Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Pre‐ and Post‐Donation Haematological Values in Plateletpheresis Donors

Pre‐ and post‐donation haematological values were measured in 112 donors undergoing plateletpheresis using Haemonetics PCS machines. We found significant differences between pre‐ and post‐donation means for males (M) and females (F) for haemoglobin (M: pre 14.73 g/dl, post 15.25 g/dl; F: pre 13.57 g/dl, post 13.94 g/dl), haematocrit (M: pre 0.418, post 0.431; F: pre 0.389, post 0.4), total protein (M: pre 73.1 g/1, post 66 g/1; F: pre 72.2 g/1, post 63.7 g/1) and albumin (M: pre 42.2 g/1, post 38.5 g/1; F: 41.4 g/1, post 37 g/1). Significant differences were also seen for platelet count (pre 258.6 times 109/1, post 229.2 times 109/1), total white cells (pre 5.3 times 109/1, post 5.55 times 109/1) and neutrophils (pre 3.15 times 109/1, post 3.33 times 109/1), but there were no differences between males and females. This information was of value in establishing post‐donation reference ranges which could be utilised when reviewing the suitability of donors for subsequent donations.
Bayesian Modeling of Complex Metabolic Pathways

Many chronic diseases are the result of a complex sequence of biochemical reactions involving exposures to various environmental agents, metabolized by a number of different genes. Routine epidemiologic analyses of such associations have tended to rely on standard contingency table or logistic regression methods, typically focusing on one variable at a time or pairwise combinations. We consider two statistical alternatives to this approach, one based on Bayesian model averaging, one based on pharmacokinetic modeling of the biochemical pathways. These approaches are illustrated using data from a case-control study of colorectal polyps in relation to tobacco smoking and consumption of well done red meat, both viewed as sources of heterocyclic amines and polycyclic aromatic hydrocarbons. The new analyses are structured in a manner that attempts to take advantage of prior knowledge of the metabolism of these classes of compounds and the various genes that regulate these pathways.
Functional Analysis of the p53 Gene in Apoptosis Induced by Heat Stress or Loss of Stem Cell Factor Signaling in Mouse Male Germ Cells

Abstract Apoptosis plays an important role in controlling germ cell numbers and restricting abnormal cell proliferation during spermatogenesis. The tumor suppressor protein, p53, is highly expressed in the testis, and is known to be involved in apoptosis, which suggests that it is one of the major causes of germ cell loss in the testis. Mice that are c-kit/SCF mutant (Sl/Sld) and cryptorchid show similar testicular phenotypes; they carry undifferentiated spermatogonia and Sertoli cells in their seminiferous tubules. To investigate the role of p53-dependent apoptosis in infertile testes, we transplanted p53-deficient spermatogonia that were labeled with enhanced green fluorescence protein into cryptorchid and Sl/Sld testes. In cryptorchid testes, transplanted p53-deficient spermatogonia differentiated into spermatocytes, but not into haploid spermatids. In contrast, no differentiated germ cells were observed in Sl/Sld mutant testes. These results indicate that the mechanism of germ cell loss in the c-kit/SCF mutant is not dependent on p53, whereas the apoptotic mechanism in the cryptorchid testis is quite different (i.e., although the early stage of differentiation of spermatogonia and the meiotic prophase is dependent on p53-mediated apoptosis, the later stage of spermatids is not).
Is it really the Transplant Renaissance in CML Acceleration Phase

