Miracle-dz/UniFAR-FTUs huggingface dataset:
Microenvironmental influences in chronic lymphocytic leukaemia: the role of antigen stimulation

Several studies suggest that immune‐mediated pathways are important in the pathogenesis of chronic lymphocytic leukaemia (CLL). The in vivo accumulation of leukaemic lymphocytes is facilitated by interactions of CLL cells with other cells and soluble factors that probably occur more often within the microenvironment through classical receptor–ligand interactions. These include CD40L–CD40 and chemokine–chemokine receptor interactions as well as B cell receptor (BCR) engagement by (auto)antigens. Indeed, the categorizations of CLL patients based on immunoglobulin heavy variable (IGHV) gene mutations and structure of the clone’s BCR suggest that CLL patient outcome could be a reflection of ongoing BCR signalling in the context of other co‐signals.
Predictive value of serum interleukin‐8 levels in ovarian cancer patients treated with paclitaxel‐containing regimens

Previous findings showed that paclitaxel induces interleukin-8 (IL-8) transcription and secretion in ovarian cancer cells in vitro. We hypothesized that paclitaxel treatment, which is a standard care for ovarian cancer patients, may increase the secretion of IL-8, resulting in the elevated serum IL-8 levels. In this study, we investigated the relationship between paclitaxel exposure and IL-8 levels of an ovarian and a breast carcinoma cell line in vitro and serums of patients with ovarian carcinoma. Both MDAH 2774 ovarian and MCF-7 breast carcinoma cell lines were sensitive to paclitaxel-mediated cytotoxicity. However, supernatant levels of IL-8 assessed by enzyme-linked immunosorbent assay before and after treatment with different concentrations of paclitaxel were significantly lower in MCF-7 than in MDAH 2774. Serum IL-8 levels were measured in serum samples from patients with ovarian carcinoma before and after paclitaxel-containing treatment regimens. Forty-eight patients were included in the study. The basal level of IL-8 after paclitaxel-containing treatment was found to be significantly higher in the serums of patients who had high tumor burden than in patients who had optimal debulking surgery and low tumor burden. These data strongly suggest that IL-8 may be an important predictive marker for tumor volume as well as sensitivity to paclitaxel.
Stepwise Movement of Preproteins in the Process of Translocation across the Cytoplasmic Membrane of Escherichia coli(*)

Derivatives of proOmpA possessing the second cysteine residue at position +302 and the first one at different positions were constructed at the DNA level. They were oxidized to form disulfide-bridged loops of different sizes at different positions. In the presence of a protonmotive force, proOmpAs possessing a smaller loop could be translocated across the membrane in vitro, whereas ones possessing loops comprising more than 16 amino acid residues were hard to translocate. The sizes of polypeptide chains that had been translocated and had become protease-resistant were determined in both the presence and absence of the protonmotive force. The size was the same for all proOmpAs possessing the first cysteine residue between +244 (proOmpA L59) and +274 (proOmpA L29). When the first cysteine residue was moved further away from the N terminus, a sudden increase in size, of approximately 30 amino acid residues, was observed, the size being the same for proOmpAs possessing the first cysteine residue between +278 (proOmpA L25) and +293 (proOmpA L10). The shift in size between proOmpA L29 and proOmpA L25 was observed with different proteases exhibiting different substrate specificities. Treatment with these proteases resulted in complete digestion of SecA on everted membrane vesicles, whereas Sec proteins integrated into membranes were considerably resistant to the treatment. These results can be best interpreted as that the translocation of preproteins through the secretory machinery takes place in every 30 amino acid residues and that SecA is responsible for the stepwise movement.
Are peripheral and neuraxial blocks with ultrasound guidance more effective and safe in children?

