tbuckley/cabot-search huggingface dataset:
The genome of oil-Camellia and population genomics analysis provide insights into seed oil domestication
Authors: Ping Lin, Kailiang Wang, Yupeng Wang, Zhikang Hu, Chao Yan, Hu Huang, Xianjin Ma, Yongqing Cao, Wei Long, Weixin Liu, Xinlei Li, Zhengqi Fan, Jiyuan Li, Ning Ye, Huadong Ren, Xiaohua Yao, Hengfu Yin
Journal: Genome biology (2022)

Abstract Background As a perennial crop, oil-Camellia possesses a long domestication history and produces high-quality seed oil that is beneficial to human health. Camellia oleifera Abel. is a sister species to the tea plant, which is extensively cultivated for edible oil production. However, the molecular mechanism of the domestication of oil-Camellia is still limited due to the lack of sufficient genomic information. Results To elucidate the genetic and genomic basis of evolution and domestication, here we report a chromosome-scale reference genome of wild oil-Camellia (2.95 Gb), together with transcriptome sequencing data of 221 cultivars. The oil-Camellia genome, assembled by an integrative approach of multiple sequencing technologies, consists of a large proportion of repetitive elements (76.1%) and high heterozygosity (2.52%). We construct a genetic map of high-density corrected markers by sequencing the controlled-pollination hybrids. Genome-wide association studies reveal a subset of artificially selected genes that are involved in the oil biosynthesis and phytohormone pathways. Particularly, we identify the elite alleles of genes encoding sugar-dependent triacylglycerol lipase 1 , β-ketoacyl-acyl carrier protein synthase III , and stearoyl-acyl carrier protein desaturases ; these alleles play important roles in enhancing the yield and quality of seed oil during oil-Camellia domestication. Conclusions We generate a chromosome-scale reference genome for oil-Camellia plants and demonstrate that the artificial selection of elite alleles of genes involved in oil biosynthesis contributes to oil-Camellia domestication.
A benchmark of structural variation detection by long reads through a realistic simulated model
Authors: Nicolas Dierckxsens, Tong Li, Joris R. Vermeesch, Zhi Xie
Journal: Genome biology (2021)

Accurate simulations of structural variation distributions and sequencing data are crucial for the development and benchmarking of new tools. We develop Sim-it, a straightforward tool for the simulation of both structural variation and long-read data. These simulations from Sim-it reveal the strengths and weaknesses for current available structural variation callers and long-read sequencing platforms. With these findings, we develop a new method (combiSV) that can combine the results from structural variation callers into a superior call set with increased recall and precision, which is also observed for the latest structural variation benchmark set developed by the GIAB Consortium.
Multicystic Biliary Hamartoma With Xanthogranulomatous Inflammation on 18F-FDG PET/CT
Authors: Nahomi Shono, Yoichi Otomi, Hideki Otsuka, Takayoshi Shinya, Masafumi Harada
Journal: Clinical Nuclear Medicine (2022)

Abstract A 70-year-old man with a liver tumor was pathologically diagnosed with multicystic biliary hamartoma with xanthogranulomatous inflammation. Plain CT revealed an inhomogeneous low-density liver tumor, measuring 43 × 35 mm. Dynamic contrast-enhanced CT revealed a cyst, measuring approximately 15 mm, with a ring-shaped enhancement, within the tumor. There was delayed enhancement on the outer portion of the tumor. Mild peripheral bile duct dilation was also observed. 18 F-FDG PET/CT showed focal high uptake with an SUV max of 5.2 near the cyst. The findings of this case mimicked that of intrahepatic cholangiocellular carcinoma.
COVID-19 vaccination in patients with multiple myeloma: a consensus of the European Myeloma Network
Authors: Heinz Ludwig, Pieter Sonneveld, Thierry Facon, Jesus San-Miguel, Hervé Avet-Loiseau, Mohamad Mohty, Maria-Victoria Mateos, Philippe Moreau, Michele Cavo, Charlotte Pawlyn, Sonja Zweegman, Monika Engelhardt, Christoph Driessen, Gordon Cook, Melitios A Dimopoulos, Francesca Gay, Hermann Einsele, Michel Delforge, Jo Caers, Katja Weisel, Graham Jackson, Laurent Garderet, Niels van de Donk, Xavier Leleu, Hartmut Goldschmidt, Meral Beksac, Inger Nijhof, Martin Schreder, Niels Abildgaard, Roman Hajek, Niklas Zojer, Efstathios Kastritis, Annemiek Broijl, Fredrik Schjesvold, Mario Boccadoro, Evangelos Terpos
Journal: The Lancet Haematology (2021)
18F-FES PET/CT for Characterization of Brain and Leptomeningeal Metastasis in Double Primary Cancer Patient
Authors: Yeongjoo Lee, Ie Ryung Yoo, Seunggyun Ha
Journal: Clinical Nuclear Medicine (2022)

