bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary Pharmacokinetics of Immediate and Controlled Release Oxycodone and its Phase I and II Metabolites Using LC–MS-MS
Authors: Truver Michael T , Jakobsson Gerd , Chermà Maria D , Swortwood Madeleine J , Gréen Henrik , Kronstrand Robert 
Published: December 2021

Abstract
Oxycodone (OC) is a schedule II semisynthetic opioid in the USA that is prescribed for its analgesic effects and has a high potential for abuse. Prescriptions for OC vary based on the dosage and formulation, immediate release (IR) and controlled release (CR). Monitoring OC metabolites is beneficial for forensic casework. The limited studies that involve pharmacokinetics of the urinary excretion of OC metabolites leave a knowledge gap regarding the excretion of conjugated and minor metabolites, pharmacokinetic differences by formulation, and the impact of CYP2D6 activity on the metabolism and excretion of OC. The objectives of this study were to compare urinary excretion of phase I and II metabolites by formulation and investigate if ratio changes over time could be used to predict the time of intake. Subjects (n = 7) received a single 10 mg IR tablet of Oxycodone Actavis. A few weeks later the same subjects received a single 10 mg CR tablet of Oxycodone Actavis. During each setting, urine was collected at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 9, 10, 12, 14, 24, 48 and 72 h. Urine samples (100 µL) were diluted with 900 µL internal standard mixture and analyzed on an Acquity UPLC® I-class coupled to a Waters Xevo TQD using a previously validated method. The CYP2D6 phenotypes were categorized as poor metabolizers (PM), intermediate metabolizers (IM), extensive metabolizers (EM) and ultrarapid metabolizers (UM). Comparisons between IR and CR were performed using two-tailed paired t-test at a significance level of P = 0.05. The metabolite ratios showed a general increase over time. Four metabolite to parent ratios were used to predict the time of intake showing that predictions were best at the early time points.
Physical, Psychological, and Social Outcomes in Pediatric Burn Survivors Ages 5 to 18 Years: A Systematic Review
Authors: Patel Khushbu F , Rodríguez-Mercedes Silvanys L , Grant Gabrielle G , Rencken Camerin A , Kinney Erin M , Austen Amelia , Hou Carina , Brady Keri J S , Schneider Jeffrey C , Kazis Lewis E , Ryan Colleen M 
Published: December 2021

Abstract
Acute pediatric burn injuries often result in chronic sequelae that affect physical, psychological, and social outcomes. To date, no review has comprehensively reported on the impact of burn injuries across all three domains in school-aged children. The aim of this systematic review was to identify published literature that focuses on the impact of burn injuries on physical, psychological, or social functioning, and report upon the nature of study characteristics and their outcomes. We included literature published after 1980, focusing on burn outcomes in children aged 5 to 18 years. Each eligible study was systematically reviewed and primary outcomes were classified into outcome domains based on existing frameworks. Fifty-eight studies met inclusion criteria, and reported on physical (n = 24), psychological (n = 47), and social (n = 29) domains. The majority of the studies had sample sizes of &lt;100 participants, burn size of &lt;40%, and findings reported by parents and/or burn survivors. Only eight of 107 different measures were used in three or more studies. Parents and burn survivors generally reported better physical and social outcomes and worse psychological functioning compared to non-burn populations. Physical disabilities were associated with psychological and social functioning in several studies. Follow-up data reported improvements across domains. This review demonstrates the importance of physical, psychological, and social status as long-term outcomes in burn survivors. Mixed findings across three outcome domains warrant long-term research. Findings of this review will guide the foundation of comprehensive burn and age-specific instruments to assess burn recovery.
Validation and effects of drying and prey hair on fecal hormone concentrations in spotted hyenas
Authors: Greenberg Julia R , Montgomery Tracy M , Holekamp Kay E , Beehner Jacinta C 
Published: December 2021

