tbuckley/cabot-search huggingface dataset:
Intervention of Polydopamine Assembly and Adhesion on Nanoscale Interfaces: State‐of‐the‐Art Designs and Biomedical Applications
Authors: Xiyue Xie, Jia Tang, Yuxin Xing, Zhenqiang Wang, Tao Ding, Jixi Zhang, Kaiyong Cai
Journal: Advanced Healthcare Materials (2021)

Abstract The translation of mussel‐inspired wet adhesion to biomedical engineering fields have catalyzed the emergence of polydopamine (PDA)‐based nanomaterials with privileged features and properties of conducting multiple interfacial interactions. Recent concerns and progress on the understanding of PDA's hierarchical structure and progressive assembly are inspiring approaches toward novel nanostructures with property and function advantages over simple nanoparticle architectures. Major breakthroughs in this field demonstrated the essential role of π – π stacking and π ‐cation interactions in the rational intervention of PDA self‐assembly. In this review, the recently emerging concepts in the preparation and application of PDA nanomaterials, including 3D mesostructures, low‐dimensional nanostructures, micelle/nanoemulsion based nanoclusters, as well as other multicomponent nanohybrids by the segregation and organization of PDA building blocks on nanoscale interfaces are outlined. The contribution of π ‐electron interactions on the interfacial loading/release of π electron‐rich molecules (nucleic acids, drugs, photosensitizers) and the exogenous coupling of optical energy, as well as the impact of wet‐adhesion interactions on the nano‐bio interface interplay, are highlighted by discussing the structure‐property relationships in their featured applications including fluorescent biosensing, gene therapy, drug delivery, phototherapy, combined therapy, etc. The limitations of current explorations, and future research directions are also discussed.
Community-based antibiotic access and use in six low-income and middle-income countries: a mixed-method approach
Authors: Nga T T Do, Huong T L Vu, Chuc T K Nguyen, Sureeporn Punpuing, Wasif Ali Khan, Margaret Gyapong, Kwaku Poku Asante, Khatia Munguambe, F Xavier Gómez-Olivé, Johannes John-Langba, Toan K Tran, Malee Sunpuwan, Esperanca Sevene, Hanh H Nguyen, Phuc D Ho, Mohammad Abdul Matin, Sabeena Ahmed, Mohammad Mahbubul Karim, Olga Cambaco, Samuel Afari-Asiedu, Ellen Boamah-Kaali, Martha Ali Abdulai, John Williams, Sabina Asiamah, Georgina Amankwah, Mary Pomaa Agyekum, Fezile Wagner, Proochista Ariana, Betuel Sigauque, Stephen Tollman, H Rogier van Doorn, Osman Sankoh, John Kinsman, Heiman F L Wertheim
Journal: The Lancet Global Health (2021)

BackgroundAntimicrobial misuse is common in low-income and middle-income countries (LMICs), and this practice is a driver of antibiotic resistance. We compared community-based antibiotic access and use practices across communities in LMICs to identify contextually specific targets for interventions to improve antibiotic use practices.MethodsWe did quantitative and qualitative assessments of antibiotic access and use in six LMICs across Africa (Mozambique, Ghana, and South Africa) and Asia (Bangladesh, Vietnam, and Thailand) over a 2·5-year study period (July 1, 2016–Dec 31, 2018). We did quantitative assessments of community antibiotic access and use through supplier mapping, customer exit interviews, and household surveys. These quantitative assessments were triangulated with qualitative drug supplier and consumer interviews and discussions.FindingsVietnam and Bangladesh had the largest proportions of non-licensed antibiotic dispensing points. For mild illness, drug stores were the most common point of contact when seeking antibiotics in most countries, except South Africa and Mozambique, where public facilities were most common. Self-medication with antibiotics was found to be widespread in Vietnam (55·2% of antibiotics dispensed without prescription), Bangladesh (45·7%), and Ghana (36·1%), but less so in Mozambique (8·0%), South Africa (1·2%), and Thailand (3·9%). Self-medication was considered to be less time consuming, cheaper, and overall, more convenient than accessing them through health-care facilities. Factors determining where treatment was sought often involved relevant policies, trust in the supplier and the drug, disease severity, and whether the antibiotic was intended for a child. Confusion regarding how to identify oral antibiotics was revealed in both Africa and Asia.InterpretationContextual complexities and differences between countries with different incomes, policy frameworks, and cultural norms were revealed. These contextual differences render a single strategy inadequate and instead necessitate context-tailored, integrated intervention packages to improve antibiotic use in LMICs as part of global efforts to combat antibiotic resistance.FundingWellcome Trust and Volkswagen Foundation.
Abstract 16599: Mutations In KCNE1 Alters Multiple K+ Channels To Cause APD Instability And Polymorphic Ventricular Tachycardia (PVT) In Transgenic Long QT Syndrome Type 5 Rabbits
Authors: Tae Yun Kim, Anatoli Kabakov, Dmitry Terentyev, Radmila Terentieva, Karuppiah Arunachalam, Yichun Li, Katja Odening, András Varró, Zsuzsanna Bosze, Gideon Koren, Bum-Rak Choi
Journal: Circulation (2018)

