Miracle-dz/UniFAR-FTUs huggingface dataset:
Oral Anticoagulation and the Risk of Stroke or Death in Patients With Atrial Fibrillation and One Additional Stroke Risk Factor: The Loire Valley Atrial Fibrillation Project.

BACKGROUND It remains uncertain whether patients with atrial fibrillation (AF) and a single additional stroke risk factor (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or thromboembolism, vascular disease, age 65-74 years, and sex category [CHA2DS2-VASc] score = 1 in men, 2 in women) should be treated with oral anticoagulation (OAC). We investigated the risk of ischemic stroke, systemic embolism, and death in a community-based cohort of unselected patients with AF with zero to one stroke risk factor based on the CHA2DS2-VASc score. METHODS Among 8,962 patients with AF seen between 2000 and 2010, 2,177 (24%) had zero or one additional stroke risk factor, of which 53% were prescribed OAC. RESULTS Over a follow-up of 979 ± 1,158 days, 151 (7%) had a major adverse event (stroke/systemic thromboembolism/death). Prescription of OAC was not associated with a better prognosis for stroke/systemic thromboembolism/death for patients in the "low-risk" category (ie, CHA2DS2-VASc score = 0 for men or 1 for women; adjusted hazard ratio [HR], 0.68; 95% CI, 0.35-1.31; P = .25). OAC use was independently associated with a better prognosis in patients with AF with a single additional stroke risk factor (ie, CHA2DS2-VASc score = 1 in men, 2 in women; adjusted HR, 0.59; 95% CI, 0.40-0.86; P = .007). CONCLUSIONS Among patients with AF with a single additional stroke risk factor (CHA2DS2-VASc score = 1 in men, 2 in women), OAC use was associated with an improved prognosis for stroke/systemic thromboembolism/death.
Hyperhemolysis during the evolution of uncomplicated acute painful episodes in patients with sickle cell anemia

BACKGROUND: Some patients with sickle cell anemia (SS) experience significant decrease in their hemoglobin (Hb) level and significant increase in reticulocyte count during the progression of uncomplicated acute painful episodes. These changes have been attributed to, but not proven, hyperhemolysis. This study provides evidence of hyperhemolysis in this group of patients.
Corporate Governance and the Sensitivity of Investments to Cash Flows

We find very strong and consistent evidence that investments in Strongâ€ Governance firms (managers not entrenched) are strongly sensitive to availability of internal cash flows while such sensitivity is not different from zero for Weakâ€ Governance firms (entrenched management). We interpret this as evidence in support of Kaplan and Zingales' (1997) contention that sensitivity of investments to cash flows is not an adequate measure of financing constraints. More importantly, our findings are consistent with Kaplan and Zingalesâ€™ conjecture that the observed sensitivity of investments to cash flows in firms that do not face financing constraints may be driven by excessive risk aversion of managers.
Endurance training and obesity: effect on substrate metabolism and insulin sensitivity.

PURPOSE Obesity and type 2 diabetes mellitus are disease states associated with hallmark features such as insulin resistance and an impaired ability to oxidize lipids. It has recently been reported that an optimal exercise intensity for fat oxidation (FATmax) exists; we hypothesize that continuous exercise training at this specific intensity can lead to greater improvements in fat oxidation and insulin sensitivity than a eucaloric interval training program. METHODS In a counterbalanced, crossover design, eight sedentary, obese, but otherwise healthy male participants performed two 4-wk blocks of endurance training, either at a predetermined intensity eliciting maximal fat oxidation (TPCON) or at 5-min intervals of +/- 20% FATmax (TPINT). During the week preceding the exercise training and 48 h after the final exercise bout, an OGTT, V O2max test, steady-state exercise, and measurements of body composition were undertaken. Diet was controlled the day before all trials (50% carbohydrate, 35% fat, and 15% protein; approximately 2900 kcal.d). Variables were compared using two-way repeated-measures analyses of variance. RESULTS It was shown that fat oxidation rates were increased by 44% after TPCON (0.24 +/- 0.01 vs 0.35 +/- 0.03 g.min, P < 0.05) but not after TPINT, and the whole-body insulin sensitivity index was increased by 27% after TPCON (P < 0.05). These changes occurred despite no change in body weight, body mass index (BMI), waist to hip ratio (WHR), percent body fat (%BF), or V O2max. CONCLUSIONS A continuous exercise training protocol that can elicit high rates of fat oxidation increases the contribution of fat to substrate oxidation during exercise and can significantly increase insulin sensitivity compared with a eucaloric interval protocol.
Neurochemical coding of myenteric neurones in the human gastric fundus

