Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in Body Composition in Patients with Chronic Obstructive Pulmonary Disease: Do They Influence Patient-Related Outcomes?

Aims: The follow-up of the ECLIPSE study, a prospective longitudinal study to identify and define parameters that predict disease progression over 3 years in chronic obstructive pulmonary disease (COPD), allows the examination of the effect of body composition changes on COPD-related outcomes. Methods: Body composition and health status were established in 2,115 COPD patients, 327 smoking and 239 nonsmoking controls at baseline and 3 years, while mortality was recorded in year 2 and 3 in the COPD patients. Associations between fat free mass index (FFMI) and fat mass index (FMI) changes to deterioration in health status and mortality were determined. Results: Change in FFMI and FMI over 3 years was small and comparable between the groups. Underweight and obese patients had the worst health status. Worsening health status was associated with FFMI decrease in underweight patients and FMI increase in overweight/obese patients. While overweight patients had the lowest mortality, FFMI or FMI decrease was associated with a higher mortality. Conclusion: Changes in body composition over 3 years were small and comparable in COPD patients and control subjects. Nevertheless, muscle mass decline in underweight and fat mass increase in overweight/obese patients is associated with worsening health status. Overweight is associated with decreased mortality, but muscle mass and fat mass decline are detrimental for mortality.
The ITMIG/IASLC Thymic Epithelial Tumors Staging Project: A Proposed Lymph Node Map for Thymic Epithelial Tumors in the Forthcoming 8th Edition of the TNM Classification of Malignant Tumors

Although the presence of nodal disease is prognostic in thymic malignancy, the significance of the extent of nodal disease has yet to be defined. Lymph node dissection has not been routinely performed, and there is currently no node map defined for thymic malignancy. To establish a universal language for reporting as well as characterize the staging of this disease more accurately, an empiric node map is proposed here. This was developed using prior classification systems, series reporting specifics of nodal involvement, anatomical studies of lymphatic drainage, and preexisting node maps of the chest as defined by the International Association for the Study of Lung Cancer and the neck as defined by the American Academy of Otolaryngology—Head and Neck Surgery and the American Society for Head and Neck Surgery. The development of this node map was a joint effort by the International Thymic Malignancy Interest Group and the Thymic Domain of the IASLC Staging and Prognostic Factors Committee. It was reviewed and subsequently approved by the members of ITMIG. This map will be used as an adjunct to define node staging as part of a universal stage classification for thymic malignancy. As more data are gathered using definitions set forth by this node map, a revision may be undertaken in the future.
Molecular analysis of the Pleistocene history of Saxifraga oppositifolia in the Alps

A recent circumpolar survey of chloroplast DNA (cpDNA) haplotypes identified Pleistocene glacial refugia for the Arctic‐Alpine Saxifraga oppositifolia in the Arctic and, potentially, at more southern latitudes. However, evidence for glacial refugia within the ice sheet covering northern Europe during the last glacial period was not detected either with cpDNA or in another study of S. oppositifolia that surveyed random amplified polymorphic DNA (RAPD) variation. If any genotypes survived in such refugia, they must have been swamped by massive postglacial immigration of periglacial genotypes. The present study tested whether it is possible to reconstruct the Pleistocene history of S. oppositifolia in the European Alps using molecular methods. Restriction fragment length polymorphism (RFLP) analysis of cpDNA of S. oppositifolia, partly sampled from potential nunatak areas, detected two common European haplotypes throughout the Alps, while three populations harboured two additional, rare haplotypes. RAPD analysis confirmed the results of former studies on S. oppositifolia; high within, but low among population genetic variation and no particular geographical patterning. Some Alpine populations were not perfectly nested in this common gene pool and contained private RAPD markers, high molecular variance or rare cpDNA haplotypes, indicating that the species could possibly have survived on ice‐free mountain tops (nunataks) in some parts of the Alps during the last glaciation. However, the overall lack of a geographical genetic pattern suggests that there was massive immigration of cpDNA and RAPD genotypes by seed and pollen flow during postglacial times. Thus, the glacial history of S. oppositifolia in the Alps appears to resemble closely that suggested previously for the species in northern Europe.
Validation of the Ottawa Ankle Rules for Acute Foot and Ankle Injuries.

