tbuckley/cabot-search huggingface dataset:
Baseline Liver Function and Subsequent Outcomes in the Phase 3 REFLECT Study of Patients with Unresectable Hepatocellular Carcinoma
Authors: Arndt Vogel, Catherine Frenette, Max Sung, Bruno Daniele, Ari Baron, Stephen L. Chan, Jean Frédéric Blanc, Toshiyuki Tamai, Min Ren, Howard J. Lim, Daniel H. Palmer, Yuko Takami, Masatoshi Kudo
Journal: Liver Cancer (2021)

Baseline liver function among patients starting treatment for unresectable hepatocellular carcinoma (uHCC) impacts survival and could impact efficacy outcomes and safety profiles of treatments. This post hoc analysis of the phase 3 REFLECT study examined the efficacy and safety outcomes for lenvatinib and for sorafenib in patients with uHCC, assessed by Child-Pugh score (CPS) and albumin-bilirubin (ALBI) grade.Efficacy and safety were assessed in patient cohorts from REFLECT according to study entry baseline ALBI grade and CPS.Lenvatinib treatment generally provided survival benefits in all groups. Median overall survival (OS) among patients with an ALBI grade of 1 was consistently higher than among patients with an ALBI grade of 2 for both the lenvatinib and sorafenib arms (lenvatinib: 17.4 vs. 8.6 months; sorafenib: 14.6 vs. 7.7 months, respectively). Median OS among patients with a CPS of 5 was consistently higher than among patients with a CPS of 6 (lenvatinib: 15.3 vs. 9.4 months; sorafenib: 14.2 vs. 7.9 months, respectively). Progression-free survival and objective response rates for these ALBI grades and CPS demonstrated similar patterns. Among patients who received lenvatinib and experienced a treatment-related treatment-emergent adverse event leading to withdrawal, 6.6% had an ALBI grade of 1, while 13.3% had an ALBI grade of 2, and 7.9% had a CPS of 5, while 12.1% had a CPS of 6.Better liver function at baseline, as measured by ALBI grade or CPS, may be prognostic for better survival outcomes in patients with uHCC undergoing treatment with lenvatinib or sorafenib.
Quality of life among people living with HIV in England and the Netherlands: a population-based study
Authors: Stephanie Popping, Meaghan Kall, Brooke E. Nichols, Evelien Stempher, Lisbeth Versteegh, David. A.M.C. van de Vijver, Ard van Sighem, M. Versteegh, Charles Boucher, Valerie Delpech, Annelies Verbon
Journal: The Lancet Regional Health - Europe (2021)

