Miracle-dz/UniFAR-FTUs huggingface dataset:
Feline Panleukopenia Virus With G299E Substitution in the VP2 Protein First Identified From a Captive Giant Panda in China

A feline panleukopenia virus (FPV), Giant panda/CD/2018, was isolated from a captive giant panda with mild diarrhea in 2018 in Chengdu, China, and further identified via indirect immunofluorescence assay (IFA), transmission electron microscopy (TEM) observation, and genetic analysis. Phylogenetic analysis based on the complete VP2 nucleotide sequences showed that it shared high homology with Chinese FPV isolates and grouped within FPV cluster 1. One unique substitution Gly(G)299Glu(E) in the capsid protein VP2 was first identified with Giant panda/CD/2018. The presence of the G299E substitution is notable as it is located on the top region of the interconnecting surface loop 3, which may be involved in controlling the host range and antigenicity of FPV. These findings first demonstrate that FPV with natural point mutation G299E in the VP2 gene is prevalent in giant panda and suggest that etiological surveillance and vaccination among all giant pandas are urgently needed to protect this endangered species against FPV infection.
A Novel Sutureless Integrated Stented (SIS) Graft Prosthesis for Type A Aortic Dissection: A Pilot Study for a Prospective, Multicenter Clinical Trial

Aims Various kinds of surgical strategies and prostheses have been advocated to improve short-term and long-term outcomes in type A aortic dissection (TAAD). Large-scale repair of the pathological aorta is hard to generalize due to complex procedures. We aimed to investigate the performance, effectiveness and safety of a novel Sutureless Integrated Stented (SIS) graft prosthesis in TAAD patients undergoing total arch replacement (TAR) and frozen elephant trunk (FET) implantation surgery. Methods All patients admitted to Fuwai Hospital were prospectively screened. Urgent or scheduled surgery was arranged for eligible patients. The primary endpoint was operative mortality. Key secondary endpoints included stroke, spinal cord injury, unexpected aortic reoperation, and 1-year survival. Discharged patients were followed up with computed tomography angiography and transthoracic echocardiography at 3 months, 6 months, and 1 year after surgery. Performance, effectiveness and safety analyses were performed in those patients. Results Between August 1 and September 3, 2020, ten TAAD patients were enrolled in this study and successfully implanted with the SIS graft prosthesis. The median (IQR) age was 56.50 (43.75, 66.75) years (range from 31 to 75), and seven patients were male (70.0%). All patients underwent ascending aorta replacement + TAR + FET and additional procedures when necessary. The median (IQR) operation time, cardiopulmonary bypass time and cross clamp time were 270.50 (218.50, 312.50), 110.00 (88.00, 125.75), 69.50 (51.25, 82.75) min, respectively. Of note, the median (IQR) circulatory arrest time was 9.00 (8.00, 9.00) min (range from 4 to 12). The median (IQR) lowest nasopharyngeal temperature was 26.75 (25.98, 27.67) °C. Follow-up was 100% completed. During the 1-year follow-up, no patients died, no severe adverse events occurred, and rate of freedom from aortic reintervention was 100%. Conclusions The SIS graft prosthesis was implanted in a novel sutureless way, which simplified the surgical procedure, shortened the circulatory arrest time and avoided deep hypothermia. The preliminary clinical outcomes and follow-up outcomes demonstrated the effectiveness and safety of this prosthesis. A large-scale trial is being conducted to further assess these findings.
Admission Random Blood Glucose, Fasting Blood Glucose, Stress Hyperglycemia Ratio, and Functional Outcomes in Patients With Acute Ischemic Stroke Treated With Intravenous Thrombolysis

