tbuckley/cabot-search huggingface dataset:
Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort
Authors: Eleni Rebelos, Marco Bucci, Tomi Karjalainen, Vesa Oikonen, Alessandra Bertoldo, Jarna C. Hannukainen, Kirsi A. Virtanen, Aino Latva-Rasku, Jussi Hirvonen, Ilkka Heinonen, Riitta Parkkola, Markku Laakso, Ele Ferrannini, Patricia Iozzo, Lauri Nummenmaa, Pirjo Nuutila
Journal: Diabetes Care (2021)

OBJECTIVE Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of study participants across a wide range of age and insulin sensitivity. RESEARCH DESIGN AND METHODS [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 participants scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acid levels, C-reactive protein levels, HbA1c, and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. RESULTS Insulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin-resistant participants BGU was enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with additional increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein and free fatty acid levels, sex, and HbA1c were not associated with BGU. CONCLUSIONS In this large cohort of participants of either sex across a wide range of age and insulin sensitivity, insulin sensitivity was the best predictor of BGU.
Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response
Authors: Korneliusz Golebski, Janice A. Layhadi, Umit Sahiner, Esther H. Steveling-Klein, Madison M. Lenormand, Rachael C.Y. Li, Suzanne M. Bal, Balthasar A. Heesters, Gemma Vilà-Nadal, Oliver Hunewald, Guillem Montamat, Feng Q. He, Markus Ollert, Oleksandra Fedina, Mongkol Lao-Araya, Susanne J.H. Vijverberg, Anke-Hilse Maitland-van der Zee, Cornelis M. van Drunen, Wytske J. Fokkens, Stephen R. Durham, Hergen Spits, Mohamed H. Shamji
Journal: Immunity (2021)
MO01.27 Three-Year Follow-up of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, as Second-Line (2L) Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: L. Paz-Ares, T.M. Kim, D. Vicente, E. Felip, D.H. Lee, K.H. Lee, C.-C. Lin, M.J. Flor, M. Di Nicola, R.M. Alvarez, C. Helwig, L.S. Ojalvo, J. Gulley, B.C. Cho
Journal: Journal of Thoracic Oncology (2021)
Comparison of Out-of-Hospital Cardiac Arrests and Fatalities in the Metro Detroit Area During the COVID-19 Pandemic With Previous-Year Events
Authors: Adrienne V. Nickles, Adam Oostema, Justin Allen, Suzanne L. O’Brien, Stacie L. Demel, Mathew J. Reeves
Journal: JAMA Network Open (2021)

Stig Nikolaj Blomberg, MsC; Helle Collatz Christensen, MD, PhD; Freddy Lippert, MD; Annette Kjær Ersbøll, MsC, PhD; Christian Torp-Petersen, MD, PhD; Michael R. Sayre, MD; Peter J. Kudenchuk, MD; Fredrik Folke, MD, PhD
춘계학술대회 : 구연 ; Insulin-Like Growth Factor 2 유전자 다형성과 B형 간염 바이러스 감염 자연 치유와의 관련성
Authors: 김윤준, 윤정환, 김정룡, 김령효, 박병래, 신형두, 이효석
Journal: Clinical and Molecular Hepatology (2005)

배경/목적: 인체가 B형 간염 바이러스(HBV)의 감염에서 회복되는 기전은 감염된 간세포에 대한 세포 매개성 면역반응에 의한 것으로 추정되어 왔다. Insulinlike growth factor (IGF) II는 T 림프구의 증식에 중요한 역할을 하는 것으로 알려졌다. 이에 본 연구에서는 HBV 감염으로부터의 회복에 cytotoxic T 림프구에 의한 감염된 간세포의 파괴와 제거가 중요하다는 점에 착안하여 IGFII 생성에 영향을 줄 수 있는 유전자 다
In Search of a Better Equation — Performance and Equity in Estimates of Kidney Function
Authors: James A. Diao, Lesley A. Inker, Andrew S. Levey, Hocine Tighiouart, Neil R. Powe, Arjun K. Manrai
Journal: New England Journal of Medicine (2021)

In Search of a Better Equation Although many experts agree that we should reconsider the use of race in equations for estimated glomerular filtration rate and in medicine more generally, precisely ...
The Cxxc1 subunit of the Trithorax complex directs epigenetic licensing of CD4+ T cell differentiation
Authors: Masahiro Kiuchi, Atsushi Onodera, Kota Kokubo, Tomomi Ichikawa, Yuki Morimoto, Eiryo Kawakami, Naoya Takayama, Koji Eto, Haruhiko Koseki, Kiyoshi Hirahara, Toshinori Nakayama
Journal: The Journal of Experimental Medicine (2021)

