bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of convolutional neural networks towards nuclei segmentation in localization-based super-resolution fluorescence microscopy images
Authors: Mela Christopher A. , Liu Yang 
Published: June 2021

Abstract
Background
Automated segmentation of nuclei in microscopic images has been conducted to enhance throughput in pathological diagnostics and biological research. Segmentation accuracy and speed has been significantly enhanced with the advent of convolutional neural networks. A barrier in the broad application of neural networks to nuclei segmentation is the necessity to train the network using a set of application specific images and image labels. Previous works have attempted to create broadly trained networks for universal nuclei segmentation; however, such networks do not work on all imaging modalities, and best results are still commonly found when the network is retrained on user specific data. Stochastic optical reconstruction microscopy (STORM) based super-resolution fluorescence microscopy has opened a new avenue to image nuclear architecture at nanoscale resolutions. Due to the large size and discontinuous features typical of super-resolution images, automatic nuclei segmentation can be difficult. In this study, we apply commonly used networks (Mask R-CNN and UNet architectures) towards the task of segmenting super-resolution images of nuclei. First, we assess whether networks broadly trained on conventional fluorescence microscopy datasets can accurately segment super-resolution images. Then, we compare the resultant segmentations with results obtained using networks trained directly on our super-resolution data. We next attempt to optimize and compare segmentation accuracy using three different neural network architectures.

Results
Results indicate that super-resolution images are not broadly compatible with neural networks trained on conventional bright-field or fluorescence microscopy images. When the networks were trained on super-resolution data, however, we attained nuclei segmentation accuracies (F1-Score) in excess of 0.8, comparable to past results found when conducting nuclei segmentation on conventional fluorescence microscopy images. Overall, we achieved the best results utilizing the Mask R-CNN architecture.

Conclusions
We found that convolutional neural networks are powerful tools capable of accurately and quickly segmenting localization-based super-resolution microscopy images of nuclei. While broadly trained and widely applicable segmentation algorithms are desirable for quick use with minimal input, optimal results are still found when the network is both trained and tested on visually similar images. We provide a set of Colab notebooks to disseminate the software into the broad scientific community (https://github.com/YangLiuLab/Super-Resolution-Nuclei-Segmentation).
Transcriptome analysis of scions grafted to potato rootstock for improving late blight resistance
Authors: Li Yuexin , Zhao Degang 
Published: June 2021

Abstract
Background
Late blight seriously threatens potato cultivation worldwide. The severe and widespread damage caused by the fungal pathogen can lead to drastic decreases in potato yield. Although grafting technology has been widely used to improve crop resistance, the effects of grafting on potato late blight resistance as well as the associated molecular mechanisms remain unclear. Therefore, we performed RNA transcriptome sequencing analysis and the late blight resistance testing of the scion when the potato late blight-resistant variety Qingshu 9 and the susceptible variety Favorita were used as the rootstock and scion, respectively, and vice versa. The objective of this study was to evaluate the influence of the rootstock on scion disease resistance and to clarify the related molecular mechanisms.

Results
A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the expression levels of genes related to plant–pathogen interactions, plant mitogen-activated protein kinase (MAPK) signaling pathways, and plant hormone signal transduction pathways were significantly up-regulated in the scion when Qingshu 9 was used as the rootstock. Some of these genes encoded calcium-dependent protein kinases (CDPKs), chitin elicitor receptor kinases (CERKs), LRR receptor serine/threonine protein kinases (LRR-LRKs), NPR family proteins in the salicylic acid synthesis pathway, and MAPKs which were potato late blight response proteins. When Favorita was used as the rootstock, only a few genes of late blight response genes were upregulated in the scion of Qingshu 9. Grafted plants using resistant variety as rootstocks inoculated with P. infestans spores showed significant reductions in lesion size while no significant difference in lesion size was observed when susceptible variety was used as the rootstock. We also showed that this induction of disease resistance in scions, especially scions derived from susceptible potato varieties was mediated by the up-regulation of expression of genes involved in plant disease resistance in scions.

