bluuebunny/crossref_metadata_2025 huggingface dataset:
Research on obstacle climbing gait structure design and gait control of hexapod wall climbing robot based on STM32F103 core controller
Authors: Hongfan Gui , Zhangyan Zhao
Published: July 2023

The hexapod wall climbing robots have the advantages of traversing complex wall surfaces. To traverse complex environments autonomously, it must possess the capability to select gait parameters and paths appropriate for the wall surface. Path planning and gait optimization is a fundamental issue in the aspect of stable, energy efficient robot navigation in complex environments with static and dynamic obstacles. Traditional statistical models have been developed to get the optimal path and gait parameters but the result obtained was very poor. Metaheuristic algorithms are gaining importance in robotic gait planning. In this paper, we proposed robust two stage gait planning approach for predicting collision-free, distance-minimal, smooth navigation path and ensuring stable, energy efficient gait patterns for robots using hybrid metaheuristic algorithms. In the first stage, optimal climbing path for robot is predicted using Tri-objective Grey Wolf Path Optimization (TGWPO) based on obstacle and target detection. In the second stage, the gait parameters adaptive to the constructed climbing path are optimized using Adaptive multi-objective Particle swarm optimization (AMPSO). The hexapod wall climbing robot is designed with STM32F103 as core controller modeled with optimal path planner (using TDWPO) and gait optimizer module (using AMPSO). STM32F103 controller commands and controls the robot to climb on wall with optimized gait parameters according to the optimal path. We analyzed the efficacy of the proposed two stage gait planning approach using TDWPO-AMPSO for hexapod wall climbing robots with existing gait planning approaches in terms of path length, climbing time, gait stability, obstacle avoidance, and energy efficiency. The result analysis showed that the suggested gait planning approach is efficient over conventional strategies for climbing robots.
Circular RNA circADAM9 Promotes Inflammation, Oxidative Stress, and
Fibrosis of Human Mesangial Cells via the Keap1-Nrf2 Pathway in Diabetic
Nephropathy
Authors: Zheng Hongwei , Liu Xuezheng , Song Bing
Published: July 2023

Objective Circular RNAs (circRNAs) have been discovered as potential
biomarkers for diabetic nephropathy (DN). In this study, the potential roles of
circADAM9 in high glucose (HG)-induced cell injury of human mesangial cells
(HMCs) were investigated, and the underlying mechanism was elucidated.

Methods DN cell model in vitro was simulated by HG treatment of
HMCs. Endogenous expressions of circADAM9, miR-545-3p, and ubiquitin-specific
protease 15 (USP15) were determined by real-time polymerase chain reaction. Cell
proliferation and migration were evaluated using Cell Counting Kit-8 and wound
healing assays. The inflammatory response was assessed by enzyme-linked
immunosorbent assay. Oxidative stress was examined using commercially available
kits. Dual-luciferase reporter and RNA pull-down assays were conducted to
confirm the interaction among circADAM9, miR-545-3p, and USP15.

Results CircADAM9 was upregulated in DN samples and HG-treated HMCs, while
its downregulation inhibited cell proliferation, inflammation, fibrosis, and
oxidative stress. Further investigation revealed that circADAM9 exerted this
influence by targeting the miR-545-3p/USP15 axis, thereby regulating the
KELCH-like ECh-associated protein 1/nuclear factor erythroid 2 related
factor 2 (Keap1/Nrf2) pathway. MiR-545-3p knockdown or USP15
overexpression reversed the effect of circADAM9 silencing in HG-induced
HMCs.

Conclusion These results indicate that the
circADAM9/miR-545-3p/USP15/Keap1/Nrf2 signaling
axis is critical for HG-induced cell injury in HMCs and might represent a novel
therapeutic target for DN treatment.
Developing Leaders: What We Can Learn From the Education, Adult, and Human Resource Development Paradigm
Authors: Chang Wei-Wen Vera
Published: July 2023

Faced with global challenges, organizations have invested heavily in leadership development, but the impact of such a large investment has been of continual concern. Studies have suggested that effective leadership development relies on the interconnection of the top leader, senior managerial team, line managers, and human resource specialists; however, the perspective of learning and learners has received relatively limited examination. Leadership development must also look at the education, adult, and human resource development (HRD) paradigms. The three key components that comprise the intersection between adult education and HRD are experience, social context, and transformation. Learning directions in leadership development have both external and internal aspects, including using invisible force to accomplish work, managing paradoxical social dynamics, extending self-identity, and integrating multiple factors. For learning approaches, the ACT model, where A stands for acquire and apply, C stands for clean and calibrate, and T stands for transform and transcend, can assist in achieving these.
1964 Freedom Schools in the United States
Authors: Clemons Kristal Moore
Published: July 2023

The 1964 Mississippi Freedom Summer Project served thousands of children and adults in over 40 Freedom Schools created to combat voter suppression and encourage youth to engage in the Civil Rights Movement. The Mississippi Freedom Summer Project included three main initiatives: Freedom Schools and community centers, voter registration on the official state rolls, and a freedom registration plan designed to independently elect a slate of delegates to the 1964 Democratic National Convention. Voter registration was the cornerstone of the Mississippi Freedom Summer, and approximately 17,000 Black residents of Mississippi attempted to register to vote in 1964, but only 1,600 of the applications were accepted by the registrars. The Freedom Schools utilized a curriculum focused on the philosophical tenets of the Civil Rights Movement, arithmetic, reading, writing, and African American history. The purpose was to supplement what children in the various counties in Mississippi were not receiving in their traditional public school setting. Marian Wright Edelman, activist and founder of the Children’s Defense Fund (CDF), reinvigorated the contemporary Freedom Schools movement in the 1990s. The CDF’s Black Community Crusade for Children saw the CDF Freedom Schools program as an intergenerational collaboration between Civil Rights Movement–era activists and younger generations.
The History of Badakhshan from the 7th to the 19th Century
Authors: Beben Daniel
Published: July 2023

