bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin Improves Pulmonary Artery Remodeling in Chronic Thromboembolic Pulmonary Hypertension Rats
Authors: Li Hong-li , Pan Yun-chang , Wang Wen-feng , Fan Qi-chao , Zhang Bing-rong , Wu Da-wen , Deng Chao-sheng 
Published: August 2022

Abstract

Background
To investigate the effect of metformin on pulmonary artery remodeling and indexes of endothelial–mesenchymal transition in rats with chronic thromboembolic pulmonary hypertension (CTEPH).

Methods
Sixty Sprague Dawley rats were randomly divided into normal control, metformin control, CTEPH, metformin low-dose (50 mg/kg d) CTEPH, and metformin high-dose group (100 mg/kg d) CTEPH groups. The autologous blood clots were repeatedly injected through the jugular vein to establish the CTEPH model. After 6 weeks treatment with or without metformin, the mean pulmonary artery pressure (mPAP), pulmonary artery wall area to total tube area ratio (WA%), and protein levels of vimentin, α-smooth muscle actin (α-SMA), CD31, E-cadherin, β-catenin, and p-adenosine 5′-monophosphate activated protein kinase (p-AMPK) in the pulmonary artery were measured.

Results
The mPAP and WA% were significantly higher in CTEPH compared with normal control rats (P &lt; 0.05). Metformin treatment dose dependently decreased mPAP and WA% in CTEPH rats (P &lt; 0.01). Compared with normal controls, protein levels of vimentin, α-SMA, and β-catenin were significantly increased while CD31 and E-cadherin levels were decreased in CTEPH rats (all P &lt; 0.05). There was no significant difference in p-AMPK levels between normal control and CTEPH groups. Metformin treatment increased p-AMPK (P &lt; 0.05) but had no significant effect on vimentin, α-SMA, CD31, E-cadherin, or β-catenin levels in control rats. Metformin treatment dose dependently decreased vimentin, α-SMA, and β-catenin levels, and increased CD31, E-cadherin, and p-AMPK levels in CTEPH rats (P &lt; 0.05).

Conclusions
Metformin reduces mPAP and improves pulmonary vascular remodeling possibly through attenuating endothelial–mesenchymal transition of the pulmonary artery in CTEPH rats.
US drug shortages compared to the World Health Organization’s Model List of Essential Medicines for Children: A cross-sectional study
Authors: Patel Ram , Samiee-Zafarghandy Samira , Ziesenitz Victoria , Fox Erin R , Van Den Anker John , Ong Hilary , Mazer-Amirshahi Maryann 
Published: August 2022

AbstractPurposeTo describe US drug shortages affecting medications on the 2019 World Health Organization (WHO) Model List of Essential Medicines for Children (EMLc).MethodsDrug shortage data from January 2014 to December 2019 were obtained from the University of Utah Drug Information Service. Shortage data for drugs on the EMLc were analyzed for the type of drug, American Hospital Formulary Service category, reason for the shortage, duration of the shortage, marketing status (generic vs brand name), and whether the agent was a single- or multisource drug.ResultsFrom 2014 to 2019, a total of 209 drug shortages impacted medications on the EMLc, of which 77 (36.8%) remained unresolved by 2019. Of all active shortages, 13 (6.2%) began before 2014. Resolved shortages had a median duration of 5.9 months (interquartile range [IQR], 3.6-13.2 months) while active shortages had a median duration of 18.3 months (IQR, 10.9-33.5 months; P ≤ 0.0001). The therapeutic categories most impacted by drug shortages were anti-infective agents (27.3%), central nervous system agents (12.9%), and antineoplastic agents (11.0%). The reason for the shortage was not reported in 46.4% of cases. When a reason was provided, the most common reason was manufacturing problems (29.2%) followed by supply/demand mismatch (15.8%).ConclusionUS drug shortages affected many medications on the WHO EMLc. Future studies should examine the global shortage climate and implications for patient care.
Different Goals, Different Needs: The Effects of Telephone- and Text Message-Based Continuing Care for Patients with Different Drinking Goals After Residential Treatment for Alcohol Use Disorder
Authors: Graser Yolanda , Stutz Sonja , Rösner Susanne , Wopfner Alexander , Moggi Franz , Soravia Leila M 
Published: August 2022

