bluuebunny/crossref_metadata_2025_split huggingface dataset:
Edoxaban, a Factor Xa-Specific Direct Oral Anticoagulant, Significantly Suppresses Tumor Growth in Colorectal Cancer Colon26-Inoculated BALB/c Mice
Authors: Hiramoto Keiichi , Akita Nobuyuki , Nishioka Junji , Suzuki Koji 
Published: January 2023

AbstractIntroduction Certain low-molecular-weight heparins have been reported to reduce tumor growth and metastasis in tumor cell-inoculated mouse models and cancer patients. Recently, direct oral anticoagulants (DOACs) have been widely used in patients with thromboembolism. This study was aimed at investigating the effect of DOACs, which target thrombin or factor Xa, on tumor growth in a syngeneic mouse model comprising BALB/c mice inoculated with colon cancer Colon26 cells.Materials and Methods DOACs targeting thrombin (dabigatran etexilate [DABE]) or factor Xa (rivaroxaban [RVX] and edoxaban [EDX]) were orally administered daily to male BALB/c mice inoculated with Colon26 cells, followed by analyses of tumor growth and plasma levels of coagulation- and tumor-related factors such as tissue factor (TF), plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6), and matrix metalloproteinase-2 (MMP-2).Results Colon26 cells expressed significant amounts of functionally active TF. Tumor growth in Colon26-inoculated mice was significantly suppressed in DABE- or RVX-treated mice (p <0.05) and was suppressed more significantly in EDX-treated mice (p <0.01). Therefore, the antitumor mechanism of action of EDX was investigated next. Plasma levels of TF, PAI-1, IL-6, and MMP-2 were elevated in Colon26-inoculated mice but were significantly reduced in EDX-treated mice (p <0.01). The expression of protease-activated receptor (PAR)1, PAR2, signal transducer and activator of transcription-3 (STAT3), cyclin D1, and Ki67 was increased in tumor tissue of Colon26-inoculated mice but (except for PAR1) was significantly decreased in tumor tissues of EDX-treated mice (p <0.01). In addition, apoptotic cells and p53 protein levels were significantly increased in tumor tissues of EDX-treated mice.Conclusion The data suggest that among the tested DOACs, EDX significantly suppresses tumor cell proliferation via the factor Xa-PAR2 pathway, which is activated by coagulation and inflammation in Colon26-inoculated mice and induces tumor cell apoptosis.
Combined effects of supplementation of amino acids and immunocastration in first antler growth of farmed fallow deer (Dama dama)
Authors: Ceacero Francisco , Ny Veit , Kotrba Radim , Bartoň Luděk , Čupić Stipan , Bureš Daniel , Turek Jiři , Komárková Martina , Needham Tersia 
Published: January 2023

Context Amino acid supplementation and immunocastration are two husbandry practices with an increasing interest in the worldwide growing industry of deer farming. Amino acids (AAs) optimise nutrition and feed costs and improve the quality of products such as venison, velvet or antlers. Immunocastration (IC) reduces agonistic behaviours, which produce carcass damage and reduced growth. Thus, both treatments have positive effects on body growth, but may interfere with hormonal regulation, subsequently affecting antler growth. Aims This study aimed to evaluate the combined use of both practices and their impact on body and antler growth. Methods Forty-four yearling male fallow deer, approximate 10 months old, were subjected to the following four combinations based on both treatments: control–control, AA–control, IC–control, and AA–IC. Immunocastration treatment started in March 2020 and was repeated after 50 and 130 days. All groups received 250 g per animal and day of grains, and those under AA supplementation received ruminally protected lysine 6.3 g and ruminally protected methionine 2.1 g per animal and day. Biometric data, antlers and metatarsus were collected at slaughter in November. Antlers and metatarsus were analysed through computer-tomography scanning and mineral spectrometry. Key results Supplementation of AAs scarcely affected antler growth, although an indirect effect through improved body condition cannot be rejected. Immunocastration showed significant but not dramatic effects: IC animals had lighter antlers, with a lower amount of cortical bone and less mineralisation (density and calcium and phosphorus concentrations) in the base of the antler than did control animals. In contrast, the effects were scarce at the top of the antler and the metatarsus. Conclusions The results suggest a reduction but not total suppression of testosterone, with almost negligible effects on body growth and internal bones, thus not raising animal welfare issues. Implications Both techniques can be used simultaneously in deer farming, especially in farms with venison-production goals. Future research should focus on optimising the vaccination schedule for the main farmed deer species to ensure that the welfare benefits are well balanced with productivity.
Beneficial effects of instrumental music on the production performance of Xiandao green-shell layers housed under different stocking densities
Authors: Cao Shiwen , Yang Fengping , Wu Ruiyong , Zhang Xueyu , Ye Manhong , Wei Wanhong 
Published: January 2023

