bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination treatment of a novel CXCR3 antagonist ACT-777991 with an anti-CD3 antibody synergistically increases persistent remission in experimental models of type 1 diabetes
Authors: Christen Urs , Pouzol Laetitia , Tunis Mélanie , Sassi Anna , Tondello Camilla , Bayer Monika , Hintermann Edith , Strasser Daniel S , Schuldes Sabrina , Mentzel Ulrich , Martinic Marianne M 
Published: July 2023

Abstract
Treatment of patients with recent-onset type 1 diabetes with an anti-CD3 antibody leads to the transient stabilization of C-peptide levels in responder patients. Partial efficacy may be explained by the entry of islet-reactive T-cells spared by and/or regenerated after the anti-CD3 therapy. The CXCR3/CXCL10 axis has been proposed as a key player in the infiltration of autoreactive T cells into the pancreatic islets followed by the destruction of β cells. Combining the blockade of this axis using ACT-777991, a novel small-molecule CXCR3 antagonist, with anti-CD3 treatment may prevent further infiltration and β-cell damage and thus, preserve insulin production.
The effect of anti-CD3 treatment on circulating T-cell subsets, including CXCR3 expression, in mice was evaluated by flow cytometry. Anti-CD3/ACT-777991 combination treatment was assessed in the virally induced RIP-LCMV-GP and NOD diabetes mouse models. Treatments started at disease onset. The effects on remission rate, blood glucose concentrations, insulitis, and plasma C-peptide were evaluated for the combination treatment and the respective monotherapies.
Anti-CD3 treatment induced transient lymphopenia but spared circulating CXCR3+ T cells. Combination therapy in both mouse models synergistically and persistently reduced blood glucose concentrations, resulting in increased disease remission rates compared to each monotherapy. At the study end, mice in disease remission demonstrated reduced insulitis and detectable plasma C-peptide levels. When treatments were initiated in non-severely hyperglycemic NOD mice at diabetes onset, the combination treatment led to persistent disease remission in all mice.
These results provide preclinical validation and rationale to investigate the combination of ACT-777991 with anti-CD3 for the treatment of patients with recent-onset diabetes.
The prognostic impact of tumor length on pathological stage IA-IC esophageal adenocarcinoma
Authors: Yan Sen , Liu Xianben , Xing Wenqun , Jiang Duo , Feng Shao-Kang , Chang Andrew C , Sun Hai-Bo 
Published: July 2023

Abstract
This study was completed to evaluate the relationship between tumor length and the prognosis of patients with pathological stage IA-IC esophageal adenocarcinoma (EAC). Patients were identified from the Surveillance, Epidemiology, and End Results Program database (United States, 2006–2015). X-tile software and ROC analysis were mainly used to explore the best threshold of tumor length for dividing patients into different groups, and then propensity score matching (PSM) was used to balance other variables between groups. The primary outcome assessed was overall survival (OS). A total of 762 patients were identified, and 500 patients were left after PSM. Twenty millimeters were used as the threshold of tumor length. Patients with longer tumor lengths showed worse OS (median: 93 vs. 128 months; P = 0.006). Multivariable Cox regression analysis showed that longer tumor length was an independent risk factor (hazard ratio 1.512, 95% confidence interval, 1.158–1.974, P = 0.002). Tumor length has an impact on patients with pathological stage IA-IC EAC who undergo surgery alone. The prognostic value of the pathological stage group may be improved after combining it with tumor length and age.
The molding of intraspecific trait variation by selection under ecological inheritance
Authors: Prigent Iris , Mullon Charles 
Published: July 2023

Abstract
Organisms continuously modify their environment, often impacting the fitness of future conspecifics due to ecological inheritance. When this inheritance is biased toward kin, selection favors modifications that increase the fitness of downstream individuals. How such selection shapes trait variation within populations remains poorly understood. Using mathematical modelling, we investigate the coevolution of multiple traits in a group-structured population when these traits affect the group environment, which is then bequeathed to future generations. We examine when such coevolution favors polymorphism as well as the resulting associations among traits. We find in particular that two traits become associated when one trait affects the environment while the other influences the likelihood that future kin experience this environment. To illustrate this, we model the coevolution of (a) the attack rate on a local renewable resource, which deteriorates environmental conditions, with (b) dispersal between groups, which reduces the likelihood that kin suffers from such deterioration. We show this often leads to the emergence of two highly differentiated morphs: one that readily disperses and depletes local resources, and another that maintains these resources and tends to remain philopatric. More broadly, we suggest that ecological inheritance can contribute to phenotypic diversity and lead to complex polymorphism.
In search of the Goldilocks zone for hybrid speciation II: hard times for hybrid speciation?
Authors: Blanckaert Alexandre , Sriram Vedanth , Bank Claudia 
Published: July 2023