AbstractAimsDrinking goal has emerged as a promising predictor variable for alcohol-related outcomes. Many patients with alcohol use disorder (AUD) choose another drinking goal than abstinence after residential AUD treatment program. We aimed to examine the effects of an abstinent drinking goal (ADG) and conditional abstinence drinking goal (CADG) 6 months after residential treatment on drinking outcomes in patients with severe AUD and investigate the effectiveness of telephone-based (TEL) or text message-based (TEX) continuing care according to the individual drinking goal.MethodsA total of 240 patients from two specialized residential treatment programs for AUD were included in the study. Patients were randomly assigned to high-frequency (nine contacts) or low-frequency (two contacts) TEL, TEX (nine contacts), or control group (no contact) from treatment discharge to the 6-month follow-up.ResultsPatients with an ADG were significantly more often abstinent (58%) at the 6-month follow-up compared to patients with a CADG (32.1%), and in the case of relapse, showed a significantly longer time to the first drink. Patients with a CADG of the high-frequency TEL showed a tendency to be more abstinent at the 6-month follow-up and reported significantly higher alcohol-related self-efficacy compared to the CADG patients of the control group.ConclusionsPatients with CADG are more vulnerable to relapse, and therefore may benefit more from high-frequency telephone contacts to deal with alcohol-related problems and reach their goal. In the case of relapse, the high-frequent contacts may help patients stay connected to health services, preventing chronification and facilitating recovery from AUD.
Evolution of long-distance signalling upon plant terrestrialization: comparison of action potentials in Characean algae and liverworts
Authors: Kisnieriene Vilma , Trębacz Kazimierz , Pupkis Vilmantas , Koselski Mateusz , Lapeikaite Indre 
Published: August 2022

Abstract

Background
In this review, we summarize data concerning action potentials (APs) – long-distance electrical signals in Characean algae and liverworts. These lineages are key in understanding the mechanisms of plant terrestrialization. Liverworts are postulated to be pioneer land plants, whereas aquatic charophytes are considered the closest relatives to land plants. The drastic change of the habitat was coupled with the adaptation of signalling systems to the new environment.

Scope
APs fulfil the ‘all-or-nothing’ law, exhibit refractory periods and propagate with a uniform velocity. Their ion mechanism in the algae and liverworts consists of a Ca2+ influx (from external and internal stores) followed by/coincident with a Cl– efflux, which both evoke the membrane potential depolarization, and a K+ efflux leading to repolarization. The molecular identity of ion channels responsible for these fluxes remains unknown. Publication of the Chara braunii and Marchantia polymorpha genomes opened up new possibilities for studying the molecular basis of APs. Here we present the list of genes which can participate in AP electrogenesis. We also point out the differences between these plant species, e.g. the absence of Ca2+-permeable glutamate receptors (GLRs) and Cl–-permeable SLAC1 channel homologues in the Chara genome. Both these channels play a vital role in long-distance signalling in liverworts and vascular plants. Among the common properties of APs in liverworts and higher plants is their duration (dozens of seconds) and the speed of propagation (mm s–1), which are much slower than in the algae (seconds, and dozens of mm s–1, respectively).

Conclusions
Future studies with combined application of electrophysiological and molecular techniques should unravel the ion channel proteins responsible for AP generation, their regulation and transduction of those signals to physiological responses. This should also help to understand the adaptation of the signalling systems to the land environment and further evolution of APs in vascular plants.
The characteristics of glucose metabolism and functional connectivity in posterior default network during nondemented aging: relationship with executive function performance
Authors: Xu Kai , Niu Na , Li Xin , Chen Yuan , Wang Dandan , Zhang Junying , Chen Yaojing , Li He , Wei Dongfeng , Chen Kewei , Cui Ruixue , Zhang Zhanjun , Yao Li 
Published: August 2022

Abstract

Background
Understanding the characteristics of intrinsic connectivity networks (ICNs) in terms of both glucose metabolism and functional connectivity (FC) is important for revealing cognitive aging and neurodegeneration, but the relationships between these two aspects during aging has not been well established in older adults.