WHO 2016 guidelines regarding chronic myeloid leukemia (CML) do not contain groundbreaking changes [1]. Mainly criteria of acceleration phase (AP) identification were revised. Despite these changes, the guidelines are still not standardized and differ significantly, even when compared to guidelines of European Leukemia Net (ELN) [2], International Bone Marrow Transplant Registry (IBMTR) or M. D. Anderson Cancer Center, to give some examples (Table 1). Compared to previous editions of the WHO classification, new parameters appeared, the presence of which requires identification of acceleration phase. In this case, one should list e.g. chronic leukocytosis (>10 × 109/L), non-responding to treatment, chronic splenomegaly non-responding to treatment, additional clonal chromosomal aberrations (the so-called "major route") in Ph+ cells on diagnosis. New provisional criteria also appeared, related to response to therapy using tyrosine kinase inhibitors (TKI). Among the latter ones the following were distinguished: hematological TKI resistance when used as a first-line or lack of complete hematological response (CHR) during first-line treatment when using TKI; hematological, cytogenetic or molecular resistance during treatment with a subsequent second TKI; presence of two or more mutations within BCR/ABL during TKI therapy. These changes resulted in necessity to diagnose acceleration phase much more frequently, compared to e.g. ELN criteria. This presents importance, particularly for patients already treated with TKI, as it increases the percentage of patients with indications for allogenic hematopoietic stem cell transplantation (allo-HSCT). It contrasts with everyday practice and tendency to marginalize the role of transplanting hematopoietic cells in case of this disease classification unit, in the TKI era. The thesis as such is best illustrated with an example.
Dynamic Lipid-dependent Modulation of Protein Topology by Post-translational Phosphorylation*

Membrane protein topology and folding are governed by structural principles and topogenic signals that are recognized and decoded by the protein insertion and translocation machineries at the time of initial membrane insertion and folding. We previously demonstrated that the lipid environment is also a determinant of initial protein topology, which is dynamically responsive to post-assembly changes in membrane lipid composition. However, the effect on protein topology of post-assembly phosphorylation of amino acids localized within initially cytoplasmically oriented extramembrane domains has never been investigated. Here, we show in a controlled in vitro system that phosphorylation of a membrane protein can trigger a change in topological arrangement. The rate of change occurred on a scale of seconds, comparable with the rates observed upon changes in the protein lipid environment. The rate and extent of topological rearrangement were dependent on the charges of extramembrane domains and the lipid bilayer surface. Using model membranes mimicking the lipid compositions of eukaryotic organelles, we determined that anionic lipids, cholesterol, sphingomyelin, and membrane fluidity play critical roles in these processes. Our results demonstrate how post-translational modifications may influence membrane protein topology in a lipid-dependent manner, both along the organelle trafficking pathway and at their final destination. The results provide further evidence that membrane protein topology is dynamic, integrating for the first time the effect of changes in lipid composition and regulators of cellular processes. The discovery of a new topology regulatory mechanism opens additional avenues for understanding unexplored structure-function relationships and the development of optimized topology prediction tools.
Turbulent Drag Reduction by Biopolymers in Large Scale Pipes

In this work, we describe drag reduction experiments performed in a large diameter pipe (i.d. 100 mm) using a semirigid biopolymer Xanthan Gum (XG). The objective is to build a self-consistent data base which can be used for validation purposes. To aim this, we ran a series of tests measuring friction factor at different XG concentrations (0.01, 0.05, 0.075, 0.1, and 0.2% w/w XG) and at different values of Reynolds number (from 758 to 297,000). For each concentration, we obtain also the rheological characterization of the test fluid. Our data is in excellent agreement with data collected in a different industrial scale test rig. The data is used to validate design equations available from the literature. Our data compare well with data gathered in small scale rigs and scaled up using empirically based design equations and with data collected for pipes having other than round cross section. Our data confirm the validity of a design equation inferred from direct numerical simulation (DNS) which was recently proposed to predict the friction factor. We show that scaling procedures based on this last equation can assist the design of piping systems in which polymer drag reduction can be exploited in a cost effective way. [DOI: 10.1115/1.4028799]
Idiopathic Factor VIII Inhibitor Autoantibody in a Man Presented After Accident