The clinical value of 16α-18F-fluoro-17 β-estradiol (18F-FES) PET in breast cancer has been widely investigated because it can visualize estrogen receptor-expressing lesions. This relatively new radiotracer adds clinical values by characterization of metastasis in double primary cancer. It also has advantage in finding small brain lesions, which has no background brain activity. Here, we present 18F-FES PET findings of brain and leptomeningeal metastases in a patient with breast and lung malignancy.
MIF but not MIF-2 recruits inflammatory macrophages in an experimental polymicrobial sepsis model
Authors: Pathricia Veronica Tilstam, Wibke Schulte, Thomas Holowka, Bong-Sung Kim, Jessica Nouws, Maor Sauler, Marta Piecychna, Georgios Pantouris, Elias Lolis, Lin Leng, Jürgen Bernhagen, Günter Fingerle-Rowson, Richard Bucala
Journal: Journal of Clinical Investigation (2021)

Excessive inflammation drives the progression from sepsis to septic shock. Macrophage migration inhibitory factor (MIF) is of interest because MIF promoter polymorphisms predict mortality in different infections, and anti-MIF antibody improves survival in experimental models when administered 8 hours after infectious insult. The recent description of a second MIF superfamily member, D-dopachrome tautomerase (D-DT/MIF-2), prompted closer investigation of MIF-dependent responses. We subjected Mif-/- and Mif-2-/- mice to polymicrobial sepsis and observed a survival benefit with Mif but not Mif-2 deficiency. Survival was associated with reduced numbers of small peritoneal macrophages (SPMs) that, in contrast to large peritoneal macrophages (LPMs), were recruited into the peritoneal cavity. LPMs produced higher quantities of MIF than SPMs, but SPMs expressed higher levels of inflammatory cytokines and the MIF receptors CD74 and CXCR2. Adoptive transfer of WT SPMs into Mif-/- hosts reduced the protective effect of Mif deficiency in polymicrobial sepsis. Notably, MIF-2 lacks the pseudo-(E)LR motif present in MIF that mediates CXCR2 engagement and SPM migration, supporting a specific role for MIF in the recruitment and accumulation of inflammatory SPMs.
Abstract P043: A Framework For The Evaluation Of Digital Tools
Authors: Hadi Danawi, Patrick Dunn
Journal: Circulation (2022)