Abstract
As fecal steroid methods increasingly are used by researchers to monitor the physiology of captive and wild populations, we need to expand our validation protocols to test the effects of procedural variation and to identify contamination by exogenous sources of steroid hormones. Mammalian carnivore feces often contain large amounts of hair from the prey they consume, which itself may contain high concentrations of hormones. In this study, we report first a validation of two steroid hormone antibodies, corticosterone and progesterone, to determine fecal concentrations of these hormones in wild spotted hyenas (Crocuta crocuta). Next, we expand on these standard validation protocols to test two additional metrics: (i) whether hair from consumed prey or (ii) the specific drying method (oven incubation vs. lyophilization) affect steroid hormone concentrations in feces. In the first biological validation for the progesterone antibody in this species, progesterone concentrations met our expectations: (i) concentrations of plasma and fecal progesterone were lowest in immature females, higher in lactating females, and highest in pregnant females; (ii) across pregnant females, fecal progesterone concentrations were highest during late pregnancy; and (iii) among lactating females, fecal progesterone concentrations were highest after parturition. Our additional validation experiments indicated that contamination with prey hair and drying method are hormone-specific. Although prey hair did not release hormones into samples during storage or extraction for either hormone, its presence appeared to “dilute” progesterone (but not corticosterone) measures indirectly by increasing the dry weight of samples. In addition, fecal progesterone, but not corticosterone, values were lower for lyophilized than for incubated samples. Therefore, in addition to the standard analytical and biological validation steps, additional methodological variables need to be tested whenever we measure fecal hormone concentrations, particularly from predatory mammals.
Papillary thyroid carcinoma from a thyroglossal cyst: case series
Authors: Gómez-Álvarez Luis Rodrigo , Treviño-Lozano Marco Antonio , de la O-Escamilla Manuel Enrique , Vergara-Miranda Héctor , Anda Lilia Andrea Mata-De , Falcón Luis Ángel Ceceñas , Tafoya Ary Rochio 
Published: December 2021

Abstract
Papillary carcinoma originating from a thyroglossal cyst represents an infrequent finding, which occurs in ~1% of cases of thyroglossal cyst and its presentation is usually the same as that of a benign cyst, which represents the most frequent benign congenital lesion of the neck. The diagnosis is usually presented as a finding on the histopathological examination. Two cases of a thyroglossal cyst with later development of malignancy are presented. The first, a 30-year-old female, and the second, a 32-year-old male. Both began their condition after presenting an increase in volume in the neck, the female presented a right sub-mental triangle of 1 year of evolution, and the male on the anterior side of the neck. In both cases, the diagnosis of thyroglossal cyst was made by the physical examination and findings of cervical ultrasound and computed axial tomography. Surgical management consisted of the Sistrunk procedure with a definitive histopathological result for papillary thyroid carcinoma originating from thyroglossal cyst. In the case of the male patient, the Sistrunk procedure was performed along a total thyroidectomy, although in the female patient, a total thyroidectomy was performed in a second stage. Patients were then discharged and referred to the endocrinology service for further medical treatment. The management of these cases continues to be controversial due to the limited number of reported cases, so the multidisciplinary management and individualization of each case plays a fundamental role in the management of this rare condition.
Ribosomal leaky scanning through a translated uORF requires eIF4G2
Authors: Smirnova Victoria V , Shestakova Ekaterina D , Nogina Daria S , Mishchenko Polina A , Prikazchikova Tatiana A , Zatsepin Timofei S , Kulakovskiy Ivan V , Shatsky Ivan N , Terenin Ilya M 
Published: December 2021

Abstract
eIF4G2 (DAP5 or Nat1) is a homologue of the canonical translation initiation factor eIF4G1 in higher eukaryotes but its function remains poorly understood. Unlike eIF4G1, eIF4G2 does not interact with the cap-binding protein eIF4E and is believed to drive translation under stress when eIF4E activity is impaired. Here, we show that eIF4G2 operates under normal conditions as well and promotes scanning downstream of the eIF4G1-mediated 40S recruitment and cap-proximal scanning. Specifically, eIF4G2 facilitates leaky scanning for a subset of mRNAs. Apparently, eIF4G2 replaces eIF4G1 during scanning of 5′ UTR and the necessity for eIF4G2 only arises when eIF4G1 dissociates from the scanning complex. In particular, this event can occur when the leaky scanning complexes interfere with initiating or elongating 80S ribosomes within a translated uORF. This mechanism is therefore crucial for higher eukaryotes which are known to have long 5′ UTRs with highly frequent uORFs. We suggest that uORFs are not the only obstacle on the way of scanning complexes towards the main start codon, because certain eIF4G2 mRNA targets lack uORF(s). Thus, higher eukaryotes possess two distinct scanning complexes: the principal one that binds mRNA and initiates scanning, and the accessory one that rescues scanning when the former fails.
Hepatitis C Virus Is Associated With Increased Mortality Among Incarcerated Hospitalized Persons in Massachusetts
Authors: Wurcel Alysse G , Guardado Rubeen , Beckwith Curt G 
Published: December 2021