Objective
This study is to assess the relationship between age-related glucose metabolism and FC in key ICNs, and their direct or indirect effects on cognitive deficits in older adults.

Methods
We estimated the individual-level standard uptake value ratio (SUVr) and FC of eleven ICNs in 59 cognitively unimpaired older adults, then analyzed the associations of SUVr and FC of each ICN and their relationships with cognitive performance.

Results
The results showed both the SUVr and FC in the posterior default mode network (pDMN) had a significant decline with age, and the association between them was also significant. Moreover, both decline of metabolism and FC in the pDMN were significantly correlated with executive function decline. Finally, mediation analysis revealed the glucose metabolism mediated the FC decline with age and FC mediated the executive function deficits.

Conclusions
Our findings indicated that covariance between glucose metabolism and FC in the pDMN is one of the main routes that contributes to age-related executive function decline.
Financialisation and firm-level investment in developing and emerging economies
Authors: Tori Daniele , Onaran Özlem 
Published: August 2022

Abstract
This article analyses the effects of financialisation on non-financial companies’ (NFCs) investment and explores the interactions between financialisation and the structural and institutional features of developing and emerging economies (DEEs). We estimate the effects of financialisation on physical investment for a sample of DEEs using panel data based on the balance sheets of publicly listed NFCs. Our main contribution is to assess the interactions between the financialisation of the NFCs and country-level financial development, financial reform, capital account openness and global value chain participation. We find that the effects of the financialisation of the NFCs in DEEs are highly context specific. Stock market development, financial reforms for liberalisation, capital account openness and participation in the global value chains are associated with more pronounced negative effects of financialisation on investment. Our analysis provides novel empirical evidence regarding the sources of variation in the financialisation of corporations in DEEs.
Orphaning stunts growth in wild African elephants
Authors: Parker Jenna M , Wittemyer George 
Published: August 2022

Orphans of several species suffer social and physiological consequences such as receiving more aggression from conspecifics and lower survival. One physiological consequence of orphaning, stunted growth, has been identified in both humans and chimpanzees, but has not been assessed in a non-primate species. Here, we tested whether wild African elephant orphans show evidence of stunted growth. We measured individually known female elephants in the Samburu and Buffalo Springs National Reserves of Kenya, with a rangefinder capable of calculating height, to estimate a von Bertalanffy growth curve for female elephants of the study population. We then compared measurements of known orphans and non-orphans of various ages, using a Bayesian analysis to assess variation around the derived growth curve. We found that orphans are shorter for their age than non-orphans. However, results suggest orphans may partially compensate for stunting through later growth, as orphans who had spent a longer time without their mother had heights more similar to non-orphans. More age mates in an individual’s family were associated with taller height, suggesting social support from peers may contribute to increased growth. Conversely, more adult females in an individual’s family were associated with shorter height, suggesting within-group competition for resources with older individuals may reduce juvenile growth. Finally, we found a counterintuitive result that less rainfall in the first 6 years of life was correlated with taller height, potentially reflecting the unavoidable bias of measuring individuals who were fit enough to survive conditions of low rainfall as young calves. Reduced growth of individuals has been shown to reduce survival and reproduction in other species. As such, stunting in wildlife orphans may negatively affect fitness and represents an indirect effect of ivory poaching on African elephants.
Turkish Sign Language Adaptation of the Turkish Health Literacy Scale-32
Authors: Bulun Mehtap Ataseven , Çepni Selden , Ermez Yusuf 
Published: August 2022