HIV is now considered a chronic condition, and people living with HIV, when treated, have a similar life expectancy as compared to the general population. Consequently, improving and ensuring a good health-related quality of life (HrQoL) among people living with HIV (people living with HIV) is increasingly important and has risen on the global agenda in recent years. A 'fourth 90' as 90% of people with viral load suppression have a good HrQoL should therefore be adopted alongside the other 90-90-90 targets. This study aims to report the progress on HrQoL as the 'fourth 90' and compare against the general population in the Netherlands and England.In the Netherlands, individuals attending the HIV outpatient clinic of a tertiary hospital were asked to complete the EQ-5D-5L from June 2016 until December 2018. In England, individuals attending one of 73 HIV outpatient clinics were randomly sampled to complete the Positive Voices survey, which included the EQ-5D-5L, from January to September 2017. HrQoL scores were combined with demographic data and compared to general population data.The EQ-5D-5L was filled-out by 895 people living with HIV in the NL and 4,137 in England. HrQoLutility was 0·85 among Dutch and 0·83 among English people living with HIV. This equated to 98% and 94% of the general population HrQoLutility in the Netherlands and England, respectively. Of the EQ-5D domains, anxiety/depression was mostly affected, with one-third in Dutch (35%) and almost half (47%) of English people living with HIV reporting symptoms. This was higher compared to their respective general populations (21% NL and 31% England).Overall, HrQoLutility for people living with HIV was high in both countries and highly comparable to the general populations Nevertheless, there should be an increased focus on anxiety and depression in the people living with HIV population The EQ-5D-5L proved an easy HrQoL measurement tool and identified areas for improvement by social and behavioural interventions.The study received funding (unrestricted grants) from: Gilead sciences, ViiV Healthcare, MSD, and Jansen pharmaceuticals.
MO13-5 Clinical features and prognosis of patients with unresectable locally advanced or metastatic olfactory neuroblastoma
Authors: Haruhi Furukawa, Emi Noguchi, Tatsunori Shimoi, Yohei Chiba, Shu Yazaki, Toshihiro Okuya, Yuki Kojima, Hitomi Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Kan Yonemori
Journal: Annals of Oncology (2021)
P51-3 Examination of CARG toxicity scores in palbociclib therapy for elderly patients with breast cancer
Authors: Ai Amioka, Kaoru Kidate, Rintaro Ito, Naoki Murao, Aki Kuwada, Akira Nakashima, Ryutaro Sakabe, Koh Tahara, Hiroshi Hotei
Journal: Annals of Oncology (2021)
AIM2 regulates anti-tumor immunity and is a viable therapeutic target for melanoma
Authors: Keitaro Fukuda, Ken Okamura, Rebecca L. Riding, Xueli Fan, Khashayar Afshari, Nazgol-Sadat Haddadi, Sean M. McCauley, Mehmet H. Guney, Jeremy Luban, Takeru Funakoshi, Tomonori Yaguchi, Yutaka Kawakami, Anastasia Khvorova, Katherine A. Fitzgerald, John E. Harris
Journal: The Journal of Experimental Medicine (2021)

The STING and absent in melanoma 2 (AIM2) pathways are activated by the presence of cytosolic DNA, and STING agonists enhance immunotherapeutic responses. Here, we show that dendritic cell (DC) expression of AIM2 within human melanoma correlates with poor prognosis and, in contrast to STING, AIM2 exerts an immunosuppressive effect within the melanoma microenvironment. Vaccination with AIM2-deficient DCs improves the efficacy of both adoptive T cell therapy and anti–PD-1 immunotherapy for “cold tumors,” which exhibit poor therapeutic responses. This effect did not depend on prolonged survival of vaccinated DCs, but on tumor-derived DNA that activates STING-dependent type I IFN secretion and subsequent production of CXCL10 to recruit CD8+ T cells. Additionally, loss of AIM2-dependent IL-1β and IL-18 processing enhanced the treatment response further by limiting the recruitment of regulatory T cells. Finally, AIM2 siRNA-treated mouse DCs in vivo and human DCs in vitro enhanced similar anti-tumor immune responses. Thus, targeting AIM2 in tumor-infiltrating DCs is a promising new treatment strategy for melanoma.
ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses
Authors: Anna-Maria Herzner, Zia Khan, Eric L. Van Nostrand, Sara Chan, Trinna Cuellar, Ronald Chen, Ximo Pechuan-Jorge, Laszlo Komuves, Margaret Solon, Zora Modrusan, Benjamin Haley, Gene W. Yeo, Timothy W. Behrens, Matthew L. Albert
Journal: The Journal of Experimental Medicine (2021)

