Miracle-dz/UniFAR-FTUs huggingface dataset:
LONEPINELLA SP. ISOLATED FROM WOUND INFECTIONS OF KOALAS

ABSTRACT: We describe two cases of wound infections of koalas (Phascolarctos cinereus), one wild and one captive, in which Lonepinella-like organisms were involved. The wild adult koala was captured with bite wound injuries, as part of a koala population management program in Queensland, Australia. In both cases, there was evidence of physical trauma causing the initial wound. The captive koala suffered injury from the cage wire, and the wild koala had injuries suggestive of intermale fighting. Gram-negative bacteria isolated from both cases proved to be challenging to identify using routine diagnostic tests. The wound in the captive koala yielded a pure culture of an organism shown by whole genome sequence (WGS) analysis to be a member of the genus Lonepinella, but not a member of the only formally described species, L. koalarum. The wound of the wild koala yielded a mixed culture of Citrobacter koseri, Enterobacter cloacae and an organism shown by WGS analysis to be Lonepinella, but again not Lonepinella koalarum. Both cases were difficult to treat; the captive koala eventually had to have the phalanges amputated, and the wild koala required removal of the affected claw. The two Lonepinella isolates from these cases have a close relationship to an isolate from a human wound caused by a koala bite and may represent a novel species within the genus Lonepinella. Wound infections in koalas linked to Lonepinella have not been reported previously. Wildlife veterinarians need to be aware of the potential presence of Lonepinella-like organisms when dealing with wound infections in koalas, and the inability of commercial kits and systems to correctly identify the isolates.
Evolutionary genetics of the mitochondrial genome: insights from Drosophila

Abstract Mitochondria are key to energy conversion in virtually all eukaryotes. Intriguingly, despite billions of years of evolution inside the eukaryote, mitochondria have retained their own small set of genes involved in the regulation of oxidative phosphorylation (OXPHOS) and protein translation. Although there was a long-standing assumption that the genetic variation found within the mitochondria would be selectively neutral, research over the past 3 decades has challenged this assumption. This research has provided novel insight into the genetic and evolutionary forces that shape mitochondrial evolution and broader implications for evolutionary ecological processes. Many of the seminal studies in this field, from the inception of the research field to current studies, have been conducted using Drosophila flies, thus establishing the species as a model system for studies in mitochondrial evolutionary biology. In this review, we comprehensively review these studies, from those focusing on genetic processes shaping evolution within the mitochondrial genome, to those examining the evolutionary implications of interactions between genes spanning mitochondrial and nuclear genomes, and to those investigating the dynamics of mitochondrial heteroplasmy. We synthesize the contribution of these studies to shaping our understanding of the evolutionary and ecological implications of mitochondrial genetic variation.
Investigating the role of Candida albicans as a universal substrate for oral bacteria using a transcriptomic approach: implications for interkingdom biofilm control?

Candida albicans is frequently identified as a colonizer of the oral cavity in health and has recently been termed a “keystone” commensal due to its role on the bacterial communities. However, the role that C. albicans plays in such interactions is not fully understood. Therefore, this study aimed to identify the relationship between C. albicans and bacteria associated with oral symbiosis and dysbiosis. To do this, we evaluated the ability of C. albicans to support the growth of the aerobic commensal Streptococcus gordonii and the anaerobic pathogens Fusobacterium nucleatum and Porphyromonas gingivalis in the biofilm environment. RNA‐Sequencing with the Illumina platform was then utilized to identify C. albicans gene expression and functional pathways involved during such interactions in dual‐species and a 4‐species biofilm model. Results indicated that C. albicans was capable of supporting growth of all three bacteria, with a significant increase in colony counts of each bacteria in the dual‐species biofilm (p < 0.05). We identified specific functional enrichment of pathways in our 4‐species community as well as transcriptional profiles unique to the F. nucleatum and S. gordonii dual‐species biofilms, indicating a species‐specific effect on C. albicans. Candida‐related hemin acquisition and heat shock protein mediated processes were unique to the organism following co‐culture with anaerobic and aerobic bacteria, respectively, suggestive that such pathways may be feasible options for therapeutic targeting to interfere with these fungal‐bacterial interactions. Targeted antifungal therapy may be considered as an option for biofilm destabilization and treatment of complex communities. Moving forward, we propose that further studies must continue to investigate the role of this fungal organism in the context of the interkingdom nature of oral diseases.
Use of Developmental Midazolam and 1-Hydroxymidazolam Data with Pediatric Physiologically Based Modeling to Assess Cytochrome P450 3A4 and Uridine Diphosphate Glucuronosyl Transferase 2B4 Ontogeny In Vivo

