bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of High‐Speed Railway Accession on Agricultural Exports: Evidence from Chinese Agriculture‐Related Enterprises
Authors: Zhou Jianjun , Fan Xiayang , Yu Aizhi
Published: August 2021

Although many studies have analyzed the transportation infrastructure effects on economic and trade development, little is known about the relationship between transportation infrastructure and trade in the agricultural sector. We take the opening of China’s high‐speed railway (HSR) as a quasi‐natural experiment and use multiperiod DID model to explore the impact and mechanism of HSR on agriculture‐related enterprises’ exports. The results show that HSR can promote export growth of agriculture‐related enterprises by 6.9%, and it will reach 10% in 5 years. However, the effect of HSR on the export of agriculture‐related enterprises only exists within 45 km around HSR stations. HSR can reduce information barriers and costs for enterprises to enter the international market by providing transportation convenience and improving market access levels. HSR also offers local areas more transportation advantage compared to other surrounding areas, which in turn makes a siphon effect on export activities. Both these mechanisms are significant within 45 km, and it is extremely obvious for poor transportation areas and enterprises with higher productivity, and the siphon effect is even stronger than market access. Heterogeneity analysis results demonstrate that HSR has different effects for different types of enterprises.
A Statistical Damage Constitutive Model of Anisotropic Rock: Development and Validation
Authors: Rong Tenglong , Guan Can , Liu Keliu , Heng Shuai , Shen Wenlong , Mou Ruiyong
Published: August 2021

The damage constitutive model is of great significance to research the stress-strain relationship and damage evolution of rock under loading in engineering. In order to investigate the effect of anisotropic characteristic on the stress-strain relationship and damage evolution, a statistical damage constitutive model of anisotropic rock under true triaxial condition was developed. In this study, the plane which existed perpendicular to the coordinate axis was extracted from representative volume element (RVE) of rock. The extracted plane was assumed to be composed of abundant mesoscopic elements whose failure strength satisfied the Weibull distribution. According to the number of failure elements on the plane in each direction under loading, the anisotropic damage variable was established based on the proposed concept of areal damage. A statistical damage constitutive model of anisotropic rock was developed by using strain equivalent hypothesis and generalized Hooke constitutive model. Subsequently, the parameters in the anisotropic damage constitutive model were determined by the method of total differential. Thus, the damage evolution of anisotropic rock under various stress conditions can be conveniently evaluated by the anisotropic damage model. The model was validated based on the tests of rocks under the stress conditions of conventional triaxial and true triaxial, respectively. Moreover, for the purpose of studying the influence of parameters on the model, sensitivity analyses of mechanical parameters and model parameters were carried out. The results of statistical damage constitutive clearly demonstrate the stress-strain and damage evolution of anisotropic rock under various stress conditions.
Clinical Analysis of Improved Particle Swarm Algorithm-Based Magnetic Resonance Imaging Diagnosis of Placenta Accreta
Authors: Ding Xiaoyan , Cao Yingying , Sun Fengtao , Ma Airong , Zhang Feiyue
Published: August 2021

The magnetic resonance imaging (MRI) image processing capabilities were investigated based on the improved particle swarm optimization (IPSO) algorithm, and the clinical application analysis of MRI images in the diagnosis of placenta accreta (PA) was evaluated in this study. The MRI uterine images were detected on the basis of IPSO. Besides, the clinical data of 89 patients with PA were selected and collected, who were diagnosed by clinical cesarean section surgery and pathological comprehensive diagnosis in hospital from January 2018 to July 2020. Then, all of them underwent the ultrasound (US) and MRI examinations, and the differences of sensitivity, specificity, and accuracy between MRI and US under IPSO in the diagnosis of PA were compared, as well as the differences in the diagnosis of adhesive, implantable, and penetrated PA. The results showed that the difference in detection between IPSO-based MRI images and US images was not statistically substantial (

p
>
0.05

), but the number of initial detections was higher than the number of US examination. MRI examination had higher sensitivity and specificity in the diagnosis of PA during pregnancy, especially for implantable PA, compared with US examination (

p
<
0.05

). In conclusion, MRI images based on the improved particle swarm optimization algorithm showed a good application effect in the diagnosis of placental implantation diseases, which was worthy of further promotion in clinical practice.
Mechanical Responses to Different Excavation Methods of Qichongcun Tunnel in Guiyang City, China
Authors: Xie Siwei , Huang Feng , Wang Guihe , Zhu Chaoyang , Su Yunji , Qian Feng
Published: August 2021

The construction method of tunnel has a critical impact on the stress and strain field during excavation. This study simulated the construction of Qichongcun tunnel by applying a different excavation method, including double‐sided method, single‐sided method, and three‐step dynamic balance excavation method. The distribution and variation of the stress, vertical displacement, horizontal displacement of surrounding rocks, and stress of initial and secondary lining were studied. The results showed that large displacement of surrounding rocks would be induced during the construction in three‐step method, but the stress of the second lining was small after completion of the construction. The displacement and stress of the three‐step dynamic balance excavation method were larger than those of the other two methods, but it still met the requirements of safety.
A Bibliometric Analysis and Visualization of Fractional Order Research in China over Two Decades (2001–2020)
Authors: Yang Yunfei , Lv Ke , Xue Jian , Huang Xi
Published: August 2021

