Miracle-dz/UniFAR-FTUs huggingface dataset:
Automatic three‐dimensional segmentation of mouse embryonic stem cell nuclei by utilising multiple channels of confocal fluorescence images

Time‐lapse confocal fluorescence microscopy images from mouse embryonic stem cells (ESCs) carrying reporter genes, histone H2B‐mCherry and Mvh‐Venus, have been used to monitor dynamic changes in cellular/differentiation characteristics of live ESCs. Accurate cell nucleus segmentation is required to analyse the ESC dynamics and differentiation at a single cell resolution. Several methods used concavities on nucleus contours to segment overlapping cell nuclei. Our proposed method evaluates not only the concavities but also the size and shape of every 2D nucleus region to determine if any of the strait, extrusion, convexity and large diameter criteria is satisfied to segment overlapping nuclei inside the region. We then use a 3D segmentation method to reconstruct simple, convex, and reasonably sized 3D nuclei along the image stacking direction using the radius and centre of every segmented region in respective microscopy images. To avoid false concavities on nucleus boundaries, fluorescence images of the H2B‐mCherry reporter are used for localisation of cell nuclei and Venus fluorescence images are used for determining the cell colony ranges. We use a series of image preprocessing procedures to remove noise outside and inside cell colonies, and in respective nuclei, and to smooth nucleus boundaries based on the colony ranges. We propose dynamic data structures to record every segmented nucleus region and solid in sets (volumes) of 3D confocal images. The experimental results show that the proposed image preprocessing method preserves the areas of mouse ESC nuclei on microscopy images and that the segmentation method effectively segment out every nucleus with a reasonable size and shape. All 3D nuclei in a set (volume) of confocal microscopy images can be accessed by the dynamic data structures for 3D reconstruction. The 3D nuclei in time‐lapse confocal microscopy images can be tracked to calculate cell movement and proliferation in consecutive volumes for understanding the dynamics of the differentiation characteristics about ESCs.
Insights into the Genetic Architecture of Bran Friability and Water Retention Capacity, Two Important Traits for Whole Grain End-Use Quality in Winter Wheat

Bran friability (particle size distribution after milling) and water retention capacity (WRC) impact wheat bran functionality in whole grain milling and baking applications. The goal of this study was to identify genomic regions and underlying genes that may be responsible for these traits. The Hard Winter Wheat Association Mapping Panel, which comprised 299 lines from breeding programs in the Great Plains region of the US, was used in a genome-wide association study. Bran friability ranged from 34.5% to 65.9% (median, 51.1%) and WRC ranged from 159% to 458% (median, 331%). Two single-nucleotide polymorphisms (SNPs) on chromosome 5D were significantly associated with bran friability, accounting for 11–12% of the phenotypic variation. One of these SNPs was located within the Puroindoline-b gene, which is known for influencing endosperm texture. Two SNPs on chromosome 4A were tentatively associated with WRC, accounting for 4.6% and 4.4% of phenotypic variation. The favorable alleles at the SNP sites were present in only 15% (friability) and 34% (WRC) of lines, indicating a need to develop new germplasm for these whole-grain end-use quality traits. Validation of these findings in independent populations will be useful for breeding winter wheat cultivars with improved functionality for whole grain food applications.
Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor

Significance The gut microbiome comprises trillions of microorganisms that inhabit the mammalian intestines. These microbes regulate many aspects of host physiology, including defense mechanisms against factors that contribute to inflammatory bowel diseases (IBDs). Despite the abundance of the gut microbiota, little is known regarding how these microbes modulate these host processes, including the barrier function of the intestinal epithelium, which controls intestinal permeability associated with IBDs. Here, we discover that three gut microbially produced, small-molecule metabolites, which derive from dietary tryptophan, improve intestinal barrier integrity and protect against inflammation caused by IBDs. Our studies identify a host receptor and downstream targets of the metabolites, which could serve as potential pathways for prophylactic and therapeutic treatments for ameliorating morbidity in IBDs. Inflammatory bowel diseases (IBDs), including Crohn’s disease and ulcerative colitis, are associated with dysbiosis of the gut microbiome. Emerging evidence suggests that small-molecule metabolites derived from bacterial breakdown of a variety of dietary nutrients confer a wide array of host benefits, including amelioration of inflammation in IBDs. Yet, in many cases, the molecular pathways targeted by these molecules remain unknown. Here, we describe roles for three metabolites—indole-3-ethanol, indole-3-pyruvate, and indole-3-aldehyde—which are derived from gut bacterial metabolism of the essential amino acid tryptophan, in regulating intestinal barrier function. We determined that these metabolites protect against increased gut permeability associated with a mouse model of colitis by maintaining the integrity of the apical junctional complex and its associated actin regulatory proteins, including myosin IIA and ezrin, and that these effects are dependent on the aryl hydrocarbon receptor. Our studies provide a deeper understanding of how gut microbial metabolites affect host defense mechanisms and identify candidate pathways for prophylactic and therapeutic treatments for IBDs.
Distress in parents of children with advanced cancer enrolled in the PediQUEST Study

