Miracle-dz/UniFAR-FTUs huggingface dataset:
Update of the Korean Clinical Practice Guidelines for Endovascular Recanalization Therapy in Patients with Acute Ischemic Stroke

Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or dead without timely reperfusion. Previously, intravenous tissue plasminogen activator (IV-TPA) within 4.5 hours after stroke onset was the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy, which enables more fast and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of endovascular recanalization therapy (ERT) when added to IV-TPA. Accordingly, to update the recommendations, we assembled members of the writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. Reviewing the evidences that have been accumulated, the writing members revised recommendations, for which formal consensus was achieved by convening a panel composed of 34 experts from the participating academic societies. The current guideline provides the evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization.
Detection of Antibodies against Paracoccidioides brasiliensis Melanin in In Vitro and In Vivo Studies during Infection

ABSTRACT Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal antibodies (MAbs). We identified five immunoglobulin G1 (IgG1) κ-chain and four IgM melanin-binding MAbs. The five IgG1 κ-chain isotypes are the first melanin-binding IgG MAbs ever reported. The nine MAbs labeled P. brasiliensis conidia and yeast cells both in vitro and in pulmonary tissues. The MAbs cross-reacted with melanin-like purified particles from other fungi and also with commercial melanins, such as synthetic and Sepia officinalis melanin. Melanization during paracoccidioidomycosis (PCM) was also further supported by the detection of IgG antibodies reactive to melanin from P. brasiliensis conidia and yeast in sera and bronchoalveolar lavage fluids from P. brasiliensis-infected mice, as well as in sera from human patients with PCM. Serum specimens from patients with other mycoses were also tested for melanin-binding antibodies by enzyme-linked immunosorbent assay, and cross-reactivities were detected for melanin particles from different fungal sources. These results suggest that melanin from P. brasiliensis is an immunologically active fungal structure that activates a strong IgG humoral response in humans and mice.
Evidence for Central Nervous System Glial Cell Plasticity in Phenylketonuria

Phenylketonuria (PKU) is caused by mutation(s) in the phenylalanine hydroxylase (PAH) gene which lead to deficient PAH activity and an accumulation of phenylalanine in the blood. The primary pathologic finding is hypomyelination and gliosis of central nervous system white matter. Similar white matter pathology is observed in the Pahcnu2 mouse, a genetic model for PKU. We studied this mouse to examine the basis for these neuropathologic changes in PKU and to determine if hypomyelination and gliosis occur independently or are interrelated. Although white matter tracts within PKU brains are hypomyelinated, immunostaining and Western blot analyses revealed that these tracts contain abundant amounts of myelin markers, i.e. myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'phosphohydrolase, and myelin/oligodendrocyte-specific protein (MOSP). However, Western blot analyses also showed that MBP isoform expression was aberrant. Investigation of individual cells was performed by extraction of tissue sections with Triton X-100. Most of the MOSP was extracted, with the remaining MOSP clearly visible in dual labeled cells, i.e. MOSP was colocalized along glial fibrillary acidic protein (GFAP) filaments. Cells expressing both MBP and GFAP were also identified in optic tract. Double labeling with a riboprobe for MBP and antibodies specific for GFAP revealed that the majority of GFAP-positive cells expressed MBP mRNA. Our in vitro studies examined the response of cultured wild type oligodendrocytes to elevated phenylalanine for 4 weeks (wk). Under these conditions, about 50% of the oligodendrocytes expressed GFAP filaments and failed to elaborate membrane sheets. Proliferation of astrocytes appears not to be the source of gliosis, since the nuclei of GFAP-positive cells in the PKU brains did not immunostain for proliferating cell nuclear antigen. Dual-labeled cells were detected in normal mouse brain sections; however, PKU mouse white matter tracts were found to contain about twice the number of dual-labeled cells compared to normal tissue. Taken together, these data suggest that both myelinating and nonmyelinating oligodendrocytes are present in the normal adult brain, and that in response to a toxic factor such as elevated phenylalanine, myelinating oligodendrocytes adopt a nonmyelinating phenotype that expresses GFAP. Since myelinating Schwann cells and GFAP-positive nonmyelinating Schwann cells are normally present in adult peripheral nerve, and the myelinating Schwann cells react to pathologic situations by switching to GFAP-positive nonmyelinating cells, it may be that oligodendrocytes and cells are more similar than previously thought.
Search for a Prion-Specific Nucleic Acid

