Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of fusarium keratitis outbreak isolates: contribution of biofilms to antimicrobial resistance and pathogenesis.

PURPOSE Fusarium is a major cause of microbial keratitis, and its ability to form biofilms was suggested as a contributing factor in recent outbreaks. We investigated the ability of outbreak Fusarium isolates (F. solani species complex [FSSC] and F. oxysporum species complex [FOSC]) to form biofilms in vitro and in vivo, and evaluated their antifungal susceptibilities. METHODS Biofilm formation was assessed using our in vitro contact lens model and in vivo murine model. Biofilm architecture was assessed using confocal laser scanning microscopy (CLSM). Susceptibility against amphotericin B (AmB), voriconazole (VCZ), and natamycin (NAT) was determined using the CLSI-M38-A2 method and XTT metabolic assay. RESULTS FSSC strains formed more biofilms than FOSC, in a strain- and clade-dependent manner. CLSM analyses revealed that "high biofilm forming" (HBF) strains had denser and thicker biofilms than "low biofilm forming" (LBF) strains of both species (thickness 51 vs. 41 μm for FSSC and 61 vs. 45 μm for FOSC strains, P < 0.05 for both comparisons). Fusarium biofilms exhibited species-dependent antifungal susceptibilities (e.g., FSSC biofilms AmB minimal inhibitory concentrations [MIC] ≥16 μg/mL, while NAT or VCZ MICs were 2-8 μg/mL). FSSC-infected mice had severe corneal opacification independent of biofilm thickness, while FOSC infection resulted in moderate corneal opacification. Corneal fungal burden of mice infected with HBF strains was higher than those of the LBF strains. In contrast, the reference ATCC isolate was unable to cause infection. CONCLUSIONS The ability to form biofilms is a key pathogenicity determinant of Fusarium, irrespective of the thickness of these biofilms. Further studies are warranted to explore this association in greater detail.
SPLITTING PRISM TEST METHOD TO EVALUATE CONCRETE-TO-CONCRETE BOND STRENGTH

This paper presents a simple test method to measure the bond strength between two concrete materials. The method uses a splitting prism test procedure similar to the American Society for Testing and Materials (ASTM) C 496 test for splitting tensile strength of cylindrical concrete specimens. The procedure can include freezing and thawing of specimens as a test variable. The required number of test specimens and the repeatability of the test method are discussed. The method can evaluate the bond strength and durability of materials used for concrete pavement or bridge deck repairs.
Osteoclasts express high levels of pp60c-src in association with intracellular membranes

Deletion of the c-src gene in transgenic mice by homologous recombination leads to osteopetrosis, a skeletal defect characterized by markedly deficient bone resorption (Soriano, P., C. Montgomery, R. Geske, and A. Bradley. 1991. Cell. 64:693-702), demonstrating a critical functional role of pp60c-src in osteoclast activity. Since decreased bone resorption could result from a defect either within the osteoclast or within other cells present in its environment, indirectly affecting osteoclast functions, we determined which cell(s) in bone expressed high levels of pp60c-src Measuring pp60c-src protein and kinase activities in osteoclasts and immunolocalizing pp60c-src in bone, we find that expression of pp60c-src is nearly as high in osteoclasts as in brain and platelets. In contrast, other bone cells contain only very low levels of the protein. In addition, expression of the c-src gene product increases when bone marrow cells are induced to express an osteoclast-like phenotype by 1,25-dihydroxy-vitamin D3, further suggesting that high expression of pp60c-src is part of the osteoclast phenotype. Three other src-like kinases, c-fyn, c-yes, and c- lyn, are also expressed in osteoclasts at ratios to pp60c-src similar to what is found in platelets. These src-related proteins do not, however, compensate for the absence of pp60c-src in the src- mice, thereby suggesting that pp60c-src may have a specific function in osteoclasts. Although further work is necessary to elucidate what the critical role of pp60c-src in osteoclasts is, our observation that the protein is associated mostly with the membranes of intracellular organelles suggests the possibility that this role might be at least in part related to the targeting or fusion of membrane vesicles.
Music and dyslexia