Purpose: Psychological distress (PD) in a parent may have an effect on their children and other members of their family. We sought to describe the prevalence and predictors of PD among parents of children with advanced cancer. Patients and Methods: Parents of children with progressive, recurrent, or refractory cancer who were treated at one of 3 large children’s hospitals and enrolled in the Pediatric Quality of Life and Evaluation of Symptoms Technology (PediQUEST) study completed the Survey of Caring for Children with Cancer (SCCC). Parent PD was measured by the Kessler-6 general psychological distress scale. K6 scores of ≥ 7 suggest high distress and those ≥ 13 indicate serious psychological distress (SPD, U.S. SPD prevalence is 3%). Linear and logistic regression models were used to evaluate associations between PD and child/ parent factors. Results: 86 of 104 enrolled parents completed SCCC (83% participation); 81 had complete K6 data. Over 50% of parents reported high distress and 16% met criteria for SPD. Parent and child demographic factors were not associated with parent PD in this study; however, parent perceptions of prognosis, goals of therapy, perceived child symptoms/suffering, as well as financial hardship were. In multivariate analyses, parent PD scores were higher among those whose care goals were incongruent with their prognostic understanding, whose child was suffering highly, and who perceived great economic hardship due to their child’s illness.
3D Printing and Bioprinting Nerve Conduits for Neural Tissue Engineering

Fabrication of nerve conduits for perfectly repairing or replacing damaged peripheral nerve is an urgent demand worldwide, but it is also a formidable clinical challenge. In the last decade, with the rapid development of manufacture technologies, 3D printing and bioprinting have been becoming remarkable stars in the field of neural engineering. In this review, we explore that the biomaterial inks (hydrogels, thermoplastic, and thermoset polyesters and composite) and bioinks have been selected for 3D printing and bioprinting of peripheral nerve conduits. This review covers 3D manufacturing technologies, including extrusion printing, inkjet printing, stereolithography, and bioprinting with inclusion of cells, bioactive molecules, and drugs. Finally, an outlook on the future directions of 3D printing and 4D printing in customizable nerve therapies is presented.
Quantifying the impact of vegetation‐based metrics on species persistence when choosing offsets for habitat destruction

Developers are often required by law to offset environmental impacts through targeted conservation actions. Most offset policies specify metrics for calculating offset requirements, usually by assessing vegetation condition. Despite widespread use, there is little evidence to support the effectiveness of vegetation‐based metrics for ensuring biodiversity persistence. We compared long‐term impacts of biodiversity offsetting based on area only; vegetation condition only; area × habitat suitability; and condition × habitat suitability in development and restoration simulations for the Hunter Region of New South Wales, Australia. We simulated development and subsequent offsetting through restoration within a virtual landscape, linking simulations to population viability models for 3 species. Habitat gains did not ensure species persistence. No net loss was achieved when performance of offsetting was assessed in terms of amount of habitat restored, but not when outcomes were assessed in terms of persistence. Maintenance of persistence occurred more often when impacts were avoided, giving further support to better enforce the avoidance stage of the mitigation hierarchy. When development affected areas of high habitat quality for species, persistence could not be guaranteed. Therefore, species must be more explicitly accounted for in offsets, rather than just vegetation or habitat alone. Declines due to a failure to account directly for species population dynamics and connectivity overshadowed the benefits delivered by producing large areas of high‐quality habitat. Our modeling framework showed that the benefits delivered by offsets are species specific and that simple vegetation‐based metrics can give misguided impressions on how well biodiversity offsets achieve no net loss.
An allele of rs619586 polymorphism in MALAT1 alters the invasiveness of meningioma via modulating the expression of collagen type V alpha (COL5A1)

The rs619586 polymorphism has been shown to alter the expression of MALAT1, which act as a competing endogenous RNA (ceRNA) against miR‐145. And miR‐145 was found to target COL5A1, the interaction between which was shown to be involved in the pathogenesis of invasive meningioma. In this study, we aimed to explore the effect of rs619586 polymorphism and its underlying molecular mechanism in invasive meningioma. Real‐time PCR and Western Blot analysis were used to study the differentiated expression of miR‐145, MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1) and COL5A1 (collagen alpha‐1(V) chain) in tumour/serum samples genotyped as rs619586 AA, AG and GG. Computational analysis and luciferase reporter assay were also conducted to identify the regulatory relationship between miR‐145 and MALAT1/COL5A1. Meanwhile, expression of miR‐145 and COL5A1 in different cell treatment groups was measured to validate the results obtained from earlier experiments. As shown by the results and in tumour/serum samples genotyped as AA, AG and GG, the expression of both MALAT1 and COL5A1 was down‐regulated in a stepwise fashion, while the expression of miR‐145 was increased, suggesting a potential negative relationship between MALAT1/COL5A1 and miR‐145. Meanwhile, miR‐145 was shown to bind to MALAT1, while COL5A1 was identified as a virtual target gene of miR‐145. As a consequence, a MALAT1/miR‐145/COL5A1 molecular pathway was established based on the above results. In particular, with the presence of rs619586 A>G polymorphism, the expression of MALAT1 and COL5A1 was both reduced, leading to reduced invasiveness of meningioma.
Structure of a collagen VI α3 chain VWA domain array: adaptability and functional implications of myopathy causing mutations

