bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, Virology, Pharmacokinetics, and Clinical Experience of High-Dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-Label Clinical Trial
Authors: Moya Jaynier , Temech Marisol , Parra Sergio , Juarez Erick , Hernandez-Loy Reinaldo , Gutierrez Juan C Moises , Diaz Jorge , Hussain Rubaba , Segal Scott , Xu Claire , Skingsley Andrew , Schnell Gretja , El-Zailik Asma , Sager Jennifer E , Aldinger Melissa , Alexander Elizabeth L , Acloque Gerard 
Published: July 2023

Abstract

Background
Five hundred milligrams of intravenous (IV) sotrovimab has been shown to be well tolerated and efficacious against pre-Omicron strains in treating patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk for disease progression.

Methods
This was an open-label, single-arm substudy of phase 3 COMET-TAIL (NCT04913675) assessing the safety and tolerability of a 2000 mg IV dose of sotrovimab. Symptomatic patients (aged ≥18 years) with COVID-19 at high risk for progression were enrolled from June 30 through July 11, 2022, when Omicron BA.5, BA.2.12.1, and BA.4 were the predominant circulating variants in the United States. The primary end point was the occurrence of adverse events (AEs), serious AEs (SAEs), AEs of special interest, and COVID-19 disease-related events (DREs) through day 8. Safety, pharmacokinetics, viral load, and hospitalization &gt;24 hours for acute management of illness or death through day 29 were assessed.

Results
All participants (n = 81) were Hispanic, 58% were female, and 51% were aged ≥55 years. Through day 8, no AEs, including infusion-related reactions or hypersensitivity, were reported; 2 participants reported DREs (mild cough, n = 2). One SAE (acute myocardial infarction), which was considered unrelated to sotrovimab or COVID-19 by the investigator, occurred on day 27 and was the only hospitalization reported. Maximum serum concentration (geometric mean) was 745.9 µg/mL. Viral load decreased from baseline through day 29; only 2 (3%) participants had a persistently high viral load (≥4.1 log10 copies/mL) at day 8.

Conclusions
Two thousand milligrams of IV sotrovimab was well tolerated, with no safety signals observed.

Trial registration
ClinicalTrials.gov Identifier: NCT04913675.
Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Intravenous Infusions of PF-07304814 (Lufotrelvir) in Participants Hospitalized With COVID-19
Authors: Robinson Philip , Toussi Sima S , Aggarwal Sudeepta , Bergman Arthur , Zhu Tong , Hackman Frances , Sathish Jean G , Updyke Lawrence , Loudon Peter , Krishna Ganesh , Clevenbergh Philippe , Hernandez-Mora Miguel Gorgolas , Cisneros Herreros Jose Miguel , Albertson Timothy E , Dougan Michael , Thacker Amber , Baniecki Mary Lynn , Soares Holly , Whitlock Mark , Nucci Gianluca , Menon Sandeep , Anderson Annaliesa S , Binks Michael 
Published: July 2023

Abstract

Background
An urgent need remains for antiviral therapies to treat patients hospitalized with COVID-19. PF-07304814—the prodrug (lufotrelvir) and its active moiety (PF-00835231)—is a potent inhibitor of the SARS-CoV-2 3CL protease.

Method
Eligible participants were 18 to 79 years old and hospitalized with confirmed COVID-19. This first-in-human phase 1b study was designed with 2 groups: single ascending dose (SAD) and multiple ascending dose (MAD). Participants could receive local standard-of-care therapy. In SAD, participants were randomized to receive a 24-hour infusion of lufotrelvir/placebo. In MAD, participants were randomized to receive a 120-hour infusion of lufotrelvir/placebo. The primary endpoint was to assess the safety and tolerability of lufotrelvir. The secondary endpoint was to evaluate the pharmacokinetics of lufotrelvir and PF-00835231.

Results
In SAD, participants were randomized to receive 250 mg lufotrelvir (n = 2), 500 mg lufotrelvir (n = 2), or placebo (n = 4) by continuous 24-hour infusion. In MAD, participants were randomized to receive 250 mg lufotrelvir (n = 7), 500 mg lufotrelvir (n = 6), or placebo (n = 4) by continuous 120-hour infusion. No adverse events or serious adverse events were considered related to lufotrelvir. At doses of 250 and 500 mg, concentrations for the prodrug lufotrelvir and active moiety PF-00835231 increased in a dose-related manner. Unbound concentrations of the lufotrelvir active metabolite reached steady state approximately 2- and 4-fold that of in vitro EC90 following 250- and 500-mg doses, respectively.