Introduction: LQT5 is caused by mutations in KCNE1, an accessory subunit of slowly activating delayed rectifier K+ channel (IKs), and is associated with polymorphic ventricular tachycardia (pVT) an...
Heart-After-Liver Transplantation Attenuates Rejection of Cardiac Allografts in Sensitized Patients
Authors: Richard C. Daly, Andrew N. Rosenbaum, Joseph A. Dearani, Alfredo L. Clavell, Naveen L. Pereira, Barry A. Boilson, Robert P. Frantz, Atta Behfar, Shannon M. Dunlay, Richard J. Rodeheffer, John A. Schirger, Timucin Taner, Manish J. Gandhi, Julie K. Heimbach, Charles B. Rosen, Brooks S. Edwards, Sudhir S. Kushwaha
Journal: Journal of the American College of Cardiology (2021)
Dynamic Changes of Post-Radiotherapy Plasma Epstein–Barr Virus DNA in a Randomized Trial of Adjuvant Chemotherapy Versus Observation in Nasopharyngeal Cancer
Authors: Edwin Pun Hui, Brigette B.Y. Ma, W.K. Jacky Lam, K.C. Allen Chan, Frankie Mo, Qi-yong Hemis Ai, Ann D. King, Chi Hang Wong, Kenneth C.W. Wong, Daisy C.M. Lam, Macy Tong, Darren M.C. Poon, Leung Li, Thomas K.H. Lau, Kwan Hung Wong, Y.M. Dennis Lo, Anthony T.C. Chan
Journal: Clinical Cancer Research (2021)

To study the dynamic changes in plasma Epstein-Barr virus (pEBV) DNA after radiotherapy in nasopharyngeal cancer (NPC).We conducted a randomized controlled trial of adjuvant chemotherapy versus observation in patients with NPC who had detectable pEBV DNA at 6 weeks post-radiotherapy. Randomized patients had a second pEBV DNA checked at 6 months post-randomization. The primary endpoint was progression-free survival (PFS).We prospectively enrolled 789 patients. Baseline post-radiotherapy pEBV DNA was undetectable in 573 (72.6%) patients, and detectable in 216 (27.4%) patients, of whom 104 (13.2%) patients were eligible for randomization to adjuvant chemotherapy (n = 52) versus observation (n = 52). The first post-radiotherapy pEBV DNA had a sensitivity of 0.48, specificity of 0.81, area under receiver-operator characteristics curve (AUC) of 0.65, false positive (FP) rate of 13.8%, and false negative (FN) rate of 14.4% for disease progression. The second post-radiotherapy pEBV DNA had improved sensitivity of 0.81, specificity of 0.75, AUC of 0.78, FP rate of 14.3%, and FN rate of 8.1%. Patients with complete clearance of post-radiotherapy pEBV DNA (51%) had survival superior to that of patients without post-radiotherapy pEBV DNA clearance (5-year PFS, 85.5% vs. 23.3%; HR, 9.6; P < 0.0001), comparable with patients with initially undetectable post-radiotherapy pEBV DNA (5-year PFS, 77.1%), irrespective of adjuvant chemotherapy or observation.Patients with NPC with detectable post-radiotherapy pEBV DNA who experienced subsequent pEBV DNA clearance had superior survival comparable with patients with initially undetectable post-radiotherapy pEBV DNA. Post-radiotherapy pEBV DNA clearance may serve as an early surrogate endpoint for long-term survival in NPC.
Preliminary analysis of a phase II, multicenter, randomized, active-control study to evaluate the efficacy and safety of eganelisib (IPI 549) in combination with nivolumab compared to nivolumab monotherapy in patients with advanced urothelial carcinoma.
Authors: Piotr Tomczak, Lazar Popovic, Philippe Barthelemy, Aleksander Janicic, Elena Sevillano Fernandez, Delphine Borchiellini, Massimo Aglietta, José Maroto, Aurelien Carnot, Brenda O'Connell, NORA ZIZLSPERGER, Halle Huihong Zhang, Begoña P. Valderrama
Journal: Journal of Clinical Oncology (2021)

