Miracle-dz/UniFAR-FTUs huggingface dataset:
Spike-induced ordering: Stochastic neural spikes provide immediate adaptability to the sensorimotor system

Significance The functional advantages of using a stochastically spiking neural network (sSNN) instead of a nonspiking neural network (NS-NN) have remained largely unknown. We developed an architecture which enabled the parametric adjustment of the spikiness (i.e., impulsive dynamics and stochasticity) of the sSNN output and observed that stochastic spikes instantaneously induced the ordered motion of a dynamical system. We demonstrated the benefits of sSNNs using a musculoskeletal bipedal walker and, moreover, showed that the decrease in the spikiness of motor neuron output leads to a reduction in adaptability. Stochastic spikes may aid the adaptation of a biological system to sudden perturbations or environmental changes. Our architecture can easily be connected to the conventional NS-NN and may superimpose the on-site adaptability. Most biological neurons exhibit stochastic and spiking action potentials. However, the benefits of stochastic spikes versus continuous signals other than noise tolerance and energy efficiency remain largely unknown. In this study, we provide an insight into the potential roles of stochastic spikes, which may be beneficial for producing on-site adaptability in biological sensorimotor agents. We developed a platform that enables parametric modulation of the stochastic and discontinuous output of a stochastically spiking neural network (sSNN) to the rate-coded smooth output. This platform was applied to a complex musculoskeletal–neural system of a bipedal walker, and we demonstrated how stochastic spikes may help improve on-site adaptability of a bipedal walker to slippery surfaces or perturbation of random external forces. We further applied our sSNN platform to more general and simple sensorimotor agents and demonstrated four basic functions provided by an sSNN: 1) synchronization to a natural frequency, 2) amplification of the resonant motion in a natural frequency, 3) basin enlargement of the behavioral goal state, and 4) rapid complexity reduction and regular motion pattern formation. We propose that the benefits of sSNNs are not limited to musculoskeletal dynamics. Indeed, a wide range of the stability and adaptability of biological systems may arise from stochastic spiking dynamics.
The rise of organ donation after circulatory death: a narrative review

Solid organ transplantation saves and transforms lives. The original type of organ donation from deceased patients was controlled donation after circulatory death, previously referred to as non‐heart beating organ donation. The rise of donation after circulatory death in the UK came about through advances in critical care and transplant medicine and support from several key organisations in developing a robust ethical, legal and professional framework. The transplant waiting list reached a historic peak in 2009–2010 of 8000 patients, but fell by 25% to 6000 in 2017–2018. There has also been a steady rise in the number of deceased donors and the number of donations after circulatory death. The contribution of donation after circulatory death to the total number of donations rose steadily between 2000 and 2012 and has remained about 40% since. Although the situation has improved for patients waiting for a transplant, deaths and long waits remain common. Changes to legislative, technical and peri‐mortem procedures may greatly change future practices in donation after circulatory death in the UK.
Silencing CCL8 inhibited the proliferation and migration of PDGF-BB-stimulated human aortic smooth muscle cells

ABSTRACT C-C motif Chemokine ligand 8 (CCL8) has been found in diseases’ pathogenesis. But its molecular mechanism in atherosclerosis (AS) remains to be elucidated. Human aortic smooth muscle cells (HASMCs) were stimulated by PDGF-BB to establish cell model. α-SMA in PDGF-BB-stimulated HASMCs was measured by immunofluorescence staining. Relative gene expressions in PDGF-BB-stimulated HASMCs were detected by quantitative real-time polymerase chain reaction and western blot. HASMCs proliferation, migration, and cell cycle were assessed by cell counting kit-8, wound-healing assay, and flow cytometry. HASMCs viability was increased after PDGF-BB stimulation, with α-SMA downregulation yet CCL8 upregulation. Silencing CCL8 inhibited PDGF-BB-stimulated HASMCs proliferation and migration, and increased cells percentage in G1 phases but decreased those in S phase. Also, silencing CCL8 decreased OPN and cyclinD1 expressions and AKT and ERK1/2 phosphorylation while increased those of α-SMA and Sm22α. However, upregulating CCL8 led to opposite effects, suggesting CCL8 could be an atherosclerosis therapeutic target. GRAPHICAL ABSTRACT Silencing CCL8 inhibited the proliferation and migration of PDGF-BB-stimulated human aortic smooth muscle cells.
Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.

INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability. METHODS Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT. RESULTS There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT. DISCUSSION FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.
mmCSM-AB: guiding rational antibody engineering through multiple point mutations

Abstract While antibodies are becoming an increasingly important therapeutic class, especially in personalized medicine, their development and optimization has been largely through experimental exploration. While there have been many efforts to develop computational tools to guide rational antibody engineering, most approaches are of limited accuracy when applied to antibody design, and have largely been limited to analysing a single point mutation at a time. To overcome this gap, we have curated a dataset of 242 experimentally determined changes in binding affinity upon multiple point mutations in antibody-target complexes (89 increasing and 153 decreasing binding affinity). Here, we have shown that by using our graph-based signatures and atomic interaction information, we can accurately analyse the consequence of multi-point mutations on antigen binding affinity. Our approach outperformed other available tools across cross-validation and two independent blind tests, achieving Pearson's correlations of up to 0.95. We have implemented our new approach, mmCSM-AB, as a web-server that can help guide the process of affinity maturation in antibody design. mmCSM-AB is freely available at http://biosig.unimelb. edu.au/mmcsm_ab/.
Advancing the Science and Management of Renal Cell Carcinoma: Bridging the Divide between Academic and Community Practices

The treatment of metastatic renal cell carcinoma (mRCC) has rapidly evolved; however, the progress made in the field is heavily contingent upon timely and efficient accrual to clinical trials. While a substantial proportion of accrual occurs at tertiary care centers, community sites are playing an increasing role in patient recruitment. In this article, we discuss strategies to optimize collaborations between academic and community sites to facilitate clinical research. Further, as the role of biomarker discovery has become increasingly important in tailoring therapy, we will discuss opportunities to bridge diverse accrual sites for the purpose of translational research.
Effects of Guar Gum and Fructooligosaccharides on Plasma Lipids and Cecal Short-Chain Fatty Acids in Adult Mice

The effects of fructooligosaccharides added to guar gum on plasma lipids and cecal short-chain fatty acids (SCFAs) in mice were studied. Male Crj:CD-1 (ICR) mice were fed an MF diet for 34 weeks, and then the MF diet was replaced with a semisynthetic diet supplemented with 5% guar gum or 5% guar gum plus 3% fructooligosaccharides. The mice fed the guar gum or guar gum-fructooligosaccharide diet for 3 weeks. There was no significant difference in cecal bacterial counts or cecal content between the two diet groups. There was, however, a significant difference in their plasma triglyceride concentrations. The plasma triglyceride concentration was significantly lower in the mice fed the guar gum diet than in those fed the guar gum-fructooligosaccharide diet. However, no significant difference in plasma total cholesterol concentration was noted between the two diet groups. The butyric acid concentration in the guar gum group was significantly higher than that in the guar gum-fructooligosaccharide group. No significant difference in propionic acid or acetic acid concentration was noted between the groups. The difference in the plasma triglyceride concentration between the guar gum and guar gum plus fructooligosaccharide groups might be related to a difference in floral metabolism, floral composition, or both.
Differences in desiccation tolerance do not explain altitudinal distribution patterns of tropical bryophytes

Abstract Bryophyte biomass and diversity vary strongly with altitude in the tropics. Low abundance and low species numbers in lowland rain forests are most likely due to reduced diurnal activity times combined with high nocturnal respiration rates at high temperatures. This may exclude many montane species from the warm lowlands. However, an alternative hypothesis explains the observed pattern, namely a limited desiccation tolerance of montane species, precipitation being more concentrated but less frequent in most lowland forests compared to montane cloud forests. To test this hypothesis, we studied the desiccation tolerance of four montane and four lowland bryophyte species. The effects of prolonged drought were quantified with chlorophyll fluorescence (Fv/Fm) and the extent of electrolyte leakage. Both montane and lowland species survived dry periods of ≧80 days, which far exceeds the duration of dry periods in the wet lowland tropics. We can thus exclude intolerance to long dry spells as an explaination for the absence of the tested montane species in the lowlands. We should continue to focus on other mechanisms to explain the altitudinal gradient of bryophyte abundance and diversity in the tropics, in order to understand this pattern, as well as to predict future trends under climatic warming.
The Neuroendocrine Neoplasms of the Digestive Tract: Diagnosis, Treatment and Nutrition

