bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemokine CXCL12 drives pericyte accumulation and airway remodeling in allergic airway disease
Authors: Bignold Rebecca , Shammout Bushra , Rowley Jessica E. , Repici Mariaelena , Simms John , Johnson Jill R. 
Published: July 2022

Abstract
Background
Airway remodeling is a significant contributor to impaired lung function in chronic allergic airway disease. Currently, no therapy exists that is capable of targeting these structural changes and the consequent loss of function. In the context of chronic allergic inflammation, pericytes have been shown to uncouple from the pulmonary microvasculature, migrate to areas of inflammation, and significantly contribute to airway wall remodeling and lung dysfunction. This study aimed to elucidate the mechanism by which pulmonary pericytes accumulate in the airway wall in a model of chronic allergic airway inflammation.

Methods
Mice were subjected to a protocol of chronic airway inflammation driven by the common environmental aeroallergen house dust mite. Phenotypic changes to lung pericytes were assessed by flow cytometry and immunostaining, and the functional capacity of these cells was evaluated using in vitro migration assays. The molecular mechanisms driving these processes were targeted pharmacologically in vivo and in vitro.

Results
Pericytes demonstrated increased CXCR4 expression in response to chronic allergic inflammation and migrated more readily to its cognate chemokine, CXCL12. This increase in migratory capacity was accompanied by pericyte accumulation in the airway wall, increased smooth muscle thickness, and symptoms of respiratory distress. Pericyte uncoupling from pulmonary vessels and subsequent migration to the airway wall were abrogated following topical treatment with the CXCL12 neutraligand LIT-927.

Conclusion
These results provide new insight into the role of the CXCL12/CXCR4 signaling axis in promoting pulmonary pericyte accumulation and airway remodeling and validate a novel target to address tissue remodeling associated with chronic inflammation.
Improvement in insulin sensitivity and prevention of high fat diet-induced liver pathology using a CXCR2 antagonist
Authors: Phillips Brett E. , Lantier Louise , Engman Carl , Garciafigueroa Yesica , Singhi Aatur , Trucco Massimo , Mantzoros Christos , Wasserman David , Giannoukakis Nick 
Published: July 2022

Abstract
Background
Liver pathology (LP) characteristic of non-alcoholic fatty acid disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is a prevalent co-morbidity of type 2 diabetes (T2D). Accumulating evidence indicates that neutrophils driving insulin resistance (IR), including hepatic IR, precipitate T2D-associated NAFLD/NASH. We hypothesized that targeting neutrophil accumulation into insulin-sensitive tissues in mice using a CXCR2 antagonist under T2D-precipitating high fat diet (HFD) could improve insulin sensitivity and prevent the progression towards liver pathology reminiscent of NAFLD/NASH.

Methods
Mice were age-matched and on standard rodent chow prior to 1:1 randomization into control and HFD formulated with the CXCR2 antagonist AZD5069 or with biologically inactive substitute. They were monitored for metabolic changes including insulin sensitivity using the hyperinsulinemic-euglycemic clamp and hepatic histopathologic evaluation in H&E-stained sections as well as via immunofluorescence microscopy of liver sections for leukocyte markers, collagen 1A1 formation, α-smooth muscle actin (SMA), and galectin-3 expression, for 16 weeks. Statistical tests used to determine significant differences among study groups and outcomes include Student’s t-test, one-way ANOVA, repeated measures two-way ANOVA, and Fisher’s exact test, depending on the analytical question.

Results
Compared to mice on HFD, mice in the AZD5069-formulated HFD exhibited improved insulin sensitivity, a modest reduction in weight gain, and a significant improvement in LP and markers related to NAFLD/NASH. Mice in the AZD5069-formulated HFD also exhibited reduced neutrophil accumulation into the liver at the end of the 16 week study period.

