Miracle-dz/UniFAR-FTUs huggingface dataset:
Optic Disc Hemorrhages and Generalized Vascular Disease

PurposeTo study the relationship between optic disc hemorrhages and four different groups of medications used in general vascular disease and diabetes. MethodsThe authors screened citizens of the city of Malmö, Sweden who were between 57 and 79 years old (32,918 subjects), in order to find individuals with undetected glaucoma. One set of optic disc photographs was taken of each participant and examined for optic disc hemorrhages. Logistic regression was used, with platelet aggregation inhibitors, antihypertensive agents, cholesterol-lowering medication, and antidiabetic agents as independent variables that were tested in isolation as well as in various combinations and adjusted for age and gender. ResultsOptic disc hemorrhages were significantly more common in individuals taking platelet aggregation inhibitors (OR 3.16, P < 0.0001). There was no significant association between ODH and the other three groups of medications. ConclusionsThe significant relationship between platelet aggregation inhibitors and optic disc hemorrhages is a new and interesting finding that could indicate an association between optic disc hemorrhages and generalized vascular disease. Alternatively, it could mean that platelet aggregation inhibitors prolong resorption of or predispose to optic disc hemorrhages.
Visual imagery and perception in posttraumatic stress disorder. A positron emission tomographic investigation.

BACKGROUND Relative regional cerebral blood flow (rCBF) changes were measured in Vietnam combat veterans with and without posttraumatic stress disorder (PTSD) during exposure to combat-related stimuli. METHODS Positron emission tomography was used to measure rCBF in 7 combat veterans with PTSD (PTSD group) and 7 healthy combat veterans (control group) who viewed and generated visual mental images of neutral, negative, and combat-related pictures. RESULTS Unlike control subjects, subjects with PTSD had increased rCBF in ventral anterior cingulate gyrus and right amygdala when generating mental images of combat-related pictures; when viewing combat pictures, subjects with PTSD showed decreased rCBF in Broca's area. CONCLUSIONS Results suggest that ventral anterior cingulate gyrus and right amygdala play a role in the response of combat veterans with PTSD to mental images of combat-related scenes. Reexperiencing phenomena of PTSD, which often involve emotional visual mental imagery, may be likewise associated with increased rCBF in these regions.
On the strain feedback control of a flexible robot arm

We consider a flexible robot arm modeled as a rigid hub which rotates in an inertial space; a light flexible link is clamped to the rigid body at one end and is free at the other. We assume that the flexible link performs only planar motion. We assume that the strain of the flexible link at the clamped end is measurable. We show that suitable control torques applied to the rigid hub stabilizes the system and achieves orientation under certain conditions. The proposed torque contains derivative, proportional and integral terms of the strain. The stability proofs depend on the passivity of the controller transfer function.
A combination method for the spectral domain system matrix computation of larger microwave structures with thin layer environments

In the last years, the performance of integral equation solvers based on the Greenpsilas function of planar multilayered media could be further increased especially by reducing the numerical complexity of the standard method of moments (MoM) with the help of fast integral equation techniques employing an efficient matrix-vector product evaluation within the iterative solution process. These methods are based e.g. on conjugate gradient solvers attached to fast Fourier transformations (CG-FFT) combined with the complex image method or combinations of the latter method with the adaptive integral equation method (AIM) [Ling et al., 1996]. Other approaches make use of the fast multipole method (FMM) combined with the complex image method or a perfectly matched layer technique [Ginste et al., 2006]. In contrast to this, we have introduced in [Vaupel et al., 2006] a new kind of a fast integral equation solver directly based on the analytically available spectral domain Greenpsilas function of the multilayered environment. Using all these methods, only a small part of the fully populated system matrix must be computed explicitly whereas the remaining matrix related to far interactions is only implicitly involved in the matrix-vector product evaluation.
The PTPN22‐1858C>T (R620W) functional polymorphism is associated with generalized vitiligo in the Romanian population

