The emergence of SARS-CoV-2 variants with mutations in the spike protein is raising concerns about the efficacy of infection- or vaccine-induced antibodies. We compared antibody binding and live ...virus neutralization of sera from naturally infected and Moderna-vaccinated individuals against two SARS-CoV-2 variants: B.1 containing the spike mutation D614G and the emerging B.1.351 variant containing additional spike mutations and deletions. Sera from acutely infected and convalescent COVID-19 patients exhibited a 3-fold reduction in binding antibody titers to the B.1.351 variant receptor-binding domain of the spike protein and a 3.5-fold reduction in neutralizing antibody titers against SARS-CoV-2 B.1.351 variant compared to the B.1 variant. Similar results were seen with sera from Moderna-vaccinated individuals. Despite reduced antibody titers against the B.1.351 variant, sera from infected and vaccinated individuals containing polyclonal antibodies to the spike protein could still neutralize SARS-CoV-2 B.1.351, suggesting that protective humoral immunity may be retained against this variant.
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•Antibodies from infected and vaccinated individuals bind to the B.1.351 RBD•Convalescent sera through eight months can neutralize the B.1.351 variant•Serum from vaccinated individuals retains neutralization against the B.1.351 variant
In this study, Edara et al. (2021) report that, despite reduced antibody binding to the B.1.351 RBD, sera from infected (acute and convalescent) and Moderna (mRNA-1273)-vaccinated individuals were still able to neutralize the SARS-CoV-2 B.1.351 variant, suggesting that protective humoral immunity may be retained against this variant.
Enrollment into online schooling at the k-12 level continues to grow. As a result, many traditional public schools have been offering an online alternative to students. A position at many schools, ...called a cyber coordinator, has been created to facilitate enrollment, provide technical and transitional support to students, and work as a liaison between the students and teachers, administration, and guidance. In spite of the best efforts of online schools, there still seems to be a high attrition rate among students. Distance education research posed theories including the Transactional Distance Theory (Moore, 1991) to explain why there may exist a gap in the communication between the instructor and the student that could potentially lead to attrition. This study focused on the secondary student with the theoretical framework being the Transactional Distance Theory and sought to find the cause of the attrition rate; the effects of attrition on the quality of a high school class; and what action can be taken to address the attrition rate by interviewing cyber coordinators in Southwestern Pennsylvania. Through semistructured interviews, it was found that the online schools largely serve as an alternative education space for at-risk students who still yearn for a sense of community with peers and instructors. It was also found that although the cyber coordinators felt that the rigor of the course was high, they also felt that the structure of the course did not meet the needs of the online learner. The final finding from the cyber coordinators was that motivation was the overwhelming key to success in the secondary online classroom.
Objective
Prehabilitation is increasingly being used to mitigate treatment‐related complications and enhance recovery. An individual's state of health at diagnosis, including obesity, physical ...fitness and comorbidities, are influencing factors for the occurrence of adverse effects. This review explores whether prehabilitation works in improving health outcomes at or beyond the initial 30 days post‐treatment and considers the utility of prehabilitation before cancer treatment.
Methods
A database search was conducted for articles published with prehabilitation as a pre‐cancer treatment intervention between 2009 and 2017. Studies with no 30 days post‐treatment data were excluded. Outcomes post‐prehabilitation were extracted for physical function, nutrition and patient‐reported outcomes.
Results
Sixteen randomised controlled trials with a combined 2017 participants and six observational studies with 289 participants were included. Prehabilitation interventions provided multi‐modality components including exercise, nutrition and psychoeducational aspects. Prehabilitation improved gait, cardiopulmonary function, urinary continence, lung function and mood 30 days post‐treatment but was not consistent across studies.
Conclusion
When combined with rehabilitation, greater benefits were seen in 30‐day gait and physical functioning compared to prehabilitation alone. Large‐scale randomised studies are required to translate what is already known from feasibility studies to improve overall health and increase long‐term cancer patient outcomes.
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•Imidazo-thienopyridine based TLR7 agonists were synthesized for use as ADC payloads.•Several compounds induced the release of proinflammatory cytokines in a PBMC assay.•Drug-linkers ...were conjugated to trastuzumab via stochastic thiol-maleimide chemistry.•Anti-tumor activity was observed in a NCI-N87 gastric carcinoma xenograft model.