Pediatric physiologically based pharmacokinetics modeling in drug development has grown in the past decade but uncertainty remains regarding ontogeny of some drug metabolizing enzymes. In this study, a midazolam and 1-hydroxymidazolam physiologically based pharmacokinetic model (PBPK) model was developed and used to define the ontogeny for hepatic cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyl transferase (UGT) 2B4. Data for model development and pharmacokinetic studies on intravenous midazolam in adults and pediatrics were collated from the literature. The PBPK model was verified in the adult population and then used to compare the performance of two ontogeny profiles for CYP3A4 in terms of parent drug elimination in pediatrics. Four studies also published data on the 1-hydroxymidazolam, and this was used to evaluate the known ontogeny for UGT2B4.For midazolam elimination, the Upreti CYP3A4 ontogeny performed better than Salem; mean error (bias) and mean squared error (precision) were 0.14 and 0.064 compared with 0.69 and 1.21, respectively. For 1-hydroxymidazolam elimination, the Simcyp default ontogeny of UGT2B4 appeared to perform best for studies covering the age range 0.5 to 15.7 years, while for a study in younger ages 0 to 1 years it was the Badee UGT2B4 ontogeny. In preterm neonates, overall expression of UGT appeared to be around 10% of that in adults.Identifying the optimal model of CYP3A4 ontogeny is important for the regulatory use of PBPK. The results for midazolam are conclusive but research about other CYP3A4 metabolized compounds will underpin generalizability of the CYP3A4 ontogeny. UGT2B4 ontogeny is less certain, but this study indicates the most likely scenarios. SIGNIFICANCE STATEMENT A PBPK model for midazolam and 1-hydroxymidazolam was developed to test various ontogeny scenarios for CYP3A4 and UGT2B4. The CYP3A4 ontogeny of Upreti resulted in more accurate prediction of midazolam CL across nine clinical studies, age range birth to 18 years. 1-Hydroxy midazolam was used as a marker of UGT. The Simcyp default ‘no ontogeny’ profiles for UGT2B4 performed the best; however, for <1 year of age, there was some evidence of overactivity of this enzyme compared to adults.
Neuropathic pain following spinal cord hemisection induced by the reorganization in primary somatosensory cortex and regulated by neuronal activity of lateral parabrachial nucleus

Neuropathic pain after spinal cord injury (SCI) remains a common and thorny problem, influencing the life quality severely. This study aimed to elucidate the reorganization of the primary sensory cortex (S1) and the regulatory mechanism of the lateral parabrachial nucleus (lPBN) in the presence of allodynia or hyperalgesia after left spinal cord hemisection injury (LHS).
Association between snus use and lipid status in Swedish men