Acquired hemophilia A is a rare but severe autoimmune bleeding disorder caused by autoantibodies against factor VIII activity and is a potentially life-threatening hemorrhagic disorder. The incidence of acquired hemophilia A has been estimated as 1.48 cases per million per year. The overall rate of death from all causes of acquired hemophilia reaches up to 22%. In this article, the authors describe the case of a 55-year-old man who presented with unusual bleeding after an accident and the fluctuation of his hemostatic parameters during 13 months of follow-up. Initially he had 43 Bethesda unit (BU) inhibitor to factor VIII and <1% of factor VIII activity. The patient was given prednisone and azathioprine therapy (30 and 100 mg/day, respectively) for 4 months, but his hemostatic parameters did not improved during this phase. Then, 2 g cyclophosphamide was injected every 2 days, but no remarkable improvement was observed. Nine months later his inhibitor titers were high. The inhibitor and factor VIII concentrations were assessed 11 times during these 13 months, and the mean level of factor VIII inhibitor was 44 BU (with a minimum of 2 BU and a maximum of 103 BU); the minimum and maximum factor VIII concentrations were <1% and 20%, respectively. The patient experienced hemarthroses, severe epistaxis, hematoma, and gastrointestinal bleeding episodes during this phase. His factor VIII concentration spontaneously and gradually improved and increased to 51.5% 8 months after stopping the treatment with undetectable factor VIII inhibitor.
Intramuscular Inoculation of Mice with the Live-Attenuated Recombinant Rabies Virus TriGAS Results in a Transient Infection of the Draining Lymph Nodes and a Robust, Long-Lasting Protective Immune Response against Rabies

ABSTRACT A single intramuscular application of the live but not UV-inactivated recombinant rabies virus (RABV) variant TriGAS in mice induces the robust and sustained production of RABV-neutralizing antibodies that correlate with long-term protection against challenge with an otherwise lethal dose of the wild-type RABV. To obtain insight into the mechanism by which live TriGAS induces long-lasting protective immunity, quantitative PCR (qPCR) analysis of muscle tissue, draining lymph nodes, spleen, spinal cord, and brain at different times after TriGAS inoculation revealed the presence of significant copy numbers of RABV-specific RNA in muscle, lymph node, and to a lesser extent, spleen for several days postinfection. Notably, no significant amounts of RABV RNA were detected in brain or spinal cord at any time after TriGAS inoculation. Differential qPCR analysis revealed that the RABV-specific RNA detected in muscle is predominantly genomic RNA, whereas RABV RNA detected in draining lymph nodes is predominantly mRNA. Comparison of genomic RNA and mRNA obtained from isolated lymph node cells showed the highest mRNA-to-genomic-RNA ratios in B cells and dendritic cells (DCs), suggesting that these cells represent the major cell population that is infected in the lymph node. Since RABV RNA declined to undetectable levels by 14 days postinoculation of TriGAS, we speculate that a transient infection of DCs with TriGAS may be highly immunostimulatory through mechanisms that enhance antigen presentation. Our results support the superior efficacy and safety of TriGAS and advocate for its utility as a vaccine.
Cushing's disease: management outcome in a tertiary care centre.

UNLABELLED Cushing's syndrome (CS) can pose a challenge in diagnosis and management. Successful management of CS needs accurate localization of the site of lesion. Present article narrates experience of a single center dealing with large number of patients with CS and highlights difficulties in diagnosis as well as management of Cushing's disease (CD). METHODS All patients with CD, where histopathological lesion was documented were studied to evaluate yield from different diagnostic tests. Diagnosis was established by standard 2 days low dose dexamethasone suppression test. Localization of the lesion was achieved with high dose dexamethasone suppression (HDDS) and imaging. Inferior petrosal sinus sampling (IPSS) was used whenever diagnosis was not arrived at with the standard tests. RESULTS Out of 100 consecutive patients of CS seen, 69 had CD. HDDS had sensitivity of 70% and specificity of 99% in localizing the lesion. Imaging localized the lesion in 68% of patients. Combination of HDDS and imaging localized the lesion in 90% of patients. IPSS helped to localise the lesion in remaining 10% of patients. Transsphenoidal surgery was carried out in 65/69 patients. Cure rate for microadenoma was 77% and for macroadenoma was 36%. Mortality and morbidity rate was 7% and 7% respectively. 2nd TSS, radiotherapy and bilateral adrenalectomy were the additional modalities used in that order, in patients who were not cured or who had recurrence. CONCLUSION Management of CS is best carried in a center where a team of experienced endocrinologist and neurosurgeon is available.
Anti-leishmanial and Anti-cancer Activities of a Pentacyclic Triterpenoid Isolated from the Leaves of Terminalia arjuna Combretaceae

