Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanism of resistance to cisplatin in a human ovarian‐carcinoma cell line selected for resistance to doxorubicin: Possible role of p53

A possible novel mechanism of cross‐resistance to cisplatin (CDDP) in the doxorubicin‐resistant ovarian‐cancer cell line A2780‐DX3, which displays atypical multidrug resistance, is presented. A2780‐DX3 is found to be more resistant than the parental line A2780 in terms of CDDP‐induced cytotoxicity and apoptosis. Resistance is not related to the amount of cross‐links. Topoisomerase‐II (topII) protein levels were similar in both cell lines, with lower cleavage activity in A2780‐DX3 cells. The parental and the doxorubicin‐resistant cells expressed the same level of c‐erb2, which could be implicated in CDDP resistance. bcl2 was almost undetectable in both cell lines. At the same time, we found strong induction of p53, waf‐1 and bax protein levels after CDDP treatment in the A2780, but not in the A2780‐DX3, cell line. Treatment of both cell lines with mitomycin C (MMC), which acts with a mechanism different from CDDP, caused equal accumulation of p53 and induction of bax. We found that A2780‐DX3 cells exhibit altered cellular localization of p53 protein in comparison with A2780. A significant proportion of p53 in A2780‐DX3 cells was found in the cytoplasmic compartment, and CDDP treatment induced a functional p53 protein in the nucleus of A2780 much more strongly than in A2780‐DX3, which coincides with an increase of transcriptional activity of p53 in treated A2780 cells. We propose that the cross‐resistance to CDDP in the A2780‐DX3 cell line may be due to inactivation of a CDDP‐dependent p53‐accumulation pathway. Int. J. Cancer 72:155–159, 1997. © 1997 Wiley‐Liss Inc.
Performance Analysis of Variable-Power Adaptive Modulation With Outdated Feedback for Space–Time Coded MIMO Systems

The performance analysis of a space-time coded multiple-input-multiple-output (MIMO) system that employs different variable-power adaptive-modulation (VP-AM) strategies with outdated channel-state information (CSI) over Rayleigh fading channels is presented. The optimal design of VP-AM with power control (PC) in time (VP-AM-TIME) is first developed. The optimum switching thresholds of VP-AM-TIME for attaining maximum spectrum efficiency (SE) subject to a target bit error rate (BER) and an average power constraint are derived. A closed-form expression of the optimal temporal PC in terms of the Lambert function is obtained. A suboptimal VP-AM-TIME is also developed to further simplify the algorithm. The existence and uniqueness of the Lagrange multiplier that was used in the constrained optimization for the optimal and suboptimal VP-AM-TIME are investigated. By using the switching thresholds, we obtain closed-form expressions of SE and average BER. Then, a VP-AM scheme with joint spatial-temporal power control (VP-AM-JOINT) is developed. The joint spatial-temporal PC problem can be solved by transforming it into an inner-outer optimization problem. Theoretical analysis and simulation results show that the proposed optimal VP-AM-TIME can obtain the same performance as the existing optimal VP-AM-TIME but with much lower computational complexity, and the new suboptimal VP-AM-TIME outperforms the existing suboptimal scheme and obtains a performance closer to the optimal scheme. The results also show that the new VP-AM-JOINT scheme is always superior to the optimal VP-AM-TIME and provides considerable gains in SE over a wide range of feedback delays, although the two schemes have almost the same performance when the feedback delay becomes large.
Ontological approach for safe and effective polypharmacy prescription

The intake of multiple medications in patients with various medical conditions challenges the delivery of medical care. Initial empirical studies and pilot implementations seem to indicate that generic safe and effective multi-drug prescription principles could be defined and reused to reduce adverse drug events and to support compliance with medical guidelines and drug formularies. Given that ontologies are known to provide well-principled, sharable, setting-independent and machine-interpretable declarative specification frameworks for modeling and reasoning on biomedical problems, we explore here their use in the context of multi-drug prescription. We propose an ontology for modeling drug-related knowledge and a repository of safe and effective generic prescription principles. To test the usability and the level of granularity of the developed ontology-based specification models and heuristic we implemented a tool that computes the complexity of multi-drug treatments, and a decision aid to check the safeness and effectiveness of prescribed multi-drug treatments.
Nerve fiber conduction velocity distributions: Studies of normal and diabetic human nerves