Abstract Snus is a common tobacco product in Sweden, but the cardiovascular risk profile for snus users is less known than for cigarette smokers. We examined the association of snus use with lipid status, particularly in comparison to non-tobacco use and cigarette smoking, using data from 5930 men in the Northern Sweden MONICA study. Tobacco use was self-reported in 1986 to 2014 (24.4% used snus) and blood samples were collected at the same time. Harmonized analyses on non-high-density lipoprotein (non-HDL) cholesterol, HDL cholesterol, and triglycerides were conducted in 2016 to 2018. Three hundred eighty-one snus users had also been examined more than once, allowing us to study the effect of discontinued use (achieved by 21.0%). In multivariable linear regression models, snus use was associated with higher HDL cholesterol and triglyceride concentrations compared to non-tobacco use (p values ≤ 0.04), and it was associated with higher HDL cholesterol concentrations and lower triglyceride concentrations compared to cigarette smoking (p values ≤ 0.02). Snus use was not associated with non-HDL cholesterol concentrations, irrespective of the comparison group (p values ≥ 0.07). There was no indication that higher intensity of snus use led to a worse lipid profile, given that high-consumers had higher HDL cholesterol concentrations than low-consumers (p value = 0.02), or that discontinuation of snus use led to a better lipid profile, given that continued users had lower triglyceride concentrations than discontinued users (p value = 0.03). Further studies are needed to confirm or refute our findings.
Epidemiology and a Predictive Model of Prognosis Index Based on Machine Learning in Primary Breast Lymphoma: Population-Based Study

Background Primary breast lymphoma (PBL) is a rare disease whose epidemiological features, treatment principles, and factors used for the patients’ prognosis remain controversial. Objective The aim of this study was to explore the epidemiology of PBL and to develop a better model based on machine learning to predict the prognosis for patients with primary breast lymphoma. Methods The annual incidence of PBL was extracted from the surveillance, epidemiology, and end results database between 1975 and 2019 to examine disease occurrence trends using Joinpoint software (version 4.9; National Cancer Institute). We enrolled data from 1251 female patients with primary breast lymphoma from the surveillance, epidemiology, and end results database for survival analysis. Univariable and multivariable analyses were performed to explore independent prognostic factors for overall survival and disease-specific survival of patients with primary breast lymphoma. Eight machine learning algorithms were developed to predict the 5-year survival of patients with primary breast lymphoma. Results The overall incidence of PBL increased drastically between 1975 and 2004, followed by a significant downward trend in incidence around 2004, with an average annual percent change (AAPC) of −0.8 (95% CI −1.1 to −0.6). Disparities in trends of PBL exist by age and race. The AAPC of the 65 years or older cohort was about 1.2 higher than that for the younger than 65 years cohort. The AAPC of White patients is 0.9 (95% CI 0.0-1.8), while that of Black patients was significantly higher at 2.1 (95% CI −2.5 to 6.9). We also identified that the risk of death from PBL is multifactorial and includes patient factors and treatment factors. Survival analysis revealed that the patients diagnosed between 2007 and 2015 had a significant risk reduction of mortality compared to those diagnosed between 1983 and 1990. The gradient booster model outperforms other models, with 0.752 for sensitivity and 0.817 for area under the curve. The important features established with the gradient booster model were the year of diagnosis, age, histologic type, and primary site, which were the 4 most relevant variables to explain 5-year survival status. Conclusions The incidence of PBL started demonstrating a tendency to decrease after 2004, which varied by age and race. In recent years, the prognosis of patients with primary breast lymphoma has been remarkably improved. The gradient booster model had a promising performance. This model can help clinicians identify the early prognosis of patients with primary breast lymphoma and therefore improve the clinical outcome by changing management strategies and patient health care.
Meager Milk: Lasting Consequences for Adult Daughters of Primiparous Mothers Among Rhesus Macaques (Macaca Mulatta).