Fractional order research has interdisciplinary characteristics and has been widely used in the field of natural sciences. Therefore, fractional order research has become an important area of concern for scholars. This paper used 2854 literatures collected from China National Knowledge Infrastructure (CNKI) database from 2001 to 2020 as the data source and used bibliometrics and two visualization methods to conduct bibliometric analysis and visualization research on China’s fractional order research. To begin with, this paper analyzed the time series distribution of publications, the distribution of research institutions, the author cooccurrence network, the distribution of important journals, and the distribution of important literature, which explained the research status of the fractional order. Furthermore, this paper used VOSviewer software to analyze the clustering and density distribution of the fractional order research keywords, which revealed the hotspots of the fractional order research. Finally, with the help of CiteSpace software, the burst keywords were analyzed to further explore the frontiers of fractional order research. This paper systematically reveals the research status, research hotspots, and research frontiers of China’s fractional order research, which can provide certain theoretical and practical references for related follow-up researchers.
Cardiac Magnetic Resonance Images Superresolution via Multichannel Residual Attention Networks
Authors: Qiu Defu , Cheng Yuhu , Wang Xuesong
Published: August 2021

The deep neural network has achieved good results in medical image superresolution. However, due to the medical equipment limitations and the complexity of the human body structure, it is difficult to reconstruct clear cardiac magnetic resonance (CMR) superresolution images. To reconstruct clearer CMR images, we propose a CMR image superresolution (SR) algorithm based on multichannel residual attention networks (MCRN), which uses the idea of residual learning to alleviate the difficulty of training and fully explore the feature information of the image and uses the back-projection learning mechanism to learn the interdependence between high-resolution images and low-resolution images. Furthermore, the MCRN model introduces an attention mechanism to dynamically allocate each feature map with different attention resources to discover more high-frequency information and learn the dependency between each channel of the feature map. Extensive benchmark evaluation shows that compared with state-of-the-art image SR methods, our MCRN algorithm not only improves the objective index significantly but also provides richer texture information for the reconstructed CMR images, and our MCRN algorithm is better than the Bicubic algorithm in evaluating the information entropy and average gradient of the reconstructed image quality.
Investigating the Effects of Coenzyme Q10 on Human Corneal Endothelial Cells
Authors: Titley Mitchell , Ahmad Sajjad , Parekh Mohit
Published: August 2021

Purpose. To investigate the effects of Coenzyme Q10 (CoQ10) treatment on immortalised human corneal endothelial cells (HCEC-12). Methods. HCEC-12 cells were cultured in different concentrations of CoQ10 (0.1%, 0.2%, 0.5%, and 1.0%) and analysed using live/dead staining assay to determine appropriate concentration for subsequent experiments. Cells were pretreated with CoQ10 before inducing apoptosis by ethanol (EtOH) treatment for 30 seconds which was followed by posttreatment with CoQ10. Viable, apoptotic, and dead cell proportions were analysed using Annexin V-FITC immunofluorescence staining. Mitochondrial intensity and respiratory functions were also investigated using MitoTracker staining and a Seahorse XFe24 analyser, respectively. Results were compared to a positive control for apoptosis. The experiments were carried out in triplicates. Graphpad prism software was used for statistical analysis where

p
<
0.05

was deemed statistically significant. Results. CoQ10 treatment at 0.5% and 1% showed 92% and 30% viable cells compared with 0.1% and 0.2% that showed 96% and 94% viable cells, respectively (

p
=
0.0562

). 0.1% and 0.2% concentrations were, thus, used for subsequent experiments. Annexin V-FITC apoptotic analysis showed 2% at 0.1% and 3% at 0.2% of apoptotic cells (

p
=
0.0824

). Mitochondrial respiratory function and mitochondrial intensity increased in apoptotic cells following 0.1% CoQ10 treatment. Conclusion. 0.1% CoQ10 was found optimal for reducing apoptosis and increasing metabolic activity on human corneal endothelial cell line. These results support the need for further ex vivo studies to investigate the safety profile of CoQ10 as an antiapoptotic agent for human corneal endothelium.
A Conjecture on Super Edge-Magic Total Labeling of 4-Cycle Books
Authors: Simanihuruk Mudin , Kusmayadi Tri Atmojo , Swita Baki , Romala Minsi , Damanik Friska
Published: August 2021

A graph

G

is called cycle books

B

4
,
m

,
2

if

G

consists of m cycles

C

4

with a common path

P

2

. Figueroa-Centeno, Ichishima, and Muntaner-Batle conjecture that the graph

B

4
,
m

,
2

is super edge-magic total if and only if

m

is even or

m
≡
5
 
mod

8

. In this article, we prove this conjecture for

m

 ≥ 36 and

m

 = 0 mod (2).
An Empirical Study on Scientific Research Performance of Universities in Different Regions of China Based on PCA and Malmquist Index Method
Authors: Xia Cun-Yang , Yuan Ze-Hui , He Wen-Yu , Zhao Ju-Hui
Published: August 2021

This paper uses principal component analysis (PCA) and entropy method to construct the evaluation index system of the scientific research performance of universities in 31 provinces and cities in China. Based on the traditional DEA model, the development trend of the scientific research performance of the research objects from 2015 to 2019 is dynamically evaluated by the Malmquist index method. The results show that the scientific research performance of universities in various regions of China is not ideal, and the level of scientific research performance is declining. The total factor productivity of scientific research in the central and western regions is much higher than that in the eastern region. The main factor that hinders the improvement of scientific research performance is the efficiency of technological progress. Finally, aiming at the existing problems, some feasible suggestions are put forward to further improve the input-output efficiency of scientific research in universities.
Multicriteria Decision-Making Approach for Pythagorean Fuzzy Hypersoft Sets’ Interaction Aggregation Operators
Authors: Zulqarnain Rana Muhammad , Siddique Imran , Ali Rifaqat , Jarad Fahd , Iampan Aiyared
Published: August 2021

