Miracle-dz/UniFAR-FTUs huggingface dataset:
Down-regulation of fecal miR-143 and miR-145 as potential markers for colorectal cancer.

OBJECTIVE To detect 4 MicroRNA (miRNA) in the stool samples of colorectal cancer (CRC) patients to determine whether these miRNAs could be biomarkers in CRC screening or treatment. METHODS A retrospective comparison study was carried out in the Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China from September 2009 to March 2011. We detected 4 miRNAs (miR-143, miR-145, miR-21, and miR-106a) in the stool samples of 38 CRC patients and 13 healthy individuals. Total RNA from the stool samples was extracted using the EZNA TM stool RNA kit R6828-01. The miRNA quantification was carried out using TaqMan miRNA assays and the TaqMan Gene Expression Master Mix. RESULTS The expression levels of miR-143 and miR-145 in the stool of the CRC patients were lower than in those of the healthy persons (p<0.005, median of 2-∆∆ct). No statistically significant difference was found in the expression levels of both miR-21 and miR-106a between the stool of CRC patients and those of the healthy persons (p>0.05). CONCLUSION The detection of fecal miRNAs is a potential method for CRC diagnosis or screening. Particularly, the down-regulation of fecal miR-143 and miR-145 could be a potential marker for CRC.
Crystal Structure of Activated CheY

The crystal structure of BeF 3 − -activated CheY, with manganese in the magnesium binding site, was determined at 2.4-Å resolution. BeF 3 − bonds to Asp57, the normal site of phosphorylation, forming a hydrogen bond and salt bridge with Thr87 and Lys109, respectively. The six coordination sites for manganese are satisfied by a fluorine of BeF 3 − , the side chain oxygens of Asp13 and Asp57, the carbonyl oxygen of Asn59, and two water molecules. All of the active site interactions seen for BeF 3 − -CheY are also observed in P-Spo0Ar. Thus, BeF 3 − activates CheY as well as other receiver domains by mimicking both the tetrahedral geometry and electrostatic potential of a phosphoryl group. The aromatic ring of Tyr106 is found buried within a hydrophobic pocket formed by β-strand β4 and helix H4. The tyrosine side chain is stabilized in this conformation by a hydrogen bond between the hydroxyl group and the backbone carbonyl oxygen of Glu89. This hydrogen bond appears to stabilize the active conformation of the β4/H4 loop. Comparison of the backbone coordinates for the active and inactive states of CheY reveals that only modest changes occur upon activation, except in the loops, with the largest changes occurring in the β4/H4 loop. This region is known to be conformationally flexible in inactive CheY and is part of the surface used by activated CheY for binding its target, FliM. The pattern of activation-induced backbone coordinate changes is similar to that seen in FixJr. A common feature in the active sites of BeF 3 − -CheY, P-Spo0Ar, P-FixJr, and phosphono-CheY is a salt bridge between Lys109 Nζ and the phosphate or its equivalent, beryllofluoride. This suggests that, in addition to the concerted movements of Thr87 and Tyr106(Thr-Tyr coupling), formation of the Lys109-PO 3 − salt bridge is directly involved in the activation of receiver domains generally.
Agency Cost under the Restriction of Free Cash Flow

Agency cost theory is an important branch of capital structural theory. Free cash flow has significant impact on agency cost. The combination of research on these two fields would help to build and extend the theoretical system. Based on agency cost theory, the present study firstly categorized the characteristics of free cash flow as well as the statistical methodologies. Furthermore, the existence of investing free cash flow in agency cost was proved by a model. Then free cash flow was introduced into agency cost theory as restriction, the analysis shows that it will change agency cost, in turn, will have an impact on the relationship between agency cost and capital structure, finally, will influence the optimal capital structure point to maintain the equilibrium. Concretely, with the increasing free cash flow, correspondingly, debt proportion will decrease.
Retinal stem cells transplanted into models of late stages of retinitis pigmentosa preferentially adopt a glial or a retinal ganglion cell fate.

