tbuckley/cabot-search huggingface dataset:
Preoperative Model and Patient Selection for Neoadjuvant Therapy for Intrahepatic Cholangiocarcinoma
Authors: Fangqiang Wei
Journal: JAMA Surgery (2021)

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OFP01.09 Economic Burden of Metastatic Non-Small Cell Lung Cancer (mNSCLC) in a Large United States (US) Claims Database
Authors: E. Chou, A.K. Ganti, K. Katranji, I. Cotarla, C. Sharma, B. Miao, M. Garg, B. Seal
Journal: Journal of Thoracic Oncology (2021)
Diabeloop DBLG1 Closed-Loop System Enables Patients With Type 1 Diabetes to Significantly Improve Their Glycemic Control in Real-Life Situations Without Serious Adverse Events: 6-Month Follow-up
Authors: Coralie Amadou, Sylvia Franc, Pierre-Yves Benhamou, Sandrine Lablanche, Erik Huneker, Guillaume Charpentier, Alfred Penfornis
Journal: Diabetes Care (2021)

To analyze safety and efficacy of the Diabeloop Generation 1 (DBLG1) hybrid closed-loop artificial pancreas system in patients with type 1 diabetes in real-world conditions.After a 1-week run-in period with their usual pump, 25 patients were provided the commercial DBLG1 system. The results are presented on time in range (TIR) and HbA1c over 6 months.The mean (SD; range) age of patients was 43 (13.8; 25-72) years. At baseline, the mean HbA1c and TIR 70-180 mg/dL were, respectively, 7.9% (0.93; 5.6-8.5%) [63 mmol/mol (10; 38-69 mmol/mol)] and 53% (16.4; 21-85%). One patient stopped using the system after 2 months. At 6 months, the mean HbA1c decreased to 7.1% [54 mmol/mol] (P < 0.001) and TIR 70-180 mg/dL increased to 69.7% (P < 0.0001). TIR <70 mg/dL decreased from 2.4 to 1.3% (P = 0.03), and TIR <54 mg/dL decreased from 0.32 to 0.24% (P = 0.42). No serious adverse event was reported during the study.The ability of the DBLG1 system to significantly improve glycemic control in real-world conditions, without serious adverse events, was confirmed in this follow-up study.
Comparison of Saliva and Nasopharyngeal Swab Nucleic Acid Amplification Testing for Detection of SARS-CoV-2
Authors: Guillaume Butler-Laporte, Alexander Lawandi, Ian Schiller, Mandy Yao, Nandini Dendukuri, Emily G. McDonald, Todd C. Lee
Journal: JAMA Internal Medicine (2021)

Nasopharyngeal swab nucleic acid amplification testing (NAAT) is the noninvasive criterion standard for diagnosis of coronavirus disease 2019 (COVID-19). However, it requires trained personnel, limiting its availability. Saliva NAAT represents an attractive alternative, but its diagnostic performance is unclear.
Influenza virus infection increases ACE2 expression and shedding in human small airway epithelial cells
Authors: Kelly S. Schweitzer, Taylor Crue, Jordan M. Nall, Daniel Foster, Satria Sajuthi, Kelly A. Correll, Mari Nakamura, Jamie L. Everman, Gregory P. Downey, Max A. Seibold, James P. Bridges, Karina A. Serban, Hong Wei Chu, Irina Petrache
Journal: European Respiratory Journal (2021)

Patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) demonstrate high rates of co-infection with respiratory viruses, including influenza A (IAV), suggesting pathogenic interactions.
Overcoming therapeutic efficiency limitations against TRAIL-resistant tumors using re-sensitizing agent-loaded trimeric TRAIL-presenting nanocages
Authors: Hyeonwoo Je, Gi-Hoon Nam, Gi Beom Kim, Wonjun Kim, Soo Rin Kim, In-San Kim, Eun Jung Lee
Journal: Journal of Controlled Release (2021)