In this paper, we examine the multicriteria decision-making (MCDM) difficulties for Pythagorean fuzzy hypersoft sets (PFHSSs). The PFHSSs are a suitable extension of the Pythagorean fuzzy soft sets (PFSSs) which deliberates the parametrization of multi-subattributes of considered parameters. It is a most substantial notion for describing fuzzy information in the decision-making (DM) procedure to accommodate more vagueness comparative to existing PFSSs and intuitionistic fuzzy hypersoft sets (IFHSSs). The core objective of this study is to plan some innovative operational laws considering the interaction for Pythagorean fuzzy hypersoft numbers (PFHSNs). Also, based on settled interaction operational laws, two aggregation operators (AOs) i.e., Pythagorean fuzzy hypersoft interaction weighted average (PFHSIWA) and Pythagorean fuzzy hypersoft interaction weighted geometric (PFHSIWG) operators for PFHSSs operators have been presented with their fundamental properties. Furthermore, an MCDM technique has been established using planned interaction AOs. To ensure the strength and practicality of the developed MCDM method, a mathematical illustration has been presented. The usefulness, influence, and versatility of the developed method have been demonstrated via comparative analysis with the help of some conventional studies.
Characterizing Macrophage Diversity in Metastasis-Bearing Lungs Reveals a Lipid-Associated Macrophage Subset
Authors: Huggins Danielle N. , LaRue Rebecca S. , Wang Ying , Knutson Todd P. , Xu Yingzheng , Williams Jesse W. , Schwertfeger Kathryn L.
Published: August 2021

While macrophages are among the most abundant immune cell type found within primary and metastatic mammary tumors, how their complexity and heterogeneity change with metastatic progression remains unknown. Here, macrophages were isolated from the lungs of mice bearing orthotopic mammary tumors for single-cell RNA sequencing (scRNA-seq). Seven distinct macrophage clusters were identified, including populations exhibiting enhanced differential expression of genes related to antigen presentation (H2-Aa, Cd74), cell cycle (Stmn1, Cdk1), and interferon signaling (Isg15, Ifitm3). Interestingly, one cluster demonstrated a profile concordant with lipid-associated macrophages (Lgals3, Trem2). Compared with nontumor-bearing controls, the number of these cells per gram of tissue was significantly increased in lungs from tumor-bearing mice, with the vast majority costaining positively with the alveolar macrophage marker Siglec-F. Enrichment of genes implicated in pathways related to lipid metabolism as well extracellular matrix remodeling and immunosuppression was observed. In addition, these cells displayed reduced capacity for phagocytosis. Collectively, these findings highlight the diversity of macrophages present within metastatic lesions and characterize a lipid-associated macrophage subset previously unidentified in lung metastases.

Significance:

scRNA-seq of macrophages isolated from lung metastases reveals extensive macrophage heterogeneity and identifies a novel subpopulation enriched for genes involved in lipid metabolism, extracellular matrix remodeling, and immunosuppression.
Going with the Flow: The Promise of Plasma-Only Circulating Tumor DNA Assays
Authors: Bent Alisha , Kopetz Scott
Published: August 2021

Circulating tumor DNA (ctDNA) has emerged as a noninvasive diagnostic and prognostic tool for colorectal cancer. Here, we discuss studies that evaluate the ability of plasma-only ctDNA assays to detect minimal residual disease and the potential benefit of integration of methylation into ctDNA assays.

See related articles by Parikh et al., p. 5586 and Taieb et al., p. 5638
Interpreting the Complex Landscape of Immune–Tumor Interface
Authors: Symmans W. Fraser
Published: August 2021

Predictive biomarkers for immune therapy must address a complex interface between the immune system and triple-negative breast cancer and still be technically reliable for diagnostic use. Two recent articles describe the assessment of spatial heterogeneity using digital methods that promise to improve the quantification of immune infiltrate or molecular targets.

See related articles by Bai et al., p. 5557 and Carter et al., p. 5628
Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer
Authors: Crawford Nyree , Stott Katie J. , Sessler Tamas , McCann Christopher , McDaid William , Lees Andrea , Latimer Cheryl , Fox Jennifer P. , Munck Joanne M. , Smyth Tomoko , Shah Alpesh , Martins Vanessa , Lawler Mark , Dunne Philip D. , Kerr Emma M. , McDade Simon S. , Coyle Vicky M. , Longley Daniel B.
Published: August 2021

Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical and therapeutic relevance of IAPs in colorectal cancer. We found that elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in patients with microsatellite stable (MSS) stage III colorectal cancer treated with 5-fluorouracil (5FU)–based adjuvant chemotherapy, suggesting their involvement in promoting chemoresistance. A novel IAP antagonist tolinapant (ASTX660) potently and rapidly downregulated cIAP1 in colorectal cancer models, demonstrating its robust on-target efficacy. In cells co-cultured with TNFα to mimic an inflammatory tumor microenvironment, tolinapant induced caspase-8–dependent apoptosis in colorectal cancer cell line models; however, the extent of apoptosis was limited because of inhibition by the caspase-8 paralogs FLIP and, unexpectedly, caspase-10. Importantly, tolinapant-induced apoptosis was augmented by FOLFOX in human colorectal cancer and murine organoid models in vitro and in vivo, due (at least in part) to FOLFOX-induced downregulation of class I histone deacetylases (HDAC), leading to acetylation of the FLIP-binding partner Ku70 and downregulation of FLIP. Moreover, the effects of FOLFOX could be phenocopied using the clinically relevant class I HDAC inhibitor, entinostat, which also induced acetylation of Ku70 and FLIP downregulation. Further analyses revealed that caspase-8 knockout RIPK3-positive colorectal cancer models were sensitive to tolinapant-induced necroptosis, an effect that could be exploited in caspase-8–proficient models using the clinically relevant caspase inhibitor emricasan. Our study provides evidence for immediate clinical exploration of tolinapant in combination with FOLFOX in poor prognosis MSS colorectal cancer with elevated cIAP1/2 expression.
Transcriptome-wideIn VitroEffects of Aspirin on Patient-derived Normal Colon Organoids
Authors: Devall Matthew A.M. , Drew David A. , Dampier Christopher H. , Plummer Sarah J. , Eaton Stephen , Bryant Jennifer , Díez-Obrero Virginia , Mo Jiancheng , Kedrin Dmitriy , Zerjav Dylan C. , Takacsi-Nagy Oliver , Jennelle Lucas T. , Ali Mourad W. , Yilmaz Ömer H. , Moreno Victor , Powell Steven M. , Chan Andrew T. , Peters Ulrike , Casey Graham
Published: August 2021

Mechanisms underlying aspirin chemoprevention of colorectal cancer remain unclear. Prior studies have been limited because of the inability of preclinical models to recapitulate human normal colon epithelium or cellular heterogeneity present in mucosal biopsies. To overcome some of these obstacles, we performed in vitro aspirin treatment of colon organoids derived from normal mucosal biopsies to reveal transcriptional networks relevant to aspirin chemoprevention. Colon organoids derived from 38 healthy individuals undergoing endoscopy were treated with 50 μmol/L aspirin or vehicle control for 72 hours and subjected to bulk RNA sequencing. Paired regression analysis using DESeq2 identified differentially expressed genes (DEG) associated with aspirin treatment. Cellular composition was determined using CIBERSORTx. Aspirin treatment was associated with 1,154 significant (q < 0.10) DEGs prior to deconvolution. We provide replication of these findings in an independent population-based RNA-sequencing dataset of mucosal biopsies (BarcUVa-Seq), where a significant enrichment for overlap of DEGs was observed (P < 2.2E−16). Single-cell deconvolution revealed changes in cell composition, including a decrease in transit-amplifying cells following aspirin treatment (P = 0.01). Following deconvolution, DEGs included novel putative targets for aspirin such as TRABD2A (q = 0.055), a negative regulator of Wnt signaling. Weighted gene co-expression network analysis identified 12 significant modules, including two that contained hubs for EGFR and PTGES2, the latter being previously implicated in aspirin chemoprevention. In summary, aspirin treatment of patient-derived colon organoids using physiologically relevant doses resulted in transcriptome-wide changes that reveal altered cell composition and improved understanding of transcriptional pathways, providing novel insight into its chemopreventive properties.

Prevention Relevance:

Numerous studies have highlighted a role for aspirin in colorectal cancer chemoprevention, though the mechanisms driving this association remain unclear. We addressed this by showing that aspirin treatment of normal colon organoids diminished the transit-amplifying cell population, inhibited prostaglandin synthesis, and dysregulated expression of novel genes implicated in colon tumorigenesis.
High L-Type Amino Acid Transporter 1 Levels Are Associated with Chemotherapeutic Resistance in Gastric Cancer Patients
Authors: Nakazawa Nobuhiro , Sohda Makoto , Ide Munenori , Shimoda Yuki , Ubukata Yasunari , Kuriyama Kengo , Hara Keigo , Sano Akihiko , Sakai Makoto , Yokobori Takehiko , Ogawa Hiroomi , Oyama Tetsunari , Shirabe Ken , Saeki Hiroshi
Published: August 2021

Introduction: We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy. Methods: Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy. Results: LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012). Conclusion: Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.
WT1 Pathogenic Variants are Associated with a Broad Spectrum of Differences in Sex Development Phenotypes and Heterogeneous Progression of Renal Disease
Authors: Ferrari Maria T.M. , Watanabe Andreia , da Silva Thatiane E. , Gomes Nathalia L. , Batista Rafael L. , Nishi Mirian Y. , de Paula Leila C.P. , Costa Eduardo C. , Costa Elaine M.F. , Cukier Priscilla , Onuchic Luiz F. , Mendonca Berenice B. , Domenice Sorahia
Published: August 2021

