tbuckley/cabot-search huggingface dataset:
Antibody response induced by the BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers, with or without prior SARS-CoV-2 infection: a prospective study
Authors: Dora Buonfrate, Chiara Piubelli, Federico Gobbi, Davide Martini, Giulia Bertoli, Tamara Ursini, Lucia Moro, Niccolò Ronzoni, Andrea Angheben, Paola Rodari, Chiara Cardellino, Francesca Tamarozzi, Stefano Tais, Eleonora Rizzi, Monica Degani, Michela Deiana, Marco Prato, Ronaldo Silva, Zeno Bisoffi
Journal: Clinical Microbiology and Infection (2021)

To assess the antibody response to BNT162b2 mRNA COVID-19 vaccine in a cohort of health-care workers (HCW), comparing individuals with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and SARS-CoV-2-naive individuals.HCW were tested at T0 (day of first dose), T1 (day of second dose) and T2 (2-3 weeks after second dose) for IgG anti-nucleocapsid protein, IgM anti-spike protein and IgG anti-receptor binding domain (IgG-RBD-S). The antibody response was compared between four main groups: group A, individuals with previous infection and positive antibodies at baseline; group B, individuals with the same history but negative antibodies; group C, individuals with no infection history but positive antibodies; group D, naive individuals. Repeated measures analysis was used to compare results over time-points.A total of 1935 HCW were included. Median IgG-RBD-S titre was significantly higher for group A (232 individuals) than for group B (56 individuals) both at T1 (A: 22 763 AU/mL, interquartile range (IQR) 14 222-37 204 AU/mL; B: 1373 AU/mL, IQR 783-3078 AU/mL, p 0.0003) and T2 (A: 30 765 AU/mL, IQR 19 841-42 813 AU/mL; B: 13 171 AU/mL, IQR 2324-22 688 AU/mL, p 0.0038) and for group D (1563 individuals; 796 AU/mL, IQR 379-1510 AU/mL at T1; 15 494 AU/mL, IQR 9122-23 916 AU/mL at T2, p < 0.0001 for both time-points). T1 values of group A were also significantly higher than T2 values of group D (p < 0.0001). Presence of symptoms, younger age and being female were associated with stronger antibody response. HCW infected in March showed a significantly stronger response (T1: 35 324 AU/mL, IQR 22 003-44 531 AU/mL; T2: 37 648 AU/mL, IQR 27 088-50 451 AU/mL) than those infected in November (T1: 18 499 AU/mL, IQR 11 492-27 283 AU/mL; T2: 23 210 AU/mL, IQR 18 074-36 086 AU/mL, p < 0.0001 for both time-points.Individuals with past SARS-CoV-2 infection had a strong antibody response after one single vaccine shot. A single dose might be sufficient for this group, regardless of the time elapsed since infection; however, the clinical correlation with antibody response needs to be studied.
Side Effects 15 Years After Lymph Node Irradiation in Breast Cancer: Randomized EORTC Trial 22922/10925
Authors: Philip M Poortmans, Henk Struikmans, Peter De Brouwer, Caroline Weltens, Catherine Fortpied, Carine Kirkove, Volker Budach, Karine Peignaux-Casasnovas, Femke van der Leij, Ernest Vonk, Mariacarla Valli, Geertjan vanTienhoven, Nicola Weidner, Georges Noel, Matthias Guckenberger, Eveline Koiter, Erik vanLimbergen, Antoine Engelen, Alain Fourquet, Harry Bartelink
Journal: JNCI Journal of the National Cancer Institute (2021)