UNLABELLED The original and modified Ottawa Ankle Rules (OARs) were developed as clinical decision rules for use in emergency departments. However, the OARs have not been evaluated as an acute clinical evaluation tool. OBJECTIVE To evaluate the measures of diagnostic accuracy of the OARs in the acute setting. METHODS The OARs were applied to all appropriate ankle injuries at 2 colleges (athletics and club sports) and 21 high schools. The outcomes of OARs, diagnosis, and decision for referral were collected by the athletic trainers (ATs) at each of the locations. Contingency tables were created for evaluations completed within 1 h for which radiographs were obtained. From these data the sensitivity, specificity, positive and negative likelihood ratios, and positive and negative predictive values were calculated. RESULTS The OARs met the criteria for radiographs in 100 of the 124 cases, of which 38 were actually referred for imaging. Based on radiographic findings in an acute setting, the OARs (n = 38) had a high sensitivity (.88) and are good predictors to rule out the presence of a fracture. Low specificity (0.00) results led to a high number of false positives and low positive predictive values (.18). CONCLUSION When applied during the first hour after injury the OARs significantly overestimate the need for radiographs. However, a negative finding rules out the need to obtain radiographs. It appears the AT's decision making based on the totality of the examination findings is the best filter in determining referral for radiographs.
The Choroid Plexus in Healthy and Diseased Brain

The choroid plexus is composed of epithelial cells resting on a basal lamina. These cells produce the cerebrospinal fluid (CSF), which has many functions including rendering mechanical support, providing a route for some nutrients, removing by-products of metabolism and synaptic activity, and playing a role in hormonal signaling. The choroid plexus synthesizes many growth factors, including insulin-like, fibroblast, and platelet-derived growth factors. The tight junctions located between the apical parts of the choroid plexus epithelial cells form the blood-CSF barrier (BCSFB), which is crucial for the homeostatic regulation of the brain microenvironment along with the blood-brain barrier (BBB). Morphological changes such as atrophy of the epithelial cells and thickening of the basement membrane suggest altered CSF production occurs in aging and in Alzheimer disease. In brain injuries and infections, leukocytes accumulate in the CSF by passing through the choroid plexus. In inflammatory CNS diseases (eg, multiple sclerosis), pathogenic autoreactive T lymphocytes may migrate through the BBB and BCSFB into the CNS. The development of therapeutic strategies to mitigate disruption of the BCSFB may be helpful to curtail the entry of inflammatory cells into the CSF and hence reduce inflammation, thereby overcoming choroid plexus dysfunction in senescence and in various diseases of the CNS.
Current status of the immunology of malaria and of the antigenic analysis of plasmodia. A five-year review.

The immunology of malaria has been intensively studied, and many reviews of separate topics have appeared. Among host factors contributing to susceptibility to malaria, the following are studied in the present paper: (1) genetic factors affecting susceptibility to human and rodent plasmodia; (2) physiological and nutritional factors affecting susceptibility of vertebrate and vector hosts; (3) sterile immunity in malaria as exemplified by radical cure and by modification of challenge infection following exposure to non-living parasite products; (4) the role of the lymphoid-macrophage system in malaria; and (5) the excessive anaemia of malaria and its etiology.Gamma-globulin levels rise in malaria and remain high during latency. Protection is associated with IgG, which is passively transferable via the human placenta. Not all gamma-globulin is antibody, and not all antibody is protective. The fluorescent antibody technique and double diffusion in gel have been extensively used in exploring the kinetics of antibody production.New methods of harvesting plasmodia attempt to avoid protein degradation and to minimize contamination by host antigens. Plasmodia have proven to consist of a mosaic of antigens, and comparative studies by most of the accepted techniques have been started. Exoantigens have been described in fowl- and rodent-malarias. Relapse-variants of primate plasmodia have been shown to differ antigenically from their parent strains.
Contrast Enhanced Magnetic Resonance Imaging for Femoral Neck Fracture