Wilms’ tumor suppressor gene 1 (WT1) plays an essential role in urogenital and kidney development. Heterozygous germline pathogenic allelic variants of WT1 have been classically associated with Denys–Drash syndrome (DDS) and Frasier syndrome (FS). Usually, exonic pathogenic missense variants in the zinc finger region are the cause of DDS, whereas pathogenic variants affecting the canonic donor lysine-threonine-serine splice site in intron 9 cause FS. Phenotypic overlap between WT1 disorders has been frequently observed. New WT1 variant-associated phenotypes, such as 46,XX testicular/ovarian-testicular disorders of sex development (DSD) and primary ovarian insufficiency, have been reported. In this report, we describe the phenotypes and genotypes of 7 Brazilian patients with pathogenic WT1 variants. The molecular study involved Sanger sequencing and massively parallel targeted sequencing using a DSD-associated gene panel. Six patients (5 with a 46,XY karyotype and 1 with a 46,XX karyotype) were initially evaluated for atypical genitalia, and a 46,XY patient with normal female genitalia sought medical attention for primary amenorrhea. Germ cell tumors were identified in 2 patients, both with variants affecting alternative splicing of WT1 between exons 9 and 10. Two pathogenic missense WT1 variants were identified in two 46,XY individuals with Wilms’ tumors; both patients were <1 year of age at the time of diagnosis. A novel WT1 variant, c.1453_1456 (p.Arg485Glyfs*14), was identified in a 46,XX patient with testicular DSD. Nephrotic proteinuria was diagnosed in all patients, including 3 who underwent renal transplantation after progressing to end-stage kidney disease. The expanding phenotypic spectrum associated with WT1 variants in XY and XX individuals confirms their pivotal role in gonadal and renal development as well as in tumorigenesis, emphasizing the clinical implications of these variants in genetic diagnosis.
Safety and Effectiveness of a Single Multiallergen Subcutaneous Immunotherapy in Polyallergic Patients
Authors: Nevot-Falcó Santiago , Mancebo Eloina Gonzalez , Martorell Antonio , Calatayud Cristina Martorell , Perotti Sheila Cabrejos , Rojas Maria Jose , Rodriguez-Rodriguez Mercedes , Padial Maria Antonia , El Qutob Lopez Francisco David , Perez-Camo Ignacio , Gomez-Brenosa Belen , Cano María del Mar Gandolfo , Gonzalez de Olano David , Ferre-Ybarz Laia , López Fernando Florido , Lara Jiménez Ángeles , Aldunate-Muruzabal Teresa , Pascual Maria Cristina , Villas Felicitas , Garcia Esther Compes , Reche Marta , Antolin-Amerigo Dario , Barbarroja-Escudero José , Romero Eva Nieto , Ruiz-Garcia Monica
Published: August 2021

Background: As the number of allergic sensitizations increases the severity of allergic respiratory diseases worsens. Multiple monoallergen immunotherapy can be accompanied by poor treatment adherence and high costs, single multiallergen immunotherapy needs to prove efficacy whilst maintaining a good safety profile. Methods: Observational, retrospective, multicenter study using a 2-pollen single undiluted multiallergen subcutaneous immunotherapy (SCIT) in routine clinical practice in Spain. Patients with rhinoconjunctivitis, with/without controlled asthma, sensitized to grass, olive, Parietaria, Cupressus, plane tree and/or Salsola pollen were included. Primary and secondary clinical efficacy endpoints were quality of life (mini Rhinitis Quality of Life Questionnaire (miniRQLQ)) and visual analogue scale (VAS) respectively. All adverse events were documented. Results: Ten centers included 97 patients, median age 32 years. SCIT treatment included combinations of grass mix with olive, Parietaria, Cupressus, plane tree or Salsola or olive with Parietaria, Cupressus or Salsola. The mean duration of SCIT was 1.8 years with a high treatment adherence (73%). Significant improvement in quality of life, nasal and ocular symptoms, activity limitations and practical problems (p< 0.0001) and other symptoms (p= 0.024) was observed. Most patients did not develop asthma-like symptoms and a significant improvement of all allergic symptom severity was perceived. VAS showed a significant improvement in rhinoconjunctivitis and asthma by patients and physicians. Twenty-nine patients experienced adverse reactions, 25 had local and 6 had systemic reactions. Conclusions: Single undiluted multiallergen SCIT treatment of two different pollens is efficacious and safe in both children and adults, showing that it is a suitable option for the treatment of polyallergic patients.
Lung Ultrasound in Bronchopulmonary Dysplasia: Patterns and Predictors in Very Preterm Infants
Authors: Aldecoa-Bilbao Victoria , Velilla Mar , Teresa-Palacio Marta , Esponera Carla Balcells , Barbero Ana Herranz , Sin-Soler María , Sanz Martín Iriondo , Salvia Roigés Maria Dolors
Published: August 2021

Introduction: Lung ultrasound (LUS) is useful for respiratory management in very preterm infants (VPI), but little is known about the echographic patterns in bronchopulmonary dysplasia (BPD), the relation between the image findings, and the severity of the disease and its long-term outcomes. We aimed to describe LUS patterns in BPD and analyze the accuracy of LUS to predict the need for respiratory support at 36 weeks postmenstrual age (PMA) in VPI. Methods: Preterm infants ≤30.6 weeks of gestational age were recruited. LUS was performed at admission, at 7th, and 28th day of life (DOL) with a standardized protocol (6 zones: anterior, lateral, and posterior fields). Clinical data, respiratory outcomes, and image findings were recorded. Results: Eighty-nine patients were studied. Infants with BPD had significantly higher LUS score at admission, at 7th, and 28th DOL. Patients with BPD exhibited more consolidations and pleural line abnormalities at 7th and 28th DOL than those without BPD (p < 0.001), regardless of the definition used for BPD. LUS at 7th DOL predicted NICHD 2001-BPD with R2 = 0.522; AUC = 0.87 (0.79–0.94), p < 0.001, and Jensen 2019-BPD with R2 = 0.315 (AUC = 0.80 [0.70–0.90], p < 0.001). A model including mechanical ventilation >5 days, oxygen therapy for 7 days and LUS score at 7th DOL accurately predicted the need for respiratory support at 36 weeks PMA (R2 = 0.655, p < 0.001) with an AUC = 0.90 (0.84–0.97), p < 0.001. Conclusion: LUS score, pleural line abnormalities, and consolidations can be useful to diagnose BPD in VPI and to predict its severity after the first week of life.
Benzalkonium Chloride-Preserved Anti-Glaucomatous Eye Drops and Their Effect on Human Conjunctival Goblet Cells in vitro
Authors: Hedengran Anne , Begun Xenia , Müllertz Olivia , Mouhammad Zaynab , Vohra Rupali , Bair Jeffrey , Dartt Darlene A. , Cvenkel Barbara , Heegaard Steffen , Petrovski Goran , Kolko Miriam
Published: August 2021