Conclusions
These results show, for the first time, the effectiveness of a selective CXCR2 antagonist to improve insulin sensitivity, concomitantly preventing the progression towards LP characteristic of NAFLD/NASH. This represents a novel approach to target IR and developing LP under T2D-susceptible conditions using a single agent. Furthermore, our data extend the growing evidence in support of neutrophils as a leukocyte population that imprints and maintains a chronic inflammatory state in the progression of dysregulated metabolism in liver-specific co-morbid conditions.
Polar mutagenesis of polycistronic bacterial transcriptional units using Cas12a
Authors: Graffeuil Antoine , Guerrero-Castro Julio , Assefa Aster , Uhlin Bernt Eric , Cisneros David A. 
Published: July 2022

Abstract
Background
Functionally related genes in bacteria are often organized and transcribed as polycistronic transcriptional units. Examples are the fim operon, which codes for biogenesis of type 1 fimbriae in Escherichia coli, and the atp operon, which codes for the FoF1 ATP synthase. We tested the hypothesis that markerless polar mutations could be efficiently engineered using CRISPR/Cas12a in these loci.

Results
Cas12a-mediated engineering of a terminator sequence inside the fimA gene occurred with efficiencies between 10 and 80% and depended on the terminator’s sequence, whilst other types of mutations, such as a 97 bp deletion, occurred with 100% efficiency. Polar mutations using a terminator sequence were also engineered in the atp locus, which induced its transcriptional shutdown and produced identical phenotypes as a deletion of the whole atp locus (ΔatpIBEFHAGDC). Measuring the expression levels in the fim and atp loci showed that many supposedly non-polar mutants induced a significant polar effect on downstream genes. Finally, we also showed that transcriptional shutdown or deletion of the atp locus induces elevated levels of intracellular ATP during the exponential growth phase.

Conclusions
We conclude that Cas12a-mediated mutagenesis is an efficient simple system to generate polar mutants in E. coli. Different mutations were induced with varying degrees of efficiency, and we confirmed that all these mutations abolished the functions encoded in the fim and atp loci. We also conclude that it is difficult to predict which mutagenesis strategy will induce a polar effect in genes downstream of the mutation site. Furthermore the strategies described here can be used to manipulate the metabolism of E. coli as showcased by the increase in intracellular ATP in the markerless ΔatpIBEFHAGDC mutant.
Remineralization and protection from demineralization: effects of a hydroxyapatite-containing, a fluoride-containing and a fluoride- and hydroxyapatite-free toothpaste on human enamel in vitro
Authors: Guntermann Leona , Rohrbach Arno , Schäfer Edgar , Dammaschke Till 
Published: July 2022

Abstract
Background
The aim was to evaluate the remineralization potential as well as the extent of protection against renewed demineralization of enamel by hydroxyapatite-containing toothpaste (Karex) in comparison to fluoride-containing (Elmex) and fluoride- and hydroxyapatite-free toothpaste (Ajona) as control.

Methods
Fifty-seven enamel samples were obtained from 19 human teeth. Five demarcated surfaces were created on each tooth (S0—S4). Four of the surfaces (S1—S4) were exposed to lactic acid (pH 3) for 8 h (demineralization). S0 was left untreated as control. S1 was solely treated with acid. After demineralization, S2 was exposed to Karex for 2 min, of which 15 s were brushing. S3 was treated with Elmex and S4 with Ajona, accordingly. Then, the samples were evaluated using a scanning electron microscope and ImageJ image analysis software to determine the percentage of demineralization. Afterwards, S2-S4 were again exposed to lactic acid for 2 h, and subjected to pixel analysis another time. Data were statistically analysed using ANOVA with post-hoc Scheffé test and the Kurskal-Wallis test.

Results
The surfaces treated with Elmex showed the lowest percentage of demineralization (mean 5.01 ± 0.98%) (p < 0.01). Thus, Elmex remineralized more effectively compared to Ajona (8.89 ± 1.41%) and Karex (9.85 ± 1.63%) (p < 0.01). Furthermore, Elmex showed the lowest percentage of demineralized enamel after new demineralization (median 6.29%), followed by Ajona (11.92%) and Karex (13.46%) (p < 0.001).