PURPOSE To characterize the potential of newborn retinal stem cells (RSCs) isolated from the radial glia population to integrate the retina, this study was conducted to investigate the fate of in vitro expanded RSCs transplanted into retinas devoid of photoreceptors (adult rd1 and old VPP mice and rhodopsin-mutated transgenic mice) or partially degenerated retina (adult VPP mice) retinas. METHODS Populations of RSCs and progenitor cells were isolated either from DBA2J newborn mice and labeled with the red lipophilic fluorescent dye (PKH26) or from GFP (green fluorescent protein) transgenic mice. After expansion in EGF+FGF2 (epidermal growth factor+fibroblast growth factor), cells were transplanted intravitreally or subretinally into the eyes of adult wild-type, transgenic mice undergoing slow (VPP strain) or rapid (rd1 strain) retinal degeneration. RESULTS Only limited migration and differentiation of the cells were observed in normal mice injected subretinally or in VPP and rd1 mice injected intravitreally. After subretinal injection in old VPP mice, transplanted cells massively migrated into the ganglion cell layer and, at 1 and 4 weeks after injection, harbored neuronal and glial markers expressed locally, such as beta-tubulin-III, NeuN, Brn3b, or glial fibrillary acidic protein (GFAP), with a marked preference for the glial phenotype. In adult VPP retinas, the grafted cells behaved similarly. Few grafted cells stayed in the degenerating outer nuclear layer (ONL). These cells were, in rare cases, positive for rhodopsin or recoverin, markers specific for photoreceptors and some bipolar cells. CONCLUSIONS These results show that the grafted cells preferentially integrate into the GCL and IPL and express ganglion cell or glial markers, thus exhibiting migratory and differentiation preferences when injected subretinally. It also appears that the retina, whether partially degenerated or already degenerated, does not provide signals to induce massive differentiation of RSCs into photoreceptors. This observation suggests that a predifferentiation of RSCs into photoreceptors before transplantation may be necessary to obtain graft integration in the ONL.
Some Delayed Complications of Inoculation

Table II gives our results with the various arterial reconstruction operations in all our patients over the last six years irrespective of the reason for the operation, and Table III lists the disease for which the artery was reconstructed. For patients with obliterative arterial disease it is only occasionally possible to resect the occluded segment and restore continuity by a direct end-to-end anastomosis, but when this can be done it is the best procedure. In my view the next most satisfactory operation is thromboendarterectomy. This is of particular value in localized occlusions of the aorta and iliac arteries, but it is sometimes of value in vessels as small as the popliteal. Two important
Identification of GABA β Receptor Protein and Farnesol in the Preputial Gland of Bandicoot Rat (Bandicota indica)

Preputial gland is one of the prime sources of pheromones in rats. The study on pheromone identification in preputial gland is well established in laboratory rat, house rat and voles. But the study was lacking in the preputial gland of bandicoot rats. Hence, the present investigation was aimed to identify the volatile and protein profiles of preputial gland of male bandicoot rat. Gas chromatography and mass spectrometry (GC-MS) profiles revealed the presence of 47 volatile compounds in the preputial gland. More specifically, the farnesol was found to be a major compound in the preputial gland which is consistent with previous reports in the preputial gland of few other rodents. The histoarchitecture results showed that the preputial gland of male exhibited more acini cells. The protein profiles of preputial gland showed 12 prominent bands in coomassie brilliant blue stained gel. The low molecular mass protein, 19 kDa has been identified as gamma-amino butyric acid type B receptor subunit I (GABAβ receptor) by MALDI-ToF analysis. Further, to the best our knowledge, this is the first time we explored the absence of alpha 2u globulin in the 19 kDa band of preputial gland of bandicoot rat. This is in contrast to the presence of alpha 2u globulin in the preputial gland of laboratory rat (Rattus norvegicus) as well as house rat (Rattus rattus). The present study concludes that among the volatiles and protein analysis performed in the preputial gland, farnesol appears to be a prominent compound and the GABAβ receptor protein was identified in 19 kDa band in bandicoot rats.
An explicit Euler scheme with strong rate of convergence for non-Lipschitz SDEs

We consider the approximation of stochastic dierential equations (SDEs) with non-Lipschitz drift or diusion coecients. We present a modified explicit EulerMaruyama discretisation scheme that allows us to prove strong convergence, with a rate. Under some regularity conditions, we obtain the optimal strong error rate. We consider SDEs popular in the mathematical finance literature, including the Cox-Ingersoll-Ross (CIR), the 3=2 and the Ait-Sahalia models, as well as a family of mean-reverting processes with locally smooth coecients.
Comparison between ultrasound-guided sciatic–femoral nerve block and unilateral spinal anaesthesia for outpatient knee arthroscopy

Objective To compare unilateral spinal anaesthesia (USA) and ultrasound-guided combined sciatic–femoral nerve block (USFB) in ambulatory arthroscopic knee surgeries in terms of haemodynamic stability, nerve block quality, bladder function, adverse events and time-to-readiness for discharge (TRD). Methods Patients undergoing ambulatory arthroscopic knee surgery were randomly assigned to one of two groups. The USA group received 2 ml (10 mg) of 0.5% levobupivacaine and the USFB group received a 25 ml mixture consisting of 10 ml of 2.0% lidocaine, 10 ml of 0.5% levobupivacaine and 5 ml of saline (15 ml for the femoral and 10 ml for the sciatic nerve block). Preparation time (PT), surgical anaesthesia time (SAT), operation time, total anaesthesia time, time-to-first spontaneous urination, time-to-first analgesia, TRD, adverse events and patient satisfaction were recorded. Results A total of 40 patients were enrolled in the study (n = 20 per group). PT, SAT, total anaesthesia time and time-to-first analgesia were significantly shorter in the USA group than the USFB group; time-to-first spontaneous urination and TRD were significantly longer in the USA group than the USFB group. Conclusions USFB provided sufficient duration of sensory blockade and it reduced the TRD and the rate of adverse events.
Partial loss of contractile marker proteins in human testicular peritubular cells in infertility patients

