Miracle-dz/UniFAR-FTUs huggingface dataset:
Preoperative C-reactive protein/albumin ratio is a significant predictor of survival in bladder cancer patients after radical cystectomy: a retrospective study

Purpose Earlier studies have indicated the prognostic value of the pretreatment C-reactive protein (CRP)/albumin ratio (CAR) in multiple tumor types. The present study attempts to investigate the predictive role of preoperative CAR in patients with bladder cancer after radical cystectomy (RC), and explores its prognostic index value. Patients and methods A total of 131 patients with bladder cancer after RC between 2009 and 2015 were analyzed in the present study. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method and Cox regression analyses. Prediction accuracy was evaluated through the area under the receiver operating characteristic curve (AUC). Results The median follow-up time for all patients in the present retrospective study was 39.72 months (15.51–53.26 months). The Kaplan–Meier curve analysis indicated that bladder cancer patients with high preoperative CAR (>0.2) were significantly associated with decreased PFS and OS (all, P<0.001). The multivariate analysis confirmed CAR as a common independent prognostic factor for PFS and OS. Furthermore, the effective combination of CAR and pathological T staging constituted a new index (CART), and was observed to be an independent risk factor for OS (CART score =2, HR=0.264; 95% CI: 0.106–0.660, P=0.004; CART score =3, HR =0.371; 95% CI: 0.208–0.661, P=0.001). However, CART did not show any prognostic significance for PFS. Importantly, the AUC values of CAR for OS and PFS were higher than other conventional clinical indices. Conclusion The present study demonstrated that CAR can be used as a new prognostic indicator of OS and PFS in patients with bladder cancer after RC. Combining the CAR score with pathological T staging as the CART score appears to be a more effective prognostic indicator of poor OS, but not PFS.
Associations between Community-Acquired Pneumonia and Proton Pump Inhibitors in the Laryngeal/Voice-Disordered Population

versial, as has some of the literature that was cited in the article. For example, the first major article on this topic, published in JAMA in 2004 by Laheij et al, contained fundamental methodological flaws, later acknowledged in a letter to the editor, and did not establish a causal relationship between acid-suppressive drugs and community-acquired pneumonia. The current article, by Cohen et al, provides a useful review of the literature and excellent new data. The authors acknowledge substantial limitations of the study that were unavoidable because of the retrospective design. While those limitations were managed as well as possible, the authors might also have discussed one important possibility that was not emphasized in the article. The authors established an association between proton pump inhibitor (PPI) use and community-acquired pneumonia (CAP). While they did not go so far as to claim a causal relationship between PPI and CAP, that possibility is likely to be inferred by readers. However, when prescribed correctly, PPIs are used to treat reflux. The authors could have pointed out that the association between PPIs and CAP might be due to a causal relationship between reflux and CAP rather than treatment for reflux. Most of us who have assessed a large number of patients through 24-hour pH impedance testing are aware that PPIs rarely suppress acid completely, even when given in double or triple the recommended doses, and that PPIs treat acidity, not reflux. Laryngopharyngeal reflux (LPR) has been associated with aspiration. It is possible that in the patients taking PPI identified in the present study, the reflux itself (rather than the PPI) was causally related to the CAP and that if there had been a control group of patients with LPR in which PPI treatment had been withheld, that group might have had an even higher incidence of CAP. If misinterpreted, research into LPR and its treatments can inadvertently result in inappropriate withholding of medication by physicians or reluctance among patients to take PPIs for reasons that might not have scientific merit. Since untreated or undertreated reflux may have serious consequences, including esophageal and laryngeal cancer, continued research should be encouraged to definitively establish the causal relationship of disease, treatment, and complications.
Recognition of dominant attractants by key chemoreceptors mediates recruitment of plant growth‐promoting rhizobacteria