Cytosolic double-stranded RNA (dsRNA) initiates type I IFN responses. Endogenous retroelements, notably Alu elements, constitute a source of dsRNA. Adenosine-to-inosine (A-to-I) editing by ADAR induces mismatches in dsRNA and prevents recognition by MDA5 and autoinflammation. To identify additional endogenous dsRNA checkpoints, we conducted a candidate screen in THP-1 monocytes and found that hnRNPC and ADAR deficiency resulted in synergistic induction of MDA5-dependent IFN responses. RNA-seq analysis demonstrated dysregulation of Alu-containing introns in hnRNPC-deficient cells via utilization of unmasked cryptic splice sites, including introns containing ADAR-dependent A-to-I editing clusters. These putative MDA5 ligands showed reduced editing in the absence of ADAR, providing a plausible mechanism for the combined effects of hnRNPC and ADAR. This study contributes to our understanding of the control of repetitive element–induced autoinflammation and suggests that patients with hnRNPC-mutated tumors might maximally benefit from ADAR inhibition-based immunotherapy.
Anti-tumor immunity in mismatch repair-deficient colorectal cancers requires type I IFN–driven CCL5 and CXCL10
Authors: Courtney Mowat, Shayla R. Mosley, Afshin Namdar, Daniel Schiller, Kristi Baker
Journal: The Journal of Experimental Medicine (2021)

Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8+ tumor-infiltrating lymphocytes (TILs) responding to the abundant neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment of CD8+ T cells into the tumors, implying that this is an essential prerequisite of successful dMMR anti-tumor immunity. We have discovered that selective recruitment and activation of systemic CD8+ T cells into dMMR CRCs strictly depend on overexpression of CCL5 and CXCL10 due to endogenous activation of cGAS/STING and type I IFN signaling by damaged DNA. TIL infiltration into orthotopic dMMR CRCs is neoantigen-independent and followed by induction of a resident memory-like phenotype key to the anti-tumor response. CCL5 and CXCL10 could be up-regulated by common chemotherapies in all CRCs, indicating that facilitating CD8+ T cell recruitment underlies their efficacy. Induction of CCL5 and CXCL10 thus represents a tractable therapeutic strategy to induce TIL recruitment into CRCs, where local priming can be maximized even in neoantigen-poor CRCs.
Age-related differences in patch testing results among children: Analysis of North American Contact Dermatitis Group Data, 2001-2018
Authors: Jonathan I. Silverberg, Alexander Hou, Erin M. Warshaw, Joel G. DeKoven, Howard I. Maibach, Donald V. Belsito, Kathryn A. Zug, James S. Taylor, Denis Sasseville, Cory A. Dunnick, Marie-Claude Houle, Amber R. Atwater, Margo J. Reeder, Vincent A. DeLeo, Melanie D. Pratt, Joseph F. Fowler, Matthew J. Zirwas, James G. Marks
Journal: Journal of the American Academy of Dermatology (2021)
Could Sodium/Glucose Co-Transporter-2 Inhibitors Have Antiarrhythmic Potential in Atrial Fibrillation? Literature Review and Future Considerations
Authors: Dimitrios A. Vrachatis, Konstantinos A. Papathanasiou, Konstantinos E. Iliodromitis, Sotiria G. Giotaki, Charalampos Kossyvakis, Konstantinos Raisakis, Andreas Kaoukis, Vaia Lambadiari, Dimitrios Avramides, Bernhard Reimers, Giulio G. Stefanini, Michael Cleman, Georgios Giannopoulos, Alexandra Lansky, Spyridon G. Deftereos
Journal: Drugs (2021)
Safety Evaluation of the Second Dose of Messenger RNA COVID-19 Vaccines in Patients With Immediate Reactions to the First Dose
Authors: Matthew S. Krantz, Jason H. Kwah, Cosby A. Stone, Elizabeth J. Phillips, Gilbert Ortega, Aleena Banerji, Kimberly G. Blumenthal
Journal: JAMA Internal Medicine (2021)

