bluuebunny/crossref_metadata_2025_split huggingface dataset:
Locations and characteristics of pharmacy deserts in the United States: a geospatial study
Authors: Wittenauer Rachel , Shah Parth D , Bacci Jennifer L , Stergachis Andy 
Published: March 2024

Abstract
Pharmacies are important health care access points, but no national map currently exists of where pharmacy deserts are located. This cross-sectional study used pharmacy address data and Census Bureau surveys to define pharmacy deserts at the census tract level in all 50 US states and the District of Columbia. We also compared sociodemographic characteristics of pharmacy desert vs non-pharmacy desert communities. Nationally, 15.8 million (4.7%) of all people in the United States live in pharmacy deserts, spanning urban and rural settings in all 50 states. On average, communities that are pharmacy deserts have a higher proportion of people who have a high school education or less, have no health insurance, have low self-reported English ability, have an ambulatory disability, and identify as a racial or ethnic minority. While, on average, pharmacies are the most accessible health care setting in the United States, many people still do not have access to them. Further, the people living in pharmacy deserts are often marginalized groups who have historically faced structural barriers to health care. This study demonstrates a need to improve access to pharmacies and pharmacy services to advance health equity.
m6A RNA methylation regulates mitochondrial function
Authors: Kahl Michael , Xu Zhaofa , Arumugam Saravanan , Edens Brittany M , Fischietti Mariafausta , Zhu Allen C , Platanias Leonidas C , He Chuan , Zhuang Xiaoxi , Ma Yongchao C 
Published: March 2024

Abstract
RNA methylation of N6-methyladenosine (m6A) is emerging as a fundamental regulator of every aspect of RNA biology. RNA methylation directly impacts protein production to achieve quick modulation of dynamic biological processes. However, whether RNA methylation regulates mitochondrial function is not known, especially in neuronal cells which require a high energy supply and quick reactive responses. Here we show that m6A RNA methylation regulates mitochondrial function through promoting nuclear-encoded mitochondrial complex subunit RNA translation. Conditional genetic knockout of m6A RNA methyltransferase Mettl14 (Methyltransferase like 14) by Nestin-Cre together with metabolomic analysis reveals that Mettl14 knockout-induced m6A depletion significantly downregulates metabolites related to energy metabolism. Furthermore, transcriptome-wide RNA methylation profiling of wild type and Mettl14 knockout mouse brains by m6A-Seq shows enrichment of methylation on mitochondria-related RNA. Importantly, loss of m6A leads to a significant reduction in mitochondrial respiratory capacity and membrane potential. These functional defects are paralleled by the reduced expression of mitochondrial electron transport chain complexes, as well as decreased mitochondrial super-complex assembly and activity. Mechanistically, m6A depletion decreases the translational efficiency of methylated RNA encoding mitochondrial complex subunits through reducing their association with polysomes, while not affecting RNA stability. Together, these findings reveal a novel role for RNA methylation in regulating mitochondrial function. Given that mitochondrial dysfunction and RNA methylation have been increasingly implicate in neurodegenerative disorders, our findings not only provide insights into fundamental mechanisms regulating mitochondrial function, but also open up new avenues for understanding the pathogenesis of neurological diseases.
Common single-base insertions in the VNTR of the carboxyl ester lipase (CEL) gene are benign and also likely to arise somatically in the exocrine pancreas
Authors: Brekke Ranveig S , Gravdal Anny , El Jellas Khadija , Curry Grace E , Lin Jianguo , Wilhelm Steven J , Steine Solrun J , Mas Eric , Johansson Stefan , Lowe Mark E , Johansson Bente B , Xiao Xunjun , Fjeld Karianne , Molven Anders 
Published: March 2024