Context Egg production rate (EPR) is the main criteria for egg producers and egg quality is important for consumers. Exposed to music, layers kept at appropriate stocking density could display optimal production performance without compromising egg quality. Aims This study aimed to investigate the possibility of employing instrumental music stimulus and regulating stocking density to maximise egg production performance and improve egg quality in Xiandao green-shell layers. Methods In total, 378 30-week-old layers were randomly distributed into nine treatments across three types of sound sources (natural sound, instrumental music, or mixed road noise) × three different stocking densities (4, 7 and 10 birds/cage corresponding to low, medium, and high density respectively), with six replicates per treatment. The 24-day experimental period was equally divided into four phases. EPR, average egg weight, and serum IgG concentration were determined at the end of each phase. Egg quality and organ indices were determined at the end of experiment. Results Hens exposed to music had a significantly higher EPR and laid eggs of better quality than did hens subjected to mixed road noise. Across all parameters, hens exposed to music did not significantly differ from hens exposed to natural sound. Stocking density had significant impacts on EPR, relative eggshell weight, and serum IgG concentration, with hens kept at high stocking density (357 cm2/hen) exhibiting the lowest values. Hens kept at medium density (510 cm2/hen) and low density (892 cm2/hen) showed no significant differences in tested parameters except that the former produced eggs with a significantly higher relative eggshell weight. Significant interactions between sound and density were observed in EPR, relative yolk weight, and spleen index, with hens exposed to music and kept at low density displaying the highest values. Conclusions Music and low stocking density had favourable effects on improving egg production and egg quality, while road noise and high stocking density exerted negative influences on them. Implications Xiandao green-shell layers are recommended to be kept at medium density to maximise the production benefits. The integration of music playback into management practices will not compromise layers’ production potential displayed under natural sound exposure.
Birth Weight, Gestational Age, and Risk of Cardiovascular Disease in Early Adulthood: Influence of Familial Factors
Authors: Lu Donghao , Yu Yongfu , Ludvigsson Jonas F , Oberg Anna Sara , Sørensen Henrik Toft , László Krisztina D , Li Jiong , Cnattingius Sven 
Published: January 2023

Abstract
The association between intrauterine growth restriction and cardiovascular disease (CVD) later in life might be confounded by familial factors. We conducted a binational register-based cohort study to assess associations of birth weight for gestational age (GA), a proxy for intrauterine growth restriction, and GA with CVD risk in early adulthood, before and after addressing familial factors via sibling comparison. We included 3,410,334 live nonmalformed singleton births from Sweden (1973–1996) and Denmark (1978–1998). During a median follow-up period of 10 years from age 18 years onwards, 29,742 individuals developed incident CVD (hypertension, ischemic heart disease, or cerebrovascular disease). Compared with individuals born with appropriate birth weight for GA (AGA; 10th–90th percentiles) or full term (39–40 gestational weeks), individuals born severely small for GA (SGA; ≤3rd percentile) or preterm (22–36 weeks) were at increased risk of CVD (hazard ratio (HR) = 1.38 (95% confidence interval (CI): 1.32, 1.45) and HR = 1.31 (95% CI: 1.25, 1.38), respectively). The association was attenuated when comparing individuals born SGA with their AGA siblings (HR = 1.11, 95% CI: 0.99, 1.25) but remained robust when comparing individuals born preterm with their term siblings (HR = 1.21, 95% CI: 1.07, 1.37). Our findings suggest that both SGA and preterm birth are associated with CVD risk in early adulthood, with greater familial confounding noted for SGA birth.
Invited Commentary: Some Social Epidemiologic Lessons From the COVID-19 Pandemic
Authors: Schnake-Mahl Alina S , Bilal Usama 
Published: January 2023