436 Background: Inhibition of the PD-1 pathway has demonstrated clinical benefit in metastatic urothelial carcinoma (mUC); however, response rates of 15% to 29% highlight the need for more effective therapies, especially for PD-L1- patients. Eganelisib is a first-in-class, novel, oral agent which selectively inhibits PI3K-γ, with the goal of improving the immune response to checkpoint inhibitors (CPI). Methods: Eligible patients (pts) with mUC who progressed on &gt; 1 platinum-based chemotherapy regimen and were CPI naïve were enrolled. Pts were randomized 2:1 to receive eganelisib in combination with nivolumab (EN) or placebo with nivolumab (PN). Pts were stratified by baseline circulating monocytic myeloid derived suppressor cells (mMDSC) level. The primary endpoint was objective response rate (ORR) per RECIST v1.1 in pts with high baseline mMDSC levels. Other endpoints included ORR, progression free survival (PFS) and overall survival (OS) in all pts and PD-L1 +/- pts. Results: We report preliminary data (as of 9/1/2020) for the first 49 pts with 33 randomized to receive EN and 16 PN. Preliminary ORR/PFS is presented in the table below. Except for the mMDSC high subgroup, ORR and PFS were improved in the EN arm compared to the PN arm. The duration of exposure was a median of 15 weeks for EN and 11 for PN. Most common all-Gr AEs (EN vs PN %) were pyrexia (33 vs 0), decreased appetite (30 vs 19), pruritis (24 vs 6), rash (24 vs 6), asthenia (21 vs 31), and transaminase elevation (21 vs 6). Most common Gr≥3 AEs (EN vs PN %) include hepatotoxicity (15 vs 0), transaminase elevation (12 vs 6), and rash (9 vs 0). Following an early safety review, eganelisib dose was reduced from 40 to 30 mg, resulting in a reduction of hepatic AEs. Conclusions: Preliminary data demonstrates that the combination of eganelisib, once reduced to 30 mg, and nivolumab was well tolerated with hepatic and skin-related toxicities more common in the EN arm. When compared to PN, the combination demonstrated an improved ORR and PFS, especially in the PD-L1- subset. Updated efficacy, including PFS and OS, safety and translational data will be presented. Clinical trial information: NCT03980041 . [Table: see text]
Abstract 11840: A Common Genetic Variant of the Cardiac Sodium Channel Predisposes to Drug-induced QT Prolongation
Authors: Yuko Wada, Laura L Daniel, Cristian M Shaffer, Andrew M Glazer, Kevin R Bersell, Marcia A Blair, Lynn Hall, Laura L Short, Tao Yang, Dan M Roden
Journal: Circulation (2019)

