tbuckley/cabot-search huggingface dataset:
Efficacy of live attenuated and inactivated influenza vaccines among children in rural India: A 2-year, randomized, triple-blind, placebo-controlled trial
Authors: Anand Krishnan, Lalit Dar, Siddhartha Saha, Venkatesh Vinayak Narayan, Rakesh Kumar, Ramesh Kumar, Ritvik Amarchand, Shivram Dhakad, Reshmi Chokker, Avinash Choudekar, Giridara Gopal, Aashish Choudhary, Varsha Potdar, Mandeep Chadha, Kathryn E. Lafond, Stephen Lindstrom, Marc-Alain Widdowson, Seema Jain
Journal: PLoS Medicine (2021)

Background Influenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years. Methods and findings In June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV ( n = 1,015), IIV ( n = 1,010), nasal placebo ( n = 507), or IPV ( n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years. Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year. In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted. Conclusions In this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children. Trial registration Clinical Trials Registry of India CTRI/2015/06/005902 .
A hypoxia responsive nanoassembly for tumor specific oxygenation and enhanced sonodynamic therapy
Authors: Kuikun Yang, Ludan Yue, Guocan Yu, Lang Rao, Rui Tian, Jianwen Wei, Zhiqing Yang, Chen Sun, Xiangjun Zhang, Mengze Xu, Zhen Yuan, Xiaoyuan Chen, Ruibing Wang
Journal: Biomaterials (2021)
INCREMENTAL PROGNOSTIC VALUE OF NT-PROBNP IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY PATIENTS
Authors: Erika Hutt, Amgad Mentias, Alaa Alashi, Agostina Fava, Zoran Popovic, Maran Thamilarasan, Per Wierup, Nicholas Smedira, Harry Lever, Milind Desai
Journal: Journal of the American College of Cardiology (2021)
BIOMARKERS OF CARDIAC DAMAGE AND STRETCH BUT NOT LEFT VENTRICULAR MASS ALONE IDENTIFY PATIENTS WITH A MALADAPTIVE RESPONSE TO AORTIC STENOSIS AT INCREASED RISK OF MORTALITY
Authors: Elliot Stein, William Fearon, Sammy Elmariah, Juyong Kim, Samir Kapadia, Dharam Kumbhani, Linda Gillam, Brian Whisenant, Nishath Quader, Alan Zajarias, Frederick Welt, Anthony Bavry, Megan Coylewright, Robert Piana, Ravinder Mallugari, Deepak Gupta, Anna Vatterott, Natalie- Jackson, Shi Huang, Brian Lindman
Journal: Journal of the American College of Cardiology (2021)
Biology and therapy of human small cell lung cancer (SCLC) in novel orthotopic nude mouse models
Authors: Takeshi Isobe, Amir Onn, Wenjuan Wu, Tomoaki Shintani, Satoshi Itasaka, Keiko Shibuya, Waun K. Hong, Michael S. O’Reilly, Roy S. Herbst
Journal: Cancer Research (2004)

