tbuckley/cabot-search huggingface dataset:
Auditory Dysfunction Among Individuals With Neurofibromatosis Type 1
Authors: Gary Rance, Julien Zanin, Alice Maier, Donella Chisari, Kristina M. Haebich, Kathryn N. North, Gabriel Dabscheck, Marc L. Seal, Martin B. Delatycki, Jonathan M. Payne
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Neurofibromatosis type 1 (NF1) affects hearing through disruption of central auditory processing. The mechanisms, functional severity, and management implications are unclear. <h3>Objective</h3> To investigate auditory neural dysfunction and its perceptual consequences in individuals with NF1. <h3>Design, Setting, and Participants</h3> This case-control study included children and adults with NF1 and control participants matched on age, sex, and hearing level. Patients were recruited through specialist neurofibromatosis and neurogenetic outpatient clinics between April and September 2019. An evaluation of auditory neural activity, monaural/binaural processing, and functional hearing was conducted. Diffusion-weighted magnetic resonance imaging (MRI) data were collected from a subset of participants (10 children with NF1 and 10 matched control participants) and evaluated using a fixel-based analysis of apparent fiber density. <h3>Main Outcomes and Measures</h3> Type and severity of auditory dysfunction evaluated via laboratory testing and questionnaire data. <h3>Results</h3> A total of 44 participants (18 [41%] female individuals) with NF1 with a mean (SD) age of 16.9 (10.7) years and 44 control participants (18 [41%] female individuals) with a mean (SD) age of 17.2 (10.2) years were included in the study. Overall, 11 participants (25%) with NF1 presented with evidence of auditory neural dysfunction, including absent, delayed, or low amplitude electrophysiological responses from the auditory nerve and/or brainstem, compared with 1 participant (2%) in the control group (odds ratio [OR], 13.03; 95% CI, 1.59-106.95). Furthermore, 14 participants (32%) with NF1 showed clinically abnormal speech perception in background noise compared with 1 participant (2%) in the control group (OR, 20.07; 95% CI, 2.50-160.89). Analysis of diffusion-weighted MRI data of participants with NF1 showed significantly lower apparent fiber density within the ascending auditory brainstem pathways. The regions identified corresponded to the neural dysfunction measured using electrophysiological assessment. <h3>Conclusions and Relevance</h3> The findings of this case-control study could represent new neurobiological and clinical features of NF1. Auditory dysfunction severe enough to impede developmental progress in children and restrict communication in older participants is a common neurobiological feature of the disorder.
Spleen and Symptom Responses with Fedratinib (FEDR) in Patients with Myelofibrosis (MF) and Substantial Splenomegaly
Authors: Jean-Jacques Kiladjian, Ayalew Tefferi, Francesco Passamonti, Alessandro Vannucchi, Moshe Talpaz, Francisco Cervantes, Claire N. Harrison, Ruben A. Mesa, John Mascarenhas, Nicolaas Schaap, Srdan Verstovsek, Timothy Devos, Shelonitda Rose, Jun Zhang, Oumar Sy, Animesh Pardanani
Journal: Blood (2021)
Genomic and transcriptomic profiling reveals distinct molecular subsets associated with outcomes in mantle cell lymphoma
Authors: Shuhua Yi, Yuting Yan, Meiling Jin, Supriyo Bhattacharya, Yi Wang, Yiming Wu, Lu Yang, Eva Gine, Guillem Clot, Lu Chen, Ying Yu, Dehui Zou, Jun Wang, An T. Phan, Rui Cui, Fei Li, Qi Sun, Qiongli Zhai, Tingyu Wang, Zhen Yu, Lanting Liu, Wei Liu, Rui Lyv, Weiwei Sui, Wenyang Huang, Wenjie Xiong, Huijun Wang, Chengwen Li, Zhijian Xiao, Mu Hao, Jianxiang Wang, Tao Cheng, Silvia Bea, Alex F. Herrera, Alexey Danilov, Elias Campo, Vu N. Ngo, Lugui Qiu, Lili Wang
Journal: Journal of Clinical Investigation (2021)

