bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extensive expertise in endocrinology: advances in the management of glucocorticoid-induced osteoporosis
Authors: Compston Juliet E 
Published: March 2023

AbstractOsteoporosis is a common consequence of long-term oral glucocorticoid therapy and the resulting fractures cause significant morbidity. Bone loss occurs rapidly after initiation of glucocorticoid therapy; the accompanying increase in risk of fracture is dose-dependent and occurs within a few months of starting therapy. The adverse effects of glucocorticoids on bone are mediated by inhibition of bone formation accompanied by an early but transient increase in bone resorption, due both to direct and indirect effects on bone remodelling.Fracture risk assessment should be performed as soon as possible after long-term glucocorticoid therapy (≥3 months) is initiated. FRAX can be adjusted for the dose of prednisolone but does not currently take fracture site, recency, or number into account and therefore may underestimate fracture risk, particularly in individuals with morphometric vertebral fractures. Vertebral fracture assessment should therefore be regarded as a routine part of fracture risk estimation in individuals receiving long-term glucocorticoid therapy. Bone protective therapy should be started promptly in individuals at high-risk, together with calcium and vitamin D supplements. Bisphosphonates are generally regarded as first-line options on the grounds of their low cost, but anabolic therapy should be considered as an alternative first-line option in very high-risk individuals.
Is human obesity an inflammatory disease of the hypothalamus?
Authors: Sonnefeld Lena , Rohmann Nathalie , Geisler Corinna , Laudes Matthias 
Published: March 2023

AbstractObesity and its comorbidities are long-standing, challenging global health problems. Lack of exercise, overnutrition, and especially the consumption of fat-rich foods are some of the most important factors leading to an increase in prevalence in modern society. The pathophysiology of obesity as a metabolic inflammatory disease has moved into focus since new therapeutic approaches are required. The hypothalamus, a brain area responsible for energy homeostasis, has recently received special attention in this regard. Hypothalamic inflammation was identified to be associated with diet-induced obesity and new evidence suggests that it may be, beyond that, a pathological mechanism of the disease. This inflammation impairs the local signaling of insulin and leptin leading to dysfunction of the regulation of energy balance and thus, weight gain. After a high-fat diet consumption, activation of inflammatory mediators such as the nuclear factor κB or c-Jun N-terminal kinase pathway can be observed, accompanied by elevated secretion of pro-inflammatory interleukins and cytokines. Brain resident glia cells, especially microglia and astrocytes, initiate this release in response to the flux of fatty acids. The gliosis occurs rapidly before the actual weight gain. Dysregulated hypothalamic circuits change the interaction between neuronal and non-neuronal cells, contributing to the establishment of inflammatory processes. Several studies have reported reactive gliosis in obese humans. Although there is evidence for a causative role of hypothalamic inflammation in the obesity development, data on underlying molecular pathways in humans are limited. This review discusses the current state of knowledge on the relationship between hypothalamic inflammation and obesity in humans.
Prospective Effects of Discrimination, Depressive Symptoms, and Cognitive Control Among Mexican-Origin Women
Authors: Muñoz Elizabeth , Yan Jinjin , Tse Hin Wing , Zavala Daisy , López Belem G , Kim Su Yeong 
Published: March 2023

Abstract

Objectives
Cognitive control predicts functional independence and cognitive health outcomes, but is yet to be known the extent to which social stress, like discrimination, may diminish cognitive control capacities in Mexican-origin women. We evaluated the prospective associations between everyday and ethnic discrimination on cognitive control and examined the mediating effects of depressive symptoms on these links. We further examined the extent to which associations varied by age and financial strain.

Methods
We used data from 596 Mexican-origin women (average age = 38.89, standard deviation = 5.74) who participated in a 3-wave longitudinal study spanning 8 years (from 2012 to 2020). Participants completed measures of everyday and ethnic discrimination at Wave 1, depressive symptoms in Waves 1 and 2, and completed computer-based tasks of cognitive control at Wave 3. Self-reported assessments of financial strain were completed at Wave 2. Moderated mediation structural equation models were implemented to test hypotheses.