Abstract
In their recent article, Dimitris et al. (Am J Epidemiol. 2022;191(6):980–986) presented a series of challenges modern epidemiology has faced during the coronavirus disease 2019 (COVID-19) pandemic, including challenges around the scientific progress, epidemiologic methods, interventions, equity, team science, and training needed to address these issues. Here, 2 social epidemiologists who have been working on COVID-19 inequities reflect on further lessons with an added year of perspective. We focus on 2 key challenges: 1) dominant biomedical individualistic narratives around the production of population health, and 2) the role of profit in policy-making. We articulate a need to consider social epidemiologic approaches, including acknowledging the importance of considering how societal systems lead to health inequities. To address these challenges, future (and current) epidemiologists should be trained in theories of population health distribution and political structures of governance. Last, we close with the need for better investment in public health infrastructure as a crucial step toward achieving population health equity.
Epidemiologic Utility of a Framework for Partition Number Selection When Dissecting Hierarchically Clustered Genetic Data Evaluated on the Intestinal Parasite Cyclospora cayetanensis
Authors: Barratt Joel L N , Plucinski Mateusz M 
Published: January 2023

Abstract
Comparing parasite genotypes to inform parasitic disease outbreak investigations involves computation of genetic distances that are typically analyzed by hierarchical clustering to identify related isolates, indicating a common source. A limitation of hierarchical clustering is that hierarchical clusters are not discrete; they are nested. Consequently, small groups of similar isolates exist within larger groups that get progressively larger as relationships become increasingly distant. Investigators must dissect hierarchical trees at a partition number ensuring grouped isolates belong to the same strain; a process typically performed subjectively, introducing bias into resultant groupings. We describe an unbiased, probabilistic framework for partition number selection that ensures partitions comprise isolates that are statistically likely to belong to the same strain. We computed distances and established a normalized distribution of background distances that we used to demarcate a threshold below which the closeness of relationships is unlikely to be random. Distances are hierarchically clustered and the dendrogram dissected at a partition number where most within-partition distances fall below the threshold. We evaluated this framework by partitioning 1,137 clustered Cyclospora cayetanensis genotypes, including 552 isolates epidemiologically linked to various outbreaks. The framework was 91% sensitive and 100% specific in assigning epidemiologically linked isolates to the same partition.
Implementation and expansion of inpatient and ambulatory pharmacist credentialing and privileging at an academic medical center
Authors: Dawson Courtney , Pham Aaron , Shipman Colleen , Lau Gary , Pham Yen 
Published: January 2023

Abstract

Purpose
This article highlights one academic medical center’s effort to implement a complete credentialing and privileging (C&P) process for both inpatient and ambulatory clinical pharmacists.

Summary
The C&P process offers a recognized method to advance pharmacy practice. Credentialing is defined as a process whereby an individual is deemed qualified in a specific subject matter area. Privileging is the process whereby an institution grants authority to an individual to perform services based on credentials. Federal guidelines permit pharmacists to obtain the same level of privileges as professional medical staff, such as physicians, if relevant state laws allow for the corresponding pharmacist scope of practice. States establish laws and regulations that specify the scope of practice for various types of licensed healthcare professionals, including pharmacists. Many health systems have attempted pharmacist C&P practices in both the inpatient and ambulatory care setting with varying degrees of success and reach. Privileged pharmacists provide established benefits and value to other members of the healthcare team. Oregon Health & Science University (OHSU) pursued C&P for both inpatient and ambulatory clinical pharmacists. Initiation and implementation processes were complex and accompanied by a variety of challenges.

Conclusion
OHSU operates with advanced pharmacy practice integrated into the interdisciplinary patient care team. Pharmacist C&P allows pharmacists to demonstrate significant clinical benefits and quality improvement in patient care delivery in both inpatient and ambulatory settings.
Exposure Monitoring Strategies for Applying Low-Cost PM Sensors to Assess Flour Dust in Industrial Bakeries
Authors: Ruiter Sander , Bard Delphine , Ben Jeddi Hasnae , Saunders John , Snawder John , Warren Nick , Gorce Jean-Philippe , Cauda Emanuele , Kuijpers Eelco , Pronk Anjoeka 
Published: January 2023