Digital health tools encompass a wide range of technologies that have been used in healthcare services including mobile applications, health information technology, smart wearable devices, remote monitoring and treatment, and health platforms. These tools walk a fine line between lifestyle consumer products and medical devices. Sleep applications can be used by consumers as a fun gadget to track sleep, but it may also be used as a medical tool to collect information concerning serious sleep disorders. The fast proliferation of these tools has put pressure on concerned stakeholders to make sense of this group of technologies. Various questions have been raised within this realm: What counts as medical as opposed to a lifestyle device? Which devices require regulation and under what standards? Which devices are allowed to be used in the medical context? And which are not? And under what conditions? Social scientists have highlighted the complexity of digital health tools that (include both medical and lifestyle characteristics and the difficulties accompanied with classifying these tools for regulatory purposes. In an attempt to do so, several regulatory bodies including the US Food and Drug Administration (FDA) have revised their existing standards to accommodate the regulation of digital health tools. As such, the FDA published a guidance document on Mobile Medical Applications; this led to various concerns questioning the boundaries between lifestyle and medical digital technologies that were defined by the FDA guidelines, which left a significant number of technologies that were considered to be low-risk, completely out of the FDA oversight and with no required compliance/quality control/effectiveness checks. This prompted many companies to develop hundreds of products that belong to the low-risk category, granting them the ability to ignore FDA regulations. Consequently, there remains considerable concern regarding the quality and safety of these digital health technologies that are being used within the medical context. Clear and well-defined regulation processes are needed to control the development and design of these tools, especially that many lack scientific evidence and data privacy. The framework ought to include a risk-based approach to classify devices for regulation in a way to ensure the safety and effectiveness of all digital health tools throughout their life cycle, even those classified as low-risk. The framework and regulatory process also need to take into consideration the rapid change in digital product development, as processes that extend for a long period of time may become obsolete in supporting decisions about these tools. As these digital health tools become more sophisticated, accessible, widespread, and cheaper, the need for classifying and regulating the sector becomes important, especially with the rapid evolution of these technologies.
Fasting-Mimicking Diet Is Safe and Reshapes Metabolism and Antitumor Immunity in Patients with Cancer
Authors: Claudio Vernieri, Giovanni Fucà, Francesca Ligorio, Veronica Huber, Andrea Vingiani, Fabio Iannelli, Alessandra Raimondi, Darawan Rinchai, Gianmaria Frigè, Antonino Belfiore, Luca Lalli, Claudia Chiodoni, Valeria Cancila, Federica Zanardi, Arta Ajazi, Salvatore Cortellino, Viviana Vallacchi, Paola Squarcina, Agata Cova, Samantha Pesce, Paola Frati, Raghvendra Mall, Paola Antonia Corsetto, Angela Maria Rizzo, Cristina Ferraris, Secondo Folli, Marina Chiara Garassino, Giuseppe Capri, Giulia Bianchi, Mario Paolo Colombo, Saverio Minucci, Marco Foiani, Valter Daniel Longo, Giovanni Apolone, Valter Torri, Giancarlo Pruneri, Davide Bedognetti, Licia Rivoltini, Filippo de Braud
Journal: Cancer Discovery (2021)