5%; 95% CI, 4%-6%; low/moderate, 7%; 95% CI, 6%-9%; high, 11%; 95% CI, 7%-15%), anxiolytics/sedatives (no loneliness, 9%; 95% CI, 7%-10%; low/moderate, 12%; 95% CI, 10%-14%; high, 20%; 95% CI, 15%-25%), antidepressants (no loneliness, 14%; 95% CI, 12%-16%; low/moderate, 19%; 95% CI, 16%-21%; high, 27%; 95% CI, 21%-33%), and polypharmacy (no loneliness, 41%; 95% CI, 38%-43%; low/moderate, 44%; 95% CI, 41%-47%; high, 50%; 95% CI, 44%-56%) (Figure ), and there was a nonsignificant trend for opioid use (no loneliness: 7%; 95% CI, 5%-8%; low/moderate, 7%; 95% CI, 6%-9%; high, 10%; 95% CI, 6%
Covid 19: More US institutes, universities, and businesses make masks mandatory as cases rise sharply
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

President Joe Biden is expected to announce on 29 July a requirement for federal government employees to be vaccinated or to be regularly tested for SARS-CoV-2 as the nation faces a surge in cases of the delta variant. Until now the president has hesitated to make vaccination mandatory because of opposition from conservatives, including many Republicans.

The Centers for Disease Control and Prevention said on 27 July that everyone, even fully vaccinated people, should wear masks in indoor spaces in hotspot areas for the virus. The CDC also called for children and teachers to wear masks when schools reopen. It said there was evidence that fully vaccinated people could nevertheless be infected with the highly transmissible delta virus and could …
Translation from bats to humans beyond infectious diseases
Authors: Matae Ahn, Lin-Fa Wang
Journal: The Journal of Experimental Medicine (2021)

Bats are attracting the greatest attention recently as a putative reservoir of SARS-CoV-2 responsible for the COVID-19 pandemic. However, less known to the public, bats also have several unique traits of high value to human health. The lessons we learn from bats can potentially help us fight many human diseases, including infection, aging, and cancer.
Covid-19: Pfizer vaccine’s efficacy declined from 96% to 84% four months after second dose, company reports
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Pfizer vaccine's efficacy declined from 96% to 84% four months after second dose, company reports Elisabeth MahaseThe Pfizer-BioNTech vaccine's efficacy against SARS-CoV-2 peaked at 96.2% at seven days to two months after the second dose and then declined to 83.7% at four months, a preprint from Pfizer has reported. 1 The preprint, which contains the latest data from the original clinical trial, found an average decline in vaccine efficacy of 6% every two months.Researchers have said that trials to evaluate the efficacy of booster trials after a longer interval are under way.A booster vaccine in England is expected to be rolled out to the people most vulnerable to covid-19 from September. 2 Around 44 000 people aged over 16 were recruited to the clinical trials from July to October 2020, including participants from the US, Argentina, Brazil, South Africa, Germany, and Turkey.Of these, half were given the Pfizer vaccine and half were given the placebo, a saline solution.The study also included around 2200 participants aged 12 to 15 at 29 US sites, recruited from October 2020 to January 2021, who were also randomly allocated 1:1 to receive the vaccine or placebo.The preprint said that from seven days after the second dose 86-100% efficacy was observed across diverse demographic profiles, including age, sex, race/ethnicity, and factors increasing the risk from covid-19, such as high body mass index and other comorbidities.The vaccine was reported as highly efficacious in various geographical regions including North America, Europe, South Africa, and Latin America.
Reducing Racial and Ethnic Disparities in Health Care
Authors: Robert Steinbrook
Journal: JAMA Internal Medicine (2021)

