Miracle-dz/UniFAR-FTUs huggingface dataset:
3D-GNOME 3.0: a three-dimensional genome modelling engine for analysing changes of promoter-enhancer contacts in the human genome

Abstract In the current update, we added a feature for analysing changes in spatial distances between promoters and enhancers in chromatin 3D model ensembles. We updated our datasets by the novel in situ CTCF and RNAPII ChIA-PET chromatin loops obtained from the GM12878 cell line mapped to the GRCh38 genome assembly and extended the 1000 Genomes SVs dataset. To handle the new datasets, we applied GPU acceleration for the modelling engine, which gives a speed-up of 30× versus the previous versions. To improve visualisation and data analysis, we embedded the IGV tool for viewing ChIA-PET arcs with additional genes and SVs annotations. For 3D model visualisation, we added a new viewer: NGL, where we provided colouring by gene and enhancer location. The models are downloadable in mmcif and xyz format. The web server is hosted and performs calculations on DGX A100 GPU servers that provide optimal performance with multitasking. 3D-GNOME 3.0 web server provides unique insights into the topological mechanism of human variations at the population scale with high speed-up and is freely available at https://3dgnome.mini. pw.edu. pl/.
The Endotoxin Hypothesis of Parkinson's Disease

The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to the pathogenesis of this disorder. LPS endotoxins are found in, and released from, the outer membrane of Gram‐negative bacteria, for example in the gut. It is proposed that gut dysfunction in early PD leads to elevated LPS levels in the gut wall and blood, which promotes both α‐synuclein aggregation in the enteric neurons and a peripheral inflammatory response. Communication to the brain via circulating LPS and cytokines in the blood and/or the gut–brain axis leads to neuroinflammation and spreading of α‐synuclein pathology, exacerbating neurodegeneration in brainstem nuclei and loss of dopaminergic neurons in the substantia nigra, and manifesting in the clinical symptoms of PD. The evidence supporting this hypothesis includes: (1) gut dysfunction, permeability, and bacterial changes occur early in PD, (2) serum levels of LPS are increased in a proportion of PD patients, (3) LPS induces α‐synuclein expression, aggregation, and neurotoxicity, (4) LPS causes activation of peripheral monocytes leading to inflammatory cytokine production, and (5) blood LPS causes brain inflammation and specific loss of midbrain dopaminergic neurons, mediated by microglia. If the hypothesis is correct, then treatment options might include: (1) changing the gut microbiome, (2) reducing gut permeability, (3) reducing circulating LPS levels, or (4) blocking the response of immune cells and microglia to LPS. However, the hypothesis has a number of limitations and requires further testing, in particular whether reducing LPS levels can reduce PD incidence, progression, or severity. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Fuel oxidation under the control of mitochondrial shape and dynamics

How mitochondrial shape and substrate‐specific metabolism are related has been a difficult question to address. Here, new work by Ngo et al (2023) reports that mitochondrial shape—long versus fragmented—determines the activity of β‐oxidation of long‐chain fatty acids, supporting a novel role for mitochondrial fission products as β‐oxidation hubs.
Total‐, LDL‐, and HDL‐cholesterol, apolipoproteins, and triglycerides with risk of total and fatal prostate cancer in Black and White men in the ARIC study

Cholesterol reduction is considered a mechanism through which cholesterol‐lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations between total cholesterol and more advanced stage and grade in White men, whether associations for total cholesterol, low (LDL)‐ and high (HDL)‐density lipoprotein cholesterol, apolipoprotein B (LDL particle) and A1 (HDL particle), and triglycerides are similar for fatal prostate cancer and in Black men, who experience a disproportionate burden of total and fatal prostate cancer, is unknown.
A method to improve the computational efficiency for fractional Laplacian viscoacoustic wave equation

