bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study and functional follow-up identify 14q12 as a candidate risk locus for cervical cancer
Authors: Ramachandran Dhanya , Dennis Joe , Fachal Laura , Schürmann Peter , Bousset Kristine , Hülse Fabienne , Mao Qianqian , Wang Yingying , Jentschke Matthias , Böhmer Gerd , Strauß Hans-Georg , Hirchenhain Christine , Schmidmayr Monika , Müller Florian , Runnebaum Ingo , Hein Alexander , Stübs Frederik , Koch Martin , Ruebner Matthias , Beckmann Matthias W , Fasching Peter A , Luyten Alexander , Dürst Matthias , Hillemanns Peter , Easton Douglas F , Dörk Thilo 
Published: February 2022

Abstract
Cervical cancer is among the leading causes of cancer-related death in females worldwide. Infection by human papillomavirus (HPV) is an established risk factor for cancer development. However, genetic factors contributing to disease risk remain largely unknown. We report on a genome-wide association study (GWAS) on 375 German cervical cancer patients and 866 healthy controls, followed by a replication study comprising 658 patients with invasive cervical cancer, 1361 with cervical dysplasia and 841 healthy controls. Functional validation was performed for the top GWAS variant on chromosome 14q12 (rs225902, close to PRKD1). After bioinformatic annotation and in silico predictions, we performed transcript analysis in a cervical tissue series of 317 samples and demonstrate rs225902 as an expression quantitative trait locus (eQTL) for FOXG1 and two tightly co-regulated long non-coding RNAs at this genomic region, CTD-2251F13 (lnc-PRKD1-1) and CTD-2503I6 (lnc-FOXG1-6). We also show allele-specific effects of the 14q12 variants via luciferase assays. We propose a combined effect of genotype, HPV status and gene expression at this locus on cervical cancer progression. Taken together, this work uncovers a potential candidate locus with regulatory functions and contributes to the understanding of genetic susceptibility to cervical cancer.
Novel diabetes gene discovery through comprehensive characterization and integrative analysis of longitudinal gene expression changes
Authors: Chen Hung-Hsin , Petty Lauren E , North Kari E , McCormick Joseph B , Fisher-Hoch Susan P , Gamazon Eric R , Below Jennifer E 
Published: February 2022

Abstract
Type 2 diabetes is a complex, systemic disease affected by both genetic and environmental factors. Previous research has identified genetic variants associated with type 2 diabetes risk; however, gene regulatory changes underlying progression to metabolic dysfunction are still largely unknown. We investigated RNA expression changes that occur during diabetes progression using a two-stage approach. In our discovery stage, we compared changes in gene expression using two longitudinally collected blood samples from subjects whose fasting blood glucose transitioned to a level consistent with type 2 diabetes diagnosis between the time points against those who did not with a novel analytical network approach. Our network methodology identified 17 networks, one of which was significantly associated with transition status. This 822-gene network harbors many genes novel to the type 2 diabetes literature but is also significantly enriched for genes previously associated with type 2 diabetes. In the validation stage, we queried associations of genetically determined expression with diabetes-related traits in a large biobank with linked electronic health records. We observed a significant enrichment of genes in our identified network whose genetically determined expression is associated with type 2 diabetes and other metabolic traits and validated 31 genes that are not near previously reported type 2 diabetes loci. Finally, we provide additional functional support, which suggests that the genes in this network are regulated by enhancers that operate in human pancreatic islet cells. We present an innovative and systematic approach that identified and validated key gene expression changes associated with type 2 diabetes transition status and demonstrated their translational relevance in a large clinical resource.
Sunitinib inhibits STAT3 phosphorylation in cardiac muscle and prevents cardiomyopathy in the mdx mouse model of Duchenne muscular dystrophy
Authors: Oliveira-Santos Ariany , Dagda Marisela , Burkin Dean J 
Published: February 2022