Generalized vitiligo is an autoimmune disorder of the skin in which autoimmune‐mediated destruction of melanocytes leads to depigmented patches of skin and overlying hair. The 1858C>T (R620W) functional polymorphism of the PTPN22 gene, which encodes lymphoid protein tyrosine phosphatase (Lyp), has been associated with susceptibility to a number of autoimmune disorders, including generalized vitiligo. The aim of this study was to test genetic association of the PTPN22 1858C>T variant and generalized vitiligo in a Romanian case‐control cohort. We observed significant association of generalized vitiligo with the 1858T risk allele of PTPN22 [P = 0.0138; OR = 2.92 (1.21–7.03)], with significantly different distribution of PTPN22 1858C>T genotypes in cases versus controls [P = 0.036; OR = 2.69 (1.07–6.80)]. Our results provide evidence that the PTPN22 1858T allele contributes to risk of generalized vitiligo in European Caucasian populations, and underscores the importance of a genetically mediated autoimmune mechanism in the pathogenesis of vitiligo.
Human-murine chimeras of ICAM-1 identify amino acid residues critical for rhinovirus and antibody binding

Human ICAM-1 is the cellular receptor for the major group of human rhinoviruses (HRVs). Previous studies have suggested that the N-terminal domain of ICAM-1 is critical for binding of the major group rhinoviruses. To further define the residues within domain 1 that are involved in virus binding, we constructed an extensive series of ICAM-1 cDNAs containing single and multiple amino acid residue substitutions. In each case, substitutions involved replacement of the human amino acids with those found in murine ICAM-1 to minimize conformational effects. To facilitate the mutagenesis process, a synthetic gene encompassing the first two domains of ICAM-1 was constructed which incorporated 27 additional restriction sites to allow mutagenesis by oligonucleotide replacement. Each of the new constructs was placed into a Rous sarcoma virus vector and expressed in primary chicken embryo fibroblast cells. Binding assays were performed with six major group HRVs, including one high-affinity binding mutant of HRV-14, and two monoclonal antibodies. Results indicated that different serotypes displayed a range of sensitivities to various amino acid substitutions. Amino acid residues of ICAM-1 showing the greatest effect on virus and antibody binding included Pro-28, Lys-29, Leu-30, Leu-37, Lys-40, Ser-67, and Pro-70.
Dofequidar fumarate sensitizes cancer stem‐like side population cells to chemotherapeutic drugs by inhibiting ABCG2/BCRP‐mediated drug export

The ATP‐binding cassette (ABC) transporters (ABC‐T) actively efflux structurally and mechanistically unrelated anticancer drugs from cells. As a consequence, they can confer multidrug resistance (MDR) to cancer cells. ABC‐T are also reported to be phenotypic markers and functional regulators of cancer stem/initiating cells (CSC) and believed to be associated with tumor initiation, progression, and relapse. Dofequidar fumarate, an orally active quinoline compound, has been reported to overcome MDR by inhibiting ABCB1/P‐gp, ABCC1/MDR‐associated protein 1, or both. Phase III clinical trials suggested that dofequidar had efficacy in patients who had not received prior therapy. Here we show that dofequidar inhibits the efflux of chemotherapeutic drugs and increases the sensitivity to anticancer drugs in CSC‐like side population (SP) cells isolated from various cancer cell lines. Dofequidar treatment greatly reduced the cell number in the SP fraction. Estimation of ABC‐T expression revealed that ABCG2/breast cancer resistance protein (BCRP) mRNA level, but not the ABCB1/P‐gp or ABCC1/MDR‐associated protein 1 mRNA level, in all the tested SP cells was higher than that in non‐SP cells. The in vitro vesicle transporter assay clarified that dofequidar had the ability to suppress ABCG2/BCRP function. Dofequidar treatment sensitized SP cells to anticancer agents in vitro. We compared the antitumor efficacy of irinotecan (CPT‐11) alone with that of CPT‐11 plus dofequidar in xenografted SP cells. Although xenografted SP tumors showed resistance to CPT‐11, treatment with CPT‐11 plus dofequidar greatly reduced the SP‐derived tumor growth in vivo. Our results suggest the possibility of selective eradication of CSC by inhibiting ABCG2/BCRP. (Cancer Sci 2009)
Two cases of the cutaneous form of sheep-associated malignant catarrhal fever in cattle