Different dynamics of gene expression are observed during cell differentiation. In T cells, genes that are turned on early or turned off and stay off have been thoroughly studied. However, genes that are initially turned off but then turned on again after stimulation has ceased have not been defined; they are obviously important, especially in the context of acute versus chronic inflammation. Using the Th1/Th2 differentiation paradigm, we found that the Cxxc1 subunit of the Trithorax complex directs transcription of genes initially down-regulated by TCR stimulation but up-regulated again in a later phase. The late up-regulation of these genes was impaired either by prolonged TCR stimulation or Cxxc1 deficiency, which led to decreased expression of Trib3 and Klf2 in Th1 and Th2 cells, respectively. Loss of Cxxc1 resulted in enhanced pathogenicity in allergic airway inflammation in vivo. Thus, Cxxc1 plays essential roles in the establishment of a proper CD4+ T cell immune system via epigenetic control of a specific set of genes.
Incidence of Cervical Cancer in Puerto Rico, 2001-2017
Authors: Ana Patricia Ortiz, Karen J. Ortiz-Ortiz, Vivian Colón-López, Guillermo Tortolero-Luna, Carlos R. Torres-Cintrón, Chi-Fang Wu, Ashish A. Deshmukh
Journal: JAMA Oncology (2021)

Zahed Shahmoradi, PhD; Haluk Damgacioglu, PhD; Megan A. Clarke, PhD, MHS; Nicolas Wentzensen, MD, PhD; Jane Montealegre, PhD; Kalyani Sonawane, PhD; Ashish A. Deshmukh, PhD, MPH
Frequency of Bowel Movements and Risk of Diverticulitis
Authors: Manol Jovani, Wenjie Ma, Kyle Staller, Amit D. Joshi, Po-Hong Liu, Long H. Nguyen, Paul Lochhead, Yin Cao, Idy Tam, Kana Wu, Edward L. Giovannucci, Lisa L. Strate, Andrew T. Chan
Journal: Clinical Gastroenterology and Hepatology (2021)
A Comprehensive Policy Framework to Understand and Address Disparities and Discrimination in Health and Health Care: A Policy Paper From the American College of Physicians
Authors: Josh Serchen, Robert Doherty, Omar Atiq, David Hilden
Journal: Annals of Internal Medicine (2021)

Racial and ethnic minority populations in the United States experience disparities in their health and health care that arise from a combination of interacting factors, including racism and discrimination, social drivers of health, health care access and quality, individual behavior, and biology. To ameliorate these disparities, the American College of Physicians (ACP) proposes a comprehensive policy framework that recognizes and confronts the many elements of U.S. society, some of which are intertwined and compounding, that contribute to poorer health outcomes. In addition to this framework, which includes high-level principles and discusses how disparities are interconnected, ACP offers specific policy recommendations on disparities and discrimination in education and the workforce, those affecting specific populations, and those in criminal justice practices and policies in its 3 companion policy papers. ACP believes that a cross-cutting approach that identifies and offers solutions to the various aspects of society contributing to poor health is essential to achieving its goal of good health care for all, poor health care for none.
Differences in TCR repertoire and T cell activation underlie the divergent outcomes of antitumor immune responses in tumor-eradicating versus tumor-progressing hosts
Authors: Rachel A Woolaver, Xiaoguang Wang, Alexandra L Krinsky, Brittany C Waschke, Samantha M Y Chen, Vince Popolizio, Andrew G Nicklawsky, Dexiang Gao, Zhangguo Chen, Antonio Jimeno, Xiao-Jing Wang, Jing Hong Wang
Journal: Journal for ImmunoTherapy of Cancer (2021)