Abstract
Duchenne muscular dystrophy (DMD) is a fatal X-linked genetic disorder affecting approximately 1 in 5000 male births worldwide. DMD is caused by mutations in the dystrophin gene. Dystrophin is essential for maintaining muscle cell membrane integrity and stability by linking the cytoskeleton to the extracellular matrix, which protects myofibers from contraction-induced damage. Loss of dystrophin leads to mechanically induced skeletal and cardiac muscle damage. Although the disease is not evident in DMD patients at birth, muscular dystrophy rapidly progresses and results in respiratory and cardiac muscle failure as early as the teenage years. Premature death in DMD patients is due to cardiac arrhythmias and left ventricular dysfunction. Currently, there is no effective treatment for DMD-related cardiac failure. Recently, we have shown that a Food and Drug Administration-approved small molecule, sunitinib, a multi-targeted tyrosine kinase inhibitor can mitigate skeletal muscle disease through an increase in myogenic capacity, cell membrane integrity, and improvement of skeletal muscle function via regulation of STAT3-related signaling pathway. Chronic activation of STAT3 has been shown to promote cardiac hypertrophy and failure. In this study, we examined the effects of long-term sunitinib treatment on cardiac pathology and function. Our results showed sunitinib treatment reduced STAT3 phosphorylation in the heart muscle of mdx mice, improved cardiac electrical function, increased cardiac output and stroke volume, decreased ventricular hypertrophy, reduced cardiomyocytes membrane damage, fibrotic tissue deposition and slightly decreased cardiac inflammation. Together, our studies support the idea that sunitinib could serve as a novel treatment to slow cardiomyopathy progression in DMD.
One Sentence Summary In this study, we determined if sunitinib, a Food and Drug Administration-approved drug, could reduce the pathology and improve cardiac function in an animal model for DMD.
Principal consumer: President Biden's approach to intelligence
Authors: Lockhart James , Moran Christopher R 
Published: February 2022

Abstract
This article assesses United States President Joe Biden's approach to intelligence. It evaluates his evolving relationship with the Central Intelligence Agency and the rest of the intelligence community from the early 1970s, when he was elected to Congress, to the early 2020s, when he became the forty-sixth president of the United States. It concludes that, against the ever-changing context of international affairs, from the late Cold War to the global ‘war on terror’, Biden's approach to intelligence has remained consistent and stable, showing, on the one hand, enthusiasm for the production of national intelligence, and, on the other, a marked uneasiness about paramilitary covert action and the militarization of intelligence. The discussion that follows speaks to a larger debate, dating to the 1940s and still ongoing, in the executive and legislative branches of government, concerning the purposes and proper use of intelligence. This will interest policy-makers, officials and lawmakers responsible for intelligence and oversight, researchers and practitioners in security and intelligence, and scholars of American foreign relations.
Similar Gut Bacterial Composition Between Patients With Ulcerative Colitis and Healthy Controls in a High Incidence Population: A Cross-sectional Study of the Faroe Islands IBD Cohort
Authors: Berbisá Marjun á Fríðirksmørk , Nielsen Kári Rubek , Ingham Anna Cäcilia , Midjord Jóngerð , Hammer Turið , Patursson Poula , Vest Nicolina M O , Gregersen Noomi O , Burisch Johan , Vang Amanda 
Published: February 2022

Abstract

Background
The Faroe Islands has the world’s highest incidence of inflammatory bowel disease (IBD). Epidemiological studies have characterized this unique cohort and a decreased risk of developing IBD with emigration. Therefore, this well-characterized Faroese IBD cohort gives the opportunity to better understand this complex disease. This study represents the first investigation of the gut microbiota for the cohort.

Methods
This cross-sectional study consisted of 41 patients with established ulcerative colitis and 144 age- and sex-matched healthy controls recruited through the Faroe Genome project. Participants donated a 1-time fecal sample and completed questionnaires on food frequency, background health, and lifestyle. 16S rRNA amplicon sequencing of the V3-V4 region was performed followed by bioinformatic analysis of taxonomy and diversity metrics.