We have assessed the clinical applicability of a previously ENscribed new method for analyzing the distribution of conduction velocities (DCV) in peripheral nerve. Surface‐recorded median sensorimotor compound action potentials (CAPs) were found to contain contributions from classes of fibers conducting between 25 and 80 m/sec in the elbow‐to‐axilla segment. Test‐retest correlation coefficients ranged from 0.91 to 0.98. Increasing stimulus intensity recruited additional fiber activity into the CAP with relative preferential activation of faster‐conducting fibers at lower stimulus levels. Changes in limb temperatur altered the conduction velocity of all fiber classes 4% per ENgree Celsius. A comparison of fiber diameter distribution and DCVs in a normal sural nerve gave a correlation of 0.70 over the range of 7 to 12 μ. Diabetic patients with minimal or no clinical polyneuropathy showed varying ENgrees of DCV shift toward the slower conduction velocities, sometimes even in the face of normal conventional nerve conduction studies. These findings indicate that the DCV may be consiENred the electrophysiological counterpart—not equivalent—of the fiber diameter distribution, with the capacity to distinguish subtle differences in conduction properties of normal and diseased human nerves.
Phosducin‐like proteins in Dictyostelium discoideum: implications for the phosducin family of proteins

Retinal phosducin is known to sequester transducin Gβγ, thereby modulating transducin activity. Phos ducin is a member of a family of phosducin‐like proteins (PhLP) found in eukaryotes. Phylogeny of 33 phosducin‐like proteins from metazoa, plants and lower eukaryotes identified three distinct groups named phosducin‐I–III. We discovered three phlp genes in Dictyostelium, each encoding a phosducin‐like protein of a different group. Disruption of the phlp1 gene strongly impaired G‐protein signalling, apparently due to mislocalization of Gβγ in phlp1‐null cells. GFP‐Gβ and GFP‐Gγ are membrane associated in wild‐type cells, but cytosolic in phlp1‐null cells. Phlp2 disruption is lethal due to a synchronous collapse of the cells after 16–17 cell divisions. Phlp3 disruptants show no abnormal phenotype. These results establish a role for phosducin‐like proteins in facilitating folding, localization or function of proteins, in addition to modulating G‐protein signalling.
Impact of sarcopenia on long-term mortality following endovascular aneurysm repair

Sarcopenia, also known as a reduction of skeletal muscle mass, is a patient-specific risk factor for vascular and cancer patients. However, there are no data on abdominal aortic aneurysm (AAA) patients treated with endovascular aneurysm repair (EVAR) who have sarcopenia. To determine the impact of sarcopenia on mortality following EVAR, we retrospectively reviewed 200 patients treated with EVAR by estimating muscle mass on abdominal computed tomography (CT) scans. Mortality was analyzed according to its presence (n=25) or absence (n=175). Sarcopenia was more common in women than men (32.0% vs 9.7%; p=0.005). Patients with sarcopenia had an increased risk of mortality compared to those without (76% vs 48%; p=0.016). Of note, the overall mortality rate was 51% with a median follow up of 8.4 years (interquartile range, 5.3–11.7). In conclusion, the presence of sarcopenia on a CT scan is an important predictor of long-term mortality in patients treated for AAA with EVAR. Pending further study, these data suggest that sarcopenia may aid in pre-procedural long-term survival assessment of patients undergoing EVAR.
[Cell ploidy: predictive factor of locally advanced prostate cancer].

OBJECTIVE This study was designed to demonstrate that the study of cell ploidy on biopsies of clinically localized prostate cancers can contribute to the diagnosis of a tumour extending beyond the prostatic capsule and can complete imaging for local staging. METHODS Analysis of the histological results of 140 patients operated for clinically localized prostate cancer distinguished two groups of patients in whom the initial tumour was Gleason score 6 or 7. The first group was composed of 33 patients whose tumour was classified as pT3 and the second group was composed of 24 patients whose tumour was classified as pT2. The cell ploidy study was performed on biopsies and operative specimens in the two groups. RESULTS In the pT3N0M0 group, 72% of tumours presented an aneuploid contingent versus 16% of tumours of the pT2N0M0 group. A strong correlation was demonstrated between cell ploidy and tumour stage (p = 0.0002) and a highly significant correlation was observed between tumour stage and the presence of a tumour contingent with ploidy greater than 5C (p = 0.0009). CONCLUSION The presence of an aneuploid contingent on biopsies of clinically localized prostate cancer significantly increases the risk of a more advanced tumour. This technique could therefore constitute a simple complementary tool in the staging of prostate cancer in combination with transrectal MRI, but this needs to be confirmed by other studies.
Prenatal tobacco smoke and postnatal secondhand smoke exposure and child neurodevelopment