Abstract The major functions of the stomach are under the control of the enteric nervous system (ENS), but the neuronal circuits involved in this control are largely unknown in humans. Enteric neurones can be characterized by their neuromediator or marker content, i.e. by neurochemical coding. The purpose of this study was to characterize the presence and co‐localization of neurotransmitters in myenteric neurones of the human gastric fundus. Choline acetyltransferase (ChAT), neurone‐specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), substance P (SP) were detected by immunohistochemical methods in whole mounts of gastric fundus myenteric plexus (seven patients). Antibodies against ChAT and NOS labelled the majority of myenteric neurones identified by NSE (57.2 ± 5.6% and 40.8 ± 4.5%, respectively; mean ± SD). The proportions of VIP‐ and SP‐immunoreactive neurones were significantly smaller, constituting 19.6 ± 6.9% and 16.0 ± 3.7%, respectively. Co‐localization studies revealed five major populations representing over 75% of the myenteric neurones: ChAT/‐, 30.1 ± 6.1%; NOS/‐, 24.2 ± 4.4%; ChAT/SP/‐, 8.3 ± 3.1%; NOS/VIP/‐, 7.2 ± 6.0%; ChAT/VIP/‐, 4.9 ± 2.6. Some similarities are apparent in the neurochemical coding of myenteric neurones in the stomach and intestine of humans, and between the stomach of humans and animals, but striking differences exist. The precise functional role of the neurochemically identified classes of neurones remains to be determined.
Paying the Price for Being Caught: The Economics of Manifest and Non-Manifest Theft in Roman Law

In Roman law, manifest theft (essentially, one in which a thief was caught in the act) was punished with a more severe penalty than non-manifest theft. This legal policy seems to contradict the economic theory of efficient deterrence. In this paper, we try to explore how economic analysis of criminal law and law enforcement points to several efficiency-based arguments to understand the puzzle, and allows us to tentatively conclude that technological changes in law enforcement in the broad sense might have been the major factor in the disappearance of the rule in modern legal systems.
Combined transcranial magnetic stimulation and ketamine for treatment of refractory mood disorder , anxiety , and pain : A case report

Treatment resistant depression (TRD) is a major public health problem, with approximately one third of patients failing to respond to multiple antidepressant medications [1]. In addition, TRD is associated with general medical costs estimated to be approximately 20 times greater than those stemming from depression that is responsive to treatment [2]. Depression occurring alongside a comorbid anxiety disorder and/or pain may contribute to treatment resistance [1-3]. To address these challenges, recent research has investigated the efficacy of transcranial magnetic stimulation (TMS) and its variant (r TMS) as a treatment for TRD and anxiety [4,5]. Most studies have used TMS to apply electromagnetic stimulation to the dorsolateral prefrontal cortex, a region implicated in both depression and anxiety [6-8]. Unfortunately, few studies have demonstrated full remission with TMS alone. A parallel body of research suggests a positive effect of ketamine, an N-methyl-D-aspartate (NMDA) antagonist, on both depression [9] and anxiety [10]. A primary benefit of ketamine is that it provides rapid albeit short-term relief from TRD symptoms relating to suicidality within approximately two hours. To date, little is known about the possible synergistic effects of combined TMS/ketamine for TRD alone, or comorbid with anxiety and/or pain.
Definitive identification of a gene that confers resistance against Toxoplasma cyst burden and encephalitis.