Femoral head perfusion was evaluated in 29 patients after acute femoral neck fracture using contrast enhanced fat saturation magnetic resonance imaging. The patients were followed up with T1 and T2 weighted spin echo magnetic resonance imaging without fat saturation, which is suitable in detecting avascular necrosis. The mean interval from injury to the initial contrast enhanced fat saturation magnetic resonance imaging was 24.5 hours. The mean age at the time of injury was 69 years, and the mean followup was 26.9 months. Three distinct patterns of femoral head enhancement were recognized in the acute phase after fracture. When the whole femoral head was well enhanced (Type 3, n = 11), no avascular necrosis developed. In contrast, when the head showed no enhancement (Type 1, n = 6), avascular necrosis developed in all patients. In patients with partial enhancement (Type 2, n = 12), avascular necrosis developed in five patients. These data showed the current method provided an accurate prediction of the development of avascular necrosis in the patients with Type 1 and Type 3 enhancement. However, overall predictive value was 59% (17 of 29 patients) because of the uncertainty in the patients with partial enhancement (Type 2), and additional study is needed for this method to become routine in clinical use.
The importance of somatic symptoms in depression in primary care.

OBJECTIVE Patients with depression present with psychological and somatic symptoms, including general aches and pains. In primary care, somatic symptoms often dominate. A review of the literature was conducted to ascertain the importance of somatic symptoms in depression in primary care. DATA SOURCES AND EXTRACTION MEDLINE, EMBASE, and PsychLIT/PsychINFO databases (1985-January 2004) were searched for the terms depression, depressive, depressed AND physical, somatic, unexplained symptoms, complaints, problems; somatised, somatized symptoms; somatisation, somatization, somatoform, psychosomatic; pain; recognition, under-recognition; diagnosis, underdiagnosis; acknowledgment, under-acknowledgment; treatment, undertreatment AND primary care, ambulatory care; primary physician; office; general practice; attribution, re-attribution; and normalising, normalizing. Only English-language publications and abstracts were considered. STUDY SELECTION More than 80 papers related to somatic symptoms in depression were identified using the content of their titles and abstracts. DATA SYNTHESIS Approximately two thirds of patients with depression in primary care present with somatic symptoms. These patients are difficult to diagnose, feel an increased burden of disease, rely heavily on health care services, and are harder to treat. Patient and physician factors that prevent discussion of psychological symptoms during consultations must be overcome. CONCLUSIONS Educational initiatives that raise awareness of somatic symptoms in depression and help patients to re-attribute these symptoms should help to improve the recognition of depression in primary care.
Enhancement of Radiation Cytotoxicity by UCN-01 in Non-small Cell Lung Carcinoma Cells

Abstract Mack, P. C. , Jones, A. A. , Gustafsson, M. H. , Gandara, D. R. , Gumerlock, P. H. and Goldberg, Z. Enhancement of Radiation Cytotoxicity by UCN-01 in Non-small Cell Lung Carcinoma Cells. Radiat. Res. 162, 623–634 (2004). Thoracic ionizing radiation is a standard component of combined-modality therapy for locally advanced non-small cell lung cancer. To improve low 5-year survival rates (5– 15%), new strategies for enhancing the effectiveness of ionizing radiation are needed. The kinase inhibitor UCN-01 has multiple cell cycle effects, including abrogation of DNA damage-induced S- and G2-phase arrest, which may limit DNA repair prior to mitosis. To test the hypothesis that therapy-induced cell cycle effects would have an impact on the efficacy of a combination of UCN-01 plus ionizing radiation, the cell cycle responses of the non-small cell lung cancer cell lines Calu1 (TP53-null) and A549 (wild-type TP53) to 2 Gy ionizing radiation were correlated with clonogenic survival after irradiation plus UCN-01. Irradiated cells were exposed to UCN-01 simultaneously and at 3-h increments after irradiation. In Calu1 cells but not A549 cells, sequence-dependent potentiation of radiation by UCN-01 was observed, with maximal interaction occurring when UCN-01 was administered 6 h after irradiation. This coincided with the postirradiation time with the greatest depletion of cells from G1. Abrogation of G2 arrest was observed regardless of TP53 status. The role of TP53 was investigated using siRNA to achieve gene silencing. These studies demonstrated that radiation plus UCN-01 was more effective in cells with diminished TP53 activity, associated with a reduced G1 checkpoint arrest. These studies indicate that simultaneous elimination of multiple DNA damage-induced checkpoints in G1, S and G2 may enhance the effects of radiation and that drug scheduling may have an impact on clinical efficacy.
Electromagnetic Performance Analysis of Less Rare-Earth Double-Stator Permanent Magnet Machine

