Miracle-dz/UniFAR-FTUs huggingface dataset:
No evidence of JC virus reactivation in natalizumab treated multiple sclerosis patients: an 18 month follow-up study

Background and aim Natalizumab, used as therapy for multiple sclerosis (MS), has been associated with progressive multifocal leucoencephalopathy (PML), a potentially fatal disease caused by JC virus (JCV), which is not predictable by specific markers. This study evaluated whether JCV reactivation occurred in the urine and/or plasma in 42 MS patients treated with natalizumab over 18 months, and followed by a thorough monitoring programme. Methods 42 patients (F/M: 24/18, mean age 34.4±8.9 years) were followed-up by: urine and plasma JCV-DNA PCR assay, immune cell subsets analysis, clinical and MRI evaluation, quality of life, fatigue and mood assessment. Results JCV data. At baseline, 11/42 (26%) patients had JCV viruria, persistent at serial controls. One patient acquired viruria at month 1 and one patient at month 12. No patient had JCV viraemia at baseline; three patients acquired viraemic (one at month 6, one at month 13 (both transiently) and one at month 12 (persistently viraemic)). The prevalence of JCV in both urine and plasma did not change significantly from baseline to months 12 and 18. No patient had clinical or MRI evidence of PML. Immunological data. Circulating B cells showed greater expansion (300% increase in absolute number) since the first infusion. NK cell count doubled with no change in percentage while T cell count increased with a reduced percentage, reflecting a clear redistribution in the lymphocyte compartment. CD4+ and CD8+ T cells increased proportionally, with no change in their percentage. Clinical data. 27 patients (64%) were disease free after 1 year. A marked improvement in quality of life was reported by 72% of patients. Conclusions No evidence of subclinical JCV reactivation was found in our natalizumab treated MS patients up to 18 months of therapy, notwithstanding the marked increase in circulating B cells observed. Moreover, the efficacy of natalizumab, its tolerability and the positive impact on quality of life were confirmed in this study.
Accounting and Cybersecurity Risk Management

As the number of cybersecurity incidents continue to rise and stakeholders are becoming increasingly concerned, companies are devoting considerable resources to their cybersecurity risk management efforts and related cybersecurity disclosures. This paper describes how accountants are uniquely positioned to assist companies with these efforts in advisory and assurance capacities. We present a model of effective cybersecurity risk management and discuss how accountants' core competencies can add significant value in each of the model's five stages. In addition, we use several recent high-profile cybersecurity incidents as illustrative examples in each of the five stages. We conclude by discussing implications for accountants.
Study of NO and VIP as non‐adrenergic non‐cholinergic neurotransmitters in the pig gastric fundus

1 The contribution of nitric oxide (NO) and vasoactive intestinal polypeptide (VIP) to non‐adrenergic non‐cholinergic (NANC) relaxations in the pig gastric fundus was investigated. 2 Circular and longitudinal muscle strips were mounted for isotonic registration in the presence of atropine and guanethidine; tone was raised with 5‐hydroxytryptamine. Electrical field stimulation with 10 s trains at 5 min intervals induced short‐lasting, frequency‐dependent relaxations while continuous stimulation with cumulative increase of the stimulation frequency induced sustained frequency‐dependent relaxations in both types of strips; the electrically induced responses were abolished by tetrodotoxin. 3 The short‐lasting as well as the sustained electrically induced NANC relaxations were significantly reduced by NG‐nitro‐L‐arginme methyl ester (l‐NAME). Pretreatment with L‐arginine but not D‐arginine, prevented the inhibitory effect of L‐NAME except for sustained relaxations in the longitudinal muscle strips. 4 Sodium nitroprusside, forskolin, zaprinast and 3‐isobutyl‐l‐methylxanthine induced concentration‐dependent relaxations. Exogenous NO mimicked the short‐lasting electrically induced relaxations, while endogenous VIP evoked sustained relaxations. The responses to exogenous NO and VIP were not influenced by tetrodotoxin and L‐NAME. 5 α‐Chymotrypsin abolished the responses to exogenous VIP but only moderately reduced NANC relaxations induced by continuous electrical stimulation. Zaprinast potentiated the relaxant responses to sodium nitroprusside and increased the duration of the NANC relaxations induced by electrical stimulation with 10 s trains in circular muscle strips but not in longitudinal muscle strips. 6 The cyclic GMP and cyclic AMP response to electrical stimulation, NO and VIP was measured in circular muscle strips. Short‐lasting as well as sustained electrical field stimulation induced an approximately 1.5 fold increase in cyclic GMP content, while NO induced nearly a 40 fold increase. An increase in cyclic AMP content was obtained only with sustained electrical field stimulation. 7 Immunocytochemistry for NO synthase (NOS) revealed immunoreactive neuronal cell bodies in the submucous and myenteric plexuses and nerve fibres in both the circular and longitudinal muscle layer; double‐labelling for NOS and VIP showed that VIP coexists in a major part of the intrinsic neurones. NADPH diaphorase‐histochemistry showed the same pattern of nitrergic neurones and nerves as NOS‐immunocytochemistry. 8 It is concluded that a cyclic GMP‐ and a cyclic AMP‐dependent pathway for relaxation is present in both the circular and longitudinal muscle layer of the pig gastric fundus. NO appears to contribute to short‐lasting as well as sustained NANC relaxations. A peptide, possibly VIP, may be involved during sustained stimulation at lower frequencies of stimulation.
Montenegro as High-Quality Sports Tourism Destination- Trends and Perspectives

