bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fate of patients after failed epicardial ablation of atrial fibrillation
Authors: Nasso Giuseppe , Lorusso Roberto , Motekallemi Arash , Dell’Aquila Angelo M. , Di Bari Nicola , Condello Ignazio , Moscarelli Marco , Iacopino Saverio , Serraino Giuseppe F. , Mastroroberto Pasquale , Santarpino Giuseppe , Speziale Giuseppe 
Published: September 2021

Abstract
Background
Much debate is still going on about the best ablation strategy—via endocardial or epicardial approach—in patients with atrial fibrillation (AF), and evidence gaps exist in current guidelines in this area. More specifically, there are no clear long-term outcome data after failed surgical AF ablation.

Methods
Since June 2008, 549 surgical AF ablation procedures through a right minithoracotomy were performed at our institution. From 2008 to 2011, a unipolar radiofrequency device was used (151 patients), whereas from 2011 to 2020 a bipolar radiofrequency device was used (398 patients). Patients were scheduled for surgery on the basis of the following criteria: recurrent episodes of paroxysmal or persistent lone AF refractory to maximally tolerated antiarrhythmic drug dosing and at least one failed cardioversion attempt. Besides the recommended follow-up by the local cardiologist, starting from 2021, surviving patients were asked to undergo assessment of left ventricular function and to complete a questionnaire addressing quality of life and predisposing factors for recurrent AF.

Results
At a mean follow-up of 77 months, the rate of AF recurrence was 20.7% (n = 114). On multivariate analysis, impaired left ventricular ejection fraction (58 patients, 51%, p = 0.002), worsening of European Heart Rhythm Association (EHRA) symptom class (37 patients, 32%, p = 0.003) and cognitive decline or depression (23 patients, 20%, p = 0.023) during follow-up were found to be significantly associated with AF recurrence.

Conclusions
Surgical AF ablation through a right minithoracotomy is safe, but a better outcome could be achieved using a hybrid approach. Patients after initial failed surgical AF ablation show worsening of cardiac function, clinical status and quality of life at follow-up compared to patients with successful AF ablation.
Cannabinoid use and effects in patients with epidermolysis bullosa: an international cross-sectional survey study
Authors: Schräder Nicholas H. B. , Gorell Emily S. , Stewart Roy E. , Duipmans José C. , Harris Nicole , Perez Victoria A. , Tang Jean Y. , Wolff André P. , Bolling Marieke C. 
Published: September 2021

Abstract
Background
Epidermolysis bullosa (EB) patient anecdotes and case reports indicate that cannabinoid-based medicines (CBMs) may alleviate pain and pruritus and improve wound healing. CBM use has not been characterized in the EB patient population.

Objectives
To evaluate CBM use among EB patients, including CBM types, effects on symptoms (e.g., pain and pruritus), disease process (e.g., blistering, wounds, and inflammation), well-being (e.g., sleep, appetite) and concomitant medications.

Methods
English-speaking EB patients or caregivers completed an online international, anonymous, cross-sectional survey regarding CBM use. Respondents reported the types of CBMs, subsequent effects including perceived EB symptom alteration, changes in medication use, and side effects.

Results
Seventy-one EB patients from five continents reported using or having used CBMs to treat their EB. Missing question responses ranged between 0 (0%) and 33 (46%). Most used more than one CBM preparation (mean: 2.4 ± 1.5) and route of administration (mean: 2.1 ± 1.1). Topical and ingested were the most common routes. Pain and pruritus were reported retrospectively to decrease by 3 points (scale: 0–10; p < 0.001 for both) after CBM use. Most reported that CBM use improved their overall EB symptoms (95%), pain (94%), pruritus (91%) and wound healing (81%). Most participants (79%) reported decreased use of pain medications. The most common side-effect was dry mouth (44%).