Chemotaxis to plant root exudates is supposed to be a prerequisite for efficient root colonization by rhizobacteria. This is a highly multifactorial process since root exudates are complex compound mixtures of which components are recognized by different chemoreceptors. Little information is available as to the key components in root exudates and their receptors that drive colonization related chemotaxis. We present here the first global assessment of this issue using the plant growth-promoting rhizobacterium (PGPR) Bacillus velezensis SQR9 (formerly B. amyloliquefaciens). This strain efficiently colonizes cucumber roots, and here, we show that chemotaxis to cucumber root exudates was essential in this process. We conducted chemotaxis assays using cucumber root exudates at different concentrations, individual exudate components as well as recomposed exudates, taking into account their concentrations detected in root exudates. Results indicated that two key chemoreceptors, McpA and McpC, were essential for root exudate chemotaxis and root colonization. Both receptors possess a broad ligand range and recognize most of the exudate key components identified (malic, fumaric, gluconic and glyceric acids, Lys, Ser, Ala and mannose). The remaining six chemoreceptors did not contribute to exudate chemotaxis. This study provides novel insight into the evolution of the chemotaxis system in rhizobacteria.
Dynamic Feature Scaling for K-Nearest Neighbor Algorithm

Nearest Neighbors Algorithm is a Lazy Learning Algorithm, in which the algorithm tries to approximate the predictions with the help of similar existing vectors in the training dataset. The predictions made by the K-Nearest Neighbors algorithm is based on averaging the target values of the spatial neighbors. The selection process for neighbors in the Hermitian space is done with the help of distance metrics such as Euclidean distance, Minkowski distance, Mahalanobis distance etc. A majority of the metrics such as Euclidean distance are scale variant, meaning that the results could vary for different range of values used for the features. Standard techniques used for the normalization of scaling factors are feature scaling method such as Z-score normalization technique, Min-Max scaling etc. Scaling methods uniformly assign equal weights to all the features, which might result in a non-ideal situation. This paper proposes a novel method to assign weights to individual feature with the help of out of bag errors obtained from constructing multiple decision tree models.
Silencing SOCS3 Markedly Deteriorates Spondyloarthritis in Mice Induced by Minicircle DNA Expressing IL23

Objective: Despite extensive studies, the precise mechanism underlying spondyloarthritis, especially ankylosing spondylitis, remains elusive. This study aimed to develop an ideal animal model for an insight into mechanism of spondyloarthritis and functional relevance of SOCS3 in spondyloarthritis. Methods: Since SOCS3 is a major regulator of IL23-STAT3 signaling, we generated SOCS3 knockdown transgenic (TG) mice for development of an animal model of spondyloarthritis. A hydrodynamic delivery method was employed to deliver minicircle DNA expressing IL23 (mc-IL23) into wild-type (WT) and the TG mice. Knockdown/overexpression systems mediated by lentivirus and retrovirus were used to determine whether SOCS3 regulated osteoblast differentiation. Results: Forced expression of IL23 induced severe joint destruction and extensive bone loss in SOCS3 knockdown TG mice, while this treatment only caused moderate symptoms in WT mice. Furthermore, severe spondyloarthritis was found in IL23-injected TG mice as compared to mild disease observed in WT controls under same condition. Moreover, our studies showed that IL23 promoted osteoblast differentiation via activation of STAT3 pathway and disruption of SOCS3 expression greatly increased phosphorylation of STAT3. In addition, silencing SOCS3 resulted in enhanced osteoblast differentiation through activation of Smad1/5/9 signaling, as evidenced by elevated phosphorylation level of Smad1/5/9. Experiments further demonstrated that SOCS3 interacted with Smad1 and thus suppressed the BMP2-Smad signaling. Conclusions: The results reveal that SOCS3 is involved in IL23-induced spondyloarthritis and acts as a key regulator of osteoblast differentiation, and suggest that SOCS3 knockdown TG mice may be an ideal animal model for further studies of spondyloarthritis.
Design and Implementation of SDN-Based Proactive Firewall System in Collaboration with Domain Name Resolution