Results
Depressive symptoms significantly mediated the prospective association between everyday/ethnic discrimination to cognitive control. Higher levels of everyday and ethnic discrimination at baseline were associated with more depressive symptoms at Wave 2, which were then related to poorer cognitive control (i.e., longer reaction time in congruent and/or incongruent trials) at Wave 3. There was no significant moderation of age. Among those with low financial strain, higher levels of everyday discrimination were related to faster response times.

Discussion
Results revealed the long-term consequences of experiences with discrimination on cognitive control that operate through increased depressive symptoms and that may have some subtle differential effects across levels of financial strain.
Are the New Biologics Effective in the Management of Postoperative Crohn’s Disease?
Authors: Mourad Fadi H , Maalouf Rami G , Aoun Roni , Gustavo Kotze Paulo , Hashash Jana G 
Published: March 2023

Abstract

Background
Despite the growing therapeutic armamentarium, at least half of the patients with Crohn’s disease will require surgery during their lifetime. Current evidence for the prevention and treatment of postoperative Crohn’s disease supports the use of anti-tumor necrosis factor agents with limited data about the use of the newer biologics, vedolizumab and ustekinumab.

Methods
We performed a systematic review of available data to determine the efficacy of the newer biologics in the management of postoperative Crohn’s disease. We included noncomparative and comparative studies. The main outcomes of interest were clinical and endoscopic postoperative recurrence rates.

Results
The search strategy identified 1231 citations, with 32 eligible for review. Several studies showed that the postoperative Crohn’s disease recurrence rates with the use of the newer biologics were comparable to previously published results with the use of anti-tumor necrosis factor agents, while other studies failed to show their efficacy. It is important to note that the studies were heterogeneous and included a relatively small sample size, making it difficult to draw a definite conclusion about the efficacy of the newer biologics in the management of postoperative Crohn’s disease.

Conclusion
The newer biologics do play a role in the management of postoperative Crohn’s disease. After our review, we proposed an updated algorithm on the role of newer biologics in the approach to patients with postoperative Crohn’s disease. Yet, until we have better-designed studies, their definite positioning remains to be determined.
Critically Assessing Undergraduate Field Experiences: Understanding Conceptualizations and Opportunities for Building Inclusive Programs
Authors: Morales Nia , Reano Darryl 
Published: March 2023

Abstract
Undergraduate field experiences (UFEs) are key components of many biology, ecology, and geoscience programs and important steps to successful recruitment into careers. Through semistructured interviews of diverse field program leaders, we seek to understand how field program leaders conceptualize both their scientific disciplines and the intentional design factors they implemented within the UFE itself. Additionally, this study explores critical considerations these program leaders use to approach designing inclusive UFEs as well as the institutional and practical challenges of designing and implementing their UFEs. We acknowledge the limitations of the small sample of respondents, and our intent with this article is to explore these responses as a way to share critical design factors for designing and implementing inclusive UFEs with the broader geoscience community. Building an early understanding of these factors will help new field program leaders address multiple, simultaneous challenges that currently foment the underrepresentation of students from marginalized backgrounds in biology, ecology, and the geosciences. Through these explicit conversations, we hope to support the professional development of a scientific community that values the creation of safe, encouraging field experiences in which students can enhance their self-identity in the sciences, build peer and professional networks, and develop memorable field experiences that support their trajectories toward successful careers.
The Impacts of Early-Life Experience on Bee Phenotypes and Fitness
Authors: Rittschof Clare C , Denny Amanda S 
Published: March 2023