Abstract
The CEL gene encodes carboxyl ester lipase, a pancreatic digestive enzyme. CEL is extremely polymorphic due to a variable number tandem repeat (VNTR) located in the last exon. Single-base deletions within this VNTR cause the inherited disorder MODY8, whereas little is known about VNTR single-base insertions in pancreatic disease. We therefore mapped CEL insertion variants (CEL-INS) in 200 Norwegian patients with pancreatic neoplastic disorders. Twenty-eight samples (14.0%) carried CEL-INS alleles. Most common were insertions in repeat 9 (9.5%), which always associated with a VNTR length of 13 repeats. The combined INS allele frequency (0.078) was similar to that observed in a control material of 416 subjects (0.075). We performed functional testing in HEK293T cells of a set of CEL-INS variants, in which the insertion site varied from the first to the 12th VNTR repeat. Lipase activity showed little difference among the variants. However, CEL-INS variants with insertions occurring in the most proximal repeats led to protein aggregation and endoplasmic reticulum stress, which upregulated the unfolded protein response. Moreover, by using a CEL-INS-specific antibody, we observed patchy signals in pancreatic tissue from humans without any CEL-INS variant in the germline. Similar pancreatic staining was seen in knock-in mice expressing the most common human CEL VNTR with 16 repeats. CEL-INS proteins may therefore be constantly produced from somatic events in the normal pancreatic parenchyma. This observation along with the high population frequency of CEL-INS alleles strongly suggests that these variants are benign, with a possible exception for insertions in VNTR repeats 1–4.
Hypoxic Functional Regulation Pathways in the GI Tract: Focus on the HIF-1α and Microbiota’s Crosstalk
Authors: Di Mattia Miriam , Sallese Michele , Neri Matteo , Lopetuso Loris Riccardo 
Published: March 2024

Abstract
Hypoxia is an essential gastrointestinal (GI) tract phenomenon that influences both physiologic and pathologic states. Hypoxia-inducible factors (HIFs), the primary drivers of cell adaptation to low-oxygen environments, have been identified as critical regulators of gut homeostasis: directly, through the induction of different proteins linked to intestinal barrier stabilization (ie, adherent proteins, tight junctions, mucins, integrins, intestinal trefoil factor, and adenosine); and indirectly, through the regulation of several immune cell types and the modulation of autophagy and inflammatory processes. Furthermore, hypoxia and HIF-related sensing pathways influence the delicate relationship existing between bacteria and mammalian host cells. In turn, gut commensals establish and maintain the physiologic hypoxia of the GI tract and HIF-α expression. Based on this premise, the goals of this review are to (1) highlight hypoxic molecular pathways in the GI tract, both in physiologic and pathophysiologic settings, such as inflammatory bowel disease; and (2) discuss a potential strategy for ameliorating gut-related disorders, by targeting HIF signaling, which can alleviate inflammatory processes, restore autophagy correct mechanisms, and benefit the host-microbiota equilibrium.
A data-driven framework for fast building energy demand estimation across future climate conditions
Authors: Zou Yukai , Chen Zhuoxi , Guo Jialiang , Zheng Yingsheng , Yang Xiaolin 
Published: March 2024

Abstract
The rapid and precise forecasting of building energy requirements plays a crucial role in decision-making processes for architects during the early design phase. This study introduces a data-driven framework capable of projecting energy demands in the context of evolving climate conditions. We evaluated four widely-used machine learning algorithms. Our results indicated that a hybrid approach, integrating Catboost and Bayesian optimization, excelled in both accuracy and efficiency for predicting building energy demand under climate change conditions. The framework proposed herein has potential applications in fostering sustainability in early-stage architectural design.
Microallopatric speciation in the relict dung beetle genus Grebennikovius (Coleoptera: Scarabaeidae) in the Eastern Arc Mountains
Authors: Montanaro Giulio , Grebennikov Vasily V , Rossini Michele , Grapputo Alessandro , Ruzzier Enrico , Tarasov Sergei 
Published: March 2024