ABSTRACT Diversity of prion strains was attributed to an elusive nucleic acid, yet a search spanning nearly two decades has failed to identify a prion-specific polynucleotide. In our search for a prion-specific nucleic acid, we analyzed nucleic acids in purified fractions from the brains of Syrian hamsters infected with Sc237 prions. Purification of Sc237 prions removed nucleic acids larger than 50 nucleotides as measured by return refocusing electrophoresis (RRGE). To determine the size of the largest polynucleotide present in purified fractions at an abundance of one molecule per infectious (ID50) unit, we measured prions present after inoculation. In order to account for the rapid clearance of prions after intracerebral inoculation, we determined the number of PrPSc molecules and ID50 units of prions that were retained in brain. Factoring in clearance after inoculation, we estimate that the largest polynucleotide present in our purified fractions at one molecule per ID50 unit is ≈25 nucleotides in length. In the same fractions, there were ≈3,000 protease-resistant PrPSc molecules per ID50 unit after accounting for clearance of PrPSc following inoculation. We compared the resistance of Sc237 and 139H prions to inactivation by UV irradiation at 254 nm. Irradiation of homogenates and microsomes diminished prion infectivity by a factor of ≈1,000 but did not alter the strain-specified properties of the Sc237 and 139H prions. The data reported here combined with the production of synthetic prions argue that the 25-mer polynucleotides found in purified prion preparations are likely to be host encoded and of variable sequence; additionally, these 25-mers are unlikely to be prion specific.
Oligopeptidase-deficient mutants of Salmonella typhimurium

An oligopeptidase that hydrolyzes N-acetyl-L-alanyl-L-alanyl-L-alanyl-L-alanine (AcAla4) has been identified in extracts of Salmonella typhimurium. Mutants lacking this activity have been isolated in dcp mutant strains by screening extracts of mutagenized clones for failure to hydrolyze AcAla4 or by screening colonies for inability to use AcAla4 as a nitrogen source. Double mutants (dcp optA) lacking both oligopeptidase A and dipeptidyl carboxypeptidase cannot use AcAla4 as a nitrogen source, although dcp+ optA and dcp optA+ strains grow on this peptide. The mutations responsible for the loss of activity map at a locus (optA) between asd (75 map units) and xylA (78 map units). Oligopeptidase A hydrolyzes certain N-blocked tetrapeptides, unblocked pentapeptides, and unblocked hexapeptides, usually but not always liberating the C-terminal tripeptide. These two activities seem to be responsible for the production of a large fraction of the dipeptides that accumulate during protein breakdown in a pepN pepA pepB pepD strain.
Overexpression of L1 cell adhesion molecule correlates with aggressive tumor progression of patients with breast cancer and promotes motility of breast cancer cells.