AbstractLow-cost particulate matter (PM) sensors provide new methods for monitoring occupational exposure to hazardous substances, such as flour dust. These devices have many possible benefits, but much remains unknown about their performance for different exposure monitoring strategies in the workplace. We explored the performance of PM sensors for four different monitoring strategies (time-weighted average and high time resolution, each quantitative and semi-quantitative) for assessing occupational exposure using low-cost PM sensors in a field study in the industrial bakery sector. Measurements were collected using four types of sensor (PATS+, Isensit, Airbeam2, and Munisense) and two reference devices (respirable gravimetric samplers and an established time-resolved device) at two large-scale bakeries, spread over 11 participants and 6 measurement days. Average PM2.5 concentrations of the low-cost sensors were compared with gravimetric respirable concentrations for 8-h shift periods and 1-min PM2.5 concentrations of the low-cost sensors were compared with time-resolved PM2.5 data from the reference device (quantitative monitoring strategy). Low-cost sensors were also ranked in terms of exposure for 8-h shifts and for 15-min periods with a shift (semi-quantitative monitoring strategy). Environmental factors and methodological variables, which can affect sensor performance, were investigated. Semi-quantitative monitoring strategies only showed more accurate results compared with quantitative strategies when these were based on shift-average exposures. The main factors that influenced sensor performance were the type of placement (positioning the devices stationary versus personal) and the company or workstation where measurements were collected. Together, these findings provide an overview of common strengths and drawbacks of low-cost sensors and different ways these can be applied in the workplace. This can be used as a starting point for further investigations and the development of guidance documents and data analysis methods.
Knowing the past to conserve the future: a commentary on ‘Evolutionary history of marginal habitats regulates the diversity of tree communities in the Atlantic Forest’
Authors: Rezende Vanessa L , de Miranda Pedro L Silva , Pontara Vanessa 
Published: January 2023

This article comments on:
Jhonny Capichoni Massante, and Markus Gastauer. Evolutionary history of marginal habitats regulates the diversity of tree communities in the Atlantic Forest, Annals of Botany, Volume 131, Issue 2, 1 February 2023, Pages 261–274, https://doi.org/10.1093/aob/mcac111
Comparison of Various Metrics of Repetitive Head Impact Exposure And Their Associations With Neurocognition in Collegiate-Aged Athletes
Authors: Amadon Grace K , Goeckner Bryna D , Brett Benjamin L , Meier Timothy B 
Published: January 2023

Abstract

Objective
Characterize the levels of various metrics of repetitive head impacts (RHI) in contact (CS) and non-contact (NCS) sport athletes and determine the extent to which they are associated with fluid cognition.

Methods
Collegiate-aged athletes (n = 176) completed semi-structured interviews about participation in contact sport. RHI was operationalized based on current sport (CS/NCS), the cumulative number of years of participation, age at first exposure (AFE), and based on recently proposed traumatic encephalopathy syndrome (TES) categories. The NIH Toolbox Cognition Battery assessed fluid cognition. General linear models compared RHI metrics between CS and NCS athletes and tested associations of RHI measures with fluid cognition.

Results
CS athletes had more years of RHI exposure, higher rates of “extensive” exposure based on TES criteria, and were more likely to have AFE before age 12 relative to NCS (ps &lt; .001). A subset of NCS athletes, however, reported prior RHI at levels categorized as being “extensive” based on TES criteria (5%), while a larger minority had AFE before 12 (34%). No adverse associations of RHI and fluid cognition were observed (ps &gt; .05). Across all RHI metrics, more or earlier RHI was associated with better episodic memory (ps ≤ .05). Secondary analyses showed this effect was driven by women.

Conclusions
Current results find no evidence that RHI in collegiate-aged athletes is associated with worse neurocognition. Although there was extensive overlap among RHI measures, results demonstrate that categorizing athletes based on their current sport undercounts the lifetime RHI exposure in many NCS athletes.
Active Vitamin D3 (Calcitriol) Increases Adipose Graft Retention in a Xenograft Model
Authors: Loder Shawn , Wang Sheri , Amurgis Charles , DeSanto Marisa , Stavros Alexander G , Patadji Stell , Olevian Dane , Lee Phoebe , Guerrero David , Gusenoff Jeffrey A , Peter Rubin J , Kokai Lauren E 
Published: January 2023

Abstract

Background
Autologous fat grafting, although broadly indicated, is limited by unsatisfactory retention and often requires multiple procedures to achieve durable outcomes. Graft survival is strongly influenced by the magnitude and duration of post-engraftment ischemia. Calcitriol is a pleiotropic, safe nutrient with cell-specific influence on viability and metabolic flux.