Abstract
The Eastern Arc Mountains (EAMs) in Tanzania and Kenya are renowned for their exceptional species endemism often restricted to isolated mountain blocks. Forest fragmentation during the Pliocene–Pleistocene played a significant role in shaping the EAMs’ biodiversity by facilitating allopatric speciation between different mountains. However, only a few studies focused on species diversification within the same mountain block. In this article, we investigated the taxonomy and evolution of the dung beetle genus Grebennikovius, endemic to the Uluguru Mountains. Our goal was to unravel factors promoting allopatric speciation within a confined geographic area like the Ulugurus. We used an integrative taxonomic approach, combining phenotypic data and COI barcodes to delimit species and reconstructed a timetree of the genus. Molecular and morphological evidence consistently recovered 4 distinct Grebennikovius species, of which 3 are new to science: G. armiger n. sp., G. basilewskyi (Balthasar, 1960), G. lupanganus n. sp., and G. pafelo n. sp. Grebennikovius represents a rare case of microallopatry, with all species occurring in close proximity within different regions of the limited Uluguru forest (∼230 km2). We infer that speciation was driven by the interplay between climate fluctuations during the Miocene and mid-Pleistocene, Uluguru topography, and the stability of rainforest ecological conditions. The latter factor probably favored the loss of wings and a specialization for Uluguru microhabitats, reinforcing population isolation and divergence. This study highlights a unique instance of diversification resulting from small-scale speciation events, providing valuable insights into the evolution of Eastern African rainforest arthropods and underscoring the importance of microhabitats conservation.
Foreign Policy as Compensation: Why Brexit Became a Foreign and Security Policy Issue
Authors: Martill Benjamin , Mesarovich Alexander 
Published: March 2024

Abstract
Exogenous reform demands can put leaders in a tight spot where change runs up against structural impediments. Yet, where asymmetries in reform costs occur across domains, leaders can seek to re-frame the impetus of change from one domain to another. Such compensatory behavior is commonplace but is not adequately captured by existing research on linkage politics, forum shopping, or diversionary conflict. This article develops the concept of compensatory foreign policy, whereby leaders use foreign policy change to compensate for unviable economic reforms when they have greater capacity and choice in the former domain. Empirically, we use elite interviews to reconstruct the politics of security policy in the post-Brexit United Kingdom, showing how party leaders focused on foreign policy change when beneficial economic arrangements were precluded. Our argument contributes to recent research on linkage politics by demonstrating the conditions under which leaders seek foreign policy reforms to compensate for economic weakness.
Centralized Interactive Phenomics Resource: an integrated online phenomics knowledgebase for health data users
Authors: Honerlaw Jacqueline , Ho Yuk-Lam , Fontin Francesca , Murray Michael , Galloway Ashley , Heise David , Connatser Keith , Davies Laura , Gosian Jeffrey , Maripuri Monika , Russo John , Sangar Rahul , Tanukonda Vidisha , Zielinski Edward , Dubreuil Maureen , Zimolzak Andrew J , Panickan Vidul A , Cheng Su-Chun , Whitbourne Stacey B , Gagnon David R , Cai Tianxi , Liao Katherine P , Ramoni Rachel B , Gaziano J Michael , Muralidhar Sumitra , Cho Kelly 
Published: March 2024

Abstract

Objective
Development of clinical phenotypes from electronic health records (EHRs) can be resource intensive. Several phenotype libraries have been created to facilitate reuse of definitions. However, these platforms vary in target audience and utility. We describe the development of the Centralized Interactive Phenomics Resource (CIPHER) knowledgebase, a comprehensive public-facing phenotype library, which aims to facilitate clinical and health services research.

Materials and Methods
The platform was designed to collect and catalog EHR-based computable phenotype algorithms from any healthcare system, scale metadata management, facilitate phenotype discovery, and allow for integration of tools and user workflows. Phenomics experts were engaged in the development and testing of the site.

Results
The knowledgebase stores phenotype metadata using the CIPHER standard, and definitions are accessible through complex searching. Phenotypes are contributed to the knowledgebase via webform, allowing metadata validation. Data visualization tools linking to the knowledgebase enhance user interaction with content and accelerate phenotype development.

