Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Progressive Calcineurin Nephrotoxicity: An Overstated Concept

It has long been believed that, for kidney transplant recipients, acute rejection episodes were a risk factor for, and a forerunner of, late graft dysfunction and graft loss. Thus, when the introduction of calcineurin inhibitor (CNI)-based immunosuppression was associated with a significant decease in acute rejection rates and improvement in short-term graft survival, there was optimism that there would be significant improvement in long-term graft survival rates. This hope has not been realized. At the same time, some CNI-immunosuppressed extra-renal transplant recipients have developed progressive native kidney dysfunction and renal failure. One possible explanation for these clinical observations is chronic CNI nephrotoxicity. There is no doubt that acute CNI nephrotoxicity exists (reviewed in 1). Numerous reports attest to renal dysfunction or even anuria related to high CNI blood levels, and this toxicity has been associated with specific histologic lesions (1). The acute dysfunction, however, is usually reversible when the CNI is withdrawn (2). In contrast to acute nephrotoxicity, data supporting chronic progressive CNI-related nephrotoxicity is less clear (3, 4). Although some kidney and extrarenal transplant recipients develop late renal dysfunction, there have been no studies that define what proportion of this dysfunction is due to CNI use vs. other causes. Yet much of the progressive late graft dysfunction after a kidney transplant, or progressive native kidney dysfunction after an extrarenal transplant, has been attributed to CNI toxicity. In my opinion, the importance of progressive chronic CNI nephrotoxicity has been overstated as a cause of late renal dysfunction. This overemphasis on chronic CNI nephrotoxicity has resulted in negative consequences for our recipients. First, the diagnosis of “CNI toxicity” in individual patients has led to lowering of CNI doses (and levels); for some dose reduction had resulted in increased immunologic activity. Second, we have spent two decades attempting to minimize “CNI nephrotoxicity” instead of studying and minimizing other more prevalent causes of late dysfunction. CNIs have numerous side effects and there may be many reasons to consider minimization or elimination of CNI use. However, in the subsequent sections, I will suggest that: a) for the great majority of cases, the existing data does not support chronic progressive calcineurin nephrotoxicity, and b) there are other more plausible explanations for late kidney dysfunction after kidney and extrarenal transplantation.
Opportunity identification and development in Chinese private high-tech enterprise: Hangzhou homewell case

This case describes the establishment, particularly entrepreneurial opportunity searching, identification and development of a private enterprise specialized in high tech in Zhejiang, a province with the most active and developed private economy in China. Focusing on the entrepreneurpsilas personal experiences and feelings, together with major events of the enterprise and relevant personspsila comments, the case verifies certain hypotheses formulated from the theory of opportunity identification and development. The present economic and technological environments in China, and difficulties and opportunities during transition are also presented. These have practical significance for local entrepreneurship and foreign investment in China.
Experimental chronic cerebral hypoperfusion results in decreased pericyte coverage and increased blood–brain barrier permeability in the corpus callosum

Murine chronic cerebral hypoperfusion (CCH) results in white matter (WM) injury and behavioral deficits. Pericytes influence blood–brain barrier (BBB) integrity and cerebral blood flow. Under hypoxic conditions, pericytes detach from perivascular locations increasing vessel permeability and neuronal injury. This study characterizes the time course of BBB dysfunction and pericyte coverage following murine experimental CCH secondary to bilateral carotid artery stenosis (BCAS). Mice underwent BCAS or sham operation. On post-procedure days 1, 3, 7 and 30, corpus callosum BBB permeability was characterized using Evans blue (EB) extravasation and IgG staining and pericyte coverage/count was calculated. The BCAS cohort demonstrated increased EB extravasation on postoperative days 1 (p = 0.003) 3 (p = 0.002), and 7 (p = 0.001) when compared to sham mice. Further, EB extravasation was significantly greater (p = 0.05) at day 3 than at day 30 in BCAS mice. BCAS mice demonstrated a nadir in pericyte coverage and count on post-operative day 3 (p < 0.05, compared to day 7, day 30 and sham). Decreased pericyte coverage/count and increased BBB permeability are most pronounced on postoperative day 3 following murine CCH. This precedes any notable WM injury or behavioral deficits.
Targeted Therapies for Prostate Cancer

New therapies for prostate cancer have emerged over the past three years. Nevertheless, none of these agents is curative, and unfortunately, patients often ultimately develop resistance to these agents. Therefore, the development of innovative and effective therapies that overcome these resistances is necessary. Unfortunately, the results of a phase III trial evaluating docetaxel in combination with targeted therapies demonstrated no difference in survival. Moreover, scarce data on the combination of a targeted therapy with new agents are currently available. New trials are investigating these possible combination treatments; the results of these (on-going) clinical studies are awaited.
Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability.