The contemporary development of tourism is characterized by the development of specific forms of tourism, among which is sports tourism. Tourism and sport are two forms of interconnected activities in the sphere of tourist recreation and their relationship dates back to the very beginning of their development. Sport in modern tourism has not only a perceptive role, but it is also an important content of the stay in which tourists become active participants of various sports: water sports, tennis, golf, skiing, riding, sports games, etc. Having on mind the potential of Montenegro for tourism development, the fact that it represents one of the main pillars of economic progress of the country, as well as the trends and perspectives on global tourist market, it is necessary to identify key advantages and disadvantages of sports tourism in Montenegro in order to improve the quality of this segment of tourist offer.
Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood.

BACKGROUND The debate over a role for n-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) in depressed mood continues. OBJECTIVE The objective was to update a previous systematic review and meta-analysis of published randomized controlled trials investigating the effects of n-3 PUFAs on depressed mood and to explore potential sources of heterogeneity. DESIGN Eight databases were searched for trials that randomly assigned participants to receive n-3 PUFAs/fish, measured depressed mood, used human participants, and included a comparison group up to April 2009. RESULTS Thirty-five randomized controlled trials were identified; 17 were not included in the previous review. The pooled standardized difference in mean outcome of the 29 trials that provided data to allow pooling (fixed-effects model) was 0.10 SD (95% CI: 0.02, 0.17) in those who received n-3 PUFAs compared with placebo, with strong evidence of heterogeneity (I(2) = 65%, P < 0.01). The presence of funnel plot asymmetry suggested that publication bias was a likely source of this heterogeneity. Depressive symptom severity and participant diagnosis also explained some of the observed heterogeneity. Greater effects of n-3 PUFAs were found in individuals with more-severe depressive symptoms. In trials that enrolled individuals with a diagnosed depressive disorder, the combined mean difference was 0.41 (95% CI: 0.26, 0.55), although evidence of heterogeneity was also found (I(2) = 71%). In trials that enrolled individuals without a depressive diagnosis, no beneficial effects of n-3 PUFAs were found (largest combined mean difference: 0.22; 95% CI: -0.01, 0.44; I(2) = 0%). CONCLUSIONS Trial evidence of the effects of n-3 PUFAs on depressed mood has increased but remains difficult to summarize because of considerable heterogeneity. The evidence available provides some support of a benefit of n-3 PUFAs in individuals with diagnosed depressive illness but no evidence of any benefit in individuals without a diagnosis of depressive illness.
Miniaturized coupled-line directional coupler designed with the use of photoimageable Thick-Film technology

A quarterwave-long coupled-line single-section directional coupler has been developed using the combination of Phtoimageable Thick-Film technology and Laminate technology in an asymmetric dielectric structure. In order to obtain a significant miniaturization of the directional coupler, a high permittivity thin dielectric film between coupled lines has been used. Such an approach allows achieving compact size of the designed circuit, especially at the lower frequency ranges. The presented approach has been verified by the electromagnetic simulations and measurements of a 3-dB single-section coupled-line directional coupler operating at the center frequency f0 = 1 GHz.
The role of electron trap creation in enhanced hot-carrier degradation during AC stress (n-channel MOSFET)