AbstractHepatitis C virus (HCV) is curable, but incarcerated populations face barriers to treatment. In a cohort of incarcerated hospitalized patients in Boston, Massachusetts, HCV infection was associated with increased mortality. Access to HCV treatment in carceral settings is crucial to avoid unnecessary death and to support HCV elimination efforts.
Effectiveness of Dalbavancin Compared With Standard of Care for the Treatment of Osteomyelitis: A Real-world Analysis
Authors: Cain Alexander R , Bremmer Derek N , Carr Dustin R , Buchanan Carley , Jacobs Max , Walsh Thomas L , Moffa Matthew A , Shively Nathan R , Trienski Tamara L 
Published: December 2021

Abstract

Background
Preliminary data suggest that the effectiveness of dalbavancin may be similar to current standard-of-care (SoC) treatment options for osteomyelitis with an advantageous dosing schedule.

Methods
This was a retrospective, observational cohort study of adult patients diagnosed with osteomyelitis. Patients were matched 1:2 to dalbavancin (administered as 2 doses separated by 1 week) or SoC treatment for osteomyelitis according to the Charlson Comorbidity Index, site of infection, and causative pathogen. The primary objective was to determine the incidence of treatment failure after a 1-year follow-up period. Secondary objectives included hospital length of stay (LOS), infection-related 1-year readmission rates, and treatment-related adverse events.

Results
A total of 132 patients received dalbavancin (n = 42) or SoC (n = 90). Baseline characteristics, including rates of surgical intervention, were similar between the 2 treatment groups. Treatment failure was similar between those who received dalbavancin and SoC (21.4% vs 23.3%; P = .81). Patients who received dalbavancin had a shorter hospital LOS (5.2 days vs 7.2 days; P = .01). There was no difference in the rates of infection-related readmission between the dalbavancin and the SoC group (31% vs 31.1%; P = .99). There were numerically fewer adverse events in the dalbavancin group compared with the SoC group (21.4% vs 36.7%; P = .08). Peripherally inserted central catheter line–related complications were reported in 17.8% of patients in the SoC group.

Conclusions
Dalbavancin administered as a 2-dose regimen is a safe and effective option for the treatment of osteomyelitis.
Immunogenicity, Safety, and Tolerability of V114, a 15-Valent Pneumococcal Conjugate Vaccine, in Immunocompetent Adults Aged 18–49 Years With or Without Risk Factors for Pneumococcal Disease: A Randomized Phase 3 Trial (PNEU-DAY)
Authors: Hammitt Laura L , Quinn Dean , Janczewska Ewa , Pasquel Francisco J , Tytus Richard , Rajender Reddy K , Abarca Katia , Khaertynova Ilsiyar M , Dagan Ron , McCauley Jennifer , Cheon Kyeongmi , Pedley Alison , Sterling Tina , Tamms Gretchen , Musey Luwy , Buchwald Ulrike K 
Published: December 2021

AbstractBackgroundAdults with certain medical and behavioral factors are at increased risk for pneumococcal disease (PD). Sequential vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for at-risk adults in some countries.MethodsThis phase 3 trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 6 months later by PPSV23, in immunocompetent adults aged 18–49 years with or without predefined risk factors for PD (NCT03547167). Overall, 1515 participants were randomized 3:1 to receive either V114 or PCV13, followed by PPSV23.ResultsMost common solicited adverse events (AEs) following administration of V114 or PCV13 as well as PPSV23 were injection-site pain and fatigue. The proportion of participants with AEs was comparable in both groups. V114 and PCV13 were immunogenic based on opsonophagocytic activity (OPA) geometric mean titers (GMTs) 30 days postvaccination for all serotypes contained in each respective vaccine. OPA GMTs to the 2 unique serotypes in V114 were robust in the V114 group. PPSV23 was immunogenic for all 15 serotypes contained in V114 in both vaccination groups, including 22F and 33F.ConclusionsV114 administered alone or sequentially with PPSV23 is well tolerated and immunogenic for all 15 serotypes, including those not contained in PCV13, in immunocompetent adults aged 18–49 years with or without certain medical or behavioral risk factors for PD.Clinical Trials RegistrationNCT03547167 and EudraCT 2017-004915-38.
Clinical Significance of Staphylococcus aureus in a Single Positive Blood Culture Bottle
Authors: Go John Raymond , Challener Douglas , Corsini Campioli Cristina , Sohail M Rizwan , Palraj Raj , Baddour Larry M , Abu Saleh Omar 
Published: December 2021