Abstract
Hybridization opens a unique window for observing speciation mechanisms and is a potential engine of speciation. One controversially discussed outcome of hybridization is homoploid hybrid speciation by reciprocal sorting, where a hybrid population maintains a mixed combination of the parental genetic incompatibilities, preventing further gene exchange between the newly formed population and the two parental sources. Previous work showed that, for specific linkage architectures (i.e., the genomic location and order of hybrid incompatibilities), reciprocal sorting could reliably result in hybrid speciation. Yet, the sorting of incompatibilities creates a risk of population extinction. To understand how the demographic consequences of the purging of incompatibilities interact with the formation of a hybrid species, we model an isolated hybrid population resulting from a single admixture event. We study how population size, linkage architecture, and the strength of the incompatibility affect survival of the hybrid population, resolution/purging of the genetic incompatibilities and the probability of observing hybrid speciation. We demonstrate that the extinction risk is highest for intermediately strong hybrid incompatibilities. In addition, the linkage architecture displaying the highest hybrid speciation probabilities changes drastically with population size. Overall, this indicates that population dynamics can strongly affect the outcome of hybridization and the hybrid speciation probability.
CRISPR-Cas9 engineering in the hybrid yeast Zygosaccharomyces parabailii can lead to loss of heterozygosity in target chromosomes
Authors: Jayaprakash Pooja , Barroso Liliane , Vajente Matteo , Maestroni Letizia , Louis Edward J , Morrissey John P , Branduardi Paola 
Published: July 2023

Abstract
The hybrid yeast Zygosaccharomyces parabailii holds potential as a cell factory mainly because of its robustness in withstanding stressors that often characterize bio-based processes. However, a complex genome and a lack of gene editing tools hinder the capacity to engineer this yeast. In this work, we developed a CRISPR-Cas9 gene editing system for Z. parabailii that allows simultaneous disruption or deletion of both alleles of a gene. We evaluated four different gRNA expression systems consisting of combinations of tRNAs, tRNA and ribozyme or ribozymes as self-cleaving flanking elements and established that the most efficient systems used an RNA Pol II promoter followed by a 5’tRNA flanking the gRNA. This gRNA system was then used to construct a strain of Z. parabailii in which both alleles of DNL4 were inactivated and so relied on homologous recombination to repair double-stranded breaks. Our system can be used for gene inactivation in a wild-type strain and precise deletion with marker insertion in a dnl4 mutant. In some cases, we observed inter-chromosomal recombination around the site of the DSB that could cause loss of heterozygosity through gene conversion or deletion. Although an additional aspect that needs to be monitored during strain engineering, this phenomenon also offers opportunities to explore genome plasticity in hybrid yeasts.
Joint Gramian inversion of gravity, magnetic and gravity gradient tensor data for the modelling of Mesoproterozoic iron oxide deposits, southeast Missouri, USA
Authors: Vatankhah Saeed , Huang Xingguo , Renaut Rosemary A , Mickus Kevin , Lin Jun 
Published: July 2023