5136  SCLC is one of the most aggressive phenotypes of human lung cancer and conveys a poor prognosis due to the limited efficacy of existing treatment strategies. To provide clinically relevant strategies for studying new therapeutics and tumor biology, we developed three orthotopic models of human SCLC in nude mice. Three different human SCLC cell lines (H69A, a variant of the NCI-H69 cell line selected for invasiveness in vitro on semisolid agarose; NCI-H187; and NCI-N417) were studied. Tumor cells (1.5 x 106 cells in growth factor reduced Matrigel) were injected into the left lung of anesthetized nude mice. Tumors developed within 8 to 12 weeks and new cell lines were established from the lung tumors (H69ALu, H187Lu, and N417Lu) to select for a reproducible growth pattern for the orthotopic tumors and to minimize variation of tumor size. For each model, tumors started as a solitary mass in the left lung tumor that then spread to mediastinal and axillary lymph nodes, and to the right lung in a pattern similar to that observed in the clinic. N417Lu and H187Lu formed a 100 mm3 left lung mass within 30-40 days of injection, and mice were moribund within 50 to 60 days of injection. H69ALu tumors reached a volume of 100 mm3 within 60 days of injection and mice became moribund within 4 to 6 months. All tumors larger than 100mm3 expressed the proangiogenic factors bFGF and IL-8 (at the tumor periphery), and VEGF/VPF (tumor center and periphery).To compare the efficacy of different chemotherapeutic agents in each of our models, groups of mice (n = 5) were randomized to weekly i.p. treatment with saline (control), 6 mg/kg/mouse of cisplatin (CDDP), 50 mg/kg/mouse of paclitaxel, 125 mg/kg/mouse of irinotecan (CPT-11), or 40 mg/kg/mouse of etoposide. Therapy was initiated on day 10 (H187Lu and N417Lu) or day 20 (H69ALu) after tumor injection coincident with the formation of microscopic lesions. Therapy was well tolerated and mice were killed after five (H187Lu and N417Lu) or seven (H69ALu) weeks of therapy. Tumor burden was assessed by lung and tumor weight (g) and primary tumor volume (mm3). CPT-11 significantly inhibited the growth and progression of N417Lu tumors as compared to control (lung and tumor weight 0.23 ± 0.01 vs. 0.62 ± 0.15, p = 0.02; tumor volume 0.3 ± 0.1 vs. 364 ± 156, p = 0.03) and CDDP significantly inhibited the growth and progression of H69ALu tumors as compared to control (tumor volume 0.3 ± 0.1 vs. 100 ± 0.01, p = 0.04). The development of our orthotopic models of SCLC provides a better understanding the biology of this disease and will enable evaluation of novel therapeutic strategies (supported by a grant from the Department of Defense (DAMD 17-02-1-0706 to W.K.H.).
Abstract 13324: Prolonged Accumulation of Macrophages in Endo-Myocardial Biopsies After Remission of Heart Failure With Preserved Ejection Fraction
Authors: Hiroyuki Takahama, Yasuo Sugano, Keiko Ogo, Yasuhiro Hamatani, Masashi Amano, Atsushi Okada, Makoto Amaki, Takuya Hasegawa, Hideaki Kanzaki, Toshihisa Anzai, Satoshi Yasuda, Hatsue Ishibashi-Ueda, Chisato Izumi
Journal: Circulation (2019)

Introduction: Recent studies suggest that coronary microvascular endothelial dysfunction may play an important role in stiffening myocardium in heart failure with preserved ejection fraction (HFpEF...
In recently detoxified alcohol-dependent adults, acamprosate increases abstinence maintenance and reduces dropout
Authors: Hemraj Pal
Journal: Annals of Internal Medicine (2021)

Source Citation Cheng HY, McGuinness LA, Elbers RG, et al. Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis. BMJ. 2020;371:m3934. 33239318
Overcoming bacteriophage insensitivity in <i>Staphylococcus aureus</i> using clindamycin and azithromycinat subinhibitory concentrations
Authors: Sha Liu, Yin Zhao, Andrew Hayes, Karen Hon, Guimin Zhang, Catherine Bennett, Hua Hu, John Finnie, Sandra Morales, Linda Shearwin, Alkis J. Psaltis, Keith Shearwin, Peter‐John Wormald, Sarah Vreugde
Journal: Allergy (2021)

Staphylococcus aureus is a pathogen of major concern in both acute infections and chronic conditions such as chronic rhinosinusitis (CRS). Bacteriophage (phage) therapy has recently regained interest for its potential to treat infections caused by antibiotic resistant strains including Methicillin Resistant Staphylococcus aureus (MRSA). However, bacteria can adapt and become resistant to phages. The aim of this study is to determine the potential for antibiotics to overcome phage resistance.The susceptibility of S. aureus clinical isolates (CIs) to phages J-Sa36, Sa83 and Sa87 alone or in combination with protein synthesis inhibitor (PSI) antibiotics clindamycin, azithromycin and erythromycin was assessed using plaque spot assays, minimum inhibitory concentration (MIC) assays, double layer spot assays and resazurin assays. The safety and efficacy of subinhibitory PSI antibiotics in combination with phage was tested in a Sprague Dawley rat model of sinusitis infected with a phage resistant S. aureus CI.All three antibiotics at subinhibitory concentrations showed synergy when combined with all 3 phages against S. aureus CIs in planktonic and biofilm form and could sensitize phage-resistant S. aureus to promote phage infection. The combination of topical subinhibitory clindamycin or azithromycin and phage was safe and could eradicate S. aureus sinonasal biofilms in vivo.Subinhibitory concentrations of PSI antibiotics could sensitize phage-resistant S. aureus and MRSA strains to phages in vitro and in vivo. This data supports the potential use of phage-PSI antibiotic combination therapies, in particular for difficult-to-treat infections with phage-resistant S. aureus and MRSA strains.
Chinese Clinical Ethicists Accept Physicians’ Benevolent Deception of Patients
Authors: Hui Zhang, Li Tian, Hongmei Zhang, Zhenxiang Zhang, Yuming Wang
Journal: The American Journal of Bioethics (2021)