Microbiological examinations, including attempts to isolate pathogenic bacteria and to demonstrate the presence of bovine viral diarrhoea and infectious bovine rhinotracheitis viruses, yielded negative results (Elad and others 2002, Levisohn and others 2004). The heminested PCR for OvHV-2 confirmed that the animal had died of SA-MCF disease. Some of the macroscopic and microscopic lesions found at postmortem examination were consistent with the lesions of MCF (Rossiter 1985, OIE 2000). However, a variety of non-specific and inconsistent gross lesions were seen in the heifer: the dermis presented hyperkeratosis and diffuse alopecia of the entire body, and several small ulcers were noted on the ventral part of the tongue and in the nasal mucosa. Histopathological examination revealed a multifocal perivascular encephalitis with severe mononuclear infiltrates in the brain. Diffuse hyperkeratotic processes and a neutrophilic and histiocytic infiltrate that accompanied the cutaneous ulcers were observed. None of the specimens from the parenchyma of other internal organs presented any microscopic lesions, but OvHV-2 DNA was detected in lymph node, liver and brain tissues. In a second case, a 16-month-old heifer was diagnosed as a carrier of SA-MCF by application of the heminested PCR for
Correlation of monoclonal and polyclonal somatostatin receptor 5 antibodies in pancreatic neuroendocrine tumors.

AIMS To evaluate the frequency of somatostatin-receptor 5 (SSTR 5) in pancreatic neuroendocrine tumors by using monoclonal and polyclonal antibodies. MATERIAL AND METHOD we analyzed 66 proven pancreatic neuroendocrine tumors immunohistochemically with monoclonal (clone UMB-4) and polyclonal SSTR 5-antibodies. Immunoreactive score (IRS) and DAKO-score Her2/neu were evaluated. RESULTS Immunohistochemistry analysis demonstrated for the IRS a significant higher staining of all specimen using the monoclonal antibodies ( IRS SSTR5 poly vs IRS SSTR 5 mono; 20.0% vs 30.3% p < 0.001) by a correlation of 0.21; p = 0.04. For the HER2 score there was also a significant higher staining in the monoclonal group (Her2 SSTR 5 poly vs Her2 SSTR 5 mono; 21.5% vs 28.8% p < 0.001) by a correlation of 0.20; p = 0.08. CONCLUSION Both antibodies are useful in staining of SSTR, although UMB-4 demonstrated a 10% higher SSTR 5 staining. Due to the previous underestimated expression rate of SSTR 5, current standards in diagnostics and therapy should be reconsidered. The increasing usage of long-acting pansomatostatin receptor analogues will rise the adverse effects connected to SSTR5 binding.
Efficacy of Conversion Surgery Following S-1 plus Cisplatin or Oxaliplatin Chemotherapy for Unresectable Gastric Cancer.

BACKGROUND/AIM To evaluate the efficacy of conversion surgery following S-1 plus cisplatin (CS) or oxaliplatin (SOX) chemotherapy. PATIENTS AND METHODS We retrospectively analyzed clinicopathological and survival data of 74 patients with unresectable gastric cancer receiving CS or SOX. RESULTS Fifty-five and nineteen patients received CS and SOX, respectively. Conversion surgery (odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.64; p=0.01) was the only significant independent predictor of longer survival in multivariate Cox regression analysis. Patients (median age, 74 years) receiving SOX were significantly older than those receiving CS (median age=67 years) (p<0.01), although the rates of response, severe toxicity or conversion surgery did not differ significantly between the two treatment groups. CONCLUSION Conversion surgery after a response to CS or SOX chemotherapy may have survival benefit in selected unresectable gastric cancer patients, for both non-elderly and elderly patients responding to SOX.
Herbal Medicine for Low Back Pain: A Cochrane Review