Results
The overall bacterial composition in both groups was dominated by Firmicutes and Bacteroidetes. No significant differences were found based on metrics of alpha or beta diversity. However, discriminatory analysis identified differential abundance of several indicator taxa in healthy controls and ulcerative colitis participants, whereas Akkermansia was completely absent from 27% of all study participants. Food frequency questionnaires revealed similar dietary patterns between the 2 groups.

Conclusion
The similarity in bacterial community composition and absence of the beneficial Akkermansia genus in both groups raise further questions concerning the underlying susceptibility toward inflammatory disorders within this high-risk population. Results vary widely by study design and geographic location, which speaks to the need for regionally tuned reference groups and disease-based studies on the Faroe Islands.
Quantifying risk assessments for monitoring control and surveillance of illegal fishing
Authors: Ford Jessica H , Wilcox Chris 
Published: February 2022

Abstract
One of the key international efforts to reduce Illegal, Unreported,and Unregulated (IUU) fishing is the United Nations Food and Agriculture Organization's Port State Measures Agreement. The agreement is designed to close off the opportunities for non-compliance, such as vessels engaging in illegal practices to land their catch. However, with thousands of vessels at sea and relatively limited inspection capacity, enhanced communication and information sharing to identify priority high-risk vessels is fundamental to successful implementation. Moving from traditional qualitative to quantitative risk assessments is one key step in ensuring the effective and efficient implementation. Risk profiling is in its infancy in the field of IUU fishing. Here, we present a transparent and repeatable method for eliciting quantitative weightings for indicators of IUU fishing using the Analytical Hierarchy Process. The method highlights the improvements in discrepancy with quantitative rankings, in comparison to traditional qualitative approach used, and the inherent ambiguity associated. This method can help to improve decision support systems used by fisheries surveillance agencies around the world. Knowing which vessels are high-risk is key to decision-making. Working towards a quantitative risk-based approach is fundamental step to improving oversight and control of IUU.
Climate-mediated stock redistribution causes increased risk and challenges for fisheries management
Authors: Jacobsen Nis S , Marshall Kristin N , Berger Aaron M , Grandin Chris , Taylor Ian G 
Published: February 2022

Abstract
The environmental conditions that marine populations experience are being altered because of climate change. In particular, changes in temperature and increased variability can cause shifts in spatial distribution, leading to changes in local physiological rates and recruitment success. Yet, management of fish stocks rarely accounts for variable spatial dynamics or changes in movement rates when estimating management quantities such as stock abundance or maximum sustainable yield. To address this concern, a management strategy evaluation (MSE) was developed to evaluate the robustness of the international management system for Pacific hake, an economically important migratory stock, by incorporating spatio-temporal population dynamics. Alternative hypotheses about climate-induced changes in age-specific movement rates, in combination with three different harvest control rules (HCR), were evaluated using a set of simulations that coupled single-area estimation models with alternative operating models representing spatial stock complexity. Movement rates intensified by climate change caused a median decline in catches, increased annual catch variability, and lower average spawning biomass. Impacts varied by area and HCR, underscoring the importance of spatial management. Incorporating spatial dynamics and climate change effects into management procedures for fish stocks with spatial complexity is warranted to mitigate risk and uncertainty for exploited marine populations.
Effect of Glucocorticoid and 11β-Hydroxysteroid-Dehydrogenase Type 1 (11β-HSD1) in Neurological and Psychiatric Disorders
Authors: Dodd Seetal , Skvarc David R , Dean Olivia M , Anderson Anna , Kotowicz Mark , Berk Michael 
Published: February 2022

Abstract
11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity is implicated as a moderator of the progression of multiple diseases and disorders in medicine and is actively subject to investigation as a therapeutic target. Here we summarize the mechanisms of the enzyme and detail the novel agents under investigation. Such agents modulate peripheral cortisol and cortisone levels in hypertension, type 2 diabetes, metabolic disorders, and Alzheimer’s disease models, but there is mixed evidence for transduction into symptom management. There is inchoate evidence that 11β-HSD1 modulators may be useful pharmacotherapies for clinical improvement in psychiatry and neurology; however, more research is required.
New and emerging concepts and therapies for the treatment of food allergy
Authors: Hwang David W , Nagler Cathryn R , Ciaccio Christina E 
Published: February 2022

