bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding the Stress Testing Characteristics of Apixaban, Structural Elucidation of a Novel Degradation Impurity, and Stability-Indicating Method Development for Quantification of Related Substances
Authors: Surukonti Srikanth Reddy , Surendrababu M S 
Published: September 2023

Abstract

Background
People who have non-valvular atrial fibrillation may benefit from taking a new oral anticoagulant called apixaban, which has recently been given the green light by the U.S. Food and Drug Administration. During stress testing, apixaban was found to have a high degree of degradability when subjected to both acidic and basic conditions, and one significant unknown impurity was observed in addition to the major known impurities.

Objective
Our aim is the isolation and characterization of degradation product observed in stress/forced degradation studies, and also the development of a single HPLC method that is both reliable and accurate for quantifying all 10 related impurities of apixaban.

Methods
Preparative HPLC was used to isolate the degradation product, and 1H NMR, 13C NMR, and MS were used to elucidate the structure of the product. Additionally, a single reverse-phase (RP) HPLC method was developed for quantification of all related impurities of apixaban.

Results
Based on the spectral characterization data, the identified unknown degradation impurity was found to be a pH-independent hydrolysis degradation impurity of apixaban. The developed method is specific, linear, accurate, robust, and rugged.

Conclusion
The isolated and characterized impurities were the same as those found during stress testing. The developed method has been validated for its intended purpose in accordance with the regulatory requirements that were outlined.

Highlights
The unknown impurity is a new apixaban degradation impurity that helps us understand its toxicity. The scientific community will benefit from the developed analytical method information as it relates to understanding drug product impurity profiling.
Effects of exogenous spermidine on autophagy and antioxidant capacity in ovaries and granulosa cells of Sichuan white geese
Authors: Jiang Dongmei , Sun Qian , Jiang Yilong , Zhou Xuemin , Kang Lijuan , Wang Zelong , Wang Xin , An Xiaoguang , Ji Chengweng , Ling Weikang , Wang Yinglian , Yang Yujie , Kang Bo 
Published: September 2023

Abstract
Autophagy can inhibit ovarian senescence induced by oxidative stress and regulate follicle development and atresia, but its mechanism is still unclear. Exogenous spermidine can induce autophagy and scavenge reactive oxygen species (ROS). In this experiment, oxidative stress in Sichuan white geese ovaries and follicular granulosa cells (GCs) was caused by 3-nitropropionic acid (3-NPA) and spermidine was added to explore the effect of exogenous spermidine inducing autophagy and inhibiting oxidative stress in vivo and in vitro. Research results showed that putrescine, spermidine and spermine contents in goose ovaries in the group treated with spermidine combined with 3-NPA were 2.70, 1.94, and 1.70 times higher than those in the group treated with 3-NPA, respectively (P &lt; 0.05). The contents of spermidine and spermine in GCs were 1.37 and 0.89 times higher in the spermidine in combination with the 3-NPA group than in the 3-NPA group, respectively (P &lt; 0.05). LC3 and p62 were mainly expressed in the follicular granulosa layer. The LC3-II/I ratio and p62 level in GCs in the spermidine combined with 3-NPA treatment group were 1.37 and 0.77 times higher than that of the 3-NPA treatment group, respectively (P &lt; 0.05). 3-NPA treatment significantly increased ROS level and the apoptosis rate in GCs, while the combined treatment of spermidine and 3-NPA reversed this change (P &lt; 0.05).
In conclusion, spermidine alleviated the oxidative damage induced by 3-NPA by improving the antioxidant capacity of ovaries and follicular GCs of Sichuan white geese and may be alleviated by inducing autophagy in GCs.
Reducing Ophthalmic Antibiotic Use for Non-severe Conjunctivitis in Children
Authors: Sebastian Thresia , Durfee Josh , Wittmer Nancy , Jack Jessica , Keith Amy , Jenkins Timothy C , Frost Holly M 
Published: September 2023

Abstract

Background
Antibiotics are often overprescribed for pediatric conjunctivitis. We implemented a system-level quality improvement (QI) intervention to reduce unnecessary ophthalmic antibiotic use.