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Prevalence of Clonal Hematopoiesis and Mutation Patterns in Unexplained Anemia of Community-Dwelling Elderly Individuals: A Case-Control Study
Authors: Luca Malcovati, Anna Gallì, Cinzia F Sala, Ettore Rizzo, Elisabetta Molteni, Silvia Zibellini, Eulalia Catamo, Erica Travaglino, Silvia Catricalà, Chiara Elena, Gabriele Todisco, Elisa Bono, Antonio Bianchessi, Virginia Valeria Ferretti, Paolo Gasparini, Clara Camaschella, Daniela Toniolo, Mario Cazzola
Journal: Blood (2017)
Duration of Diabetes and Incident Heart Failure
Authors: Justin B Echouffo-Tcheugui, Sui Zhang, Roberta Florido, Carine Hamo, James S Pankow, Erin D Michos, Ronald B Goldberg, Vijay Nambi, Gary Gerstenblith, Wendy S Post, Roger S Blumenthal, Christie M Ballantyne, Josef Coresh, Elizabeth Selvin, Chiadi E Ndumele
Journal: JACC Heart Failure (2021)
Abstract 14916: Difference of Neointimal Growth Patterns in Bifurcation Lesion among 4 Kinds of Drug-Eluting Stents : Optical Coherence Tomography Study.
Authors: Takahiro Yoshimura, Masami Nishino, Naotaka Okamoto, Akihiro Tanaka, Atsushi Kikuchi, Takeshi Masaki, Naoki Mori, Daisuke Nakamura, Yasuharu Lee, Masayuki Taniike, Nobuhiko Makino, Hiroyasu Kato, Yasuyuki Egami, Ryu Shutta, Hisaki Morita, Jun Tanouchi, Yoshio Yamada
Journal: Circulation (2011)

Background: The bifurcation lesion is a one of major risk factors for stent thrombosis, but the detailed evaluation of neointimal formation at bifurcation lesion after implantation of drug-eluting ...
MO29-2 Osimertinib for RT-naïve CNS metastasis of EGFRm NSCLC: pll OCEAN study (LOGIK 1603/WJOG 9116L), part of T790M cohort
Authors: Kenji Chibana, Hiroyuki Yamaguchi, Kazushige Wakuda, Minoru Fukuda, Hirotsugu Kenmotsu, Kenichi Yoshimura, Koji Inoue, Satoru Miura, Kazuhiko Nakagawa, Nobuyuki Yamamoto, Kenji Sugio
Journal: Annals of Oncology (2021)
Rectally shed SARS-CoV-2 lacks infectivity: time to rethink faecal–oral transmission?
Authors: Rune M. Pedersen, Ditte S. Tornby, Line L. Bang, Lone W. Madsen, Marianne N. Skov, Thøger G. Jensen, Isik S. Johansen, Thomas E. Andersen
Journal: Nature Reviews Gastroenterology & Hepatology (2021)
Exploration of Identity-Based Bullying by Race/Ethnicity and Other Marginalized Identities Among Adolescents
Authors: Sandra Graham
Journal: JAMA Network Open (2021)

Chardée A. Galán, PhD; Lynissa R. Stokes, PhD; Nicholas Szoko, MD; Kaleab Z. Abebe, PhD; Alison J. Culyba, MD, PhD, MPH
Effect of cytisine vs varenicline on smoking cessation: A randomized clinical trial
Authors: RJ Courtney, H McRobbie, P Tutka, NA Weaver, CP Mendelsohn, A Shakeshaft, S Talukder, C Macdonald, D Thomas, Bch Kwan, N Walker, C Gartner, RP Mattick, C Paul, SG Ferguson, NA Zwar, RL Richmond, CM Doran, VC Boland, W Hall, R West, M Farrell
Journal: JAMA Network Open (2021)

