Measurement of HIV Rev-Rev Response Element Functional Activity.

Retroviruses must overcome cellular restrictions to the nucleocytoplasmic export of viral mRNAs that retain introns in order to complete their replication cycle. HIV accomplishes this using a system comprised of a trans-acting viral protein, Rev, and a cis-acting RNA secondary structure in the viral genome, the Rev-Response Element (RRE). HIV primary isolates differ with respect to the sequence and functional activity of the Rev-RRE system.

Machine Learning-based Analysis of Publications Funded by the National Institutes of Health's Initial COVID-19 Pandemic Response.

Background: The National Institutes of Health (NIH) mobilized more than $4 billion in extramural funding for the COVID-19 pandemic. Assessing the research output from this effort is crucial to understanding how the scientific community leveraged federal funding and responded to this public health crisis.

Methods: NIH-funded COVID-19 grants awarded between January 2020 and December 2021 were identified from NIH Research Portfolio Online Reporting Tools Expenditures and Results using the "COVID-19 Response" filter.

Analysis of National Institutes of Health Funding for the COVID-19 Pandemic.

Background: Evaluating the National Institute's Health's (NIH's) response to the coronavirus disease 2019 (COVID-19) pandemic via grants and clinical trials is crucial to determining the impact they had on aiding US citizens. We determined how the NIH's funding for COVID-19 research was disbursed and used by various institutions across the United States.

Methods: We queried NIH RePORTER and isolated COVID-19-related grants from January 2020 to December 2021.

Pulmonary Function and Survival 1 Year After Dupilumab Treatment of Acute Moderate to Severe Coronavirus Disease 2019: A Follow-up Study From a Phase 2a Trial.

Background: We previously conducted a phase 2a randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in people hospitalized with coronavirus disease 2019 (COVID-19) (NCT04920916). Based on our preclinical data suggesting that downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our phase 2a study at 1 year for assessment of post-COVID-19 conditions.

Methods: Subjects at 1 year after treatment underwent pulmonary function tests, high-resolution computed tomographic imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored.

Spatial patterns of reproduction suggest marginal habitat limits continued range expansion of black bears at a forest-desert ecotone.

Investigating spatial patterns of animal occupancy and reproduction in peripheral populations can provide insight into factors that form species range boundaries. Following historical extirpation, American black bears () recolonized the western Great Basin in Nevada from the Sierra Nevada during the late 1900s. This range expansion, however, has not continued further into the Great Basin despite the presence of additional habitat.

Rev-Rev Response Element Activity Selection Bias at the Human Immunodeficiency Virus Transmission Bottleneck.

Background: Sexual transmission of human immunodeficiency virus (HIV) is inefficient and results in selection of viral variants based on incompletely understood factors. Functional variation in the Rev-Rev response element (RRE) regulatory axis of HIV affect replication kinetics and relative expression of viral proteins. We explored whether differences in this axis among viral isolates affect transmission fitness.

Phase 1 Study of Hypofractionated Proton Beam Radiation Therapy in Adjuvant Pancreatic Cancer (PROTON-PANC).

Purpose: Despite improvement in systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) frequently experience local recurrence. We sought to determine the safety of hypofractionated proton beam radiation therapy (PBT) during adjuvant chemotherapy.

Methods And Materials: Nine patients were enrolled in a single-institution phase 1 trial (NCT03885284) between 2019 and 2022.

Pulmonary function and survival one year after dupilumab treatment of acute moderate to severe COVID-19: A follow up study from a Phase IIa trial.

Background: We previously conducted a Phase IIa randomized placebo-controlled trial of 40 subjects to assess the efficacy and safety of dupilumab use in those hospitalized with COVID-19 (NCT04920916). Based on our pre-clinical data suggesting downstream pulmonary dysfunction with COVID-19 induced type 2 inflammation, we contacted patients from our Phase IIa study at 1 year for assessment of Post Covid-19 Conditions (PCC).