A less rare-earth double-stator flux-switching permanent magnet (LR-DSFSPM) motor is proposed in this paper, in which the permanent magnets (PMs) and windings are all located in the inner and outer stator, resulting in a simple and robust rotor structure. By adopting V-shaped ferrite PMs in the outer stator, an enhanced flux-focusing effect can be obtained in the outer motor, contributing to obtaining a relatively high torque capability without rare-earth PMs. Meanwhile, since the two types of PMs are embedded in the inner stator, the inner motor can still maintain a desirable torque capability for general operation. And the middle rotor of the motor is designed with different pole numbers in its inner and outer sides, thus the requirements of multiple driving cycles can be obtained successfully. Moreover, by using the finite element analysis (FEA) method, the no-load characteristics and torque performances are investigated in details. The corresponding results reveal that the proposed motor can not only offer a relatively high torque capability with extremely less rare-earth PMs, but also provide a enrich operation modes in motor operation, indicating a potential application in electric vehicles.
Farnesyltransferase and geranylgeranyltransferase I inhibitors in cancer therapy: important mechanistic and bench to bedside issues

The fact that proteins such as Ras, Rac and RhoA require farnesylation or geranylgeranylation to induce malignant transformation prompted many investigators to develop farnesyltransferase (FTase) and geranylgeranyltransferase I (GGTase I) inhibitors (FTIs and GGTIs, respectively) as novel anticancer drugs. Although FTIs have been shown to antagonise oncogenic signalling, reverse malignant transformation, inhibit human tumour growth in nude mice and induce tumour regression in transgenic mice without any signs of toxicity, their mechanism of action is not known. This review will focus on important mechanistic issues as well as bench to bedside translational issues. These will include the relevance to cancer therapy of the alternative geranylgeranylation of K-Ras when FTase is inhibited; a thorough discussion about evidence for and against the involvement of inhibition of prenylation of Ras and RhoB in the mechanism of FTIs’ antitumour activity as well as effects of FTIs and GGTIs on the cell cycle machinery and the dynamics of bipolar spindle formation and chromosome alignment during mitosis. Bench to bedside issues relating to the design of hypothesis-driven clinical trials with biochemical correlates for proof-of-concept in man will also be discussed. This will include Phase I issues such as determining maximally tolerated dose (MTD) versus effective biological dose (EBD), as well as whether Phase II trials are still needed for clinical evaluations of anti-signalling agents. Other questions that will be addressed include: what levels of inhibition of FTase activity are required for tumour response in Phase II clinical evaluations? What FTase substrates are most relevant as biochemical correlates? Are signalling pathways such as H-Ras/PI3K/Akt and K-Ras/Raf/MEK/Erk significant biological readouts? Does Ras mutation status predict response? What are appropriate clinical end-points for FTI Phase II trials? For this latter important question, time to tumour progression, median survival, percentage of patients that progress, clinical benefits and improvement in quality of life will all be discussed.
Apoptosis and proliferation differences between CD34+ and CD34– leukemic subpopulations in childhood acute leukemia

Abstract In view of the clinical and biological significance of leukemic heterogeneity we studied the efficacy of spontaneous apoptosis and cell cycle distribution in CD34+ and CD34− leukemic subpopulations. Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) leukemic samples with CD34 heterogeneous expression were separated into CD34+ and CD34− fractions using fluorescence activated cell sorting. Cell cycle distribution, and apoptosis of the sorted subpopulations were estimated. CD34+ leukemic subpopulations had lower ability to apoptosis than that of CD34− fractions in 6 out of 8 ALL samples and in 4 out of 5 AML samples. CD34+ fractions showed a higher percentage of proliferating cells compared to CD34− cells in T-lineage ALL. These differences may lead to a more resistant phenotype of one of the subpopulations and reappearance this population in relapse.
Cyclic lipopeptide production by plant-associated Pseudomonas spp.: diversity, activity, biosynthesis, and regulation.