Mantle cell lymphoma (MCL) is a phenotypically and genetically heterogeneous malignancy in which the genetic alterations determining clinical indications are not fully understood. Here, we performed a comprehensive whole-exome sequencing analysis of 152 primary samples derived from 134 MCL patients, including longitudinal samples from 16 patients and matched RNA-Seq data from 48 samples. We classified MCL into 4 robust clusters (C1-C4). C1 featured mutated immunoglobulin heavy variable (IGHV), CCND1 mutation, amp(11q13), and active B cell receptor (BCR) signaling. C2 was enriched with del(11q)/ATM mutations and upregulation of NF-κB and DNA repair pathways. C3 was characterized by mutations in SP140, NOTCH1, and NSD2, with downregulation of BCR signaling and MYC targets. C4 harbored del(17p)/TP53 mutations, del(13q), and del(9p), and active MYC pathway and hyperproliferation signatures. Patients in these 4 clusters had distinct outcomes (5-year overall survival [OS] rates for C1-C4 were 100%, 56.7%, 48.7%, and 14.2%, respectively). We also inferred the temporal order of genetic events and studied clonal evolution of 16 patients before treatment and at progression/relapse. Eleven of these samples showed drastic clonal evolution that was associated with inferior survival, while the other samples showed modest or no evolution. Our study thus identifies genetic subsets that clinically define this malignancy and delineates clonal evolution patterns and their impact on clinical outcomes.
97P Trends and disparities in real-world (RW) biomarker testing (BT) and overall survival (OS) among US patients (pts) with advanced non-small cell lung cancer (aNSCLC), 2015–2020
Authors: S.J. Antonia, W. Ge, N. Wu, R.G. Quek, H. Dietz, J-F. Pouliot, J. Jalbert, J. Harnett
Journal: Annals of Oncology (2021)
Abstract 13358: Pediatric Defibrillation; Safety and Efficacy of Shocks in Both Ventricular Fibrillation and Sinus Rhythm in a Porcine Model
Authors: Ben McCartney, Adam Harvey, Amy Kernaghan, Sara Morais, Olibhear McAlister, Hannah Torney, Paul Crawford, Pardis Biglarbeigi, Raymond Bond, Dewar Finlay, David McEneaney
Journal: Circulation (2021)

Introduction: Pediatric sudden cardiac arrest may require the delivery of a defibrillating shock to promote return of spontaneous circulation (ROSC). Fear of harm is a barrier for the use of automated external defibrillators by lay personnel, particularly when the patient is a child. The aim of this study was to observe the effects of delivering pediatric defibrillation shocks to pediatric weight swine who are in a perfusing rhythm or ventricular fibrillation (VF). Methods: Eight swine (10.3-26.8 kg) were studied under anesthesia. Up to 30 shocks were applied using modified samaritan AEDs (HeartSine, UK) to animals either in sinus rhythm or after 30 seconds of VF. Shocks delivered in sinus rhythm were unsynchronized. Four different shock types were applied, utilizing two different waveforms (Waveform-A at 50 J, Waveform-A at 75 J, Waveform-A at 90J and Waveform-B at 50 J). Left ventricular (LV) pressures were recorded invasively (Millar, USA). If the shock was successful, the animal entered a rest period of approximately 5 minutes, after which the next shock was applied. Results: Data presented in Table 1. Out of a total of 77 shocks delivered in sinus rhythm, 2 (2.6%) resulted in conversion to a cardiac arrest rhythm. Analysis of LV pressures demonstrated no significant differences in the change of LV dP/dt from baseline at 1, 10 and 60 seconds post-shock. There was no significant difference in shock success or ROSC between the shock types for defibrillation of VF. Analysis of LV pressures demonstrated no significant differences in the change of LV dP/dt from baseline at at 1, 10 and 60 seconds post-shock between the groups. Conclusions: The results of this study indicate defibrillation shocks applied to swine in sinus rhythm rarely result in conversion to an arrhythmia. Additionally, the variety of shock types demonstrated similar levels of safety and efficacy in this porcine model.
Prevalence and duration of detectable SARS-CoV-2 nucleocapsid antibodies in staff and residents of long-term care facilities over the first year of the pandemic (VIVALDI study): prospective cohort study in England
Authors: Maria Krutikov, Tom Palmer, Gokhan Tut, Christopher Fuller, Borscha Azmi, Rebecca Giddings, Madhumita Shrotri, Nayandeep Kaur, Panagiota Sylla, Tara Lancaster, Aidan Irwin-Singer, Andrew Hayward, Paul Moss, Andrew Copas, Laura Shallcross
Journal: The Lancet Healthy Longevity (2021)