Conclusions
These safety and pharmacokinetic findings support the continued evaluation of lufotrelvir in clinical studies.
Clinical Trials Registration. ClinicalTrials.gov NCT04535167.
Abundance, composition and distribution of carnivorous gelatinous zooplankton in the Northern Gulf of Alaska
Authors: Cotea Islas Heidi Michelle , Hopcroft Russell R 
Published: July 2023

Abstract
Abundance, biomass, size and distribution of macro-jellyfish were measured in the Northern Gulf of Alaska (NGA). Nearly 1000 kg dispersed among ~13 800 jellyfish were collected using a 5-m2 Methot net. We present length-weight regressions for seven most-common taxa. Catches were dominated by the hydrozoan Aequorea victoria and the scyphozoan Chrysaora melanaster. During 2018, epipelagic macro-jellyfish biomass averaged 1.46 ± 0.36 g WW m−3 for July and 1.14 ± 0.23 g WW m−3 for September, while during 2019 they averaged 0.86 ± 0.19 g WW m−3 for July and 0.72 ± 0.21 g WW m−3 by September. Despite similar biomass among seasons within a year, July abundances were fivefold greater than abundances in September, with July catches dominated by smaller-sized jellyfish over the inner shelf, while during September larger jellyfish were more prominent and most predominant at offshore stations. Comparison to 20 years of data from standard towed nets allowed determination of the relative magnitude of the dominant carnivorous zooplankton components: scyphozoans, hydrozoans and chaetognaths in the NGA. The biomass of these smaller epipelagic predators (5.4 mg WW m−3 for hydrozoans and 10.5 mg WW m−3 for chaetognaths) is a low percentage of the macro-jellyfish, despite their much higher numerical abundance.
Evaluating the Use of Postharvest Decomposition Treatments on Peanut Residues for Reducing Subsequent Infection by Nothopassalora personata
Authors: Renfroe-Becton H. , Ye R. , Anco D. J. 
Published: July 2023

The late leaf spot (LLS) pathogen Nothopassalora personata overwinters on peanut residues left in the field. In this study, decomposition treatments were evaluated for their potential use in increasing the rate of decomposition of residues and potentially reducing LLS incidence. Treatments including urea ammonium nitrate (UAN) only, UAN plus a microbial stubble digestor (SD25), or UAN plus an adjuvant (Bond Max, BM), as well as timing of application in fall or spring, were assessed. Fall applications were not effective in reducing or delaying subsequent LLS epidemics. Although there were differences observed among treatments in the spring 2019 test, with UAN plus Bond Max-treated plots having significantly less defoliation from LLS at the end of the growing season, these results were not consistent in the 2020 experiments. Using the litterbag method, no consistent increase in decomposition was observed from treated residues compared with the nontreated control. Based on these results, the examined decomposition treatments were not considered to be useful in increasing the decomposition of peanut residues and subsequently reducing or delaying LLS epidemics. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Trends in Cannabis-positive Urine Toxicology Test Results: US Veterans Health Administration Emergency Department Patients, 2008 to 2019
Authors: Fink David S. , Malte Carol , Cerdá Magdalena , Mannes Zachary L. , Livne Ofir , Martins Silvia S. , Keyhani Salomeh , Olfson Mark , McDowell Yoanna , Gradus Jaimie L. , Wall Melanie M. , Sherman Scott , Maynard Charles C. , Saxon Andrew J. , Hasin Deborah S. 
Published: July 2023

Objectives
This study aimed to examine trends in cannabis-positive urine drug screens (UDSs) among emergency department (ED) patients from 2008 to 2019 using data from the Veterans Health Administration (VHA) health care system, and whether these trends differed by age group (18–34, 35–64, and 65–75 years), sex, and race, and ethnicity.

Method
VHA electronic health records from 2008 to 2019 were used to identify the percentage of unique VHA patients seen each year at an ED, received a UDS, and screened positive for cannabis. Trends in cannabis-positive UDS were examined by age, race and ethnicity, and sex within age groups.

Results
Of the VHA ED patients with a UDS, the annual prevalence positive for cannabis increased from 16.42% in 2008 to 27.2% in 2019. The largest increases in cannabis-positive UDS were observed in the younger age groups. Male and female ED patients tested positive for cannabis at similar levels. Although the prevalence of cannabis-positive UDS was consistently highest among non-Hispanic Black patients, cannabis-positive UDS increased in all race and ethnicity groups.