Background Stress hyperglycemia ratio (SHR), calculated as glucose/glycated hemoglobin, has recently been developed for assessing stress hyperglycemia and could provide prognostic information for various diseases. However, calculating SHR using random blood glucose (RBG) drawn on admission or fasting blood glucose (FBG) could lead to different results. This study intends to evaluate the association between SHR and functional outcomes in patients with acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (r-tPA) intravenous thrombolysis. Methods Data from 230 patients with AIS following thrombolytic therapy with r-tPA in the Third Affiliated Hospital of Wenzhou Medical University from April 2016 to April 2019 were retrospectively reviewed. SHR1 was defined as [RBG (mmol/L)]/[HbA1c (%)] and SHR2 was defined as [FBG (mmol/L)]/[HbA1c (%)]. The outcomes included early neurological improvement (ENI), poor function defined as a modified Rankin Scale score (mRS) of 3–6, and all-cause death in 3 months. Multivariable logistic regression was performed to estimate the association between SHR and adverse outcomes. Results After adjustment for possible confounders, though patients with AIS with higher SHR1 tend to have a higher risk of poor outcome and death and unlikely to develop ENI, these did not reach the statistical significance. In contrast, SHR2 was independently associated with poor functional outcome (per 0.1-point increases: odds ratios (OR) = 1.383 95% CI [1.147–1.668]). Further adjusted for body mass index (BMI), triglyceride-glucose index (TyG), and diabetes slightly strengthen the association between SHR (both 1 and 2) and adverse outcomes. In subgroup analysis, elevated SHR1 is associated with poor functional outcomes (per 0.1-point increases: OR = 1.246 95% CI [1.041–1.492]) in non-diabetic individuals and the association between SHR2 and the poor outcomes was attenuated in non-cardioembolic AIS. Conclusion SHR is expected to replace random or fasting glucose concentration as a novel generation of prognostic indicator and a potential therapeutic target.
Natural History Studies in NCL and Their Expanding Role in Drug Development: Experiences From CLN2 Disease and Relevance for Clinical Trials

Conducting clinical trials in rare diseases is challenging. In trials that aim to use natural history control cohorts for evaluation of efficacy, lack of data on natural history of disease prolongs development of future therapies significantly. Therefore, collection of valid natural history data in clinical settings is needed to advance drug development. These data need to fulfill requirements on type of collection, quantifiable measures on the course of disease, verification and monitoring as well as compliance to strict data protection and sharing policies. Disease registries can be a source for patient data. Late-infantile CLN2 disease is characterized by rapid psychomotor decline and epilepsy. Natural-history data of 140 genotype-confirmed CLN2 patients from two independent, international cohorts were analyzed in a natural history study. Both datasets included quantitative ratings with disease-specific clinical scores. Among 41 patients for whom longitudinal assessments spanning an extended disease course were available within the DEM-CHILD DB (an international NCL disease patient database, NCT04613089), a rapid loss of motor and language abilities was documented in quantitative detail. Data showed that the course of disease in late-infantile CLN2 disease is highly predictable with regard to the loss of language and motor function and that the results were homogeneous across multiple and international sites. These data were accepted by EMA and FDA as valid natural-history controls for the evaluation of efficacy in experimental therapies for CLN2 disease and led to an expedited approval of intracerebroventricular enzyme replacement therapy with cerliponase alpha in May 2017.
Toward Exploring Topographic Effects on Evolution and Propagation of Ocean Mesoscale Eddies Through Life Cycle Across Izu-Ogasawara Ridge in Northwestern Pacific Ocean

Ocean mesoscale eddies contribute significantly to water transport on a global scale, constituting the ubiquitous, irregular, discrete, nonlinear components. In this manuscript, we propose to explore whether and how the topographic effect of one meridional ridge, could exert considerable influences on the evolution and propagation of mesoscale eddies through their life cycle, directly from the perspectives of real observation statistics. We systematically investigate the known variability of mesoscale eddy trajectories, derived by multimission satellite altimetry from 1993 to 2018, of a life cycle more than 6 months, over the Izu-Ogasawara Ridge, and quantitatively examined the eddy-ridge interaction by observation statistics and wavelet coherence map, with respect to the intrinsic attributes, namely, the amplitude, the rotation speed, the radius. Due to the spatial-temporal diversity, a series of correlative steps have been particularly designed along time-frequency domain to trace back mesoscale eddy trajectories in a variety of origins, location, lifespan, polarity, either completely or partially passing over the ridge, and to facilitate the standardization in statistics across three phases of their life cycle, i.e., before, during and after the interaction with the ridge. It has been revealed in our experiment that three intrinsic attributes of mesoscale eddies within 25 years, all demonstrated noticeable correlation with the variation of topographic relief over the ridge. We observed that most of the cyclonic eddies obviously tended to begin to decay or even demise, while on the contrary, some of the anticyclonic eddies preferred to intensify slightly, or making no significant difference when encountering the upslope until climbing across the top, basically consistent with the expectation of potential vorticity (PV) conservation. The drifting velocity agreed with the tendency that the direction would be more probably modified toward equatorward or poleward by forcing to meridional component, with zonal component reduced at the beginning. The mesoscale eddies with the passage over the ridge exhibited the relatively high average horizontal scales, amplitude, rotation speed on the whole, compared to those with only partially passage. The developed scheme could integrate more evidences on how mesoscale eddies response to the topographic effects during their time-varying evolution and propagation process, and help provide opportunities to potentially identify and predict the underlying dynamic patterns and mechanisms that mesoscale eddies engage in ocean dynamics when proceeding toward meridional ridges on a global scale, with the promise of the end-to-end data-driven solution, such as deep learning architecture involved in the future.
Synthetic Spatial Foraging With Active Inference in a Geocaching Task