OBJECTIVE By producing instability in mouse knee joints, we attempted to determine the involvement of runt-related transcription factor 2 (RUNX-2), which is required for chondrocyte hypertrophy, in the development of osteoarthritis (OA). METHODS An experimental mouse OA model was created by surgical transection of the medial collateral ligament and resection of the medial meniscus of the knee joints of heterozygous RUNX-2-deficient (Runx2+/-) mice and wild-type littermates. Cartilage destruction and osteophyte formation in the medial tibial cartilage were compared by histologic and radiographic analyses. Localization of type X collagen and matrix metalloproteinase 13 (MMP-13) was examined by immunohistochemistry. Localization of RUNX-2 was determined by X-Gal staining in heterozygous RUNX-2-deficient mice with the lacZ gene insertion at the Runx2-deletion site (Runx2+/lacZ). Messenger RNA levels of type X collagen, MMP-13, and RUNX-2 were examined by real-time reverse transcriptase-polymerase chain reaction analysis. RESULTS RUNX-2 was induced in the articular cartilage of wild-type mice at the early stage of OA, almost simultaneously with type X collagen but earlier than MMP-13. Runx2+/- and Runx2+/lacZ mice showed normal skeletal development and articular cartilage; however, after induction of knee joint instability, they exhibited decreased cartilage destruction and osteophyte formation, along with reduced type X collagen and MMP-13 expression, as compared with wild-type mice. CONCLUSION RUNX-2 contributes to the pathogenesis of OA through chondrocyte hypertrophy and matrix breakdown after the induction of joint instability.
Critical Review : The Effect of Cochlear Implantation on Speech Perception and Neural Integrity for Children with Auditory Neuropathy / Dyssynchrony Compared to Children with Sensory Hearing Loss

This critical review examines the speech perception and electrophysiological outcomes of cochlear implanted children who have been identified with Auditory Neuropathy/Dyssynchrony compared to cochlear implanted children with a sensory hearing loss. Study designs include: case study and non-randomized clinical trials. Overall, research supports the idea that cochlear implants can provide benefit in terms of improved speech perception and neural integrity for implanted children with Auditory Neuropathy/Dyssynchrony. However, a concrete statement cannot be made regarding the ability of these children to perform on speech perception measures compared to implanted children with a sensory hearing loss. This is due to the limited availability of research, small sample sizes, and lack of statistically significant calculations of results.
A New Convergence Analysis of Finite Element Methods for Elliptic Distributed Optimal Control Problems with Pointwise State Constraints

We consider finite element methods for elliptic distributed optimal control problems with pointwise state constraints on two and three dimensional convex polyhedral domains formulated as fourth order variational inequalities. We develop a new convergence analysis that is applicable to C-1 finite element methods, classical nonconforming finite element methods and discontinuous Galerkin methods.
Orbitofrontal gray matter deficits as marker of Internet gaming disorder: converging evidence from a cross‐sectional and prospective longitudinal design

Internet gaming disorder represents a growing health issue. Core symptoms include unsuccessful attempts to control the addictive patterns of behavior and continued use despite negative consequences indicating a loss of regulatory control. Previous studies revealed brain structural deficits in prefrontal regions subserving regulatory control in individuals with excessive Internet use. However, because of the cross‐sectional nature of these studies, it remains unknown whether the observed brain structural deficits preceded the onset of excessive Internet use. Against this background, the present study combined a cross‐sectional and longitudinal design to determine the consequences of excessive online video gaming. Forty‐one subjects with a history of excessive Internet gaming and 78 gaming‐naive subjects were enrolled in the present study. To determine effects of Internet gaming on brain structure, gaming‐naive subjects were randomly assigned to 6 weeks of daily Internet gaming (training group) or a non‐gaming condition (training control group). At study inclusion, excessive Internet gamers demonstrated lower right orbitofrontal gray matter volume compared with Internet gaming‐naive subjects. Within the Internet gamers, a lower gray matter volume in this region was associated with higher online video gaming addiction severity. Longitudinal analysis revealed initial evidence that left orbitofrontal gray matter volume decreased during the training period in the training group as well as in the group of excessive gamers. Together, the present findings suggest an important role of the orbitofrontal cortex in the development of Internet addiction with a direct association between excessive engagement in online gaming and structural deficits in this brain region.
High‐throughput image analysis in the diagnosis of papillary thyroid carcinoma

Thyroid cancer is the most common endocrine cancer, and its incidence has been increasing worldwide in the past decades. The increasing demand in medicine for rapid and accurate diagnosis enabled the application of digital imaging analysis in order to increase workflow efficiency and accurate analyses. The present study aimed to automatically differentiate papillary thyroid carcinoma from normal thyroid cells using high‐throughput image analysis.
Regulating Financial Conglomerates