Pairing immunostimulatory small molecules with the targeting capability of an antibody has emerged as a novel therapeutic modality with the potential to treat a variety of solid tumors. A series of compounds based on an imidazo-thienopyridine scaffold were synthesized and tested for their ability to agonize the innate immune sensors toll-like receptor 7 and 8 (TLR7/8). Structure-activity relationship (SAR) studies revealed that certain simple amino-substituents could enable TLR7 agonism at low nanomolar concentrations. Drug-linkers containing either payload 1 or 20h were conjugated to the HER2-targeting antibody trastuzumab at the interchain disulfide cysteine residues using a cleavable valine-citrulline dipeptide linker and stochastic thiol-maleimide chemistry. In vitro, these immune-stimulating antibody drug-conjugates (ADCs) were found to induce cytokine release in a murine splenocyte assay when co-cultured with the HER2-high NCI-N87 cancer cell line. In vivo, tumor regression was observed with a single dose in an NCI-N87 gastric carcinoma xenograft model in BALB/c nude mice.
Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.
To investigate if ensovibep, in addition to ...remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.
Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).
Multinational, multicenter trial.
Adults hospitalized with COVID-19.
Intravenous ensovibep, 600 mg, or placebo.
Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.
An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep (
= 247) or placebo (
= 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30;
= 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio sHR, 1.06 CI, 0.88 to 1.28; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 CI, 0.77 to 1.47; HR < 1 would favor ensovibep).
The trial was prematurely stopped because of futility, limiting power for the primary outcome.
Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified.
National Institutes of Health.
PURPOSE:The 2013 American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults recommends ...high-intensity statin therapy in patients aged ≤75 y with clinical coronary artery disease (CAD). The effectiveness of cardiac rehabilitation (CR) in lipid management and guideline adherence is unknown. The purpose of this study is to determine whether CR participation affects guideline-driven achievement for statin use.
METHODS:This multicenter retrospective study evaluated statin utilization in patients pre- and post-CR between January 1, 2014, and August 31, 2015. Records for patients with known CAD who completed 18 or more CR sessions were reviewed for statin-drug use and dose before and after CR and documented statin intolerance.
RESULTS:Of the total 468 patients, 76% were male with mean age ± SD = 66.0 ± 10.8 y and range of 32 to 89 y. Patients aged ≤75 y (n = 375) showed a modest but statistically significant increase (P = .0006) in high-intensity statin use post-CR (56.3%-61.1%). Males demonstrated a significant increase in high-intensity statin use (P = .0005). Of the 146 patients aged ≤75 y not on high-intensity statins post-CR, only 21 had history of statin intolerance. Of the subjects aged >75 y (n = 93), 91% were already on high- or moderate-intensity statins with no significant change during CR.
CONCLUSIONS:Patients aged ≤75 y following CR completion increased high-intensity statin use but only by 4.8% and 33% of subjects were inadequately treated. The updated 2013 treatment recommendations simplified statin use, yet substantial data continue to reveal that guideline achievement even post-CR remains limited.
A critical inquiry into the politics, practices, and infrastructures of open access and the reconfiguration of scholarly communication in digital societies. The Open Access Movement proposes to ...remove price and permission barriers for accessing peer-reviewed research work—to use the power of the internet to duplicate material at an infinitesimal cost-per-copy. In this volume, contributors show that open access does not exist in a technological or policy vacuum; there are complex social, political, cultural, philosophical, and economic implications for opening research through digital technologies. The contributors examine open access from the perspectives of colonial legacies, knowledge frameworks, publics and politics, archives and digital preservation, infrastructures and platforms, and global communities. The contributors consider such topics as the perpetuation of colonial-era inequalities in research production and promulgation; the historical evolution of peer review; the problematic histories and discriminatory politics that shape our choices of what materials to preserve; the idea of scholarship as data; and resistance to the commercialization of platforms. Case studies report on such initiatives as the Making and Knowing Project, which created an openly accessible critical digital edition of a sixteenth-century French manuscript, the role of formats in Bruno Latour's An Inquiry into Modes of Existence, and the Scientific Electronic Library Online (SciELO), a network of more than 1,200 journals from sixteen countries. Taken together, the contributions represent a substantive critical engagement with the politics, practices, infrastructures, and imaginaries of open access, suggesting alternative trajectories, values, and possible futures.
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