Background and aims: The efficacy and safety of ultrasound guided (USG) pediatric peripheral nerve and neuraxial blocks in children have not been evaluated. In this review, we have looked at the success rate, efficacy and complications with USG peripheral nerve blocks and compared with nerve stimulation or anatomical landmark based techniques in children.
Effects of juniper essential oil on growth performance, some rumen protozoa, rumen fermentation and antioxidant blood enzyme parameters of growing Saanen kids

This study aimed to evaluate the effects of juniper essential oil on the growth performance, rumen fermentation parameters, rumen protozoa population, blood antioxidant enzyme parameters and faecal content in growing Saanen kids. Thirty-six male Saanen kids (36 ± 14 days of age) were used in the study. Each group consisted of 9 kids. The control group (G1) was fed with a diet that consisted of the above concentrated feed and oat hay, whereas the experimental groups consumed the same diet but with the concentrated feed uniformly sprayed with juniper essential oil 0.4 ml/kg (G2), 0.8 ml/kg (G3) or 2 ml/kg (G4). There were no differences (p > 0.05) in live weight, live weight gain or feed consumption between the control and experimental groups. There was a significant improvement (p < 0.05) in feed efficiency in the G3 group. There were no differences in the rumen pH, rumen volatile fatty acid (VFA) profile or faecal pH of the control and experimental groups. The rumen NH3 N values were similar at the middle and end of the experiment, but at the start of the experiment, the rumen NH3 N values differed between the control and experimental groups (p < 0.05). The faecal score value was significantly (p < 0.05) decreased in the experimental groups. The addition of juniper essential oil supplementation to the rations caused significant effects on the kids' antioxidant blood parameters. Although the superoxide dismutase (SOD) activity, total antioxidant capacity (TAC) and catalase values were significantly (p < 0.05) increased in the experimental groups (G2, G3 and G4), especially group G4, the blood glutathione peroxidase (GPX) value significantly decreased in the experimental groups. The results of this study suggest that supplementation of juniper oil is more effective on antioxidant parameters than on performance parameters and may be used as a natural antioxidant product.
Tracking of myelin‐reactive T cells in experimental autoimmune encephalomyelitis (EAE) animals using small particles of iron oxide and MRI

Myelin‐reactive T cells are responsible for initiating the cascade of autoreactive immune responses leading to the development of multiple sclerosis. For better insights into the disease mechanism, it is of major importance to have knowledge on the sites at which these cells are active during disease progression. Herein, we investigated the feasibility of tracking myelin‐reactive T cells, upon labelled with SPIO particles, in the central nervous system (CNS) of experimental autoimmune encephalomyelitis (EAE) animals by MRI. First, we determined the optimal labelling condition leading to a high particle uptake and minimal SPIO–Poly‐l‐lysine (PLL) aggregate formation using Prussian blue staining and inductively coupled plasma spectroscopy measurements. Results from labelling of myelin reactive T cells with low concentrations of SPIO particles (i.e. 25 µg/ml) combined with different concentrations of PLL (0–1.5 µg/ml) showed that increasing amounts of PLL led to augmented levels of free remnant SPIO‐PLL aggregates. In contrast, a low PLL concentration (i.e. 0.5 µg/ml) combined with high concentrations of SPIO (i.e. 400 µg Fe/ml) led to a high labelling efficiency with minimal amounts of aggregates. Second, the labelled myelin‐reactive T cells were transferred to control rats to induce EAE. At the occurrence of hindlimb paralysis, the SPIO labelled myelin‐reactive T cells were detected in the sacral part of the spinal cord and shown to be highly confined to this region. However, upon transfer in already primed rats, T cells were more widely distributed in the CNS and shown present in the spinal cord as well as in the brain. Our study demonstrates the feasibility of tracking SPIO labelled myelin‐reactive T cells in the spinal cord as well as the brain of EAE rats upon systemic administration. Furthermore, we provide data on the optimal labelling conditions for T cells leading to a high particle uptake and minimal aggregate formation. Copyright © 2010 John Wiley & Sons, Ltd.
Frequencies of Six (Five Novel) STR Markers Linked to TUSC3 (MRT7) or NSUN2 (MRT5) Genes Used for Homozygosity Mapping of Recessive Intellectual Disability.