Enhanced AC degradation during gate voltage transients is shown to be related to neutral electron traps created at low gate voltages under conditions of hole injection and filled at high gate voltages under conditions of electron injection. During DC stress, where interface state damage dominates, electron trap damage is not seen because the created traps are neutral. In experiments where inductive ringing is eliminated, AC degradation rates are independent of the type of edge (falling versus rising) and independent of the rise/fall time. <<ETX>>
Oncologic PET/MRI, Part 2: Bone Tumors, Soft-Tissue Tumors, Melanoma, and Lymphoma

With integrated whole-body PET/MRI, a novel metabolic–anatomic imaging technique recently has been introduced into clinical practice. This review addresses PET/MRI of bone tumors, soft-tissue sarcoma, melanoma, and lymphoma. If PET/MRI literature is not yet available for some types of tumors, potential indications are based on available PET/CT and MRI data. PET/MRI seems to be of benefit in T-staging of primary bone tumors and soft-tissue sarcomas. With regard to N-staging, PET/MRI can be considered similarly accurate to PET/CT when applied as a whole-body staging approach. M-staging will benefit from MRI accuracy in the brain, the liver, and bone.
Compositional Effect and Distance Sensitivity: Examining the Distance Elasticity in China and Indonesia Trade Activities

This paper analyzes the change in distance elasticity of trade using bilateral trade data among China and Indonesia and their main trading partners. The empirical method used in this study derived from the gravity model that considers the effect of distance on trade activities behavior. Two causes of change in the elasticity of trade to distance will be exposed, i.e., the distance sensitivity effect (within industries) and the compositional effect (among industries). Specifically, this study would like to prove whether the distance sensitivity effect is more dominant than the compositional effect in explaining the change in distance elasticity of trade. By using four sub-periods and around two hundred industries involved, the result shows that the increase in the role of distance in trade heavily caused by the escalation of distance sensitivity effect in most industries.
Skin biopsy in allogeneic and autologous bone marrow transplant patients: a histologic and immunohistochemical study and review of the literature.

Histologic criteria and grading system for diagnosis of cutaneous manifestations of graft vs. host disease (GvHD) have been established, and the diagnosis of high-grade GvHD is readily made by pathologists. There have been, however, increasing reports of skin rash occurring in patients treated with autologous bone marrow transplant (aBMT) that cannot be distinguished clinically or histologically from GvHD following allogeneic bone marrow transplant (alloBMT). We studied the histologic and immunohistochemical features of 25 skin biopsy specimens obtained from 22 patients with skin rashes who had undergone either aBMT or alloBMT, or who suffered from a malignancy. Tissue sections were immunoreacted with pan-T lymphocyte-associated antibody Leu 22 (CD43); pan-B antibody L26 (CD20); macrophage/myeloid antibody for CD68 antigens; and LN-3 antibody specific for HLA Class II antigens. The clinical suspicion of GvHD was confirmed in 8 of 10 alloBMT patients. Seven of the 10 aBMT patients also clinically diagnosed to have GvHD, had histologic changes consistent with Grades I, II, or III. The rest of the patients showed changes consistent with drug reaction. T-cell lymphocytes (Leu22), macrophages (CD68), and HLA-DR expression on Langerhans cells were in general more prominent in allogeneic chronic GvHD, but this was not statistically significant. No significant differences were seen in the degree of HLA-DR expression on endothelial cells and keratinocytes in any of the groups. The current histologic criteria are inadequate to differentiate cutaneous GvHD following alloBMT from the skin rash occurring in the setting of aBMT. (ABSTRACT TRUNCATED AT 250 WORDS)
Repolarization of the cardiac action potential. Does an increase in repolarization capacity constitute a new anti‐arrhythmic principle?