BACKGROUND AND PURPOSE L1 cell adhesion molecule (L1CAM) has been observed to be aberrantly expressed and implicated in progression of several types of human cancers. However, its roles in breast cancer have not been fully elucidated. In this study, we aimed to investigate the clinical significance of L1CAM in human breast cancer and to validate whether it participates in cancer cell migration and invasion. METHODS Immunohistochemical analysis of 100 breast cancer and matched non-cancerous breast tissues was performed to detect the expression and sub-cellular localization of L1CAM protein. Its associations with clinicopathological characteristics of breast cancer patients were statistically analyzed and its phenotypic effects were also evaluated in vitro. RESULTS Of the 100 breast cancer patients, 89 (89.0%) were positive for L1CAM immunostaining localized in the membrane of cancer cells. The immunoreactive scores of L1CAM protein in breast cancer tissues were significantly higher than those in matched non-cancerous breast tissues (P<0.05). Chi-Square analysis showed the significant associations between L1CAM overexpression and high tumor stage (P=0.01), advanced tumor grade (P=0.03), positive lymph node metastasis (P=0.01) and tumor recurrence (P=0.01) in breast cancer patients. Moreover, we found that RNA interference-mediated knockdown of L1CAM could inhibit the migration and invasion abilities of breast cancer cells in vitro. CONCLUSIONS Our results suggest that the overexpression of L1CAM may be related to several established markers of poor prognosis in breast cancer patients. L1CAM might be a potential therapeutic target against metastatic breast cancer.
Cytotoxic effects of pemetrexed in gastric cancer cells

Pemetrexed is a newly developed multitargeted antifolate with promising clinical activity in many solid tumors including gastric cancer. The aim of the present study was to evaluate the cytotoxicity of pemetrexed and its mode of interaction with cisplatin in gastric cancer cell lines, and to identify genes associated with sensitivity to pemetrexed. The cytotoxic activity of pemetrexed was assessed by tetrazolium‐based colorimetric assay (MTT assay) and the interaction between pemetrexed and cisplatin was evaluated by the isobologram method. Western immunoblotting and real time RT‐PCR analysis of thymidylate synthase (TS), folylpoly‐γ‐glutamate synthetase (FPGS) and reduced folate carrier (RFC1) were performed in order to determine whether sensitivity to pemetrexed would be predictable by protein or mRNA expression levels. Pemetrexed was more cytotoxic than 5‐fluorouracil, with IC50 between 17 and 310 nM in most of the gastric cancer cell lines examined and the pemetrexed/cisplatin combination resulted in additive or synergistic interaction. The protein expressions of TS, FPGS, and RFC1 were significantly associated with IC50 for 5‐fluorouracil, but no such association was found for pemetrexed chemosensitivity. The mRNA expressions of RFC1, FPGS and other target and resistance related genes revealed no significant association with pemetrexed sensitivity. In conclusion, pemetrexed is active against gastric cancer cell lines and the pemetrexed/cisplatin combination showed a synergistic or additive interaction, supporting its clinical use in gastric cancer. Drug sensitivity toward pemetrexed could not be predicted by the expressions of TS, RFC1, or FPGS and we suggest that it is determined by interactions between multiple genes. (Cancer Sci 2005; 96: 365–371)
Investigation on thermal aging characteristics of vegetable oil-paper insulation with flowing dry air

In order to investigate the thermal aging characteristics of oil-paper insulation in open-type transformers, a thermally accelerated aging experiment with flowing dry air is performed. The vegetable oil, NOMEX paper, pressboard, copper and silicon steel are sealed into the aging vessels and further aged, for 216 hours, by supply of flowing dry air at 170 °C. Several important parameters associated with the aging are observed and evaluated during the aging process. It is shown that the degree of polymerization (DP) of pressboard gradually decreases and fits well into the second-order kinematic model. Little deterioration of the NOMEX paper under 170 ° is confirmed by the tensile strength which stabilizes at a certain level after aging. In addition, the logarithm of the furfural concentration in oil is found to have a good linear relationship with DP of pressboard. Interestingly, when the aging time is about 150 hours and DP is 329, the aging process reaches an inflection point at which the DP approaches the leveling off degree of polymerization (LODP) value, the moisture content and the furfural content of oil begin to fall down while the acid number and the dissipation factor of oil increase with a faster rate. However, the viscosity of the fluid, one of the important parameters of transformer operation, does not change significantly. The obtained results demonstrate that exposure to air leads to serious oxidation of oil and rapid increase of acid and dissipation factor, and this way oxygen should be avoided for the open-type transformer filled with vegetable oil.
A Gendered Perspective on Human Trafficking Perpetrators: Evidence from Russia