BACKGROUND Non-syndromic autosomal recessive intellectual disability (NS-ARID) is an extremely heterogeneous genetic disorder. Therefore, to investigate these genes, more research is required. One approach to investigate the NS-ARID loci is homozygosity mapping which requires appropriate STR markers within or flanking the gene/s of interest. In this research, we aimed to find novel STRs for two common NS-ARID genes (TUSC3 and NSUN2) and, in addition, to identify allele frequencies of those STR markers. METHODS The study group included 119 unrelated healthy individuals. STR markers were investigated using the UCSC genome browser web site and SERV software. Genotyping was determined by multiplex PCR. Data were evaluated using Gene Mapper software. Allele frequencies and observed heterozygosity rates were calculated using PowerStatV12. Deviation from Hardy-Weinberg equilibrium and expected heterozygosity were assessed using the DNAView software. RESULTS In total, 56 alleles were detected. According to our research, D8TUSC3SU8.3 and D5NSUN2SU0.5 were the most informative STR markers in MRT7 and MRT5 loci, respectively and showed a high percentage of heterozygosity in Iranian population. The observed range of allele frequencies was from 3.4% to 32.4% and 0.8% to 18.9% for MRT5 and MRT7 loci, respectively. Further, we have evaluated other statistical surveys of these STR markers and discovered that all of the six listed STRs were informative and five meet the Hardy-Weinberg equilibrium for the tester group. CONCLUSIONS Finding novel STRs, with high allele heterozygosity, is one of the most significant current finding in the present study for the two common NSARID genes. The recognized heterozygosity of these markers make MRT flanking STR markers very efficient to be used in diagnostic medical genetics labs or homozygosity mapping on NS-ARID.
Insights in public health: perspectives on pain in the low back and neck: global burden, epidemiology, and management.

Low back pain (LBP) is a major public health problem worldwide. All age groups are affected, including children and adolescents,1 with 1%–2% of adults in the United States being disabled as a result.2 Back and neck pain (NP) are two of the most common reasons for visits to primary care physicians and chiropractors in the United States and cause considerable disability and financial burden.3 Although people don't die from low back or neck pain, the morbidity toll is enormous from both personal and societal perspectives. Both are reported by more patients and have a higher impact in the workforce, as well as financially, than any other musculoskeletal disorder and most other clinical conditions. 4 In 2005 only heart disease and stroke had substantially higher medical expenditures than spine disorders in the United States.5 The large and rising spine-related health-care expenditures over the last decade do not seem to be associated with improved self-assessed health status, or improvement in functional ability, work limitations or social functioning.5 In this article, we take a step back to look at this toll, and look ahead to see where we, as individuals and as a society, should go in order to reduce the burden of back and neck pain.
Multiple Vehicles Collaborative Data Download Protocol via Network Coding

Data services (i.e., office on wheels and entertainment on wheels) are expected to become a primary driver in the development of future connected cars. However, the sparse spatial distribution of roadside stationary units (RSUs) along the road renders the downloading of data via roadside-to-vehicle (R2V) connections intermittent. As a result, data services, particularly for those dealing with large volumes of data, may not achieve a good quality of service. In this paper, we propose a multiple-vehicle protocol for collaborative data downloading by using network coding (NC). When multiple vehicles that are approaching each other have a common interest in certain data, they can collaboratively download the data from an RSU to significantly reduce their download time. We first derive the probability mass functions (PMFs) of the downloading completion time for three downloading methods, i.e., random, feedback, and NC based, to quantify the benefits of the proposed scheme. Our analytical derivations show that, compared with random- and feedback-based methods, the proposed approach can significantly improve the download time and will remove any need for uplink communications from vehicles to the infrastructure. Moreover, we discuss the cooperative group formation issues and vehicle-to-vehicle (V2V) data sharing in detail. Simulation results show that the proposed protocol has a more robust performance compared with random- and feedback-based schemes. In addition, we constitute simulations to show that the proposed scheme can apply to the scenarios with dynamic network topology and imperfect V2V data sharing.
Host-specific Wolbachia strains in widespread populations of Phlebotomus perniciosus and P. papatasi (Diptera: Psychodidae), and prospects for driving genes into these vectors of Leishmania