The cardiac action potential can be divided into five distinct phases designated phases 0–4. The exact shape of the action potential comes about primarily as an orchestrated function of ion channels. The present review will give an overview of ion channels involved in generating the cardiac action potential with special emphasis on potassium channels involved in phase 3 repolarization. In humans, these channels are primarily Kv11.1 (hERG1), Kv7.1 (KCNQ1) and Kir2.1 (KCNJ2) being the responsible α‐subunits for conducting IKr, IKs and IK1. An account will be given about molecular components, biophysical properties, regulation, interaction with other proteins and involvement in diseases. Both loss and gain of function of these currents are associated with different arrhythmogenic diseases. The second part of this review will therefore elucidate arrhythmias and subsequently focus on newly developed chemical entities having the ability to increase the activity of IKr, IKs and IK1. An evaluation will be given addressing the possibility that this novel class of compounds have the ability to constitute a new anti‐arrhythmic principle. Experimental evidence from in vitro, ex vivo and in vivo settings will be included. Furthermore, conceptual differences between the short QT syndrome and IKr activation will be accounted for.
A Mathematical Formulation for 3D Quasi-Static Multibody Models of Diarthrodial Joints

This study describes a genera] set of equations for quasi-static analysis of three-dimensional multibody systems, with a particular emphasis on modeling of diarthrodial joints. The model includes articular contact, muscle forces, tendons and tendon pulleys, ligaments, and the wrapping of soft tissue structures around bone and cartilage surfaces. The general set of equations governing this problem are derived using a consistent notation for all types of links, which can be converted conveniently into efficient computer codes. The computational efficiency of the model is enhanced by the use of analytical Jacobians, particularly in the analysis of articular surface contact and wrapping of soft tissue structures around bone and cartilage surfaces. The usefulness of the multibody model is demonstrated by modeling the patellofemoral joint of six cadaver knees, using cadaver-specific data for the articular surface and bone geometries, as well as tendon and ligament insertions and muscle lines of actions. Good accuracy was observed when comparing the model patellar kinematic predictions to experimental data (mean ± stand, dev. error in translation: 0.63 ± 1.19 mm, 0.10 ± 0.71 mm, -0.29 ± 0.84 mm along medial, proximal, and anterior directions, respectively; in rotation: -1.41 ± 1.71°, 0.27 ±2.38°, -1.13 ± 1.83° in flexion, tilt and rotation, respectively). The accuracy which can be achieved with this type of model, and the computational efficiency of the algorithm employed in this study may serve in many applications such as computer-aided surgical planning, and real-time computer-assisted surgery in the operating room.
Feed Restriction and Insulin Treatment Affect Subsequent Luteal Function in the Immediate Postovulatory Period in Pigs: Progesterone Production In Vitro and Messenger Ribonucleic Acid Expression for Key Steroidogenic Enzymes1

Abstract Progesterone production and release in vitro, and mRNA expression for key steroidogenic enzymes, were studied in luteal tissue recovered in the immediate postovulatory period from cyclic gilts allocated to one of three treatments: moderate feed restriction during the first (RH) or second week of the estrous cycle, with (HR+I) or without (HR) concomitant injections of long-acting insulin. Time of feed restriction affected neither progesterone production or release, nor mRNA expression for several key steroidogenic enzymes. However, luteal tissue from RH but not from HR gilts responded to LH stimulation by increasing progesterone production and release (P < 0.05). Insulin treatment increased progesterone production and release, restored luteal tissue responsiveness to LH, up-regulated steroidogenic enzyme mRNA expression, and down-regulated the tissue inhibitor of metalloproteinase-I mRNA expression in HR+I compared with HR gilts (P < 0.05). In vitro progesterone production and gene expression were affected by time of tissue collection after ovulation in RH and HR gilts but not in HR+I gilts, and were correlated with temporal changes in oviductal and peripheral plasma progesterone concentrations. Inherent differences in luteal function therefore appear to mediate latent effects of nutrition and insulin treatment on circulating progesterone concentrations in the critical postovulatory period in gilts.
Efficient movement detection for human actions using triaxial accelerometer