Conclusions
CBMs improve the perception of pain, pruritus, wound healing, and well-being in EB patients and reduced concomitant medication use. Nevertheless, a direct relation between the use of CBMs and reduction of the above-mentioned symptoms cannot be proven by these data. Therefore, future controlled studies using pharmaceutically standardised CBM preparations in EB are warranted to delineate the risks and benefits of CBMs.
GDF11 expressed in the adult brain negatively regulates hippocampal neurogenesis
Authors: Mayweather Brittany A. , Buchanan Sean M. , Rubin Lee L. 
Published: September 2021

AbstractGrowth differentiation factor 11 (GDF11) is a transforming factor-β superfamily member that functions as a negative regulator of neurogenesis during embryonic development. However, when recombinant GDF11 (rGDF11) is administered systemically in aged mice, it promotes neurogenesis, the opposite of its role during development. The goal of the present study was to reconcile this apparent discrepancy by performing the first detailed investigation into the expression of endogenous GDF11 in the adult brain and its effects on neurogenesis. Using quantitative histological analysis, we observed that Gdf11 is most highly expressed in adult neurogenic niches and non-neurogenic regions within the hippocampus, choroid plexus, thalamus, habenula, and cerebellum. To investigate the role of endogenous GDF11 during adult hippocampal neurogenesis, we generated a tamoxifen inducible mouse that allowed us to reduce GDF11 levels. Depletion of Gdf11 during adulthood increased proliferation of neural progenitors and decreased the number of newborn neurons in the hippocampus, suggesting that endogenous GDF11 remains a negative regulator of hippocampal neurogenesis in adult mice. These findings further support the idea that circulating systemic GDF11 and endogenously expressed GDF11 in the adult brain have different target cells or mechanisms of action. Our data describe a role for GDF11-dependent signaling in adult neurogenesis that has implications for how GDF11 may be used to treat CNS disease.
Intracellular delivery of anti-BCR/ABL antibody by PLGA nanoparticles suppresses the oncogenesis of chronic myeloid leukemia cells
Authors: Jiang Guoyun , Huang Zhenglan , Yuan Ying , Tao Kun , Feng Wenli 
Published: September 2021

Abstract
Background
The pathogenesis of chronic myeloid leukemia (CML) is the formation of the BCR/ABL protein, which is encoded by the bcr/abl fusion gene, possessing abnormal tyrosine kinase activity. Despite the wide application of tyrosine kinase inhibitors (TKIs) in CML treatment, TKIs drug resistance or intolerance limits their further usage in a subset of patients. Furthermore, TKIs inhibit the tyrosine kinase activity of the BCR/ABL oncoprotein while failing to eliminate the pathologenic oncoprotein. To develop alternative strategies for CML treatment using therapeutic antibodies, and to address the issue that antibodies cannot pass through cell membranes, we have established a novel intracellular delivery of anti-BCR/ABL antibodies, which serves as a prerequisite for CML therapy.

Methods
Anti-BCR/ABL antibodies were encapsulated in poly(d, l-lactide-co-glycolide) nanoparticles (PLGA NPs) by a double emulsion method, and transferrin was labeled on the surface of the nanoparticles (Ab@Tf-Cou6-PLGA NPs). The characteristics of nanoparticles were measured by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Cellular uptake of nanoparticles was measured by flow cytometry (FCM). The effect of nanoparticles on the apoptosis and proliferation of CML cells was testified by FCM and CCK-8 assay. In addition, the anti-cancer impact of nanoparticles was evaluated in mouse models of CML.

Results
The results demonstrated that the Ab@Tf-Cou6-PLGA NPs functioned as an intracellular deliverer of antibodies, and exhibited an excellent effect on degrading BCR/ABL oncoprotein in CML cells via the Trim-Away pathway. Treatment with Ab@Tf-Cou6-PLGA NPs inhibited the proliferation and induced the apoptosis of CML cells in vitro as well as impaired the oncogenesis ability of CML cells in vivo.