Methods: Subjects at 1 year after treatment underwent pulmonary function testing (PFTs), high resolution computed tomography (HRCT) imaging, symptom questionnaires, neurocognitive assessments, and serum immune biomarker analysis, with subject survival also monitored.

The Elephant in the Room: Racial Microaggressions and Implicit Bias in Surgical Training.

Objective: The aim of this study was to examine the association between race, experience of microaggressions, and implicit bias in surgical training.

Background: There is persistent underrepresentation of specific racial and ethnic groups in the field of surgery. Prior research has demonstrated significant sex differences among those who experience microaggressions during training.

Rev-Rev Response Element Activity Selection Bias at the HIV Transmission Bottleneck.

HIV is not efficiently transmitted between hosts, and selection of viral variants occurs during the process of sexual transmission. The factors that confer selective advantage at the transmission bottleneck remain incompletely understood. We explored whether differences in the Rev-Rev Response Element (RRE) regulatory axis of HIV affect transmission fitness, since functional variation in the Rev-RRE axis in different viral isolates has been shown to affect replication kinetics and relative expression of many HIV proteins.

Inhibition of the mitochondrial pyruvate carrier simultaneously mitigates hyperinflammation and hyperglycemia in COVID-19.

The relationship between diabetes and coronavirus disease 2019 (COVID-19) is bidirectional: Although individuals with diabetes and high blood glucose (hyperglycemia) are predisposed to severe COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can also cause hyperglycemia and exacerbate underlying metabolic syndrome. Therefore, interventions capable of breaking the network of SARS-CoV-2 infection, hyperglycemia, and hyperinflammation, all factors that drive COVID-19 pathophysiology, are urgently needed. Here, we show that genetic ablation or pharmacological inhibition of mitochondrial pyruvate carrier (MPC) attenuates severe disease after influenza or SARS-CoV-2 pneumonia.

HIV-1 Rev-RRE functional activity in primary isolates is highly dependent on minimal context-dependent changes in Rev.

During HIV infection, intron-containing viral mRNAs are exported from the cell nucleus to the cytoplasm to complete the replication cycle. Cellular restrictions on the export of incompletely spliced transcripts are overcome by a viral protein, Rev, and an RNA structure found in all unspliced and incompletely spliced viral mRNAs, the Rev Response Element (RRE). Primary HIV isolates display substantial variation in the sequence and functional activity of Rev proteins.

Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients With Moderate to Severe Coronavirus Disease 2019: A Phase 2a Trial.

Background: Based on studies implicating the type 2 cytokine interleukin 13 (IL-13) as a potential contributor to critical coronavirus disease 2019 (COVID-19), this trial was designed as an early phase 2 study to assess dupilumab, a monoclonal antibody that blocks IL-13 and interleukin 4 signaling, for treatment of inpatients with COVID-19.

Methods: We conducted a phase 2a randomized, double-blind, placebo-controlled trial (NCT04920916) to assess the safety and efficacy of dupilumab plus standard of care vs placebo plus standard of care in mitigating respiratory failure and death in those hospitalized with COVID-19.

Results: Forty eligible subjects were enrolled from June to November of 2021.

Frequency and Characteristics of Social Media Use among General Surgery Trainees.

Introduction: With increased social isolation due to COVID-19, social media has been increasingly adopted for communication, education, and entertainment. We sought to understand the frequency and characteristics of social media usage among general surgery trainees.

Materials And Methods: General surgery trainees in 15 American training programs were invited to participate in an anonymous electronic survey.

Safety and Efficacy of Dupilumab for the Treatment of Hospitalized Patients with Moderate to Severe COVID 19: A Phase IIa Trial.

Background: A profound need remains to develop further therapeutics for treatment of those hospitalized with COVID-19. Based on data implicating the type 2 cytokine interleukin (IL)-13 as a significant factor leading to critical COVID-19, this trial was designed to assess dupilumab, a monoclonal antibody that blocks IL-13 and IL-4 signaling, for treatment of inpatients with COVID-19.