Abstract In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor Th1/cytotoxic responses and an enrichment of IFNγ and other immune signatures associated with better clinical outcomes in patients with cancer. Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments. Significance: Cyclic FMD is well tolerated and causes remarkable systemic metabolic changes in patients with different tumor types and treated with concomitant antitumor therapies. In addition, the FMD reshapes systemic and intratumor immunity, finally activating several antitumor immune programs. Phase II/III clinical trials are needed to investigate FMD antitumor activity/efficacy. This article is highlighted in the In This Issue feature, p. 1
UPREGULATED MONOCYTE EXPRESSION OF PLIN2 IS ASSOCIATED WITH PLAQUE INSTABILITY IN CORONARY ARTERY DISEASE
Authors: Francesco Canonico, Anna Severino, Massimiliano Camilli, Stefano Migliaro, Ramona Vinci, Mattia Galli, Eugenia Pisano, Alessandra Arcudi, Alice Bonanni, Marianna Di Sario, Astrid De Ciutiis, Sara Russo, Giulia Angelini, Daniela Pedicino, Rocco Montone, Giampaolo Niccoli, Giovanna Liuzzo, Filippo Crea, Domenico D’Amario
Journal: Journal of the American College of Cardiology (2022)
Inflammasome Activation: A Keystone of Proinflammatory Response in Obstructive Sleep Apnea
Authors: Elena Díaz-García, Sara García-Tovar, Enrique Alfaro, Ana Jaureguizar, Raquel Casitas, Begoña Sánchez-Sánchez, Ester Zamarrón, Juan Fernández-Lahera, Eduardo López-Collazo, Carolina Cubillos-Zapata, Francisco García-Río
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: As the mechanism that links obstructive sleep apnea (OSA) with the regulation of inflammatory response is not well known, it is important to understand the inflammasome activation, mainly of NLRP3 (nucleotide-binding oligomerization domain-like receptor 3). Objectives: To assess the NLRP3 activity in patients with severe OSA and to identify its role in the systemic inflammatory response of patients with OSA. Methods: We analyzed the NLRP3 activity as well as key components of the inflammasome cascade, such as adaptor molecule apoptosis-associated speck-like protein, caspase-1, Gasdermin D, IL-1β, IL-18, and tissue factor, in monocytes and plasma from patients with severe OSA and control subjects without sleep apnea. We explored the association of the different key markers with inflammatory comorbidities. Measurements and Main Results: Monocytes from patients with severe OSA presented higher NLRP3 activity than those from control subjects, which directly correlated with the apnea-hypopnea index and hypoxemic indices. NLRP3 overactivity triggered inflammatory cytokines (IL-1β and IL-18) via caspase-1 and increased Gasdermin D, allowing for tissue factor to be released. In vitro models confirmed that monocytes increase NLRP3 signaling under intermittent hypoxia in a hypoxia-inducible factor-1α-dependent manner, and/or in combination with plasma from patients with OSA. Plasma concentrations of tissue factor were higher in patients with OSA with systemic inflammatory comorbidities than in those without them. Conclusions: In patients with severe OSA, NLRP3 activation might be a linking mechanism between intermittent hypoxia and other OSA-induced immediate changes with the development of systemic inflammatory response.
Dynamics of humoral and T-cell immunity after three BNT162b2 vaccinations in adults older than 80 years
Authors: Addi J Romero-Olmedo, Axel Ronald Schulz, Svenja Hochstätter, Dennis Das Gupta, Heike Hirseland, Daniel Staudenraus, Bärbel Camara, Kirsten Volland, Véronique Hefter, Siddhesh Sapre, Verena Krähling, Helena Müller-Kräuter, Ho-Ryun Chung, Henrik E Mei, Christian Keller, Michael Lohoff
Journal: The Lancet Infectious Diseases (2022)
Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated <i>MGMT</i> promoter
Authors: Michael Lim, Michael Weller, Ahmed Idbaih, Joachim Steinbach, Gaetano Finocchiaro, Raju R Raval, George Ansstas, Joachim Baehring, Jennie W Taylor, Jerome Honnorat, Kevin Petrecca, Filip De Vos, Antje Wick, Ashley Sumrall, Solmaz Sahebjam, Ingo K Mellinghoff, Masashi Kinoshita, Mustimbo Roberts, Ruta Slepetis, Deepti Warad, David Leung, Michelle Lee, David A Reardon, Antonio Omuro
Journal: Neuro-Oncology (2022)

Abstract Background Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587). Methods Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days 1-5 of every 28-day cycle × 6)] or PBO + RT + TMZ following the same regimen. The primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients without baseline corticosteroids and in all randomized patients. Results As of December 22, 2020, median (m)PFS (blinded independent central review) was 10.6 months (95% CI, 8.9-11.8) with NIVO + RT + TMZ vs 10.3 months (95% CI, 9.7-12.5) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.3) and mOS was 28.9 months (95% CI, 24.4-31.6) vs 32.1 months (95% CI, 29.4-33.8), respectively (HR, 1.1; 95% CI, 0.9-1.3). In patients without baseline corticosteroids, mOS was 31.3 months (95% CI, 28.6-34.8) with NIVO + RT + TMZ vs 33.0 months (95% CI, 31.0-35.1) with PBO + RT + TMZ (HR, 1.1; 95% CI, 0.9-1.4). Grade 3/4 treatment-related adverse event rates were 52.4% vs 33.6%, respectively. Conclusions NIVO added to RT + TMZ did not improve survival in patients with newly diagnosed glioblastoma with methylated or indeterminate MGMT promoter. No new safety signals were observed.
Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis
Authors: Jose Dianti, Manuel Tisminetzky, Bruno L. Ferreyro, Marina Englesakis, Lorenzo Del Sorbo, Sachin Sud, Daniel Talmor, Lorenzo Ball, Maureen Meade, Carol Hodgson, Jeremy R. Beitler, Sarina Sahetya, Alistair Nichol, Eddy Fan, Bram Rochwerg, Laurent Brochard, Arthur S. Slutsky, Niall D. Ferguson, Ary Serpa Neto, Neill K. J. Adhikari, Federico Angriman, Ewan C. Goligher
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable. Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS. Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology. Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60–0.96, high certainty), the posterior probability of benefit of the esophageal pressure–guided strategy was 87% (RR, 0.77; 95% CrI, 0.48–1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67–1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89–1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04–1.81, moderate certainty). Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.
Gingival Infiltration in Acute Monocytic Leukemia
Authors: Everett Rogers, Mike Cusnir
Journal: New England Journal of Medicine (2022)