Discussion
The CIPHER knowledgebase was developed in the largest healthcare system in the United States and piloted with external partners. The design of the CIPHER website supports a variety of front-end tools and features to facilitate phenotype development and reuse. Health data users are encouraged to contribute their algorithms to the knowledgebase for wider dissemination to the research community, and to use the platform as a springboard for phenotyping.

Conclusion
CIPHER is a public resource for all health data users available at https://phenomics.va.ornl.gov/ which facilitates phenotype reuse, development, and dissemination of phenotyping knowledge.
B-1a cells scavenge NETs to attenuate sepsis
Authors: Murata Kensuke , Murao Atsushi , Tan Chuyi , Wang Ping , Aziz Monowar 
Published: March 2024

Abstract
B-1a cells, a regulatory subset of B lymphocytes, produce natural IgM and interleukin-10. Neutrophil extracellular traps (NETs) play a crucial role in pathogen defense, but their excessive formation during sepsis can cause further inflammation and tissue damage. In sepsis, extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern, is released to induce NET formation. We hypothesize that B-1a cells clear NETs to prevent sepsis-induced injury. Sepsis in mice was induced by injecting 1 × 107 and 5 × 107 colony-forming units of Escherichia coli intraperitoneally. After 4 and 20 h, we assessed the number of B-1a cells in the peritoneal cavity using flow cytometry. Our results showed that the number of peritoneal B-1a cells was significantly decreased in E. coli sepsis mice. Importantly, replenishing B-1a cells via intraperitoneal injection in sepsis mice significantly decreased NETs in peritoneal neutrophils. We also observed a decrease in serum inflammation and injury markers and a significant increase in the overall survival rate in B-1a cell–treated septic mice. To understand the mechanism, we cocultured bone marrow–derived neutrophils with peritoneal B-1a cells in a contact or noncontact condition using an insert and stimulated them with eCIRP. After 4 h, we found that eCIRP significantly increased NET formation in bone marrow–derived neutrophils. Interestingly, we observed that B-1a cells inhibited NETs by 67% in a contact-dependent manner. Surprisingly, when B-1a cells were cultured in inserts, there was no significant decrease in NET formation, suggesting that direct cell-to-cell contact is crucial for this inhibitory effect. We further determined that B-1a cells promoted NET phagocytosis, and this was mediated through natural IgM, as blocking the IgM receptor attenuated the engulfment of NETs by B-1a cells. Finally, we identified that following their engulfment, NETs were localized into the lysosomal compartment for lysis. Thus, our study suggests that B-1a cells decrease NET content in eCIRP-treated neutrophils and E. coli sepsis mice.
Evolutionary correspondence analysis of the semantic dynamics of frames
Authors: Baden Christian , Motta Giovanni 
Published: March 2024

Abstract
We introduce and implement a novel dimension-reduction method for high-dimensional time-varying contingency-tables: the Evolutionary Correspondence Analysis (ECA). ECA enables a comparative analysis of high-dimensional, diachronic processes by identifying a small number of shared latent variables that shape co-evolving data patterns. ECA offers new opportunities for the study of complex social phenomena, such as co-evolving public debates: Its capacity to inductively extract time-varying latent variables from observed contents of evolving debates permits an analysis of meanings shared by linked sub-discourses, such as linked national public spheres or the discourses led by distinct political camps within a shared public sphere. We illustrate the utility of our approach by studying how the Greek and German right-, centre-, and left-leaning news coverage of the European financial crisis evolved between its outbreak in 2009 until its institutional containment in 2012. Comparing the use of 525 unique concepts in six German and Greek outlets with different political leaning over an extended period of time, we identify two common factors accounting for those evolving meanings and analyse how the different sub-discourses influenced one another over time. We allow the factor loadings to be time-varying, and fit to the latent factors a time-varying vector-auto-regressive model with time-varying mean.
GENIUS-MAWII: for robust Mendelian randomization with many weak invalid instruments
Authors: Ye Ting , Liu Zhonghua , Sun Baoluo , Tchetgen Tchetgen Eric 
Published: March 2024