Real-time sampling with high speed using a triaxial accelerometer is the fundamental purpose of using consumer devices over all-gesture operation. A welldesigned fall-down detection system uses a triaxial accelerometer influenced on gravitation to calculate an included angle between surfaces and axis of accelerometer and the accelerometer is spread on fixed position and pose of body. A triaxial accelerometer is difficult to employ to detect fall-down without postural orientation under an undetermined body position. This work presents a novel fall detection system based on unrestricted position, called Fall-Down Detection based on Unrestricted Position (FDUP), to provide an unrestricted measure for solving the undetermined position problem. The FDUP system provides an algorithm for unrestricted fall detection, which includes thresholds for acceleration and angle variation. Five volunteers were invited to simulate fall-down over 400 times to collect statistics, and to build the fall-down acceleration threshold. Analytical results show the feasibility of implementing a fall-down detection mechanism based on undetermined position.
HBV core promoter mutations prevail in patients with hepatocellular carcinoma from Guangxi, China

The development of primary liver cancer frequently is associated with persistent HBV infection, and tumours may arise in individuals who are anti‐HBe positive. However, it is unlear whether viruses with an HBeAg‐negative phenotype are associated with tumour development or are selected, during seroconversion, after chromosomal integration of wild‐type viral DNA. In order to investigate the temporal evolution of the HBV genome in such individuals, the polymerase chain reaction was used to amplify HBV DNA from tumour tissue and serum of 14 patients from Guangxi, China with hepatocellular carcinoma. Comparison of nucleotide and amino acid sequences of the precore and proximal core region of HBV from the two sites in each patient produced evidence of divergence following integration in the tumour, but in most cases, HBeAg‐negativity could not be explained by precore mutations. Sequences from the core promoter region were therefore examined and mutations were found in the majority, which are believed to upregulate transcription of the core (and pregenomic) RNA but to downregulate precore mRNA. To determine whether this finding merely reflected sequence variation among geographical isolates of HBV, the same region of HBV DNA from asymptomatic controls was sequenced and these mutations were found to be rare. We hypothesise that HBV with the core promoter mutations replicates at higher levels than the wild type, with the consequence that more integrations occur into the hepatocyte chromosomes during the early stages of infection. These hepatocytes may expand clonally and be targets for further mutagenic events leading to tumour development. J. Med. Virol. 56:18–24, 1998. © 1998 Wiley‐Liss, Inc.
Exacerbated chronic obstructive pulmonary disease: a frequently unrecognized condition

Abstract. Incalzi RA, Fuso L, Serra M, Basso S, Carosella L, Tramaglino LM, Pistelli R, Carbonin P. (Department of Geriatrics and Department of Respiratory Physiology, Catholic University, Rome, Italy). Exacerbated chronic obstructive pulmonary disease: a frequently unrecognized condition. J Intern Med 2002; 252: 48–55.
Involvement of Oxidative Stress–Induced DNA Damage, Endoplasmic Reticulum Stress, and Autophagy Deficits in the Decline of β-Cell Mass in Japanese Type 2 Diabetic Patients

OBJECTIVE Deficits of β-cells characterize the islet pathology in type 2 diabetes. It is yet to be clear how the β-cell loss develops in type 2 diabetes. We explored the implication of oxidative stress, endoplasmic reticulum (ER)–induced stress, and autophagy deficit in the β-cell decline in Japanese type 2 diabetic patients. RESEARCH DESIGN AND METHODS Pancreases from recent autopsy cases of 47 type 2 diabetic and 30 nondiabetic subjects were investigated on the islet structure with morphometric analysis. Volume densities of islet (Vi), β-cell (Vβ), and α-cell (Vα) were measured. To evaluate cell damage of endocrine cells, immunohistochemical expressions of oxidative stress–related DNA damage as expressed by γH2AX, ER stress–related cell damage as CCAAT/enhancer 1 binding protein-β (C/EBP-β), and autophagy deficit as P62 were semiquantified, and their correlations to islet changes were sought. RESULTS Compared with nondiabetic subjects, Vβ was reduced in diabetic subjects. Contrariwise, there was an increase in Vα. There was a significant link between reduced Vβ and increased HbA1c levels (P < 0.01) and a trend of inverse correlation between Vβ and duration of diabetes (P = 0.06). Expressions of γH2AX, P62, and C/EBP-β were all enhanced in diabetic islets, and reduced Vβ correlated with the intensity of γH2AX expression but not with C/EBP-β or P62 expressions. Combined expressions of γH2AX, P62, and C/EBP-β were associated with severe reduction of Vβ. CONCLUSIONS β-Cell deficit in type 2 diabetes was associated with increased oxidative stress and may further be augmented by autophagic deficits and ER stress.