A 48-year-old woman presented with fatigue and painful, swollen, whitened gums. Her white-cell count was 225,000 per cubic millimeter, and peripheral-blood flow cytometry and bone marrow biopsy revealed 89% myeloblasts. A diagnosis of acute monocytic leukemia was made, and the gingival swelling abated with chemotherapy.
Daprodustat for the Treatment of Anemia in Patients Not Undergoing Dialysis
Authors: Ajay K. Singh, Kevin Carroll, John J.V. McMurray, Scott Solomon, Vivekanand Jha, Kirsten L. Johansen, Renato D. Lopes, Iain C. Macdougall, Gregorio T. Obrador, Sushrut S. Waikar, Christoph Wanner, David C. Wheeler, Andrzej Więcek, Allison Blackorby, Borut Cizman, Alexander R. Cobitz, Rich Davies, Tara L. DiMino, Lata Kler, Amy M. Meadowcroft, Lin Taft, Vlado Perkovic
Journal: New England Journal of Medicine (2021)

Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown.
139P KRAS-G12C NSCLC linked to female sex and high risk of CNS metastasis: Real-world data from the National Swedish Lung Cancer Registry 2016-2019
Authors: J. Isaksson, A. Berglund, K. Louie, A. Hamidian, A. Edsjö, M. Johansson, A. Hallqvist, G. Wagenius, L. Willén, J. Botling
Journal: Annals of Oncology (2022)
A 3-Part, Phase 2 Study of Bezuclastinib (CGT9486), an Oral, Selective, and Potent KIT D816V Inhibitor, in Adult Patients with Nonadvanced Systemic Mastocytosis (NonAdvSM)
Authors: Frank Siebenhaar, Jason Gotlib, Michael W. Deininger, Daniel J. DeAngelo, Francis Payumo, George Mensing, Hina Jolin, Jessica Sachs, Tracy I. George
Journal: Blood (2021)
Continued Refinement of the Treatment for Light-Chain Cardiac Amyloidosis
Authors: Justin L. Grodin, Larry D. Anderson, Ankit Kansagra
Journal: Circulation (2021)

ight chain cardiac amyloidosis (AL-CA) is a devastating disease caused by a buildup of abnormal, misfolded light chain aggregates in the myocardium.When untreated, AL-CA leads to progressive heart failure and premature death.The long-term prognosis of AL-CA is dependent on the disease stage at diagnosis and then the response to treatment.Median survival of advanced stage AL-CA at diagnosis may approximate 6 months. 1 These sobering metrics have served to motivate the detection of AL-CA in earlier stages and the continued advancements of treatment for AL-CA.
Vas Deferens and Inguinal Canal Metastasis of Prostate Cancer Revealed by 68Ga-Prostate-Specific Membrane Antigen PET/CT
Authors: Özge Erol Fenercioğlu, Göksel Alçin, Esra Arslan, Tevfik Fikret Çermik, Nurhan Ergül
Journal: Clinical Nuclear Medicine (2022)

A 71-year-old man with prostate adenocarcinoma underwent 68 Ga-prostate-specific membrane antigen (PSMA) PET/CT for staging. 68 Ga-PSMA PET/CT showed the primary lesion along with bladder, rectum, bilateral seminal vesicle invasion, and metastatic pelvic lymph nodes with intense 68 Ga-PSMA uptake. Also, PET/CT showed rarely seen bilateral vas deferens invasion and metastasis to the inguinal canal. These rare metastases may be indicative of poor biological behavior and prognosis.