Synopsis
Across diverse animal species, early-life experiences have lifelong impacts on a variety of traits. The scope of these impacts, their implications, and the mechanisms that drive these effects are central research foci for a variety of disciplines in biology, from ecology and evolution to molecular biology and neuroscience. Here, we review the role of early life in shaping adult phenotypes and fitness in bees, emphasizing the possibility that bees are ideal species to investigate variation in early-life experience and its consequences at both individual and population levels. Bee early life includes the larval and pupal stages, critical time periods during which factors like food availability, maternal care, and temperature set the phenotypic trajectory for an individual’s lifetime. We discuss how some common traits impacted by these experiences, including development rate and adult body size, influence fitness at the individual level, with possible ramifications at the population level. Finally, we review ways in which human alterations to the landscape may impact bee populations through early-life effects. This review highlights aspects of bees’ natural history and behavioral ecology that warrant further investigation with the goal of understanding how environmental disturbances threaten these vulnerable species.
Ideological Topography in World Politics: A Guide to the End of the Unipolar-Homogeneous Moment
Authors: Casey Justin S , Dolan Lucas 
Published: March 2023

AbstractThe immediate post–Cold War era was defined by the material and ideological dominance of the United States. Thirty years on, challenges to both types of dominance proliferate. What explains the systemic change currently underway? The conventional wisdom of a shift to bipolarity or multipolarity ignores the possibility of changes within unipolarity. Recent instability is better explained by the decreased dominance of liberal-democratic ideology and the re-emergence of ideological competition. Building on Raymond Aron's analysis of homogeneous and heterogeneous international systems, we propose a typology exploring the intersections of systemic distributions of power and ideological topographies. Homogeneous topographies operate on a principle of collusion, reducing uncertainty while promoting restraint, transnational society, and gatekeeping against challenger ideologies. Heterogeneous topographies follow a crisscrossing logic, raising the stakes of relations, contributing to breakdowns in norms of nonintervention, enabling subversion by splitting loyalties, and encouraging repression and the fragmentation of transnational society. Applying this framework, we reappraise the 1990s as a unipolar-homogeneous moment. The emergence of heterogeneity in the mid-2000s, with the rise of authoritarianism and transnational illiberalism, put greater pressure on US unipolarity. This work has implications for debates about US foreign policy, the stability of unipolar systems, and the consequences of systemic change.
Harnessing Intuition and Disciplining Abstraction: Thought Experiments in International Relations
Authors: Lerner Adam B 
Published: March 2023

Abstract
Although often omitted from final texts, armchair speculation is vital to much politics research. This article argues that thought experiments are a powerful tool for harnessing scholarly imagination with enormous potential for international relations (IR). To provide guidance for thought experiments’ incorporation into IR research, the article begins by clarifying thought experiments’ epistemological foundations and expanding existing best practices criteria for minimal-rewrite counterfactuals. Doing so enables consideration of the diversity of thought experiments useful to the discipline, ranging from alien invasions to zombie apocalypses. Then, the article outlines five ways in which thought experiments prove particularly useful in researching international politics: probing modal consequences of macro-level theories; refining concepts; formulating hypotheses; speculating about rare events; and conveying theories’ real-world implications. To facilitate thought experiments’ incorporation into mixed- and multi-methods research, the article's final section offers a novel typology to guide scholars in not only formulating new thought experiments, but also adapting and comparing them, including in conjunction with empirical methods.
Social Media Use and COVID-19 Vaccination Intent: An Exploratory Study on the Mediating Role of Information Exposure
Authors: Suhaimi Nurul M , Zhang Yixuan , Yongsatianchot Nutchanon , Gaggiano Joseph , Okrah Anne , Patel Shivani , Marsella Stacy , Kim Miso , Parker Andrea G , Griffin Jacqueline 
Published: March 2023