Background and Aim: Gain-of-function (GOF) variants in the cardiac voltage-gated sodium-channel (SCN5A) can cause type 3 Long QT syndrome (LQTS), which can lead to sudden cardiac death. However, so...
Oncolytic adenovirus with hyaluronidase activity that evades neutralizing antibodies: VCN-11
Authors: Ana Mato-Berciano, Sara Morgado, María V. Maliandi, Martí Farrera-Sal, Marta Gimenez-Alejandre, Mireia M. Ginestà, Rafael Moreno, Silvia Torres-Manjon, Paz Moreno, Marcel Arias-Badia, Luis A. Rojas, Gabriel Capellà, Ramon Alemany, Manel Cascallo, Miriam Bazan-Peregrino
Journal: Journal of Controlled Release (2021)
Real-world application of pre-orchiectomy miR-371a-3p test in testicular germ cell tumor (GCT) management.
Authors: Rohit R Badia, Dreaux Abe, Daniel Wong, Nirmish Singla, Anna Savelyeva, Nathan Chertack, Liwei Jia, Payal Kapur, Matthew Murray, James F. Amatruda, John T. Lafin, Aditya Bagrodia
Journal: Journal of Clinical Oncology (2021)

387 Background: Current serum tumor markers (STMs) for testicular germ cell tumor (GCT) are limited by low sensitivity. Growing evidence supports the use of circulating miR-371a-3p as a superior marker for malignant (viable) GCT management. We evaluated the real-world application of serum miR-371a-3p levels in detecting viable GCT among patients undergoing partial or radical orchiectomy. Methods: Serum samples were collected from 69 consecutive patients pre-orchiectomy. Performance characteristics of serum miR-371a-3p were compared with conventional STMs (AFP/β-hCG/LDH) between viable GCT patients and those without viable GCT on orchiectomy pathology. Relative miR-371a-3p levels were correlated with clinical course. Kruskal-Wallis test and linear and ordinal regression models were used for analysis. Results: For detecting viable GCT, combined conventional STMs had a specificity of 100%, sensitivity of 58%, and area under the curve (AUC) of 0.79 (Table). The miR-371a-3p test showed a specificity of 100%, sensitivity of 93%, and AUC of 0.978. Median relative expression of miR-371a-3p in viable GCT patients was &gt;6,800-fold higher than in patients lacking viable GCT. MiR-371a-3p levels correlated with composite stage (CS) (p=0.006), and, among CS I patients, independently associated with embryonal carcinoma percentage (p=0.0012) and tumor diameter (p&lt;0.0001). Six patients received orchiectomy after chemotherapy and were correctly predicted to have presence or absence of viable GCT by the miR-371a-3p test. Conclusions: If validated, the miR-371a-3p test can be used in conjunction with conventional STMs to aid clinical decision-making. A positive miR-371a-3p test in patients after preoperative chemotherapy or with solitary testes could potentially guide subsequent orchiectomy or observation. [Table: see text]
Illustration of temporal evolution in patients with metastatic renal cell carcinoma (mRCC) using both circulating tumor DNA (ctDNA) and tissue-based genomic data.
Authors: Zeynep Busra Zengin, Caroline Weipert, Joann Hsu, Nicholas Salgia, Chuck Hensel, Benjamin Louis Maughan, Nityam Rathi, Divyam Goel, Neeraj Agarwal, Toni K. Choueiri, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2021)