Summary In this abstract, we propose a method to improve the computational efficiency of viscoacoustic wave equation with fractional Laplacian operator. For the sudden changes of velocity and Q, we have to compute the wave field with a block computing for every value of velocity and Q, otherwise strong noise is produced during computation. As a result the amount of calculation is huge for complex structure models. We use linear operators to replace fractional Laplacians operators to speed up the simulation. Numerical examples show that the new method is 25% faster than the conventional blocked method and the accuracy of our method is almost the same as the blocked
TRAF4-mediated nonproteolytic ubiquitination of androgen receptor promotes castration-resistant prostate cancer

Significance We identified an AR ubiquitination site undergoing TRAF4-mediated nonclassical K27-linked ubiquitination under castration conditions. This ubiquitination enhances the interaction between AR and the pioneer factor FOXA1 and triggers a switch of AR genomic binding and AR-regulated transcriptome. Ubiquitinated AR subsequently hyperactivates E2F to promote CRPC. Our studies lay the foundation for identifying an appropriate CRPC patient population sensitive to CDK4/6 inhibitor treatment.
Representation and rendering of implicit surfaces

Implicit surfaces are a versatile representation of closed manifolds for modeling, simulation and rendering. They are defined as the isocontour of a volumetric scalar function, which allows intuitive handling of complex topology. Surfaces deformed by physics-based simulation or modeling operations can undergo large changes including tearing and merging without loosing their consistent definition or producing self-intersections or holes. Implicit surfaces can be rendered directly from their volumetric representation with a ray-casting approach, or they can be converted to a parametric representation like triangle meshes for display. This thesis focuses on different approaches for representing the scalar function which defines the implicit surface and methods to render the surface directly from those representations with real-time performance. A fundamental concept of the algorithms presented in this thesis is to harness the computational power of consumer graphics hardware. Their highly parallel design provides the working ground for very efficient processing and rendering of implicit surfaces. The main obstacle for such algorithms is to comply with the rendering APIs and hardware restrictions of current generation hardware, which are designed for triangle rasterization. In computer graphics, arbitrary functions are most commonly discretized as a regular grid of sample values. Sampling and reconstruction of a continuous function have been studied extensively in signal processing theory. One fundamental result that can also be applied to implicit surfaces, specifies the sampling frequency required to faithfully capture fine detail in the input data. For intricate objects, a dense regular grid of sufficient resolution can become challenging in terms of memory requirement and processing power. However, for the small reconstruction kernels commonly used, most of the samples do not contribute to the actual surface shape, but only serve as a binary insideoutside classification. Adaptive sampling can be used to reduce the sampling density in those regions where accurate reconstruction is not required. The octree provides a semi-regular sampling that can significantly reduce storage requirements without sacrificing accuracy in critical areas containing fine surface detail. The semi-regular structure was employed to develop a hashed octree which can be more efficient in terms of performance and memory footprint than the common pointer-based variant. To increase numerical stability, the surfaces deformed by the levelset method are represented by a field with constant gradient length. The signed distance
Exercise prehabilitation for patients with end-stage liver disease: a best practice implementation project

ABSTRACT Objectives: This study aimed to promote exercise prehabilitation in patients with end-stage liver disease during their waiting period for liver transplantation. Introduction: End-stage liver disease indirectly contributes to the development of sarcopenia and affects survival after liver transplantation because of low physiological reserves and insufficient aerobic capacity while awaiting transplantation. Exercise prehabilitation could reduce postoperative complications and promote postoperative recovery. Methods: Following the JBI Practical Application of Clinical Evidence System, this study used six audit criteria derived from the JBI Evidence Summary. A baseline audit of six patients and nine nurses was conducted, analyzed barriers, established a prehabilitation process and improved interventions, followed by the implementation of exercise prehabilitation and follow-up audit. Results: In the baseline audit, the results of the six criteria [(1) multimodal prehabilitation that includes exercise and other interventions where appropriate is offered to patients scheduled for abdominal surgery; (2) prior to the commencement of an exercise program an assessment of exercise contraindications, health status, treatments, physical activity level, functional capacity and quality of life is completed; (3) exercise programs are designed by appropriately qualified personnel; (4) exercise is delivered and supervised by appropriately qualified personnel; (5) exercise prescription is tailored to each individual patient; and (6) patient response to exercise is monitored throughout prehabilitation] were 0–22%. After implementing the best-practice strategies, all six criteria were set to 100%. Patients were aware of and had high compliance with exercise prehabilitation, nurses’ and patients’ knowledge of exercise rehabilitation improved, and nurses’ implementation rate was significantly higher than before implementation (P < 0.05). The differences in the 6 min walking distance and Borg Fatigue Score between the preimplementation and postimplementation were statistically significant (all P < 0.05). Conclusions: This best-practice implementation project is feasible. These results indicate that exercise prehabilitation could improve the preoperative walking capacity and fatigue of patients with end-stage liver disease. Ongoing best practices will be expected to develop in the future.
Inhibition skills in children with developmental coordination disorder