Dyslexic readers present deficits in phonological processing, including in the ability to represent and manipulate representations of phonemes consciously and intentionally. An association between such phonological deficits and poor musical skills has been reported in some published work. From this triple association – reading, phonology and music – some authors, referenced in the text, concluded that dyslexia may result from a musical or, more generally, auditory impairment, and some of them suggested that music therapy helps dyslexics to overcome their reading difficulties beyond phonological training. In this article, we attempt to show that, in light of both theoretical reasons and the available evidence, there is no justification either for that causality inference or for the consequent practical recommendation.
Modified Alderman‐Grant resonator with high‐power stability for proton electron double resonance imaging

Proton‐electron double resonance imaging (PEDRI) requires a dual EPR/NMR resonator. In order to saturate electron spins, long high‐power RF EPR pulses are needed. Dissipated power causes resonator and sample heating, resulting in instability of the resonator frequency and coupling, which in turn causes a reduction in sensitivity. To overcome this problem, we designed, built, and tested a modified Alderman‐Grant (MAG) resonator for in vivo and in vitro applications. We improved the temperature stability by using fused quartz in critical structural components of the resonator and employing a design that minimized moving parts. All of the components of the resonator and matching circuit, including coupling capacitors, were rigidly positioned on the surface of the quartz tube. Electrical coupling circuitry between the feeding cable and resonator was employed to provide independent coupling and tuning adjustments, which improved the ease and speed of operation. The equivalent schematic of the matching circuit is presented along with calculations of critical parameters. The resonator exhibits no frequency shift with 20 W of continuous power irradiation, and can handle intermittent power of 60 W for up to 3 min without detuning, enabling stable and reliable data acquisition for PEDRI of biological samples. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
A dose-response relationship between short sleeping hours and childhood obesity: results of the Toyama Birth Cohort Study.

BACKGROUND Short sleeping hours could cause obesity through increased sympathetic activity, elevated cortisol secretion and decreased glucose tolerance. The aim of this study was to clarify parental and lifestyle factors, particularly sleeping habits, associated with obesity in Japanese children. METHODS Between June and July 1996, 8274 children (4194 males and 4080 females) aged 6-7 years living in Toyama prefecture, Japan, were investigated by questionnaire survey and the collection of anthropometric data. Subjects with a body mass index (BMI; weight in kg divided by square of height in m) greater than the age- and sex-specific cut-off points linked to adulthood overweight (BMI of 25 kg/m2 or more) were defined as obese subjects. Parental obesity was defined as a BMI of 25 kg/m2 or more. Logistic regression analysis was performed to evaluate the strength of the relationships between parental obesity or lifestyle factors and childhood obesity, adjusted for possible confounding factors. RESULTS Parental obesity, long hours of TV watching and physical inactivity were significantly associated with childhood obesity. Although wake-up time was not related to obesity, there was a significant dose-response relationship between late bedtime or short sleeping hours and childhood obesity. Compared with children with 10 or more hours of sleep, the adjusted odds ratio was 1.49 (95% confidence interval 1.08-2.14) for those with 9-10 h sleep, 1.89 (1.34-2.73) for those with 8-9 h sleep and 2.87 (1.61-5.05) for those with <8 h sleep, after adjustment for age, sex, parental obesity and other lifestyle factors. CONCLUSION A strong inverse association was observed in the relationship between sleeping hours and childhood obesity. Longitudinal research will be required to confirm this causality.
Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson’s disease