Antitumor immunity is highly heterogeneous between individuals; however, underlying mechanisms remain elusive, despite their potential to improve personalized cancer immunotherapy. Head and neck squamous cell carcinomas (HNSCCs) vary significantly in immune infiltration and therapeutic responses between patients, demanding a mouse model with appropriate heterogeneity to investigate mechanistic differences. We developed a unique HNSCC mouse model to investigate underlying mechanisms of heterogeneous antitumor immunity. This model system may provide a better control for tumor-intrinsic and host-genetic variables, thereby uncovering the contribution of the adaptive immunity to tumor eradication. We employed single-cell T-cell receptor (TCR) sequencing coupled with single-cell RNA sequencing to identify the difference in TCR repertoire of CD8 tumor-infiltrating lymphocytes (TILs) and the unique activation states linked with different TCR clonotypes. We discovered that genetically identical wild-type recipient mice responded heterogeneously to the same squamous cell carcinoma tumors orthotopically transplanted into the buccal mucosa. While tumors initially grew in 100% of recipients and most developed aggressive tumors, ~25% of recipients reproducibly eradicated tumors without intervention. Heterogeneous antitumor responses were dependent on CD8 T cells. Consistently, CD8 TILs in regressing tumors were significantly increased and more activated. Single-cell TCR-sequencing revealed that CD8 TILs from both growing and regressing tumors displayed evidence of clonal expansion compared with splenic controls. However, top TCR clonotypes and TCR specificity groups appear to be mutually exclusive between regressing and growing TILs. Furthermore, many TCRα/TCRβ sequences only occur in one recipient. By coupling single-cell transcriptomic analysis with unique TCR clonotypes, we found that top TCR clonotypes clustered in distinct activation states in regressing versus growing TILs. Intriguingly, the few TCR clonotypes shared between regressors and progressors differed greatly in their activation states, suggesting a more dominant influence from tumor microenvironment than TCR itself on T cell activation status. We reveal that intrinsic differences in the TCR repertoire of TILs and their different transcriptional trajectories may underlie the heterogeneous antitumor immune responses in different hosts. We suggest that antitumor immune responses are highly individualized and different hosts employ different TCR specificities against the same tumors, which may have important implications for developing personalized cancer immunotherapy.
Role of dietary fiber in the recovery of the human gut microbiome and its metabolome
Authors: Ceylan Tanes, Kyle Bittinger, Yuan Gao, Elliot S. Friedman, Lisa Nessel, Unmesha Roy Paladhi, Lillian Chau, Erika Panfen, Michael A. Fischbach, Jonathan Braun, Ramnik J. Xavier, Clary B. Clish, Hongzhe Li, Frederic D. Bushman, James D. Lewis, Gary D. Wu
Journal: Cell Host & Microbe (2021)
Injury and illness epidemiology in professional Asian football: lower general incidence and burden but higher ACL and hamstring injury burden compared with Europe
Authors: Montassar Tabben, Cristiano Eirale, Gurcharan Singh, Abdulaziz Al-Kuwari, Jan Ekstrand, Hakim Chalabi, Roald Bahr, Karim Chamari
Journal: British Journal of Sports Medicine (2021)

While football injury and illness epidemiology surveillance at professional club level in Europe is available, epidemiological data from other continents are lacking.Investigating injury and illness epidemiology in professional Asian football.Descriptive prospective study.Professional teams from the Asian Football Confederation (AFC) league were followed prospectively for three consecutive AFC seasons (2017 through 2019, 13 teams per season, 322 team months). Time-loss injuries and illnesses in addition to individual match and training exposure were recorded using standardised digital tools in accordance with international consensus procedures.In total, 232 665 hours of exposure (88.6% training and 11.4% matches) and 1159 injuries were recorded; 496 (42.8%) occurred during matches, 610 (52.6%) during training; 32 (2.8%) were reported as 'not applicable' and for 21 injuries (1.8%) information was missing. Injury incidence was significantly greater during match play (19.2±8.6 injuries per 1000 hours) than training (2.8±1.4, p<0.0001), resulting in a low overall incidence of 5.1±2.2.The injury burden for match injuries was greater than from training injuries (456±336 days per 1000 hours vs 54±34 days, p<0.0001). The two specific injuries causing the greatest burden were complete ACL ruptures (0.14 injuries (95% CI 0.9 to 0.19) and 29.8 days lost (29.1 to 30.5) per 1000 hours) and hamstring strains (0.86 injuries (0.74 to 0.99) and 17.5 days (17.0 to 18.1) lost per 1000 hours).Reinjuries constituted 9.9% of all injuries. Index injuries caused 22.6±40.8 days of absence compared with 25.1±39 for reinjuries (p=0.62). The 175 illnesses recorded resulted in 1.4±2.9 days of time loss per team per month.Professional Asian football is characterised by an overall injury incidence similar to that reported from Europe, but with a high rate of ACL ruptures and hamstring injury, warranting further investigations.
A Colon‐Targeted Oral Probiotics Delivery System Using an Enzyme‐Triggered Fuse‐Like Microcapsule
Authors: Qikun Cheng, Lu Liu, Mingzhi Xie, Hang Li, Dong Ma, Wei Xue
Journal: Advanced Healthcare Materials (2021)