Methods
The multi-faceted intervention in Denver, CO comprised a clinical care pathway, nurse protocol modifications, electronic health record (EHR) changes, parent education materials, and clinician education. We evaluated children aged 6 months–17 years with conjunctivitis seen between November 2018 and December 2022. A multi-interrupted time series model evaluated the effectiveness of the intervention over three time periods: Pre-COVID, Pre-Intervention (November 2018–February 2020), COVID, Pre-Intervention (March 2020–March 2021), and Post-Intervention (April 2021–December 2022). Fisher’s exact tests compared treatment failure and healthcare utilization rates between time periods and among children receiving or not receiving ophthalmic antibiotics.

Results
Among 6960 eligible encounters, ophthalmic antibiotic use was reduced by 18.8% (95% CI: 16.3, 21.3) from Pre-COVID, Pre-Intervention to Post-Intervention. During the Pre-Intervention period following the onset of COVID, a reduction of 16.1% (95% CI: 12.9, 19.3) was observed. Implementation of the intervention resulted in an additional 2.7% (95% CI: −0.4, 5.7) reduction in antibiotic prescribing, primarily in younger children (ages 6 months–5 years). The greatest reduction in prescribing occurred for nurse triage encounters with an 82.1% (95% CI: 76.8, 87.5) reduction in prescribing rates (92.6%–10.5%). Treatment failure occurred in 1301 (18.7%) children and was more common among children that received an ophthalmic antibiotic than those that did not (20.0 vs 17.9%; P = .03).

Conclusion
The QI intervention significantly reduced ophthalmic antibiotic prescribing for pediatric conjunctivitis without increasing treatment failure rates or health care utilization.
Laboratory Testing Strategies, Detection, and Diagnosis
Authors: Yagnik Kruti J. , Meisner Jessica A. 
Published: September 2023

Abstract
The history of testing, as well as the immunology behind testing, is detailed in this chapter. The various laboratory and home testing methods used for screening and diagnosis of HIV infections are discussed. A comprehensive overview of virologic immunoassays is provided to the reader to explain how available immunoassays can be used for screening and diagnosing most early and primary HIV infections and when virologic assays should be considered as complementary diagnostics to immunoassays for screening and confirmation of HIV-1 and HIV-2 infections. Algorithms for screening and diagnosing HIV infections are discussed, and special attention is given to screening and detecting HIV in newborns and children.
The HIV Reservoir and Cure and Remission Strategies
Authors: Juelg Boris , Gandhi Rajesh T. , Jilg Nikolaus 
Published: September 2023

Abstract
HIV-1 persists quiescently in cellular reservoirs not detected by the immune system because of the lack of active viral replication; these reservoirs represent the biggest obstacle to cure approaches. Reversal of HIV-1 latency and induction of virus expression by a variety of interventions may render infected cells susceptible to immune recognition and active clearance. Strategies to boost immune responses via active or passive immunization, immunomodulation, or gene therapy are being evaluated with the aim of achieving HIV-1 control or remission without antiretroviral therapy (ART), if not viral eradication. This chapter covers HIV reservoir and cure and remission strategies. It details the importance of why we should try to cure HIV and includes clinical observations where the concept of a “functional cure” has been introduced. Early establishment and persistence of the latent HIV-1 reservoir is discussed as well as latency reversal approaches and latency silencing. A variety of immune enhancing and/or modulating strategies and immunomodulatory treatments are reviewed. Special attention is paid to therapeutic and preventive vaccines.
Antiretroviral Therapy for Children and Newborns
Authors: Nielsen-Saines Karin 
Published: September 2023

Abstract
HIV-infected infants and children have a different, more progressive disease course as compared to adults given that early infection leads to sustained, high-magnitude viremia with significant seeding of reservoirs in the first months of life, prior to full maturation of the immune system. Early diagnosis of HIV infection is pivotal in the management of infants and in the prevention of HIV-associated morbidity and mortality. This chapter discusses advances in antiretroviral therapy for the prevention of mother-to-child transmission of HIV. Pediatric-specific issues of early HIV diagnosis, timing, and pathogenesis of HIV disease, and use of surrogate markers of HIV infection in this population are reviewed in the text. The difference between the concepts of HIV exposure and HIV infection is highlighted. The chapter concludes with a brief discussion citing the benefits of antiretroviral therapy in children.
Understanding and Managing Antineoplastic and Antiretroviral Therapy
Authors: Sherman Elizabeth M. , Gill Taylor K. 
Published: September 2023