347 Background: We have previously demonstrated the feasibility of ctDNA assessment in mRCC and preliminarily showed agreement between ctDNA and tissue-based genomic findings (Zengin et al ESMO 2020). Our data suggested that the degree of agreement is dependent upon the temporal separation of blood and tissue samples. We sought to further explore this temporal impact in a separate validation cohort. Methods: Patients (pts) with mRCC who underwent ctDNA genomic profiling were identified. ctDNA analysis was performed using a CLIA-certified 73-74 gene panel (Guardant360). From this cohort we identified a subset of pts who also underwent tissue-based genomic profiling using either a whole exome sequencing platform (GemExtra [TGen, Phoenix, AZ]) or a targeted next generation sequencing platform (Foundation Medicine [Cambridge, MA] or Tempus [Chicago, IL]). Only alterations covered by both assays were included for the current analysis. The difference in the proportion of alterations detected on tissue and ctDNA was compared between these cohorts and at a 6-mo landmark using the χ 2 test. Results: In total, ctDNA and tissue based genomic profiling was assessed in 112 pts (M:F, 81:31); with most common histology was clear cell (85.7%). Median time between ctDNA and tissue assessments was 9.8 months (IQR 1.15-23.7). When examining paired samples in which &gt;1 ctDNA alteration was detected, 32% (43/133) of alterations detected on tissue were also detected in ctDNA. This proportion increased to 43% (29/67) when samples collected within 6 months of each other, and was 51% (28/55) in samples collected within 3 months of each other. There was no significant difference in the frequency of shared mutations between the cohorts (P=0.09; Table). Conclusions: Our study confirms that ctDNA and tissue-based genomic profiling continue to provide consistently high levels of agreement. Notably, the percentage of samples with ≥1 ctDNA alteration detected was significantly lower in both cohorts compared to previous studies in RCC. More shared alterations were found on ctDNA when both ctDNA and tissue-based assessment were obtained at closer intervals. [Table: see text]
Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys
Authors: Yunlong Tao, Scott C. Vermilyea, Matthew Zammit, Jianfeng Lu, Miles Olsen, Jeanette M. Metzger, Lin Yao, Yuejun Chen, Sean Phillips, James E. Holden, Viktoriya Bondarenko, Walter F. Block, Todd E. Barnhart, Nancy Schultz-Darken, Kevin Brunner, Heather Simmons, Bradley T. Christian, Marina E. Emborg, Su-Chun Zhang
Journal: Nature Medicine (2021)
Patient-reported outcomes of patients with advanced renal cell carcinoma (aRCC) treated with first-line nivolumab plus cabozantinib versus sunitinib: The CheckMate 9ER trial.
Authors: David Cella, Toni K. Choueiri, Steven I. Blum, Flavia Ejzykowicz, Melissa Hamilton, Joshua Zhang, Cristina Ivanescu, Robert J. Motzer
Journal: Journal of Clinical Oncology (2021)

285 Background: In the phase III, open-label CheckMate 9ER trial (NCT03141177), patients with aRCC were randomized 1:1 (stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk score, tumor programmed death ligand 1 expression, geographic region) to nivolumab 240 mg IV Q2W + cabozantinib 40 mg PO QD (N+C; n = 323) or sunitinib (S) 50 mg PO (4 weeks of 6-week cycles; n = 328) for first-line treatment until disease progression or unacceptable toxicity (max N treatment, 2 years). N+C met primary and secondary efficacy endpoints by significantly improving progression-free survival, overall survival, and objective response rate versus S in aRCC patients with a clear cell component. Here, we present in-depth health-related quality of life (HRQoL) patient-reported outcome (PRO) results, including overall between-group comparisons of treatment groups and time to confirmed deterioration (TCD). Methods: PROs in all randomized patients were an exploratory endpoint assessed using the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19) and EQ-5D-3L instruments. PRO assessments at baseline, common on-treatment scheduled visits, and common follow-up visits for both arms were analyzed. Changes from baseline were assessed using mixed-model repeated measures (MMRM), adjusting for baseline scores and stratification factors. TCD was calculated from Kaplan–Meier estimates and Cox proportional hazards models. Results: Median follow-up for overall survival was 18.1 months. PRO completion rates were &gt; 90% at baseline, and ≥ 80% at all on-treatment assessments (≥ 10 patients) through week 91 in both arms. The overall least squares mean difference in change from baseline favored N+C over S in FKSI-19 (all domains) and in EQ-5D-3L. Patients treated with N+C experienced less treatment burden, with decreased risk of confirmed deterioration across most measurements versus S, including FKSI-19 total, disease-related symptoms (DRS), DRS-physical (DRS-P), DRS-emotional (DRS-E), functional well-being (FWB), and EQ-5D-3L visual analog scale (VAS) scores (Table). Conclusions: Patients reported statistically significant HRQoL benefits with N+C versus S. Treatment with N+C significantly reduced the risk of deterioration in HRQoL scores, including in disease-related symptoms of kidney cancer. These results suggest that the superior efficacy of N+C over S comes with the additional benefit of improved HRQoL. Clinical trial information: NCT03141177 . [Table: see text]
Nosocomial Legionnaires' Disease
Authors: Paul L. Garbe
Journal: JAMA (1985)