Abstract Probiotics are closely related to human health. However, it is hard to find an appropriate disintegration mode for encapsulation to balance the survival, release, and adhesion of probiotics simultaneously during the current colon‐targeted oral delivery, which leads to limited colonization. In this study, an enzyme‐triggered fuse‐like microcapsule is constructed using alginate and protamine via the electrostatic droplet combined with the layer by layer self‐assembly. The multilayer microcapsule can protect the probiotics in the stomach and disintegrate layer by layer under the catalysis of trypsin in the intestine. The formulation with two protamine layers showed the best protection for Escherichia coli MG1655 (EM) during the oral delivery; as well the minimal release at the gastric pH value but a burst release after 1 h at the intestinal pH value. In particular, the adhesion strength of EM is improved with the increase of the layer number. In vivo experiments demonstrate that the EM enters into the stationary phase within 12 h in the colon. Moreover, the blood biochemistry and histological analysis demonstrates the safety of the microcapsule formulation. It can be concluded that this microcapsule can help the probiotics survive during the delivery, then release and colonize in the colon.
Feasibility and Techniques of Securing 3D-Safety Margin in Superselective Transarterial Chemoembolization to Improve Local Tumor Control for Small Hepatocellular Carcinoma: An Intend-to-Treat Analysis
Authors: Ching Charoenvisal, Toshihiro Tanaka, Hideyuki Nishiofuku, Hiroshi Anai, Takeshi Sato, Takeshi Matsumoto, Nagaaki Marugami, Kimihiko Kichikawa
Journal: Liver Cancer (2021)

The aim of this study was to investigate the technical success rate of obtaining 3D-safety margin in superselective conventional transarterial chemoembolization (cTACE) using 3D images for small hepatocellular carcinoma (HCC).Consecutive 48 HCC nodules (diameter, 1-3 cm) in 44 patients were intentionally treated by superselective cTACE in an attempt to achieve 3D-safety margin. Superselective CT during hepatic arteriography (CTHA) was obtained before cTACE. When negative 3D-safety margin was found, branches supplied into the margin area were detected by using a 3D workstation. The technical success rate to obtain 3D-safety margin was investigated by intend-to-treat analysis. Local tumor recurrence rate and adverse events were also evaluated.Nine of 48 tumors (18.8%) had 3D-safety margin in the initial superselective CTHA. After pulling back of the catheter and/or selection of another branch based on 3D images, 3D-safety margin was finally achieved in 45 (93.8%). There were 8 of 46 tumors (17.4%) with local recurrence after 5-year follow-up. Grade 3-4 of aspartate aminotransferase, alanine aminotransferase, and total bilirubin were found in 38.6, 36.4, and 2.3%, respectively. One portal vein thrombus and 3 biliary dilation or biloma were developed.Superselective cTACE obtaining 3D-safety margin in small HCC was feasible with a high success rate by using 3D images, which could be tolerable and prevent local tumor recurrence.
Adjunctive treatment with oral dexamethasone in non-ICU patients hospitalised with community-acquired pneumonia: a randomised clinical trial
Authors: Esther Wittermans, Stefan M.T. Vestjens, Simone M.C. Spoorenberg, Willem L. Blok, Jan C. Grutters, Rob Janssen, Ger T. Rijkers, Frank W.J.M. Smeenk, G. Paul Voorn, Ewoudt M.W. van de Garde, Willem Jan W. Bos
Journal: European Respiratory Journal (2021)