Control of resistance to cyst burden following per-oral infection with Toxoplasma gondii has been mapped previously to a region of mouse chromosome 17 of approximately 140 kb. This region is contiguous with and contains the class I gene, Ld. Resistance to development of toxoplasmic encephalitis has also been reported to be controlled by genes in this region of H-2. TNF-alpha, D and L genes, as well as unidentified genes, are also in this region. The work described here was performed to identify definitively the gene(s) in this 140 kb region that confers resistance to cysts and encephalitis. The study demonstrates that relative resistance to T. gondii organisms and cyst burden in brain, and toxoplasmic encephalitis, 30 days following per-oral T. gondii infection is correlated absolutely with the presence of the Ld gene in inbred, recombinant, mutant and C3H.Ld transgenic mice. Mice with the Ld gene had lower cyst burdens and less encephalitis than those without the Ld gene. Specifically, 30 days after infection mice with the Ld gene had minimal perivascular inflammation and meningeal inflammation and very few Toxoplasma cysts or organisms in immunoperoxidase-stained preparations of their brains. Mice without the Ld gene had a similar pattern of inflammation, but in addition they had collections of inflammatory cells in the brain parenchyma. Free tachyzoites were found within these foci of inflammation and cysts were present in these areas as well as in contiguous areas without inflammatory cells. There were CD4+ and CD8+ T lymphocytes in the areas of inflammation and throughout the brain parenchyma. Mice that were resistant to cysts and encephalitis had little detectable brain cytokine mRNA expression, while mice that were susceptible had elevated levels of mRNA for a wide range of cytokines, consistent with their greater amounts of inflammation. The present work definitively demonstrates that a Ld-restricted response decreases the number of organisms and cysts within the brain and thereby limits toxoplasmic encephalitis and levels of interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), IL-6, IL-10, transforming growth factor-beta (TGF-beta), IL-1 alpha, IL1 beta and macrophage inhibiting protein (MIP) mRNA in the brain 30 days after per-oral infection.
Impacts of Owner Race and Geographic Context on Access to Small-Business Financing

Multiple studies document both the scarcity of small-business financing in inner-city minority communities and the higher loan application rejection rates among minority business enterprises (MBEs), compared with equally creditworthy White-owned firms. When MBEs do receive bank financing, they get smaller loans than Whites. Two aspects of these findings are troublesome. First, urban MBEs are heavily concentrated geographically in minority communities, raising the issue of whether difficulties accessing financing reflect firm location, minority ownership, or both. Second, applicable studies rest on weak theoretical foundations. The authors’ findings suggest that banks engage in discriminatory practices limiting credit availability to MBEs. Controlling for risk factors, however, firm location in a minority or inner-city neighborhood has no apparent impact on loan availability or size. Owner race/ethnicity, in contrast, is important. Subtle processes discourage MBEs from seeking bank loans. Owner race and wealth both powerfully shape loan access: high wealth opens doors, minority ownership closes them.
Ocular HSV-1 Latency, Reactivation and Recurrent Disease

Ocular infection with HSV-1 continues to be a serious clinical problem despite the availability of effective antivirals. Primary infection with HSV-1 can involve ocular and adenaxial sites and can manifest as blepharitis, conjunctivitis, or corneal epithelial keratitis. After initial ocular infection, HSV-1 can establish latent infection in the trigeminal ganglia for the lifetime of the host. During latency, the viral genome is retained in the neuron without producing viral proteins. However, abundant transcription occurs at the region encoding the latency-associated transcript, which may play significant roles in the maintenance of latency as well as neuronal reactivation. Many host and viral factors are involved in HSV-1 reactivation from latency. HSV-1 DNA is shed into tears and saliva of most adults, but in most cases this does not result in lesions. Recurrent disease occurs as HSV-1 is carried by anterograde transport to the original site of infection, or any other site innervated by the latently infected ganglia, and can reinfect the ocular tissues. Recurrent corneal disease can lead to corneal scarring, thinning, stromal opacity and neovascularization and, eventually, blindness. In spite of intensive antiviral and anti-inflammatory therapy, a significant percentage of patients do not respond to chemotherapy for herpetic necrotizing stromal keratitis. Therefore, the development of therapies that would reduce asymptomatic viral shedding and lower the risks of recurrent disease and transmission of the virus is key to decreasing the morbidity of ocular herpetic disease. This review will highlight basic HSV-1 virology, and will compare the animal models of latency, reactivation, and recurrent ocular disease to the current clinical data.
Contactless biometric hand geometry recognition using a low-cost 3D camera