Discussion
The increasing prevalence of cannabis-positive UDS supports the validity of previously observed population-level increases in cannabis use and cannabis use disorder from survey and administrative records. Time trends via UDS results provide additional support that previously documented increases in self-reported cannabis use and disorder from surveys and claims data are not spuriously due to changes in patient willingness to report use as it becomes more legalized, or due to greater clinical attention over time.
Effects of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) Trial on Elective Induction and Obstetric Outcomes in Term Nulliparous Patients
Authors: Nethery Elizabeth , Levy Barbara , McLean Kate , Sitcov Kristin , Souter Vivienne L. 
Published: July 2023

OBJECTIVE:
To evaluate the effect of publication of the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial on perinatal outcomes in singleton, term, nulliparous patients.

METHODS:
An interrupted time series analysis was performed using clinical data for nulliparous singleton births at 39 weeks of gestation or later at 13 hospitals in the Northwest region of the United States (January 2016–December 2020). A modified Poisson regression was used to model time trends and changes after the ARRIVE trial (August 9, 2018). Outcomes of interest were elective induction, unplanned cesarean births, hypertensive disorders of pregnancy, a composite of perinatal adverse outcomes, and neonatal intensive care unit admissions.

RESULTS:
The analysis included 28,256 births (15,208 pre-ARRIVE and 13,048 post-ARRIVE). The rate of elective labor induction was 3.6% during the pre-ARRIVE period (January 2016–July 2018) and 10.8% post-ARRIVE (August 2018–December 2020). In the interrupted time series analysis, elective induction increased by 42% (relative risk [RR] 1.42; 95% CI 1.18–1.71) immediately after the ARRIVE trial publication. Thereafter, the trend was unchanged compared with the pre-ARRIVE period. There was no statistically significant change in cesarean birth (RR 0.96; 95% CI 0.89–1.04) or hypertensive disorders of pregnancy (RR 0.91; 95% CI 0.79–1.06) immediately after the trial, and no change in trend. After the ARRIVE trial, there was no immediate change in adverse perinatal outcomes, but a statistically significant increase in trend of adverse perinatal events (1.03; 95% CI 1.01–1.05) when compared with a declining trend observed in the pre-ARRIVE period.

CONCLUSION:
Publication of the ARRIVE trial was associated with an increase in elective induction, and no change in cesarean birth or hypertensive disorders of pregnancy in singleton nulliparous patients giving birth at 39 weeks or later. There was a flattening of the pre-ARRIVE decreasing trend in perinatal adverse events.
Neovaginal Human Papillomavirus Prevalence in Transfeminine Individuals
Authors: Nandwana Devika , Hawes Kenna , Zuend Christina Farr , Pope Rachel 
Published: July 2023

OBJECTIVE:
To assess the prevalence of high-risk human papillomavirus (hrHPV) and human papillomavirus (HPV)–associated abnormalities in the neovaginas of postvaginoplasty transfeminine patients to inform potential HPV-screening guidelines for this patient population.

DATA SOURCES:
MEDLINE, ClinicalTrials.gov, the Cochrane Library, Scopus, and Google Scholar were searched through September 30, 2022.

METHODS OF STUDY SELECTION:
The population included transfeminine individuals who had undergone vaginoplasty with an outcome of subsequent positive HPV diagnosis or HPV-related lesions. Randomized clinical trials, cohort studies, cross-sectional studies, and case reports available in English were included in the analysis. Identified articles were doubly screened, and accepted articles were doubly extracted.

TABULATION, INTEGRATION, AND RESULTS:
Of 59 abstracts identified, 30 were screened for eligibility, of which 15 met the criteria for review. Included studies were assessed for vaginoplasty procedure type, time elapsed between vaginoplasty and HPV testing, HPV type, location and manner of sample collection, method of HPV diagnosis, and classification and location of HPV-associated neovaginal lesions. Studies were assigned a grade of evidence of very low, low, moderate, or high based on study design, precision, directness, and risk of bias. Prevalence of neovaginal hrHPV ranged from 8.3% to 20% in identified studies, and per-study prevalence of HPV-related neovaginal abnormalities ranged from 0% to 8.3% in patients.