Tumor-specific apoptosis-inducing ligands have attracted considerable attention in cancer therapy. But, the evasion of apoptosis by tumors can cause acquired resistance to the therapy. TNF-related apoptosis-inducing ligand (TRAIL) has been investigated as an ideal antitumor agent owing to its inherent tumor cell-specific apoptotic activity. However, there are several barriers to its wider application, including the inability for stable formation of the trimeric structure, poor stability and pharmacokinetics, and differences in the sensitivity of different tumor types. Especially, almost 70% of tumor cells have acquired resistance to TRAIL, leading to failure of TRAIL-based therapeutics in clinical trials. To overcome therapeutic efficiency limitations against TRAIL-resistant tumors, we exploited the characteristic of a naturally derived nanocage that not only delivers TRAIL in its native-like trimeric structure, but also delivers a drug (doxorubicin [DOX]) that re-sensitizes TRAIL-resistant tumor cells. These TRAIL-presenting nanocages (TTPNs) showed high loading efficiency, pH-dependent release profiles, and effective intracellular delivery of the re-sensitizing agent DOX. As a result, DOX-TTPNs efficiently re-sensitized TRAIL-resistant tumor cells to TRAIL-mediated apoptosis in vitro by regulating levels of the TRAIL receptor, DR5, and anti- and pro-apoptotic proteins involved in extrinsic and intrinsic apoptosis pathways. We further demonstrated the antitumor efficacy of DOX-TTPNs in vivo, showing that even at a very low dose, the incorporated DOX successfully re-sensitized tumors to the apoptotic effects of TRAIL, underscoring the potential of this platform as an antitumor agent. Given that other homotrimeric TNF superfamily ligands and immunotherapeutic agents can be substituted for TRAIL ligand and re-sensitizing drugs on the surface and in the inner cavity of the nanocage, respectively, this platform is potentially suitable for development of a broad range of anticancer or immunotherapeutic combinations.
Interim Results of a Phase 1–2a Trial of Ad26.COV2.S Covid-19 Vaccine
Authors: Jerald Sadoff, Mathieu Le Gars, Georgi Shukarev, Dirk Heerwegh, Carla Truyers, Anne M de Groot, Jeroen Stoop, Sarah Tete, Wim Van Damme, Isabel Leroux-Roels, Pieter-Jan Berghmans, Murray Kimmel, Pierre Van Damme, Jan de Hoon, William Smith, Kathryn E Stephenson, Stephen C De Rosa, Kristen W Cohen, M Juliana McElrath, Emmanuel Cormier, Gert Scheper, Dan H Barouch, Jenny Hendriks, Frank Struyf, Macaya Douoguih, Johan Van Hoof, Hanneke Schuitemaker
Journal: New England Journal of Medicine (2021)

Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A candidate vaccine, Ad26.COV2.S, is a recombinant, replication-incompetent adenovirus serotype 26 (Ad26) vector encoding a full-length and stabilized SARS-CoV-2 spike protein.In this multicenter, placebo-controlled, phase 1-2a trial, we randomly assigned healthy adults between the ages of 18 and 55 years (cohort 1) and those 65 years of age or older (cohort 3) to receive the Ad26.COV2.S vaccine at a dose of 5×1010 viral particles (low dose) or 1×1011 viral particles (high dose) per milliliter or placebo in a single-dose or two-dose schedule. Longer-term data comparing a single-dose regimen with a two-dose regimen are being collected in cohort 2; those results are not reported here. The primary end points were the safety and reactogenicity of each dose schedule.After the administration of the first vaccine dose in 805 participants in cohorts 1 and 3 and after the second dose in cohort 1, the most frequent solicited adverse events were fatigue, headache, myalgia, and injection-site pain. The most frequent systemic adverse event was fever. Systemic adverse events were less common in cohort 3 than in cohort 1 and in those who received the low vaccine dose than in those who received the high dose. Reactogenicity was lower after the second dose. Neutralizing-antibody titers against wild-type virus were detected in 90% or more of all participants on day 29 after the first vaccine dose (geometric mean titer [GMT], 212 to 354), regardless of vaccine dose or age group, and reached 96% by day 57 with a further increase in titers (GMT, 288 to 488) in cohort 1a. Titers remained stable until at least day 71. A second dose provided an increase in the titer by a factor of 2.6 to 2.9 (GMT, 827 to 1266). Spike-binding antibody responses were similar to neutralizing-antibody responses. On day 15, CD4+ T-cell responses were detected in 76 to 83% of the participants in cohort 1 and in 60 to 67% of those in cohort 3, with a clear skewing toward type 1 helper T cells. CD8+ T-cell responses were robust overall but lower in cohort 3.The safety and immunogenicity profiles of Ad26.COV2.S support further development of this vaccine candidate. (Funded by Johnson & Johnson and the Biomedical Advanced Research and Development Authority of the Department of Health and Human Services; COV1001 ClinicalTrials.gov number, NCT04436276.).
Pneumatic dilation for persistent dysphagia after antireflux surgery, a multicentre single-blind randomised sham-controlled clinical trial
Authors: Jeroen M Schuitenmaker, Froukje B van Hoeij, Marlies P Schijven, Jan Tack, José M Conchillo, Eric J Hazebroek, André J P M Smout, Albert J Bredenoord
Journal: Gut (2021)