ABSTRACT Background Inhibition (Response Inhibition – RI and Interference Control – IC) have been inconsistently examined in Developmental Coordination Disorder (DCD) with response modalities often not considered. Aims To examine RI and IC in children with DCD. Method Twenty-five children 6-10 years with DCD, plus 25 matched typically developing peers completed motor and verbal RI and IC tasks. Results Children with DCD made significantly more errors in the motor and verbal RI tasks, had slower movement time and RT in the motor IC task, and longer completion time in the verbal IC task. Conclusions Children with DCD have RI and IC difficulties in motor and verbal responses.
ACFIS 2.0: an improved web-server for fragment-based drug discovery via a dynamic screening strategy

Abstract Drug discovery, which plays a vital role in maintaining human health, is a persistent challenge. Fragment-based drug discovery (FBDD) is one of the strategies for the discovery of novel candidate compounds. Computational tools in FBDD could help to identify potential drug leads in a cost-efficient and time-saving manner. The Auto Core Fragment in silico Screening (ACFIS) server is a well-established and effective online tool for FBDD. However, the accurate prediction of protein-fragment binding mode and affinity is still a major challenge for FBDD due to weak binding affinity. Here, we present an updated version (ACFIS 2.0), that incorporates a dynamic fragment growing strategy to consider protein flexibility. The major improvements of ACFIS 2.0 include (i) increased accuracy of hit compound identification (from 75.4% to 88.5% using the same test set), (ii) improved rationality of the protein-fragment binding mode, (iii) increased structural diversity due to expanded fragment libraries and (iv) inclusion of more comprehensive functionality for predicting molecular properties. Three successful cases of drug lead discovery using ACFIS 2.0 are described, including drugs leads to treat Parkinson's disease, cancer, and major depressive disorder. These cases demonstrate the utility of this web-based server. ACFIS 2.0 is freely available at http://chemyang.ccnu. edu.cn/ccb/server/ACFIS2/.
Mean platelet volume: a prognostic marker in heart failure with preserved ejection fraction