CONCLUSION:
The current body of research demonstrates that, after vaginoplasty, transfeminine individuals may develop neovaginal HPV infection with associated cytologic abnormalities or grossly apparent lesions. In some included studies, neovaginal HPV-associated lesions were highly advanced before they were identified. A small number of studies assessed neovaginal HPV prevalence in transfeminine individuals, with hrHPV prevalence ranging from 8.3% to 20%. However, broader conclusions about neovaginal HPV prevalence are limited by a lack of high-grade evidence in the existing literature. More rigorous prevalence research is needed to inform preventative care guidelines for transfeminine individuals at risk of developing HPV-related neovaginal complications.

SYSTEMATIC REVIEW REGISTRATION:
PROSPERO, CRD42022379977.
Weekday-dependent long-term outcomes in gastrointestinal cancer surgery: a german population-based retrospective cohort study
Authors: Maier Christopher Fabian , Schölch Caroline , Zhu Lei , Nzomo Martial Mboulla , L’hoest Helmut , Marschall Ursula , Reißfelder Christoph , Schölch Sebastian 
Published: July 2023

Background:
For most solid cancers, surgery represents the mainstay of curative treatment. Several studies investigating the effects of the weekday of surgery (WOS) on patient outcomes have yielded conflicting results. Barmer, the second-largest health insurance company in Germany, serves roughly 10% of the German population. We have used the Barmer database to evaluate how the weekday on which the surgery is performed influences long-term oncologic outcomes.

Methods:
For this retrospective cohort study, the Barmer database was used to investigate the effect of the WOS (Monday–Friday) on outcomes following oncological resections of the colorectum (n=49,003), liver (n=1,302), stomach (n=5027), esophagus (n=1126), and pancreas (n=6,097). In total, 62,555 cases from 2008 to 2018 were included in the analysis. The endpoints were overall survival (OS), postoperative complications, and necessity for therapeutic interventions or re-operations. We furthermore examined whether the annual caseload or certification as a cancer center influenced the weekday effect.

Results:
We observed a significantly impaired OS for patients receiving gastric or colorectal resections on a Monday. Colorectal surgery performed on Mondays was associated with more postoperative complications and higher probability of re-operations. The annual caseload or a certification as a colorectal cancer center had no bearing on the observed weekday effect. There is evidence that hospitals schedule older patients with more comorbidities earlier in the week, possibly explaining these findings.

Conclusion:
This is the first study investigating the influence of the WOS on long-term survival in Germany. Our findings indicate that, in the German healthcare system, patients undergoing colorectal cancer surgery on Mondays have more postoperative complications and, therefore, require significantly more re-operations, ultimately lowering OS. This surprising finding appears to reflect an attempt to schedule patients with higher postoperative risk earlier in the week as well as semi-elective patients admitted on weekends scheduled for surgery on the next Monday.
Interstitial lung disease-associated pulmonary hypertension – what the future holds
Authors: Cottin Vincent , Diesler Rémi , Turquier Ségolène , Valenzuela Claudia 
Published: July 2023

Purpose of review
Pulmonary hypertension associated with interstitial lung disease (ILD-PH) is associated with significant alteration of quality of life, exercise capacity, and survival. Over the past 2 years, there were changes in the guideline definition and classification of ILD-PH, and positive randomized controlled trials were published.

Recent findings
Pulmonary hypertension associated with chronic lung disease is now hemodynamically defined as a mean pulmonary artery pressure more than 20 mmHg, with pulmonary artery wedge pressure 15 mmHg or less, and pulmonary vascular resistance (PVR) at least 2 Wood units. Severe ILD-PH is defined by PVR more than 5 Wood units. In the INCREASE trial, patients receiving inhaled treprostinil had favorable significant changes in 6-min walk distance, NT-proBNP level, clinical worsening events, and forced vital capacity, which were maintained in the open label extension study. Promising results were obtained in a placebo-controlled pilot trial using escalated doses of inhaled nitric oxide. According to European guidelines, patients with ILD-PH should be referred to pulmonary hypertension centers, where inhaled treprostinil may be considered; phosphodiesterase type-5 inhibitors may also be considered in patients with severe ILD-PH.