In “Deception and the Clinical Ethicist,” Meyers (2021) defends the argument that the clinical ethicist should sometimes be an active participant in the deception of patients and their families. Me...
Next-generation microbiology: from comparative genomics to gene function
Authors: Carolin M. Kobras, Andrew K. Fenton, Samuel K. Sheppard
Journal: Genome biology (2021)

Abstract Microbiology is at a turning point in its 120-year history. Widespread next-generation sequencing has revealed genetic complexity among bacteria that could hardly have been imagined by pioneers such as Pasteur, Escherich and Koch. This data cascade brings enormous potential to improve our understanding of individual bacterial cells and the genetic basis of phenotype variation. However, this revolution in data science cannot replace established microbiology practices, presenting the challenge of how to integrate these new techniques. Contrasting comparative and functional genomic approaches, we evoke molecular microbiology theory and established practice to present a conceptual framework and practical roadmap for next-generation microbiology.
Macrophage membrane-mediated targeted drug delivery for treatment of spinal cord injury regardless of the macrophage polarization states
Authors: Wei Tang, Yi Yang, Ling Yang, Mei Tang, Ying Chen, Chong Li
Journal: Asian Journal of Pharmaceutical Sciences (2021)

Targeted delivery of therapeutics for spinal cord injury (SCI) has been a long-term challenge due to the complexity of the pathological procession. Macrophage, as an immune cell, can selectively accumulate at the trauma site after SCI. This intrinsic targeting, coupled with good immune-escaping capacity makes macrophages an ideal source of biomimetic delivery carrier for SCI. Worth mentioning, macrophages have multiple polarization states, which may not be ignored when designing macrophage-based delivery systems. Herein, we fabricated macrophage membrane-camouflaged liposomes (RM-LIPs) and evaluated their abilities to extend drug circulation time and target the injured spinal cord. Specially, we detected the expression levels of the two main targeted receptors Mac-1 and integrin α4 in three macrophage subtypes, including unactivated (M0) macrophages, classically activated (M1) macrophages and alternatively activated (M2) macrophages, and compared targeting of these macrophage membrane-coated nanoparticles for SCI. The macrophage membrane camouflage decreased cellular uptake of liposomes in RAW264.7 immune cells and strengthened binding of the nanoparticle to the damaged endothelial cells in vitro. RM-LIPs can prolong drug circulation time and actively accumulate at the trauma site of the spinal cord in vivo. Besides, RM-LIPs loaded with minocycline (RM-LIP/MC) showed a comprehensive therapeutic effect on SCI mice, and the anti-pyroptosis was found to be a novel mechanism of RM-LIP/MC treatment of SCI. Moreover, the levels of Mac-1 and integrin α4 in macrophages and the targeting of RM-LIP for SCI were found to be independent of macrophage polarization states. Our study provided a biomimetic strategy via the biological properties of macrophages for SCI targeting and treatment.
Cancer Mutational Processes Vary in Their Association with Replication Timing and Chromatin Accessibility
Authors: Adar Yaacov, Oriya Vardi, Britny Blumenfeld, Avraham Greenberg, Dashiell J. Massey, Amnon Koren, Sheera Adar, Itamar Simon, Shai Rosenberg
Journal: Cancer Research (2021)