BackgroundLong-term care facilities (LTCFs) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion of infected people among those who have survived, and duration of the antibody response to natural infection, is unknown. We determined the prevalence and stability of nucleocapsid antibodies (the standard assay for detection of previous infection) in staff and residents in LTCFs in England.MethodsThis was a prospective cohort study of residents 65 years or older and of staff 65 years or younger in 201 LTCFs in England between March 1, 2020, and May 7, 2021. Participants were linked to a unique pseudo-identifier based on their UK National Health Service identification number. Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein using the Abbott ARCHITECT i-system (Abbott, Maidenhead, UK) immunoassay. Primary endpoints were prevalence and cumulative incidence of antibody positivity, which were weighted to the LTCF population. Incidence rate of loss of antibodies (seroreversion) was estimated from Kaplan-Meier curves.Findings9488 samples were included, 8636 (91·0%) of which could be individually linked to 1434 residents and 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 34·6% (29·6–40·0) in residents and 26·1% (23·0–29·5) in staff over 11 months. 239 (38·6%) residents and 503 women (81·3%) were included in the antibody-waning analysis, and median follow-up was 149 days (IQR 107–169). The incidence rate of seroreversion was 2·1 per 1000 person-days at risk, and median time to reversion was 242·5 days.InterpretationAt least a quarter of staff and a third of surviving residents were infected with SAR-CoV-2 during the first two waves of the pandemic in England. Nucleocapsid-specific antibodies often become undetectable within the first year following infection, which is likely to lead to marked underestimation of the true proportion of people with previous infection. Given that natural infection might act to boost vaccine responses, better assays to identify natural infection should be developed.FundingUK Government Department of Health and Social Care.
<i>Lactobacillus gallinarum</i> modulates the gut microbiota and produces anti-cancer metabolites to protect against colorectal tumourigenesis
Authors: Naoki Sugimura, Qing Li, Eagle Siu Hong Chu, Harry Cheuk Hay Lau, Winnie Fong, Weixin Liu, Cong Liang, Geicho Nakatsu, Anthony Chin Yang Su, Olabisi Oluwabukola Coker, William Ka Kei Wu, Francis Ka Leung Chan, Jun Yu
Journal: Gut (2021)

Objective Using faecal shotgun metagenomic sequencing, we identified the depletion of Lactobacillus gallinarum in patients with colorectal cancer (CRC). We aimed to determine the potential antitumourigenic role of L. gallinarum in colorectal tumourigenesis. Design The tumor-suppressive effect of L. gallinarum was assessed in murine models of CRC. CRC cell lines and organoids derived from patients with CRC were cultured with L. gallinarum or Escherichia coli MG1655 culture-supernatant to evaluate cell proliferation, apoptosis and cell cycle distribution. Gut microbiota was assessed by 16S ribosomal DNA sequencing. Antitumour molecule produced from L. gallinarum was identified by liquid chromatography mass spectrometry (LC-MS/MS) and targeted mass spectrometry. Results L. gallinarum significantly reduced intestinal tumour number and size compared with E. coli MG1655 and phosphate-buffered saline in both male and female murine intestinal tumourigenesis models. Faecal microbial profiling revealed enrichment of probiotics and depletion of pathogenic bacteria in L. gallinarum -treated mice. Culturing CRC cells with L. gallinarum culture-supernatant (5%, 10% and 20%) concentration-dependently suppressed cell proliferation and colony formation. L. gallinarum culture-supernatant significantly promoted apoptosis in CRC cells and patient-derived CRC organoids, but not in normal colon epithelial cells. Only L. gallinarum culture-supernatant with fraction size &lt;3 kDa suppressed proliferation in CRC cells. Using LC-MS/MS, enrichments of indole-3-lactic acid (ILA) was identified in both L. gallinarum culture-supernatant and the gut of L. gallinarum -treated mice. ILA displayed anti-CRC growth in vitro and inhibited intestinal tumourigenesis in vivo . Conclusion L. gallinarum protects against intestinal tumourigenesis by producing protective metabolites that can promote apoptosis of CRC cells.
Nutritional Supplements, Ginseng and Leucine, Increase Erythropoiesis in Diamond Blackfan Anemia Models through Inhibition of Nemo-like Kinase
Authors: Mark C Wilkes, Aya Shibuya, Jacqueline D Mercado, Anupama Narla, Bert Glader, Kathleen M. Sakamoto
Journal: Blood (2021)
24P Using real-world evidence data and machine learning to identify molecular biomarkers for patient response to immune checkpoint inhibitors in metastatic melanoma
Authors: V. Siozopoulou, A. Khmelevskiy, A. Rodlauer-Kriegl, T. de Caluwe, A. Churov, A. Valyaeva, L. De Bruyen, R. Wener, P. Specenier, C. Cuvelier, M. Thienpont, E. Richtig, P. Pauwels
Journal: Annals of Oncology (2021)
A RAD Approach to iBlastoids with a Moral Principle of Complexity
Authors: Andrew J. Barnhart, Kris Dierickx
Journal: The American Journal of Bioethics (2021)