Badakhshan is a historical region spanning the present-day territories of northeastern Afghanistan and eastern Tajikistan, as well as bordering districts of northern Pakistan and northwestern China. This mountainous region was historically significant on account of its position as a key transit point for trade between China and western Eurasia, as well as for its gem mines. The region held a largely peripheral position within the Muslim world down to the 12th century. Its status changed significantly in the wake of the Mongol conquests, from which Badakhshan emerged as a notably enlarged and autonomous kingdom, one which thereafter played an important role in the political history of Central Asia and Afghanistan. However, neighboring empires continued to encroach on the region throughout the 18th and 19th century, and by the end of the 19th century, the region had permanently lost its autonomy and was partitioned between Afghanistan and the Russian Empire.
Pastoralism in Mongolia
Authors: Undargaa Sandagsuren
Published: July 2023

Equestrian mobile pastoralism and its governance form in contemporary Mongolia date back to the 13th century Mongol Empire. The Mongol Empire succeeded a series of predecessor nomadic states in Inner Asia. The rulers of the empire adjusted the sociopolitical institutions of these preceding nomadic polities and turned the limitations imposed by the existing geographical environment to their own advantage, drawing benefits from pastoralism. They governed both pastoral and agricultural people and obtained political and economic benefits from Eurasia. After the empire collapsed, the remaining independent states encountered enormous change to their sociopolitical order, though certain aspects of the preceding political institutions for governing pastoral people and their production continued. In the early 20th century, the rulers of Outer Mongolia, while securing their geopolitical positions and independence, encountered pressure to modernize with the global trend of political and socioeconomic development via socialism and later capitalism. Looking at pastoralism in Mongolia from a historical perspective, it is important to acknowledge the dynamic relationship between pastoral governance and path-dependent historical changes to governance institutions within a narrative of the larger political history of Mongolia. Historical and contemporary states in different periods employed various statutory mechanisms to define basic sociopolitical and primary production units and their social and resource use boundaries to manage human and natural resources. Historical changes in these institutional arrangements more often maintained interdependent relationships between state rulers, local jurisdictional authorities, and their residents to pursue formal and informal control over the integrated governance of livestock, labor, and land to benefit from pastoralism. The changes at the end of the 20th century, however, resulted in dismantling the historical governance institutions in an attempt to adjust to market economy and to benefit from alternative economic development. Hence, Mongolia faces enormous public and environmental governance challenges in unpredictable socio-economic, geopolitical, and ecological contexts, in which pastoralism is now combined with urbanization and intensive agriculture.
Territorial and Institutional Settlements in the Global South and Beyond
Authors: McCulloch Allison , Aboultaif Eduardo Wassim
Published: July 2023

Territorial and institutional settlements—from federalism and regional autonomy to consociationalism, centripetalism, and other forms of power-sharing—represent leading strategies by which to end protracted ethnicized conflicts. Yet there remains considerable debate as to the long-term merits of such approaches. Does consociationalism entrench divisions and immobilize government decision-making? Is federalism merely a precursor to secession? Or are territorial and institutional settlements the best prospect by which to deliver peace, democracy, and stability to deeply divided societies? The debate remains unsettled.

Two main iterations of the debate regarding institutional design choices in divided societies in the Global South can be identified: one—accommodation versus integration—tends to present the options in zero-sum terms. In these earlier stages of the debate, consociationalism and centripetalism are frequently cast as opposing and irreconcilable forms of government in deeply divided societies (e.g., consociationalism versus centripetalism). Later scholarship tracks a different approach. In the second iteration—what can be labeled the turn to hybridity—scholars have shifted toward emphasizing their compatibility (e.g., consociationalism and centripetalism) or charting a path between them (consociationalism, then centripetalism).

Beyond scholarly debates, institutional and territorial settlements in the Global South, including from across Latin and South America, Africa, the Middle East, and Asia, exhibit a wide variety of forms and manifestations, some of which support accommodation while others tend toward integration.
Liberal Peacebuilding and Its Critiques
Authors: Bargués Pol
Published: July 2023

Critical perspectives not only evaluate and assess critically the wrongs of peace operations but also open new avenues for peacebuilding. At their best, critiques become lessons learned, sources of inspiration and regulative norms that contribute to the advancement of policy thinking and practice. Three imaginaries of critiques of liberal peace stand out: a locally driven peace that emerges from below; nonlinear interventions to tackle different aspects of crises ; and indirect forms of facilitation and strengthening resilience. Scholarly critiques have been influential in pushing the practice of peace operations away from the top-down, short-term, and direct mechanisms of governance of the liberal peace.
The California Missions
Authors: Hackel Steven W.
Published: July 2023