ABSTRACT The dominant depiction of human trafficking is that of a violent man trafficking an innocent, subordinate female victim for sexual exploitation. However, this does not represent the diversity of the experience of human trafficking. Increasingly, research has suggested that women are also perpetrators of human trafficking and that men and boys are frequently victims. Using a content analysis of Russian media articles on trafficking cases from 2003 to 2013, I examine women perpetrators of trafficking. I show that women have leveraged gender stereotypes and their positions in society to participate in trafficking in a variety of ways and that they are also enabled by particular structural characteristics of the trafficking business. I argue that a gendered perspective on perpetrators combined with deep empirical analysis can help us better understand what trafficking looks like in reality and how the experiences of women in trafficking are more complex than stereotypes would have us believe.
DONOR BONE MARROW-DERIVED CHIMERIC CELLS PRESENT IN RENAL TRANSPLANT RECIPIENTS INFUSED WITH DONOR MARROW. I. POTENT REGULATORS OF RECIPIENT ANTIDONOR IMMUNE RESPONSES1

Background. Even though a number of transplant centers have adopted donor-specific bone marrow cell (DBMC) infusions to enhance donor cell chimerism, to date there has been no direct evidence linking chimerism with tolerance induction in human organ transplant recipients. Methods. Cells of donor phenotype were isolated 1 year postoperatively from the peripheral blood lymphocytes and iliac crest bone marrow of 11 living-related-donor (LRD) renal transplant recipients, who had received perioperative donor bone marrow cell infusions. These recipient-derived donor (RdD) cells were characterized phenotypically by flow cytometric analysis and functionally as modulators in mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. Results. The yield of RdD cells ranged from 0.1 to 0.9% of the starting material with the majority being TcR&agr;&bgr;, CD3 positive T cells, a substantial percentage of which coexpressed CD28. At 1 year posttransplant almost 50% of the LRD-kidney/DBMC recipients tested so far exhibited donor-specific unresponsiveness in MLR (7/17) and CML (6/13) reactions and this trend was further enhanced at 2–3 years. In the recipients with residual positive antidonor immune responses, the RdD cells inhibited recipient antidonor MLR and CML responses significantly more strongly than freshly isolated and similarly treated iliac crest bone marrow cells from the donor. RdD cells also inhibited the MLR of the recipient to third party allogeneic stimulator cells; however, this nonspecific effect was significantly weaker than specific inhibition. We also established long-term bone marrow cultures stimulated every 2 weeks with irradiated allogeneic feeder cells, that had similar functional properties thus possibly providing us with an in vitro correlate the RdD cells. Conclusions. These results clearly support the notion that the infused donor cells play a positive role in the induction and/or maintenance of transplant tolerance.
Sampling strategy for intraoral detection of periodontal pathogens before and following periodontal therapy.

BACKGROUND The aim of this study was to identify a sampling strategy with high probability for detecting oral colonization by Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Tannerella forsythensis, Prevotella intermedia, Prevotella nigrescens, and Treponema denticola before and following mechanical periodontal therapy. METHODS Samples were taken from the following intraoral sites in 35 patients with untreated chronic periodontitis before and 1.5, 3, and 6 months after non-surgical periodontal therapy: supra- and subgingival plaque from the deepest pockets in each sextant; pooled supra- and subgingival plaque from another six randomly selected, less affected teeth; mucosal swab samples from the tongue, tonsils, throat, and buccal mucosa; and stimulated and unstimulated saliva. Microbial species were identified by polymerase chain reaction (PCR). RESULTS Of the sampling of all assessed sites, the highest probability for simultaneously detecting the tested pathogens was found in respect to the combination of supra- and subgingival plaque samples taken from the most affected tooth in each sextant in untreated patients (probability: 83% to 95% for the assessed bacteria). These results were consistently observed throughout the study period. CONCLUSIONS For determining the intraoral carrier state of patients with periodontitis, a combined sample of supra- and subgingival plaque taken from the deepest periodontal pocket in each sextant may yield the most reliable result. This sampling strategy may be used in routine microbial testing and clinical research.
The contribution of expanding portion sizes to the US obesity epidemic.