Objective There is no evidence-based treatment for persistent dysphagia after laparoscopic fundoplication. The aim of this study was to evaluate the effect of pneumatic dilation on persistent dysphagia after laparoscopic fundoplication. Design We performed a multicentre, single-blind, randomised sham-controlled trial of patients with persistent dysphagia (&gt;3 months) after laparoscopic fundoplication. Patients with an Eckardt symptom score ≥4 were randomly assigned to pneumatic dilation (PD) using a 35 mm balloon or sham dilation. Primary outcome was treatment success, defined as an Eckardt score &lt;4 and a minimal reduction of 2 points in the Eckardt score after 30 days. Secondary outcomes included change in stasis on timed barium oesophagogram, change in high-resolution manometry parameters and questionnaires on quality of life, reflux and dysphagia symptoms. Results Forty-two patients were randomised. In the intention-to-treat analysis, the success rates of PD (7/21 patients (33%)) and sham dilation (8/21 patients (38%)) were similar after 30 days (risk difference −4.7% (95% CI (−33.7% to 24.2%) p=0.747). There was no significant difference in change of stasis on the timed barium oesophagogram after 2 min (PD vs sham: median 0.0 cm, p25–p75 range 0.0–4.3 cm vs median 0.0 cm, p25–p75 range 0.0–0.0; p=0.122) or change in lower oesophageal sphincter relaxation pressure (PD vs sham: 10.54±6.25 vs 14.60±6.17 mm Hg; p=0.052). Quality of life, reflux and dysphagia symptoms were not significantly different between the two groups. Conclusion Pneumatic dilation with a 35 mm balloon is not superior to sham dilation for the treatment of persistent dysphagia after fundoplication.
Polyoxypregnanes as safe, potent, and specific ABCB1-inhibitory pro-drugs to overcome multidrug resistance in cancer chemotherapy in vitro and in vivo
Authors: Xu Wu, Chun Yin, Jiang Ma, Stella Chai, Chunyuan Zhang, Sheng Yao, Onat Kadioglu, Thomas Efferth, Yang Ye, Kenneth Kin-Wah To, Ge Lin
Journal: Acta Pharmaceutica Sinica B (2021)

Multidrug resistance (MDR) mediated by ATP binding cassette subfamily B member 1 (ABCB1) is significantly hindering effective cancer chemotherapy. However, currently, no ABCB1-inhibitory drugs have been approved to treat MDR cancer clinically, mainly due to the inhibitor specificity, toxicity, and drug interactions. Here, we reported that three polyoxypregnanes (POPs) as the most abundant constituents of Marsdenia tenacissima (M. tenacissima) were novel ABCB1-modulatory pro-drugs, which underwent intestinal microbiota-mediated biotransformation in vivo to generate active metabolites. The metabolites at non-toxic concentrations restored chemosensitivity in ABCB1-overexpressing cancer cells via inhibiting ABCB1 efflux activity without changing ABCB1 protein expression, which were further identified as specific non-competitive inhibitors of ABCB1 showing multiple binding sites within ABCB1 drug cavity. These POPs did not exhibit ABCB1/drug metabolizing enzymes interplay, and their repeated administration generated predictable pharmacokinetic interaction with paclitaxel without obvious toxicity in vivo. We further showed that these POPs enhanced the accumulation of paclitaxel in tumors and overcame ABCB1-mediated chemoresistance. The results suggested that these POPs had the potential to be developed as safe, potent, and specific pro-drugs to reverse ABCB1-mediated MDR. Our work also provided scientific evidence for the use of M. tenacissima in combinational chemotherapy.
Past, present and future role of retinal imaging in neurodegenerative disease
Authors: Amir H. Kashani, Samuel Asanad, Jane W. Chan, Maxwell B. Singer, Jiong Zhang, Mona Sharifi, Maziyar M. Khansari, Farzan Abdolahi, Yonggang Shi, Alessandro Biffi, Helena Chui, John M. Ringman
Journal: Progress in Retinal and Eye Research (2021)
Quality of life in newly diagnosed and relapsed Danish multiple myeloma patients: A national longitudinal study of Danish myeloma study group
Authors: Lene Kongsgaard Nielsen, Mary Ellen Jarden, C L Andersen, Henrik Frederiksen, H Gregersen, Anja Klostergaard, M S Steffensen, Per T. Pedersen, Bettina Broch, Mikael Frederiksen, Bo Amdi Jensen, Carsten Helleberg, A K Mylin, Niels Abildgaard
Journal: HemaSphere (2018)
Insights into kinetics, release, and behavioral effects of brain-targeted hybrid nanoparticles for cholesterol delivery in Huntington's disease
Authors: Giulia Birolini, Marta Valenza, Ilaria Ottonelli, Alice Passoni, Monica Favagrossa, Jason T. Duskey, Mauro Bombaci, Maria Angela Vandelli, Laura Colombo, Renzo Bagnati, Claudio Caccia, Valerio Leoni, Franco Taroni, Flavio Forni, Barbara Ruozi, Mario Salmona, Giovanni Tosi, Elena Cattaneo
Journal: Journal of Controlled Release (2021)
The BMJ interview: Fixing America’s covid response in the Biden era
Authors: Joanne Silberner
Journal: BMJ (2021)