We analyse a model of financial intermediation in which intermediaries are subject to moral hazard and they do not invest socially optimally, because they ignore the systemic costs of failure and, in the case of banks, because they fail to account for risks which are assumed by the deposit insurance fund. Capital adequacy requirements are designed to minimise the social costs of these effects. We show that banks should always have higher regulatory capital requirements than insurance companies. Contrary to received wisdom, when banks and insurance companies combine to form financial conglomerates we show that it is socially optimal to separate their balance sheets. Moreover, the practice of "regulatory arbitrage", or of transfering assets from one balance sheet to another, is welfare increasing.
Chemistry and antioxidant activity of plants containing some phenolic compounds

Natural antioxidants inhibit the adverse effects of the Reactive Oxygen Species produced in living things and enable to survive. Depending on this principle, humans started using some plant products to cure from various diseases. Natural products have proved of great health impact on human traditionally and scientifically. Moreover, the research has so far done in the field of natural antioxidants. Therefore, antioxidants have been traditionally used as well as experimentally proved beneficial. The antioxidant components of the natural products constitute the major source of human health promotion and maintenance. The nature is still the perfect source for health promotion and for the supplementation of safe drugs. Great attention is mandatory to explore many underestimated plants with highly effective antioxidant activity. Few classes of natural products have received as much attention as phenolics and polyphenols.
Composition of the antigenic material removed from Campylobacter jejuni by heat

The antigenic material removed form Campylobacter jejuni by the boiling of whole cells in saline was examined biochemically. Analyses showed that the extracted material contained 3 micrograms of protein per ml per mg of wet cells and ca. 2.6 micrograms of carbohydrate per ml per mg of wet cells. Further extraction of the material with chloroform-methanol produced about 0.5 microgram of water-insoluble residue per ml per mg of wet cells, suggesting the presence of lipid as well. Additional analyses revealed the presence of hexose, pentose, heptose, hexosamine, and 2-keto-3-deoxyoctonic acid, and the extract was also positive by the Limulus amoebocyte lysate assay for lipopolysaccharide. An examination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that at least 10 different protein bands could be detected. One of the major bands corresponded to the major outer membrane protein, as determined by comparison with an outer membrane protein preparation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Another major protein in the heated extract corresponded to a band previously shown to be flagellin. An analysis of the time course of the release of material showed that a significant amount was removed after 3 to 10 min at 100 degrees C, but the release of material seemed to be delayed at lower temperatures. These results show that the treatment of C. jejuni with heat produces a complex mixture of components, including cell wall lipopolysaccharide, the major outer membrane protein, and flagellin. It is likely that some cytoplasmic components are present as well. Blebs of outer membrane have been observed with this organism by electron microscopy. Our results confirm this and suggest that the heating of cells accelerates this blebbing process.
Auction Settings and Performance of Electronic Marketplaces for Truckload Transportation Services

This paper compares the performance of different sequential auction settings for the procurement of truckload services. In this environment, demands arrive randomly over time and are described by pick up, delivery locations and hard time-windows. Upon demand arrival, carriers compete for the loads. Different auction and information disclosure settings are studied. Learning methodologies are discussed and analyzed. Simulation results are presented.
Targeting voltage-gated calcium channels for the treatment of neuropathic pain: a review of drug development

Introduction: Pain is a major burden for affected individuals and society, and controlling neuropathic pain is especially challenging. The number of drugs available is limited and treatments are often marginally effective and burdened by side effects. Voltage-gated calcium channels (VGCC) play a major role in the development and maintenance of neuropathic pain and are thus prime targets for its treatment. Areas covered: Currently available drugs that target the calcium channel include ziconotide, gabapentin and pregabalin. While there are no VGCC blockers currently in clinical trials, there are many in development. Recently, orally available, use-dependent compounds have been reported. We will review, in detail, compounds currently in development and include a brief review of VGCC and the drugs currently in use. Expert opinion: There is real hope that new drugs targeting calcium channels will soon be available. This hope is based on advancing technologies for peptide synthesis, more efficient drug screening and orally available, use-dependent compounds. Some form of direct VGCC blockade or modulation will always have a place in the treatment of neuropathic pain, but given the complexity and neuroplasticity of pain transmission, polypharmacy will likely be required for many chronic pain sufferers for the foreseeable future.
Differential response patterns of kisspeptin and RFamide‐related peptide to photoperiod and sex steroid feedback in the Djungarian hamster (Phodopus sungorus)