Methods: We conducted a phase IIa randomized double-blind placebo-controlled trial to assess the safety and efficacy of dupilumab plus standard of care versus placebo plus standard of care in mitigating respiratory failure and death in those hospitalized with COVID-19.

Selection of Analytical Technology and Development of Analytical Procedures Using the Analytical Target Profile.

A structured approach to method development can help to ensure an analytical procedure is robust across the lifecycle of its use. The analytical target profile (ATP), which describes the required quality of the reportable value to be produced by the analytical procedure, enables the analytical scientist to select the best analytical technology on which to develop their procedure(s). Once the technology has been identified, screening of potentially fit for purpose analytical procedures should take place.

Efficacy of interferon beta-1a plus remdesivir compared with remdesivir alone in hospitalised adults with COVID-19: a double-bind, randomised, placebo-controlled, phase 3 trial.

Background: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19.

Methods: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA).

An apex carnivore's life history mediates a predator cascade.

Apex predators can shape communities via cascading top-down effects, but the degree to which such effects depend on predator life history traits is largely unknown. Within carnivore guilds, complex hierarchies of dominance facilitate coexistence, whereby subordinate species avoid dominant counterparts by partitioning space, time, or both. We investigated whether a major life history trait (hibernation) in an apex carnivore (black bears Ursus americanus) mediated its top-down effects on the spatio-temporal dynamics of three sympatric mesocarnivore species (coyotes Canis latrans, bobcats Lynx rufus, and gray foxes Urocyon cinereoargenteus) across a 15,000 km landscape in the western USA.

Microaggressions and Implicit Bias in Surgical Training: An Undocumented but Pervasive Phenomenon.

Objective: To examine the prevalence, nature, and source of microaggressions experienced by surgical residents during training.

Summary And Background Data: The role of microaggressions in contributing to workplace culture, individual performance, and professional satisfaction has become an increasingly studied topic across various fields. Little is known about the prevalence and impact of microaggressions during surgical training.

How We Do It: Implementing a Virtual, Multi-Institutional Collaborative Education Model for the COVID-19 Pandemic and Beyond.

Objective: To describe the implementation of a virtual, multi-institutional educational collaboration involving over 50 general surgery residency programs during the COVID-19 pandemic that enabled enhanced learning for surgical residents despite social-distancing requirements.

Design: Description of Virginia Commonwealth University's virtual educational augmentation program and the development of a collaborative teaching network during the coronavirus pandemic.

Setting: This collaboration was initiated by Virginia Commonwealth University's Department of Surgery, Richmond, VA, and grew to include general surgery residency programs from across the nation.

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19.

Background: Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known.

Methods: We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19.

General surgery involvement with ventriculoperitoneal shunt insertions reduces revision rates.

Background: Ventriculoperitoneal shunts (VPS) are placed for a variety of etiologies. It is common for general surgery to assist with insertion of the distal portion in the peritoneum.

Objective: To determine if there is a difference in revision rates in patients undergoing VPS placement with general surgery as well as those undergoing laparoscopic insertion.

Sequence and Functional Variation in the HIV-1 Rev Regulatory Axis.

Background: To complete its replication cycle, HIV-1 requires the nucleocytoplasmic export of intron-containing viral mRNAs. This process is ordinarily restricted by the cell, but HIV overcomes the block by means of a viral protein, Rev, and an RNA secondary structure found in all unspliced and incompletely spliced viral mRNAs called the Rev Response Element (RRE). In vivo activity of the Rev-RRE axis requires Rev binding to the RRE, oligomerization of Rev to form a competent ribonucleoprotein complex, and recruitment of cellular factors including Crm1 and RanGTP in order to export the targeted transcript.

HIV-1 Rev interacts with HERV-K RcREs present in the human genome and promotes export of unspliced HERV-K proviral RNA.

Background: The HERV-K (HML-2) viruses are the youngest of the human endogenous retroviruses. They are present as several almost complete proviral copies and numerous fragments in the human genome. Many HERV-K proviruses express a regulatory protein Rec, which binds to an element present in HERV-K mRNAs called the RcRE.