Investigation of a recent outbreak of nosocomial legionnaires' disease—initially thought to be due to the documented presence of<i>Legionella pneumophila</i>in the hospital potable water—showed that aerosols from one or more cooling towers were the actual source of infection. From June 27 to Aug 25, 1983, nosocomial legionnaires' disease developed in 15 persons at a hospital in Rhode Island. Twelve (80%) of 15 case-patients occupied rooms in building 1, unit B, compared with eight (28%) of 29 control patients (odds ratio=10.8; 95% confidence interval=1.4 to 85.6). Subsequent investigation demonstrated that water in a cooling tower located 100 ft upwind of unit B was heavily contaminated with<i>L pneumophila</i>, serogroup 1, subgroup 1, 2, 4, 5. The same strain was isolated from nine of the patients and from the make-up water for the tower. Active surveillance during the ten months following decontamination of the cooling tower identified no additional cases of nosocomial legionnaires' disease, although the hospital potable water had not been treated. While recommendations have been made for controlling nosocomial legionnaires' disease by heating or hyperchlorination of hospital potable water, this outbreak demonstrates the importance of an adequate epidemiologic-environmental investigation in choosing the appropriate control strategy. (<i>JAMA</i>1985;254:521-524)
Correlation of NKG2D and CD158b receptor expression and NK cell cytotoxicity in metastatic melanoma patients
Authors: Gordana Konjevi, Katarina Mirja, Martinovi, Vladimir Jurisi, Nada Babovi
Journal: Cancer Research (2007)

4308  The first line of antitumor immune defense is mediated by natural killer (NK) cells, as the main effector subpopulation of the innate immune system. The activity of NK cells is regulated by activating and inhibitory receptors whose balance determines whether tumor target cells will be susceptible to NK cell lysis. In this study we evaluated in 66 metastatic melanoma (MM) patients and 50 controls NK cytotoxic activity by the 51-Cr release assay and the expression of activating NKG2D and CD161 receptors and KIR CD158a and CD158b receptors on CD3-CD16+ NK cells by Flow cytometry. We show that MM patients have significantly impaired NK cell activity compared to healthy controls against K562 and a melanoma, FemX, tumor target cell lines. We show for the first time that the expression of NKG2D and CD161 receptor on CD3-CD16+NK cells of MM patients is significantly lower compared to controls, while the expression of KIR receptors, CD158a and CD158b, on CD3-CD16+ NK did not differ significantly in MM patients compared to controls.Also, the expression of NKG2D, CD161, CD158a and CD158b receptors on CD16bright and CD16dim NK cell subsets shows significantly decreased expression of CD161 and CD158b receptors on CD16bright NK cell subpopulation and the expression of CD158b receptor on CD16dim NK cell subpopulation in MM patients compared to controls. Further analyses of antigen density indicates a decrease in CD161 and an increase in CD158b fluorescence intensity geomean on CD16bright NK cell subset. Further analyses indicate a new finding of significant positive correlation of NK cell cytotoxicity of MM patients and expression of NKG2D activating receptor, as well as negative correlation of NK cell cytotoxicity with the expression of CD158b on CD3-CD16+ NK cell subset. Therefore, in this study we show for the first time that impaired NK cell cytotoxicity of MM patients may be due to decreased expression of NKG2D and CD161 receptors on CD3-CD16+ NK cells. In the CD16bright mature and cytotoxic NK cell subset a significant decrease of CD161 and CD158b receptors, and their unfavorably changed antigen fluorescence intensity geomeans, may contribute to their dysfunction. Moreover, we show that, contrary to healthy controls, a positive correlation between NKG2D activating receptor expression and NK cell cytotoxicity, as well as a negative correlation of NK cell activity and the expression of CD158b receptor in MM patients.