bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treating metabolic dysfunction‐associated steatohepatitis: The fat‐trimming FGF21 approach
Authors: Li Xiaokun , Rao Zhiheng , Hu Wenhao , Lu Weiqin , Luo Yongde 
Published: November 2024

SummaryMetabolic dysfunction‐associated steatohepatitis (MASH) is a condition characterized by hepatosteatosis, inflammation, and tissue damage, with steatosis as the initial stage, which involves chronic, excess deposition of lipids in hepatic lipid droplets. Despite the growing prevalence and serious risks it poses, including liver decompensation, the need for transplantation, and increased patient mortality, MASH currently faces no approved pharmacotherapy. Several promising treatment candidates have emerged from recent clinical trials, including analogs of FGF21 and agonists of the associated FGFR1‐KLB complex. These agents were well‐tolerated in trials and have demonstrated significant improvements in both histological and biochemical markers of liver fat content, inflammation, injury, and fibrosis in patients with MASH. Endocrine FGF21 plays a vital role in maintaining homeostasis of lipid, glucose, and energy metabolism. It achieves this through pathways that target lipids or lipid droplets in adipocytes and hepatocytes. Mechanistically, pharmacological FGF21 acts as a potent catabolic factor to promote lipid or lipid droplet lipolysis, fatty acid oxidation, mitochondrial catabolic flux, and heat‐dissipating energy expenditure, leading to effective clearance of hepatic and systemic gluco‐lipotoxicity and inflammatory stress, thereby preventing obesity, diabetes, and MASH pathologies. In this review, we aim to provide an update on the outcomes of clinical trials for several FGF21 mimetics. We compare these outcomes with preclinical studies and offer a lipid‐centric perspective on the mechanisms underlying the clinical benefits of these agents for MASH.
Genetic improvement of eating and cooking quality of rice cultivars in southern China
Authors: Cai Yue , Chen Zichun , Liu Jianju , Yu Ling , Wang Zhiping , Zhu Shuhao , Shi Wei , Pan Cunhong , Wu Yunyu , Li Yuhong , Ji Hongjuan , Huang Niansheng , Zhang Xiaoxiang , Gao Peng , Xiao Ning , Zuo Shimin , Li Aihong 
Published: November 2024

SummaryThe genetic improvement of rice eating and cooking quality (ECQ) is an important goal in rice breeding. It is important to understand the genetic regulation of ECQ at the genomic level for effective breeding to improve ECQ. However, the mechanisms underlying the improvement of ECQ of indica and japonica cultivars in southern China remain unclear. In this study, 290 rice cultivars (155 indica and 135 japonica cultivars) bred in southern China in the past 30 years were collected. Physicochemical indicators, namely, apparent amylose content (AAC), protein content (PC), lipid content and taste value, were measured and correlation analysis was performed. A decrease in AAC and PC was a crucial factor for the ECQ improvement of the rice cultivars in southern China. Genome‐wide association analysis and selective domestication analysis preliminarily clarified that the comprehensive utilization of major and minor genes was an important genetic basis for improvement of ECQ. An elite allele, RAmy1AA, with potential application in breeding to improve starch viscosity characteristics and ECQ, was mined. The Wxb/OsmtSSB1LT/OsDML4G/RPBFT/Du3T and Wxb/OsEro1T/Glup3G/OsNAC25G/OsBEIIbC/RAmy1AA/FLO12A gene modules, neither of which have been widely used, are proposed as the optimal allele combinations for ECQ improvement of indica and japonica cultivars in southern China. The results clarify the genetic regulation of rice ECQ improvement in southern China and provide novel genetic resources and breeding strategies for ECQ improvement in rice.
Linear Psoriasis in a Pediatric Patient Successfully Treated With Ixekizumab
Authors: Walterscheid Brooke , Martinez Nandi , Tarbox Michelle 
Published: November 2024

ABSTRACTLinear psoriasis is a rare clinical presentation of psoriasis characterized by erythematous scaly plaques distributed along Blaschko's lines. We describe an 8‐year‐old male with a linear Blaschkoid plaque in which biopsy findings and clinical history were consistent with linear psoriasis. The lesion showed only mild improvement with topical steroid therapy but exhibited significant clearance with the biologic agent ixekizumab, an IL‐17A inhibitor. With limited supporting literature regarding management, this case report illustrates the clinical manifestation, diagnosis, and an effective management strategy for linear psoriasis in a pediatric patient.
Four Diaporthe species associated with grapevine nursery plants and commercial vineyards in Uruguay
Authors: Carbone María Julia , Reyna Rossana , Moreira Victoria , González‐Barrios Pablo , Mondino Pedro , Alaniz Sandra 
Published: November 2024

