Miracle-dz/UniFAR-FTUs huggingface dataset:
Overview of transplant mycology.

PURPOSE The epidemiology, clinical manifestation, diagnosis, and management of invasive mycoses in transplant patients are described. SUMMARY The incidence of and mortality from invasive mycoses have increased in transplant patients. Candida and Aspergillus are the two most common fungal pathogens in this patient population. The use of immunosuppressive and myeloablative therapies and other factors increases the risk of invasive mycoses. A high index of suspicion and clinical clues are needed for the diagnosis of Candida and Aspergillus infections because reliable diagnostic techniques are not available and the patient presentation is nonspecific. Targeted prophylaxis for patients at high risk for morbidity and mortality and early, aggressive treatment using broad-spectrum antifungal agents are recommended. Prophylaxis using itraconazole reduces the risk of treatment failure due to resistant pathogens compared with fluconazole. Voriconazole might prove advantageous compared with fluconazole and itraconazole for prophylaxis because of its extended spectrum and predictable blood levels. Caspofungin seems as effective as and less toxic than amphotericin B for this use. Voriconazole is more effective than amphotericin B for the treatment of aspergillosis. Caspofungin is comparable to voriconazole in efficacy as salvage treatment after failure to respond to other antifungal agents. CONCLUSION Caspofungin plus voriconazole and other combination therapies often are used for the treatment of aspergillosis yet data to support such use are yet to be produced. The investigational agents posaconazole, micafungin, and anidulafungin appear promising as salvage treatment of various invasive mycoses.
Plasma Membrane Localization Is Required for RasA-Mediated Polarized Morphogenesis and Virulence of Aspergillus fumigatus

ABSTRACT Ras is a highly conserved GTPase protein that is essential for proper polarized morphogenesis of filamentous fungi. Localization of Ras proteins to the plasma membrane and endomembranes through posttranslational addition of farnesyl and palmitoyl residues is an important mechanism through which cells provide specificity to Ras signal output. Although the Aspergillus fumigatus RasA protein is known to be a major regulator of growth and development, the membrane distribution of RasA during polarized morphogenesis and the role of properly localized Ras signaling in virulence of a pathogenic mold remain unknown. Here we demonstrate that Aspergillus fumigatus RasA localizes primarily to the plasma membrane of actively growing hyphae. We show that treatment with the palmitoylation inhibitor 2-bromopalmitate disrupts normal RasA plasma membrane association and decreases hyphal growth. Targeted mutations of the highly conserved RasA palmitoylation motif also mislocalized RasA from the plasma membrane and led to severe hyphal abnormalities, cell wall structural changes, and reduced virulence in murine invasive aspergillosis. Finally, we provide evidence that proper RasA localization is independent of the Ras palmitoyltransferase homolog, encoded by erfB, but requires the palmitoyltransferase complex subunit, encoded by erfD. Our results demonstrate that plasma membrane-associated RasA is critical for polarized morphogenesis, cell wall stability, and virulence in A. fumigatus.
Hemispheric Asymmetries in Striatal Reward Responses Relate to Approach–Avoidance Learning and Encoding of Positive–Negative Prediction Errors in Dopaminergic Midbrain Regions