Abstract
The disease states of HIV and cancer are constantly evolving. New therapies are introduced, and literature published advancing each area. The use of combination antiretroviral therapy in people with HIV and malignancies is associated with improved HIV- and cancer-related outcomes. Combining antiretroviral therapy (ART) and antineoplastic therapy is often complicated by significant drug–drug interactions, drug–disease state monitoring interactions, and overlapping toxicities. Definitive studies including both antineoplastics and antiretrovirals are uncommon, and clinical judgment must often be used to determine the appropriate course of treatment. Adjusting ART in response to significant drug interactions or overlapping toxicities is often more feasible than modifying antineoplastic protocols. A multidisciplinary care team that includes primary care providers, infectious disease clinicians, hematologists/oncologists, and clinical pharmacists should be utilized to address the challenges of combining HIV and cancer treatment. Specifically, new oral agents and long-acting antiretrovirals for HIV and immuno-therapy for cancer treatment bring exciting advancements. This chapter reviews concepts regarding the safe and effective use of ART and antineoplastic therapy in people living with HIV and cancer. Drug interaction mechanisms and medication toxicities are discussed as well as drug–disease interactions. The chapter concludes with an overview of strategies for clinical management of people with cancer and HIV.
Caring for Older People with HIV
Authors: Sangarlangkarn Aroonsiri , Zeuli John D. , Avihingsanon Anchalee 
Published: September 2023

Abstract
This chapter describes the differences in HIV care and management for persons with HIV who are aged 50 years or older compared to their younger counterparts. Importantly, older patients with HIV present unique and complex cases, and disease-centric guidelines do not apply to every patient. Management of diseases in older patients with HIV should be individualized based on aging phenotypes identified by the Veterans Aging Cohort Study index, interactions with multimorbidities, and patient preferences. Learners will understand how to conduct a Comprehensive Geriatric Assessment to assess function, mobility/fall risk, frailty, cognition, mood, and issues related to polypharmacy. Learners will also discuss a comprehensive medication assessment, nutrition and weight changes, social and monetary issues impacting care, symptom burdens and pain, and advanced planning. Lastly, learners will be presented with specific co-exiting conditions common to aging that are impacted by HIV, including diabetes mellitus, hypertension, bone disease, peripheral neuropathy, certain cancers, and recommended vaccinations.
Dermatologic Complications of HIV
Authors: Mutyambizi Kudakwashe , Weeks Craig S. , Bolduc Philip 
Published: September 2023

Abstract
This chapter describes the dermatologic complications of HIV infection and treatment. The chapter includes information about the incidence, presentation, and management of inflammatory dermatoses in HIV including seborrheic dermatitis, psoriasis, atopic dermatitis and xerosis, papular pruritic eruption of AIDS, and HIV-associated eosinophilic pustular folliculitis. In addition, common and important cutaneous adverse drug reactions among people with HIV and management factors are presented for antiretroviral drug classes. Lastly, learners are presented with the diagnosis and management of viral, fungal, bacterial, and parasitic opportunistic infections occurring in HIV patients and presentation and treatment of cancers associated with HIV and aging. An important addition in this edition is a review of recent monkeypox data.
Neurological Effects of HIV Infection
Authors: Hasbun Rodrigo , Kass Joseph S. 
Published: September 2023

Abstract
There is a high prevalence of HIV-associated neurocognitive disorder (HAND) in antiretroviral treatment (ART)-naive patients and in patients treated with ART with virologic suppression. Rapid screening tools such as the Montreal Cognitive Assessment test and the Frontal Assessment Battery test have been evaluated for their use in diagnosing HAND in the clinic. HAND is associated with significant cognitive, behavioral, and motor abnormalities that can impact ART adherence, retention-in-care in older individuals, virologic success, and quality of life. The differential diagnosis of meningitis in people living with HIV (PWH) is broad (e.g., viral, bacterial, fungal, mycobacterial, or lymphomatous). All adults with meningitis should be tested for HIV. Meningitis in PWH is usually treatable, and a cause should be investigated. This chapter delineates the clinical features, differential diagnosis, and management of the neurologic effects of HIV, including HIV-associated neurocognitive disorders, meningitis, myelopathy, distal symmetric polyneuropathy, inflammatory demyelinating polyneuropathy, neurologic complications that people living with HIV experience with cytomegalovirus (CMV) infections and intracranial lesions.
HIV Health Care Programs and Insurance Coverage in the U.S. Health Care System
Authors: McGorman Leslie , Packett Bruce J. 
Published: September 2023