SUMMARY
Within the iron metallogenic province of southeast Missouri, USA, there are several mines that contain not only economic iron resources, magnetite and/or hematite, but also contain rare earth elements, copper and gold. An area including three major deposits, Pea Ridge, Bourbon and Kratz Spring, was selected for detailed modelling for the upper crustal magnetic susceptibility and density structures. For the study area, ground gravity and high-resolution airborne magnetic and gravity gradiometry data sets are available. An efficient and novel joint inversion algorithm for the simultaneous inversion of these multiple data sets is presented. The Gramian coupling constraint is used to correlate the reconstructed density and magnetic susceptibility models. The implementation relies on the structures of the sensitivity matrices and an efficient minimization algorithm to achieve significant reductions in the memory requirements and computational costs. Consequently, it is feasible to use a laptop computer for the inversion of multiple data sets, each containing thousands of data points, for the recovery of models on the study area, each including approximately one million model parameters. This is the first time that these multiple data sets have been simultaneously inverted for this area. The L1-norm stabilizer is used to provide compact and focused images of the ore deposits. For contrast, independent inversions of each data set are also discussed. In general, our results provide new insights about the concealed ore deposits in the Mesoproterozoic basement rocks of southeast Missouri. Both short- and long-wavelength anomalies exist in the recovered models; these provide a high-resolution image of the subsurface. The geometry and physical properties of the known deposits are determined very well. Additionally, some unknown concealed deposits are revealed; these could be economically valuable and should be considered in future geophysical and geological investigations.
Assessing the impact of antimicrobial stewardship implementation at a district hospital in Ghana using a health partnership model
Authors: Amponsah Obed Kwabena Offe , Courtenay Aaron , Ayisi-Boateng Nana Kwame , Abuelhana Ahmed , Opoku Douglas Aninng , Blay Lawrence Kobina , Abruquah Nana Akua , Osafo Annabella Bensusan , Danquah Charlotte Boachie , Tawiah Phyllis , Opare-Addo Mercy Naa Aduele , Owusu-Ofori Alex , Buabeng Kwame Ohene 
Published: July 2023

Abstract

Background
Antimicrobial stewardship (AMS) is imperative in addressing the menace of antimicrobial resistance (AMR) in health systems. Commonwealth Partnerships for Antimicrobial Stewardship uses a health partnership model to establish AMS in Commonwealth countries. The Hospital of Kwame Nkrumah University of Science and Technology in partnership with Ulster University, Northern Ireland, undertook an AMS project from November 2021 to May 2022. We report on implementation of the AMS, its impact on antibiotic use and infections management at the University Hospital; Kumasi, Ghana.

Methods
The Global-Point Prevalence Survey (PPS) protocol was used to assess antibiotics use at the hospital at baseline, midpoint and end of the project. Feedback on each PPS was given to the hospital to inform practice, behavioural change and improve antibiotic use.

Results
Antibiotic use reduced from 65% at baseline to 59.7% at the end of the project. The rate of healthcare-associated infections also reduced from 17.5% at baseline to 6.5%. Use of antibiotics from the WHO Access group was 40% at baseline but increased to 50% at the endpoint. Watch antibiotics reduced from 60% to 50% from baseline. Culture and susceptibility requests increased from baseline of 111 total requests to 330 requests in the intervention period to inform antimicrobial therapy

Conclusion
The model AMS instituted improved antibiotic use and quality of antimicrobial therapy within the study period. Continuous staff education and training in AMS, and use of standard tools for assessment and application of local data to inform infections management will ensure sustenance and improvement in the gains made.
Description of a new Pavlovskyella species (Acari: Argasidae) from Chile
Authors: Muñoz-Leal Sebastián , Venzal José M , Kneubehl Alexander R , Lopez Job E , Martins Thiago F , Labruna Marcelo B 
Published: July 2023

Abstract
Soft ticks (Argasidae) of the Pavlovskyella Pospelova-Shtrom subgenus are important vectors of relapsing fever spirochetes, which are agents of disease globally. South American representatives of the Pavlovskyella subgenus include 3 species: Ornithodoros (Pavlovskyella) brasiliensis Aragão, Ornithodoros (Pavlovskyella) furcosus Neumann, and Ornithodoros (Pavlovskyella) rostratus Aragão. Here, we describe a fourth species based on morphological and mitogenomic evidence of ticks collected in burrows of unknown hosts in central Chile. The larva of the new species separates from other South American soft ticks by the following combination of characters: 13 pairs of dorsolateral setae, dorsal plate hexagonal, hypostome blunt with denticles from apex almost to the base. Adults of this new species lack cheeks, possess a dorsoventral groove, and have humps, similar to O. (P.) brasiliensis; however, they lack bulging structures on the flanks of idiosoma. Moreover, females and males differ from O. (P.) rostratus by having 3 humps instead of spurs in tarsi I and from O. (P.) furcosus because of their smaller size and thinner anterior lip of the genital aperture in females. The phylogenetic analysis performed with mitogenomes of the Argasidae family depicts the new Pavlovskyella species from Chile in a monophyletic clade with other South American species in the subgenus, confirming a regional group.
The role of miRNA-144-3p/Oprk1/KOR in nicotine dependence and nicotine withdrawal in male rats
Authors: Shao Jiali , Fei Yanxia , Xiao Ji , Wang Lijuan , Zou Shuangfa , Yang Jinfeng 
Published: July 2023

Abstract

Introduction
The kappa-opioid receptor (KOR) has been implicated in mediating the behavioral and biochemical effects associated with nicotine reward and withdrawal; however, its underlying mechanisms remain to be further explored.