SUMMARY Security facilities such as ﬁrewall system and IDS / IPS (Intrusion Detection System / Intrusion Prevention System) have become fundamental solutions against cyber threats. With the rapid change of cyber attack tactics, detail investigations like DPI (Deep Packet Inspection) and SPI (Stateful Packet Inspection) for incoming tra ﬃ c become necessary while they also cause the decrease of network throughput. In this paper, we propose an SDN (Software Deﬁned Network) - based proactive ﬁrewall system in collaboration with domain name resolution to solve the problem. The system consists of two ﬁrewall units (lightweight and normal) and a proper one will be assigned for checking the client of incoming tra ﬃ c by the collaboration of SDN controller and internal authoritative DNS server. The internal authoritative DNS server obtains the client IP address using EDNS (Extension Mechanisms for DNS) Client Subnet Option from the external DNS full resolver during the name resolution stage and notiﬁes the client IP address to the SDN controller. By checking the client IP address on the whitelist and blacklist, the SDN controller assigns a proper ﬁrewall unit for investigating the incoming tra ﬃ c from the client. Consequently, the incoming tra ﬃ c from a trusted client will be directed to the lightweight ﬁrewall unit while from others to the normal ﬁrewall unit. As a result, the incoming tra ﬃ c can be distributed properly to the ﬁrewall units and the congestion can be mitigated. We implemented a prototype system and evaluated its performance in a local experimental network. Based on the results, we conﬁrmed that the prototype system presented expected features and acceptable performance when there was no ﬂooding attack. We also conﬁrmed that the prototype system showed better performance than conventional ﬁrewall system under ICMP ﬂooding attack.
Self-nanoemulsifying drug-delivery systems for potentiated anti-inflammatory activity of diacerein

Background Effective treatment of osteoarthritis necessitates both symptomatic relief and hindrance of joint degeneration progression. Non-steroidal anti-inflammatory drugs permit symptomatic relief only and can cause mucosal injury in the gut. Before absorption, diacerein (Dcn) is converted into rhein that counteracts cartilage degeneration without affecting prostaglandin production. Yet, low solubility and laxative action of unabsorbed rhein in the colon hindered its use. Thus, enhanced Dcn dissolution would allow absorption at the upper gut improving its bioavailability and possibly abolishing the laxative action. Methods Therefore, self-nanoemulsifying drug delivery systems (SNEDDSs) with each of gelucire 44/14 (Glc) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at different drug:carrier weight ratios of 1:1, 1:2, 1:4, 1:6, 1:8 and 1:10 were prepared by melt method and filled into hard gelatin capsules. The optimized binary systems were selected based on solid state characterization, scanning electron microscopy (SEM) and in vitro evaluation of the prepared SNEDDSs in comparison with their corresponding physical mixtures (PMs) and Dcn. The optimized systems were further examined with respect to their morphology, size distribution and ζ-potential. Moreover, the anti-inflammatory activity of the optimized systems against carrageenan-induced paw edema in rats was assessed through estimation of edema and edema inhibition percentages as well as histopathological examination and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α) and caspase-3. Results Significantly (P<0.05) enhanced in vitro drug release was recorded for SNEDDSs with either carrier when compared to Dcn and the corresponding PMs. SNEDDSs based on 1:10 Dcn:Glc and 1:8 Dcn:TPGS showed significantly (P<0.05) reduced edema and inflammation as well as expression of TNF-α and caspase-3 relative to positive control and Dcn pretreated groups. Conclusion These SNEDDSs can be represented as potential oral drug delivery systems of Dcn for enhanced dissolution and anti-inflammatory activity against carrageenan-induced paw edema.
Activation of trigeminal ganglion satellite glial cells in CFA-induced tooth pulp pain in rats