Abstract
It has been more than 12 years since passage of the landmark Affordable Care Act (ACA), and more than 8 years since implementation of the Health Insurance Marketplace, which greatly expanded the availability of health coverage for persons living with HIV (PWH) in the United States. However, serious challenges such as affordability and access to treatment still remain and are especially evident in the 12 states that have chosen not to expand their Medicaid coverage. The ACA required all US citizens to have some form of health coverage, although the nature of that coverage varied widely. Subsequently, the passage of the Tax Cuts and Jobs Act of 2017 repealed the ACA’s “individual mandate” to purchase insurance. As a result, individuals who were unable to afford insurance may have been heavily impacted by chronic lack of access to health coverage. Health care programs and insurance coverage for PWH in the United States continues to involve a mix of governmental funding and private systems because of the lack of universal health care coverage. Medicaid remains the largest source of coverage for PWH: to date, 38 states and the District of Columbia have chosen to adopt Medicaid expansion in some form. The federally administered Ryan White HIV/AIDS Program continues to provide “safety net” medical and supportive services for PWH.
Cysteine Enrichment Mediates Co-Option of Uricase in Reptilian Skin and Transition to Uricotelism
Authors: Mori Giulia , Liuzzi Anastasia , Ronda Luca , Di Palma Michele , Chegkazi Magda S , Bui Soi , Garcia-Maya Mitla , Ragazzini Jasmine , Malatesta Marco , Della Monica Emanuele , Rivetti Claudio , Antin Parker B , Bettati Stefano , Steiner Roberto A , Percudani Riccardo 
Published: September 2023

Abstract
Uric acid is the main means of nitrogen excretion in uricotelic vertebrates (birds and reptiles) and the end product of purine catabolism in humans and a few other mammals. While uricase is inactivated in mammals unable to degrade urate, the presence of orthologous genes without inactivating mutations in avian and reptilian genomes is unexplained. Here we show that the Gallus gallus gene we name cysteine-rich urate oxidase (CRUOX) encodes a functional protein representing a unique case of cysteine enrichment in the evolution of vertebrate orthologous genes. CRUOX retains the ability to catalyze urate oxidation to hydrogen peroxide and 5-hydroxyisourate (HIU), albeit with a 100-fold reduced efficiency. However, differently from all uricases hitherto characterized, it can also facilitate urate regeneration from HIU, a catalytic property that we propose depends on its enrichment in cysteine residues. X-ray structural analysis highlights differences in the active site compared to known orthologs and suggests a mechanism for cysteine-mediated self-aggregation under H2O2-oxidative conditions. Cysteine enrichment was concurrent with the transition to uricotelism and a shift in gene expression from the liver to the skin where CRUOX is co-expressed with β-keratins. Therefore, the loss of urate degradation in amniotes has followed opposite evolutionary trajectories: while uricase has been eliminated by pseudogenization in some mammals, it has been repurposed as a redox-sensitive enzyme in the reptilian skin.
Kinematics of the Upper Eyelid and the Globe During Downward Excursion With Comparative Analysis in Patients With Thyroid Eye Disease
Authors: Abboud Jean-Paul J. , Badawe Heba , Nguyen John , Khraiche Massoud L. , Sivak-Callcott Jennifer A. 
Published: September 2023

Purpose:
To analyze the kinematics of the upper eyelid and the globe on downward excursion for potential use in monitoring thyroid eye disease (TED) progression in an objective manner.