Twenty-one colonial-era missions traversed California stretching northward from San Diego to just beyond San Francisco. Founded by Franciscan missionaries beginning in 1769, these missions—along with four presidios (forts) and three pueblos (towns)—were central to Spain’s attempt to incorporate the Pacific Coast of northern New Spain into its enormous transatlantic colonial empire. Established in the late 18th century, just as Spain was secularizing missions elsewhere in New Spain, the California missions were cultural and institutional throwbacks and controversial from their inception. They prompted consistent and occasionally violent resistance from Native Californians. Furthermore, Europeans who visited Spanish California saw them as repressive colonial institutions. Indeed, during their sixty years of existence, the missions proved most adept at damaging the culture and shortening the lives of California’s Native Americans, the very people missionaries thought they would save by bringing them into the Catholic faith. By the time that Mexican government officials secularized the missions in the 1830s and parceled their lands and resources out to Mexican settlers, associates of the Mexican ruling elite, and a small number of Natives, California missions had shown themselves to be transformative and lethal agents of change. In the 21st century, their legacies are increasingly seen as negative, forever linked to the indefatigable and uncompromising missionary Junípero Serra, who was controversially canonized by Pope Francis in 2015.
Minced Free Fat Graft Versus Pedicle Fat Flap to Efface Orbital Rim Hollow in Lower Blepharoplasty
Authors: Karimi Nasser , Kashkouli Mohsen Bahmani , Enayatollahi Shayesteh , Ghahvehchian Hossein , Abdolalizadeh Parya , Ramadan Mohammad
Published: July 2023

Background

Lower eyelid fat flap repositioning during transconjunctival lower blepharoplasty (TCLB) is a widely accepted technique for preventing postoperative tear trough deformity. Its drawbacks include retraction, limited volume, transcutaneous fixation, and a complex insertion technique. The minced lower eyelid fat graft was introduced to overcome these drawbacks.

Objectives

The aim of this study was to compare the outcome of preperiosteal pedicle fat flaps with minced free fat graft in TCLB.

Methods

Participants who underwent the pedicle fat flap procedure from April 2019 to April 2020 (Group A) and the minced free fat graft from May 2020 to May 2021 (Group B) with at least 6 months of follow-up were included. Subjective (pain, infraorbital numbness) and objective (chemosis, residual skin wrinkles, hyperpigmentation, tear trough deformity, bumps) postoperative outcomes, satisfaction (visual analogue scale score) at the last follow-up, and reoperation rates were compared.

Results

There were 142 participants (94% females) with a mean age of 48.4 years (range: 21-71) and a follow-up of 8.2 months (range: 6-36). There were 73 participants in Group A and 69 in Group B, with no significant differences in age (P = .6), sex (P = .7), or follow-up (P = .3). In addition to TCLB, Groups A and B had simultaneous upper eyelid and eyebrow procedures (53% vs 49%, P = .2), lateral canthal plication (77% vs 83%, P = .4), and pinch skin excision (82% vs 88%, P = .3). Groups A and B did not have significant differences in postoperative numbness (6.8% vs 1.4%, P = .2), chemosis (11% vs 10%, P = 1), skin wrinkles (12.3% vs 8.7%, P = .6), hyperpigmentation (1.4% in both groups), bumps (2.7% vs 7.2%, P = .3), tear trough deformity (0.0% in both groups), satisfaction score (97.7% vs 98.1%, P = .4), or reoperation rate (12.3% vs 5.8%, P = .2).

Conclusions

The desired aim of fat redistribution in TCLB seems to be equally achievable with minced fat graft and pedicle fat flap techniques.

Level of Evidence: 4
Stem Profile Patterns ofPinus nigraandPinus sylvestrisGrowing in Mixed Stands
Authors: Özçelik Ramazan , Poudel Krishna P , Crecente-Campo Felipe , Kaya Bora , Alkan Onur
Published: July 2023

Taper equations provide one of the most successful approaches of calculating tree volume to specified top diameters from standing tree measurements. This study assessed the stem profile patterns of Black pine (Pinus nigra Arnold.) and Scots pine (Pinus sylvestris L.) trees growing in mixed stands in northwestern Türkiye using a segmented polynomial taper equation. Models were fitted with the continuous second-order autoregressive structure to correct for the autocorrelation. The models fit the data well, describing more than 99%, 98%, and 97% of variation in diameter, merchantable volume, and total stem volume, respectively. However, the prediction errors were slightly larger for black pine than for Scots pine. Results also revealed that the model coefficients for these species were significantly different. Models developed in this study should provide more accurate upper stem diameter and volume estimates when the objective is to estimate such attributes for black pine and Scots pine growing in the mixed stands.