In the past decade, the interest in using 3D data for biometric person authentication has increased significantly, propelled by the availability of affordable 3D sensors. The adoption of 3D features has been especially successful in face recognition applications, leading to several commercial 3D face recognition products. In other biometric modalities such as hand recognition, several studies have shown the potential advantage of using 3D geometric information, however, no commercial-grade systems are currently available. In this paper, we present a contactless 3D hand recognition system based on the novel Intel RealSense camera, the first mass-produced embeddable 3D sensor. The small form factor and low cost make this sensor especially appealing for commercial biometric applications, however, they come at the price of lower resolution compared to more expensive 3D scanners used in previous research. We analyze the robustness of several existing 2D and 3D features that can be extracted from the images captured by the RealSense camera and study the use of metric learning for their fusion.
Decreased microRNA(miR)‐145 and increased miR‐224 expression in T cells from patients with systemic lupus erythematosus involved in lupus immunopathogenesis

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with abnormal T cell immune responses. We hypothesized that aberrant expression of microRNAs (miRNAs) in T cells may contribute to the pathogenesis of SLE. First, we analysed the expression profiles of 270 human miRNAs in T cells from five SLE patients and five healthy controls and then validated those potentially aberrant‐expressed miRNAs using real‐time polymerase chain reaction (PCR). Then, the expression of mRNAs regulated by these aberrant‐expressed miRNAs was detected using real‐time PCR. Finally, miRNA transfection into Jurkat T cells was conducted for confirming further the biological functions of these miRNAs. The initial analysis indicated that seven miRNAs, including miR‐145, miR‐224, miR‐513‐5p, miR‐150, miR‐516a‐5p, miR‐483‐5p and miR‐629, were found to be potentially abnormally expressed in SLE T cells. After validation, under‐expressed miR‐145 and over‐expressed miR‐224 were noted. We further found that STAT1 mRNA targeted by miR‐145 was over‐expressed and apoptosis inhibitory protein 5 (API5) mRNA targeted by miR‐224 was under‐expressed in SLE T cells. Transfection of Jurkat cells with miR‐145 suppressed STAT1 and miR‐224 transfection suppressed API5 protein expression. Over‐expression of miR‐224 facilitates activation‐induced cell death in Jurkat cells. In the clinical setting, the increased transcript levels of STAT1 were associated significantly with lupus nephritis. In conclusion, we first demonstrated that miR‐145 and miR‐224 were expressed aberrantly in SLE T cells that modulated the protein expression of their target genes, STAT1 and API5, respectively. These miRNA aberrations accelerated T cell activation‐induced cell death by suppressing API5 expression and associated with lupus nephritis by enhancing signal transducer and activator of transcription‐1 (STAT)‐1 expression in patients with SLE.
Thoracic Aortic Aneurysm (TAAD)-causing Mutation in Actin Affects Formin Regulation of Polymerization*

Background: The biochemical mechanisms underlying α-smooth muscle actin-mediated vascular disease are unknown. Results: The R256H mutation in actin alters polymerization kinetics and causes misregulation by the nucleation factor, formin. Conclusion: Mutation-based changes in conformation affect filament stability and regulation of polymerization. Significance: The Arg-256 residue stabilizes the actin helix and maintains filament conformation required for formin regulation. More than 30 mutations in ACTA2, which encodes α-smooth muscle actin, have been identified to cause autosomal dominant thoracic aortic aneurysm and dissection. The mutation R256H is of particular interest because it also causes patent ductus arteriosus and moyamoya disease. R256H is one of the more prevalent mutations and, based on its molecular location near the strand-strand interface in the actin filament, may affect F-actin stability. To understand the molecular ramifications of the R256H mutation, we generated Saccharomyces cerevisiae yeast cells expressing only R256H yeast actin as a model system. These cells displayed abnormal cytoskeletal morphology and increased sensitivity to latrunculin A. After cable disassembly induced by transient exposure to latrunculin A, mutant cells were delayed in reestablishing the actin cytoskeleton. In vitro, mutant actin exhibited a higher than normal critical concentration and a delayed nucleation. Consequently, we investigated regulation of mutant actin by formin, a potent facilitator of nucleation and a protein needed for normal vascular smooth muscle cell development. Mutant actin polymerization was inhibited by the FH1-FH2 fragment of the yeast formin, Bni1. This fragment strongly capped the filament rather than facilitating polymerization. Interestingly, phalloidin or the presence of wild type actin reversed the strong capping behavior of Bni1. Together, the data suggest that the R256H actin mutation alters filament conformation resulting in filament instability and misregulation by formin. These biochemical effects may contribute to abnormal histology identified in diseased arterial samples from affected patients.
Nitro-L-arginine methyl ester: A potential protector against gentamicin ototoxicity