Some individuals are better at learning about rewarding situations, whereas others are inclined to avoid punishments (i.e., enhanced approach or avoidance learning, respectively). In reinforcement learning, action values are increased when outcomes are better than predicted (positive prediction errors [PEs]) and decreased for worse than predicted outcomes (negative PEs). Because actions with high and low values are approached and avoided, respectively, individual differences in the neural encoding of PEs may influence the balance between approach–avoidance learning. Recent correlational approaches also indicate that biases in approach–avoidance learning involve hemispheric asymmetries in dopamine function. However, the computational and neural mechanisms underpinning such learning biases remain unknown. Here we assessed hemispheric reward asymmetry in striatal activity in 34 human participants who performed a task involving rewards and punishments. We show that the relative difference in reward response between hemispheres relates to individual biases in approach–avoidance learning. Moreover, using a computational modeling approach, we demonstrate that better encoding of positive (vs negative) PEs in dopaminergic midbrain regions is associated with better approach (vs avoidance) learning, specifically in participants with larger reward responses in the left (vs right) ventral striatum. Thus, individual dispositions or traits may be determined by neural processes acting to constrain learning about specific aspects of the world. SIGNIFICANCE STATEMENT Individuals differ in how they behave toward rewards or punishments. Here, we demonstrate that functional hemispheric asymmetries measured in dopaminergic reward regions dictate whether someone will learn to choose rewarding options or instead avoid punishing outcomes. We also show that hemispheric reward asymmetries involve a differential neural encoding of signals controlling approach and avoidance learning. We thus provide experimental evidence for a mechanism that accounts for individual differences in approach and avoidance learning. Disabling mental illnesses have previously been associated with hemispheric asymmetries in dopamine function and extreme biases in approach–avoidance behavior. By showing that these observations implicate biased learning processes, the present study may offer important insights into the development and maintenance of some psychiatric disorders.
To freeze or not to freeze embryos: clarity, confusion and conflict

Abstract Although embryo freezing is a routine clinical practice, there is little contemporary evidence on how couples make the decision to freeze their surplus embryos, or of their perceptions during that time. This article describes a qualitative study of 16 couples who have had in vitro fertilisation (IVF) treatment. The study question was ‘What are the personal and social factors that patients consider when deciding whether to freeze embryos? ’ We show that while the desire for a baby is the dominant drive, couples’ views revealed more nuanced and complex considerations in the decision-making process. It was clear that the desire to have a baby influenced couples’ decision-making and that they saw freezing as ‘part of the process’. However, there were confusions associated with the term ‘freezing’ related to concerns about the safety of the procedure. Despite being given written information, couples were confused about the practical aspects of embryo freezing, which suggests they were preoccupied with the immediate demands of IVF. Couples expressed ethical conflicts about freezing ‘babies’. We hope the findings from this study will inform clinicians and assist them in providing support to couples confronted with this difficult decision-making.
Relative roles of signals upstream of AAUAAA and promoter proximity in regulation of human immunodeficiency virus type 1 mRNA 3' end formation

At least two mechanisms have been implicated in regulating poly(A) site use in human immunodeficiency virus type 1 (HIV-1): inhibition of basal signals within 500 nucleotides (nt) of the cap site, leading to specific suppression of the 5' poly(A) site, and stimulation of basal signals by long terminal repeat U3 sequences, leading to specific activation of the 3' poly(A) site. We determined the relative contributions of these mechanisms in a HeLa cell transcription/processing reaction and by transient transfection analysis. In vitro, the efficiency of basal signals is equivalent close to (270 nt) and far from (1,080 nt) the promoter and is stimulated at least 30-fold in both positions by upstream U3 sequences. In vivo, U3 sequences also enhance processing at both positions. There are two additional effects when the poly(A) site is close to the cap site: at least a 15-fold reduction in total RNA levels and a 5-fold decrease in relative levels of RNA processed at the HIV-1 site in constructs containing U3. Both effects are overcome by insertion of upstream splicing signals in an orientation-dependent manner. Splicing appears to influence poly(A)+ RNA levels by two distinct mechanisms: stabilizing nuclear transcripts and directly stimulating 3' end formation. It is proposed that upstream elements play major roles in regulating poly(A) site choice and in controlling the subsequent fate of polyadenylated RNA. The impact of these findings on mechanisms of mRNA biogenesis in the HIV-1 provirus is discussed.
Linear arrays of homogeneous mast cells in the dura mater of the rat.