Introduction: Most intraocular pressure (IOP)-lowering eye drops are preserved with benzalkonium chloride (BAK). This can increase side effects and decrease adherence. Particularly, damage to the mucin-producing conjunctival goblet cells may be an issue due to instability of the tear film. We aimed to investigate the effect of IOP-lowering eye drops preserved with BAK on cultured human conjunctival goblet cells. Methods: Eye drops Brimonidine Tartrate Teva (BT) with 0.005% BAK, Dorzolamide Stada (DS) with 0.0075% BAK, Optimol® (OP) with 0.01% BAK, and Latanoprost Teva (LT) with 0.02% BAK were included. Human primary cultured goblet cell survival was evaluated using a lactate dehydrogenase assay on human goblet cells after treatment for 30 min and 6 h with the different anti-glaucoma drug formulations. Results: All eye drops examined, except BT, reduced goblet cell survival. The impact of eye drops on goblet cell viability was correlated with the time of exposure as well as to the concentration of BAK. After 30 min of exposure, cell viability was 93% for BT (0.005% BAK; p = 0.93), 71% for DS (0.0075% BAK; p = 0.067), 70% for OP (0.01% BAK; p = 0.054), and 69% for LT (0.02% BAK; p = 0.022), and exposure for 6 h reduced cell survival to 74% for BT (p = 0.217), 52% for DS (p = 0.011), 34% for OP (p = 0.017), and 31% for LT (p = 0.0007). Conclusion: LT, OP, and DS reduced human goblet cell survival in a time-dependent manner. BT did not affect goblet cell survival. Cell survival was correlated with the BAK concentration in the eye drops making 0.02% BAK-preserved LT most toxic and 0.005% BAK-preserved BT least toxic. Based on the present study, decreasing BAK in eye drops for chronic use seems important to reduce damage to the goblet cells. However, future studies are needed to further explore this finding.
Onychomycosis Caused by Kloeckera apiculata: A Case Report in a Patient with Multiple Sclerosis
Authors: Sánchez-Cárdenas Carlos Daniel , Vega-Sánchez Diana Carolina , González-Suárez Tania Rosalia , Flores-Rivera José , Arenas Roberto G. , Corona Teresa
Published: August 2021

We report the first case of onychomycosis caused by Kloeckera apiculata in a woman with multiple sclerosis. Video-dermoscopic examination showed a spiked pattern and distal irregular aspect. Colonies on Sabouraud agar were white, creamy, and smooth. A microscopic examination showed blastoconidia. MALDI-TOF confirmed Kloeckera apiculata as the causal agent.
Erratum: Investigation of Feline calicivirus infection in cats with upper respiratory tract disease in Diyarbakir, Turkey
Authors: Baksi Nazan , Simsek Aynur
Published: August 2021

Feline calicivirus is among the most common pathogenic microorganisms in upper respiratory tract disease (URTD) and oral lesions of cats. It leads to stomatitis, oral ulceration, ocular and nasal discharge, conjunctivitis, fever, lameness, anorexia, hypersalivation, pneumonia, respiratory distress, coughing, and depression in infected cats. This study aimed to determine the role of Feline calicivirus (FCV) in cats with the upper respiratory tract disease in the Diyarbakir region, Turkey, to provide treatment for infected cats and contribute to the disease prophylaxis. The study material consisted of 10 cats (control group) considered to be healthy according to the clinical examination and 20 cats with URTD that were not vaccinated against Feline calicivirus infection of different breeds, ages, and genders brought to Dicle University Veterinary Faculty Prof. Dr. Servet SEKIN Polyclinic with URTD. After routine clinical examinations of the animals, oral and conjunctival swabs and blood samples were taken. Hematological and biochemical analyzes of blood samples were performed. Swab samples were analyzed by the polymerase chain reaction (PCR) method for the diagnosis of the agent. Oral lesions, hypersalivation, ocular and nasal discharge, coughing, and breathing difficulties were seen in clinical examinations of cats with URTD. Feline calicivirus was detected in only one cat's conjunctival swab sample in PCR analyses. As a result, we found that Feline calicivirus infection was present in cats with URTD in the Diyarbakir region, and 5% positivity was found in cats with clinical symptoms according to PCR analysis.
Expressões cartográficas da região das Guianas
Authors: Silva Gutemberg de Vilhena
Published: August 2021

A partir da metade do século XX, proliferaram estudos em diversos campos de conhecimento sobre a região das Guianas. Mesmo assim, até hoje há uma grande lacuna na atualização de cartografias temáticas que expliquem suas geografias. O objetivo deste texto é tecer reflexões sobre a construção de cinco mapas que elaboramos para evidenciar aspectos do ordenamento territorial da região e, com isso, elucidar questões relevantes de seu passado e presente. Para compor os mapas e nossa argumentação, recorremos à revisão de literatura, à coleta e tabulação de dados primários (estatísticas) e ao trabalho de campo como balizas metodológicas.
Território usado e cultura urbana: o circuito hip hop na metrópole de Havana (1979-2015)
Authors: Alves Cristiano Nunes
Published: August 2021