Conclusion
In terms of remineralization and protection against renewed demineralization, a hydroxyapatite-containing toothpaste (Karex) appears to be inferior to a fluoride-containing toothpaste (Elmex) and a fluoride- and hydroxyapatite-free toothpaste (Ajona). Hence, the recommendation to use Karex to protect against demineralization should be critically questioned.
SH3GLB1-related autophagy mediates mitochondrial metabolism to acquire resistance against temozolomide in glioblastoma
Authors: Chien Chia-Hung , Yang Wen-Bin , Chuang Jian-Ying , Lee Jung-Shun , Liao Wei-An , Huang Chih-Yuan , Chen Pin-Yuan , Wu An-Chih , Yang Shun-Tai , Lai Chien-Cheng , Chi Pei-I , Chu Jui-Mei , Cheng Siao Muk , Liu Chan-Chuan , Hwang Daw-Yang , Chen Shang-Hung , Chang Kwang-Yu 
Published: July 2022

AbstractBackgroundThe mechanism by which glioblastoma evades temozolomide (TMZ)-induced cytotoxicity is largely unknown. We hypothesized that mitochondria plays a role in this process.MethodsRNA transcriptomes were obtained from tumor samples and online databases. Expression of different proteins was manipulated using RNA interference or gene amplification. Autophagic activity and mitochondrial metabolism was assessed in vitro using the respective cellular and molecular assays. In vivo analysis were also carried out in this study.ResultsHigh SH3GLB1 gene expression was found to be associated with higher disease grading and worse survival profiles. Single-cell transcriptome analysis of clinical samples suggested that SH3GLB1 and the altered gene levels of oxidative phosphorylation (OXPHOS) were related to subsets expressing a tumor-initiating cell signature. The SH3GLB1 protein was regulated by promoter binding with Sp1, a factor associated with TMZ resistance. Downregulation of SH3GLB1 resulted in retention of TMZ susceptibility, upregulated p62, and reduced LC3B-II. Autophagy inhibition by SH3GLB1 deficiency and chloroquine resulted in attenuated OXPHOS expression. Inhibition of SH3GLB1 in resistant cells resulted in alleviation of TMZ-enhanced mitochondrial metabolic function, such as mitochondrial membrane potential, mitochondrial respiration, and ATP production. SH3GLB1 modulation could determine tumor susceptibility to TMZ. Finally, in animal models, resistant tumor cells with SH3GLB1 knockdown became resensitized to the anti-tumor effect of TMZ, including the suppression of TMZ-induced autophagy and OXPHOS.ConclusionsSH3GLB1 promotes TMZ resistance via autophagy to alter mitochondrial function. Characterizing SH3GLB1 in glioblastoma may help develop new therapeutic strategies against this disease in the future.
Genomics analysis and degradation characteristics of lignin by Streptomyces thermocarboxydus strain DF3-3
Authors: Tan Fangyun , Cheng Jun , Zhang Yu , Jiang Xingfu , Liu Yueqiu 
Published: July 2022

Abstract
Background
Lignocellulose is an important raw material for biomass-to-energy conversion, and it exhibits a complex but inefficient degradation mechanism. Microbial degradation is promising due to its environmental adaptability and biochemical versatility, but the pathways used by microbes for lignin degradation have not been fully studied. Degradation intermediates and complex metabolic pathways require more study.

Results
A novel actinomycete DF3-3, with the potential for lignin degradation, was screened and isolated. After morphological and molecular identification, DF3-3 was determined to be Streptomyces thermocarboxydus. The degradation of alkali lignin reached 31% within 15 days. Manganese peroxidase and laccase demonstrated their greatest activity levels, 1821.66 UL−1 and 1265.58 UL−1, respectively, on the sixth day. The highest lignin peroxidase activity was 480.33 UL−1 on the fourth day. A total of 19 lignin degradation intermediates were identified by gas chromatography–mass spectrometry (GC–MS), including 9 aromatic compounds. Genome sequencing and annotation identified 107 lignin-degrading enzyme-coding genes containing three core enzymatic systems for lignin depolymerization: laccases, peroxidases and manganese peroxidase. In total, 7 lignin metabolic pathways were predicted.