Conclusions
Our results showed that potato grafting using late blight resistant varieties as rootstocks could render or enhance resistance to late blight in scions derived from susceptible varieties via up-regulating the expression of disease resistant genes in scions. The results provide the basis for exploring the molecular mechanism underlying the effects of rootstocks on scion disease resistance.
An NADPH oxidase regulates carbon metabolism and the cell cycle during root nodule symbiosis in common bean (Phaseolus vulgaris)
Authors: Fonseca-García Citlali , Nava Noreide , Lara Miguel , Quinto Carmen 
Published: June 2021

Abstract
Background
Rhizobium–legume symbiosis is a specific, coordinated interaction that results in the formation of a root nodule, where biological nitrogen fixation occurs. NADPH oxidases, or Respiratory Burst Oxidase Homologs (RBOHs) in plants, are enzymes that generate superoxide (O2•−). Superoxide produces other reactive oxygen species (ROS); these ROS regulate different stages of mutualistic interactions. For example, changes in ROS levels are thought to induce ROS scavenging, cell wall remodeling, and changes in phytohormone homeostasis during symbiotic interactions. In common bean (Phaseolus vulgaris), PvRbohB plays a key role in the early stages of nodulation.

Results
In this study, to explore the role of PvRbohB in root nodule symbiosis, we analyzed transcriptomic data from the roots of common bean under control conditions (transgenic roots without construction) and roots with downregulated expression of PvRbohB (by RNA interference) non-inoculated and inoculated with R. tropici. Our results suggest that ROS produced by PvRBOHB play a central role in infection thread formation and nodule organogenesis through crosstalk with flavonoids, carbon metabolism, cell cycle regulation, and the plant hormones auxin and cytokinin during the early stages of this process.

Conclusions
Our findings provide important insight into the multiple roles of ROS in regulating rhizobia–legume symbiosis.
Outcomes after EVAR in females are similar to males
Authors: Tumer Naim Boran , Askin Goktan , Akkaya Bekir Bogachan , Civelek Isa , Unal Ertekin Utku , Iscan Hakki Zafer 
Published: June 2021

Abstract
Introduction
Women are less likely to develop infrarenal abdominal aortic aneurysm; however, when they do, it is almost always associated with challenging anatomy, more rapid aneurysmal growth rate and earlier rupture. Women generally have poorer outcomes following open aneurysm repair; and in this respect, the present study aims to evaluate if it is so after endovascular repair.

Methods
A retrospective analysis of our database was performed for patients underwent endovascular aneurysm repair (EVAR) between January 2013–March 2020. 249 elective EVAR patients were evaluated. Patients were categorized according to gender and 26 patients (10.4%) were female. Demographics and pre-peri-postoperative findings were compared. Propensity score matching (ratio 1:1) was performed to reduce selection bias.

Results
In the overall unmatched cohort, female population had more diabetes mellitus (p = 0.016) and hypertension (p = 0.005). However, coronary artery disease (p = 0.005) and coronary artery bypass grafting (p = 0.006) were more in male gender. Non-IFU implantation was higher in female group (38.5% vs. 11.5%, p = 0.025). After propensity matching, even though it was not statistically significant, early mortality for female gender was higher when compared to male gender (7.7% and 0%, respectively, p = 0.490). In the follow-up period, no difference in all-cause mortality, secondary interventions or complications have been observed between the genders.