US president elect Joe Biden wasted no time in appointing a special advisory board of experts to guide America out of its coronavirus crisis. Among them is a woman who has extensive experience of previous epidemics in Africa and elsewhere, and sees lessons for her own country, she tells <b>Joanne Silberner</b>
User-life of ICS/LABA inhaler devices should be considered when prescribed as relievers
Authors: Roy A. Pleasants, Stephen L. Tilley, Anthony J. Hickey, Omar S. Usmani
Journal: European Respiratory Journal (2021)

<b>Prescribers and asthma patients should know that ICS/LABA combination inhalers used as reliever therapy may expire under patient use sooner than the expiration shown on the inhaler, compromising effectiveness if not considered by the prescriber and patient</b>https://bit.ly/3fhHMX2
Epigenetic and Posttranscriptional Modulation of SOS1 Can Promote Breast Cancer Metastasis through Obesity-Activated c-Met Signaling in African-American Women
Authors: Fei Xing, Dan Zhao, Shih-Ying Wu, Abhishek Tyagi, Kerui Wu, Sambad Sharma, Yin Liu, Ravindra Deshpande, Yuezhu Wang, Jacob Cleary, Lance D. Miller, Amar G. Chittiboyina, Chinni Yalamanchili, Yin-Yuan Mo, Kounosuke Watabe
Journal: Cancer Research (2021)

Ethnicity is considered to be one of the major risk factors in certain subtypes of breast cancer. However, the mechanism of this racial disparity remains poorly understood. Here, we demonstrate that SOS1, a key regulator of Ras pathway, is highly expressed in African-American (AA) patients with breast cancer compared with Caucasian-American patients. Because of the higher obesity rate in AA women, increased levels of SOS1 facilitated signal transduction of the c-Met pathway, which was highly activated in AA patients with breast cancer via hepatocyte growth factor secreted from adipocytes. Elevated expression of SOS1 also enhanced cancer stemness through upregulation of PTTG1 and promoted M2 polarization of macrophages by CCL2 in metastatic sites. SOS1 was epigenetically regulated by a super-enhancer identified by H3K27ac in AA patients. Knockout of the super-enhancer by CRISPR in AA cell lines significantly reduced SOS1 expression. Furthermore, SOS1 was posttranscriptionally regulated by miR-483 whose expression is reduced in AA patients through histone trimethylation (H3K27me3) on its promoter. The natural compound, taxifolin, suppressed signaling transduction of SOS1 by blocking the interaction between SOS1 and Grb2, suggesting a potential utility of this compound as a therapeutic agent for AA patients with breast cancer. SIGNIFICANCE: These findings elucidate the signaling network of SOS1-mediated metastasis in African-American patients, from the epigenetic upregulation of SOS1 to the identification of taxifolin as a potential therapeutic strategy against SOS1-driven tumor progression.
HOMER3 facilitates growth factor-mediated β-Catenin tyrosine phosphorylation and activation to promote metastasis in triple negative breast cancer
Authors: Qinghua Liu, Lixin He, Siqi Li, Fengyan Li, Guangzheng Deng, Xinjian Huang, Muwen Yang, Yunyun Xiao, Xiangfu Chen, Ying Ouyang, Jinxin Chen, Xuxia Wu, Xi Wang, Libing Song, Chuyong Lin
Journal: Journal of Hematology & Oncology (2021)