This study further investigated the mechanisms underlying the rat model of tooth pulp inflammatory pain elicited by complete Freund’s adjuvant (CFA), in comparison to other pulpitis models. Pulps of the left maxillary first molars were accessed. In the CFA group, the pulps were exposed, and CFA application was followed by dental sealing. In the open group, the pulps were left exposed to the oral cavity. For the closed group, the pulps were exposed, and the teeth were immediately sealed. Naïve rats were used as negative controls. Several parameters were evaluated at 1, 2, 3 and 8 days. There was no statistical significant difference among the groups when body weight variation, food or water consumption were compared. Analysis of serum cytokines (IL-1β, TNF or IL-6) or differential blood cell counts did not reveal any evidence of systemic inflammation. The CFA group displayed a significant reduction in the locomotor activity (at 1 and 3 days), associated with an increased activation of satellite glial cells in the ipsilateral trigeminal ganglion (TG; for up to 8 days). Amygdala astrocyte activation was unaffected in any experimental groups. We provide novel evidence indicating that CFA-induced pulp inflammation impaired the locomotor activity, with persistent activation of ipsilateral TG satellite cells surrounding sensory neurons, without any evidence of systemic inflammation or amygdala astrogliosis.
Tryptophan-Derived Uremic Toxins and Thrombosis in Chronic Kidney Disease

Patients with chronic kidney disease (CKD) display an elevated risk of thrombosis. Thrombosis occurs in cardiovascular events, such as venous thromboembolism, stroke, and acute coronary syndrome, and is a cause of hemodialysis vascular access dysfunction. CKD leads to the accumulation of uremic toxins, which exerts toxic effects on blood and the vessel wall. Some uremic toxins result from tryptophan metabolization in the gut through the indolic and the kynurenine pathways. An increasing number of studies are highlighting the link between such uremic toxins and thrombosis in CKD. In this review, we describe the thrombotic mechanisms induced by tryptophan-derived uremic toxins (TDUT). These mechanisms include an increase in plasma levels of procoagulant factors, induction of platelet hyperactivity, induction of endothelial dysfunction/ impairment of endothelial healing, decrease in nitric oxide (NO) bioavailability, and production of procoagulant microparticles. We focus on one important prothrombotic mechanism: The induction of tissue factor (TF), the initiator of the extrinsic pathway of the blood coagulation. This induction occurs via a new pathway, dependent on the transcription factor Aryl hydrocarbon receptor (AhR), the receptor of TDUT in cells. A better understanding of the prothrombotic mechanisms of uremic toxins could help to find novel therapeutic targets to prevent thrombosis in CKD.
Spore-autonomous fluorescent protein expression identifies meiotic chromosome mis-segregation as the principal cause of hybrid sterility in yeast

Genome-wide sequence divergence between populations can cause hybrid sterility through the action of the anti-recombination system, which rejects crossover repair of double strand breaks between nonidentical sequences. Because crossovers are necessary to ensure proper segregation of homologous chromosomes during meiosis, the reduced recombination rate in hybrids can result in high levels of nondisjunction and therefore low gamete viability. Hybrid sterility in interspecific crosses of Saccharomyces yeasts is known to be associated with such segregation errors, but estimates of the importance of nondisjunction to postzygotic reproductive isolation have been hampered by difficulties in accurately measuring nondisjunction frequencies. Here, we use spore-autonomous fluorescent protein expression to quantify nondisjunction in both interspecific and intraspecific yeast hybrids. We show that segregation is near random in interspecific hybrids. The observed rates of nondisjunction can explain most of the sterility observed in interspecific hybrids through the failure of gametes to inherit at least one copy of each chromosome. Partially impairing the anti-recombination system by preventing expression of the RecQ helicase SGS1 during meiosis cuts nondisjunction frequencies in half. We further show that chromosome loss through nondisjunction can explain nearly all of the sterility observed in hybrids formed between two populations of a single species. The rate of meiotic nondisjunction of each homologous pair was negatively correlated with chromosome size in these intraspecific hybrids. Our results demonstrate that sequence divergence is not only associated with the sterility of hybrids formed between distantly related species but may also be a direct cause of reproductive isolation in incipient species.
Feature Engineering for Tree Leaf Classifier