IMPORTANCE: Cytisine is more effective than placebo and nicotine replacement therapy for
smoking cessation. However, cytisine has not been tested against the most effective smoking
cessation medication, varenicline, which is associated with adverse events known to lead to
discontinuation of therapy.  OBJECTIVE: To examine whether standard cytisine treatment (25 days) was at least as
effective as standard varenicline treatment (84 days) for smoking cessation.  DESIGN, SETTING, AND PARTICIPANTS: This noninferiority, open-label randomized clinical trial
with allocation concealment and blinded outcome assessment was undertaken in Australia
from November 2017 through May 2019; follow-up was completed in January 2020. A total
of 1452 Australian adult daily smokers willing to make a quit attempt were included. Data
collection was conducted primarily by computer-assisted telephone interview, but there was
an in-person visit to validate the primary outcome.  INTERVENTIONS: Treatments were provided in accordance with the manufacturers’
recommended dosage: cytisine (n = 725), 1.5-mg capsules taken 6 times daily initially then
gradually reduced over the 25-day course; varenicline (n = 727), 0.5-mg tablets titrated to
1 mg twice daily for 84 days (12 weeks). All participants were offered referral to standard
telephone behavioral support.  MAIN OUTCOMES AND MEASURES: The primary outcome was 6-month continuous abstinence
verified using a carbon monoxide breath test at 7-month follow-up. The noninferiority margin
was set at 5% and the 1-sided significance threshold was set at .025.  RESULTS: Among 1452 participants who were randomized (mean [SD] age, 42.9 [12.7] years;
742 [51.1%] women), 1108 (76.3%) completed the trial. Verified 6-month continuous
abstinence rates were 11.7% for the cytisine group and 13.3% for the varenicline group (risk
difference, −1.62% [1-sided 97.5% CI, −5.02% to ]; P = .03 for noninferiority). Self-reported
adverse events occurred less frequently in the cytisine group (997 events among 482
participants) compared with the varenicline group (1206 events among 510 participants) and
the incident rate ratio was 0.88 (95% CI, 0.81 to 0.95; P = .002).  CONCLUSIONS AND RELEVANCE: Among daily smokers willing to quit, cytisine treatment for 25
days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority
regarding smoking cessation.
Covid-19: Daily testing of schoolchildren does not lead to substantial increase in cases, preliminary data show
Authors: Ingrid Torjesen
Journal: BMJ (2021)

Daily testing of secondary school pupils who have been exposed to a positive covid-19 case does not lead to a substantial rise in the number of covid-19 cases and could reduce covid related absences by as much as 39%, a pilot study shows.1

The Daily Contact Testing in Schools trial, funded by the Department of Health and Social Care and supported by the Department for Education and the Office for National Statistics, was set up to investigate whether daily testing was as safe as sending close contacts home to isolate and whether it would reduce absences. It is led by Tim Peto, professor of medicine at the University of Oxford.

The non-inferiority trial’s protocol specified that a relative increase in transmission of up to 50% was acceptable. The researchers concluded that they were 97.5% confident that, on the basis of participation rates in the trial, any increase in the rate of symptomatic infection in the intervention arm did not exceed 22% more than in the control arm, and if all people eligible to participate …
PD1-1-5 Frequency of immune-related adverse events of immune-checkpoint inhibitors for non-small cell lung cancer in our single institution
Authors: Kenichi Chikamori, Toshiaki Utsunomiya, Keisuke Aoe, Ryo Suetake, Kosuke Ito, Hisayuki Osoreda, Akihiko Ikeda, Maeda Tadashi, Haruhito Kamei
Journal: Annals of Oncology (2021)
Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder
Authors: Mitchell G Miglis, Charles H Adler, Elena Antelmi, Dario Arnaldi, Luca Baldelli, Bradley F Boeve, Matteo Cesari, Irene Dall'Antonia, Nico J Diederich, Kathrin Doppler, Petr Dušek, Raffaele Ferri, Jean-François Gagnon, Ziv Gan-Or, Wiebke Hermann, Birgit Högl, Michele T Hu, Alex Iranzo, Annette Janzen, Anastasia Kuzkina, Jee-Young Lee, Klaus L Leenders, Simon J G Lewis, Claudio Liguori, Jun Liu, Christine Lo, Kaylena A Ehgoetz Martens, Jiri Nepozitek, Giuseppe Plazzi, Federica Provini, Monica Puligheddu, Michal Rolinski, Jan Rusz, Ambra Stefani, Rebekah L S Summers, Dallah Yoo, Jennifer Zitser, Wolfgang H Oertel
Journal: The Lancet Neurology (2021)