Among mammals, primipara who initiate reproduction before full maturity can be constrained in their maternal investment, both due to fewer somatic resources and tradeoffs between their own continued development and reproductive effort. Primipara are particularly limited in their capacity to synthesize milk during lactation, the costliest aspect of reproduction for most mammals, especially primates due to long periods of postnatal development. Due to reduced milk transfer, Firstborns may be at elevated risk for long-term consequences of deficits in early life endowment from their primiparous mothers. Here we investigated mass, growth, stature, and lactation performance among N = 273 adult daughters across N = 335 reproductions, who were their own mother's Firstborn or Laterborn progeny, among rhesus macaques (Macaca mulatta) at the California National Primate Research Center. We further explored mass during infancy of the offspring of Firstborn and Laterborn mothers. Firstborns had accelerated growth during infancy, but had slowed growth during juvenility, compared to Laterborns. Although both Firstborns and Laterborns were the same age at reproductive debut, Firstborns had lower body mass, an effect that persisted throughout the reproductive career. Available milk energy, the product of milk energetic density and milk yield, was on average 16% lower for Firstborns compared to Laterborns, a difference that was only partially mediated by their lower mass. Despite differences in their mothers' energy provision through milk, the mass of infants of Firstborn and Laterborn mothers did not differ at peak lactation, suggesting that infants of Firstborns devote a higher proportion of milk energy to growth than infants of Laterborns. To date few studies have explored how early life conditions shape capacities to synthesize milk and milk composition. Our findings contribute new information among primates on how early life maternal endowments are associated with persistent effects long after the period of maternal dependence well into reproductive maturity.
Random intercept cross-lagged relations among trauma coping self-Efficacy, trauma coping, and PTSD symptoms among rural hurricane survivors

ABSTRACT Background and Objectives The trajectories of recovery and non-recovery following a disaster are well-documented, but the mechanisms of post-disaster adaptation remain poorly understood. Rooted in social cognitive theory and the transactional model of stress and coping, this study longitudinally investigated the reciprocal relations among coping self-efficacy (CSE), coping behaviors (approach and avoidant), and posttraumatic stress symptoms (PTSS) among highly exposed hurricane survivors. Design: 261 Hurricane Florence survivors completed measures of hurricane-related CSE, coping behaviors, and hurricane-related PTSS across three timepoints, beginning 5–8.5 months after Hurricane Florence. Method: Random-intercept cross-lagged panel models investigated the relations among study variables. Results: Reciprocal, cross-lagged relations were identified between higher CSE and approach coping from T2 to T3. The lagged relations between approach coping at T1 and T2 were significant, as well as between avoidant coping at T2 and T3. Significant cross-sectional relations were also present for CSE, coping behaviors, and PTSS at T3. Conclusions: Results provide partial support for the positive feedback loop involving CSE and approach coping, but not for the negative feedback loop involving avoidant coping. CSE may be an important mechanism in longer-term disaster recovery, in part by increasing use of approach coping.
Statistical Inference for Expectile‐based Risk Measures

Expectiles were introduced by Newey and Powell in 1987 in the context of linear regression models. Recently, Bellini et al. revealed that expectiles can also be seen as reasonable law‐invariant risk measures. In this article, we show that the corresponding statistical functionals are continuous w.r. t. the 1‐weak topology and suitably functionally differentiable. By means of these regularity results, we can derive several properties such as consistency, asymptotic normality, bootstrap consistency and qualitative robustness of the corresponding estimators in nonparametric and parametric statistical models.
Data set representativeness during data collection in three UK social surveys: generalizability and the effects of auxiliary covariate choice

We consider the use of representativeness indicators to monitor risks of non‐response bias during survey data collection. The analysis benefits from use of a unique data set linking call record paradata from three UK social surveys to census auxiliary attribute information on sample households. We investigate the utility of census information for this purpose and the performance of representativeness indicators (the R‐indicator and the coefficient of variation of response propensities) in monitoring representativeness over call records. We also investigate the extent and effects of misspecification of auxiliary covariate sets used in indicator computation and design phase capacity points in call records beyond which survey data set improvements are minimal, and whether such points are generalizable across surveys. Given our findings, we then offer guidance to survey practitioners on the use of such methods and implications for optimizing data collection and efficiency savings.
Distributed Multiagent-Based Event-Driven Fault-Tolerant Control of Islanded Microgrids