AbstractDiaporthe species cause Diaporthe dieback (DD) in many grape‐growing countries causing general vine decline, shoot dieback and dead spurs, with perennial cankers and internal trunk necrosis. These pathogens are also the causal agents of Phomopsis cane and leaf spot, a common foliar disease affecting grapevine around the world. In this study, we specifically investigated DD affecting nursery vines and commercial vineyards in Uruguay. A collection of 59 Diaporthe isolates obtained from symptomatic and asymptomatic wood samples of commercial grapevines (nine cultivars) and nursery vines (including cuttings of four scion cultivars and two rootstocks, and six scion–rootstock combinations of grafted plants), was characterized based on DNA phylogenetic analysis, phenotypical characteristics and pathogenicity tests. Diaporthe ampelina was the most frequent species (86%), followed by D. foeniculina (9%), D. eres (3%) and D. terebinthifolii (2%). All species were isolated from nursery material, but D. ampelina was the only one found in field vines. The pathogenicity of all species was confirmed, with D. ampelina being the most virulent, causing the longest necrotic lesions on both green shoots and lignified canes. Further studies are needed to comprehend the epidemiology of DD and to better understand its relationship with Phomopsis cane and leaf spot in order to design a management programme to prevent the disease development.
Weakly Compressible Approximation of the Taylor–Green Vortex Solution
Authors: Antuono Matteo , Marrone Salvatore 
Published: November 2024

ABSTRACTThe Taylor–Green vortex represents an exact solution of the Navier–Stokes equations in . In this work, an approximation of this solution in two spatial dimensions is proposed for weakly compressible flows. These flows are characterized by small compressibility (or, equivalently, by a small Mach number) and are often employed in computational fluid dynamics to approximate the behaviour of incompressible Newtonian fluids. In this framework, the proposed solution is expected to be a useful benchmark for numerical solvers that implement the weakly compressibility approximation. To this end, some numerical examples are reported in the final section of this work.
Effect of Collagen Fiber Tortuosity Distribution on the Mechanical Response of Arterial Tissues
Authors: Agrawal Yamnesh , Fortunato Ronald N. , Asadbeygi Alireza , Hill Michael R. , Robertson Anne M. , Maiti Spandan 
Published: November 2024

Abstract
This study investigated the effect of collagen fiber tortuosity distribution on the biomechanical failure and prefailure properties of arterial wall tissue. An in-silico model of the arterial wall was developed using data obtained from combined multiphoton microscopy imaging and uni-axial tensile testing. Layer-dependent properties were prescribed for collagen, elastin, and ground substance. Collagen fibers were modeled as discrete anisotropic elements, while elastin and ground substance were modeled as homogeneous isotropic components. Our parametric analysis, using a finite element approach, revealed that different parameters of collagen fibers tortuosity distribution significantly influence both prefailure and failure biomechanical properties. Increased fiber tortuosity improved the tissue strength whereas the dispersion in the tortuosity distribution reduced it. This study provides novel insights into the structural-mechanical interdependencies in arterial walls, offering potential targets for clinical assessments and therapeutic interventions aimed at mitigating rupture risks.
ChIP-seq and structural analyses delineating the regulatory mechanism of master regulator EsrB in
Edwardsiella piscicida
Authors: Zhang Boya , Zhang Yi , Liu Jingjing , Reverter David , Wang Qiyao , Choi Sang Ho , Liu Bing , Shao Shuai 
Published: November 2024