Abstract Cancer somatic mutations are the product of multiple mutational and repair processes, both of which are tightly associated with DNA replication. Distinctive patterns of somatic mutation accumulation, termed mutational signatures, are indicative of processes sustained within tumors. However, the association of various mutational processes with replication timing (RT) remains an open question. In this study, we systematically analyzed the mutational landscape of 2,787 tumors from 32 tumor types separately for early and late replicating regions using sequence context normalization and chromatin data to account for sequence and chromatin accessibility differences. To account for sequence differences between various genomic regions, an artificial genome–based approach was developed to expand the signature analyses to doublet base substitutions and small insertions and deletions. The association of mutational processes and RT was signature specific: Some signatures were associated with early or late replication (such as SBS7b and SBS7a, respectively), and others had no association. Most associations existed even after normalizing for genome accessibility. A focused mutational signature identification approach was also developed that uses RT information to improve signature identification; this approach found that SBS16, which is biased toward early replication, is strongly associated with better survival rates in liver cancer. Overall, this novel and comprehensive approach provides a better understanding of the etiology of mutational signatures, which may lead to improved cancer prevention, diagnosis, and treatment. Significance: Many mutational processes associate with early or late replication timing regions independently of chromatin accessibility, enabling development of a focused identification approach to improve mutational signature detection.
Oral delivery of micro/nanoparticulate systems based on natural polysaccharides for intestinal diseases therapy: Challenges, advances and future perspectives
Authors: Aline Martins dos Santos, Suzana Gonçalves Carvalho, Andréia Bagliotti Meneguin, Rafael Miguel Sábio, Maria Palmira Daflon Gremião, Marlus Chorilli
Journal: Journal of Controlled Release (2021)
SINGLE-DOSE PHARMACOKINETICS OF BMS-986177/JNJ-70033093 (BMS-177/JNJ-3093) IN PARTICIPANTS WITH NORMAL RENAL FUNCTION AND PARTICIPANTS WITH MODERATE OR SEVERE RENAL IMPAIRMENT
Authors: Vidya Perera, Grigor Abelian, Danshi Li, Zhaoqing Wang, Liping Zhang, Susan Lubin, Akintunde Bello, Bindu Murthy
Journal: Journal of the American College of Cardiology (2021)
Effect of a Scalable School-Based Intervention on Cardiorespiratory Fitness in Children
Authors: Chris Lonsdale, Taren Sanders, Philip Parker, Michael Noetel, Timothy Hartwig, Diego Vasconcellos, Jane Lee, Devan Antczak, Morwenna Kirwan, Philip Morgan, Jo Salmon, Marj Moodie, Heather McKay, Andrew Bennie, Ronald C. Plotnikoff, Renata Cinelli, David Greene, Louisa Peralta, Dylan Cliff, Gregory Kolt, Jennifer Gore, Lan Gao, James Boyer, Ross Morrison, Charles Hillman, Tatsuya T. Shigeta, Elise Tan, David R. Lubans
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> Cardiorespiratory fitness is an important marker of childhood health and low fitness levels are a risk factor for disease later in life. Levels of children's fitness have declined in recent decades. Whether school-based physical activity interventions can increase fitness at the population level remains unclear. <h3>Objective</h3> To evaluate the effect of an internet-based intervention on children's cardiorespiratory fitness across a large number of schools. <h3>Design, Setting, and Participants</h3> In this cluster randomized clinical trial, 22 government-funded elementary schools (from 137 providing consent) including 1188 students stratified from grades 3 and 4 in New South Wales, Australia, were randomized. The other schools received the intervention but were not included in the analysis. Eleven schools received the internet-based intervention and 11 received the control intervention. Recruitment and baseline testing began in 2016 and ended in 2017. Research assistants, blinded to treatment allocation, completed follow-up outcome assessments at 12 and 24 months. Data were analyzed from July to August 2020. <h3>Interventions</h3> The internet-based intervention included standardized online learning for teachers and minimal in-person support from a project mentor (9-10 months). <h3>Main Outcomes and Measures</h3> Multistage 20-m shuttle run test for cardiorespiratory fitness. <h3>Results</h3> Of 1219 participants (49% girls; mean [SD] age, 8.85 [0.71] years) from 22 schools, 1188 students provided baseline primary outcome data. At 12 months, the number of 20-m shuttle runs increased by 3.32 laps (95% CI, 2.44-4.20 laps) in the intervention schools and 2.11 laps (95% CI, 1.38-2.85 laps) in the control schools (adjusted difference = 1.20 laps; 95% CI, 0.17-2.24 laps). By 24 months, the adjusted difference was 2.22 laps (95% CI, 0.89-3.55 laps). The cost per student was AUD33 (USD26). <h3>Conclusions and Relevance</h3> In this study, a school-based intervention improved children's cardiorespiratory fitness when delivered in a large number of schools. The low cost and sustained effect over 24 months of the intervention suggests that it may have potential to be scaled at the population level. <h3>Trial Registration</h3> http://anzctr.org.auIdentifier:ACTRN12616000731493
CIRCULATING GUT METABOLITES IN PATIENTS WITH HEART FAILURE WITH PRESERVED, REDUCED OR RECOVERED EJECTION FRACTION, AND IN THE AGE- AND SEX-MATCHED CONTROLS: RESULTS FROM THE PRESERVED VS. REDUCED EJECTION FRACTION BIOMECHANICAL MARKER REGISTRY FOR AMBULATORY HEART FAILURE PATIENTS (PREFER-HF) STUDY
Authors: Neyat Fiseha, Andrew Abboud, Austin Nguonly, Asher Bean, David Dudzinski, Roy Chen, Kevin Wei, Daniel Zlotoff, Kemar Brown, Melvin Joice, Svati Shah, Sanjiv Shah, Priscilla Hsue, James Januzzi, Hanna Gaggin
Journal: Journal of the American College of Cardiology (2021)
GLOBAL LONGITUDINAL STRAIN ASSESMENT BY COMPUTED TOMOGRAPHY IN PATIENTS WITH VARIOUS DEGREES OF EPICARDIAL CORONARY ARTERY DISEASE
Authors: Erasmo De La Pena-Almaguer, Jose G. Paredes-Vazquez, Mariana Vanoye-Tamez, Cecilia Marini, Jaime A. Guajardo-Lozano, Luis F. De Los Rios, Daniela Mares-Custodio
Journal: Journal of the American College of Cardiology (2021)
Covid-19: Vaccines will be tested against variants of concern after £29m funding boost from UK government
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Covid-19: Vaccines will be tested against variants of concern after £29m funding boost from UK government Elisabeth MahaseThe efficacy of different covid-19 vaccines against variants of concern, including those first identified in the UK and South Africa, will be assessed by Public Health England after a funding boost from the government.The UK government's Vaccine Taskforce has announced £29.3m (€34m; $40.8m) in extra funding for new facilities at Porton Down in Wiltshire, which will increase the site's capacity for testing variant samples from 1500 to 3000 a week.This is on top of a £19.7m investment approved last September to increase capacity for clinical testing of vaccines.The government has said that the Porton Down facilities will also be used for work to update existing vaccines to specifically target variants.Data are currently limited on the efficacy of vaccines against SARS-CoV-2 variants, as many of the earlier vaccine trials were carried out before these variants emerged. 1
Abstract 17320: Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Clinical Outcomes in COVID-19
Authors: Michael Pan, Tariq Azam, Husam Shadid, Hanna Berlin, Chelsea Meloche, Rafey Feroze, Jeff Leya, Patrick O'Hayer, Elizabeth Anderson, Rayan Kaakati, abbas bitar, Kishan Padalia, Daniel Perry, Pennelope Blakely, Peiyao Zhao, Lili Zhao, Salim Hayek
Journal: Circulation (2020)