Summary
Recent changes in the definitions and a new therapeutic option have an impact on the diagnosis and management of ILD-PH.
The Effect of Aquatic Exercise on Balance in Ambulatory Individuals With Down Syndrome: An Interventional Feasibility Study
Authors: Michaels Natalie Norman , Darr Nancy , Alama Courtney , Callahan Kopplin Carly , Jacobs Taylor , Rungee Taylor Anna , Youngblood Madeleine 
Published: July 2023

Background:
People with Down syndrome (DS) often present with ligamentous laxity, coordination difficulties, and decreased strength, which can lead to impaired balance. These impairments may contribute to delayed development of age-appropriate motor skills and can contribute to increased risk of falls. Although aquatic exercises have been found to improve balance in various populations, the effectiveness of aquatic exercise to improve balance for individuals with DS has not been thoroughly studied.

Methods:
Five participants with DS were tested using the second edition of the Pediatric Balance Scale (PBS-2), while their parents completed the Activities-specific Balance Confidence (ABC) scale. They then participated in an aquatic exercise intervention twice per week for 6 weeks. Following the 6-week intervention, the participants were tested again using the PBS-2 and the ABC scale.

Results:
Parents' ABC scores increased for 3 of the 5 participants, and there was a statistically significant difference between pre– and post–aquatic intervention PBS-2 total test scores for the group (P < .05).

Relevance:
The results of this small feasibility study support the practicality of aquatic exercise to improve balance for children and young adults with DS. Further research using a larger sample size is recommended.
Breakthrough HIV-1 infection in setting of cabotegravir for HIV pre-exposure prophylaxis
Authors: Hazra Aniruddha , Landovitz Raphael J. , Marzinke Mark A. , Quinby Connor , Creticos Catherine 
Published: July 2023

Objective(s):
We describe the first case of HIV-1 infection in the setting of long-acting injectable cabotegravir (CAB-LA) for HIV pre-exposure prophylaxis (PrEP) to occur in the real world.

Design:
Case report

Methods:
Electronic medical records were reviewed to assess patient history and CABLA administration details. Plasma 4th generation HIV-1/2 Ag/Ab combination immunoassay and HIV-1 RNA quantitative PCR were performed at each injection visit.

Results:
We report a 28-year-old gender diverse person assigned male at birth who acquired HIV-1 infection 91 days after transitioning from tenofovir alafenamideemtricitabine (TAF/FTC) to CAB-LA despite on-time dosing and appropriate laboratory monitoring.

Conclusions:
This patient's history suggests HIV infection despite on-time and appropriate CAB-LA injections. To our knowledge, this is the first case of CAB-LA PrEP failure outside the setting of a clinical trial and highlights diagnostic and management challenges that may occur with such breakthrough infections.
Achieving the 3rd 95 in sub-saharan Africa: application of machine learning approaches to predict viral failure
Authors: Esber Allahna L. , Dear Nicole F. , King David , Francisco Leilani V. , Sing’oei Valentine , Owuoth John , Maswai Jonah , Iroezindu Michael , Bahemana Emmanuel , Kibuuka Hannah , Shah Neha , Polyak Christina S. , Ake Julie A. , Crowell Trevor A. 
Published: July 2023

Objective:
Viral failure in people living with HIV (PLWH) may be influenced by multiple socio-behavioral, clinical, and context-specific factors, and supervised learning approaches may identify novel predictors. We compared the performance of two supervised learning algorithms to predict viral failure in four African countries.

Design:
Cohort study

Methods:
The African Cohort Study is an ongoing, longitudinal cohort enrolling PLWH at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. Participants underwent physical examination, medical history-taking, medical record extraction, socio-behavioral interviews, and laboratory testing. In cross-sectional analyses of enrollment data, viral failure was defined as a viral load ≥1000 copies/mL among participants on antiretroviral therapy (ART) for at least six months. We compared the performance of lasso-type regularized regression and random forests by calculating area under the curve (AUC) and used each to identify factors associated with viral failure; 94 explanatory variables were considered.

Results:
Between January 2013 and December 2020, 2,941 PLWH were enrolled, 1,602 had been on ART for at least 6 months, and 1,571 participants with complete case data were included. At enrollment, 190 (12.0%) had viral failure. The lasso regression model was slightly superior to the random forest in its ability to identify PLWH with viral failure (AUC: 0.82 vs 0.75). Both models identified CD4 count, ART regimen, age, self-reported ART adherence and duration on ART as important factors associated with viral failure.

Conclusion:
These findings corroborate existing literature primarily based on hypothesis-testing statistical approaches and help to generate questions for future investigations that may impact viral failure.