Conclusions
Streptomyces thermocarboxydus strain DF3-3 has good lignin degradation ability. Degradation products and genomics analyses of DF3-3 show that it has a relatively complete lignin degradation pathway, including the β-ketoadipate pathway and peripheral reactions, gentisate pathway, anthranilate pathway, homogentisic pathway, and catabolic pathway for resorcinol. Two other pathways, the phenylacetate–CoA pathway and the 2,3-dihydroxyphenylpropionic acid pathway, are predicted based on genome data alone. This study provides the basis for future characterization of potential biotransformation enzyme systems for biomass energy conversion.
Ipilimumab- and nivolumab-induced myocarditis in a patient with metastatic cholangiocarcinoma: a case report
Authors: Delombaerde Danielle , Vervloet Delphine , Berwouts Dieter , Beckers Roel , Prenen Hans , Peeters Marc , Gremonprez Félix , Croes Lieselot , Vulsteke Christof 
Published: July 2022

Abstract
Background
Myocarditis in patients treated with immune checkpoint inhibitors has previously been reported to be rare, though it has most likely been underreported owing to misdiagnosis in the absence of overt clinical presentation. Early detection and characterization of this potentially life-threatening immune-related adverse event is of major importance. Herein we report a case of early-onset myocarditis in an asymptomatic patient treated with dual checkpoint inhibition for metastatic cholangiocarcinoma.

Case presentation
A 69-year-old male Caucasian patient with metastatic cholangiocarcinoma presented with mild epigastric pain and troponinemia prior to the third dose of dual checkpoint inhibition (ipilimumab 1 mg/kg body weight and nivolumab 3 mg/kg body weight). Initial workup showed no significant abnormalities (physical/neurological examination, electrocardiogram, 72-hour Holter monitoring, and a transthoracic echocardiogram). However, cardiac magnetic resonance imaging revealed a zone of contrast enhancement in the inferior segment of the left ventricular wall indicating a recent episode of myocarditis. Despite steroid initiation (0.5 mg/kg oral prednisolone per day), troponin levels kept increasing, in the absence of coronary disease, for which steroids were increased to 1.5 mg/kg/day. Fluorodeoxyglucose positron emission tomography/computed tomography, 28 days after detecting elevated troponin levels, depicted multiple zones of active myocardial inflammation (basal septal, mid-anterior, and apical inferior). The patient is currently stable, and troponinemia is slowly decreasing while steroids are steadily being tapered.

Conclusion
As the number of cancers treated with immune checkpoint inhibitors is expanding, the incidence of immune checkpoint inhibitor-induced myocarditis is likely to increase. Moreover, the emerging combination of immune checkpoint inhibitors with non-immune checkpoint inhibitor therapies with potential synergistic cardiotoxic side effects (for example, tyrosine kinase inhibitors) will further complicate the diagnosis of immune-related cardiotoxicity. This case highlights the urgent need for predictive biomarkers to stratify patients at risk and to develop a standardized and multidisciplinary management approach for early diagnosis and treatment of this severe immune-related adverse event.
Potentials and limitations of NFIs and remote sensing in the assessment of harvest rates: a reply to Breidenbach et al.
Authors: Ceccherini Guido , Duveiller Gregory , Grassi Giacomo , Lemoine Guido , Avitabile Valerio , Pilli Roberto , Cescatti Alessandro 
Published: July 2022

AbstractThe timely and accurate monitoring of forest resources is becoming of increasing importance in light of the multi-functionality of these ecosystems and their increasing vulnerability to climate change. Remote sensing observations of tree cover and systematic ground observations from National Forest Inventories (NFIs) represent the two major sources of information to assess forest area and use. The specificity of two methods is calling for an in-depth analysis of their strengths and weaknesses and for the design of novel methods emerging from the integration of satellite and surface data. On this specific debate, a recent paper by Breidenbach et al. published in this journal suggests that the detection of a recent increase in EU forest harvest rate—as reported in Nature by Ceccherini et al.—is largely due to technical limitations of satellite-based mapping. The article centers on the difficulty of the approaches to estimate wood harvest based on remote sensing. However, it does not discuss issues with the robustness of validation approaches solely based on NFIs. Here we discuss the use of plot data as a validation set for remote sensing products, discussing potentials and limitations of both NFIs and remote sensing, and how they can be used synergistically. Finally, we highlight the need to collect in situ data that is both relevant and compatible with remote sensing products within the European Union.
Towards inclusive and accessible parks in Pathum Thani Province, Thailand
Authors: Selanon Pattamon , Puggioni Federico , Dejnirattisai Supanut , Rutchamart Autchariya 
Published: July 2022