Uncertainty about the benefit-risk ratio of regional lymph node irradiation led to varying clinical protocols. We investigated long-term late side effects after internal mammary and medial supraclavicular (IM-MS) lymph node irradiation to improve shared decision making.The multicenter European Organization for Research and Treatment of Cancer trial (ClinicalTrials.gov, NCT00002851) randomly assigned stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. We analyzed late side effects both longitudinally at every follow-up and cross-sectionally at 5-year intervals. All statistical tests were 2-sided.Between 1996 and 2004, 46 departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. Longitudinal follow-up data showed cumulative incidence rates at 15 years of 2.9% (95% confidence interval [CI] = 2.2% to 3.8%) vs 5.7% (95% CI = 4.7% to 6.9%) (P < .001) for lung fibrosis, 1.1% (95% CI = 0.7% to 1.7%) vs 1.9% (95% CI = 1.3% to 2.6%) (P = .07) for cardiac fibrosis, and 9.4% (95% CI = 8.0% to 10.8%) vs 11.1% (95% CI = 9.6% to 12.7%) (P = .04) for any cardiac disease when treated without or with IM-MS lymph node irradiation. There was no evidence for differences between left- and right-sided breast cancer (Wald χ2 test of treatment by breast side interaction, P = .33 and P = .35, for cardiac fibrosis and for any cardiac disease, respectively). The cumulative incidence probabilities of cross-sectionally reported side effects with a score of 2 or greater at 15 years were 0.1% (95% CI = 0.0% to 0.5%) vs 0.8% (95% CI = 0.4% to 1.4%) for pulmonary (P = .02), 1.8% (95% CI = 1.1% to 2.8%) vs 2.6% (95% CI = 1.8% to 3.7%) for cardiac (P = .15), and 0.0% (95% CI not evaluated) vs 0.1% (95% CI = 0.0% to 0.4%) for esophageal (P = .16), respectively. No difference was observed in the incidence of second malignancies, contralateral breast cancer, or cardiovascular deaths.The incidence of late pulmonary side effects was statistically significantly higher after IM-MS lymph node irradiation, as were some of the cardiac events, without a difference between left- and right-sided treatments. Absolute rates and differences were very low, without increased non-breast cancer-related mortality, even before introducing heart-sparing techniques.
Bioengineering CXCR4-overexpressing cell membrane functionalized ROS-responsive nanotherapeutics for targeting cerebral ischemia-reperfusion injury
Authors: Li Luo, Guangchao Zang, Boyan Liu, Xian Qin, Yuchan Zhang, Yidan Chen, Haijun Zhang, Wei Wu, Guixue Wang
Journal: Theranostics (2021)

Rationale: As a potentially life-threatening disorder, cerebral ischemia-reperfusion (I/R) injury is associated with significantly high mortality, especially the irreversible brain tissue damage associated with increased reactive oxygen radical production and excessive inflammation.Currently, the insufficiency of targeted drug delivery and "on-demand" drug release remain the greatest challenges for cerebral I/R injury therapy.Bioengineered cell membrane-based nanotherapeutics mimic and enhance natural membrane functions and represent a potentially promising approach, relying on selective interactions between receptors and chemokines and increase nanomedicine delivery efficiency into the target tissues.Methods: We employed a systematic method to synthesize biomimetic smart nanoparticles.The CXCR4-overexpressing primary mouse thoracic aorta endothelial cell (PMTAEC) membranes and RAPA@HOP were extruded through a 200 nm polycarbonate porous membrane using a mini-extruder to harvest the RAPA@BMHOP.The bioengineered CXCR4-overexpressing cell membrane-functionalized ROS-responsive nanotherapeutics, loaded with rapamycin (RAPA), were fabricated to enhance the targeted delivery to lesions with pathological overexpression of SDF-1.Results: RAPA@BMHOP exhibited a three-fold higher rate of target delivery efficacy via the CXCR4/SDF-1 axis than its non-targeting counterpart in an in vivo model.Additionally, in response to the excessive pathological ROS, nanotherapeutics could be degraded to promote "on-demand" cargo release and balance the ROS level by p-hydroxy-benzyl alcohol degradation, thereby scavenging excessive ROS and suppressing the free radical-induced focal damage and local inflammation.Also, the stealth effect of cell membrane coating functionalization on the surface resulted in extended circulation time and high stability of nanoparticles. Conclusion:The biomimetic smart nanotherapeutics with active targeting, developed in this study, significantly improved the therapeutic efficacy and biosafety profiles.Thus, these nanoparticles could be a candidate for efficient therapy of cerebral I/R injury.
Antrodia cinnamomea exerts an anti-hepatoma effect by targeting PI3K/AKT-mediated cell cycle progression in vitro and in vivo
Authors: Yan Zhang, Pin Lv, Junmei Ma, Ning Chen, Huishan Guo, Yan Chen, Xiaoruo Gan, Rong Wang, Xuqiang Liu, Sufang Fan, Bin Cong, Wenyi Kang
Journal: Acta Pharmaceutica Sinica B (2021)