Many animals synchronise their reproductive activity with the seasons to optimise the survival of their offspring. This synchronisation involves switching on and off their gonadotrophic axis. Ever since their discovery as key regulators of gonadotrophin‐releasing hormone (GnRH) neurones, the hypothalamic RF‐amide peptides kisspeptin and RFamide‐related peptide (RFRP) have been a major focus of research on the seasonal regulation of the gonadotrophic axis. In the present study, we investigated the regulation of both neuropeptides in the Djungarian hamster, a major animal model for the study of seasonal reproduction. During the long‐day breeding period, kisspeptin neurones in the anteroventral periventricular area are solely controlled by a positive sex steroid feedback and, in the arcuate nucleus, they are subject to a very strong negative sex steroid feedback associated with a minor photoperiodic effect. During short‐day sexual quiescence, the disappearance of this hormonal feedback leads to high levels of kisspeptin in arcuate neurones. Notably, chronic central administration of kisspeptin is able to over‐ride the photoperiodic inhibition of the gonadotrophic axis and reactivate the reproductive function. Therefore, our data suggest that kisspeptin secretion by arcuate neurones during sexual quiescence is inhibited by mechanisms upstream of kisspeptin neurones. RFRP expression is solely controlled by photoperiod, being strongly reduced in short days independently of the sex steroid feedback. Thus, kisspeptin and RFRP display contrasting patterns of expression and regulation. Upstream mechanisms controlling these neurones should be the focus of further studies on the roles of these RFamide neuropeptides in the seasonal control of reproduction.
Clustering with Modified Cosine Distance Learned from Constraints

In this paper we present a modiﬁed cosine similarity metric that helps to make features more discriminative. The new metric is deﬁned via various linear transformations of the original feature space to a space in which these samples are better separated. These transformations are learned from a set of constraints representing available domain knowledge by solving related optimization problems. We present results on two natural language call routing datasets that show signiﬁcant improvements ranging from 3% to 5% absolute in the purity of clusters obtained in an unsupervised fashion
Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q− syndrome patients

Myelodysplastic syndromes (MDSs) are a group of hematopoietic stem cell disorders characterized by ineffective hematopoiesis and peripheral blood cytopenias. Lenalidomide has dramatic therapeutic effects in patients with low-risk MDS and a chromosome 5q31 deletion, resulting in complete cytogenetic remission in >60% of patients. The molecular basis of this remarkable drug response is unknown. To gain insight into the molecular targets of lenalidomide we investigated its in vitro effects on growth, maturation, and global gene expression in isolated erythroblast cultures from MDS patients with del(5)(q31). Lenalidomide inhibited growth of differentiating del(5q) erythroblasts but did not affect cytogenetically normal cells. Moreover, lenalidomide significantly influenced the pattern of gene expression in del(5q) intermediate erythroblasts, with the VSIG4, PPIC, TPBG, activin A, and SPARC genes up-regulated by >2-fold in all samples and many genes involved in erythropoiesis, including HBA2, GYPA, and KLF1, down-regulated in most samples. Activin A, one of the most significant differentially expressed genes between lenalidomide-treated cells from MDS patients and healthy controls, has pleiotropic functions, including apoptosis of hematopoietic cells. Up-regulation and increased protein expression of the tumor suppressor gene SPARC is of particular interest because it is antiproliferative, antiadhesive, and antiangiogenic and is located at 5q31-q32, within the commonly deleted region in MDS 5q− syndrome. We conclude that lenalidomide inhibits growth of del(5q) erythroid progenitors and that the up-regulation of SPARC and activin A may underlie the potent effects of lenalidomide in MDS with del(5)(q31). SPARC may play a role in the pathogenesis of the 5q− syndrome.
Score normalization of ensemble SVMs for brain-computer interface P300 speller

Brain-computer interface (BCI) P300 speller can be used as a powerful aid for severely disabled people in their everyday life. The character recognition using P300 speller involves two stages for classification. First stage is to detect the P300 signal and second one is to determine the right character from the detected P300. Classification of P300 is a challenging task in character recognition process. Ensemble of classifiers is a robust method for classification as it reduces the classifier variability. In multiclassifier system the averaged score can be effected by one classifier as the score of different classifiers are not in the same level. To reduce the effect of one classifier, the score of the each classifiers are normalized. The proposed method includes different score normalization techniques for ensemble of SVMs (ESVM) for classification. Here min-max normalization, Z-score normalization and median and median absolute deviation (MAD) normalization techniques are used. The proposed algorithms have been evaluated on data set II of the BCI Competition III. It is observed that the performance of the proposed normalization technique is better compared to the earlier reported techniques for 5th and 15th epoch to classify different characters.
The clinical application of monoclonal antibody therapies in renal transplantation

Monoclonal antibodies have become valuable tools for the precise clinical manipulation of the immune system. These highly specific proteins have proven their usefulness in both the treatment and prevention of organ transplant rejection. Indeed, they are the centrepieces of many evolving regimens designed to reduce or eliminate the need for chronic immunosuppression. This manuscript will review the monoclonal antibodies that have made their way into the clinic either as experimental therapies or approved drugs. It will provide a general overview of this class of agents and their mechanisms of action. Standard therapies and potential new applications will be described.