Introduction: COVID-19 is caused by infection with SARS-CoV2 which uses ACE2 as its host receptor. RAS inhibitors such as ACE-inhibitors and ARBs (ACEI/ARB) may increase ACE2 levels. ACE2 levels may also have a lung protective role in ARDS. There is concern over the safety of using these medications in patients with COVID-19. Hypothesis: To characterize the association of a history of ACEI/ARB use by hospitalized patients with COVID-19 and with in-hospital outcomes. Methods: The Michigan Medicine Covid-19 Cohort (M 2 C 2 ) is an ongoing prospective observational study in which detailed clinical, laboratory and outcomes data were collected from chart review of consecutive adult patients hospitalized for COVID-19. Patients who were positive for SARS-CoV-2 infection but without symptoms of COVID-19 were not included in this cohort. We identified 490 patients admitted between March 1 st and May 1 st for COVID-19, of whom all 490 had data on whether they took ACEI/ARB prior to hospitalization. We examined the association between ACEI/ARB use and all-cause death, respiratory failure and acute kidney injury (AKI) during their hospitalization. Results: 175 (35.7%) patients were taking ACEI/ARB prior to hospitalization (ACEI/ARB group; mean age 63.6 [SD 13.9]; 64% men) and 315 (64.3%) were not taking ACEI/ARB (non-ACEI/ARB group; median age 58.6 [SD 16.1]; 54.3% men). The risk of developing ARDS was not significantly different between the ACEI/ARB group and non-ACEI/ARB group (47.4% vs 43.5%, p-value 0.53) and neither was the risk death (15.4% vs 16.8%, p-value 0.97), despite a higher prevalence of comorbidities in the ACEI/ARB group including hypertension (96.6% vs 51.4%, p-value &lt;0.001), diabetes mellitus (58.9% vs 34.6%, p-value &lt;0.001), coronary artery disease (22.9% vs 11.4%, p-value 0.002), CHF (16.0% vs 12.1%, p-value 0.26), and CKD (32.0% vs 13.7%, p-value &lt;0.001). Conclusions: Among hospitalized patients with COVID-19, prior to hospitalization use ACEI/ARB was not associated with significantly different risk of ARDS or mortality despite having higher rates of comorbidities in the ACEI/ARB group.
ANOMALOUS LEFT CORONARY ARTERY FROM RIGHT CORONARY CUSP: AN FFRCT PERSPECTIVE
Authors: Gurjaspreet Bhattal, Karim Al-Azizi, Chadi Dib, John Hollowell, Srinivasa Potluri, Molly Szerlip, Sameh Sayfo
Journal: Journal of the American College of Cardiology (2021)