Nuroendocrine neoplasms (NENs) are a group of rare neoplasms originating from dispersed neuroendocrine cells, mainly of the digestive and respiratory tract, showing characteristic histology and immunoprofile contributing to classification of NENs. Some NENs have the ability to produce biogenic amines and peptide hormones, which may be associated with clinical syndromes like, e.g., the carcinoid syndrome caused by unmetabolized overproduced serotonin, hypoglycemic syndrome in case of insulinoma, or Zollinger-Ellison syndrome accompanying gastrinoma. Diagnostics for these include ultrasound with endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography/computed tomography (PET/CT). Different nuclear medicine procedures can also be used, like somatostatin analogues scintigraphy (SRS) and 68Ga-Dota-Peptide PET/CT, as well as biochemical methods to determine the level of general neuroendocrine markers, such as chromogranin A (CgA), 5-hydroxyindolacetic acid (5-HIAA), synaptopfysin and cell type-specific peptide hormones, and neurotransmitters like gastrin, insulin, serotonin, and histamine. NENs influence the whole organism by modulating metabolism. The treatment options for neuroendocrine neoplasms include surgery, somatostatin analogue therapy, radionuclide therapy, chemotherapy, molecular targeted therapies, alpha-interferon therapy, and inhibitors of serotonin production. In the case of hypersensitivity to biogenic amines, a diet that limits the main sources of amines should be used. The symptoms are usually connected with histamine, tyramine and putrescine. Exogenic sources of histamine are products that take a long time to mature and ferment. Patients with a genetic insufficiency of the diamine oxidase enzyme (DAO), and those that take medicine belonging to the group of monoamine oxidases (MAO), are particularly susceptible to the negative effects of amines. Diet plays an important role in the initiation, promotion, and progression of cancers. As a result of the illness, the consumption of some nutrients can be reduced, leading to nutritional deficiencies and resulting in malnutrition. Changes in metabolism may lead to cachexia in some patients suffering from NENs. The aim of this narrative review was to advance the knowledge in this area, and to determine possibilities related to dietary support. The authors also paid attention to role of biogenic amines in the treatment of patients with NENs. We can use this information to better understand nutritional issues faced by patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and to help inform the development of screening tools and clinical practice guidelines.
The complete mitochondrial genome of Epomophorus gambianus (Chiroptera: Pteropodidae) and its phylogenetic analysis

Abstract The Gambian epauletted fruit bat, Epomophorus gambianus, is widely distributed across sub-Saharan Africa. Its assembled and annotated mitochondrial genome (GenBank accession no. KT963027) is 16,702 bases in length, containing 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and two non-coding regions: the control region (D-loop) and the origin of light-strand replication (OL). The average base composition is 32.2% A; 27.6% C; 14% G; and 26.1% T. The mitogenome presented a structural composition greatly conserved between members of the Pteropodidae family.
The use of the green fluorescent protein as a biomarker for sapstain fungi

To understand wood colonization by sapstain fungi and their potential biocontrol agents, it is necessary to differentiate these organisms directly on their natural substrates. In the present study the feasibility of transforming with the green fluorescent protein (GFP), the sapstain fungus Ophiostoma piceae and a potential biocontrol agent Cartapip®, an Ophiostoma piliferum albino strain was assessed. Transformants of the two fungal species were screened by polymerase chain reaction and Southern blot analyses. The GFP was expressed in spores, synnemata and mycelia of the transformants grown in artificial media or wood. The growth, pigmentation and wood colonization of the transformants were similar to that of the non-transformants, suggesting that the presence of the gfp gene had no negative effect on the biology of the transformants. Using fluorescence and confocal microscopy, the GFP-expressing fungi were easily differentiated from the wild-type strains and other fungal species in wood, even 4 months after inoculation. The results show that the use of the GFP system is feasible to monitor Ophiostoma fungi in wood.
Across‐session consistency of context‐driven language processing: A magnetoencephalography study