Purpose: Terminalia arjuna Roxb (Combretaceae) is commonly known as Arjjhan and Arjun in Bengal, India. The anti-leishmanial and anticancer activities of a pentacyclic triterpenoid isolated from its leaves were evaluated. Methods: Dried and crushed leaves of Terminalia arjuna were de-fatted with petroleum ether (40-60°C) and extracted with methanol. The extract was subjected to column chromatography and column fractions were monitored on TLC plates developed in a suitable solvent system. Structures of the isolated pure compounds were elucidated by infra-red spectroscopy, mass spectrometry and nuclear magnetic resonance spectroscopy. One of the compounds was screened for anti-leishmanial activity against promastigotes of Leishmania donovani, and anti-cancer activity on K562 leukaemic cell line. Results: A pentacyclic triterpenoid, characterized as 3s-hydroxyurs-12-en-28-oic acid (together with s- D-glucoside) and designated ursolic acid, was successfully isolated. The structure was determined on the basis of spectroscopic analyses. In vitro anti-leishmanial activity against promastigotes of Leishmania donovani (strain AG 83) and anti-cancer activity on K562 leukaemic cell line were shown by the isolated ursolic acid. Conclusion: The methanol extract of the leaves of Terminalia arjuna led to the isolation of a pentacyclic triterpenoid, ursolic acid. This compound demonstrated in vitro anti-leishmanial and anti-cancer activities Keywords: Terminalia arjuna Roxb, Pentacyclic triterpenoid, Ursolic acid, Spectroscopy, Antileishmanial, Anti-cancer
The Neural Reality of Syntactic Transformations

The functional anatomy of syntactic transformations, a major computational operation invoked in sentence processing, was identified through a functional magnetic resonance imaging investigation. A grammaticality judgment task was used, presented through a novel hidden-blocks design. Subjects listened to transformational and non-transformational sentences in which a host of other complexity generators (number of words, prepositions, embeddings, etc.) were kept constant. A series of analyses revealed that the neural processing of transformations is localizable, evoking a highly lateralized and localized activation in the left inferior frontal gyrus (Broca's region) and bilateral activation in the posterior superior temporal sulcus. The pattern of activation associated with transformational analysis was distinct from the one observed in neighboring regions, and anatomically separable from the effects of verb complexity, which yielded significant activation in the left posterior superior temporal sulcus. Taken together with neuropsychological evidence, these results uncover the neural reality of syntactic transformations.
Evaluation of apoptotic leukocytes in peripheral blood smears.

OBJECTIVES Apoptosis is a phenomenon of physiological cell death in which each step is regulated, similar to the process of mitosis. We observed apoptosis in leukocytes during the review of peripheral blood smears. This study was undertaken to evaluate the morphologic features of apoptotic leukocytes in peripheral blood smears and to ascertain their clinical significance. DESIGN Sixty cases (23 males and 37 females, aged newborn to 92 years) exhibiting apoptotic leukocytes in peripheral blood smears were studied. Medical records for each case were reviewed, and patients were categorized according to their clinical diagnoses. RESULTS Neutrophils were the most common apoptotic leukocytes identified (85%), followed by lymphocytes (18%) and eosinophils (2%). The diagnosis most frequently associated with the presence of apoptotic leukocytes was infection (55%). Apoptosis in lymphocytes was comparatively less common, but when present, the most common associations were diabetes mellitus, glucocorticoid administration, and neoplastic diseases. CONCLUSIONS Our findings suggest that the presence of apoptotic leukocytes in peripheral blood smears may help in the differential diagnosis and may be related to the severity of disease. We recommend further evaluation using additional special techniques for detecting apoptotic leukocytes.
Challenges in exploring the cytochrome P450 system as a source of variation in canine drug pharmacokinetics