Background: We investigated the cognitive and psychiatric outcome 6 months after bilateral subthalamic nucleus deep brain stimulation (DBS) for the treatment of Parkinson’s disease (PD) using a disease control group. Methods: 23 patients who underwent DBS were compared with 28 medically treated patients with PD at baseline and at 6 months for neuropsychological measures. In addition to the group outcomes, we report reliable change indices (RCI) and a dementia caseness analysis. Results: Patients who underwent DBS demonstrated a significant decline in verbal memory compared with the control group (p<0.003), and trends for decline on oral information processing, including verbal fluency, timed transcription and word naming. Patients who underwent DBS demonstrated declines in attention, set shifting and semantic fluency but these changes were similar to the rate of decline in the PD group. RCI indicated that patients who underwent DBS demonstrated clinically significant declines in verbal fluency (p<0.01) and inhibition of a dominant response (p<0.003), with trends for declines in set shifting (p<0.02) and verbal long term recall (p<0.08), indicative of frontostriatal dysfunction. Patients who underwent DBS did not demonstrate significant changes in depression, anxiety or psychological distress scores. The caseness analysis revealed that one of the patients who underwent DBS (4%) converted to dementia over 6 months compared with none of the PD controls. Conclusions: Our findings demonstrated that patients who underwent DBS experienced declines in verbal recall and trends for declines in oral information processing 6 months following surgery, even when good motor outcome was achieved. Potential candidates should be counselled about the risk of mild frontostriatal cognitive declines following DBS to weigh the risks and benefits of surgery.
Clinicians should assess the benefits and risks of using bezlotoxumab for reducing the risk of recurrent Clostridium difficile infection

Commentry on: Wilcox MH, Gerding DN, Poxton IR, et al . Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection. N Engl J Med 2017;376:305–317. Clostridium difficile is an anaerobic gram-positive spore-forming bacillus that plays a major role in healthcare antibiotic-associated diarrhoea. A continued rise in antibiotic use, specifically, cephalosporins and fluoroquinolones, has been linked to the development of more resistant strains of this toxin-forming pathogen, triggering more recurrences and severe manifestations of the disease across USA and Europe.1 The high burden of recurrence and increased healthcare costs associated with C. difficile infection (CDI) have encouraged the development of new treatments to prevent recurrence including the use of pulsed/tapered oral vancomycin, fidaxomicin and faecal microbiota transplantation (FMT). 2 Monoclonal antibodies for C. difficile therapy (MODIFY) trials I and II are two global phase 3 trials aimed at examining the efficacy and safety of a single dose (10 mg/kg) of human monoclonal antibodies actoxumab and bezlotoxumab against C. …
Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma

Significance Mutations in the PI3K/PTEN/Akt signaling pathway occur frequently across multiple tumor types. These mutations primarily serve to activate PI-3 and Akt kinases. PREX2 is a guanine nucleotide exchanger for Rac1 that is significantly mutated in melanoma and pancreatic ductal adenocarcinoma. Here we report that a mouse model of a truncating PREX2 mutation shows accelerated melanoma development in the context of mutant NRAS. Truncating PREX2 mutations have increased Rac1 guanine nucleotide exchange factor activity, and tumors harboring these mutations have elevated PI3K/Akt pathway activation and reduced expression of critical negative cell cycle regulators leading to increased cell proliferation. This work provides evidence for a previously unidentified mechanism of activating Rac1, the PI3K pathway, and regulation of cell cycle progression in melanoma. PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac-exchange factor 2) is a PTEN (phosphatase and tensin homolog deleted on chromosome 10) binding protein that is significantly mutated in cutaneous melanoma and pancreatic ductal adenocarcinoma. Here, genetic and biochemical analyses were conducted to elucidate the nature and mechanistic basis of PREX2 mutation in melanoma development. By generating an inducible transgenic mouse model we showed an oncogenic role for a truncating PREX2 mutation (PREX2E824*) in vivo in the context of mutant NRAS. Using integrative cross-species gene expression analysis, we identified deregulated cell cycle and cytoskeleton organization as significantly perturbed biological pathways in PREX2 mutant tumors. Mechanistically, truncation of PREX2 activated its Rac1 guanine nucleotide exchange factor activity, abolished binding to PTEN and activated the PI3K (phosphatidyl inositol 3 kinase)/Akt signaling pathway. We further showed that PREX2 truncating mutations or PTEN deletion induces down-regulation of the tumor suppressor and cell cycle regulator CDKN1C (also known as p57KIP2). This down-regulation occurs, at least partially, through DNA hypomethylation of a differentially methylated region in chromosome 11 that is a known regulatory region for expression of the CDKN1C gene. Together, these findings identify PREX2 as a mediator of NRAS-mutant melanoma development that acts through the PI3K/PTEN/Akt pathway to regulate gene expression of a cell cycle regulator.
A dose‐intensive, cyclophosphamide‐based regimen for the treatment of recurrent/Progressive or advanced solid tumors of childhood