AbstractFood allergy is an increasingly common disease that often starts in early childhood and lasts throughout life. Self-reported food allergy has risen at a rate of 1.2% per decade since 1988, and by 2018, the prevalence of food allergy in the United States was estimated to be 8% in children and 11% in adults.- This prevalence has led to an economic burden of almost $25 billion annually. Despite these staggering statistics, as of the time of this writing, the Food and Drug Administration (FDA) has only approved one treatment for food allergy, which is limited to use in children with peanut allergy. Fortunately, a new horizon of therapeutic interventions, in all stages of development, lay ahead and hold promise for the near future.
On Inhomogeneous Extension of Thue–Roth’s Type Inequality with Moving Targets
Authors: Kumar Veekesh 
Published: February 2022

AbstractLet $\Gamma \subset \overline{\mathbb Q}^{\times }$ be a finitely generated multiplicative group of algebraic numbers. Let $\delta ,\linebreak\beta \in \overline{\mathbb Q}^\times $ be algebraic numbers with $\beta $ irrational. In this paper, we prove that there exist only finitely many triples $(u, q, p)\in \Gamma \times \mathbb{Z}^2$ with $d = [\mathbb{Q}(u):\mathbb{Q}]$ such that $|\delta qu|&gt;1$ and $$\begin{align*} & 0&lt;|\delta qu+\beta-p|&lt;\frac{1}{H(u)^\varepsilon q^{d+\varepsilon}}, \end{align*}$$where $H(u)$ denotes the absolute Weil height. This is an inhomogeneous analogue of the main theorem in [ 2]. As an application of our result, we also prove a transcendence result, which states as follows: let $\alpha&gt;1$ be a real number. Let $\beta $ be an algebraic irrational number and $\lambda $ be a non-zero real algebraic number. For a given real number $\varepsilon&gt;0$, if there are infinitely many natural numbers $n$ for which $||\lambda \alpha ^n+\beta || &lt; 2^{- \varepsilon n}$ holds true, then $\alpha $ is transcendental, where $||x||$ denotes the distance from its nearest integer. When $\alpha $ and $\beta $ both are algebraic numbers satisfying same conditions, then a particular result of Kulkarni et al. [ 3] asserts that $\alpha ^d$ is a Pisot number. When $\beta $ is an algebraic irrational, our result implies that no algebraic number $\alpha $ satisfies the inequality for infinitely many natural numbers $n$. Also, our result strengthens a result of Wagner and Ziegler [ 7].
Collection Tubes Can Cause False Elevations in Occupational and Clinical Evaluation of Antimony Exposure
Authors: Yang Yifei K , Genesi Bryce , Adams Austin H 
Published: February 2022

Abstract
Occupational exposure to antimony has become rare in the past decades due to antimony mine closures and technological improvement in antimony processing plants in the USA. Although antimony’s ubiquitous presence in plasticwares does not pose known health risk, it can present as a potential contaminant to antimony analysis for occupational exposure assessment. To understand the level of antimony contamination from plastic collection devices, we evaluated two different whole-blood plastic collection tubes that are routinely used for trace and toxic element assessment: royal blue BD Vacutainer® EDTA tube and Greiner VACUETTE® trace elements sodium heparin tube. We analyzed how different fill volumes may impact the concentrations of antimony detected. Although both collection tubes can introduce antimony contaminations to nitric acid and neutral buffer rinse, the Greiner heparin tube introduces a significantly lower amount of antimony to freshly collected whole-blood samples compared to the BD EDTA tube. When patients’ samples are collected with BD EDTA tubes, they would exhibit elevated antimony concentrations that can be interpreted as potential antimony exposure. We conclude that the royal blue BD EDTA plastic tube is not suitable to evaluate blood antimony levels, and laboratories need to validate their own alternative sources when the glass tubes are not available.
Urban wage premia, cost of living, and collective bargaining
Authors: Belloc Marianna , Naticchioni Paolo , Vittori Claudia 
Published: February 2022