Abstract
We stumble upon new and repeating information daily. As information comes from many sources, social media continues to play a predominant role in disseminating information, ultimately impacting individuals’ perceptions and behaviors. A prime example of this impact was observed during the COVID-19 pandemic, in which social media use was influencing willingness to receive the COVID-19 vaccine. While studies on this relationship between social media use and vaccination intent have been widely investigated, less is known about the mechanisms that link these two variables, specifically the types of information seen on social media platforms and the effects of these different types of information. In this exploratory study, we demonstrate the mediator role of information exposure (to include both types of information and frequency) between social media use and vaccination intent. Our results show that different types of information mediate this relationship differently and demonstrate how these relationships were further moderated by the income level of the participant. We conclude with the implications of these findings and how our findings can inform the direction of future research within the field of human–computer interaction.
Genetic and phenotypic relationships between ewe reproductive performance and wool and growth traits in Uruguayan Ultrafine Merino sheep
Authors: Ramos Zully , Garrick Dorian J , Blair Hugh T , De Barbieri Ignacio , Ciappesoni Gabriel , Montossi Fabio , Kenyon Paul R 
Published: March 2023

AbstractThis study reports genetic parameters for yearling and adult wool and growth traits, and ewe reproductive performance. Data were sourced from an Uruguayan Merino flock involved in a long-term selection program focused on reduced fiber diameter (FD), and increased clean fleece weight (CFW) and live weight (LW). Pedigree and performance data from approximately 5,700 mixed-sex yearling lambs and 2,000 mixed-age ewes born between 1999 and 2019 were analyzed. The number of records ranged from 1,267 to 5,738 for yearling traits, and from 1,931 to 7,079 for ewe productive and reproductive performance. Data on yearling and adult wool traits, LW and body condition score (BCS), yearling eye muscle area (Y_EMA), and fat thickness (Y_FAT), and several reproduction traits were analyzed. The genetic relationships between FD and reproduction traits were not different from zero. Moderate unfavorable genetic correlations were found between adult CFW and ewe lifetime reproduction traits (−0.34 ± 0.08 and −0.33 ± 0.09 for the total number of lambs weaned and total lamb LW at weaning, respectively). There were moderate to strong positive genetic correlations between yearling LW and all reproduction traits other than ewe-rearing ability (−0.08 ± 0.11) and pregnancy rate (0.18 ± 0.08). The genetic correlations between Y_EMA and reproduction traits were positive and ranged from 0.15 to 0.49. Moderate unfavorable genetic correlations were observed between yearling FD and Y_FAT and between adult FD and BCS at mating (0.31 ± 0.12 and 0.23 ± 0.07, respectively). The genetic correlations between adult fleece weight and ewe BCS at different stages of the cycle were negative, but generally not different from zero. This study shows that selection for reduced FD is unlikely to have any effect on reproduction traits. Selection for increased yearling LW and Y_EMA will improve ewe reproductive performance. On the other hand, selection for increased adult CFW will reduce ewe reproductive performance, whereas selection for reduced FD will negatively impact body fat levels. Although unfavorable genetic relationships between wool traits and both FAT and ewe reproductive performance existed, simultaneous improvements in the traits would occur using appropriately designed indexes.
Effects of weight loss and feeding specially formulated diets on the body composition, blood metabolite profiles, voluntary physical activity, and fecal metabolites and microbiota of obese dogs
Authors: Oba Patrícia M , Kelly Janelle , Kostiuk Darcia , Swanson Kelly S 
Published: March 2023