Methods:
Ten normal volunteers and 10 patients with TED were studied. A high-speed (240 fps) digital camera with a coaxial light source set at a constant distance from the subjects’ eyes was used to record the excursion of the upper eyelid and the globe from extreme upgaze to extreme downgaze. Clinical data, including age, gender, race, thyroid function tests, Vision, Inflammation/Congestion, Strabismus/motility restriction, Appearance/exposure score (primary surgeons’ preference of TED grading system), exophthalmometry, and eyelid measurements were collected for all patients with TED. Frame-by-frame analyses of the videos were performed using Python software (version 3.6) and the Open Source Computer Vision Library. Temporal resolution was obtained by measuring the number of frames from initiation of eyelid and globe movement from extreme upgaze (t0) to extreme downgaze (tf). Spatial resolution was obtained by measuring the number of pixels the eyelid margin and the globe traversed from t0 to tf. The data were then plotted on a graph to calculate the velocity of the upper eyelid and the globe during downward excursion.

Results:
Velocimetric calculations using high-speed photography suggests that downward excursion of the upper eyelid, and the globe occurs in 2 phases: the acceleration phase and the deceleration phase. Comparative analysis of slow-motion videography demonstrates that patients with TED were found to have attenuation in the early acceleration phase of upper eyelid excursion compared with normal subjects. In patients with TED, the difference in velocity between the eyelid and the globe occurs in the early deceleration phase.

Conclusions:
The upper eyelid normally synchronizes intimately with the globe during downward eye movement. Data from this study reveal that attenuation mostly in the early deceleration phase of eyelid movement relative to the globe accounts for the dynamic eyelid lag seen on clinical examination. Further analysis is needed to show if a quantified von Graefe sign can be used as an objective means of monitoring progression in TED.
“They Talk to Me Like a Person” Experiences of People in an Injectable Opioid Agonist Treatment Program
Authors: Jackson Jennifer , Colborne Marnie , Gadimova Farida , Kennedy Mary Clare 
Published: September 2023

Abstract

Objective
The aim of this study was to explore client experiences in a community-based injectable opioid agonist therapy (iOAT) program.

Study Setting
The study occurred across two cities in Alberta, Canada.

Study Design
The research team conducted secondary interpretive description analysis on qualitative interview transcripts.

Data Collection
Twenty-three iOAT clients were interviewed as part of a prior quality improvement initiative. Using secondary analysis of the transcripts, interviews were analyzed for themes, to create an understanding of clients' experiences.

Principal Findings
Participants accessed iOAT through other health services, for treatment of opioid use disorder. Participants reported that building trusting and supportive relationships with nurses was crucial to their success in the program. Through these relationships, participants experienced stopping and starting. They stopped behaviors such as illicit drug use, having withdrawal symptoms and anxiety, and prohibited income generation activities. They started taking care of themselves, accessing housing, increasing financial stability, receiving primary care, and connecting with friends and family. The global experience of iOAT was one of positive change for participants.

Conclusions
The findings of this study are largely consistent with other published examples—iOAT programs create benefits for both clients and their communities. Although clients may join the program to access the hydromorphone, the relationships between staff and clients are the key driver of success.
A Pathway to Treatment for Pregnant Women With Opioid Use Disorder
Authors: Clark Roshunya Shavon , Pares-Avila Jose A. 
Published: September 2023

Abstract

Background
Addiction to opioids, a well-known public health crisis, is now more prevalent in pregnant women as evidenced by the parallel rise with pregnant women in the epidemic with the general population. Evidence is now available that substantiates the need for global awareness to increase efforts in the treatment of pregnant women with opioid use disorder (OUD) as this vulnerable population lacks equal access to opioid abuse treatment across the United States.

Aim
The overarching aim and purpose of this quality improvement project was to increase access to treatment for pregnant women with OUD who are currently underserved in a community located in Florida.

Methods
Between January and April 2022, the 4Ps (parents, partners, past, and pregnancy), a validated screening tool, was implemented in an organization that accepts individuals with substance abuse. Each positive screen was referred for assessment for buprenorphine induction and medication-assisted treatment follow-up. Descriptive statistics were collected counting the number of screens completed, the number of positive screens, the number of referrals, and the number of patients remaining in treatment for 30 and 60 days.

Results
Twenty-two screens were completed. The results yielded an increase in referrals, a 75% increase in treatment of pregnant women, and an average of 83% of participants remained in treatment.

Conclusion
The implementation of a validated screening tool assisted in increasing access to treatment for pregnant women with OUD. Once implemented, the screening tool forges a pathway for referrals and evidence-based treatment for pregnant women with OUD.