Study Implications: Estimates of total and merchantable tree volume in a stand are essential for forest management and planning. Taper models are one of the most accurate approaches to estimating upper stem diameters and volume to any merchantability limit. There has been an increasing interest in managing mixed-species stands but limited work has been done on taper equations for trees growing in mixed stands. This study assessed the stem profile patterns of black pine and Scots pine trees growing in mixed-species stands in northwestern Türkiye. As has been reported for pure stands, species-specific taper equations were more accurate upper stem diameter and volume estimations in mixed-species stands. The developed taper models should play an important role in planning and inventorying mixed Black pine and Scots pine stands in Türkiye.
Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers–Danlos syndrome
Authors: Simon Rebecca , Kiener Sarah , Thom Nina , Schäfer Laura , Müller Janina , Schlohsarczyk Elfi K , Gärtner Ulrich , Herden Christiane , Leeb Tosso , Lühken Gesine
Published: July 2023

We investigated 4 European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers–Danlos syndrome, a connective tissue disorder. The kittens were sired by the same tomcat but were born by 3 different mothers. The kittens had easily torn skin resulting in nonhealing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All 4 affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect cosegregation with the autosomal recessive Ehlers–Danlos syndrome phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of Ehlers–Danlos syndrome in humans, mice, dogs, cattle, and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allows to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed Ehlers–Danlos syndrome.
Benefits and Drawbacks of Trait Competitiveness
Authors: Parks Craig D.
Published: July 2023

While evolutionary theory predicts that everyone has some degree of competitive inclination, there is ample evidence that, all else being equal, some people are just simply more highly competitive than others. High competitiveness is colloquially seen as a valuable trait for tasks such as sales, athletic performance, and entrepreneurship, as is low competitiveness for situations which require, or will benefit from, interpersonal or intergroup collaboration. However, the research on trait competitiveness suggests a more complex relationship between one’s level of the trait and actual performance than is often assumed. This chapter will review this research, along with the challenges associated with the measurement of competitiveness, the development of competitiveness in children, and cultural differences in trait competitiveness. The chapter will also examine the contribution of competitive inflexibility to a variety of social challenges.
Notes from the Anatolian underground: two new mole taxa from Eastern Turkey, together with a revised phylogeny of the genus Talpa (Mammalia: Eulipotyphla: Talpidae)
Authors: Gündüz İslam , Demirtaş Sadık , Silsüpür Metin , Özmen Medine , Polly P David , Bilton David T
Published: July 2023

Subterranean life is associated with strong adaptive constraints, leading to the frequent occurrence of morphologically cryptic lineages. This is true of most small mammals, including moles (Eulipotyphla: Talpidae), where a number of species have been recognized recently, particularly following the application of molecular genetics. Here, we use mitochondrial and nuclear DNA sequence data and geometric morphometrics to explore the systematics and evolution of some of the least-known Western Palaearctic moles: the Talpa davidiana group of Eastern Anatolia/Iran. We show that T. davidiana includes four taxa, two of which we describe herein: T. hakkariensissp. nov.,T. davidiana davidiana, T. davidiana tatvanensisssp. nov., and T. streetorumvalid species. For the first time, we apply molecular species delimitation analyses to Talpa, confirming taxonomic hypotheses and suggesting the existence of further morphologically cryptic lineages. These analyses also support the recognition of T. transcaucasica as a valid species distinct from T. levantis. We present a revised phylogeny for Eurasian Talpa and increase the number of known extant taxa to 18, most of which are found in Anatolia, the global hotspot of diversity in this genus. This probably results from the isolation of suitable habitats by a combination of climatic and topographical heterogeneity.
Pleiotrophin ameliorates white matter injury of neonatal rats by activating the mTOR/YY1/Id4 signaling pathway
Authors: Qiu Xia , Zhou Ruixi , Su Xiaojuan , Ying Junjie , Qu Yi , Mu Dezhi
Published: July 2023

Brain white matter injury (WMI) is a serious disease of the central nervous system. Pleiotrophin (PTN) promotes the differentiation and myelination of oligodendrocytes (OLs) in vitro. However, the role of PTN in WMI remains unknown. Therefore, this study aimed to investigate the neuroprotective role and potential mechanisms of PTN function in neonatal rats with WMI. The PTN and mammalian target of rapamycin (mTOR) inhibitor everolimus was used to treat a WMI model in postnatal day 3 Sprague–Dawley rats, in which the right common carotid arteries of these rats were isolated, ligated, and exposed to a hypoxic environment (6% O2 + 94% N2) for 2 h. OL differentiation and myelination, as well as the spatial learning and memory abilities of the rats were evaluated to examine the effects of PTN. Two proteins of the mTOR signaling pathway, YingYang1 (YY1) and inhibitor of DNA binding 4 (Id4), were detected and were used to explore the potential mechanisms of PTN in rat WMI experiment and oxygen glucose deprivation (OGD) model. We found that the differentiation and myelination of OLs were impaired after WMI. PTN administration rescued this injury by activating mTOR/YY1 and inhibiting Id4. Everolimus administration inhibited mTOR/YY1 and activated Id4, which blocked the neuroprotective role of PTN in WMI. PTN plays a neuroprotective role in neonatal rats with WMI, which could be involved in the mTOR/YY1/Id4 signaling pathway.
Unique Immune Blood Markers Between Severe Dengue and Sepsis in Children
Authors: Salgado Doris M. , Rivera Gina M. , Pinto William A. , Rodríguez Jairo , Acosta Gladys , Castañeda Diana M. , Vega Rocío , Perdomo-Celis Federico , Bosch Irene , Narváez Carlos F.
Published: July 2023

Background:

Pediatric dengue and sepsis share clinical and pathophysiologic aspects. Multiple inflammatory and regulatory cytokines, decoy receptors and vascular permeability factors have been implicated in the pathogenesis of both diseases. The differential pattern and dynamic of these soluble factors, and the relationship with clinical severity between pediatric dengue and sepsis could offer new diagnosis and therapeutic strategies.

Methods:

We evaluated the concentration levels of 11 soluble factors with proinflammatory, regulatory and vascular permeability involvement, in plasma from children with dengue or sepsis, both clinically ranging from mild to severe, in the early, late and convalescence phases of the disease.