Abstract The cytochrome P450 (CYP) superfamily constitutes a collection of enzymes responsible for the metabolism of a wide array of endo- and xenobiotic compounds. Much of the knowledge on substrate specificity and genetic identification of the various CYP isoforms is derived from research in rodents and humans and only limited information has been captured in the dog. Currently, there exist many gaps in our knowledge of canine CYP diversity as a result of the paucity of studies focusing on canine CYPs, canine CYP polymorphisms, and the therapeutic consequences of these genetic variants. Challenges engendered by this lack of information is further amplified by inter- and intraspecies differences in the specificity and affinity of substrates and inhibitors, prohibiting a simple extrapolation of probe substances used in human CYP research. This creates a need to develop and validate canine-specific CYP probes. Failure to understand this potential metabolic and pharmacogenomic diversity can also influence the interpretation of data generated in dogs to support human drug development. It is with these objectives in mind that we provide an overview of what is currently known about canine CYPs with the hope that it will encourage further exploration into this important area of research.
Increasing Children's Responsibility for Diabetes Self-Care: The In Control Study

The purpose of this pilot study was to test the hypothesis that children can learn to become more independent in their own diabetes self management without compromising their metabolic control. Twenty four children (ages 8 to 12 years) with insulin- dependent diabetes mellitus (IDDM) were matched by age and race, then randomly assigned either to a 6-week, self management education program (experimental) or to receive usual care (control). A questionnaire was administered to the parents to determine the frequency with which 35 diabetes management behaviors were performed and the degree to which children assumed responsibility for these behaviors. Glycohemoglobin levels were monitored at baseline and at posttreatment, 12 weeks after baseline. At the posttreatment, children in the experimental group were found to be assuming significantly more responsibility for their diabetes self-care than were children in the control group. No decrease in the frequency with which self-care behaviors were performed was observed, and metabolic control was maintained. The results suggest that a diabetes self-management education program for children ages 8 to 12 years can be effective in facilitating children becoming more responsible for their own diabetes management.
Aromatic amino acids in region 2.3 of Escherichia coli sigma 70 participate collectively in the formation of an RNA polymerase-promoter open complex.

Formation of an initiation-competent RNA polymerase-promoter complex involves DNA melting over a region of about 12 base-pairs, which includes the start site of transcription, thus enabling the template strand to base-pair with the initiating nucleoside triphosphates. By studying the effects of alanine substitutions, we have investigated the role of the aromatic amino residues in the Escherichia coli sigma(70) conserved region 2.3 in promoter strand separation. The resulting mutants were assessed for their activity in vivo in the context of a sigma(70)/sigma(32) hybrid sigma factor that could be targeted to a specific hybrid promoter in the cell. All substitutions lead to an at least twofold reduction in expression of the hybrid promoter-driven reporter gene. The in vitro assay of single substitutions indicated cold sensitivity similar to that previously observed with analogous substitutions in Bacillus subtilis sigma(A). Kinetic assays showed that these substitutions slowed the rate of open complex formation at 37 degrees C as well. RNA polymerase reconstituted with a sigma(70) containing multiple alanine substitutions readily binds to promoter DNA, but then proceeds slowly beyond the first intermediate complex on the pathway to formation of the transcription-competent complex. These data demonstrate that together the aromatic residues in region 2.3 of E. coli sigma(70) ensure that DNA strand separation proceeds efficiently, even if no individual residue may be essential for accomplishment of the process.
A simulation study of self-heating effect on junctionless nanowire transistors

The presence of buried oxide electrically isolating the active silicon region to the substrate in SOI devices leads to better performance than the conventional MOSFETs. However, the thermal resistance associated to this buried oxide causes the self-heating effect which degrades the drain current level. This paper aims at analyzing the self-heating effects influence on junctionless nanowire transistors based on three-dimensional numerical simulations.