Study Design. Systematic review of randomized controlled trials (RCTs). Objectives. To determine the effectiveness of herbal medicine for nonspecific low back pain (LBP). Summary of Background Data. Many people with chronic LBP use complementary and alternative medicine (CAM), visit CAM practitioners, or both. Several herbal medicines have been purported for use in treating people with LBP. This is an update of a Cochrane Review first published in 2006. Methods. We searched numerous electronic databases up to September 2014; checked reference lists in review articles, guidelines and retrieved trials; and personally contacted individuals with expertise in this area. We included RCTs examining adults (over 18 years of age) suffering from acute, sub-acute, or chronic nonspecific LBP. The interventions were herbal medicines that we defined as plants used for medicinal purposes in any form. Primary outcome measures were pain and function. Two review authors assessed risk of bias, GRADE criteria (GRADE 2004), and CONSORT compliance and a random subset were compared with assessments by a third individual. Two review authors assessed clinical relevance and resolved any disagreements by consensus. Results. Fourteen RCTs (2050 participants) were included. Capsicum frutescens (cayenne) reduces pain more than placebo. Although Harpagophytum procumbens (devil's claw), Salix alba (white willow bark), Symphytum officinale L. (comfrey), Solidago chilensis (Brazilian arnica), and lavender essential oil also seem to reduce pain more than placebo, evidence for these substances was of moderate quality at best. No significant adverse events were noted within the included trials. Conclusions. Additional well-designed large trials are needed to test these herbal medicines against standard treatments. In general, the completeness of reporting in these trials was poor. Trialists should refer to the CONSORT statement extension for reporting trials of herbal medicine interventions. Level of Evidence: N/A
Macular Involvement and Response to Steroid Therapy Demonstrated by Optical Coherence Tomography in Non-arteritic Anterior Ischaemic Optic Neuropathy

Abstract Two consecutive patients with anterior non-arteritic ischaemic optic neuropathy were evaluated with spectral-domain optical coherence tomography. The optical coherence tomographic scans revealed subfoveal fluid and intraretinal fluid extending from the optic disc margin toward the fovea that made us think that the submacular fluid appeared to arise from the peripapillary region. Fluorescein angiography showed no accumulation in the macular area, whereas leakage and staining of the optic nerve was present. After systemic corticosteroid therapy, the submacular fluid decreased promptly and the visual acuity improved. Subretinal-fluid-associated disc oedema may develop in some patients with NAION and contribute to the visual loss associated with this condition. Optical coherence tomography should be performed to follow macular involvement in patients with neuro-ophthalmic disease as well as to monitor patients’ response to treatment.
Mutation screening by denaturing gradient gel electrophoresis in North American patients with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is a dominantly inherited disorder of heme metabolism caused by a 50% decrease in the activity of porphobilinogen deaminase (EC 4.3.1.8.). The estimated prevalence of the disease is 1:1000 to 1.5:100 000, making it the most common of the neurologic porphyrias (1). Although its penetrance is only 10–20% (2), acute attacks of AIP are disabling and can be life-threatening. Prevention of acute attacks is the most important principle in managing the disease; however, it requires prior identification of individuals at risk. Because AIP has a genetic basis, molecular analysis for this disease is ultimately the most reliable way to identify gene carriers. More than 130 mutations in the porphobilinogen deaminase gene have been characterized to date (3). The majority have been restricted to a single family, or at most a few families, and no mutation accounts for more than a small percentage of all cases. With the exception of selected geographic areas where single mutations predominate (4)(5), testing for known mutations in a patient who has not previously been investigated is likely to be negative. Molecular analysis therefore requires an efficient strategy for finding the causative mutation. Denaturing gradient gel electrophoresis (DGGE) has been used by several groups to screen the exons and flanking intronic segments of the porphobilinogen deaminase gene for variations in the wild-type sequence (6)(7)(8)(9)(10)(11)(12)(13). This work has been carried out in European laboratories, and the mutations that have been discovered reflect the molecular defects within that population. By contrast, relatively few mutations have been described …
Cajal body‐specific small nuclear RNAs: a novel class of 2′‐O‐methylation and pseudouridylation guide RNAs

Cajal (coiled) bodies are conserved subnuclear organelles that are present in the nucleoplasm of both animal and plant cells. Although Cajal bodies were first described nearly 100 years ago, their function has remained largely speculative. Here, we describe a novel class of human small nuclear RNAs that localize specifically to Cajal bodies. The small Cajal body‐ specific RNAs (scaRNAs) are predicted or have already been demonstrated to function as guide RNAs in site‐specific synthesis of 2′‐O‐ribose‐methylated nucleotides and pseudouridines in the RNA polymerase II‐transcribed U1, U2, U4 and U5 spliceosomal small nuclear RNAs (snRNAs). Our results provide strong support for the idea that the Cajal body, this mysterious nuclear organelle, provides the cellular locale for post‐transcriptional modification of spliceosomal snRNAs.
Free fatty acids are independently associated with all-cause and cardiovascular mortality in subjects with coronary artery disease.