AbstractCanine obesity negatively influences health and well-being, but can be managed by altering diet composition and caloric intake. Restricted feeding, dietary intervention, and consequent weight loss may be used to improve health and modify gastrointestinal microbiota. In this study, we aimed to determine the effects of restricted feeding of specially formulated foods on weight loss, body composition, voluntary physical activity, serum hormones and oxidative stress markers, and fecal metabolites and microbiota populations of obese dogs. Twenty-four obese dogs [body weight (BW) = 15.2 ± 1.7 kg; body condition score (BCS) = 8.7 ± 0.4; muscle condition score (MCS) = 3.5 ± 0.3; age = 7.2 ± 1.6 yr] were used in a 24-wk study. A control (OR) food was fed during a 4-wk baseline to identify intake needed to maintain BW. After baseline, dogs were allotted to one of two diets: OR or test (FT), and then fed to lose 1.5% BW/wk. Food intake, BW, BCS, and MCS were measured, blood and fecal samples were collected, DEXA scans were performed, and voluntary physical activity was measured over time. Microbiota data were evaluated using QIIME2 and change from baseline data from other measures were evaluated using the Mixed Models procedure of SAS, with P &lt; 0.05 being significant. Restricted feeding led to reduced BW, BCS, fat mass, and blood cholesterol, triglyceride, glucose, and leptin concentrations, and increased MCS and lean body mass percentage. Blood cholesterol reduction was greater in dogs fed FT vs. OR. Fecal metabolites and bacterial alpha-diversity were affected by diet and weight loss. Dogs fed FT had greater reductions in fecal short-chain fatty acid, branched-chain fatty acid, and ammonia concentrations than those fed OR. Dogs fed OR had a higher alpha-diversity than those fed FT. Weight loss increased alpha-diversity (weeks 16, 20, and 24 &gt; weeks 0 and 4). Beta-diversity showed separation between dietary groups and between week 0 and all other time points after week 8. Weight loss increased fecal Allobaculum and Ruminococcus torques. Weight loss also increased fecal Bifidobacterium, Faecalibaculum, and Parasutterella, but were greater in dogs fed OR. Weight loss decreased fecal Collinsella, Turicibacter, Blautia, Ruminococcus gnavus, Faecalibacterium, and Peptoclostridium, but were greater in dogs fed OR. In summary, restricted feeding promoted safe weight and fat loss, reduced blood lipid and leptin concentrations, and altered fecal microbiota of obese dogs.
A61 TARGETING A GUANINE QUADRUPLEX IN THE HEPATITIS B VIRUS COVALENTLY CLOSED CIRCULAR DNA GENOME USING SINGLE DOMAIN ANTIBODIES
Authors: D'souza S , Balderas Figueroa G , D Badmalia M , R Patel T , Coffin C 
Published: March 2023

Abstract

Background
The establishment of chronic HBV infection in over 297 million people is due in part through the virus’ highly stable covalently closed circular DNA (cccDNA) persisting in the nuclei of infected hepatocytes. Thus, curing HBV will require direct targeting of the minigenome and detailed structural knowledge of the cccDNA to determine vulnerabilities.

Purpose
Previous studies have demonstrated that human protein Sp1 interacts with the HBV genome at the preCore/Core promoter - a critical interaction for viral replication. We have recently discovered that the Sp1-binding region of HBV pre-Core forms a highly ordered G-quadruplex (G4) secondary structure which presents a novel therapeutic anti-HBV target.

Method
Using phage display technologies, we have identified 11 G-quadruplex binding single domain antibodies that can target the G4 present within the cccDNA. Using recombinant protein expression we characterized the strongest binder (S10) and its interaction with a 22nt HBV pre-Core G-quadruplex forming oligo. Using MicroScale Thermophoresis (MST), the binding affinity (KD) between S10 and the target G4 was determined to be ~218 nM, which is 100x stronger for folded G4 versus unfolded oligos of the same sequence. Using oligos of (~60-90%) sequence similarity, it was observed that S10 has a KD for the target G4 that was at least 10x higher than similar sequences. To determine the effect of S10 on HBV replication, we have transduced the HepG2-NTCP-A3 cell line to express these sdAbs and are in the process of evaluating antiviral effects and target specificity for cccDNA.

Result(s)
Using biophysical in-vitro approaches, S10 has shown a great potential in being able to discriminate against different G4’s, while having a high degree of affinity as well as high complex stability.

Conclusion(s)
The ability of these G4 binding single domain antibodies to discriminate between different sequences or secondary DNA structure provides an insight into how they can be exploited in future HBV therapeutic strategies.

Disclosure of Interest
None Declared