Purpose To review the recent scientific literature examining the association of prenatal tobacco and postnatal secondhand smoke exposure and child neurodevelopment. Recent findings Low birth weight and decreased in-utero brain growth are two of multiple potential etiologic pathways proposed as mediating the effects of prenatal tobacco smoke exposure on child neurodevelopment. These negative effects of prenatal exposure have been consistently demonstrated in animal models, and in humans have been found as early as the newborn period. The literature on both prenatal and postnatal exposure is remarkably consistent in showing associations with increased rates of behavior problems, including irritability, oppositional defiant behavior, conduct disorders and attention deficit hyperactivity disorder. A more rudimentary literature also suggests deficits in intelligence quotient. Recent studies have focused on elucidating the complex interaction among tobacco exposure, genetics and environmental factors. Questions still remain about the relative roles of prenatal vs. postnatal exposure and the potential role of genetic and social confounders, limiting the ability to infer a causal nature to these associations at this time. The consistency of findings across studies is, however, highly suggestive of a causal relationship between environmental tobacco exposure and adverse behavioral and cognitive outcomes in children. Summary Prenatal tobacco and postnatal secondhand smoke exposure is consistently associated with problems in multiple domains of children's neurodevelopment and behavior.
Prevalence of the Chloroflexi-Related SAR202 Bacterioplankton Cluster throughout the Mesopelagic Zone and Deep Ocean

ABSTRACT Since their initial discovery in samples from the north Atlantic Ocean, 16S rRNA genes related to the environmental gene clone cluster known as SAR202 have been recovered from pelagic freshwater, marine sediment, soil, and deep subsurface terrestrial environments. Together, these clones form a major, monophyletic subgroup of the phylum Chloroflexi. While members of this diverse group are consistently identified in the marine environment, there are currently no cultured representatives, and very little is known about their distribution or abundance in the world's oceans. In this study, published and newly identified SAR202-related 16S rRNA gene sequences were used to further resolve the phylogeny of this cluster and to design taxon-specific oligonucleotide probes for fluorescence in situ hybridization. Direct cell counts from the Bermuda Atlantic time series study site in the north Atlantic Ocean, the Hawaii ocean time series site in the central Pacific Ocean, and along the Newport hydroline in eastern Pacific coastal waters showed that SAR202 cluster cells were most abundant below the deep chlorophyll maximum and that they persisted to 3,600 m in the Atlantic Ocean and to 4,000 m in the Pacific Ocean, the deepest samples used in this study. On average, members of the SAR202 group accounted for 10.2% (±5.7%) of all DNA-containing bacterioplankton between 500 and 4,000 m.
Analysis of Hypomorphic KitlSl Mutants Suggests Different Requirements for KITL in Proliferation and Migration of Mouse Primordial Germ Cells1

Abstract Germ cell development in mice is initiated when a small number of primordial germ cells (PGCs) are set aside from somatic cells during gastrulation. In the subsequent 4 to 5 days, PGCs enter the hindgut, undergo a directed migration away from the hindgut into the developing gonads, and undergo a massive increase in cell number. It is well established that Kit ligand (KITL, also known as stem cell factor and mast cell growth factor) is required for the survival and proliferation of PGCs. However, there is little information on a direct role for KITL in PGC migration. By comparing the effects of multiple Kitl mutations, including two N-ethyl-N-nitrosourea-induced hypomorphic mutations, we were able to distinguish stages of PGC development that are preferentially affected by certain mutations. We provide evidence that the requirements for KITL in proliferation are different in PGCs before and after they start migrating, and different levels of KITL function are required to support PGC proliferation and migration. This study illustrates the usefulness of an allelic series of mutations to dissect developmental processes and suggests that these mutants may be useful for further studies of molecular mechanisms of KITL functions in gametogenesis.
The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid arthritis.