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.
Case 23-2021: A 41-Year-Old Woman with Bloody Stools and Thrombocytopenia
Authors: Olivia C. Smibert, Onofrio A. Catalano, Katayoon Goodarzi, Matthew B. Roberts
Journal: New England Journal of Medicine (2021)

A 41-year-old woman with presumed Alport's syndrome was admitted with bloody stools and rectal pain. Six months earlier, she had undergone deceased-donor renal transplantation. On admission, the blood pressure was 85/46 mm Hg, the hemoglobin level 6 g per deciliter, and the platelet count 0 per microliter. A diagnostic test was performed.
A Phase I, Open-Label, Dose-Finding Study of GSK2636771, a PI3Kβ Inhibitor, Administered with Enzalutamide in Patients with Metastatic Castration-Resistant Prostate Cancer
Authors: Debashis Sarker, Nancy A. Dawson, Ana M. Aparicio, Tanya B. Dorff, Allan J. Pantuck, Ulka N. Vaishampayan, Lynn Henson, Lakshmi Vasist, Sumita Roy-Ghanta, Michele Gorczyca, Whitney York, Gopinath Ganji, Jerry Tolson, Johann S. de Bono
Journal: Clinical Cancer Research (2021)

Abstract Purpose: In patients with metastatic castration-resistant prostate cancer (mCRPC), resistance to androgen receptor (AR)-targeted therapies, such as enzalutamide, remains an issue. Inactivation of inhibitory PTEN activates PI3K/AKT signaling and contributes to resistance to androgen deprivation therapy and poor outcomes. Therefore, dual targeting of AR and PI3K/AKT pathways may limit tumor growth and reverse resistance. Patients and Methods: In this phase I study (NCT02215096), patients with PTEN-deficient mCRPC who progressed on prior enzalutamide received once-daily enzalutamide 160 mg plus PI3Kβ inhibitor GSK2636771 at 300 mg initial dose, with escalation or de-escalation in 100-mg increments, followed by dose expansion. Primary objectives were to evaluate safety/tolerability, determine the recommended phase II dose, and assess the 12-week non-progressive disease (PD) rate. Results: Overall, 37 patients were enrolled; 36 received ≥1 dose of GSK2636771 (200 mg: n = 22; 300 mg: n = 12; 400 mg: n = 2) plus 160 mg enzalutamide. Dose-limiting toxicities occurred in 5 patients (200 mg: n = 1; 300 mg: n = 2, 400 mg: n = 2). No new or unexpected adverse events or evidence of drug–drug interaction were observed. At the recommended dose of GSK2636771 (200 mg) plus enzalutamide, the 12-week non-PD rate was 50% (95% confidence interval: 28.2–71.8, n = 22); 1 (3%) patient achieved a radiographic partial response lasting 36 weeks. Four of 34 (12%) patients had prostate-specific antigen reduction of ≥50%. Conclusions: Although there was acceptable safety and tolerability with GSK2636771 plus enzalutamide in patients with PTEN-deficient mCRPC after failing enzalutamide, limited antitumor activity was observed.
Treatment Approved for “Undruggable” Lung Cancer
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

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Efficacy of Recombinant Zoster Vaccine in Patients With Inflammatory Bowel Disease
Authors: Nabeel Khan, Louise Wang, Chinmay Trivedi, Tyler Pernes, Manthankumar Patel, Dawei Xie, Yu-Xiao Yang
Journal: Clinical Gastroenterology and Hepatology (2021)