ABSTRACT

As a response regulator of the EsrA-EsrB two-component system, EsrB is conserved in
Hafniaceae
and plays a crucial role in virulence and pathogenicity. EsrB possesses DNA binding abilities, enabling it to regulate the transcription of virulence genes to confront different stresses and achieve systematic infections. Here, ChIP-seq analysis of EsrB in Dulbecco’s Modified Eagle’s Medium (DMEM) (mimicking
in vivo
environments) revealed that EsrB preferred to bind to virulence-associated promoters with a distinct 7'-4-7'' pseudopalindromic DNA motif and interact with metabolic-related promoters with a high AT DNA motif. The crystal structure of the C-terminal of EsrB (EsrB
C
) was solved at 2.20-Å resolution. Specifically, Lys
181
enabled the DNA-binding affinity of EsrB and promoted the
in vitro
and
in vivo
pathogenicity of
Edwardsiella piscicida
. Moreover, EsrB directly regulated the expression of genes associated with basal metabolism, including iron and tricarboxylic acid (TCA) cycles. Furthermore, EsrB enhanced iron transport capability and the enzyme activity of succinate dehydrogenase and pyruvate dehydrogenase in DMEM. Collectively, our structural and ChIP-seq analysis provides valuable insights into the DNA binding mechanism of EsrB which will facilitate our understanding of EsrB coordinating virulence and basal metabolism gene expression.

IMPORTANCE

As a crucial virulence regulator, EsrB possesses a LuxR-like superfamily domain at the C-terminal, which is conserved within the canonical NarL family regulators. Due to its critically important role in virulence and pathogenicity in fish hosts, the DNA binding ability has been believed to allow EsrB to regulate genes associated with the invasion process of host cells and basal metabolism in response to environmental stimuli. The lack of EsrB’s crystal structure has been a major obstacle in understanding the molecular mechanisms of EsrB-DNA interaction which choreographs EsrB-mediated pathogenic behavior. Here, we conducted ChIP-seq and solved the crystal structure of the C-terminal of EsrB (EsrBC) at 2.20-Å resolution, which revealed that EsrB preferred to bind to virulence-associated promoters with a distinct 7'-4-7' pseudopalindromic DNA motif and interacted with metabolic-related promoters with a high AT DNA motif in Dulbecco’s Modified Eagle’s Medium (DMEM) (mimicking
in vivo
environments). Our results facilitate a detailed understanding of EsrB’s regulatory role in
Edwardsiella piscicida
pathogenesis and expand our knowledge of virulence regulators in the family
Hafniaceae
.
Putative evolution of
Myxococcus fulvus
124B02 plasmid pMF1 from a chromosomal segment in another
Myxococcus
species
Authors: Jain Shruti , Sharma Gaurav 
Published: November 2024

ABSTRACT

Myxobacteria or order Myxococcales (old nomenclature) or phylum Myxococcota (new terminology) are fascinating organisms well known for their diverse peculiar physiological, taxonomic, and genomic properties. Researchers have long sought to identify plasmids within these organisms, yet thus far, only two organisms from different families have been found to harbor a plasmid. This study delves into the putative evolution of one of these plasmids, i.e., pMF1 present in
Myxococcus fulvus
124B02 in the suborder Cystobacterineae and family Myxococcaceae. Here, we first reannotated the pMF1 plasmid genome sequence and identified two additional open reading frames or putative genes which were not annotated until now. We further reported that all pMF1 plasmid genes depict homology with
Myxococcus stipitatus
CYD1 draft genome (contig 28) and a chromosomal segment of
M. stipitatus
DSM14675 in a syntenic manner, implying the presence of plasmid-like structure in
M. stipitatus
CYD1, integrated into its chromosome. To comprehend the relationship among these three species, we conducted phylogenetic analyses using 16S and concatenated housekeeping genes and genome-to-genome distance calculator (GGDC) analysis, which confirmed that
M. stipitatus
CYD1 is a distinct and novel species within the genus
Myxococcus
. Overall, this comparative genomic study sheds light on the putative emergence of the pMF1 plasmid from a common ancestor of closely related yet distinct species,
M. stipitatus
CYD1, possibly through the partition from its chromosome as a segment.