Abstract Heart failure (HF) with preserved ejection fraction (HFpEF) is associated with high burden of comorbidities known to increase the mean platelet volume (MPV). This parameter has been associated with morbidity and mortality in HF. However, the role of platelets and the prognostic relevance of MPV in HFpEF remain largely unexplored. We aimed to evaluate the clinical usefulness of MPV as a prognostic marker in HFpEF. We prospectively enrolled 228 patients with HFpEF (79 ± 9 years; 66% females) and 38 controls of similar age and gender (78 ± 5 years; 63% females). All subjects underwent two-dimensional echocardiography and MPV measurements. Patients were followed-up for a primary end point of all-cause mortality or first HF hospitalization. The prognostic impact of MPV was determined using Cox proportional hazard models. Mean MPV was significantly higher in HFpEF patients compared with controls (MPV: 10.7 ± 1.1fL vs. 10.1 ± 1.1fL, p = .005). HFpEF patients (n = 56) with MPV >75th percentile (11.3 fL) displayed more commonly a history of ischemic cardiomyopathy. Over a median follow-up of 26 months, 136 HFpEF patients reached the composite endpoint. MPV >75th percentile was a significant predictor of the primary endpoint (HR: 1.70 [1.08; 2.67], p = .023) adjusted for NYHA class, chronic obstructive pulmonary disease, loop diuretics, renal function, and hemoglobin. We demonstrated that MPV was significantly higher in HFpEF patients compared with controls of similar age and gender. Elevated MPV was a strong and independent predictor of poor outcome in HFpEF patients and may be relevant for clinical use. Plain Lanuage Summary What is the context? Heart failure with preserved ejection fraction (HFpEF) is associated with several comorbidities known to increase the mean platelet volume (MPV). MPV is a measure of platelet size and a potential marker of platelet reactivity. An increased MPV results from an increased platelet turnover. MPV has been associated with morbidity and mortality from heart failure. No study has previously compared MPV between HFpEF and controls and investigated the prognostic relevance of MPV in HFpEF disease. What is new? In this study, we compared the MPV between HFpEF patients and controls of similar age and gender, prospectively enrolled between 2015 and 2021. We evaluated the prognostic role of elevated MPV in HFpEF patients. Our main results: The MPV was higher in HFpEF patients compared to controls of similar age and gender. HFpEF patients with elevated MPV displayed more commonly a history of ischemic cardiomyopathy. Elevated MPV was a strong and independent predictor of poor outcome in HFpEF patients. What is the impact? MPV may be relevant for clinical use to predict clinical outcome in HFpEF patients. Elevated MPV reflecting platelet activity supports the potential role of platelets in HFpEF’s pathophysiology.
Exercise improves homeostasis of the intestinal epithelium by activation of apelin receptor–AMP‐activated protein kinase signalling

Intestinal remodelling is dynamically regulated by energy metabolism. Exercise is beneficial for gut health, but the specific mechanisms remain poorly understood. Intestine‐specific apelin receptor (APJ) knockdown (KD) and wild‐type male mice were randomly divided into two subgroups, with/without exercise, to obtain four groups: WT, WT with exercise, APJ KD and APJ KD with exercise. Animals in the exercise groups were subjected to daily treadmill exercise for 3 weeks. Duodenum was collected at 48 h after the last bout of exercise. AMP‐activated protein kinase (AMPK) α1 KD and wild‐type mice were also utilized for investigating the mediatory role of AMPK on exercise‐induced duodenal epithelial development. AMPK and peroxisome proliferator‐activated receptor γ coactivator‐1 α were upregulated by exercise via APJ activation in the intestinal duodenum. Correspondingly, exercise induced permissive histone modifications in the PR domain containing 16 (PRDM16) promoter to activate its expression, which was dependent on APJ activation. In agreement, exercise elevated the expression of mitochondrial oxidative markers. The expression of intestinal epithelial markers was downregulated due to AMPK deficiency, and AMPK signalling facilitated epithelial renewal. These data demonstrate that exercise‐induced activation of the APJ–AMPK axis facilitates the homeostasis of the intestinal duodenal epithelium.
The influence of vegetation structure on sleeping site selection by chimpanzees (Pan troglodytes troglodytes)

Sleep is an important aspect of great ape life; these animals build sleeping platforms every night. In a community of chimpanzees, each subgroup selects a sleeping site where each individual builds a sleeping platform, mostly on a tree. Previous studies have measured the heights of sleeping platforms and sleeping trees to test the predation avoidance and thermoregulation hypotheses of sleeping site selection. However, it remains unclear how components of vegetation structure (vertical and horizontal) together determine the selection of sleeping sites by chimpanzees. Using botanical inventories around sleeping sites in a tropical rainforest of Cameroon, we found that chimpanzees preferentially sleep in trees measuring 40–50 cm in diameter. Regarding height, on average, sleeping trees measured 26 m and sleeping platforms were built at 16 m. To build sleeping platforms, chimpanzees preferred four tree species, which represent less than 3% of tree species in the study area. We demonstrate that the variation in abundance of tree species and the vertical and horizontal structure of the vegetation drive chimpanzee sleeping site selection. It was previously thought that preference for vegetation types was the driver of sleeping site selection in chimpanzees. However, results from this study indicate that the importance of vegetation types in sleeping site selection depends on their botanical characteristics including the variation in tree size, the abundance of all trees, the abundance of sleeping trees, and the occurrence of preferred sleeping tree species, which predict sleeping site selection. The height and diameter of trees are considered by chimpanzees when selecting a particular tree for sleeping and when selecting a site with a specific vertical structure. In addition to tree height, the abundance of smaller neighboring trees may also play a role in the chimpanzee antipredation strategy. Our results demonstrate that chimpanzees consider several vegetation parameters to establish sleeping sites.
Hierarchical Shape-Consistent Transformer for Unsupervised Point Cloud Shape Correspondence

