. Extracellular perfusion of WNT5a induced rapid currents in both TRPV1-expressing heterologous cells and nociceptive DRG neurons. Computer simulations revealed that WNT5a has the potential to bind the residues at the extracellular S5-S6 loop of TRPV1. Using a peptide able to disrupt the predicted WNT5a/TRPV1 interaction suppressed DNP- and WNT5a-induced neuropathic pain symptoms in rodents. We confirmed GPR177/WNT5A coexpression in human DRG neurons and WNT5A secretion in CSF from patients with DNP. Thus, our results reveal a role for WNT5a as an endogenous and potent TRPV1 agonist, and the GPR177-WNT5a-TRPV1 axis as a driver of DNP pathogenesis in rodents. Our findings identified a potential analgesic target that might relieve neuropathic pain in patients with diabetes.
Prospective testing of clinical Cerenkov luminescence imaging against standard-of-care nuclear imaging for tumour location
Authors: Edwin C. Pratt, Magdalena Skubal, Benedict Mc Larney, Pamela Causa-Andrieu, Sudeep Das, Peter Sawan, Abdallah Araji, Christopher Riedl, Kunal Vyas, David Tuch, Jan Grimm
Journal: Nature Biomedical Engineering (2022)
The outcome of patients with Hodgkin lymphoma and early relapse after autologous stem cell transplant has improved in recent years
Authors: Ali Bazarbachi, Ariane Boumendil, Hervé Finel, Irma Khvedelidze, Joanna Romejko-Jarosinska, Alina Tanase, Saad Akhtar, Tarek Ben Othman, Mohammad Ma’koseh, Boris Afanasyev, Jean Cheikh, Javier Briones, Zafer Gülbas, Rose-Marie Hamladji, Tugrul Elverdi, Didier Blaise, Carmen Martínez, Eleonora Alma, Kazimierz Halaburda, Aida Botelho Sousa, Bertram Glass, Steven Robinson, Silvia Montoto, Anna Sureda
Journal: Leukemia (2022)