Results:

During early acute infection, children with sepsis exhibited specific higher concentration levels of IL-6, vascular endothelial growth factor (VEGF), and its soluble decoy receptor II (sVEGFR2) and lower concentration levels of IL-10 and the soluble tumor necrosis factor receptor 2 (sTNFR2), in comparison with children with severe dengue. In addition, the circulating amounts of soluble ST2, and VEGF/sVEGFR2 were widely associated with clinical and laboratory indicators of dengue severity, whereas secondary dengue virus infections were characterized by an enhanced cytokine response, relative to primary infections. In severe forms of dengue, or sepsis, the kinetics and the cytokines response during the late and convalescence phases of the disease also differentiate.

Conclusions:

Dengue virus infection and septic processes in children are characterized by cytokine responses of a specific magnitude, pattern and kinetics, which are implicated in the pathophysiology and clinical outcome of these diseases.
Cutaneous Manifestations of Sexually Transmitted Infections
Authors: Nguyen Yen , Russell Nancy G.
Published: July 2023

Cutaneous manifestations of human immunodeficiency virus (HIV) are commonly seen in clinical practice. Almost every person living with HIV (PLWH) will present with a dermatological complaint at some point during their care. Compared with people living without HIV, PLWHs have a greater likelihood of skin eruptions because of dysregulation of the skin immune system or drug reactions. This article reviews the most common dermatological conditions in PLWHs, as well as how they typically present in clinical practice, and discusses current evidence for treatment.
Design, Implementation, and Usability Evaluation of the Iranian Primary Vitiligo Patient Registry
Authors: Arabkermani Zahra , Sharifian Roxana , Aryanian Zeinab , Bastani Peivand , Esmaeli Nafiseh , Bashiri Azadeh , Sheikhtaheri Abbas
Published: July 2023

Introduction

Vitiligo is an acquired pigmentary disorder, which is usually progressive and irreversible if left untreated. Structured databases such as registries are required to continuously collect standard data about patients with the same disease.

Objectives

This study aimed to design and implement a vitiligo registry and evaluate its usability in Iran.

Methodology

This research was conducted in four stages: determining the minimum data set required for the registry, creating a conceptual model using unified modeling language diagrams and Sparx Enterprise Architect software, implementing the registry in the PhpStorm programming environment, and evaluating the software usability based on the responses of 17 end users to a questionnaire.

Results

The required data items, consisting of 127 items in eight categories, were approved by the experts and used to design the vitiligo registry. Then, the software was designed and implemented. In the assessment stage, the software received a 89.5% approval rate from its users.

Conclusion

Developing a vitiligo registry with high usability as well as making decisions based on the registry data can improve understanding of the disease and facilitate research in this field. As a result, high-quality services could be provided to patients nationwide.
The rare Salmonella enterica serovar Isangi: genomic characterization of the antimicrobial resistance, virulence potential and epidemiology of Brazilian strains in comparison to global isolates
Authors: Vilela Felipe Pinheiro , Rodrigues Dália dos Prazeres , Allard Marc William , Falcão Juliana Pfrimer
Published: July 2023

Introduction.

Salmonella enterica

serovar Isangi (S. Isangi) is a rare non-typhoidal serovar, related to invasive nosocomial infections in various countries and to increasing antimicrobial resistance rates.

Gap statement. Despite existing reports on S. Isangi, there is a lack of information of specific traits regarding this serovar, which could be improved through genomic analyses.

Aim. Our goals were to characterize the antimicrobial resistance, virulence potential and genomic relatedness of 11 S. Isangi strains from Brazil in comparison to 185 genomes of global isolates using whole-genome sequencing (WGS) data.

Methodology. Phenotypic resistance was determined by disc-diffusion. The search for resistance genes, plasmids, prophages,

Salmonella

pathogenicity islands (SPIs) and virulence genes, plus multi-locus sequence typing (MLST) and core-genome MLST (cgMLST) were performed using WGS.

Results. Brazilian S. Isangi strains showed phenotypic resistance to nalidixic acid, ciprofloxacin and streptomycin, and harboured antimicrobial resistance [qnrB19, aac(6’)-Iaa, mdsAB] and heavy metal tolerance (arsD, golST) genes. Col(pHAD28) and IncFII(S) plasmids, virulence genes related to adherence, macrophage induction, magnesium uptake, regulation and type III secretion systems, 12 SPIs and eight prophages were detected. The 185 additional global genomes analysed harboured resistance genes against 11 classes of antimicrobial compounds, 22 types of plasmids, 32 prophages, 14 SPIs, and additional virulence genes related to serum resistance, stress adaptation and toxins. Sequence type (ST)216 was assigned to genomes from Brazil and other countries, while ST335 was the most frequent ST, especially among South African genomes. cgMLST showed that Brazilian genomes were more closely related to genomes from European and African countries, the USA and Taiwan, while the majority of South African genomes were more closely related among each other.