Conclusion
Challenging anatomy and subsequently treated patients outside IFU may be the reasons for higher morbidity and mortality in women. However, despite these factors female and male patients revealed equivalent early and late results.
Colonization with selected antibiotic resistant bacteria among a cohort of Sri Lankan university students
Authors: Munasinghe Thilini , Vidanapathirana Gihani , Kuthubdeen Shahlina , Ekanayake Asela , Angulmaduwa Sacheera , De Silva Kunchana , Subhasinghe Susan , Kalupahana Ruwani , Liyanapathirana Veranja , Ip Margaret 
Published: June 2021

Abstract
Background
Antibiotic Resistance is an imminent global public health threat. Antibiotic resistance emerged in healthcare settings and has now moved on to the community settings.
This study was conducted to identify the rates of asymptomatic colonization with selected antibiotic resistant organisms, (Methicillin Resistant Staphylococcus aureus (MRSA), Extended Spectrum Beta Lactamase (ESBL) producing Escherichia coli and Klebsiella spp and carbapenem resistant E.coli and Klebsiella spp) - among a group of university students in Sri Lanka. Identification of genetic determinants of MRSA and ESBL was an additional objective of the study.

Methods
A self - collected nasal swab and a peri-rectal swab collected after passing stools were obtained. Routine microbiological methods were used for the isolation S.aureus from the nasal swab and E.coli and Klebsiella species from the peri-rectal swab. Antibiotic sensitivity testing was performed as recommended by clinical and laboratory standard institute (CLSI).
Three (3) genes that are responsible for ESBL production; blaCTX-M, blaSHV, and blaTEM were tested using previously described primers and PCR procedures. Identification of MecA and PVL genes attributed to MRSA was also done with PCR.

Results
A total of 322 participants between 21 and 28 years were recruited representing 5 different faculties of study. Seventy one (22.0%) were colonized with S.aureus and 14 among them with MRSA, making the MRSA colonization rate of 4.3%. Forty five (15%) of the participants were colonized with an ESBL producing E.coli or Klebsiella spp. No one was colonized with carbapenem resistant E.coli or Klebsiella species. Of the 45 ESBL producers the commonest genetic determinant identified was blaCTX-M (n = 36), while 16 isolates had blaTEM and 7 had blaSHV. Similarly, of the 14 isolates identified as MRSA, 3 (21.4%) were found to be PVL positive while 11 (78.6%) were MecA positive.

Conclusions
A high rate of colonization with ESBL producing E.coli and Klebsiella species was noted in our study group.
Comparison of the effectiveness of lecture instruction and virtual reality-based serious gaming instruction on the medical students’ learning outcome about approach to coma
Authors: Mansoory Meysam Siyah , Khazaei Mohammad Rasool , Azizi Seyyed Mohsen , Niromand Elham 
Published: June 2021

Abstract
Background
New approaches to e-learning and the use of virtual reality technology and serious game in medical education are on the rise. Therefore, the purpose of this study was to compare the effectiveness of lecture method and virtual reality-based serious gaming (VRBSG) method on students learning outcomes about the approach to coma.

Methods
We adopted a randomized trial method for this study and selected 50 medical students dividing them into experimental and control groups. Students’ learning outcome was measured with a 10-item test. Serious game usability scale was used to evaluate the usability of the serious game. Descriptive and inferential statistics were used for data analysis by SPSS-22 software.

Results
Students’ familiarity with e-learning and VRBSG was low. The mean usability of a VRBSG was 126.78 ± 10.34 out of 150. The majority of students were eager to be instructed through VRBSG. The mean score of learning outcomes in the experimental group was significantly higher than the control group (t = − 2.457, P = 0.019).