AbstractThe problem of the lack of inclusive public space in the fringes of Bangkok, Thailand, is related to multiple factors in urban development. The study-area of the Pathum Thani province offers a summary of the critical consequences of the urban development in the past decades. The partial transformation of some environmental tracks onto an urbanized system allows the creation of a nonhomogeneous privatized continuous built surface. The conditions of these urban areas suffer from vehicular traffic, car dependency, absence of differentiated mobility, limited walkability, and lack of public spaces. The research aims to bring these areas to a higher level of inclusion, accessibility and overall quality by rethinking the existent public spaces, creating the grounds for the design of inclusive and accessible park. To reach this objective, the study explores the topics of public space, park, accessibility and inclusivity for disabilities to establish some principles for future design approach for Thaklong–Klongluang, a study-area located in the Pathum Thani Province. Characteristics, features, weaknesses and existing parks of the study area are demonstrated in the subsequent section. The results’ discussion relates all the aforementioned topics, defining the guidelines for the creation of inclusive and accessible parks in the six existent sites of the study area. Because of its premises, besides being based in a specific location, the article aims to be a valid reference for the areas which present similar features and critical points.
The tale of three landslides in the Western Ghats, India: lessons to be learnt
Authors: Ajin R. S. , Nandakumar D. , Rajaneesh A. , Oommen T. , Ali Yunus P. , Sajinkumar K. S. 
Published: July 2022

AbstractIn recent years, landslides have become a typical monsoon calamity in the Western Ghats region of Kerala, India. In addition to property damage, heavy rainfall (36% above normal) and multiple landslides (4728) killed 48 people in 2018. This tendency continued throughout the monsoon seasons of 2019, 2020, and 2021, resulting in the deaths of over 100 people. Anomalous precipitation is ascribed to the frequent development of low-pressure in the surrounding oceans. Using ground real data and satellite imagery, we evaluated the features of three large landslides in the state of Kerala, which occurred during the monsoon season of 2021. Our investigation found that the Kokkayar landslide was triggered by anthropogenic-related agricultural activities, the Plappally landslide by geomorphic and tectonic processes as well as human involvement, and the Kavali landslide by forest fragmentation with dense vegetation on thin soil. The triggering mechanism for all three of these landslides, however, is the intense rainfall of 266 mm in less than 24 h. Thus, an accurate and precise forecast of rainfall can be used to define a threshold for an early warning, which will be vital for saving lives.
Protocol for a systematic review and meta-analysis of the diagnostic accuracy of artificial intelligence for grading of ophthalmology imaging modalities
Authors: Cao Jessica , Chang-Kit Brittany , Katsnelson Glen , Far Parsa Merhraban , Uleryk Elizabeth , Ogunbameru Adeteju , Miranda Rafael N. , Felfeli Tina 
Published: July 2022

Abstract
Background
With the rise of artificial intelligence (AI) in ophthalmology, the need to define its diagnostic accuracy is increasingly important. The review aims to elucidate the diagnostic accuracy of AI algorithms in screening for all ophthalmic conditions in patient care settings that involve digital imaging modalities, using the reference standard of human graders.

Methods
This is a systematic review and meta-analysis. A literature search will be conducted on Ovid MEDLINE, Ovid EMBASE, and Wiley Cochrane CENTRAL from January 1, 2000, to December 20, 2021. Studies will be selected via screening the titles and abstracts, followed by full-text screening. Articles that compare the results of AI-graded ophthalmic images with results from human graders as a reference standard will be included; articles that do not will be excluded. The systematic review software DistillerSR will be used to automate part of the screening process as an adjunct to human reviewers. After the full-text screening, data will be extracted from each study via the categories of study characteristics, patient information, AI methods, intervention, and outcomes. Risk of bias will be scored using Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) by two trained independent reviewers. Disagreements at any step will be addressed by a third adjudicator. The study results will include summary receiver operating characteristic (sROC) curve plots as well as pooled sensitivity and specificity of artificial intelligence for detection of any ophthalmic conditions based on imaging modalities compared to the reference standard. Statistics will be calculated in the R statistical software.

Discussion
This study will provide novel insights into the diagnostic accuracy of AI in new domains of ophthalmology that have not been previously studied. The protocol also outlines the use of an AI-based software to assist in article screening, which may serve as a reference for improving the efficiency and accuracy of future large systematic reviews.

Trial registration
PROSPERO, CRD42021274441