Conclusions
In conclusion, our study indicated that this approach achieved safe and efficient intracellular delivery of antibodies and degraded BCR/ABL oncoprotein via the Trim-Away pathway, which provides a promising therapeutic strategy for CML patients, particularly those with TKI resistance.
NanoCaller for accurate detection of SNPs and indels in difficult-to-map regions from long-read sequencing by haplotype-aware deep neural networks
Authors: Ahsan Mian Umair , Liu Qian , Fang Li , Wang Kai 
Published: September 2021

AbstractLong-read sequencing enables variant detection in genomic regions that are considered difficult-to-map by short-read sequencing. To fully exploit the benefits of longer reads, here we present a deep learning method NanoCaller, which detects SNPs using long-range haplotype information, then phases long reads with called SNPs and calls indels with local realignment. Evaluation on 8 human genomes demonstrates that NanoCaller generally achieves better performance than competing approaches. We experimentally validate 41 novel variants in a widely used benchmarking genome, which could not be reliably detected previously. In summary, NanoCaller facilitates the discovery of novel variants in complex genomic regions from long-read sequencing.
Gramtools enables multiscale variation analysis with genome graphs
Authors: Letcher Brice , Hunt Martin , Iqbal Zamin 
Published: September 2021

AbstractGenome graphs allow very general representations of genetic variation; depending on the model and implementation, variation at different length-scales (single nucleotide polymorphisms (SNPs), structural variants) and on different sequence backgrounds can be incorporated with different levels of transparency. We implement a model which handles this multiscale variation and develop a JSON extension of VCF (jVCF) allowing for variant calls on multiple references, both implemented in our software . We find outperforms existing methods for genotyping SNPs overlapping large deletions in M. tuberculosis and is able to genotype on multiple alternate backgrounds in P. falciparum, revealing previously hidden recombination.
Genomic basis underlying the metabolome-mediated drought adaptation of maize
Authors: Zhang Fei , Wu Jinfeng , Sade Nir , Wu Si , Egbaria Aiman , Fernie Alisdair R. , Yan Jianbing , Qin Feng , Chen Wei , Brotman Yariv , Dai Mingqiu 
Published: September 2021

Abstract
Background
Drought is a major environmental disaster that causes crop yield loss worldwide. Metabolites are involved in various environmental stress responses of plants. However, the genetic control of metabolomes underlying crop environmental stress adaptation remains elusive.

Results
Here, we perform non-targeted metabolic profiling of leaves for 385 maize natural inbred lines grown under well-watered as well as drought-stressed conditions. A total of 3890 metabolites are identified and 1035 of these are differentially produced between well-watered and drought-stressed conditions, representing effective indicators of maize drought response and tolerance. Genetic dissections reveal the associations between these metabolites and thousands of single-nucleotide polymorphisms (SNPs), which represented 3415 metabolite quantitative trait loci (mQTLs) and 2589 candidate genes. 78.6% of mQTLs (2684/3415) are novel drought-responsive QTLs. The regulatory variants that control the expression of the candidate genes are revealed by expression QTL (eQTL) analysis of the transcriptomes of leaves from 197 maize natural inbred lines. Integrated metabolic and transcriptomic assays identify dozens of environment-specific hub genes and their gene-metabolite regulatory networks. Comprehensive genetic and molecular studies reveal the roles and mechanisms of two hub genes, Bx12 and ZmGLK44, in regulating maize metabolite biosynthesis and drought tolerance.

Conclusion
Our studies reveal the first population-level metabolomes in crop drought response and uncover the natural variations and genetic control of these metabolomes underlying crop drought adaptation, demonstrating that multi-omics is a powerful strategy to dissect the genetic mechanisms of crop complex traits.
Entomological characterization of Aedes mosquitoes and arbovirus detection in Ibagué, a Colombian city with co-circulation of Zika, dengue and chikungunya viruses
Authors: Carrasquilla María C. , Ortiz Mario I. , León Cielo , Rondón Silvia , Kulkarni Manisha A. , Talbot Benoit , Sander Beate , Vásquez Heriberto , Cordovez Juan M. , González Camila ,   RADAM-LAC Research Team, Sander Beate , Kulkarni Manisha A. , Wu Jianhong , González Camila , Miretti Marcos , Espinel Mauricio , Cevallos Varsovia 
Published: September 2021

Abstract
Background
Dengue, Zika and chikungunya are arboviruses of significant public health importance that are transmitted by Aedes aegypti and Aedes albopictus mosquitoes. In Colombia, where dengue is hyperendemic, and where chikungunya and Zika were introduced in the last decade, more than half of the population lives in areas at risk. The objective of this study was to characterize Aedes spp. vectors and study their natural infection with dengue, Zika and chikungunya in Ibagué, a Colombian city and capital of the department of Tolima, with case reports of simultaneous circulation of these three arboviruses.