Individuals with inflammatory bowel disease (IBD) have an increased risk of herpes zoster (HZ) infection. Although the efficacy of recombinant zoster vaccine (RZV) is high among immunocompetent individuals, little is known about its effect among immunosuppressed individuals with IBD.We conducted a retrospective cohort study among individuals in the national Veterans Affairs Healthcare System diagnosed with IBD on or before January 3, 2018, the earliest date of RZV vaccinations. We collected data on 7008 and 26,292 eligible patients with IBD in the 50- to 60-year and >60-year age groups, respectively. We identified veterans who received RZV and compared the incidence of HZ between vaccinated versus unvaccinated individuals. We performed multivariable Cox regression with time varying analysis to determine the risk of HZ among the vaccinated (full dose and single dose separately) versus unvaccinated cohort, stratified by IBD medications.The crude HZ incidence rate after full dose vaccination of RZV when compared with the unvaccinated group was lower in both the 50- to 60-year age group (0.00 vs 3.93 per 1000 person-years) and >60-year age group (1.80 vs 4.57 per 1000 person-years). RZV vaccination was associated with a significantly lower risk of HZ among the 50- to 60-year and >60-year age groups, although this was limited by low HZ event rates.RZV vaccination was associated with decreased risk of HZ infection among both the 50- to 60-year and >60-year age groups. Greater efforts should be made to vaccinate all patients with IBD with RZV.
Synergistic effects of silver nanoparticles and cisplatin in combating inflammation and hyperplasia of airway stents
Authors: Zhaonan Li, Chuan Tian, Dechao Jiao, Jing Li, Yahua Li, Xueliang Zhou, Huiping Zhao, Yanan Zhao, Xinwei Han
Journal: Bioactive Materials (2021)

Anti-inflammatory and antihyperplasia activities are essential requirements for the successful use of airway stents. In this work, silver nanoparticles (AgNPs) and cisplatin (DDP) were combined in a synergistic modification strategy to improve the surface function of airway stents. Using polycaprolactone (PCL) as a drug carrier, a dual-functional PCL-AgNPs-DDP fiber film-coated airway stent was fabricated by electrospinning. The physicochemical and biological properties of the obtained fiber films were examined. The ATR-FTIR, XPS, SEM-EDS and TEM results suggested that AgNPs and DDP could be successfully immobilized onto the airway stent surface. The drug release and surface degradation results revealed that AgNPs and DDP can undergo sustained release from films for 30 d, and the weight loss was approximately 50% after 35 d. In addition, the dual-functional fiber film suppressed human embryonic lung fibroblast growth and exhibited excellent antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans. Furthermore, the effectiveness of the dual-functional fiber film-coated airway stent was evaluated by application to the trachea of New Zealand rabbits. The in vivo results indicated that PCL-AgNPs-DDP fiber film-coated airway stent can significantly inhibit granulation tissue formation and collagen deposition, reduced the expression of IL-8, TNF-α, IL-1α, PCNA, α-SMA and CD68, and ultimately achieved anti-inflammatory and antihyperplasia effects. Hence, this study provides a dual-functional surface-coated airway stent to address the clinical complications associated with respiratory tract inflammation and granulation tissue hyperplasia, thus inhibiting tracheal stenosis.
Eligibility for treatment with omalizumab in Italy and Germany
Authors: Roland Buhl, Giorgio Walter Canonica, Andrea Gili Marco, Christoph Ruland
Journal: European Respiratory Journal (2011)

Omalizumab is an add-on therapy for patients with uncontrolled severe allergic asthma. In Europe, patients must fulfil a number of additional criteria to become eligible for omalizumab therapy, creating a challenge for epidemiology studies to quantify the potential patient pool. Thus, and in the absence of robust data, the number of omalizumab-eligible patients has remained unclear.  To assess eligible patient numbers, the team employed an innovative chart-audit design approach to measure epidemiology variables based on patient-level data. 770 patient charts were reviewed in designated towns in Germany/Italy, in collaboration with >200 primary care physicians (PCPs) and respiratory specialists (RS). This study sample represents >50% and >70% of local RS in these designated towns of Germany and Italy, respectively.  Of patient charts evaluated, 4 patients were currently receiving omalizumab. A further 31 patients (12 PCP; 19 RS) were evaluated as omalizumab-eligible (i.e. fulfilled all product label criteria) but were not receiving the drug. Extrapolating to a national level, this yields >6500 eligible patients in Germany, >3200 in Italy.  Furthermore, this study sample revealed a significant number of PCPs treating uncontrolled severe asthma patients without referral to RS; these patients are not consistently evaluated for FEV1, aeroallergen sensitivity as well as a qualitative understanding of severe exacerbations, and day and night-time symptoms.  This study suggests that significant numbers of omalizumab-naive severe allergic asthma patients in Germany/Italy are eligible for omalizumab therapy; if treated, these patients may benefit from reduction in asthma exacerbations and improved asthma control and quality of life.
Mutation-Specific Signaling Profiles and Therapeutic Vulnerabilities of Induced Pluripotent Stem Cell Models of Juvenile Myelomonocytic Leukemia
Authors: Sarah K Tasian, Jessica A Casas, David Posocco, Shilpa Gandre-Babbe, Alyssa Gagne, Ge Liang, Mignon L. Loh, Mitchell J Weiss, Deborah L French, Stella T Chou
Journal: Blood (2017)
Outcomes of Kidney Transplant in Undocumented Immigrants
Authors: M. Siobhan Luce, Kara T. Kleber, Alexa C. Abdallah, Ugur N. Basmaci, Richard V. Perez, Christoph Troppmann
Journal: JAMA Surgery (2021)