Humans are highly proficient in learning about the environments in which they operate. They form flexible spatial representations of their surroundings that can be leveraged with ease during spatial foraging and navigation. To capture these abilities, we present a deep Active Inference model of goal-directed behavior, and the accompanying belief updating. Active Inference rests upon optimizing Bayesian beliefs to maximize model evidence or marginal likelihood. Bayesian beliefs are probability distributions over the causes of observable outcomes. These causes include an agent’s actions, which enables one to treat planning as inference. We use simulations of a geocaching task to elucidate the belief updating—that underwrites spatial foraging—and the associated behavioral and neurophysiological responses. In a geocaching task, the aim is to find hidden objects in the environment using spatial coordinates. Here, synthetic agents learn about the environment via inference and learning (e.g., learning about the likelihoods of outcomes given latent states) to reach a target location, and then forage locally to discover the hidden object that offers clues for the next location.
Comparison of the Efficacy of Anatomic and Non-anatomic Hepatectomy for Hepatic Alveolar Echinococcosis: Clinical Experience of 240 Cases in a Single Center

Background Hepatic alveolar echinococcosis (AE) is a zoonotic parasitic disease. There are more than 16,000 new cases each year, approximately 60 million people are threatened, and the annual direct economic loss is RMB 3 billion. The prevalence of AE in some areas of the Qinghai–Tibet Plateau is as high as 6.0%. Radical resection, including anatomic and non-anatomic hepatectomy, for advanced AE can significantly prolong the survival time of patients. However, there is no literature compared the efficacy of anatomic and non-anatomic hepatectomy. Therefore, by comparing various clinical evaluation indices between anatomic and non-anatomic hepatectomy, this study explored the short-term and long-term efficacy of these two surgical methods for AE. Methods The clinical data of patients with AE who underwent radical hepatectomy at Qinghai Provincial People's Hospital from January 2015 to January 2021 were retrospectively analyzed. The patients were divided into two groups by surgical method, that were, non-anatomic hepatectomy group and anatomic hepatectomy group. We compared these two groups focusing on basic preoperative data, such as age, sex, lesion size, and liver function parameters; main intraoperative evaluation indices, such as operation time, intraoperative porta hepatis occlusion time, intraoperative blood loss, and blood transfusion; and postoperative recovery evaluation indicators, such as postoperative liver function, incidence of surgical complications, and AE recurrence. Results A total of 240 patients were enrolled in this study, including 123 in anatomic hepatectomy group and 117 in non-anatomic hepatectomy group. There were no significant differences (P > 0.05) between baseline characteristics. Anatomic hepatectomy group was advantageous than non-anatomic hepatectomy group regarding intraoperative blood loss (P < 0.001), blood transfusion (P < 0.001), and porta hepatis occlusion time (P < 0.001). There were statistically significant differences in postoperative liver function (aspartate aminotransferase: P < 0.001; alanine aminotransferase: P < 0.001), surgical complications (P < 0.001), and AE recurrence rate (P = 0.003). The median survival of patients in the anatomic hepatectomy group was 66 months, compared to 65 months in the non-anatomic hepatectomy group (χ2 = 4.662, P = 0.031). Conclusions Anatomic hepatectomy was not only safe for AE but also showed better short-term and long-term superiority than non-anatomic hepatectomy.
Comparative Molecular Modelling of Capsular Polysaccharide Conformations in Streptococcus suis Serotypes 1, 2, 1/2 and 14 Identifies Common Epitopes for Antibody Binding