Conclusion. The presence of S. Isangi strains from Brazil and different countries showing a close genomic correlation, antimicrobial resistance profiles to drugs used in human therapy and a large number of virulence determinants reinforced the need for stronger initiatives to monitor rare non-typhoidal

Salmonella

serovars such as S. Isangi in order to prevent its dissemination among human and non-human sources.
Immune boosting bridges leaky and polarized vaccination models
Authors: Park Sang Woo , Li Michael , E. Metcalf C. Jessica , Grenfell Bryan T. , Dushoff Jonathan
Published: July 2023

Two different epidemiological models of vaccination are commonly used in dynamical modeling studies. The leaky vaccination model assumes that all vaccinated individuals experience a reduced force of infection by the same amount. The polarized vaccination model assumes that some fraction of vaccinated individuals are completely protected, while the remaining fraction remains completely susceptible; this seemingly extreme assumption causes the polarized model to always predict lower final epidemic size than the leaky model under the same vaccine efficacy. However, the leaky model also makes an implicit, unrealistic assumption: vaccinated individuals who are exposed to infection but not infected remain just as susceptible as they were prior to exposures (i.e., independent of previous exposures). To resolve the independence assumption, we introduce an immune boosting mechanism, through which vaccinated, yet susceptible, individuals can gain protection without developing a transmissible infection. The boosting model further predicts identical epidemic dynamics as the polarized vaccination model, thereby bridging the differences between two models. We further develop a generalized vaccination model to explore how the assumptions of immunity affect epidemic dynamics and estimates of vaccine effectiveness.

Significance statement

Different assumptions about the long- and medium-term effects of protective vaccination can predict sharply different epidemiological dynamics. However, there has been limited discussion about which assumptions are more realistic and therefore more appropriate for making public health decisions. Here, we show that the differences between the two most common assumptions (the “leaky” and “polarized” vaccination models) are bridged by immune boosting, a mechanism by which individuals who resist infectious challenge due to partial immunity have their immunity increased. We demonstrate that this mechanism has important implications for measuring vaccine effectiveness. Our study challenges fundamental assumptions about commonly used vaccination models and provides a novel framework for understanding the epidemiological impact of vaccination.
Biosensor-Assisted Laboratory Evolution of Malonyl-CoA production inSaccharomyces cerevisiae
Authors: Ferreira Raphael , Hedin Karl Alex , Nielsen Jens , David Florian
Published: July 2023

The production of bio-based chemicals and fuels through microbial engineering offers a promising and sustainable alternative to petroleum-based fuels and chemicals, with the potential for scalability. However, engineering microbes and continuously evolving them to enhance the production of industrially relevant products is a complex and challenging task, requiring precise selection of genetic traits to achieve desired outcomes. In this study, we report the development of a novel counter-selectable growth-sensitive malonyl-CoA platform strain by coupling the malonyl-CoA repressor FapR fromBacillus subtilisto essential gene promoters involved in glucose growth and the plasma membrane arginine permease. This platform strain was then coupled with a CRISPR-dCas9 guide-RNA (gRNA) library, which after multiple rounds of dilutions and library sequencing, resulted in the enrichment for gRNAs that increased fluxes towards malonyl-CoA. The enriched gRNAs were validated for their effects on growth enhancement, gene regulation, and the production of an industrially relevant malonyl-CoA product, namely 3-hydroxypropionic acid. This study highlights an innovative approach to microbial engineering and opens up avenues for further exploration in the field of laboratory continuous evolution.
BIN3rs2280104 T allele is associated with excessive daytime sleepiness and altered network topology in Parkinson’s disease
Authors: Chen Zhichun , Wu Bin , Li Guanglu , Zhou Liche , Zhang Lina , Liu Jun
Published: July 2023

Background

Excessive daytime sleepiness (EDS) is one of the most common non-motor symptoms in Parkinson’s disease (PD). Previous studies showed that PD patients with EDS exhibited more severe motor and non-motor symptoms. Our recent studies revealed thatBIN3rs2280104 was negatively associated with scores of Epworth Sleepiness Scale (ESS) in PD patients. The objective of this study is to examine whetherBIN3rs2280104 shapes brain networks of PD patients and whether network metrics associated withBIN3rs2280104 mediate the effects ofBIN3rs2280104 on EDS.

Methods

PD patients (n = 144) receiving functional magnetic resonance imaging in Parkinson’s Progression Markers Initiative (PPMI) database were investigated. The clinical manifestations and graphical metrics of structural and functional network were compared among different genotype groups ofBIN3rs2280104. The mediation analysis was used to explore the causal associations between network metrics modified byBIN3rs2280104 and EDS of PD patients.

Results

ESS scores were associated with more severe motor and non-motor symptoms.BIN3rs2280104 T allele was negatively associated with ESS scores in PD patients. Additionally,BIN3rs2280104 significantly shaped structural and functional network metrics of PD patients. The nodal Cp of left superior temporal pole in functional network and the degree centrality of left calcarine in structural network were negatively associated with ESS scores, however, only the degree centrality of left calcarine in structural network mediated the effects ofBIN3rs2280104 on EDS of PD patients.