Conclusion
Students’ learning outcomes in the VRBSG group in the test approach to coma were significantly better than the lecture group. The usability of the serious game instruction method was high. Taken together, instruction through VRBSG had an effective role in medical students’ learning.
Large-scale genomic analysis reveals the genetic cost of chicken domestication
Authors: Wang Ming-Shan , Zhang Jin-Jin , Guo Xing , Li Ming , Meyer Rachel , Ashari Hidayat , Zheng Zhu-Qing , Wang Sheng , Peng Min-Sheng , Jiang Yu , Thakur Mukesh , Suwannapoom Chatmongkon , Esmailizadeh Ali , Hirimuthugoda Nalini Yasoda , Zein Moch Syamsul Arifin , Kusza Szilvia , Kharrati-Koopaee Hamed , Zeng Lin , Wang Yun-Mei , Yin Ting-Ting , Yang Min-Min , Li Ming-Li , Lu Xue-Mei , Lasagna Emiliano , Ceccobelli Simone , Gunwardana Humpita Gamaralalage Thilini Nisank , Senasig Thilina Madusanka , Feng Shao-Hong , Zhang Hao , Bhuiyan Abul Kashem Fazlul Haque , Khan Muhammad Sajjad , Silva Gamamada Liyanage Lalanie Pradeepa , Thuy Le Thi , Mwai Okeyo A. , Ibrahim Mohamed Nawaz Mohamed , Zhang Guojie , Qu Kai-Xing , Hanotte Olivier , Shapiro Beth , Bosse Mirte , Wu Dong-Dong , Han Jian-Lin , Zhang Ya-Ping 
Published: June 2021

Abstract
Background
Species domestication is generally characterized by the exploitation of high-impact mutations through processes that involve complex shifting demographics of domesticated species. These include not only inbreeding and artificial selection that may lead to the emergence of evolutionary bottlenecks, but also post-divergence gene flow and introgression. Although domestication potentially affects the occurrence of both desired and undesired mutations, the way wild relatives of domesticated species evolve and how expensive the genetic cost underlying domestication is remain poorly understood. Here, we investigated the demographic history and genetic load of chicken domestication.

Results
We analyzed a dataset comprising over 800 whole genomes from both indigenous chickens and wild jungle fowls. We show that despite having a higher genetic diversity than their wild counterparts (average π, 0.00326 vs. 0.00316), the red jungle fowls, the present-day domestic chickens experienced a dramatic population size decline during their early domestication. Our analyses suggest that the concomitant bottleneck induced 2.95% more deleterious mutations across chicken genomes compared with red jungle fowls, supporting the “cost of domestication” hypothesis. Particularly, we find that 62.4% of deleterious SNPs in domestic chickens are maintained in heterozygous states and masked as recessive alleles, challenging the power of modern breeding programs to effectively eliminate these genetic loads. Finally, we suggest that positive selection decreases the incidence but increases the frequency of deleterious SNPs in domestic chicken genomes.

Conclusion
This study reveals a new landscape of demographic history and genomic changes associated with chicken domestication and provides insight into the evolutionary genomic profiles of domesticated animals managed under modern human selection.
A method for cryopreservation and single nucleus RNA-sequencing of normal adult human interventricular septum heart tissue reveals cellular diversity and function
Authors: Larson Amy , Chin Michael T. 
Published: June 2021

Abstract
Background
Single cell sequencing of human heart tissue is technically challenging and methods to cryopreserve heart tissue for obtaining single cell information have not been standardized. Studies published to date have used varying methods to preserve and process human heart tissue, and have generated interesting datasets, but development of a biobanking standard has not yet been achieved. Heart transcription patterns are known to be regionally diverse, and there are few single cell datasets for normal human heart tissue.

Methods
Using pig tissue, we developed a rigorous and reproducible method for tissue mincing and cryopreservation that allowed recovery of high quality single nuclei RNA. We subsequently tested this protocol on normal human heart tissue obtained from organ donors and were able to recover high quality nuclei for generation of single nuclei RNA-seq datasets, using a commercially available platform from 10× Genomics. We analyzed these datasets using standard software packages such as CellRanger and Seurat.

Results
Human heart tissue preserved with our method consistently yielded nuclear RNA with RNA Integrity Numbers of greater than 8.5. We demonstrate the utility of this method for single nuclei RNA-sequencing of the normal human interventricular septum and delineating its cellular diversity. The human IVS showed unexpected diversity with detection of 23 distinct cell clusters that were subsequently categorized into different cell types. Cardiomyocytes and fibroblasts were the most commonly identified cell types and could be further subdivided into 5 different cardiomyocyte subtypes and 6 different fibroblast subtypes that differed by gene expression patterns. Ingenuity Pathway analysis of these gene expression patterns suggested functional diversity in these cell subtypes.