HOMER family scaffolding proteins (HOMER1-3) play critical roles in the development and progression of human disease by regulating the assembly of signal transduction complexes in response to extrinsic stimuli. However, the role of HOMER protein in breast cancer remains unclear.
Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis
Authors: Hagop M. Kantarjian, Timothy P. Hughes, Richard A. Larson, Dong-Wook Kim, Surapol Issaragrisil, Philipp le Coutre, Gabriel Etienne, Carla Boquimpani, Ricardo Pasquini, Richard E. Clark, Viviane Dubruille, Ian W. Flinn, Slawomira Kyrcz-Krzemien, Ewa Medras, Maria Zanichelli, Israel Bendit, Silvia Cacciatore, Ksenia Titorenko, Paola Aimone, Giuseppe Saglio, Andreas Hochhaus
Journal: Leukemia (2021)

Abstract In the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR 4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.
PET Imaging of TIGIT Expression on Tumor-Infiltrating Lymphocytes
Authors: Travis Shaffer, Arutselvan Natarajan, Sanjiv S. Gambhir
Journal: Clinical Cancer Research (2021)

Therapeutic checkpoint inhibitors on tumor-infiltrating lymphocytes (TIL) are being increasingly utilized in the clinic. The T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor expressed on T and natural killer cells. The TIGIT signaling pathway is an alternative target for checkpoint blockade to current PD-1/CTLA-4 strategies. Elevated TIGIT expression in the tumor microenvironment correlates with better therapeutic responses to anti-TIGIT therapies in preclinical models. Therefore, quantifying TIGIT expression in tumors is necessary for determining whether a patient may respond to anti-TIGIT therapy. PET imaging of TIGIT expression on TILs can therefore aid diagnosis and in monitoring therapeutic responses.Antibody-based TIGIT imaging radiotracers were developed with the PET radionuclides copper-64 (64Cu) and zirconium-89 (89Zr). In vitro characterization of the imaging probes was followed by in vivo evaluation in both xenografts and syngeneic tumor models in mouse.Two anti-TIGIT probes were developed and exhibited immunoreactivity of >72%, serum stability of >95%, and specificity for TIGIT with both mouse TIGIT-expressing HeLa cells and ex vivo-activated primary splenocytes. In vivo, the 89Zr-labeled probe demonstrated superior contrast than the 64Cu probe due to 89Zr's longer half-life matching the TIGIT antibody's pharmacokinetics. The 89Zr probe was used to quantify TIGIT expression on TILs in B16 melanoma in immunocompetent mice and confirmed by ex vivo flow cytometry.This study develops and validates novel TIGIT-specific 64Cu and 89Zr PET probes for quantifying TIGIT expression on TILs for diagnosis of patient selection for anti-TIGIT therapies.
Outbreak of Candida auris infection in a COVID-19 hospital in Mexico
Authors: Hiram Villanueva-Lozano, Rogelio de J. Treviño-Rangel, Gloria M. González, María Teresa Ramírez-Elizondo, Reynaldo Lara-Medrano, Mary Cruz Aleman-Bocanegra, Claudia E. Guajardo-Lara, Natalia Gaona-Chávez, Fernando Castilleja-Leal, Guillermo Torre-Amione, Michel F. Martínez-Reséndez
Journal: Clinical Microbiology and Infection (2021)
Increased air pollution exposure among the Chinese population during the national quarantine in 2020
Authors: Huizhong Shen, Guofeng Shen, Yilin Chen, Armistead G. Russell, Yongtao Hu, Xiaoli Duan, Wenjun Meng, Yang Xu, Xiao Yun, Baolei Lyu, Shunliu Zhao, Amir Hakami, Jianping Guo, Shu Tao, Kirk R. Smith
Journal: Nature Human Behaviour (2021)

The COVID-19 quarantine in China is thought to have reduced ambient air pollution. The overall exposure of the population also depends, however, on indoor air quality and human mobility and activities. Here, by integrating real-time mobility data and a questionnaire survey on time-activity patterns during the pandemic, we show that despite a decrease in ambient PM2.5 during the quarantine, the total population-weighted exposure to PM2.5 considering both indoor and outdoor environments increased by 5.7 μg m-3 (95% confidence interval, 1.2-11.0 μg m-3). The increase in population-weighted exposure was mainly driven by a nationwide urban-to-rural population migration before the Spring Festival coupled with the freezing of the migration backward due to the quarantine, which increased household energy consumption and the fraction of people exposed to rural household air pollution indoors. Our analysis reveals an increased inequality of air pollution exposure during the quarantine and highlights the importance of household air pollution for population health in China.