OBJECTIVES Because larger food portions could be contributing to the increasing prevalence of overweight and obesity, this study was designed to weigh samples of marketplace foods, identify historical changes in the sizes of those foods, and compare current portions with federal standards. METHODS We obtained information about current portions from manufacturers or from direct weighing; we obtained information about past portions from manufacturers or contemporary publications. RESULTS Marketplace food portions have increased in size and now exceed federal standards. Portion sizes began to grow in the 1970s, rose sharply in the 1980s, and have continued in parallel with increasing body weights. CONCLUSIONS Because energy content increases with portion size, educational and other public health efforts to address obesity should focus on the need for people to consume smaller portions.
Risk assessment in cancer patients with fever and neutropenia: a prospective, two-center validation of a prediction rule.

PURPOSE The study was undertaken to validate a clinical model for predicting the medical risk of cancer patients with fever and neutropenia. PATIENTS AND METHODS A consecutive sample of 444 cancer patients with fever and neutropenia (granulocyte count less than 500/microL) at two hospitals, a specialized cancer referral center and a university-affiliated general medical hospital, was studied to identify clinical characteristics in the first 24 hours that predict subsequent serious medical complications during the hospital stay. To control for bias, major risk factors and complications were subject to blinded review. RESULTS Serious medical complications occurred in 34% of patients with risk factors identified in a prior study, including prior inpatient status (group I), outpatients with a serious independent comorbidity (group II), or uncontrolled cancer (group III), compared with 5% of the remaining patients (group IV) (P less than .000001). Two of the complications in group IV patients were transient asymptomatic hypotension, and the remaining three complications occurred after at least 1 week of progressive medical deterioration. These risk groups were independently significant in stepwise logistic regression analysis. Multiple complications (17%) and death (10%) were common among patients in groups I through III but did not occur in group IV patients. CONCLUSIONS This risk assessment model accurately stratified the medical risk of these patients using only clinical information available on the first day of their course. Low-risk patients are an appropriate population in which to study less intensive treatment strategies.
The Efficacy and Tolerability of a Fixed Combination Clindamycin (1.2%) and Benzoyl Peroxide (3.75%) Aqueous Gel in Adult Female Patients with Facial Acne Vulgaris.

OBJECTIVE To investigate the efficacy and tolerability of clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel or vehicle monotherapy in adult female acne patients. METHODS A post hoc analysis in 72 adult female patients (aged ≥25 years) with moderate-to-severe acne receiving clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel or vehicle for 12 weeks. RESULTS The efficacy of clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel was significantly greater than vehicle. The mean percent change from baseline in inflammatory and noninflammatory lesion counts and the percentage of patients who achieved a 2-grade reduction in the Evaluator's Global Severity Score was 68.7%, 60.4, and 52.7 percent, respectively (P=0.019, 0.020 and 0.074 versus vehicle). In addition, 44 percent of patients reported their acne to be "clear" or "almost clear" at Week 12 (P=0.026 versus vehicle). No substantive differences were seen in cutaneous tolerability among treatment groups, and no patients discontinued treatment because of adverse events. LIMITATIONS It is not possible to determine the contributions of the individual active ingredients, and this study was not set up specifically to investigate the treatment of adult female acne. CONCLUSION Clindamycin phosphate 1.2%/benzoyl peroxide 3.75% gel provides statistically significant greater efficacy than vehicle in treating acne in adult female patients and has a favorable safety and tolerability profile.