Collagen VI is a ubiquitous heterotrimeric protein of the extracellular matrix (ECM) that plays an essential role in the proper maintenance of skeletal muscle. Mutations in collagen VI lead to a spectrum of congenital myopathies, from the mild Bethlem myopathy to the severe Ullrich congenital muscular dystrophy. Collagen VI contains only a short triple helix and consists primarily of von Willebrand factor type A (VWA) domains, protein–protein interaction modules found in a range of ECM proteins. Disease-causing mutations occur commonly in the VWA domains, and the second VWA domain of the α3 chain, the N2 domain, harbors several such mutations. Here, we investigate structure-function relationships of the N2 mutations to shed light on their possible myopathy mechanisms. We determined the X-ray crystal structure of N2, combined with monitoring secretion efficiency in cell culture of selected N2 single-domain mutants, finding that mutations located within the central core of the domain severely affect secretion efficiency. In longer α3 chain constructs, spanning N6-N3, small-angle X-ray scattering demonstrates that the tandem VWA array has a modular architecture and samples multiple conformations in solution. Single-particle EM confirmed the presence of multiple conformations. Structural adaptability appears intrinsic to the VWA domain region of collagen VI α3 and has implications for binding interactions and modulating stiffness within the ECM.
Entrofy your cohort: A transparent method for diverse cohort selection

Selecting a cohort from a set of candidates is a common task within and beyond academia. Admitting students, awarding grants, and choosing speakers for a conference are situations where human biases may affect the selection of any particular candidate, and, thereby the composition of the final cohort. In this paper, we propose a new algorithm, entrofy, designed to be part of a human-in-the-loop decision making strategy aimed at making cohort selection as just, transparent, and accountable as possible. We suggest embedding entrofy in a two-step selection procedure. During a merit review, the committee selects all applicants, submissions, or other entities that meet their merit-based criteria. This often yields a cohort larger than the admissible number. In the second stage, the target cohort can be chosen from this meritorious pool via a new algorithm and software tool called entrofy. entrofy optimizes differences across an assignable set of categories selected by the human committee. Criteria could include academic discipline, home country, experience with certain technologies, or other quantifiable characteristics. The entrofy algorithm then yields the approximation of pre-defined target proportions for each category by solving the tie-breaking problem with provable performance guarantees. We show how entrofy selects cohorts according to pre-determined characteristics in simulated sets of applications and demonstrate its use in a case study of Astro Hack Week. This two stage candidate and cohort selection process allows human judgment and debate to guide the assessment of candidates’ merit in step 1. Then the human committee defines relevant diversity criteria which will be used as computational parameters in entrofy. Once the parameters are defined, the set of candidates who meet the minimum threshold for merit are passed through the entrofy cohort selection procedure in step 2 which yields a cohort of a composition as close as possible to the computational parameters defined by the committee. This process has the benefit of separating the meritorious assessment of candidates from certain elements of their diversity and from some considerations around cohort composition. It also increases the transparency and auditability of the process, which enables, but does not guarantee, fairness. Splitting merit and diversity considerations into their own assessment stages makes it easier to explain why a given candidate was selected or rejected, though it does not eliminate the possibility of objectionable bias.
Polymorphism of internal transcribed spacer 2 [ITS-2] sequences and genetic relationships between Fasciola hepatica and F.gigantica

Nucleotide sequences of internal transcribed spacer 2 (ITS-2) of nuclear DNA were obtained from 58 adult worms Fasciola hepatica and F. gigantica of naturally infected cattle and sheep in Russia, Ukraine, Belarus, Armenia, Uzbekistan, Turkmenistan and Tajikistan. No variation was observed between 43 liver flukes F. hepatica from Russia, Belarus, Ukraine, Armenia and Turkmenistan. Only one specimen from Armenia had a single unique transversion C-G (0.3% variation). F. gigantica from Turkmenistan, Tajikistan and Uzbekistan differed at four nucleotide transitions (1.1% variations). For comparative purpose, the ITS-2 sequences of two species from Europe, Africa, Asia, America, Australia and Oceania were used and evolution history of ITS-2 sequences of Fasciola species was reconstructed with statistical parsimony network (SPN) method. The relationships between F. hepatica and F. gigantica from different regions were discussed.
Long-term BMI change trajectories in Chinese adults and its association with the hazard of type 2 diabetes: evidence from a 20-year China Health and Nutrition Survey