CONTEXT Free fatty acids (FFAs) are associated with several cardiovascular risk factors and exert harmful effects on the myocardium. OBJECTIVE The aim of our study was to elucidate the relationship between FFAs and mortality in subjects who underwent coronary angiography. DESIGN, SETTING, AND PARTICIPANTS Ludwigshafen Risk and Cardiovascular Health is a prospective cohort study of Caucasians who had undergone coronary angiography at baseline (1997-2000). During a median time of follow-up of 5.38 yr, 513 deaths had occurred among 3315 study participants with measured FFAs. MAIN OUTCOME MEASURE Hazard ratios for mortality according to FFA levels were measured. RESULTS At the fourth quartile of FFAs, fully adjusted hazard ratios for death from any cause and cardiovascular causes were 1.58 (P = 0.002) and 1.83 (P = 0.001), respectively. In persons with angiographic coronary artery disease (CAD), stable CAD, and unstable CAD, the predictive value of FFAs was similar to that in the entire cohort, but the association did not attain statistical significance in persons without CAD analyzed separately. FFA levels were not related to the presence of angiographic CAD but were elevated in subjects with unstable CAD, compared with probands with stable CAD. Furthermore, FFAs increased with the severity of heart failure and were positively correlated with N-terminal pro-B-type natriuretic peptide (P < 0.001). CONCLUSIONS FFA levels independently predict all-cause and cardiovascular mortality in subjects with angiographic CAD. A possible diagnostic use of FFAs warrants further studies, but our results may underline the importance of therapeutic approaches to influence FFA metabolism.
Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans

In animals, microRNAs frequently form families with related sequences. The functional relevance of miRNA families and the relative contribution of family members to target repression have remained, however, largely unexplored. Here, we used the Caenorhabditis elegans miR-58 miRNA family, composed primarily of the four highly abundant members miR-58.1, miR-80, miR-81, and miR-82, as a model to investigate the redundancy of miRNA family members and their impact on target expression in an in vivo setting. We found that miR-58 family members repress largely overlapping sets of targets in a predominantly additive fashion. Progressive deletions of miR-58 family members lead to cumulative up-regulation of target protein and RNA levels. Phenotypic defects could only be observed in the family quadruple mutant, which also showed the strongest change in target protein levels. Interestingly, although the seed sequences of miR-80 and miR-58.1 differ in a single nucleotide, predicted canonical miR-80 targets were efficiently up-regulated in the mir-58.1 single mutant, indicating functional redundancy of distinct members of this miRNA family. At the aggregate level, target binding leads mainly to mRNA degradation, although we also observed some degree of translational inhibition, particularly in the single miR-58 family mutants. These results provide a framework for understanding how miRNA family members interact to regulate target mRNAs.
Quality Learning Experiences, Self-Determination, and Academic Success

Although fostering self-determination has emerged as a central element of recommended and evidence-based transition practices for adolescents with disabilities, few studies have examined the paths through which students develop the skills and dispositions that can enhance their self-determination and successful transitions. The authors used path analyses to examine the ways in which exposure to quality secondary learning environments contributed to the development of self-efficacy, motivation, and academic achievement among 135 high school students receiving special education services. Students with disabilities who reported having greater involvement in learning environments reflecting recommended transition practices (i.e., high-quality learning environments) demonstrated increased career-search self-efficacy. Students with greater career-search self-efficacy were more highly engaged in goal setting, which further predicted their motivation to attend school and academic self-efficacy. Finally, students with higher academic self-efficacy were found to have higher grades. The authors offer recommendations for enhancing the self-determination skills and opportunities of youth with disabilities by strengthening the quality and impact of transition education.