OBJECTIVE The ubiquitously expressed intracellular protein formerly designated p68 has been identified as autoantigen at both the antibody and the T cell level in rheumatoid arthritis (RA). METHODS We used 2 independent approaches, Edman degradation and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, to characterize p68, and we compared its features with those of the endoplasmic reticulum stress protein BiP. RESULTS In synovial sections from RA patients, BiP was highly overexpressed as compared with control sections. Under in vitro stress conditions, BiP was found to translocate to the nucleus and the cell surface. BiP-specific autoantibodies were present in 63% of 400 RA patients, in 7% of 200 patients with other rheumatic diseases, and in none of the healthy subjects. Thus, BiP-specific autoantibodies represent a new diagnostic marker in RA. Furthermore, we found that BiP-specific T cell reactivity was altered in RA. In healthy individuals and patients with other rheumatic diseases, BiP-reactive T cells were undetectable. In RA, overt T cell reactivity to BiP was observed or could be induced by specifically blocking antigen presentation to potentially regulatory T cells. CONCLUSION Since overexpression of BiP has been shown to decrease the sensitivity of cells to killing by cytotoxic T cells, BiP overexpression and BiP-specific autoimmunity may be involved in the pathogenesis of RA.
Dermatan Sulfate Binds and Potentiates Activity of Keratinocyte Growth Factor (FGF-7)*

FGF-7 is induced after injury and induces the proliferation of keratinocytes. Like most members of the FGF family, the activity of FGF-7 is strongly influenced by binding to heparin, but this glycosaminoglycan is absent on keratinocyte cell surfaces and minimally present in the wound environment. In this investigation we compared the relative activity of heparan sulfate and chondroitin sulfate B (dermatan sulfate), glycosaminoglycans that are present in wounds. A lymphoid cell line (BaF/KGFR) containing the FGF-7 receptor (FGFR2 IIIb) was treated with FGF-7 and with various glycosaminoglycans. FGF-7 did not support cell proliferation in the absence of glycosaminoglycan or with addition of heparan sulfate or chondroitin sulfate A/C but did stimulate BaF/KGFR division in the presence of dermatan sulfate or highly sulfated low molecular weight fractions of dermatan. Dermatan sulfate also enabled FGF-7-dependent phosphorylation of mitogen-activated protein kinase and promoted binding of radiolabeled FGF-7 to FGFR2 IIIb. In addition, dermatan sulfate and FGF-7 stimulated growth of normal keratinocytes in culture. Thus, dermatan sulfate, the predominant glycosaminoglycan in skin, is the principle cofactor for FGF-7.
Neurotoxic effects of apolipoprotein E4 are mediated via dysregulation of calcium homeostasis

The association of the E4 allele of apolipoprotein E (apoE4) as a genetic risk factor for Alzheimer's disease (AD) has been well established. Although recent studies in neuronal cell lines and transgenic mice have shown that apoE4 promotes neurodegeneration, the mechanisms through which apoE4 impairs neuronal viability are not completely understood. In this context, the main objective of the present study was to determine whether the neurotoxic effects of apoE4 are mediated by an alteration in calcium homeostasis. For this purpose, effects of recombinant apoE3 and apoE4 on cell viability and intracellular calcium levels were analyzed in a murine hippocampal cell line (HT22) and in primary rat cortical neurons, in the presence or absence of calcium inhibitors. Under basal conditions, apoE4‐treated cells displayed increased levels of cytosolic calcium associated with cell death in a dose‐dependent manner. Furthermore, apoE4 treatment potentiated the rise in cytosolic calcium and cell death following the administration of a calcium ionophore. The effects of apoE4 on cell viability and calcium homeostasis were inhibited by calcium chelators or by blocking calcium channels, but not by inhibitors of intracellular calcium reserves. Taken together, these results indicate that the neurotoxic effects of apoE4 are dependent on extracellular calcium influx via calcium channels. © 2002 Wiley‐Liss, Inc.
A randomized clinical trial on the effectiveness of a symbiotic product to decolonize patients harboring multidrug-resistant Gram-negative bacilli.