Abstract
In this article, we estimate urban wage premia (UWPs) in Italy, with its economy characterized by the interplay between collective wage bargaining and spatial heterogeneity in the cost of living. Our dataset for the 2005–2015 period exploits detailed information on the universe of workers in the private sector and price measures disaggregated at a fine spatial level. For employees under collective bargaining, we find a zero UWP in nominal terms and a negative UWP in real terms. When we turn to consider various groups of self-employed workers, who are not covered by national labor agreements, we instead find a positive nominal UWP and no real wage penalties.
Thermal biology and roost selection of free-ranging male little forest bats, Vespadelus vulturnus, during winter
Authors: Chenery Melissa , Geiser Fritz , Stawski Clare 
Published: February 2022

Abstract
Insectivorous bats are particularly susceptible to heat loss due to their relatively large surface area to volume ratio. Therefore, to maintain a high normothermic body temperature, bats require large amounts of energy for thermoregulation. This can be energetically challenging for small bats during cold periods as heat loss is augmented and insect prey is reduced. To conserve energy many bats enter a state of torpor characterized by a controlled reduction of metabolism and body temperature in combination with selecting roosts based upon thermal properties. Our study aimed to quantify torpor patterns and roost preferences of free-ranging little forest bats (Vespadelus vulturnus) during winter to identify physiological and behavioral mechanisms used by this species for survival of the cold season. All bats captured were male (body mass 4.9 ± 0.7 g, n = 6) and used torpor on every day monitored, with bouts lasting up to 187.58 h (mean = 35.5 ± 36.7 h, n = 6, total number of samples [N] = 61). Torpor bout duration was significantly correlated with daily minimum and maximum ambient temperature, mean skin temperature, insect mass, and body mass of individuals and the multiday torpor bouts recorded in the cold qualify as hibernation. The lowest skin temperature recorded was 5.2°C, which corresponded to the lowest ambient temperature measurement of −5.8°C. Most bats chose tall, large, live Eucalyptus trees for roosting and to leave their roost for foraging on warmer days. Many individuals often switched roosts (every 3–5 days) and movements increased as spring approached (every 1–2 days). Our data suggest that V. vulturnus are capable of using the environmental temperature to gauge potential foraging opportunities and as a cue to reenter torpor when conditions are unsuitable. Importantly, frequent use of torpor and appropriate roost selection form key roles in the winter survival of these tiny bats.
Predator niche overlap and partitioning and potential interactions in the mountains of Central Asia
Authors: Kachel Shannon M , Karimov Khalil , Wirsing Aaron J 
Published: February 2022

AbstractDirect and indirect interactions among predators affect predator fitness, distribution, and overall community structure. Yet, outside of experimental settings, such interactions are difficult to observe and thus poorly understood. Patterns of niche overlap among predators reflect and shape community interactions and may therefore help elucidate the nature and intensity of intraguild interactions. To better understand the coexistence of two apex predators, snow leopards (Panthera uncia) and wolves (Canis lupus), we investigated their spatial, temporal, and dietary niche overlap in summer in the Pamir Mountains of Tajikistan. We estimated population-level space use via spatial capture–recapture models based on noninvasive genetics and camera traps, diel activity patterns based on camera trap detections, and diet composition from prey remains in carnivore scats, from which we estimated coefficients between 0 and 1 for overlap in space, time, and diet, respectively. Snow leopards and wolves displayed moderate spatial partitioning (0.26, 95% confidence interval [CI]: 0.17–37), but overlapping temporal (0.77, 95% CI: 0.64–0.90) and dietary (0.97, 95% CI: 0.80–0.99) niches. Both predators relied on seasonally abundant marmots (Marmota caudata) rather than wild ungulates, their typical primary prey, suggesting that despite patterns of overlap that were superficially conducive to exploitation competition and predator facilitation, prey were likely not a limiting factor. Therefore, prey-mediated interactions, if present, were unlikely to be a major structuring force in the ecosystem. By implication, carnivore conservation planning and monitoring in the mountains of Central Asia should more fully account for the seasonal importance of marmots in the ecosystem.