Children with solid tumors that progress or recur after conventional multimodality therapies have a very poor prognosis. In a pilot study, vincristine, etoposide, and dose‐escalated cyclophosphamide (VETOPEC) was shown to be a promising salvage regimen. Continued accrual of patients and increased duration of follow‐up has resulted in substantial experience with VETOPEC.
Low-load deformation of InP under contact loading; comparison with GaAs

Abstract Nanoindentation has been used to explore the plasticity onset under contact loading in InP. Under low indenting loads ranging between 0.2 and 10mN, fracture of the sample is avoided and plastic zones can be observed by transmission electron microscopy. The zone-size variation with load could be measured and analysed using the work of Johnson and of Kramer et al. The results were compared with those obtained in GaAs deformed under the same conditions. Furthermore, characterization of the dislocations was made and it was shown that the twinning formation in InP differed strongly from that in GaAs. The results are compared with previously reported arrangements obtained in the microindentation domain.
Adequacy and Consistency of Animal Studies to Evaluate the Neurotoxicity of Chronic Low-Level Manganese Exposure in Humans

The adequacy of existing animal studies to understand the effects of chronic low-level manganese exposures in humans is unclear. Here, a collection of subchronic to chronic rodent and nonhuman primate studies was evaluated to determine whether there is a consistent dose-response relationship among studies, whether there is a progression of effects with increasing dose, and whether these studies are adequate for evaluating the neurotoxicity of chronic low-level manganese exposures in humans. Neurochemical and behavioral effects were compared along the axis of estimated internal cumulative manganese dose, independent of the route of exposure. In rodents, motor effects emerged at cumulative doses below those where occupationally exposed humans start to show motor deficits. The main neurochemical effects in rodents were an increase in striatal gamma-aminobutyric acid (GABA) concentration throughout the internal cumulative dose range of 18 to 5300 mg Mn/kg but a variable effect on striatal dopamine concentration emerging at internal cumulative doses above ∼200 mg Mn/kg. Monkey studies showed motor deficits and effects on the globus pallidus at relatively low doses and consistent harmful effects on both the globus pallidus and the caudate and putamen at higher doses (> 260 mg Mn/kg). Internal cumulative manganese doses of animal studies extend more than two orders of magnitude (< 1 to 5300 mg Mn/kg) above the doses at which occupationally exposed humans show neurological dysfunction (10–15 mg Mn/kg). Since the animal data indicate that manganese neurotoxicity may be different at low compared to elevated exposures, most existing animal model studies might be of limited relevance for the risk assessment of chronic low-level manganese exposure to humans.
PROCESSING AND PROPERTIES OF MICROCRYSTALLINE, SUBMICROCRYSTALLINE, AND NANOCRYSTALLINE ALLOY 718