Abstract
Clinical significance of a single positive blood culture bottle (SPBCB) with Staphylococcus aureus is unclear. We aimed to assess the significance of an SPBCB by looking at the associated outcomes. We performed a retrospective, multicenter study of patients with an SPBCB with S aureus using data collected from both electronic health records and the clinical microbiology laboratory. Overall, 534 patients with S aureus bacteremia were identified and 118 (22.1%) had an SPBCB. Among cases with an SPBCB, 106 (89.8%) were classified as clinically significant whereas 12 (10.2%) were considered contaminated or of unclear significance. A majority (92.4%) of patients received antibiotic therapy, but patients with clinically significant bacteremia were treated with longer courses (25.9 vs 5.7 days, P &lt; .001). Significant differences in both frequency of echocardiography (65.1% vs 84.6%, P &lt; .001) and infective endocarditis diagnosis (3.8% vs 14.2%, P = .002) were seen in those with an SPBCB compared to those with multiple positive bottles. A longer hospital length of stay and higher 90-day, 6-month, and 1-year mortality rates were seen in patients with multiple positive blood culture bottles. An SPBCB with S aureus was common among our patients. While this syndrome has a more favorable prognosis as compared to those with multiple positive blood cultures, clinicians should remain concerned as it portends a risk of infective endocarditis and mortality.
Competitive exposure and existential recognition: Visibility and legitimacy on academic social networking sites
Authors: Francke Helena , Hammarfelt Björn 
Published: December 2021

AbstractOver the past decade, academic social networking sites, such as ResearchGate and Academia.edu, have become a common tool in academia for accessing publications and displaying metrics for research evaluation and self-monitoring. In this conceptual article, we discuss how these academic social networking sites, as devices of evaluation that build on both traditional values, objects, and metrics in academic publishing and on social media logics and algorithmic metrics, come to fulfil a need in the current academic (publishing) ecosystem. We approach this issue by identifying key affordances that arise in the interaction between platform and user. We then position these affordances in relation to potential needs of academics in today’s publishing landscape by drawing on Hafermalz’s metaphor of the ‘fear of exile’, which provides an alternative way of understanding the importance of visibility in the networked world, as a combination of competitive exposure and existential recognition. We end by considering the grounds on which the platforms may be attributed some level of legitimacy. This is done in order to understand the inherent contradiction between the broad use of the platforms and the fact that their integrity has been questioned repeatedly. We seek an answer to a legitimacy for the platforms in the fact that a pragmatic, mutual benefit exists between them and the research community; a benefit that is enhanced by the audit society influencing current academia.
Between-person and within-person associations of sleep and working-memory in the everyday lives of old and very old adults: initial level, learning, and variability
Authors: Lücke Anna J , Wrzus Cornelia , Gerstorf Denis , Kunzmann Ute , Katzorreck Martin , Schmiedek Florian , Hoppmann Christiane , Schilling Oliver K 
Published: December 2021