This article is referred to by:Response to Open Peer Commentaries on “Developing a Reflexive, Anticipatory, and Deliberative Approach to Unanticipated Discoveries: Ethical Lessons from iBlastoids”
Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers
Authors: Kanika Vanshylla, Chengcheng Fan, Marie Wunsch, Nareshkumar Poopalasingam, Matthijs Meijers, Christoph Kreer, Franziska Kleipass, Denis Ruchnewitz, Meryem S. Ercanoglu, Henning Gruell, Friederike Münn, Kai Pohl, Hanna Janicki, Tobias Nolden, Simone Bartl, Saskia C. Stein, Max Augustin, Felix Dewald, Lutz Gieselmann, Philipp Schommers, Thomas F. Schulz, Leif Erik Sander, Manuel Koch, Marta Łuksza, Michael Lässig, Pamela J. Bjorkman, Florian Klein
Journal: Cell Host & Microbe (2021)
Abstract 12508: Nicotinamide Restores Tissue NAD <sup>+</sup> and Improves Mouse Survival After Cardiac Arrest
Authors: Xiangdong Zhu, Jing Li, Filip Gasior, Huashan Wang, Shaoxia Lin, CODY JUSTICE, J Michael Odonnell, Terry L Vanden Hoek
Journal: Circulation (2021)

Introduction: Metabolic suppression in the ischemic heart is characterized by NAD + depletion. How nicotinamide (NAM) supplementation affects NAD + repletion and cardiac arrest outcomes is unknown. Hypothesis: We hypothesized that NAM supplementation restores tissue NAD + and promotes glucose oxidation and sorbitol clearance, resulting in improved cardiac function and survival in a mouse model of cardiac arrest. Methods: Adult C57BL6 mice were subjected to an established KCL-induced 8 min cardiac arrest, randomly assigned to receive saline (NS) or 100 mg/kg NAM during cardiopulmonary resuscitation (CPR). Survival, MAP, ETCO 2, and ECG were monitored for 4 h after the return of spontaneous circulation (ROSC). Direct cardiac effects were assessed using a cardiomyocyte stunning model and an isolated rat heart Langendroff model to measure the contraction recovery and cardiac function, respectively. NAD + , lactate and ATP were measured by assay kits and AMPK phosphorylation was measured by Western blot. Results: Cardiomyocyte NAD + content decreased from 4.51 ± 0.03 nMol/g pre-ischemia to 2.69 ± 0.42 nMol/g at the end of ischemia. Treatment with 0.01 mM NAM completely restored the cellular level of NAD + and improved contractile recovery by 10 min reperfusion (58.1 ± 7.3% of baseline contractile velocity vs.18.5 ± 3.7% in control cells). NAM administered immediately after ROSC significantly improved mouse survival, with 10/10 survival at 4 h as compared to 5/10 in the NS group. NAM-treated mice displayed improved NAD + content in hearts obtained at 4 h post-ROSC compared to saline treated hearts (4.5 ± 0.1 nMol/g vs. 2.4 ± 0.1 nMol/g). NAM significantly reduced sorbitol accumulation in heart from saline control of 20.4 ± 2.7 μMol/g to 7.2 ± 1.5 μMol/g at 30 min post-ROSC, indicating less glucose shunting to polyol pathway. Cardiac contractile function was completely recovered with 1 mM NAM treatment in the isolated perfused rat heart. Compared with buffer control, NAM treatment increased heart content of NAD + , lactate, ATP and phosphorylated AMPK. Conclusion: NAM is efficacious for restoring cardiac NAD + and promotes metabolic and contractile recovery, with improved survival of cardiac arrest.
The longevity society
Authors: Andrew J Scott
Journal: The Lancet Healthy Longevity (2021)

As the demographic transition enters a new stage of a longevity transition, focus needs to extend beyond an ageing society towards a longevity society.An ageing society focuses on changes in the age structure of the population, whereas a longevity society seeks to exploit the advantages of longer lives through changes in how we age.Achieving a longevity society requires substantial changes in the life course and social norms, and involves an epidemiological transition towards a focus on delaying the negative effects of ageing.The broad changes required to achieve healthy longevity include an increased focus on healthy life expectancy, a shift from intervention towards preventive health, a major public health agenda to avoid increases in health inequality, the establishment of longevity councils to ensure coordinated policy across government departments, and intergenerational assessment of policies, to ensure that in adapting to longer lives, policies are not skewed towards older people.A longevity society represents a new stage for humanity and requires deep-seated notions about age and ageing to be challenged if society is to make the best use of the additional time that longevity brings.
Winter of Omicron—The Evolving COVID-19 Pandemic
Authors: Carlos del Rio, Saad B. Omer, Preeti N. Malani
Journal: JAMA (2021)