The article presents an approach to classify trees based on the image of a leaf. In this work, 1464 images of 18 species of trees that are typical for Russian flora were used, and the method of k-nearest neighbors was used for classification model. The process of feature retrieval includes image verification, binarization and removal of the leaf petiole. The selected 22 features are based on the analysis of the image moments and distances from the centroid to the boundary coordinates. An accuracy of more than 95% is obtained on the testing set.
The anatomy of concussion and chronic traumatic encephalopathy: A comprehensive review

Concussion is defined as a complex pathophysiological process that affects the brain as a result of traumatic biomechanical forces. Repeated unrecovered concussions can result in chronic brain injury syndrome which is referred to in the literature today as chronic traumatic encephalopathy. ” There is an exponential increase in public and political interest in this condition in the recent times resulting in a significant investment in research to improve the current understanding of the disease, ways to decrease its incidence and determine its prognosis. Broadly the research involves three main disciplines of medicine including neuropathology, neuroradiology and biological markers. Although progress has been made, to date there is no definite pathological, radiological or neurobiological marker which has shown consistent promise to make the diagnosis and prognosticate the disease. Possible reasons are multiple such as inconsistencies in the methods studies have used, different time periods in which the tests were conducted, the small numbers of subjects included in the studies, and inconsistencies in the definitions of concussion or mild traumatic brain injury. Herein, we present a comprehensive review of the current literature on this topic. Positron emission tomography scans with radioactive ligands such as T807 as an imaging biomarker, and neurofilament light and ubiquitin C‐terminal hydrolase as serum biomarkers have shown some promise lately in diagnosing concussion and chronic traumatic encephalopathy and also determining their prognosis. Clin. Anat. 32:310–318, 2019. © 2018 Wiley Periodicals, Inc.
Reaction mechanism of the bioluminescent protein mnemiopsin1 revealed by X-ray crystallography and QM/MM simulations

Bioluminescence of a variety of marine organisms, mostly cnidarians and ctenophores, is carried out by Ca2+-dependent photoproteins. The mechanism of light emission operates via the same reaction in both animal families. Despite numerous studies on the ctenophore photoprotein family, the detailed catalytic mechanism and arrangement of amino acid residues surrounding the chromophore in this family are a mystery. Here, we report the crystal structure of Cd2+-loaded apo-mnemiopsin1, a member of the ctenophore family, at 2.15 Å resolution and used quantum mechanics/molecular mechanics (QM/MM) to investigate its reaction mechanism. The simulations suggested that an Asp-156–Arg-39–Tyr-202 triad creates a hydrogen-bonded network to facilitate the transfer of a proton from the 2-hydroperoxy group of the chromophore coelenterazine to bulk solvent. We identified a water molecule in the coelenteramide-binding cavity that forms a hydrogen bond with the amide nitrogen atom of coelenteramide, which, in turn, is hydrogen-bonded via another water molecule to Tyr-131. This observation supports the hypothesis that the function of the coelenteramide-bound water molecule is to catalyze the 2-hydroperoxycoelenterazine decarboxylation reaction by protonation of a dioxetanone anion, thereby triggering the bioluminescence reaction in the ctenophore photoprotein family.
A review of automatic differentiation and its efficient implementation

Derivatives play a critical role in computational statistics, examples being Bayesian inference using Hamiltonian Monte Carlo sampling and the training of neural networks. Automatic differentiation (AD) is a powerful tool to automate the calculation of derivatives and is preferable to more traditional methods, especially when differentiating complex algorithms and mathematical functions. The implementation of AD, however, requires some care to insure efficiency. Modern differentiation packages deploy a broad range of computational techniques to improve applicability, run time, and memory management. Among these techniques are operation overloading, region‐based memory, and expression templates. There also exist several mathematical techniques which can yield high performance gains when applied to complex algorithms. For example, semi‐analytical derivatives can reduce by orders of magnitude the runtime required to numerically solve and differentiate an algebraic equation. Open and practical problems include the extension of current packages to provide more specialized routines, and finding optimal methods to perform higher‐order differentiation.