Conclusion The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this. Objective Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. Material and methods In this experimental study we used 30 Sprague–Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. Results L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.
Occupational history and genetic N-acetyltransferase polymorphism in urothelial cancer patients of Leverkusen, Germany.

OBJECTIVES The study was designed to realize possible shifts in the ratio of slow to fast acetylators within a group of 196 urothelial cancer patients in an area with earlier benzidine production. METHODS The subjects were interviewed for occupational and nonoccupational risk factors. The patients were phenotyped for N-acetyltransferase 2 (NAT2) by Grant's caffeine test. A subgroup of 54 patients was additionally genotyped for NAT2. RESULTS The antimode in the NAT2 phenotyping with the caffeine test (AFMU: IX ratio) was 1.0, as evidenced by additional genotyping of the subgroup of 54 patients. The prevalence of slow acetylators in the entire group of bladder cancer patients was 55%, in accordance with published figures for European populations. In a subgroup of 40 patients with occupational histories as workers in chemical or rubber industries 65% were slow acetylators. In a further subgroup of 28 cases having specifically worked at chemical production sites of the local chemical industry, 68% were slow acetylators. CONCLUSIONS In contrast to earlier studies, this study shows no increased prevalence of slow acetylators among urothelial cancer patients in comparison with the normal population. However, in subgroups of cases with a likelihood of past occupational contacts with aromatic amines, there was a trend towards a higher representation of slow acetylators. This finding is in accordance with observations of others that the percentage of slow acetylators in urothelial cancer patients is generally decreasing, possibly because the production of benzidine and benzidine-based dyes ceased in the early 1970s.
The in vivo pharmacology of CP-80, 633, a selective inhibitor of phosphodiesterase 4.

The following studies were conducted to characterize the bron-chodilatory and antiinflammatory activity of the novel, selective phosphodiesterase-IV inhibitor, CP-80,633 (2'S)5-[3-(2'-exobicyclo[2.2.1]heptyloxy-4-methoxy-phenyl]te trahydro- 2(1H)-pyrimidone, a compound in clinical development for atopic disease. In IgG1 passively sensitized guinea pigs, aerosolized ovalbumin challenge increases both pulmonary eosinophil peroxidase levels and airway obstruction. CP-80,633, administered before ovalbumin challenge, significantly attenuated both the increase in tissue eosinophil peroxidase levels (ED50 = 1.4 mg/kg, p.o.) and airway obstruction (ED50 = 0.93 +/- 0.14 mg/kg,p.o.) 10 to 30 times more potently than theophyl-line. Intraarterially administered CP-80,633 also reversed an established bronchoconstriction initiated by continuous infusion of histamine to guinea pigs (ED50 of 8.2 micrograms/kg vs. 5.6 mg/kg for theophylline). The antiinflammatory effect of CP-80,633 was also examined in atopic monkeys challenged with Ascaris suum (Ag) aerosol. CP-80,633 (1 mg/kg, qid, s.c., 1 hr before antigen challenge) significantly reduced antigen-induced increases in bronchoalveolar lavage neutrophils (72.8 +/- 15.8% inhibition) and eosinophils (61.1 +/- 5.7% inhibition) 4 hr postchallenge, but did not reduce leukocytes 24 hr postchallenge. CP-80,633 did not inhibit antigen-induced increases in BAL levels of interleukin-1 beta, -6 or -8 as measured by enzyme-linked immunosorbant assay. These results indicate that CP-80,633 possesses bronchodilatory activity in guinea pigs and some antiinflammatory effects in both guinea pigs and monkeys.