Conclusions

To summarize,BIN3rs2280104 is significantly associated with EDS and network topology of PD patients. Additionally, the degree centrality of left calcarine in structural network mediated the effects ofBIN3rs2280104 on EDS. Future studies were required to identify the molecular mechanisms underlying the effects ofBIN3rs2280104 on EDS and brain network metrics of PD patients.
PolyGR and polyPR knock-in mice reveal a conserved neuroprotective extracellular matrix signature inC9orf72ALS/FTD neurons
Authors: Milioto Carmelo , Carcolé Mireia , Giblin Ashling , Coneys Rachel , Attrebi Olivia , Ahmed Mhoriam , Harris Samuel S. , Lee Byung Il , Yang Mengke , Nirujogi Raja S. , Biggs Daniel , Salomonsson Sally , Zanovello Matteo , Oliveira Paula De , Katona Eszter , Glaria Idoia , Mikheenko Alla , Geary Bethany , Udine Evan , Vaizoglu Deniz , Rademakers Rosa , van Blitterswijk Marka , Devoy Anny , Hong Soyon , Partridge Linda , Fratta Pietro , Alessi Dario R. , Davies Ben , Busche Marc Aurel , Greensmith Linda , Fisher Elizabeth M.C. , Isaacs Adrian M.
Published: July 2023

A GGGGCC repeat expansion inC9orf72is the most common genetic cause of ALS and FTD (C9ALS/FTD). The presence of dipeptide repeat (DPR) proteins, generated by translation of the expanded repeat, is a major pathogenic feature of C9ALS/FTD pathology, but their most relevant effects in a physiological context are not known. Here, we generatedC9orf72DPR knock-in mouse models characterised by physiological expression of 400 codon-optimised polyGR or polyPR repeats, and heterozygousC9orf72reduction. (GR)400 and (PR)400 knock-in mice exhibit cortical neuronal hyperexcitability, age-dependent spinal motor neuron loss and progressive motor dysfunction, showing that they recapitulate key features of C9FTD/ALS. Quantitative proteomics revealed an increase in extracellular matrix (ECM) proteins in (GR)400 and (PR)400 spinal cord, with the collagen COL6A1 the most increased protein. This signature of increased ECM proteins was also present in C9ALS patient iPSC-motor neurons indicating it is a conserved feature of C9ALS/FTD. TGF-β1 was one of the top predicted regulators of this ECM signature and polyGR expression in human iPSC-neurons was sufficient to induce TGF-β1 followed by COL6A1, indicating TGF-β1 is one driver of the ECM signature. Knockdown of the TGF-β1 or COL6A1 orthologue inDrosophiladramatically and specifically exacerbated neurodegeneration in polyGR flies, showing that TGF-β1 and COL6A1 protect against polyGR toxicity. Altogether, our physiologicalC9orf72DPR knock-in mice have revealed a neuroprotective and conserved ECM signature in C9FTD/ALS.
Association between serum LDL‐C concentrations and risk of diabetes: A prospective cohort study
Authors: Huang Jiaojiao , Lin Hong , Wang Shuangyuan , Li Mian , Wang Tiange , Zhao Zhiyun , Xu Yu , Xu Min , Lu Jieli , Chen Yuhong , Ning Guang , Wang Weiqing , Bi Yufang , Wang Long
Published: July 2023

Background

Low‐density lipoprotein cholesterol (LDL‐C) and diabetes mellitus are both modifiable risk factors for cardiovascular disease; however, whether elevated LDL‐C levels confer a risk for diabetes remains unclear.

Objective

We aimed to examine the association between serum LDL‐C concentrations at baseline and the risk of developing diabetes at follow‐up in the general population of Chinese adults.

Methods

This study included 5274 adults aged ≥ 40 years from a community cohort who were without diabetes and followed for a median of 4.4 years. A standard 75‐g oral glucose tolerance test was conducted at baseline and follow‐up visits to diagnose diabetes. Logistic regression models and a restricted cubic spline were used to examine the association between baseline serum LDL‐C levels and the risk of diabetes development. Subgroup analyses were conducted stratifying on age, sex, body mass index, hypertension, family history of diabetes, and LDL‐C levels.

Results

A total of 652 participants (12%) developed diabetes during the follow‐up period. Compared to quartile 1 of serum LDL‐C, quartiles 2, 3, and 4 were associated with a 30%, 33%, and 30% significantly higher risk of diabetes, respectively after adjustment for confounders including homeostatic model assessment for insulin resistance. The linear relationship between baseline LDL‐C down to 30.1 mg/dL and incident diabetes was demonstrated by restricted cubic spline analysis, and each 1‐SD increase in LDL‐C concentration (28.5 mg/dL) was associated with a 12% increase in the risk of diabetes (odds ratio 1.12, 95% confidence interval 1.03–1.22).

Conclusion

In this community‐based general population, higher serum LDL‐C levels were linearly associated with an elevated risk of incident diabetes.
Association between daily aspirin therapy and risk of hepatocellular carcinoma according to metabolic risk factor burden in non‐cirrhotic patients with chronic hepatitis B
Authors: Lee Cheol‐Hyung , Lee Yun Bin , Moon Hyemi , Chung Jong‐Won , Cho Eun Ju , Lee Jeong‐Hoon , Yu Su Jong , Kim Yoon Jun , Lee Juneyoung , Yoon Jung‐Hwan
Published: July 2023

Background

Several studies have demonstrated chemopreventive effects of aspirin against hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).

Aims

To investigate the associations of aspirin use with risks of HCC, liver‐related mortality, and major bleeding according to metabolic risk factor burden among non‐cirrhotic patients with CHB

Methods

Using the Korean National Health Insurance Service database, we identified 282,611 non‐cirrhotic adults with CHB. Data on obesity, diabetes, high blood pressure, and hypercholesterolemia were collected. Subjects were stratified into lower and higher metabolic risk groups (≤2 and ≥3 risk factors, respectively). Propensity score‐matched cohorts of aspirin users and non‐users were generated. Risks of HCC, liver‐related death and major bleeding were analyzed.