This article proposes an observer-based event-driven fault-tolerant (OBEDFT) secondary control strategy for AC microgrids (MGs) to achieve load voltage regulation. First, the input-output feedback linearization method transforms the voltage regulation issue into an output feedback tracking problem for linear multiagent systems (MASs) with nonlinear dynamics. This transformation provides the necessary preprocessing for load voltage regulation. Then, an OBEDFT secondary control protocol that considers full-state immeasurability is proposed. The actuators of distributed generators (DGs) may experience partial loss of effectiveness (PLOE) and bias faults, and these fault parameters may be heterogeneous and time-varying. The protocol introduces adaptive techniques to avoid information related to fault parameters while using event-driven mechanisms to achieve discrete measurements of neighboring DG. Additionally, the protocol uses boundary layers to construct smooth controllers that prevent the chattering effect caused by nonsmooth controllers. Finally, simulation results confirm the effectiveness of this load voltage regulation strategy.
Clinical outcome and safety profile of metastatic pancreatic cancer patients treated with more than six cycles of nab-paclitaxel plus gemcitabine

Abstract The phase III MPACT trial demonstrated the superiority of gemcitabine plus nab-paclitaxel (NABGEM) versus gemcitabine alone in previously untreated patients with metastatic pancreatic cancer (mPC). The aim of this study was to evaluate the responses in terms of efficacy and safety in patients treated with more than 6 cycles of chemotherapy. From January 2015 to December 2018, patients with mPC receiving first-line treatment with NABGEM were included in a multicentre retrospective observational study. Exploratory analyses of efficacy and safety were performed. The cohort included 153 patients with performance status of 1. The median overall survival and progression-free survival were 20 months (hazard ratio [HR] 0.28, 95% confidence interval [CI]: 0.17–0.44) and 10 months (HR 0.24 95% CI: 0.16–0.38) respectively, in patients who received >6 cycles compared to 9 and 5 months in those treated with ≤6 cycles (p < 0.001). The disease control rate was 100% versus 56% in patients receiving >6 and ≤6 cycles, respectively. No progression of disease was recorded in patients who received >6 cycles. Grade 1 neuropathy and grade 3 neutropenia were more frequent in patients treated with >6 cycles compared to patients receiving ≤6 cycles (p = 0.01; p = 0.03, respectively). Dose reduction was necessary for 70.1% and 53.4% of patients treated with >6 or ≤6 cycles, whereas treatment interruption occurred in 37.1% and 21.6%, respectively. Our results confirmed the efficacy and safety of NABGEM in untreated mPC. In particular, we highlighted significant clinical efficacy in patients who received >6 cycles of chemotherapy compared to those who received ≤6 cycles, with manageable toxicity profile.
Measuring Quantitative Cerebral Blood Flow in Healthy Children: A Systematic Review of Neuroimaging Techniques

Cerebral blood flow (CBF) is an important hemodynamic parameter to evaluate brain health. It can be obtained quantitatively using medical imaging modalities such as magnetic resonance imaging and positron emission tomography (PET). Although CBF in adults has been widely studied and linked with cerebrovascular and neurodegenerative diseases, CBF data in healthy children are sparse due to the challenges in pediatric neuroimaging. An understanding of the factors affecting pediatric CBF and its normal range is crucial to determine the optimal CBF measuring techniques in pediatric neuroradiology. This review focuses on pediatric CBF studies using neuroimaging techniques in 32 articles including 2668 normal subjects ranging from birth to 18 years old. A systematic literature search was conducted in PubMed, Embase, and Scopus and reported following the preferred reporting items for systematic reviews and meta‐analyses (PRISMA). We identified factors (such as age, gender, mood, sedation, and fitness) that have significant effects on pediatric CBF quantification. We also investigated factors influencing the CBF measurements in infants. Based on this review, we recommend best practices to improve CBF measurements in pediatric neuroimaging.
Pharmacokinetic and pharmacodynamic exploration of various combinations of tegoprazan immediate and delayed‐release formulations

The new modified‐release formulation of tegoprazan, a novel potassium‐competitive acid blocker, is expected to improve the management of acid‐related disease, including nocturnal acid breakthrough, by prolonging the duration of acid suppression. This study aimed to explore the pharmacokinetics (PK) and pharmacodynamics (PD) of various combinations of tegoprazan with immediate‐release (IR) and delayed‐release (DR) formulations.