This cohort study investigates kidney transplant outcomes among undocumented immigrants at a single US center.
Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Mikhail N Kosiborod, Russell Esterline, Remo H M Furtado, Jan Oscarsson, Samvel B Gasparyan, Gary G Koch, Felipe Martinez, Omar Mukhtar, Subodh Verma, Vijay Chopra, Joan Buenconsejo, Anna Maria Langkilde, Philip Ambery, Fengming Tang, Kensey Gosch, Sheryl L Windsor, Emily E Akin, Ronaldo V P Soares, Diogo D F Moia, Matthew Aboudara, Conrado Roberto Hoffmann Filho, Audes D M Feitosa, Alberto Fonseca, Vishnu Garla, Robert A Gordon, Ali Javaheri, Cristiano P Jaeger, Paulo E Leaes, Michael Nassif, Michael Pursley, Fabio Serra Silveira, Weimar Kunz Sebba Barroso, José Roberto Lazcano Soto, Lilia Nigro Maia, Otavio Berwanger
Journal: The Lancet Diabetes & Endocrinology (2021)
Acoustic Cluster Therapy (ACT®) enhances accumulation of polymeric micelles in the murine brain
Authors: Marieke Olsman, Melina Mühlenpfordt, Emma Bøe Olsen, Sverre H Torp, Spiros Kotopoulis, Cristianne J F Rijcken, Qizhi Hu, Marielle Thewissen, Sofie Snipstad, Catharina de Lange Davies
Journal: Journal of Controlled Release (2021)

The restrictive nature of the blood-brain barrier (BBB) prevents efficient treatment of many brain diseases. Focused ultrasound in combination with microbubbles has shown to safely and transiently increase BBB permeability. Here, the potential of Acoustic Cluster Therapy (ACT®), a microbubble platform specifically engineered for theranostic purposes, to increase the permeability of the BBB and improve accumulation of IRDye® 800CW-PEG and core-crosslinked polymeric micelles (CCPM) in the murine brain, was studied. Contrast enhanced magnetic resonance imaging (MRI) showed increased BBB permeability in all animals after ACT®. Near infrared fluorescence (NIRF) images of excised brains 1 h post ACT® revealed an increased accumulation of the IRDye® 800CW-PEG (5.2-fold) and CCPM (3.7-fold) in ACT®-treated brains compared to control brains, which was retained up to 24 h post ACT®. Confocal laser scanning microscopy (CLSM) showed improved extravasation and penetration of CCPM into the brain parenchyma after ACT®. Histological examination of brain sections showed no treatment related tissue damage. This study demonstrated that ACT® increases the permeability of the BBB and enhances accumulation of macromolecules and clinically relevant nanoparticles to the brain, taking a principal step in enabling improved treatment of various brain diseases.
P32-5 Eosinophilia predicted longer survival for solid tumor cancer patients treated with anti-PD-1 monoclonal antibody
Authors: Kazuhito Suzuki, Kaichi Nishiwaki, Jun Miki, Naoto Takahashi, Makoto Odaka, Masamichi Takagi, Mitsuji Katori, Shingo Yano
Journal: Annals of Oncology (2021)