IMPORTANCE

Myxobacteria are not well known to have plasmids. Until now, only two organisms have been shown to have plasmids, raising a pertinent question about how these plasmids evolved randomly within the phylum Myxococcota. The study presented in this manuscript delves into the emergence of the pMF1 plasmid found in
Myxococcus fulvus
124B02, a member of the suborder Cystobacterineae and family Myxococcaceae. Our research addresses this intriguing topic of plasmid identification and evolution within myxobacteria, which are a group of fascinating organisms that have garnered significant interest due to their diverse physiological, taxonomic, and genomic properties.
Antimicrobial susceptibility testing of
Dermabacter hominis
Authors: Kintzinger Tim , Knaack Dennis , Schubert Sören , Groß Uwe , Köck Robin , Schaumburg Frieder 
Published: November 2024

ABSTRACT

Dermabacter hominis,
a short gram-positive rod, is a part of the human skin flora, but can also cause infections (e.g., skin and soft tissue infections, bone and joint infections, abscesses, peritoneal dialysis-associated peritonitis, and bacteremia). Only limited data are available for antimicrobial resistance rates. Although CLSI does include coryneform genera in
Corynebacterium
spp. clinical breakpoints, they point out that only limited data are available on resistance rates. The aim of this study was to assess the minimal inhibitory concentration (MIC) of clinical isolates of
D. hominis
and to deduce breakpoints for disk diffusion.
D. hominis
(n = 30) from five laboratories in Germany were tested by broth microdilution and disk diffusion method. MICs were interpreted according to current clinical breakpoints for
Corynebacterium
spp. or pharmacokinetic–pharmacodynamic breakpoints (EUCAST). To deduce breakpoints for disk diffusion, MICs were correlated with inhibition zone diameters. All isolates were susceptible to vancomycin, rifampicin, and linezolid (100%,
n
= 30/30). Lower susceptibility rates were found for ampicillin (83%,
n
= 25/30) followed by ceftriaxone (37%,
n
= 11/30) and clindamycin (27%,
n
= 8/30). All isolates were resistant to benzylpenicillin and daptomycin. Good correlations between disk diffusion and MIC (suggested breakpoints for susceptibility in brackets) were found for ampicillin (S ≥ 10 mm), ceftriaxone (S ≥ 24 mm), clindamycin (S ≥ 19 mm), levofloxacin (I ≥ 24 mm), linezolid (S ≥ 29 mm), rifampicin (S ≥ 38 mm), and vancomycin (S ≥ 21 mm). Due to limited variances in both MIC values and inhibition zone diameters, no disk diffusion breakpoint could be deduced for gentamicin and benzylpenicillin in our dataset.
D. hominis
has favorable susceptibility rates for vancomycin, rifampicin, and linezolid and shows correlations between MIC and disk diffusion diameter for selected antimicrobial agents. Thus, the development of clinical breakpoints for disk diffusion appears feasible.

IMPORTANCE

Dermabacter hominis
can cause infections in humans (e.g., skin and soft tissue infections, bone and joint infections, abscesses, peritoneal dialysis-associated peritonitis, and bacteremia). Currently, only limited data are available regarding the resistance rates of this specific pathogen. Data for the easy accessible disk diffusion method are missing. We were able to provide additional data on resistance rates of clinical
D. hominis
isolates to common antimicrobial agents and correlate these with disk diffusion diameters to derive breakpoints to further improve the antimicrobial susceptibility testing for this specific pathogen. In addition to that, we created a current overview of resistance rates from the existing literature. Our data provide deeper insight into resistance rates and antimicrobial susceptibility testing of this specific pathogen.
Physical activity and life expectancy: a life-table analysis
Authors: Veerman Lennert , Tarp Jakob , Wijaya Ruth , Wanjau Mary Njeri , Möller Holger , Haigh Fiona , Lucas Peta , Milat Andrew 
Published: November 2024

ObjectiveLow physical activity (PA) levels are associated with increased mortality. Improved measurement has resulted in stronger proven associations between PA and mortality, but this has not yet translated to improved estimates of the disease burden attributable to low PA. This study estimated how much low PA reduces life expectancy, and how much life expectancy could be improved by increasing PA levels for both populations and individuals.MethodsWe applied a predictive model based on device-measured PA risk estimates and a life-table model analysis, using a life-table of the 2019 US population based on 2017 mortality data from the National Centre for Health Statistics. The participants included were 40+ years with PA levels based on data from the 2003–2006 National Health and Nutritional Examination Survey. The main outcome was life expectancy based on PA levels.ResultsIf all individuals were as active as the top 25% of the population, Americans over the age of 40 could live an extra 5.3 years (95% uncertainty interval 3.7 to 6.8 years) on average. The greatest gain in lifetime per hour of walking was seen for individuals in the lowest activity quartile where an additional hour’s walk could add 376.3 min (~6.3 hours) of life expectancy (95% uncertainty interval 321.5 to 428.5 min).ConclusionHigher PA levels provide a substantial increase in population life expectancy. Increased investment in PA promotion and creating PA promoting living environments can promote healthy longevity.
Treatment of intracranial hypertension secondary to superior sagittal sinus stenosis from invasive meningioma
Authors: Baker Amanda , Vaishnav Dhrumil , Essibayi Muhammed Amir , Khatri Deepak , Altschul David J 
Published: November 2024

Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure without a clear cause, often linked to cerebral venous sinus constriction from embryological or acquired factors. Although less common, brain tumors like parasagittal meningiomas can compress the superior sagittal sinus, leading to IIH. Venous stenting has become a minimally invasive and effective intervention for managing IIH caused by superior sagittal sinus stenosis, particularly when residual meningiomas continue to exert pressure on the sinus.1–6Video 1 presents a step-by-step technique for deploying dual Onyx cardiac stents to treat stenosis in the superior sagittal sinus, which is complemented by middle meningeal artery embolization. This helps to reduce the vascular supply to the remaining meningioma tissue. This combined approach not only provides immediate relief from IIH symptoms but also minimizes surgical risks, such as venous infarction and excessive blood loss. It serves as a valuable adjunct in cases where complete surgical tumor removal is challenging.Video 1- Techinical video of a case of superior sagittal sinus stenosis from an invasive meningioma causing intracranial hypertension successfully treated with a coronary balloon mounted stent.­
Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals
Authors: Sukhonpanich Nontapat , Koohi Fatemeh , Jolly Amy A , Markus Hugh S 
Published: November 2024

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype is becoming milder with better risk factor treatments and other care improvements is unknown. In a large longitudinal CADASIL cohort, we determined whether the prognosis has changed over 23 years.MethodsPatients were identified from the Cambridge CADASIL register and the UK Familial stroke study. Change in age at stroke over the time of recruitment was determined using linear mixed-effects model, and the impact of genetic and vascular risk factors on stroke and dementia risk was further evaluated using Cox proportional hazard regression.ResultsA total of 555 patients with CADASIL were recruited between 2001 and 2023. The age of stroke onset significantly increased over time (p<0.001), with the mean age of stroke onset for patients recruited before 2016 (n=265) at 46.7±9.2 years and 51.6±9.5 years for those recruited since 2016 (n=290). Patients recruited since 2016 had lower risks of both stroke (HR 0.36, 95% CI 0.26 to 0.50, p<0.001) and dementia (HR 0.43, 95% CI 0.19 to 0.99, p=0.046) after adjusting for sex, hypertension history, smoking status, epidermal growth factor-like repeat position and calendar effect.ConclusionsThe clinical phenotype of CADASIL is improving. While this may be partly explained by reduced vascular risk factors such as smoking and the identification of milder cases, differences persisted after controlling for risk factors and mutation sites. These updated risk estimates should be used when counselling patients with CADASIL on prognosis.
Optical performance enhancement of solar flux distribution uniformity of solar parabolic dish cavity system
Authors: Khan Shehzaib Yousuf , Uzair Muhammad 
Published: November 2024

The design of the cavity receiver plays a crucial role in the conversion from solar to thermal energy that is absorbed in the cavity receiver to the heat transfer fluid. Nonuniform heat flux at the surface of cavities generates structural failure due to thermal unbalance. This research focuses on the optimization of cavity design based on position, aperture diameter, and eccentricities of elliptical-shaped cavity to enhance the uniformity of solar flux distribution on the cavity walls. The optical analysis is performed using Monte Carlo ray tracing using COMSOL Multiphysics on conical, cylindrical, rectangular, spherical, and elliptical shapes to determine the solar heat flux distribution. The validation of the computational model is performed through published experimental and analytical data. The flux distribution is more dispersed in spherical and elliptical-shaped cavities when positioned above the focal plane. The flux distribution uniformity increases when the cavities are positioned at a higher distance from the focal plane whereas the larger aperture opening eases the absorption of radiation flux on the surface. Partial obstruction of incoming rays starts to occur when positioning the cavity at a higher distance as well as in smaller aperture openings. The optimum configuration of the elliptical cavity is with 30% eccentricity, 100 mm above the focal plane, and 250 mm opening, providing a solar flux distribution uniformity factor of 0.585.