Using fluorescence histochemistry, 5-HT, histamine and heparin were colocalized in a large population of cells in the dura mater thereby identifying them as mast cells. In addition, because these cells were highly sensitive to compound 48/80 and were densely packed with granules of a consistent density, they were identified specifically as 'connective tissue' mast cells. Other types of mast cells, i.e. 'mucosal' or 'neurolipomastocytes', were not present in the rat dura mater. 5-HT immunohistochemistry was the best technique for demonstrating that there were populations of mast cells, one associated with each of the two layers of dura. Although shaped differently the type of mast cell in each layer was the same. It was observed that mast cell shape is dependent on the contiguity, density and orientation of its surrounding elements, not its type. In general, mast cells in the outer layer were aligned parallel to the middle meningeal artery and those in the inner layer were parallel to trigeminal nerve branches that coursed obliquely across the middle meningeal artery. Examination of cross-sections of dura revealed that most mast cells also were aligned at the interface between the two dural layers. The linear orientation of mast cells in two planes of each layer suggests a programmed lamellar seeding of these cells during development of the dura. This study also demonstrated that the majority of dural mast cells were more closely related to other connective tissue elements than to blood vessels and nerves. These results (1) are compatible with the suggestion that dural mast cells play a non-obligatory role in the neuroinflammatory response, (2) leave open to question the role of the dural mast cell in headache or the regulation of blood flow, and (3) support evidence that dural mast cells play an important role in connective tissue related functions, e.g. development, inflammatory response to injury and wound repair.
MicroRNAs and tRNA-derived fragments predict the transformation of myelodysplastic syndromes to acute myeloid leukemia

Abstract Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders of the elderly that carry an increased risk of progression to acute myeloid leukemia (AML). Since small non-coding RNAs (sRNAs), including microRNA (miRNAs), act as regulators of cellular differentiation, we hypothesized that changes to sRNAs might be implicated in the progression of MDS to AML. We conducted sRNA sequencing on three sets of patients: Group A (MDS patients who never progressed to AML); Group B (MDS patients who later progressed to an AML); and Group C (AML patients with myelodysplasia-related changes, including patients with a known preceding diagnosis of MDS). We identified five miRNAs that differentiated Groups A and B, independent of bone marrow blast percentage, including three members of the miR-181 family, as well as differential patterns of miRNA isoforms (isomiRs) and tDRs. Thus, we have identified sRNA biomarkers that predict MDS cases that are likely to progress to AML.
The effects of proton irradiation on SiGe:C HBTs

The effects of 63 MeV proton irradiation on SiGe:C heterojunction bipolar transistors (HBTs) are reported for the first time. The dc characteristics and neutral base recombination of these SiGe:C HBTs were investigated for proton fluences up to 5/spl times/10/sup 13/ p/cm/sup 2/. A comparison is made with SiGe HBTs fabricated in the same technology. Despite the fact that these SiGe:C HBTs degrade significantly during proton exposure, there is no indication that the carbon doping has any significant impact on the radiation response.
State Prevailing Wage Laws and School Construction Costs

Critics of prevailing wage laws claim that their elimination will cut total public construction costs by 15 to 25 percent. Justification for this assertion may be found in a 1983 study comparing the cost of public construction regulated by the Davis-Bacon Act with the cost of similar private construction. However, this study failed to account for the difference in the cost of public and private buildings absent. Using F. W. Dodge data for 1991 to 1999, we show that the inclusion of the appropriate controls in a study of new school construction costs finds no statistically significant difference between the cost of public schools built with prevailing wage regulations.
A Small Membrane-peripheral Region Close to the Active Center Determines Regioselectivity of Membrane-bound Fatty Acid Desaturases from Aspergillus nidulans*