Methods
Mosquito collections were carried out monthly between June 2018 and May 2019 in neighborhoods with different levels of socioeconomic status. We used the non-parametric Friedman, Mann–Whitney and Kruskal–Wallis tests to compare mosquito density distributions. We applied logistic regression analyses to identify associations between mosquito density and absence/presence of breeding sites, and the Spearman correlation coefficient to analyze the possible relationship between climatic variables and mosquito density.

Results
We collected Ae. aegypti in all sampled neighborhoods and found for the first time Ae. albopictus in the city of Ibagué. A greater abundance of mosquitoes was collected in neighborhoods displaying low compared to high socioeconomic status as well as in the intradomicile compared to the peridomestic space. Female mosquitoes predominated over males, and most of the test females had fed on human blood. In total, four Ae. aegypti pools (3%) were positive for dengue virus (serotype 1) and one pool for chikungunya virus (0.8%). Interestingly, infected females were only collected in neighborhoods of low socioeconomic status, and mostly in the intradomicile space.

Conclusions
We confirmed the co-circulation of dengue (serotype 1) and chikungunya viruses in the Ae. aegypti population in Ibagué. However, Zika virus was not detected in any mosquito sample, 3 years after its introduction into the country. The positivity for dengue and chikungunya viruses, predominance of mosquitoes in the intradomicile space and the high proportion of females fed on humans highlight the high risk for arbovirus transmission in Ibagué, but may also provide an opportunity for establishing effective control strategies.

Graphical abstract
Bactericidal activity of avian complement: a contribution to understand avian-host tropism of Lyme borreliae
Authors: Sürth Valerie , Lopes de Carvalho Isabel , Núncio Maria Sofia , Norte Ana Cláudia , Kraiczy Peter 
Published: September 2021

AbstractComplement has been considered as an important factor impacting the host–pathogen association of spirochetes belonging to the Borrelia burgdorferi sensu lato complex, and may play a role in the spirochete’s ecology. Birds are known to be important hosts for ticks and in the maintenance of borreliae. Recent field surveys and laboratory transmission studies indicated that certain avian species act as reservoir hosts for different Borrelia species. Nevertheless, our current understanding of the molecular mechanisms determining host tropism of Borrelia is still in its fledgling stage. Concerning the role of complement in avian-host tropism, only a few bird species and Borrelia species have been analysed so far. Here, we performed in vitro serum bactericidal assays with serum samples collected from four bird species including the European robin Erithacus rubecula, the great tit Parus major, the Eurasian blackbird Turdus merula, and the racing pigeon Columba livia, as well as four Borrelia species (B. afzelii, B. garinii, B. valaisiana, and B. burgdorferi sensu stricto). From July to September 2019, juvenile wild birds were caught using mist nets in Portugal. Racing pigeons were sampled in a loft in October 2019. Independent of the bird species analysed, all Borrelia species displayed an intermediate serum-resistant or serum-resistant phenotype except for B. afzelii challenged with serum from blackbirds. This genospecies was efficiently killed by avian complement, suggesting that blackbirds served as dead-end hosts for B. afzelii. In summary, these findings suggest that complement contributes in the avian–spirochete–tick infection cycle and in Borrelia-host tropism.
Complete mitogenomes of Anopheles peditaeniatus and Anopheles nitidus and phylogenetic relationships within the genus Anopheles inferred from mitogenomes
Authors: Guo Jing , Yan Zhen-Tian , Fu Wen-Bo , Yuan Huan , Li Xu-Dong , Chen Bin 
Published: September 2021

Abstract
Background
Despite the medical importance of mosquitoes of the genus Anopheles in the transmission of malaria and other human diseases, its phylogenetic relationships are not settled, and the characteristics of mitochondrial genome (mitogenome) are not thoroughly understood.