Objectives
Evaluate the efficacy of activated vitamin D3 (calcitriol) in improving grafting outcomes and examine its mechanisms.

Methods
Lipoaspirate was collected for ex vivo culture (7 unique donors), in vitro bioenergetic analysis (6 unique donors), and in vivo transplantation (5 unique donors). Ex vivo samples were incubated for up to 2 weeks before extraction of the stromal vascular fraction (SVF) for viability or flow cytometry. SVF was collected for Seahorse (Agilent; Santa Clara, CA) analysis of metabolic activity. Human endothelial cell lines were utilized for analyses of endothelial function. In vivo, samples were implanted into athymic mice with calcitriol treatment either (1) once locally or (2) 3 times weekly via intraperitoneal injection. Grafts were assessed photographically, volumetrically, and histologically at 1, 4, and 12 weeks. Hematoxylin and eosin (H&E), Sirius red, perilipin, HIF1α, and CD31 tests were performed.

Results
Calcitriol-treated lipoaspirate demonstrated dose-dependent increases in SVF viability and metabolic reserve during hypoxic stress. Calcitriol treatment enhanced endothelial mobility ex vivo and endothelial function in vitro. In vivo, calcitriol enhanced adipocyte viability, reduced fibrosis, and improved vascularity. Continuous calcitriol was sufficient to improve graft retention at 12 weeks (P &lt; .05).

Conclusions
Calcitriol increased fat graft retention in a xenograft model. Calcitriol has potential to be a simple, economical means of increasing fat graft retention and long-term outcomes.
Upregulation of MAP kinase HOG1 gene of white-rot fungus Phlebia sp. MG-60 inhibits the ethanol fermentation and mycelial growth
Authors: Motoda Taichi , Chen Fu-Chia , Tsuyama Taku , Tokumoto Yuji , Kijidani Yoshio , Kamei Ichiro 
Published: January 2023

ABSTRACT
Wood biomass conversion for fossil resource replacement could result in the sustainable production of chemicals, although lignin represents an obstacle to efficient polysaccharide use. White-rot fungus Phlebia sp. MG-60 reportedly selectively and aerobically degrades lignin in hardwood, then it begins cellulose saccharification from the delignified wood to produce ethanol. Environmental conditions might change white-rot fungi-driven biomass conversion. However, how the environmental response sensor affects ethanol fermentation in white-rot fungi remains elusive. In this study, we focused on MGHOG1, the yeast Hog1 homolog in Phlebia sp. MG-60, a presumably important player in osmoresponse. We generated MGHOG1 overexpressing (OE) transformants in Phlebia sp. MG-60, exhibiting slower mycelial growth compared with the wild-type under salinity stress. MGHOG1 overexpressing liquid cultures displayed suppressed mycelial growth and ethanol fermentation. Therefore, MGHOG1 potentially influences ethanol fermentation and mycelial growth in Phlebia sp. MG-60. This study provides novel insights into the regulation of white-rot fungi-mediated biomass conversion.
Overexpression of a predicted transketolase gene and disruption of an α-1,3-glucan synthase gene inAspergillus oryzaeDGLA3 strain enhances the yield of free dihomo-γ-linolenic acid
Authors: Tamano Koichi , Nakai Shiori , Takayama Haruka , Imai Yasuhiko 
Published: January 2023

ABSTRACTFree dihomo-γ-linolenic acid (DGLA), a polyunsaturated free fatty acid (FFA), can potentially be used to produce eicosanoid pharmaceuticals, such as prostaglandin E1. Previously, we constructed an Aspergillus oryzae mutant strain, named DGLA3, which produced free DGLA at an increased yield by faaA gene disruption and cooverexpression of one elongase and two desaturase genes. In this study, we achieved a further increase. Since FFA production is increased by enhancing the pentose phosphate pathway, we overexpressed a predicted transketolase gene composing the pathway in DGLA3, which consequently increased the free DGLA yield by 1.9-fold to 403 mg/L. Additionally, we disrupted the α-1,3-glucan synthase gene agsB involved in cell-wall biosynthesis, which further increased it by 1.3-fold to 533 mg/L. Overall, the yield increased by 2.5-fold. Free DGLA productivity and biomass increased similarly, but residual glucose concentration decreased. Increased hyphal dispersion appeared to cause additional glucose consumption, resulting in an increase in biomass and yield.