Abstract
Mendelian randomization (MR) addresses causal questions using genetic variants as instrumental variables. We propose a new MR method, G-Estimation under No Interaction with Unmeasured Selection (GENIUS)-MAny Weak Invalid IV, which simultaneously addresses the 2 salient challenges in MR: many weak instruments and widespread horizontal pleiotropy. Similar to MR-GENIUS, we use heteroscedasticity of the exposure to identify the treatment effect. We derive influence functions of the treatment effect, and then we construct a continuous updating estimator and establish its asymptotic properties under a many weak invalid instruments asymptotic regime by developing novel semiparametric theory. We also provide a measure of weak identification, an overidentification test, and a graphical diagnostic tool.
Plant metabolomics
Authors: Li-Beisson Yonghua , Hirai Masami Yokota , Nakamura Yuki 
Published: March 2024

Abstract
Plants are a treasure trove of metabolic compounds. The chemical diversity of plant cells has developed and been maintained through evolution and metabolic regulation, and plays a crucial role in plant physiology, development, and adaption to changing environmental situations. Metabolomics, when combined with genomics and proteomics, has opened up unprecedented opportunities to address the biological importance of metabolic diversity. It has also provided an avenue for metabolic engineering to produce a particular compound of interest to meet societal and economical demands, an important effort to achieve sustainable development. This Special Issue therefore focuses on current trends in plant metabolomics research, providing examples in the development of analytical technologies, the functional study of plant metabolism, and applications to synthetic and engineering biology.
Alternative pathways leading to ascorbate biosynthesis in plants: lessons from the last 25 years
Authors: Quiñones Cherryl O , Gesto-Borroto Reinier , Wilson Rachael V , Hernández-Madrigal Sara V , Lorence Argelia 
Published: March 2024

Abstract
l-Ascorbic acid (AsA) is an antioxidant with important roles in plant stress physiology, growth, and development. AsA also plays an essential role in human health, preventing scurvy. Humans do not synthesize AsA, which needs to be supplied via a diet rich in fresh produce. Research efforts have provided progress in the elucidation of a complex metabolic network with at least four routes leading to AsA formation in plants. In this review, three alternative pathways, namely the d-galacturonate, the l-gulose, and the myo-inositol pathways, are presented with the supporting evidence of their operation in multiple plant species. We critically discuss feeding studies using precursors and their conversion to AsA in plant organs, and research where the expression of key genes encoding enzymes involved in the alternative pathways showed &gt;100% AsA content increase in the transgenics and in many cases accompanied by enhanced tolerance to multiple stresses. We propose that the alternative pathways are vital in AsA production in response to stressful conditions and to compensate in cases where the flux through the d-mannose/l-galactose pathway is reduced. The genes and enzymes that have been characterized so far in these alternative pathways represent important tools that are being used to develop more climate-tolerant crops.
Comparison of markers to estimate microbial adherence and fibrolytic activity in forages after in vitro incubation
Authors: Mezzomo Mariana P , Stefanello Simone , Castro Luis A S , Kozloski Gilberto V 
Published: March 2024

Abstract
The aims of this study were to evaluate the relationship between attached microbial markers and degradability of forage samples incubated in vitro and to compare these microbial markers. In Trial 1, the content of 15N, purines, and phosphorus (P) as well as xylanase activity in residue of different forage species were measured after 24 h of incubation in a conventional in vitro system at pH 6.8. Trial 2 used the same procedures as those of Trial 1 except that forage samples were incubated in media with different initial pH (5.5, 6.0, 6.5, or 7.0). There was no correlation (P &gt; 0.10) between forage degradability and either microbial marker in Trial 1. Degradability of both, bermuda and ryegrass, and the content of all markers in the incubation residues was positively affected by increased pH (P &lt; 0.05). The content of 15N in residues was linearly related to xylanase activity (P &lt; 0.05) but not with P or purines content. In conclusion, the nutritional potential of different forage species may not to be compared, based on the content of microbial markers in the incubation residues. In other way, within a forage species, the in vitro degradation was directly associated to either marker. However, P presents analytical advantage over other markers.