Conclusions
Here we report a simple technical method for cryopreservation and subsequent nuclear isolation of human interventricular septum tissue that can be done with common laboratory equipment. We show how this method can be used to generate single nuclei transcriptomic datasets that rival those already published by larger groups in terms of cell diversity and complexity and suggest that this simple method can provide guidance for biobanking of human myocardial tissue for complex genomic analysis.
miR-181a-regulated pathways in T-cell differentiation and aging
Authors: Kim Chulwoo , Ye Zhongde , Weyand Cornelia M. , Goronzy Jörg J. 
Published: June 2021

AbstractMicroRNAs (miRNAs) are regulatory noncoding RNAs important for many aspects of cellular processes including cell differentiation and proliferation. Functions of numerous miRNAs have been identified in T cells, with miR-181a regulating T cell activation thresholds during thymic T cell development and during activation of peripheral T cells. Intriguingly, miR-181a is implicated in defective antiviral and vaccine responses in older individuals, as its expression declines in naïve T cells with increasing age. Here, we review the pathways that are regulated by miR-181a and that explain the unique role of miR-181a in T cell development, T cell activation and antiviral T cell responses. These studies provide a framework for understanding how a decline in miR-181a expression in T cells could contribute to age-related defects in adaptive immunity. We furthermore review the mechanisms that cause the age-related decline in miR-181a expression and discuss the potential of restoring miR-181a expression or targeting miR-181a-regulated pathways to improve impaired T cell responses in older individuals.
Serious games for upper limb rehabilitation after stroke: a meta-analysis
Authors: Doumas Ioannis , Everard Gauthier , Dehem Stéphanie , Lejeune Thierry 
Published: June 2021

AbstractBackgroundApproximately two thirds of stroke survivors maintain upper limb (UL) impairments and few among them attain complete UL recovery 6 months after stroke. Technological progress and gamification of interventions aim for better outcomes and constitute opportunities in self- and tele-rehabilitation.ObjectivesOur objective was to assess the efficacy of serious games, implemented on diverse technological systems, targeting UL recovery after stroke. In addition, we investigated whether adherence to neurorehabilitation principles influenced efficacy of games specifically designed for rehabilitation, regardless of the device used.MethodThis systematic review was conducted according to PRISMA guidelines (PROSPERO registration number: 156589). Two independent reviewers searched PubMed, EMBASE, SCOPUS and Cochrane Central Register of Controlled Trials for eligible randomized controlled trials (PEDro score ≥ 5). Meta-analysis, using a random effects model, was performed to compare effects of interventions using serious games, to conventional treatment, for UL rehabilitation in adult stroke patients. In addition, we conducted subgroup analysis, according to adherence of included studies to a consolidated set of 11 neurorehabilitation principles.ResultsMeta-analysis of 42 trials, including 1760 participants, showed better improvements in favor of interventions using serious games when compared to conventional therapies, regarding UL function (SMD = 0.47; 95% CI = 0.24 to 0.70;P < 0.0001), activity (SMD = 0.25; 95% CI = 0.05 to 0.46;P = 0.02) and participation (SMD = 0.66; 95% CI = 0.29 to 1.03;P = 0.0005). Additionally, long term effect retention was observed for UL function (SMD = 0.42; 95% CI = 0.05 to 0.79;P = 0.03). Interventions using serious games that complied with at least 8 neurorehabilitation principles showed better overall effects. Although heterogeneity levels remained moderate, results were little affected by changes in methods or outliers indicating robustness.ConclusionThis meta-analysis showed that rehabilitation through serious games, targeting UL recovery after stroke, leads to better improvements, compared to conventional treatment, in three ICF-WHO components. Irrespective of the technological device used, higher adherence to a consolidated set of neurorehabilitation principles enhances efficacy of serious games. Future development of stroke-specific rehabilitation interventions should further take into consideration the consolidated set of neurorehabilitation principles.