Background Adjunctive intravenous corticosteroid treatment has been shown to reduce length of stay (LOS) in adults hospitalised with community-acquired pneumonia (CAP). We aimed to assess the effect of oral dexamethasone on LOS and whether this effect is disease severity dependent. Methods In this multicentre, stratified randomised, double-blind, placebo-controlled trial, immunocompetent adults with CAP were randomly assigned (1:1 ratio) to receive oral dexamethasone (6 mg once daily) or placebo for 4 days in four teaching hospitals in the Netherlands. Randomisation (blocks of four) was stratified by CAP severity (pneumonia severity index class I–III and IV–V). The primary outcome was LOS. Results Between December 2012 and November 2018, 401 patients were randomised to receive dexamethasone (n=203) or placebo (n=198). Median LOS was shorter in the dexamethasone group (4.5 days, 95% CI 4.0–5.0 days) than in the placebo group (5.0 days, 95% CI 4.6–5.4 days; p=0.033). Within both CAP severity subgroups, differences in LOS between treatment groups were not statistically significant. The secondary ICU admission rate was lower in the dexamethasone arm (5 (3%) versus 14 (7%); p=0.030); 30-day mortality did not differ between groups. In the dexamethasone group the rate of hospital readmission tended to be higher (20 (10%) versus 9 (5%); p=0.051) and hyperglycaemia (14 (7%) versus 1 (1%); p=0.001) was more prevalent. Conclusion Oral dexamethasone reduced LOS and ICU admission rate in adults hospitalised with CAP. It remains unclear for which patients the risk–benefit ratio is optimal.
Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation
Authors: Jan Dudeck, Johanna Kotrba, Roland Immler, Aaron Hoffmann, Martin Voss, Vasileia Ismini Alexaki, Lorena Morton, Stephan René Jahn, Konstantinos Katsoulis-Dimitriou, Simon Winzer, Georg Kollias, Thomas Fischer, Sergei A. Nedospasov, Ildiko Rita Dunay, Triantafyllos Chavakis, Andreas J. Müller, Burkhart Schraven, Markus Sperandio, Anne Dudeck
Journal: Immunity (2021)
Estrogen receptor binding and bioactivity of tamoxifen, active tamoxifen metabolites and their glucuronides
Authors: Yan Zheng, Arun Sharma, Philip Lazarus
Journal: Cancer Research (2008)

4804  Tamoxifen (TAM), (1-[4-(2-dimethylaminoethoxy)-phenyl]-1,2-diphenylbut-1-(Z)-ene), is a non-steroidal anti-estrogen that has been commonly used for the prevention and treatment of estrogen receptor-positive breast cancer. TAM and the active metabolites of TAM including 4-hydroxy-TAM and endoxifen are subjected to conjugation with glucuronic acid and excretion via the biliary system. Although the loss of anti-estrogenic activity of glucuronides of both 4-OH-TAM and endoxifen has been reported, studies examining the mechanism of this loss of activity have not been previously performed. In the present study, the estrogen receptor (ER) binding affinity for glucuronides of TAM and active TAM metabolites were determined by in vitro competitive binding assay and their anti-estrogenic properties were further evaluated by 17β-estradiol (E2)-induced MCF-7 cell proliferation as compared to their unconjugated counterparts. Both trans-4-OH-TAM and trans-endoxifen exhibited significantly higher relative binding affinity (RBA) for ER-alpha (RBA=195 and 158, respectively) than their respective cis isomers (RBA = 2.9 for cis-4-OH-TAM and 4.5 for cis-endoxifen; p
Addiction and the kynurenine pathway: A new dancing couple?
Authors: Nuria Morales-Puerto, Pablo Giménez-Gómez, Mercedes Pérez-Hernández, Cristina Abuin-Martínez, Leticia Gil de Biedma-Elduayen, Rebeca Vidal, María Dolores Gutiérrez-López, Esther O'Shea, María Isabel Colado
Journal: Pharmacology & Therapeutics (2021)
Covid-19: Biden calls for science, vaccines, and masks
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

President elect Joe Biden has said he would rely on science, the broad distribution of vaccines, and increased mask wearing to tackle covid-19. His presidency will begin on Wednesday 20 January.

“Science will always be at the forefront of my administration,” he said.1

He promised 100 million vaccinations within his first 100 days in office and asked Americans to wear masks on federal properties and during interstate travel during that time.

Biden had proposed releasing the vaccine supplies held back by the federal government to use as second doses, and President Donald Trump has released the supplies. State governors discovered there were no stored vaccines. Biden’s team said that new doses from pharmaceutical manufacturers should fill the need.

Last week …
Delivery of eupenifeldin via polymer-coated surgical buttresses prevents local lung cancer recurrence
Authors: Zeinab Y. Al Subeh, Ngoc-Quynh Chu, Jeremy T. Korunes-Miller, Lillian L. Tsai, Tyler N. Graf, Yin P. Hung, Cedric J. Pearce, Mark W. Grinstaff, Aaron H. Colby, Yolonda L. Colson, Nicholas H. Oberlies
Journal: Journal of Controlled Release (2021)