Methods
The present study sequenced and analyzed the complete mitogenomes of An. peditaeniatus and An. nitidus, investigated genome characteristics, and inferred the phylogenetic relationships of 76 Anopheles spp.

Results
The complete mitogenomes of An. peditaeniatus and An. nitidus are 15,416 and 15,418 bp long, respectively, and both include 13 PCGs, 22 tRNAs, two tRNAs and one control region (CR). Mitogenomes of Anopheles spp. are similar to those of other insects in general characteristics; however, the trnR and trnA have been reversed to “trnR-trnA,” as has been reported in other mosquito genera. Genome variations mainly occur in CR length (493–886 bp) with six repeat unit types identified for the first time that demonstrate an evolutionary signal. The subgenera Lophopodomyia, Stethomyia, Kerteszia, Nyssorhynchus, Anopheles and Cellia are inferred to be monophyletic, and the phylogenetic analyses support a new phylogenetic relationship among the six subgenera investigated, in that subgenus Lophopodomyia is the sister to all other five subgenera, and the remaining five subgenera are divided into two clades, one of which is a sister-taxon subgenera Stethomyia + Kerteszia, and the other consists of subgenus Nyssorhynchus as the sister to a sister-group subgenera Anopheles + Cellia. Four series (Neomyzomyia, Pyretophorus, Neocellia and Myzomyia) of the subgenus Cellia, and two series (Arribalzagia and Myzorhynchus) of the subgenus Anopheles were found to be monophyletic, whereas three sections (Myzorhynchella, Argyritarsis and Albimanus) and their subdivisions of the subgenus Nyssorhynchus were polyphyletic or paraphyletic.

Conclusions
The study comprehensively uncovered the characteristics of mitogenome and the phylogenetics based on mitogenomes in the genus Anopheles, and provided information for further study on the mitogenomes, phylogenetics and taxonomic revision of the genus.

Graphical abstract
Schistosoma japonicum peptide SJMHE1 inhibits acute and chronic colitis induced by dextran sulfate sodium in mice
Authors: Shan Wenqi , Zhang Wenzhe , Xue Fei , Ma Yongbin , Dong Liyang , Wang Ting , Zheng Yu , Feng Dingqi , Chang Ming , Yuan Guoyue , Wang Xuefeng 
Published: September 2021

Abstract
Background
Harnessing helminth-based immunoregulation is a novel therapeutic strategy for many immune dysfunction disorders, including inflammatory bowel diseases (IBDs). We previously identified a small molecule peptide from Schistosoma japonicum and named it SJMHE1. SJMHE1 can suppress delayed-type hypersensitivity, collagen-induced arthritis and asthma in mice. In this study, we assessed the effects of SJMHE1 on dextran sulfate sodium (DSS)-induced acute and chronic colitis.

Methods
Acute and chronic colitis were induced in C57BL/6 mice by DSS, following which the mice were injected with an emulsifier SJMHE1 or phosphate-buffered saline. The mice were then examined for body weight loss, disease activity index, colon length, histopathological changes, cytokine expression and helper T (Th) cell subset distribution.

Results
SJMHE1 treatment significantly suppressed DSS-induced acute and chronic colitis, improved disease activity and pathological damage to the colon and modulated the expression of pro-inflammatory and anti-inflammatory cytokines in splenocytes and the colon. In addition, SJMHE1 treatment reduced the percentage of Th1 and Th17 cells and increased the percentage of Th2 and regulatory T (Treg) cells in the splenocytes and mesenteric lymph nodes of mice with acute colitis. Similarly, SJMHE1 treatment upregulated the expression of interleukin-10 (IL-10) mRNA, downregulated the expression of IL-17 mRNA and modulated the Th cell balance in mice with chronic colitis.

Conclusions
Our data show that SJMHE1 provided protection against acute and chronic colitis by restoring the immune balance. As a small molecule, SJMHE1 might be a novel agent for the treatment of IBDs without immunogenicity concerns.

Graphical abstract