Streptococcus suis is an encapsulated, commensal, potentially pathogenic bacterium that infects swine globally and causes sporadic life-threatening zoonotic septicemia and meningitis infections in humans. The capsular polysaccharide is a primary virulence factor for S. suis. As S. suis serotype 2 is the most prevalent serotype globally, the serotype 2 CPS is the primary target of current efforts to develop an effective glycoconjugate veterinary vaccine against S. suis. Possible cross-protection with related serotypes would broaden the coverage of a vaccine. The CPS in serotypes 2 and 1/2 differ at a single residue (Gal versus GalNAc), and both are similar to serotypes 1 and 14: all contain a terminal sialic acid on a side chain. However, despite this similarity, there is complex pattern of cross-protection for these serotypes, with varying estimations of the importance of sialic acid in a protective epitope. Further, a pentasaccharide without the terminal sialic acid has been identified as minimal epitope for serotype 2. Here we use molecular simulation to model the molecule conformations of the CPS in serotypes 2, 1/2, 1 and 14, as well as three vaccine candidate oligosaccharides. The common epitopes we identify assist in rationalizing the apparently contradictory immunological data and provide a basis for rational design of S. suis vaccines in the future.
Intracranial Arterial Calcification and Intracranial Atherosclerosis: Close but Different

Background and Purpose Intracranial arterial calcification (IAC) may be present in the intimal or medial arterial layer. This study aimed to elucidate the link between the calcification and atherosclerotic disease in the intracranial vasculature. Methods Consecutive patients with acute ischemic stroke were included. Bilateral intracranial segment of the internal carotid artery, M1 segment of the middle cerebral artery, intracranial segment of the vertebral artery, and the basilar artery were visualized by the multi-detector computed tomography (CT) and vessel-wall magnetic resonance imaging (vwMRI) within 14 days after stroke onset. IAC was into the intimal or medial pattern. Subsequently, on the vwMRI, we assessed the luminal stenosis, eccentricity, plaque burden, and intraplaque hemorrhage (IPH) as markers of atherosclerosis at each IAC site. Results Among 69 patients with stroke, IAC was identified in 35% of (161/483) artery segments, of which 61.5% were predominantly intimal calcification and 38.5% were predominantly medial calcification. About 79.8% of intimal calcifications and 64.5% of medial calcifications co-existed with atherosclerotic plaques. Intimal calcification was associated with luminal stenosis (p = 0.003) caused by atherosclerotic lesions. Compared with the medial IAC, intimal IAC was more often accompanied by eccentric plaques (p = 0.02), larger plaque burden (p = 0.001), and IPH (p = 0.001). Conclusion Our multimodal imaging-based comparison study on intracranial arteriosclerosis demonstrated that intimal IAC, compared with medial IAC, was more often accompanied by the luminal stenosis, larger plaque burden, eccentricity, and IPH, providing strong evidence for clinical evaluation on the mechanism, risk, and prognosis of ischemic stroke.
Long-Term Improvement in a Chinese Cohort of Glucocorticoid-Resistant Childhood-Onset Myasthenia Gravis Patients Treated With Tacrolimus

Objectives To evaluate the long-term outcome of tacrolimus for childhood-onset myasthenia gravis (CMG) with an inadequate response to glucocorticoids, and investigate factors associated with favorable outcomes following tacrolimus treatment. Methods A retrospective, observational cohort study was performed for CMG patients who had not improved satisfactorily after sufficient prednisone therapy for at least 8 weeks. All patients were given tacrolimus in doses of 2–3 mg for more than 6 months. The primary efficacy outcome was assessed using the prednisone dose, quantitative MG (QMG), and MG-activity of daily living (ADL) scores. The participants were divided into improved and unimproved groups based on changes in QMG scores to investigate the risk factors that affected tacrolimus efficacy. Results A total of 149 glucocorticoid resistant CMG patients were finally enrolled in our study, with 113 (75.8%) responding well to tacrolimus (defined as minimal manifestation status or better). One month after initiating tacrolimus, there was a noticeable improvement in prednisone dose, QMG, and ADL scores, which continued to improve throughout the study. More importantly, the prednisone was eventually stopped in 89 of the patients (78.8%). Thymus type [odds ratio (OR) = 3.156, 95% confidence interval (CI) 1.427–6.978; P = 0.005] and pre-intervention status (OR = 0.284, 95%CI 0.109–0.741; P = 0.010) were independent predictors of tacrolimus efficacy after controlling for confounding factors in multiple logistic regression. Conclusion The majority of glucocorticoid-resistant CMG patients have a good long-term prognosis after adding tacrolimus. Thymus type and pre-intervention status can serve as potential predictors affecting the efficacy of tacrolimus.
Ankk1 Loss of Function Disrupts Dopaminergic Pathways in Zebrafish