INTRODUCTION: We aimed to evaluate the effectiveness of a symbiotic product to decolonize the intestinal tract of patients harboring multidrug-resistant (MDR) Gram-negative bacilli and to prevent nosocomial infections. METHODS: This was a randomized, double blind, placebo-controlled clinical trial, conducted in a tertiary-care university hospital. All adult hospitalized patients with a positive clinical culture and a positive rectal swab for any MDR Gram-negative bacilli were potentially eligible. Exclusion criteria were pregnancy, immunosuppression, and bowel obstruction/perforation. The intervention consisted of administering a symbiotic product (Lactobacillus bulgaricus, Lactobacillus rhamnosus, and fructo-oligosaccharides) twice a day for seven days via the oral/enteral route. RESULTS: Between August 1, 2012 and December 22, 2013, 116 of 275 eligible patients were allocated to treatment (n=57) and placebo (n=59). Overall, 101 patients received at least four doses of the study products and were included in the modified intention-to-treat analysis. The primary study outcome, a negative rectal swab for MDR Gram-negative bacilli after treatment, was identified in 16.7% (8/48) and 20.7% (11/53) of patients in the experimental and placebo group, respectively (p=0.60). The secondary outcome, the combined incidence of nosocomial respiratory and urinary tract infections, was 37.5% (18/48) in the experimental group versus 22.6% (12/53) in the control group (adjusted odds ratio: 1.95, 95% confidence interval: 0.69-5.50, p=0.21). Length of stay after the beginning of the intervention, incidence of adverse events, and in-hospital mortality rates were similar in both study groups. CONCLUSIONS: Under the present study conditions, symbiotic administration was not effective for decolonizing hospitalized patients harboring MDR Gram-negative bacilli.
Major histocompatibility complex class II polymorphisms in forest musk deer (Moschus berezovskii) and their probable association with purulent disease

Genes of the major histocompatibility complex (MHC) family are crucial in immune responses because they present pathogenic peptides to T cells. In this study, we analysed the genetic variation in forest musk deer (Moschus berezovskii) MHC II genes and its potential association with musk deer purulent disease. In total, 53 purulent disease‐susceptible and 46 purulent disease‐resistant individuals were selected for MHC II exon 2 fragment analysis. Among them, 16 DQ alleles and four additional DR alleles were identified, with DQ exon 2 fragments displaying a low level of polymorphism. The nonsynonymous substitutions exceeded the synonymous substitutions in the peptide‐binding sites of DQA2, DQB1 and DQB2. Then, 28 MHC II alleles were used to analyse the distribution patterns of purulent disease between the susceptible and resistant groups. Among them, three alleles (DQA1*01, DQA1*02 and DQA2*04) were found to be resistant, and five alleles (DRB3*07, DQA1*03, DQA1*04, DQA2*05 and DQA2*06) were found to increase susceptibility. Additionally, three haplotypes were found to be putatively associated with musk deer purulent disease. However, these three haplotypes were only found in the resistant or susceptible group, and their frequencies were low. The results from our study support a contributory role of MHC II polymorphisms in the development of purulent disease in forest musk deer.
Effect of Whole-Body Vibration on Muscle Strength and Balance in Diplegic Cerebral Palsy: A Randomized Controlled Trial

Objective The purpose of this study was to investigate the effects of whole-body vibration training on muscle strength and balance in children with diplegic cerebral palsy. Design Fifteen children were assigned to the experimental group, which received whole-body vibration training (9 mins per day, 5 days per week). Another 15 were assigned to the control group, which participated in a traditional physical therapy exercise program for 3 successive months. Baseline and posttreatment assessments were performed using the Biodex isokinetic dynamometer to evaluate the knee extensors peak torque at 60 degrees per second and 90 degrees per second and using the Biodex balance system to evaluate stability index. Results The children in the experimental group showed a significant improvement when compared with those in the control group (P < 0.001). The peak torque at 60 degrees per second and 90 degrees per second after treatment was 28.8 ± 0.45 and 47.5 ± 0.7 N · m and 30.9 ± 0.68 and 54.2 ± 1.7 N · m for the control and the experimental group, respectively. The overall stability index after treatment was 2.75 and 2.2 for the control group and the experimental group, respectively. Conclusions Whole-body vibration training may be a useful tool for improving muscle strength and balance in children with diplegic cerebral palsy.