Fatty acid desaturases catalyze the introduction of double bonds at specific positions of an acyl chain and are categorized according to their substrate specificity and regioselectivity. The current understanding of membrane-bound desaturases is based on mutant studies, biochemical topology analysis, and the comparison of related enzymes with divergent functionality. Because structural information is lacking, the principles of membrane-bound desaturase specificity are still not understood despite of substantial research efforts. Here we compare two membrane-bound fatty acid desaturases from Aspergillus nidulans: a strictly monofunctional oleoyl-Δ12 desaturase and a processive bifunctional oleoyl-Δ12/linoleoyl-ω3 desaturase. The high similarities in the primary sequences of the enzymes provide an ideal starting point for the systematic analysis of factors determining substrate specificity and bifunctionality. Based on the most current topology models, both desaturases were divided into nine domains, and the domains of the monofunctional Δ12 desaturase were systematically exchanged for their respective corresponding matches of the bifunctional sister enzyme. Catalytic capacities of hybrid enzymes were tested by heterologous expression in yeast, followed by biochemical characterization of the resulting fatty acid patterns. The individual exchange of two domains of a length of 18 or 49 amino acids each resulted in bifunctional Δ12/ω3 activity of the previously monofunctional parental enzyme. Sufficient determinants of fatty acid desaturase substrate specificity and bifunctionality could, thus, be narrowed down to a membrane-peripheral region close to the catalytic site defined by conserved histidine-rich motifs in the topology model.
Acceleration-Based Running Intensities of Professional Rugby League Match Play.

Rugby league involves frequent periods of high-intensity running including acceleration and deceleration efforts, often occurring at low speeds. PURPOSE To quantify the energetic cost of running and acceleration efforts during rugby league competition to aid in prescription and monitoring of training. METHODS Global positioning system (GPS) data were collected from 37 professional rugby league players across 2 seasons. Peak values for relative distance, average acceleration/deceleration, and metabolic power (Pmet) were calculated for 10 different moving-average durations (1-10 min) for each position. A mixed-effects model was used to assess the effect of position for each duration, and individual comparisons were made using a magnitude-based-inference network. RESULTS There were almost certainly large differences in relative distance and Pmet between the 10-min window and all moving averages <5 min in duration (ES = 1.21-1.88). Fullbacks, halves, and hookers covered greater relative distances than outside backs, edge forwards, and middle forwards for moving averages lasting 2-10 min. Acceleration/deceleration demands were greatest in hookers and halves compared with fullbacks, middle forwards, and outside backs. Pmet was greatest in hookers, halves, and fullbacks compared with middle forwards and outside backs. CONCLUSIONS Competition running intensities varied by both position and moving-average duration. Hookers exhibited the greatest Pmet of all positions, due to high involvement in both attack and defense. Fullbacks also reached high Pmet, possibly due to a greater absolute volume of running. This study provides coaches with match data that can be used for the prescription and monitoring of specific training drills.
Helicobacter pylori DNA in recurrent aphthous stomatitis.

BACKGROUND Considering not only the fact that recurrent aphthous stomatitis (RAS) and stomach ulcers are immunologically mediated ulcers associated with Helicobacter pylori, but also the recent evidence that anaemia can be associated with both diseases, and the discovery of H. pylori in the oral mucosa led us to hypothesize that this bacteria may be related to RAS pathogenesis. METHODS Thirty-six consecutive subjects affected by minor and major forms of RAS and 48 healthy volunteers were included in the present study. The nested polymerase chain reaction (PCR) technique was used to detect the presence of H. pylori in the oral lesion, the normal contralateral mucosa of patients affected by RAS and the oral mucosa of control subjects. The chi2- and Fisher's tests were used for statistical analysis. RESULTS No association between RAS lesions and H. pylori was observed. However, 14 out of 36 (38.9%) of the patients with RAS were found to show the presence of H. pylori DNA in the lesion and/or contralateral mucosa. Sixteen out of 48 (33.3%) of the patients without RAS (control subjects) were positive (P > 0.05). CONCLUSION The present study does not give support to the assumption that H. pylori could be involved in RAS development.
Response and Remission After Cognitive and Exposure Therapy for Hypochondriasis