Ankyrin repeat and kinase domain containing 1 (ANKK1) is a member of the receptor-interacting protein serine/threonine kinase family, known to be involved in cell proliferation, differentiation and activation of transcription factors. Genetic variation within the ANKK1 locus is suggested to play a role in vulnerability to addictions. However, ANKK1 mechanism of action is still poorly understood. It has been suggested that ANKK1 may affect the development and/or functioning of dopaminergic pathways. To test this hypothesis, we generated a CRISPR-Cas9 loss of function ankk1 zebrafish line causing a 27 bp insertion that disrupts the ankk1 sequence introducing an early stop codon. We found that ankk1 transcript levels were significantly lower in ankk1 mutant (ankk127ins) fish compared to their wild type (ankk1+/+) siblings. In ankk1+/+ adult zebrafish brain, ankk1 protein was detected in isocortex, hippocampus, basolateral amygdala, mesencephalon, and cerebellum, resembling the mammalian distribution pattern. In contrast, ankk1 protein was reduced in the brain of ankk127ins/27ins fish. Quantitative polymerase chain reaction analysis revealed an increase in expression of drd2b mRNA in ankk127ins at both larval and adult stages. In ankk1+/+ adult zebrafish brain, drd2 protein was detected in cerebral cortex, cerebellum, hippocampus, and caudate homolog regions, resembling the pattern in humans. In contrast, drd2 expression was reduced in cortical regions of ankk127ins/27ins being predominantly found in the hindbrain. No differences in the number of cell bodies or axonal projections detected by anti-tyrosine hydroxylase immunostaining on 3 days post fertilization (dpf) larvae were found. Behavioral analysis revealed altered sensitivity to effects of both amisulpride and apomorphine on locomotion and startle habituation, consistent with a broad loss of both pre and post synaptic receptors. Ankk127ins mutants showed reduced sensitivity to the effect of the selective dopamine receptor antagonist amisulpride on locomotor responses to acoustic startle and were differentially sensitive to the effects of the non-selective dopamine agonist apomorphine on both locomotion and habituation. Taken together, our findings strengthen the hypothesis of a functional relationship between ANKK1 and DRD2, supporting a role for ANKK1 in the maintenance and/or functioning of dopaminergic pathways. Further work is needed to disentangle ANKK1’s role at different developmental stages.
Advances in Mechanism Research on Polygonatum in Prevention and Treatment of Diabetes

Diabetes mellitus is a fast-growing disease with a major influence on people’s quality of life. Oral hypoglycemic drugs and insulin are currently the main effective drugs in the treatment of diabetes, but chronic consumption of these drugs has certain side effects. Polysaccharides, saponins, flavonoids, and phenolics are the primary secondary metabolites isolated from the rhizomes of Polygonatum sibiricum Redouté [Asparagaceae], Polygonatum kingianum Collett & Hemsl [Asparagaceae], or Polygonatum cyrtonema Hua [Asparagaceae], which have attracted much more attention owing to their unique therapeutic role in the treatment and prevention of diabetes. However, the research on the mechanism of these three Polygonatum spp. in diabetes has not been reviewed. This review provides a summary of the research progress of three Polygonatum spp. on diabetes and its complications, reveals the potential antidiabetic mechanism of three Polygonatum spp. , and discusses the effect of different processed products of three Polygonatum spp. in treating diabetes, for the sake of a thorough understanding of its effects on the prevention and treatment of diabetes and diabetes complications.