Changes in brain organization following damage are commonly observed, but they remain poorly understood. These changes are often studied with imaging techniques that overlook the temporal granularity at which language processes occur. By contrast, electrophysiological measures provide excellent temporal resolution. To test the suitability of magnetoencephalography (MEG) to track language‐related neuroplasticity, the present study aimed at establishing the spectro‐temporo‐spatial across‐session consistency of context‐driven picture naming in healthy individuals, using MEG in two test–retest sessions. Spectro‐temporo‐spatial test–retest consistency in a healthy population is a prerequisite for studying neuronal changes in clinical populations over time. For this purpose, 15 healthy speakers were tested with MEG while performing a context‐driven picture‐naming task at two time points. Participants read a sentence missing the final word and named a picture completing the sentence. Sentences were constrained or unconstrained toward the picture, such that participants could either retrieve the picture name through sentence context (constrained sentences), or could only name it after the picture appeared (unconstrained sentences). The context effect (constrained versus unconstrained) in picture‐naming times had a strong effect size and high across‐session consistency. The context MEG results revealed alpha–beta power decreases (10–20 Hz) in the left temporal and inferior parietal lobule that were consistent across both sessions. As robust spectro‐temporo‐spatial findings in a healthy population are required for working toward longitudinal patient studies, we conclude that using context‐driven language production and MEG is a suitable way to examine language‐related neuroplasticity after brain damage.
Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: A population-based cohort study

Background The relation between prepregnancy average glucose concentration and a woman’s risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM). Methods and findings A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16–50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks’ gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14–1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13–1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07–1.14; p < 0.001) and without (1.15, 95% CI 1.02–1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11–1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04–1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06–1.62; p = 0.01) in those with a preconception A1c of 5.8%–6.4%, and 2.84 (95% CI 2.31–3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76–6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women. Conclusions Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.
Acyltransferases from basic science to modified seed oils

Different discrete acyltransferases are involved in glycerolipid biosynthesis, which occurs in plastids, mitochondria and endomembranes, mainly in the endoplasmic reticulum of plant cells. In each compartment a glycerol-3-phosphate and 1-acylglycerol-3-phosphate acyltransferase catalyze the stepwise acylation of glycerol-3-phosphate to 1,2-diacylglycerol-3-phosphate, the key intermediate in the biosynthesis of the various glycerolipids. These acyltansferases play an important role in establishing the typical fatty acid patterns of the major polar membrane lipids. This also holds true for the microsomal acyltransferases involved in triacylglycerol synthesis where a 1,2-diacylglycerol acyltransferase catalyzes the third acylation reaction. Consequently, the activities of plant acyltransferases are indispensable for the formation of both membrane and storage lipids, and their properties can be decisive determinants of certain plant traits. Recently, the importance of acyltransferases, especially of 1-acylglycerol-3-phosphate acyltransferases, in determining oil quality and usability for specific markets has been confirmed by genetic engineering. Chimeric 1-acylglycerol-3-phosphate acyltransferase genes have been successfully utilized to achieve the synthesis of rapeseed oil with homogeneous fatty acid distributions, such as trierucin and trilaurin, desired for industrial applications. Moreover, evidence has been provided that expression of acyltransferase genes in transgenic rapeseed plants can improve not only oil quality but also oil yield.
A Teleophthalmology Support System Based on the Visibility of Retinal Elements Using the CNNs

This paper proposes a teleophthalmology support system in which we use algorithms of object detection and semantic segmentation, such as faster region-based CNN (FR-CNN) and SegNet, based on several CNN architectures such as: Vgg16, MobileNet, AlexNet, etc. These are used to segment and analyze the principal anatomical elements, such as optic disc (OD), region of interest (ROI) composed by the macular region, real retinal region, and vessels. Unlike the conventional retinal image quality assessment system, the proposed system provides some possible reasons about the low-quality image to support the operator of an ophthalmoscope and patient to acquire and transmit a better-quality image to central eye hospital for its diagnosis. The proposed system consists of four steps: OD detection, OD quality analysis, obstruction detection of the region of interest (ROI), and vessel segmentation. For the OD detection, artefacts and vessel segmentation, the FR-CNN and SegNet are used, while for the OD quality analysis, we use transfer learning. The proposed system provides accuracies of 0.93 for the OD detection, 0.86 for OD image quality, 1.0 for artefact detection, and 0.98 for vessel segmentation. As the global performance metric, the kappa-based agreement score between ophthalmologist and the proposed system is calculated, which is higher than the score between ophthalmologist and general practitioner.