Results

During the median follow‐up of 7.4 years, positive associations between metabolic risk factor burden and outcomes were verified (all ptrend < 0.001). In the lower metabolic risk group (13,104 pairs), the association between aspirin use and HCC risk was not significant after multivariable adjustment (adjusted subdistribution hazard ratio [aSHR]: 0.93; 95% CI: 0.84–1.03); however, aspirin use was associated with elevated major bleeding risk (aSHR: 1.22; 95% CI: 1.08–1.39). In the higher metabolic risk group (2984 pairs), aspirin use was associated with reduced risks of HCC (aSHR: 0.72; 95% CI: 0.57–0.91) and liver‐related mortality (aSHR: 0.69; 95% CI: 0.50–0.96) without an increase in risk of major bleeding (aSHR: 1.02; 95% CI: 0.79–1.32).

Conclusions

Aspirin therapy was associated with reduced risks of HCC and liver‐related death without excess risk of major bleeding, in non‐cirrhotic patients with CHB who had a higher metabolic risk factor burden.
Current situation of allergological health care at German hospitals
Authors: Hollstein Moritz Maximilian , Schober Anna , Treudler Regina , Becker Sven , Epping Jelena , Hamelmann Eckard , Taube Christian , Wagenmann Martin , Wedi Bettina , Worm Margitta , Zink Alexander , Buhl Timo , Werfel Thomas , Traidl Stephan
Published: July 2023

Background

Allergic medical care in Germany is organized on an interdisciplinary basis. An overview of the current care situation is necessary to manage and improve interdisciplinary cooperation.

Methods

Between January and February 2022, questionnaires were sent online and by mail to chief physicians of inpatient clinical departments to which most allergological diseases are assigned (dermatology, otorhinolaryngology [ENT], pulmonology, pediatrics, environmental/occupational medicine, gastroenterology; n = 899).

Results

The response rate was 52.1%. Allergology departments of dermatology, ENT and pulmonology were predominantly located in metropolitan areas (> 100,000 inhabitants), whereas responses of pediatric departments were mostly from smaller towns. 76.8% of the respondents reported existing interdisciplinary treatment plans with other specialties. Pediatric and pulmonology clinics stated disproportionately few interdisciplinary treatment concepts with dermatology and ENT clinics, especially in smaller cities with < 100,000 inhabitants. Diagnosis and therapy of allergic rhinitis were performed in particular by the departments of ENT, asthma mainly by the pulmonology departments. Care of other allergological diseases was most frequently reported by chief physicians of dermatology and pediatrics.

Conclusions

In metropolitan areas, participating departments provide allergology care in a cooperative manner. A large spectrum of care is covered in cooperation with dermatological clinics. In more rural areas, cooperation is rarer; here, mainly pediatric departments provide allergological care, which may explain the more limited range of services compared to metropolitan areas.
(Asymmetric) tariff‐driven foreign direct investment: Evidence from Korean firm‐level data
Authors: Pyun Ju Hyun
Published: July 2023

This study examines the effects of identified industry tariff shocks on firms' outward foreign direct investment (FDI) into their destinations. Using rich Korean firm‐level data for 2010–18, the study decomposes FDI outflows from multinational enterprises (MNEs) into the number of subsidiaries (extensive margin) and average FDI for individual subsidiaries (intensive margin) in the destination. New evidence of tariff‐driven FDI reveals that the tariff decrease shocks (TDS) (significant tariff decreases) lower the number of existing subsidiaries rather than the average FDI volume for the existing subsidiaries. In addition, more productive firms investing in developing countries lower the number of existing subsidiaries to a greater extent in response to TDS, implying that productive MNEs reallocate resources into selective core subsidiaries when a significant tariff decrease occurs.
PAR recognition by PARP1 regulates DNA‐dependent activities and independently stimulates catalytic activity of PARP1
Authors: Deeksha Waghela , Abhishek Suman , Rajakumara Eerappa
Published: July 2023

Poly(ADP‐ribosyl)ation is predominantly catalyzed by Poly(ADP‐ribose) polymerase 1 (PARP1) in response to DNA damage, mediating the DNA repair process to maintain genomic integrity. Single‐strand (SSB) and double‐strand (DSB) DNA breaks are bona fide stimulators of PARP1 activity. However, PAR‐mediated PARP1 regulation remains unexplored. Here, we report ZnF3, BRCT, and WGR, hitherto uncharacterized, as PAR reader domains of PARP1. Surprisingly, these domains recognize PARylated protein with a higher affinity compared with PAR but bind with weak or no affinity to DNA breaks as standalone domains. Conversely, ZnF1 and ZnF2 of PARP1 recognize DNA breaks but bind weakly to PAR. In addition, PAR reader domains, together, exhibit a synergy to recognize PAR or PARylated protein. Further competition‐binding studies suggest that PAR binding releases DNA from PARP1, and the WGR domain facilitates DNA release. Unexpectedly, PAR showed catalytic stimulation of PARP1 but hampered the DNA‐dependent stimulation. Altogether, our work discovers dedicated high‐affinity PAR reader domains of PARP1 and uncovers a novel mechanism of allosteric regulation of DNA‐dependent and DNA‐independent activities of PARP1 by its catalytic product PAR.