Refletindo sobre o território usado, operacionalizamos a noção de circuito cultural, destacando materialidades e ações dinamizadas pela cultura hip hop na metrópole de Havana, capital de Cuba. Baseados em levantamento bibliográfico e documental, além do trabalho de campo, propomos uma periodização (1979-2003) para o hip hop havaneiro, e, em seguida, apresentamos uma análise da contemporaneidade do circuito (2015), abordando: (i) seus discursos e (ii) a tipologia-topologia de seus fixos, fluxos e agentes. Observa-se um circuito periférico dinamizado sobretudo por ações de resistência, fortemente caracterizadas pelo improviso, impondo o protagonismo dos sujeitos que, fundindo estética e política, conferem amarração à metrópole a partir dos lugares.
O perfil facial e a prevalência de canal mandibular bífido
Authors: Oliveira Isaura Cristina Senna de , Zenith Milena Bortolotto Felippe Silva , Raitz Ricardo
Published: August 2021

Objetivo: Avaliar a prevalência dos canais mandibulares bífidos (CMB) e correlacioná-los com os tipos faciais (TF) por meio de tomografia computadorizada de feixe cônico (TCFC). Material e método: A amostra, composta por 180 hemimandíbulas (90 pacientes), foi determinada por: TF, sexo, idade e lado da face. O TF foi determinado utilizando o índice VERT de Ricketts. As TCFC foram dispostas em três grupos de acordo com os TF: 30 pacientes braquifaciais, 30 mesofaciais e 30 dolicofaciais. Os CMB foram classificados de acordo com Naitoh et al. (2011). As imagens foram classificadas e avaliadas por um radiologista treinado, utilizando os softwares Dolphin Imaging® 11.0 e XoranCat®. A comparação entre os grupos em relação ao sexo, lado acometido e classe do CMB foi feita pelo teste Qui-quadrado ou Exato de Fisher; a influência da idade em relação ao sexo e presença de CMB, pelo teste de Mann-Whitney e, em relação ao TF, pelo teste de Kruskal-Wallis. A relação entre o sexo dos pacientes e presença do CMB, pelo teste Exato de Fisher. O nível de significância considerado foi de 5% para todos os testes. Resultados: A proporção de pacientes com CMB na amostra foi de 14.4%, sendo o mais frequente o tipo C sentido alveolar (53.8%), seguidos dos tipos D sentido retromolar (15.4%), tipo E sentido lingual (15.4%) e tipo F sentido base da mandíbula (7.7%). Quando o CMB estava presente, não houve predominância de lado nem influência pelo sexo. Conclusão: O TF não afeta a presença ou o tipo de CMB.
Objetivo: Avaliar a prevalência dos canais mandibulares bífidos (CMB) e correlacioná-los com os tipos faciais (TF) por meio de tomografia computadorizada de feixe cônico (TCFC). Material e método: A amostra, composta por 180 hemimandíbulas (90 pacientes), foi determinada por: TF, sexo, idade e lado da face. O TF foi determinado utilizando o índice VERT de Ricketts. As TCFC foram dispostas em três grupos de acordo com os TF: 30 pacientes braquifaciais, 30 mesofaciais e 30 dolicofaciais. Os CMB foram classificados de acordo com Naitoh et al. (2011). As imagens foram classificadas e avaliadas por um radiologista treinado, utilizando os softwares Dolphin Imaging® 11.0 e XoranCat®. A comparação entre os grupos em relação ao sexo, lado acometido e classe do CMB foi feita pelo teste Qui-quadrado ou Exato de Fisher; a influência da idade em relação ao sexo e presença de CMB, pelo teste de Mann-Whitney e, em relação ao TF, pelo teste de Kruskal-Wallis. A relação entre o sexo dos pacientes e presença do CMB, pelo teste Exato de Fisher. O nível de significância considerado foi de 5% para todos os testes. Resultados: A proporção de pacientes com CMB na amostra foi de 14.4%, sendo o mais frequente o tipo C sentido alveolar (53.8%), seguidos dos tipos D sentido retromolar (15.4%), tipo E sentido lingual (15.4%) e tipo F sentido base da mandíbula (7.7%). Quando o CMB estava presente, não houve predominância de lado nem influência pelo sexo. Conclusão: O TF não afeta a presença ou o tipo de CMB.
Interpretation of Incidental Genetic Findings Localizing to Genes Associated With Cardiac Channelopathies and Cardiomyopathies
Authors: Ezekian Jordan E. , Rehder Catherine , Kishnani Priya S. , Landstrom Andrew P.
Published: August 2021

Recent advances in next-genetic sequencing technology have facilitated an expansion in the use of exome and genome sequencing in the research and clinical settings. While this has aided in the genetic diagnosis of individuals with atypical clinical presentations, there has been a marked increase in the number of incidentally identified variants of uncertain diagnostic significance in genes identified as clinically actionable by the American College of Medical Genetics guidelines. Approximately 20 of these genes are associated with cardiac diseases, which carry a significant risk of sudden cardiac death. While identification of at-risk individuals is paramount, increased discovery of incidental variants of uncertain diagnostic significance has placed a burden on the clinician tasked with determining the diagnostic significance of these findings. Herein, we describe the scope of this emerging problem using cardiovascular genetics to illustrate the challenges associated with variants of uncertain diagnostic significance interpretation. We review the evidence for diagnostic weight of these variants, discuss the role of clinical genetics providers in patient care, and put forward general recommendations about the interpretation of incidentally identified variants found with clinical genetic testing.
Preconditioning by Preceding Ischemic Cerebrovascular Events
Authors: Correia Pamela N. , Meyer Ivo A. , Eskandari Ashraf , Amiguet Michael , Hirt Lorenz , Michel Patrik
Published: August 2021

Background

Emerging yet contrasting evidence from animal and human studies associates ischemic preconditioning with improvement of subsequent stroke severity, although long‐term outcome remains unclear. The purpose of this study was to analyze how preceding cerebral ischemic events influence subsequent stroke severity and outcome.