Abstract A single strain of Wolbachia (α-proteobacteria, Rickettsiales) was found in widespread geographical populations of each of two Phlebotomus species, within which there was no indication of ‘infectious speciation’. The two strains were identified by sequencing a fragment of wsp (a major surface protein gene), amplified by polymerase chain reaction from DNA extracted from the body parts of individual sandflies. Infection rates were high in the males and females of both sandflies, but they were lower for the B-group wPrn strain of Wolbachia in Phlebotomus perniciosus Newstead (60.3% overall) than for the A-group wPap strain in P. papatasi (Scopoli) (81.7%). Infections were frequent in the thorax, where Leishmania develops infective forms, as well as in the abdomen, where Wolbachia must infect the reproductive tissues to ensure its vertical transmission. These findings were related to knowledge of the population biology of Wolbachia in other insects, leading to the conclusion that this endosymbiont could be useful for driving transgenes through wild populations of both sandflies. This will require characterizing the cytoplasmic incompatibility phenotypes of Wolbachia–sandfly combinations, as well as estimating for them the incidence of paternal transmission and the fidelity of maternal transmission. Paternal transmission is one explanation for finding a single Wolbachia strain associated with all mitochondrial haplotypes and lineages of each sandfly species. However, this distribution pattern could also result from multiple horizontal transmissions or the failure of wsp to provide strain markers.
Dietary Factors Modulate Iron Uptake in Caco-2 Cells from an Iron Ingot Used as a Home Fortificant to Prevent Iron Deficiency

Iron deficiency is a major public health concern and nutritional approaches are required to reduce its prevalence. The aim of this study was to examine the iron bioavailability of a novel home fortificant, the “Lucky Iron Fish™” (LIF) (www.luckyironfish.com/shop, Guelph, Canada) and the impact of dietary factors and a food matrix on iron uptake from LIF in Caco-2 cells. LIF released a substantial quantity of iron (about 1.2 mM) at pH 2 but this iron was only slightly soluble at pH 7 and not taken up by cells. The addition of ascorbic acid (AA) maintained the solubility of iron released from LIF (LIF-iron) at pH 7 and facilitated iron uptake by the cells in a concentration-dependent manner. In vitro digestion of LIF-iron in the presence of peas increased iron uptake 10-fold. However, the addition of tannic acid to the digestion reduced the cellular iron uptake 7.5-fold. Additionally, LIF-iron induced an overproduction of reactive oxygen species (ROS), similar to ferrous sulfate, but this effect was counteracted by the addition of AA. Overall, our data illustrate the major influence of dietary factors on iron solubility and bioavailability from LIF, and demonstrate that the addition of AA enhances iron uptake and reduces ROS in the intestinal lumen.
Influence of urinary sodium on calcium excretion in normal individuals

The twenty‐four hour urinary excretion of calcium and sodium was measured in 38 normal volunteers after a week on a diet containing 400 mg of calcium per day. There was a significant correlation (P < 0.001) between calcium and sodium excretion. The normal range of calcium excretion as a function of sodium excretion has been determined. This approach sharpens the definition of hypercalciuria by taking into account the influence of dietary sodium intake. It also removes the necessity of regulating dietary sodium as well as calcium intake before measuring calcium excretion in patients who form recurrent renal stones.
Expression and Distribution of Tumor Necrosis Factor Alpha in Human Lumbar Intervertebral Discs: A Study in Surgical Specimen and Autopsy Controls