This paper will describe the refinement of a coarse-grained alloy 718 microstructure to microcrystalline (MC), submicrocrystalline (SMC), and nanocrystalline (NC) structures by high-strain plastic deformation. Dynamic recrystallization occurs during high-strain hot plastic deformation leading to the formation of an MC structure with a grain size of 1-4 pm. The 6 phase precipitated as plates, and during deformation, these plates were broken up into smaller particles. These particles take the form of ellipsoids located mainly at the triple junctions of the recrystallized grains. A SMC structure was formed in alloy 7 18 during severe plastic deformation in the temperature range 0.67-0.60 T,. During dynamic and static recrystallization, the MC structure transformed to the SMC structure, and 6-phase plates precipitated uniformly throughout the matrix. The size of these precipitates was similar to the matrix grain size (0.2-0.5 pm). Further reduction in the processing temperature to 0.5 T, provided additional refinement of the microstructure to a grain size of less than 0.1 pm. The formation of NC structures in alloy 718 by cold severe plastic deformation (0.18 T,) was also studied. The microstructure evolution during combined torsion and compression was examined. With increasing strain, a cellular structure was formed, which was then refined to a granular structure with a grain size of 30-40 nm, with high angle grain boundaries and a high level of residual stress within the grains. The influence of the initial grain size on deformation mechanisms during superplastic deformation of alloy 718 was also studied. For grain sizes of 0.1-0.08 pm, superplasticity (6=350%, m=0.37) was observed at a temperature of 600°C and a strain rate of 1.5~ ~O-~s-l.
Risk Factors for Suicide Ideation Differ From Those for the Transition to Suicide Attempt: The Importance of Creativity, Rigor, and Urgency in Suicide Research

We were invited to comment on the article by May and Klonsky (2016) titled “What Distinguishes Suicide Attempters From Suicide Ideators? A Meta-Analysis of Potential Factors. ” We were delighted to see the authors calling attention to the fact that the risk factors for onset of suicide ideation differ from those for the transition from suicide ideation to attempt. Our commentary focuses on three points: (a) despite the authors' framing it as such, this is not a new research question, but one with a substantial history; (b) this meta-analysis excludes most of the available data on this topic and focuses instead on results from small and nonrepresentative studies, limiting the validity of the inferences that can be drawn from this analysis; and (c) this meta-analysis was designed in a way that precludes the examination of actual risk factors for the transition from suicidal thought to action. We conclude by discussing some important considerations for future research.
Glucose, lactate, and pyruvate response in an experimental model of microvascular flap ischemia and reperfusion: A microdialysis study

Early diagnosis of postoperative perfusion failure is essential in microsurgical tissue transfer. In order to determine if microdialysis could be used in diagnosing flap ischemia, we tested this method in an experimental pig model. Sixty‐six flaps (34 myocutaneous and 29 cutaneous) were created in 18 anesthetized pigs. During the experiment, secondary ischemia was induced for 5 h by selective clamping of the artery (20 flaps) or vein (21 flaps). Glucose, lactate, and pyruvate concentrations were measured hourly from the muscular and dermal layers. We found that decreasing glucose levels and increasing lactate concentrations were associated with arterial and venous occlusions from the first hour of ischemia. In venous ischemia, lactate concentrations remained lower than those in arterial ischemia. The increase in lactate‐to‐pyruvate and lactate‐to‐glucose ratios was related to ischemia and also discriminated arterial occlusion from venous occlusion. In conclusion, microdialysis can be used to facilitate early detection of ischemia. © 2004 Wiley‐Liss, Inc.
Corrosion behaviour of glass‐bead blasted stainless steel sheets and other sheets with dull surface finish in a chloride solution

Glass‐bead blasted stainless steel sheets are used in recent time for many applications in architecture or design of machines. If chloride can be accumulated on the surface, glass‐bead blasted stainless steel show a worse corrosion behaviour than ground stainless steel. The corrosion behaviour of glass‐bead blasted stainless steel is characterised by electrochemical, topographic and roughness investigations. The results of glass‐bead blasted stainless steel will be compared with results of other surface treated steels like ground, structure rolled, sand‐blasted and electropolished stainless steel. It is shown that not only the roughness parameter Ra has an influence on the corrosion behaviour but also the shape of the valleys and peaks, which are produced during different surface treatments. The investigations lead to advices for the use of these materials in practice.