Methods
Adult male Sprague-Dawley rats were used to establish a nicotine dependence and withdrawal model by injecting nicotine (3 mg/kg/day, s.c.) or vehicle for 14 days, followed by the termination of nicotine for 7 days. Body weight gain, pain behaviors, and withdrawal scores were assessed in succession. MicroRNA (miRNA) sequencing was performed, and quantitative real-time PCR was used to detect the expression of candidate miRNAs and Oprk1. Western blotting was performed to examine KOR protein expression of KOR. Luciferase assay was conducted to validate the relationship of certain miRNAs/Oprk1.

Results
The behavioral results showed that nicotine dependence and withdrawal induced behavioral changes. Biochemical analyses demonstrated that miR-144-3p expression decreased and Oprk1/KOR expression increased in the prefrontal cortex, nucleus accumben, and hippocampus. Further investigation suggested that miR-144-3p exerted an inhibitory effect on Oprk1 expression in PC12 cells.

Conclusions
This study revealed that miR-144-3p/Oprk1/KOR might be a potential pathway underlying the adverse effects induced by nicotine dependence and withdrawal, and might provide a novel therapeutic target for smoking cessation.

Implications
This study demonstrates an impact of nicotine dependence and nicotine withdrawal on behavioral outcomes and the expressions of miR-144-3p/Oprk1/KOR in male rats. These findings have important translational implications given the continued use of nicotine and the difficulty in smoking cessation worldwide, which can be applied to alleviated the adverse effects induced by nicotine dependence and withdrawal, thus assist smokers to quit smoking.
Espalier: Efficient Tree Reconciliation and Ancestral Recombination Graphs Reconstruction Using Maximum Agreement Forests
Authors: Rasmussen David A , Guo Fangfang 
Published: July 2023

AbstractIn the presence of recombination individuals may inherit different regions of their genome from different ancestors, resulting in a mosaic of phylogenetic histories across their genome. Ancestral recombination graphs (ARGs) can capture how phylogenetic relationships vary across the genome due to recombination, but reconstructing ARGs from genomic sequence data is notoriously difficult. Here, we present a method for reconciling discordant phylogenetic trees and reconstructing ARGs using maximum agreement forests (MAFs). Given two discordant trees, a MAF identifies the smallest possible set of topologically concordant subtrees present in both trees. We show how discordant trees can be reconciled through their MAF in a way that retains discordances strongly supported by sequence data while eliminating conflicts likely attributable to phylogenetic noise. We further show how MAFs and our reconciliation approach can be combined to select a path of local trees across the genome that maximizes the likelihood of the genomic sequence data, minimizes discordance between neighboring local trees, and identifies the recombination events necessary to explain remaining discordances to obtain a fully connected ARG. While heuristic, our ARG reconstruction approach is often as accurate as more exact methods while being much more computationally efficient. Moreover, important demographic parameters such as recombination rates can be accurately estimated from reconstructed ARGs. Finally, we apply our approach to plant infecting RNA viruses in the genus Potyvirus to demonstrate how true recombination events can be disentangled from phylogenetic noise using our ARG reconstruction methods.
HM-chromanone alleviates hyperglycemia and inflammation in mice with endotoxin-induced insulin resistance
Authors: Lim Ha J , Park Jae E , Han Ji S 
Published: July 2023