Fibrotic remodelling of the testicular tubular wall is common in human male infertility caused by impaired spermatogenesis. We hypothesized that this morphological change bears witness of an underlying fundamentally altered state of the cells building this wall, that is, peritubular smooth muscle‐like cells. This could include a loss of the contractile abilities of these cells and thus be a factor in male infertility. Immune cells are increased in the tubular wall in these cases, hence local immune cell‐related factors, including a prostaglandin (PG) metabolite may be involved. To explore these points in the human, we used testicular biopsies, in which tubules with normal spermatogenesis and impaired spermatogenesis are next to each other [mixed atrophy (MA)], normal biopsies and cultured human testicular peritubular cells. Proteins essential for contraction, myosin heavy chain (MYH11), calponin (Cal) and relaxation, cGMP‐dependent protein kinase 1 (cGKI), were readily detected by immunohistochemistry and were equally distributed in all peritubular cells of biopsies with normal spermatogenesis. In all biopsies, vascular smooth muscle cells also stained and served as important intrinsic controls, which showed that in MA samples when spermatogenesis was impaired, staining was restricted to only few peritubular cells or was absent. When spermatogenesis was normal, regular peritubular staining became obvious. This pattern suggests complex regulatory influences, which in face of the identical systemic hormonal situation in MA patients, are likely caused by the local testicular micromilieu. The PG metabolite 15dPGJ2 may represent such a factor and it reduced Cal protein levels in peritubular cells from patients with/without impaired spermatogenesis. The documented phenotypic switch of peritubular, smooth muscle‐like cells in MA patients may impair the abilities of the afflicted seminiferous tubules to contract and relax and must now be considered as a part of the complex events in male infertility.
Life history evolution and comparative developmental biology of echinoderms

SUMMARY Evolutionary biologists studying life history variation have used echinoderms in experimental, laboratory, and field studies of life history evolution. This focus on echinoderms grew originally from the tradition of comparative embryology, in which echinoderms were central. The tools for obtaining and manipulating echinoderm gametes and larvae were taken directly from comparative embryological research. In addition, the comparative embryologists employed a diverse array of echinoderms, not a few model species, and this diversity has led to a broad understanding of the development, function, and evolution of echinoderm larvae. As a result, this branch of life history evolution has deep roots in comparative developmental biology of echinoderms. Here two main aspects of this relationship are reviewed. The first is a broad range of studies of fertilization biology, dispersal, population genetics, functional morphology, and asexual reproduction in which developmental biologists might take a keen interest because of the historical origins of this research in echinoderm comparative embryology. The second is a similarly broad variety of topics in life history research in which evolutionary biologists require techniques or data from developmental biology in order to make progress on understanding patterns of life history variation among echinoderm species and higher taxa. Both sets of topics provide opportunities for interaction and collaboration.
A Comprehensive Framework for Classifying the Benefits of ERP Systems

This paper presents a framework for assessing the business benefits of Enterprise Resource Planning (ERP) systems. After analyzing the features of ERP systems, the literature on IT benefits, data from 233 ERP-vendor success stories published on the web, and interviews with 34 ERP cases, we have produced a consolidated framework of five benefit dimensions. This framework tries to classify the types of benefit that organizations can achieve by using ERP systems and provide a comprehensive foundation for planning, justifying, and managing the system. The framework focuses on benefits only, from the point of view of management as stakeholders; it does not consider costs.
Health-related quality of life in patients with different stages of liver disease induced by hepatitis C

Objective. Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis. Material and methods. Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire. Results. The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (p<0.001). In comparison with the CHC group, the HCV CC group had lower scores on the SF-36 general health dimension (p<0.05) and lower SF-36 physical component summary (PCS) scores (p<0.05). No major differences were seen in patients with HCV- and non-HCV-induced cirrhosis. Conclusions. Impairment in HRQoL in patients with HCV was associated with the severity of liver disease, patients with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The etiology of liver disease does not seem to be important in determining HRQoL in cirrhosis.
Multigene tracking of quasispecies in viral persistence and clearance of hepatitis C virus.