Cyclic lipopeptides (CLPs) are versatile molecules produced by a variety of bacterial genera, including plant-associated Pseudomonas spp. CLPs are composed of a fatty acid tail linked to a short oligopeptide, which is cyclized to form a lactone ring between two amino acids in the peptide chain. CLPs are very diverse both structurally and in terms of their biological activity. The structural diversity is due to differences in the length and composition of the fatty acid tail and to variations in the number, type, and configuration of the amino acids in the peptide moiety. CLPs have received considerable attention for their antimicrobial, cytotoxic, and surfactant properties. For plant-pathogenic Pseudomonas spp. , CLPs constitute important virulence factors, and pore formation, followed by cell lysis, is their main mode of action. For the antagonistic Pseudomonas sp. , CLPs play a key role in antimicrobial activity, motility, and biofilm formation. CLPs are produced via nonribosomal synthesis on large, multifunctional peptide synthetases. Both the structural organization of the CLP synthetic templates and the presence of specific domains and signature sequences within peptide synthetase genes will be described for both pathogenic and antagonistic Pseudomonas spp. Finally, the role of various genes and regulatory mechanisms in CLP production by Pseudomonas spp. , including two-component regulation and quorum sensing, will be discussed in detail.
The effects of thermal softening of double-lumen endobronchial tubes on postoperative sore throat, hoarseness and vocal cord injuries: a prospective double-blind randomized trial.

BACKGROUND It is well known that thermal softening of polyvinyl chloride tracheal tubes reduces nasal damage during nasotracheal intubation. We hypothesized that thermal softening of double-lumen endobronchial tubes (DLTs) may be effective for reducing airway injury. This randomized double-blind study was performed to investigate whether thermal softening of DLTs decreased postoperative sore throat, hoarseness or vocal cord injuries. METHODS Patients (n=140) undergoing one lung anaesthesia were randomized into two groups (n=70 each) depending on whether the DLT was softened by warming or not before tracheal intubation. The DLTs were placed in warm saline [40(1)°C] in the thermal softening group or in room temperature saline in the control group for 10 min. The vocal cords were examined by using flexible laryngoscopy immediately after extubation. Sore throat and hoarseness were evaluated for three postoperative days. The primary outcomes were the incidence of sore throat, hoarseness, and vocal cord injuries. RESULTS Sore throat and vocal cord injuries occurred less frequently in the thermal softening group than in the control group [14/70 vs 27/70, risk ratio (95% CI): 0.52 (0.30-0.90), P=0.025 for sore throat; 15/70 vs 27/70, risk ratio (95% CI): 0.56 (0.32-0.95), P=0.042 for vocal cord injuries]. However, the incidence of hoarseness was comparable between the two groups. CONCLUSION Tracheal intubation with DLTs softened by warming decreased the postoperative incidence of sore throat and vocal cord injuries. Therefore, thermal softening of DLTs before intubation seems to be helpful in reducing airway injuries associated with DLT intubation. CLINICAL TRIAL REGISTRATION NCT 01626365.
Splicing of U12-type introns deposits an exon junction complex competent to induce nonsense-mediated mRNA decay

Metazoan cells have two pathways for intron removal involving the U2- and U12-type spliceosomes, which contain mostly nonoverlapping sets of small nuclear ribonucleoproteins. We show that in vitro splicing of a U12-type intron assembles an exon junction complex (EJC) that is comparably positioned and contains many of the same components as that deposited by the U2-type spliceosome. The presence of a U12-type intron downstream of a premature termination codon within an open reading frame (ORF) induces nonsense-mediated decay of the mRNA in vivo. These findings suggest a common pathway for EJC assembly by the two spliceosomes and highlight the evolutionary age of the EJC and its downstream functions in gene expression.