Point cloud shape correspondence aims at accurately mapping one point cloud to another point cloud with various 3D shapes. Since point clouds are usually sparse, disordered, irregular, and with diverse shapes, it is challenging to learn consistent point cloud representations and achieve the accurate matching of different point cloud shapes. To address the above issues, we propose a Hierarchical Shape-consistent TRansformer for unsupervised point cloud shape correspondence (HSTR), including a multi-receptive-field point representation encoder and a shape-consistent constrained module in a unified architecture. The proposed HSTR enjoys several merits. In the multi-receptive-field point representation encoder, we set progressively larger receptive fields in different blocks to simultaneously consider the local structure and the long-range context. In the shape-consistent constrained module, we design two novel shape selective whitening losses, which can complement each other to achieve suppression of features sensitive to shape change. Extensive experimental results on four standard benchmarks demonstrate the superiority and generalization ability of our approach to existing methods at the similar model scale, and our method achieves the new state-of-the-art results.
Evaluation of Er,Cr:YSGG laser technique for fiber post removal of endodontically treated teeth using micro‐computed tomography

Various clinical techniques such as removal kits, ultrasonic tips, burs, and drills, have been used for fiber post removal in endodontically treated teeth. In most clinical cases, the dental practitioners prefer to use ultrasonic tips, despite the heat generation and the formation of microcracks induced in the radicular dentin. The purpose of this study was to investigate the effectiveness of using erbium, chromium: yttrium‐scandium‐gallium‐garnet (Er,Cr:YSGG) laser (2780 nm) as an alternative fiber post removal technique and to compare it to an ultrasonic method using micro‐computed tomography (micro‐CT). The operating parameters of the X‐ray tube were set to 50 kVp and 300 mA. This approach allowed the generation of 2D lateral projections that were then used to reconstruct the 3D volume in DICOM format. Fiber posts were removed from 20 endodontically treated single‐rooted premolars (n = 10) using an ultrasonic vibrator with diamond‐coated ultrasonic tip (control method), or Er,Cr:YSGG laser irradiation protocol; average power 2.5 W, repetition rate 20 Hz, pulse duration 140 μs, 40% air and 20% water, and close‐contact mode. The number of sections with newly formed microcracks, the loss of dentinal tissue, the amount of the residual resin cement, and the removal time were evaluated for both methods. The data were analyzed using paired t‐test, Wilcoxon signed‐rank and Mann–Whitney U tests at level of significance a = . 05. In the laser‐treated group the parameters regarding microcracks formation (21 ± 16) and removal time (4.7 ± 1.1 min) were advantageous compared to the ultrasonic‐treated group (42 ± 27 and 9.2 ± 1.0 min, respectively), indicating that Er,Cr:YSGG laser could be an alternative fiber post removal technique.
The Relative Importance of Characters Affecting Genetic Divergence

The method for the identification of the most potent character contributing to divergence used by several workers is faulty. They have mistakenly treated the uncorrelated transformed variables (Yi) as biological characters having one-to-one correspondence with the original characters (Xi). A more rational approach has been given in the present work. It is suggested that the vector derived from the canonical vector corresponding to the largest root of the “between” populations matrix of the uncorrelated transformed variables and the triangular matrix of the transformation involved be used to identify the character contributing the most to the overall divergence. Further confirmation of the results could be made by distributing the components of D2 values in the form of a two-way table, obtaining the column totals over all possible values of D2 and identifying the character with the column giving the largest total.