AIM To investigate the evaluation of hepatitis C virus (HCV) quasispecies in the envelope region and its relationship with the outcome of acute hepatitis C. METHODS HCV quasispecies were characterized in specimens collected every 2-6 mo from a cohort of acutely HCV-infected subjects. We evaluated two individuals who spontaneously cleared viremia and three individuals with persistent viremia by cloning 33 1-kb amplicons that spanned E1 and the 5' half of E2, including hypervariable region 1 (HVR1). To assess the quasispecies complexity and to detect variants for sequencing, 33 cloned cDNAs representing each specimen were assessed by a combined method of analysis of a single-stranded conformational polymorphism and heteroduplex analysis. The rates of both synonymous and nonsynonymous substitutions for the E1, HVR1 and E2 regions outside HVR1 were analyzed. RESULTS Serum samples collected from chronic phase of infection had higher quasispecies complexity than those collected from acute phase of infection in all individuals examined. The genetic diversity (genetic distance) within HVR1 was consistently higher than that in the complete E1 (0.0322+/-0.0068 vs -0.0020+/-0.0014, P<0.05) and E2 regions outside HVR1 (0.0322+/-0.0068 vs 0.0017+/-0.0011, P<0.05) in individuals with persistent viremia, but did not change markedly over time in those with clearance of viremia. For individuals with persistent viremia, the rate of nonsynonymous substitutions within the HVR1 region (2.76X10(-3)+/-1.51X10(-3)) predominated and gradually increased, as compared with that in the E1 and E2 regions outside HVR1 (0.23X10(-3)+/-0.15X10(-3), 0.50X10(-3)+/-0.10X10(-3)). By contrast, the rates of both nonsynonymous and synonymous substitutions for the E1 and E2 regions including HVR1 were consistently lower in individuals with clearance of viremia. CONCLUSION HCV persistence is associated with a complexity quasispecies and positive selection of HVR1 by the host immune system.
Vav deficiency impedes peripheral nerve regeneration in mice.

PURPOSE The regeneration of adult peripheral nerves is a complex, multi-step process that is often incomplete, resulting in pain and/or loss of muscle innervation. Success is based on a fine-tuned interplay of neurons, Schwann cells, fibrocytes and macrophages realizing Wallerian degeneration, fiber regrowth and revascularization. Following trauma, the nerves distal to the injury site undergo Wallerian degeneration, an event that includes the phagocytosis of debris and the formation of Schwann cell scaffolds that guide the sprouting nerve fibers. The actin cytoskeleton is critical to all of these processes; therefore, activators of the cytoskeleton such as Rho GTPases and RhoGEFS such as Vav2 and Vav3 represent attractive targets for therapeutic intervention. METHODS Sciatic nerve segments were surgically resected and reconstructed, and the degenerative/regenerative outcomes were compared in wild-type and Vav2/3 double knockout mice. RESULTS Vav2/3 knockout nerves showed delayed Wallerian degeneration and revascularization, a broadly control-like morphometry of the regenerated nerves including remyelination, and contradictory motor function recovery, whereby impaired toe spreading was accompanied by enhanced muscle weight recreation. CONCLUSIONS The data suggest that Vav2 and Vav3 are required for normal peripheral nerve degeneration/regeneration, revascularization and functional recovery. Functional redundancy, compensatory mechanisms, and muscle (pseudo)hypertrophy, however, impede the understanding of and intervention in Vav-mediated processes.
Chronic right ventricular pressure overload results in a hyperplastic rather than a hypertrophic myocardial response

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2–3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age‐matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right‐to‐left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly (P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.
An In Vitro Cynomolgus Vascular Surrogate System for Preclinical Drug Assessment and Human Translation

Objectives—The predictive value of animal and in vitro systems for drug development is limited, particularly for nonhuman primate studies as it is difficult to deduce the drug mechanism of action. We describe the development of an in vitro cynomolgus macaque vascular system that reflects the in vivo biology of healthy, atheroprone, or advanced inflammatory cardiovascular disease conditions. Approach and Results—We compare the responses of the in vitro human and cynomolgus vascular systems to 4 statins. Although statins exert beneficial pleiotropic effects on the human vasculature, the mechanism of action is difficult to investigate at the tissue level. Using RNA sequencing, we quantified the response to statins and report that most statins significantly increased the expression of genes that promote vascular health while suppressing inflammatory cytokine gene expression. Applying computational pathway analytics, we identified statin-regulated biological themes, independent of cholesterol lowering, that provide mechanisms for off-target effects, including thrombosis, cell cycle regulation, glycogen metabolism, and ethanol degradation. Conclusions—The cynomolgus vascular system described herein mimics the baseline and inflammatory regional biology of the human vasculature, including statin responsiveness, and provides mechanistic insight not achievable in vivo.