Study Design. Immunohistochemical study of tumor necrosis factor &agr; expression in autopsy and surgical specimens of human lumbar intervertebral discs. Objectives. To investigate the occurrence and localization of tumor necrosis factor &agr; in intervertebral disc tissue and to correlate its expression with age and the degree of disc degeneration. Summary of Background Data. The source and origin of discogenic pain are as yet unknown. Recently identified changes of the cellular phenotype during senescence and disc pathology with partly phagocytic properties suggest an ‘inflammatory’ phenotype. Tumor necrosis factor &agr; is one of the most potent proinflammatory cytokines possibly modulating cellular phenotypes. It may also promote pain induction. Very little is known about the occurrence and localization of tumor necrosis factor &agr; in intervertebral disc tissue of defined age and degree of histologic tissue degeneration. Methods. The study population comprised 20 cross-sections of the complete motion segment of human lumbar vertebrae (age range 0–86 years) obtained at autopsy and 28 surgical disc specimens of individuals undergoing lumbar surgical interventions for various reasons. The temporospatial distribution of tumor necrosis factor &agr;-positive cells using a polyclonal antibody was correlated with a histologic degeneration score. Results. Tumor necrosis factor &agr; is expressed substantially in (nonsymptomatic) autopsy material in fetal/infantile and older adult nucleus pulposus, whereas it is sparsely expressed in adolescent and young adult nucleus pulposus. In the anulus fibrosus, tumor necrosis factor &agr; is not found in young adults (<25 years), but then significantly increases in extent. In contrast, symptomatic nucleus pulposus and anulus fibrosus (surgical material) contain substantially more tumor necrosis factor &agr;-positive cells. A significant positive correlation of tumor necrosis factor &agr; expression and disc degeneration (histologic degeneration score) was found for the anulus fibrosus in both sample groups. In the surgical material, an additional significant positive correlation was identified for nuclear tumor necrosis factor &agr;, disc degeneration, and age. Conclusions. Tumor necrosis factor &agr; is substantially expressed in disc material of symptomatic patients (surgical specimens) in comparison to samples taken at autopsy. The expression of tumor necrosis factor &agr; in early fetal/infantile nucleus pulposus may indicate ‘physiologic’ tissue disarrangement with closure of the blood vessel canals. The expression of tumor necrosis factor &agr; in adult discs, in contrast, is statistically associated with disc degeneration. Its occurrence in adults of more advanced age suggests that tumor necrosis factor &agr; is not involved in the initiation of disc degeneration, but may be associated with further promotion of degenerative disarrangement and pain induction.
Cardiovagal Autonomic Function in HIV-Infected Patients with Unsuppressed HIV Viremia

Abstract Purpose: HIV infection has been implicated in dysregulationofthe autonomic nervous system. Method: Cross-sectional study exam ining the relationship between the presence of persistent detectable HIV viral load with autonomic function, measured by heart rate variability (HRV). Non-virologic suppression (NVS) was defined as having a detectable viral load for at least 3 months prior to autonomic function testing. HRV was measured during the following 4 maneuvers: resting and paced respirations and sustained handgrip and tilt. Inferences on parasympathetic and sympathetic modulations were determined by analyzing time and frequency domains of HRV. Results: 57 participants were enrolled in 3 groups: 22 were HIV-infected participants with HIVvirologic suppression (VS; undetectable HIV viral load), 9 were HIV-infected participants who had NVS, and 26 were HIV seronegative controls. There were lower time domain parameters in the HIV-infected group as a whole compared to controls. There were no significant differences in time domain parameters among HIV-infected participants. There were no differences in frequency domain parameters during any of the maneuvers between controls and all HIV-infected participants, nor between the NVS and VS groups. Conclusion: There were differences in autonomic function between HIV-infected individuals and HIV seronegative controls, but not between the NVS and VS groups.
NADPH oxidases as regulators of tumor angiogenesis: current and emerging concepts.

SIGNIFICANCE Reactive oxygen species (ROS) such as superoxide, hydrogen peroxide, and peroxynitrite are generated ubiquitously by all mammalian cells and have been understood for many decades as inflicting cell damage and as causing cancer by oxidation and nitration of macromolecules, including DNA, RNA, proteins, and lipids. RECENT ADVANCES A current concept suggests that ROS can also promote cell signaling pathways triggered by growth factors and transcription factors that ultimately regulate cell proliferation, differentiation, and apoptosis, all of which are important hallmarks of tumor cell proliferation and angiogenesis. Moreover, an emerging concept indicates that ROS regulate the functions of immune cells that infiltrate the tumor environment and stimulate angiogenesis, such as macrophages and specific regulatory T cells. CRITICAL ISSUES In this article, we highlight that the NADPH oxidase family of ROS-generating enzymes are the key sources of ROS and, thus, play an important role in redox signaling within tumor, endothelial, and immune cells thereby promoting tumor angiogenesis. FUTURE DIRECTIONS Knowledge of these intricate ROS signaling pathways and identification of the culprit NADPH oxidases is likely to reveal novel therapeutic opportunities to prevent angiogenesis that occurs during cancer and which is responsible for the revascularization after current antiangiogenic treatment.