Methods and Results

Data for this retrospective cohort study were extracted from ASTRAL (Acute Stroke Registry and Analysis of Lausanne). This registry includes a sample of all consecutive patients with acute ischemic strokes admitted to the stroke unit and/or intensive care unit of the Lausanne University Hospital, Switzerland. We investigated associations between preceding ischemic events (transient ischemic attacks or ischemic strokes) and the impact on subsequent stroke severity and clinical improvement within 24 hours, measured through National Institute of Health Stroke Scale, as well as 3‐month outcome, determined through a shift in the modified Rankin Scale. Of 3530 consecutive patients with ischemic stroke (43% women, median age 73 years), 1001 (28%) had ≥1 preceding cerebral ischemic events (45% transient ischemic attack, 55% ischemic stroke; 31% multiple events). After adjusting for multiple prehospital, clinical, and laboratory confounders, admission stroke severity was significantly lower in patients preconditioned through a preceding ischemic event, but 24‐hour improvement was not significant and 3‐month outcome was unfavorable.

Conclusions

Preceding ischemic events were independently associated with a significant reduction in subsequent stroke severity but worsened long‐term clinical outcome. These results, if confirmed by future randomized studies, may help design neuroprotective strategies. The unfavorable effect on stroke outcome is probably a consequence of the cumulative disability burden after multiple ischemic events.
Cerebral Edema in Patients With Large Hemispheric Infarct Undergoing Reperfusion Treatment: A HERMES Meta-Analysis
Authors: Ng Felix C. , Yassi Nawaf , Sharma Gagan , Brown Scott B. , Goyal Mayank , Majoie Charles B.L.M. , Jovin Tudor G. , Hill Michael D. , Muir Keith W. , Saver Jeffrey L. , Guillemin Francis , Demchuk Andrew M. , Menon Bijoy K. , San Roman Luis , Liebeskind David S. , White Philip , Dippel Diederik W.J. , Davalos Antoni , Bracard Serge , Mitchell Peter J. , Wald Michael J. , Davis Stephen M. , Sheth Kevin N. , Kimberly W. Taylor , Campbell Bruce C.V. ,   for the HERMES Collaborators
Published: August 2021

Background and Purpose:

Whether reperfusion into infarcted tissue exacerbates cerebral edema has treatment implications in patients presenting with extensive irreversible injury. We investigated the effects of endovascular thrombectomy and reperfusion on cerebral edema in patients presenting with radiological evidence of large hemispheric infarction at baseline.

Methods:

In a systematic review and individual patient-level meta-analysis of 7 randomized controlled trials comparing thrombectomy versus medical therapy in anterior circulation ischemic stroke published between January 1, 2010, and May 31, 2017 (Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration), we analyzed the association between thrombectomy and reperfusion with maximal midline shift (MLS) on follow-up imaging as a measure of the space-occupying effect of cerebral edema in patients with large hemispheric infarction on pretreatment imaging, defined as diffusion-magnetic resonance imaging or computed tomography (CT)-perfusion ischemic core 80 to 300 mL or noncontrast CT-Alberta Stroke Program Early CT Score ≤5. Risk of bias was assessed using the Cochrane tool.

Results:

Among 1764 patients, 177 presented with large hemispheric infarction. Thrombectomy and reperfusion were associated with functional improvement (thrombectomy common odds ratio =2.30 [95% CI, 1.32–4.00]; reperfusion common odds ratio =4.73 [95% CI, 1.66–13.52]) but not MLS (thrombectomy β=−0.27 [95% CI, −1.52 to 0.98]; reperfusion β=−0.78 [95% CI, −3.07 to 1.50]) when adjusting for age, National Institutes of Health Stroke Score, glucose, and time-to-follow-up imaging. In an exploratory analysis of patients presenting with core volume >130 mL or CT-Alberta Stroke Program Early CT Score ≤3 (n=76), thrombectomy was associated with greater MLS after adjusting for age and National Institutes of Health Stroke Score (β=2.76 [95% CI, 0.33–5.20]) but not functional improvement (odds ratio, 1.71 [95% CI, 0.24–12.08]).

Conclusions:

In patients presenting with large hemispheric infarction, thrombectomy and reperfusion were not associated with MLS, except in the subgroup with very large core volume (>130 mL) in whom thrombectomy was associated with increased MLS due to space-occupying ischemic edema. Mitigating cerebral edema-mediated secondary injury in patients with very large infarcts may further improve outcomes after reperfusion therapies.
Edges in brain networks: Contributions to models of structure and function
Authors: Faskowitz Joshua , Betzel Richard F. , Sporns Olaf
Published: August 2021

Network models describe the brain as sets of nodes and edges that represent its distributed organization. So far, most discoveries in network neuroscience have prioritized insights that highlight distinct groupings and specialized functional contributions of network nodes. Importantly, these functional contributions are determined and expressed by the web of their interrelationships, formed by network edges. Here, we underscore the important contributions made by brain network edges for understanding distributed brain organization. Different types of edges represent different types of relationships, including connectivity and similarity among nodes. Adopting a specific definition of edges can fundamentally alter how we analyze and interpret a brain network. Furthermore, edges can associate into collectives and higher order arrangements, describe time series, and form edge communities that provide insights into brain network topology complementary to the traditional node-centric perspective. Focusing on the edges, and the higher order or dynamic information they can provide, discloses previously underappreciated aspects of structural and functional network organization.