AbstractStudy ObjectivesSleep duration affects various aspects of cognitive performance, such as working-memory and learning, among children and adults. However, it remains open, whether similar or even stronger associations exist in old and very old age when changes in sleep and cognitive decrements are common.MethodsUsing repeated daily-life assessments from a sample of 121 young-old (66–69 years old) and 39 old-old adults (84–90 years old), we assessed links between sleep duration and different aspects of working-memory (initial level, practice-related learning, and residualized variability) between and within persons. Participants reported their sleep durations every morning and performed a numerical working-memory updating task six times a day for seven consecutive days.ResultsBoth people who slept longer and those who slept shorter than the sample average showed lower initial performance levels, but a stronger increase of WM over time (i.e. larger learning effects), relative to people with average sleep. Sleep duration did not predict performance variability. Within-person associations were found for people sleeping relatively little on average: For them, working-memory performance was lower on days with shorter than average sleep, yet higher on days with longer than average sleep. Except for lower initial levels of working-memory in old-old adults, no differences between young-old and old-old adults were observed.ConclusionWe conclude that sufficient sleep remains important for working-memory performance in older adults and that it is relevant to include different aspects of working-memory performance, because effects differed for initial performance and learning.
Clozapine Induces an Acute Proinflammatory Response That Is Attenuated by Inhibition of Inflammasome Signaling: Implications for Idiosyncratic Drug-Induced Agranulocytosis
Authors: Sernoskie Samantha Christine , Lobach Alexandra R , Kato Ryuji , Jee Alison , Weston Joseph Kyle , Uetrecht Jack 
Published: December 2021

Abstract
Although clozapine is a highly efficacious schizophrenia treatment, it is under-prescribed due to the risk of idiosyncratic drug-induced agranulocytosis (IDIAG). Clinical data indicate that most patients starting clozapine experience a transient immune response early in treatment and a similar response has been observed in clozapine-treated rats, but the mechanism by which clozapine triggers this transient inflammation remains unclear. Therefore, the aim of this study was to characterize the role of inflammasome activation during the early immune response to clozapine using in vitro and in vivo models. In both differentiated and nondifferentiated human monocytic THP-1 cells, clozapine, but not its structural analogues fluperlapine and olanzapine, caused inflammasome-dependent caspase-1 activation and IL-1β release that was inhibited using the caspase-1 inhibitor yVAD-cmk. In Sprague Dawley rats, a single dose of clozapine caused an increase in circulating neutrophils and a decrease in lymphocytes within hours of drug administration along with transient spikes in the proinflammatory mediators IL-1β, CXCL1, and TNF-α in the blood, spleen, and bone marrow. Blockade of inflammasome signaling using the caspase-1 inhibitor VX-765 or the IL-1 receptor antagonist anakinra attenuated this inflammatory response. These data indicate that caspase-1-dependent IL-1β production is fundamental for the induction of the early immune response to clozapine and, furthermore, support the general hypothesis that inflammasome activation is a common mechanism by which drugs associated with the risk of idiosyncratic reactions trigger early immune system activation. Ultimately, inhibition of inflammasome signaling may reduce the risk of IDIAG, enabling safer, more frequent use of clozapine in patients.
Age-related epithelial defects limit thymic function and regeneration
Authors: Kousa Anastasia I. , Jahn Lorenz , Zhao Kelin , Flores Angel E. , Granadier David , Cooper Kirsten , Sheridan Julie M. , Lemarquis Andri , Sikkema Lisa , Argyropoulos Kimon V. , Tsai Jennifer , Lazrak Amina , Nichols Katherine , Lee Nichole , Ghale Romina , Malard Florent , Andrlova Hana , Gomes Antonio L.C. , Velardi Enrico , Youssef Salma , da Silva Marina B. , Docampo Melissa , Sharma Roshan , Mazutis Linas , Wimmer Verena C. , Rogers Kelly L. , DeWolf Susan , Gipson Brianna , Setty Manu , Pe’er Dana , Manley Nancy R. , Gray Daniel H.D. , Dudakov Jarrod A. , van den Brink Marcel R.M. 
Published: December 2021

SUMMARYThe thymus is essential for establishing adaptive immunity yet undergoes age-related atrophy leading to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age. Focusing on non-hematopoietic stromal cells, and using single-cell and spatial transcriptomics, lineage-tracing, and advanced imaging, we discovered two atypical thymic epithelial cell (TEC) states that emerged with age. Age-associated (aa)TECs formed atypical high-density epithelial clusters that were devoid of thymocytes, an accretion of non-functional thymic tissue that worsened with age and exhibited features of partial epithelial-to-mesenchymal transition (EMT).In silicointeraction analysis revealed that aaTEC emergence drew tonic signals from other TEC populations at baseline, acting as a sink for TEC growth factors. Following damage, aaTEC expanded substantially, further perturbing trophic pathways, and correlating with defective regeneration of the involuted thymus. These findings define a unique feature of thymic involution linked to immune aging.