Introduction To investigate the relationship between long-term change trajectory in body mass index (BMI) and the hazard of type 2 diabetes among Chinese adults. Research design and methods Data were obtained from the China Health and Nutrition Survey (CHNS). Type 2 diabetes was reported by participants themselves in each survey wave. The duration of follow-up was defined as the period from the first visit to the first time self-reported type 2 diabetes, death, or other loss to follow-up from CHNS. The patterns of change trajectories in BMI were derived by latent class trajectory analysis method. The Fine and Gray regression model was used to estimate HRs with corresponding 95% CIs for type 2 diabetes. Results Four patterns of the trajectories of change in BMI were identified among Chinese adults, 42.7% of participants had stable BMI change, 40.8% for moderate BMI gain, 8.9% for substantial BMI gain and 7.7% for weight loss. During the follow-up with mean 11.2 years (158 637 person-years contributed by 14 185 participants), 498 people with type 2 diabetes (3.7%) occurred. Risk of type 2 diabetes was increased by 47% among people who gained BMI more substantially and rapidly (HR: 1.47, 95% CI 1.08 to 2.02, p=0.016) and increased by 20% among those in people with the moderate BMI gain (HR: 1.20, 95% CI 0.98 to 1.48, p=0.078), compared with those with stable BMI change. Conclusions Long-term substantial gain of BMI was significantly associated with an increased risk of type 2 diabetes in the Chinese adults.
Discontinuation of anticoagulants after successful surgical ablation of atrial fibrillation.

BACKGROUND The decision of whether to continue oral anticoagulation therapy (OAT) after successful surgical ablation of atrial fibrillation is challenging, and current guidelines provide no specific recommendations on whether or not it is safe to terminate OAT. Therefore, the aim of this study was to assess long-term outcomes in patients who either did or did not, receive OAT after surgical ablation of atrial fibrillation. METHODS In a prospective follow-up study, patients were included if surgical ablation of atrial fibrillation concomitantly with other cardiac surgery was done, between 2004 and 2018 at Aarhus University Hospital, Denmark. After 12 months, OAT was discontinued if: (a) sinus rhythm was documented by electrocardiogram, (b) atrial fibrillation was absent on 5-day Holter monitoring, (c) CHADS2 score ≤2, and (d) no other indications for OAT were present. Follow-up was ended in April 2019. RESULTS A total of 560 patients underwent surgical ablation of which 436 patients reached the baseline at 12 months; 286 patients received OAT, and 150 had OAT discontinued. Survival analysis revealed no differences between the two groups (P = .723). Mean survival time in the group receiving OAT was 5.3 ± 3.3 years, compared to 5.1 ± 3.0 years in the group where OAT was discontinued (P = .784). There was no difference in major adverse cardiac and cerebrovascular events between the two groups (P = .846). CONCLUSION Discontinuation of OAT is safe in patients with a CHADS2 score ≤2 following successful surgical ablation and left atrial appendage occlusion. This conclusion needs to be confirmed in randomized trials.
Effect of serotonin modulation on dystrophin-deficient zebrafish

ABSTRACT Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease caused by mutation of the dystrophin gene. Pharmacological therapies that function independently of dystrophin and complement strategies aimed at dystrophin restoration could significantly improve patient outcomes. Previous observations have suggested that serotonin pathway modulation ameliorates dystrophic pathology, and re-application of serotonin modulators already used clinically would potentially hasten availability to DMD patients. In our study, we used dystrophin-deficient sapje and sapje-like zebrafish models of DMD for rapid and easy screening of several classes of serotonin pathway modulators as potential therapeutics. None of the candidate drugs tested significantly decreased the percentage of zebrafish exhibiting the dystrophic muscle phenotype in the short-term birefringence assay or lengthened the lifespan in the long-term survival assay. Although we did not identify an effective drug, we believe our data is of value to the DMD research community for future studies, and there is evidence that suggests serotonin modulation may still be a viable treatment strategy with further investigation. Given the widespread clinical use of selective serotonin reuptake inhibitors, tricyclic antidepressants and reversible inhibitors of monoamine oxidase, their reapplication to DMD is an attractive strategy in the field's pursuit to identify pharmacological therapies to complement dystrophin restoration strategies. Summary: Phenotypic screening of serotonin pathway modulators has been performed in DMD zebrafish in order to identify small-molecules that limit the dystrophic muscle phenotype and lengthen the lifespan as potential therapeutics.