Abstract Cognitive behavioral therapy has demonstrated large effect sizes for the treatment of hypochondriasis. However, response and remission rates, which provide important additional information about clinically significant improvements, have seldom been reported. In the current study, rates of response and remission after cognitive therapy and exposure therapy were evaluated. The study was based on a randomized controlled trial that treated patients with hypochondriasis (N = 75). The primary outcome measure was a clinician-administered structured interview for hypochondriasis. At posttreatment, response was found for 72.0% and remission for 45.3% of the patients. At 12-month follow-up, the response rate was 68.0%, and the remission rate was 54.7%. No significant differences in the frequency of response/remission were found between the cognitive therapy and the exposure therapy groups. Patients' and therapists' perspectives of clinical improvement corresponded with remission rather than response rates. Improvement rates were compared with those of other mental disorders, and implications for the treatment of hypochondriasis were discussed.
Polymethylmethacrylate Coated Alginate Matrix Microcapsules for Controlled Release of Diclofenac Sodium

Polymethylmethacrylate (PMMA) coated microcapsules of diclofenac sodium (DFS) were prepared by a modified wa-ter-in-oil-in-water (W1/O/W2) emulsion solvent evaporation method using sodium alginate (SAL) as a matrix material in the internal aqueous phase (W1). Their performance with respect to controlled release of the drug in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) were evaluated, and compared with non-matrix microcapsules prepared by the conventional W1/O/W2 emulsion solvent evaporation method. Scanning electron micrographs (SEM) revealed that all the microcapsules were discrete and spherical in shape; however, the surface porosity of the matrix microcap-sules appeared to be less than that of the non-matrix microcapsules. In case of non-matrix microcapsules, an increase in the volume of water in W1 phase resulted in decrease in the drug entrapment efficiency (DEE) along with increase in release of the drug in both SGF and SIF. While in case of matrix microcapsules increase in the amount of SAL in W1 phase and concentration of the coating polymer in organic phase led to increase in DEE of the matrix microcapsules and considerable decrease in the drug release in both SGF and SIF. No interaction between the drug and any of the polymers used to prepare microcapsules was evident from Fourier transform infra-red (FTIR) analysis. The matrix microcapsules prepared using higher concentration of SAL and PMMA released the drug following zero order or Case-II transport model. The matrix microcapsules appeared to be suitable for releasing lesser amounts of DFS in SGF and providing extended release in SIF.
The Geo-n localization algorithm

We introduce Geo-n, a highly precise, distancebased, general-purpose localization algorithm for use in cluttered and indoor environments, where the estimated distances between an unlocalized node and anchor nodes may contain large errors due to NLOS signal propagation. Geo-n is very resilient to outliers and to a wide range of geometrical constellations of the nodes. Geo-n uses a two stage filtering technique to obtain the most representative intersection points between every pair of circles induced by anchor coordinates and distance measurements and uses these to estimate the position of unlocalized nodes. If no intersection exists between two circles, Geo-n approximates one to further improve localization accuracy. We compare Geo-n to LLS, NLLS, AML, Min-Max, and ICLA using simulations and real world experiments, and show analysis of the spatial distribution of position errors. Results demonstrate that Geo-n outperforms the other algorithms. Like NLLS, its spatial error distribution is very homogeneous. However, Geo-n is much more robust and achieves lower average position error while retaining reasonable computational complexity.
System pharmacogenomics application in infectious diseases

Abstract The new era in systems pharmacology has revolutionized the human biology. Its applicability, precise treatment, adequate response and safety measures fit into all the paradigm of medical/clinical practice. The importance of mathematical models in understanding the disease pathology and epideomology is now being realized. The advent of high-throughput technologies and the emergence of systems biology have resulted in the creation of systems pharmacogenomics and the focus is now on personalized medicine. However, there are some regulatory issues that need to be addresssed; are we ready for this universal adoption? This article details some of the infectious disease pharmacogenomics to the developments in this area.
Sex ratios in otosclerotic families

Abstract The sex ratio (proportion of males) of offspring of otosclerotics is significantly and substantially below expectation. To account for this and other features of the condition, it has been suggested elsewhere that otosclerosis is subject to autosomal dominant transmission with intrauterine selection against male heterozygotes. To test this hypothesis, a search was made for published data on the sexes of sibs of otosclerotics. These sibs do not have an unusual sex ratio, thus casting doubt on the hypothesis. Accordingly it is suggested here that both the condition and the sex ratios are causally related to levels of steroid hormones.