Abstract
This study was designed to investigate whether (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone alleviates inflammation and hyperglycemia in mice with endotoxin-induced insulin resistance. (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone (10, 30, and 50 mg/kg bodyweight) was orally pre-administered to C57BL/6 J mice. An hour later, lipopolysaccharides (20 mg/kg bodyweight) was administered intraperitoneally to induce endotoxins. Blood samples were collected from the tail vein of the mice every 0, 30, and 90 min. The results indicated that (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone effectively regulated blood glucose levels in mice with endotoxin-induced insulin resistance. Furthermore, (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone significantly reduced the phosphorylation of mammalian target of rapamycin, ribosomal protein S6 kinase 1, and protein kinase C θ. Additionally, (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone suppressed the phosphorylation of c-Jun-NH2-terminal kinase and IkB kinase β, thereby decreasing the phosphorylation of inhibitor of nuclear factor kappa-B α and activating the nuclear factor-κB and activator protein-1 in the liver. Therefore, the expression of tumor necrosis factor-α, interleukin-6, and interleukin-1β was significantly reduced by suppressing the nuclear factor-κB and activator protein 1 activity. Suppression of mammalian target of rapamycin, S6 kinase 1, protein kinase C θ, c-Jun-NH2-terminal kinase, and IkB kinase β also ameliorated insulin resistance by reducing the phosphorylation of insulin receptor substrate-1 serine 307, thereby decreasing hyperglycemia. These findings suggest that (E)-5-hydroxy-7-methoxy-3-(2′-hydroxybenzyl)-4-chromanone can alleviate hyperglycemia and inflammation in mice with endotoxin-induced insulin resistance.
Asynchrony Injures Lung and Diaphragm in Acute Respiratory Distress Syndrome*
Authors: Hashimoto Haruka , Yoshida Takeshi , Firstiogusran Andi Muhammad Fadlillah , Taenaka Hiroki , Nukiwa Ryota , Koyama Yukiko , Uchiyama Akinori , Fujino Yuji 
Published: July 2023

OBJECTIVES:
Patient-ventilator asynchrony is often observed during mechanical ventilation and is associated with higher mortality. We hypothesized that patient-ventilator asynchrony causes lung and diaphragm injury and dysfunction.

DESIGN:
Prospective randomized animal study.

SETTING:
University research laboratory.

SUBJECTS:
Eighteen New Zealand White rabbits.

INTERVENTIONS:
Acute respiratory distress syndrome (ARDS) model was established by depleting surfactants. Each group (assist control, breath stacking, and reverse triggering) was simulated by phrenic nerve stimulation. The effects of each group on lung function, lung injury (wet-to-dry lung weight ratio, total protein, and interleukin-6 in bronchoalveolar lavage), diaphragm function (diaphragm force generation curve), and diaphragm injury (cross-sectional area of diaphragm muscle fibers, histology) were measured. Diaphragm RNA sequencing was performed using breath stacking and assist control (n = 2 each).

MEASUREMENTS AND MAIN RESULTS:
Inspiratory effort generated by phrenic nerve stimulation was small and similar among groups (esophageal pressure swing ≈ –2.5 cm H2O). Breath stacking resulted in the largest tidal volume (>10 mL/kg) and highest inspiratory transpulmonary pressure, leading to worse oxygenation, worse lung compliance, and lung injury. Reverse triggering did not cause lung injury. No asynchrony events were observed in assist control, whereas eccentric contractions occurred in breath stacking and reverse triggering, but more frequently in breath stacking. Breath stacking and reverse triggering significantly reduced diaphragm force generation. Diaphragmatic histology revealed that the area fraction of abnormal muscle was ×2.5 higher in breath stacking (vs assist control) and ×2.1 higher in reverse triggering (vs assist control). Diaphragm RNA sequencing analysis revealed that genes associated with muscle differentiation and contraction were suppressed, whereas cytokine- and chemokine-mediated proinflammatory responses were activated in breath stacking versus assist control.

CONCLUSIONS:
Breath stacking caused lung and diaphragm injury, whereas reverse triggering caused diaphragm injury. Thus, careful monitoring and management of patient-ventilator asynchrony may be important to minimize lung and diaphragm injury from spontaneous breathing in ARDS.
Post-tuberculosis lung disease and chronic obstructive pulmonary disease
Authors: Gai Xiaoyan , Allwood Brian , Sun Yongchang 
Published: July 2023

Abstract
The burden of chronic airway diseases, including chronic obstructive pulmonary disease (COPD), continues to increase, especially in low- and middle-income countries. Post-tuberculosis lung disease (PTLD) is characterized by chronic lung changes after the "cure" of pulmonary tuberculosis (TB), which may be associated with the pathogenesis of COPD. However, data on its prevalence, clinical manifestations, computed tomography features, patterns of lung function impairment, and influencing factors are limited. The pathogenic mechanisms underlying PTLD remain to be elucidated. This review summarizes the recent advances in PTLD and TB-associated COPD. Research is urgently needed both for the prevention and management of PTLD.