This Viewpoint discusses the Omicron variant of SARS-CoV-2, including its likely origin, the importance of vaccination, the other tools available to combat a surge in COVID-19 cases, and the possibility of a "twindemic" with influenza.
Construct Validity of Pa<sub>O<sub>2</sub></sub>/F<scp>i</scp><sub>O<sub>2</sub></sub> Ratios in Defining Acute Respiratory Distress Syndrome
Authors: Sheng-Yuan Ruan, Chun-Ta Huang, Hou-Tai Chang, Wei-Lun Liu, Wei-Jhen Wang, Yun-Ting Tseng, Han-Ching Yang, Lu-Cheng Kuo, Jung-Yien Chien, Huey-Dong Wu
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Construct Validity of PaO2/FiO2 Ratios in Defining Acute Respiratory Distress Syndrome." American Journal of Respiratory and Critical Care Medicine, 205(3), pp. 364–366
COVID-19 vaccine strategies must focus on severe disease and global equity
Authors: Peter B McIntyre, Rakesh Aggarwal, Ilesh Jani, Jaleela Jawad, Sonali Kochhar, Noni MacDonald, Shabir A Madhi, Ezzeddine Mohsni, Kim Mulholland, Kathleen M Neuzil, Hanna Nohynek, Folake Olayinka, Punnee Pitisuttithum, Andrew J Pollard, Alejandro Cravioto
Journal: The Lancet (2021)
Flimma: a federated and privacy-aware tool for differential gene expression analysis
Authors: Olga Zolotareva, Reza Nasirigerdeh, Julian Matschinske, Reihaneh Torkzadehmahani, Mohammad Bakhtiari, Tobias Frisch, Julian Späth, David B. Blumenthal, Amir Abbasinejad, Paolo Tieri, Georgios Kaissis, Daniel Rückert, Nina K. Wenke, Markus List, Jan Baumbach
Journal: Genome biology (2021)

Abstract Aggregating transcriptomics data across hospitals can increase sensitivity and robustness of differential expression analyses, yielding deeper clinical insights. As data exchange is often restricted by privacy legislation, meta-analyses are frequently employed to pool local results. However, the accuracy might drop if class labels are inhomogeneously distributed among cohorts. Flimma ( https://exbio.wzw.tum.de/flimma/ ) addresses this issue by implementing the state-of-the-art workflow limma voom in a federated manner, i.e., patient data never leaves its source site. Flimma results are identical to those generated by limma voom on aggregated datasets even in imbalanced scenarios where meta-analysis approaches fail.
Abstract 10861: Determining the Importance of Gender, Race, and Body Shape for Cardiopulmonary Resuscitation Education Using Manikins
Authors: Kiera Liblik, Jin Byun, JUAN FARINA, Andrew Lloyd-Kuzik, Lucrecia Maria M Burgos, Daniel Howes, Adrian M Baranchuk
Journal: Circulation (2021)

Introduction: Cardiopulmonary resuscitation (CPR) education plays a critical role in reducing cardiovascular deaths. Thus, it is crucial that trainees engage in practice simulations that accurately replicate a cardiovascular emergency. Recent work has shown that certain demographic groups such as Black Americans and women are less likely to receive efficient CPR, and technique may vary on individuals who have an increased body mass index or who are pregnant. Poor representation of these groups in the manikins used for CPR simulation may play a substantial role in these inequities. Hypothesis: There is a deficiency in the diversity of race, gender, and body habitus of manikins used for CPR training in North and South America. Methods: Institutions, businesses, and non-governmental organizations which administer CPR certification in North and South America were identified for survey distribution through a collaboration with the Inter-American Society of Cardiology. A survey was administered using the online platform Qualtrics (Provo, USA) consisting of 18 questions about manikin supply, usage, and diversity. Results and Conclusions: A total of 52 survey responses were received from North America (n=20; 854 total manikins) and South America (n=32; 1,169 total manikins). Of the total manikins (n=2,023), 318 (16%) were non-white, 114 (6%) were female, 20 (1%) represented a non-lean body habitus, and 18 (1%) were pregnant. The importance of diverse manikin representation in simulation training is underscored by literature detailing deficiencies in CPR initiation and associated outcomes in individuals who are not lean white males. Yet, the majority of manikins used in North and South America still disproportionally represent this population. It is pertinent that manikins used for CPR training reflect all populations at risk for major adverse cardiovascular events.