Abstract
Sign language speakers are at a disadvantage in terms of health literacy due to the lack of health education materials in sign languages. Deaf and hard of hearing (DHH) individuals are excluded from health literacy research due to the lack of measurement tools in their language of excellent fluency. This study aims to provide the literature with a tool that allows the measurement of health literacy among DHH individuals. The Turkish Health Literacy Scale (THLS)-32 was translated into Turkish Sign Language (TSL). After the THLS-32 was translated into TSL in video format, it was tested for validity and reliability. The translated version of the scale was administered to participants from a DHH association in Turkey who are fluent in TSL. Subsequently, a study was conducted with 207 DHH individuals. The study group was assessed in terms of their mean index scores and evaluated to have “limited health literacy” according to the THLS-32 classification. We conclude that the THLS-32 in TSL is suitable to measure health literacy in DHH individuals and to assess the impact of the health education system.
Biodiversity of Parasitic Hymenoptera Across Sky Islands of Arkansas, United States
Authors: Monroe Allison F , Hubbard Sierra C , Rodriguez Reynol , Kuhns Faith M , McClung Maureen R , Moran Matthew D , Gates Michael W 
Published: August 2022

Abstract
Sky islands are often areas of endemism and high species diversity around the world. In central North America, the Ozark and Ouachita Highlands contain numerous modestly high elevational islands that are slightly cooler and wetter than surrounding lowlands and these areas are known to contain many unique species. We studied parasitic Hymenoptera biodiversity on three sky islands in Arkansas, both in canopy and understory strata of mature post oak forests. We found that morphospecies diversity was high, and community structure varied both within (canopy versus understory) and between sky islands. Each mountaintop showed a high level of distinctiveness with few morphospecies found in multiple locations. The high intersky island variation indicates that individual sky islands in the region harbor unique Hymenoptera assemblages, a pattern that likely extends to the broader insect community. Our study suggests that these highland areas are important regions of North American biodiversity and that they should be evaluated individually for conservation efforts in order to preserve their distinctive community structure.
The role of pre-existing weaknesses in intraplate metamorphic core complex formation during slab retreat: 2-D thermomechanical modelling
Authors: Tang Jiaxuan , Chen Lin , Liu Lijun , Yan Zhiyong , Lin Wei , Meng Qingren 
Published: August 2022

SUMMARYA number of metamorphic core complexes (MCCs) developed in the North China Craton and adjacent regions in the Early Cretaceous and were characterized by consistent extensional orientations. These MCCs formed in the continental interior and were conceptually attributed to the retreat of the Palaeo-Pacific (Izanagi) Plate, but the exact physical mechanism remains enigmatic. Here we utilize 2-D thermomechanical simulations to study how mechanical conditions of the continental crust respond to stresses derived from oceanic subduction and their roles in the formation of MCCs. Our results demonstrate that pre-existing weaknesses are key for localized formation within the continental interior. These weaknesses first undergo compression to form thrust faults in response to shallow subduction of the oceanic slab. These thrust faults gradually transform into extensional ones as the oceanic slab starts to retreat, eventually causing the synchronous exhumation of middle-to-lower crustal rocks that form the MCCs. The P-T paths of metamorphic rocks in the core of MCCs reveal a two-stage exhumation, with isothermal decompression followed by rapid isobaric cooling. Sensitivity tests show that (1) stronger upper crust and weaker lower crust favour MCC formation, while lithospheric strength could exert an influence on the formation time of MCCs and (2) when the continental crust is hot (TMoho = 800 °C), a new magmatic dome could form along the continental margin. We suggest that pre-existing weaknesses in the North China Craton played a key role in generating the quasi-simultaneous MCC series in response to the retreating Palaeo-Pacific Plate.
A haplotype resolved chromosomal level avocado genome allows analysis of novel avocado genes
Authors: Nath Onkar , Fletcher Stephen J , Hayward Alice , Shaw Lindsay M , Masouleh Ardashir Kharabian , Furtado Agnelo , Henry Robert J , Mitter Neena 
Published: August 2022

Abstract
Avocado (Persea americana) is a member of the magnoliids, an early branching lineage of angiosperms that has high value globally with the fruit being highly nutritious. Here, we report a chromosome-level genome assembly for the commercial avocado cultivar Hass, which represents 80% of the world’s avocado consumption. The DNA contigs produced from Pacific Biosciences HiFi reads were further assembled using a previously published version of the genome supported by a genetic map. The total assembly was 913 Mb with a contig N50 of 84 Mb. Contigs assigned to the 12 chromosomes represented 874 Mb and covered 98.8% of benchmarked single-copy genes from embryophytes. Annotation of protein coding sequences identified 48 915 avocado genes of which 39 207 could be ascribed functions. The genome contained 62.6% repeat elements. Specific biosynthetic pathways of interest in the genome were investigated. The analysis suggested that the predominant pathway of heptose biosynthesis in avocado may be through sedoheptulose 1,7 bisphosphate rather than via alternative routes. Endoglucanase genes were high in number, consistent with avocado using cellulase for fruit ripening. The avocado genome appeared to have a limited number of translocations between homeologous chromosomes, despite having undergone multiple genome duplication events. Proteome clustering with related species permitted identification of genes unique to avocado and other members of the Lauraceae family, as well as genes unique to species diverged near or prior to the divergence of monocots and eudicots. This genome provides a tool to support future advances in the development of elite avocado varieties with higher yields and fruit quality.
Efficacy of ensitrelvir against SARS-CoV-2 in a delayed-treatment mouse model
Authors: Nobori Haruaki , Fukao Keita , Kuroda Takayuki , Anan Naomi , Tashima Ryoichi , Nakashima Masaaki , Noda Sayuri , Tajiri Minako , Torii Mikinori , Toba Shinsuke , Uemura Kentaro , Sanaki Takao , Shishido Takao , Tachibana Yuki , Kato Teruhisa 
Published: August 2022

Abstract

Objectives
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19) and a devastating worldwide health concern. Development of safe and effective treatments is not only important for interventions during the current pandemic, but also for providing general treatment options moving forward. We have developed ensitrelvir, an antiviral compound that targets the 3C-like protease of SARS-CoV-2. In this study, a delayed-treatment mouse model was used to clarify the potential in vivo efficacy of ensitrelvir.

Methods
Female BALB/cAJcl mice of different ages were infected with the SARS-CoV-2 gamma strain (hCoV-19/Japan/TY7-501/2021) or mouse-adapted SARS-CoV-2 MA-P10 and then 24 h post-infection orally administered various doses of ensitrelvir or vehicle. Viral titres and RNA levels in the lungs were quantified using VeroE6/TMPRSS2 cells and RT–qPCR, respectively. Body weight loss, survival, lung weight, cytokine/chemokine production, nucleocapsid protein expression and lung pathology were evaluated to investigate the in vivo efficacy of ensitrelvir.

Results
Based on infectious viral titres and viral RNA levels in the lungs of infected mice, ensitrelvir reduced viral loads in a dose-dependent manner. The antiviral efficacy correlated with increased survival, reduced body weight loss, reduced pulmonary lesions and suppression of inflammatory cytokine/chemokine levels.

Conclusions
This was the first evaluation of the in vivo anti-SARS-CoV-2 efficacy of ensitrelvir in a delayed-treatment mouse model. In this model, ensitrelvir demonstrated high antiviral potential and suppressed lung inflammation and lethality caused by SARS-CoV-2 infection. The findings support the continued clinical development of ensitrelvir as an antiviral agent to treat patients with COVID-19.
Molecular and biochemical regulation of skeletal muscle metabolism
Authors: Zumbaugh Morgan D , Johnson Sally E , Shi Tim H , Gerrard David E 
Published: August 2022

AbstractSkeletal muscle hypertrophy is a culmination of catabolic and anabolic processes that are interwoven into major metabolic pathways, and as such modulation of skeletal muscle metabolism may have implications on animal growth efficiency. Muscle is composed of a heterogeneous population of muscle fibers that can be classified by metabolism (oxidative or glycolytic) and contractile speed (slow or fast). Although slow fibers (type I) rely heavily on oxidative metabolism, presumably to fuel long or continuous bouts of work, fast fibers (type IIa, IIx, and IIb) vary in their metabolic capability and can range from having a high oxidative capacity to a high glycolytic capacity. The plasticity of muscle permits continuous adaptations to changing intrinsic and extrinsic stimuli that can shift the classification of muscle fibers, which has implications on fiber size, nutrient utilization, and protein turnover rate. The purpose of this paper is to summarize the major metabolic pathways in skeletal muscle and the associated regulatory pathways.