Miracle-dz/UniFAR-FTUs huggingface dataset:
Early stages of spindle formation and independence of chromosome and microtubule cycles in Haemanthus endosperm.

We analyzed transformation of the interphase microtubular cytoskeleton into the prophase spindle and followed the pattern of spindle axis determination. Microtubules in endosperm of the higher plant Haemanthus (Scadoxus) were stained by the immunogold and immunogold silver-enhanced methods. Basic structural units involved in spindle morphogenesis were "microtubule converging centers. " We emphasized the importance of relative independence of chromosomal and microtubular cycles, and the influence of these cycles on the progress of mitosis. Cells with moderately desynchronized cycles were functional, but extreme desynchronization led to aberrant mitosis. There were three distinct phases of spindle development. The first one comprised interphase and early to mid-prophase. During this phase, the interphase microtubule meshwork radiating from the nuclear surface into the cytoplasm rearranged and formed a dense microtubule cage around the nucleus. The second phase comprised mid to late prophase, and resulted in the formation of normal (bipolar) or transitory aberrant (apolar or multipolar) prophase spindles. The third phase comprised late prophase with prometaphase. The onset of prometaphase was accompanied by a rapid association of microtubule converging centers with kinetochores. In this stage aberrant spindles transformed invariably into bipolar ones. Lateral association of a few bipolar kinetochore fibers at early prometaphase established the core of the bipolar spindle and its alignment. We concluded that (1) spindle formation is a largely independent microtubular process modified by the chromosomal/kinetochore cycle; and (2) the initial polarity of the spindle is established by microtubule converging centers, which are a functional substitute of the centrosome/MTOC. We believe that the dynamics of microtubule converging centers is an expression of microtubule self-organization driven by motor proteins as proposed by Mitchison [1992: Philos. Trans. R. Soc. Lond. B. 336:99].
A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older.

This phase 3, multicenter, open-label study evaluated the efficacy and safety of tipifarnib compared with best supportive care (BSC), including hydroxyurea, as first-line therapy in elderly patients (>or=70 years) with newly diagnosed, de novo, or secondary acute myeloid leukemia. A total of 457 patients were enrolled with 24% 80 years of age or older. Tipifarnib 600 mg orally twice a day was administered for the first 21 consecutive days, in 28-day cycles. The primary endpoint was overall survival. The median survival was 107 days for the tipifarnib arm and 109 days for the BSC arm. The hazard ratio (tipifarnib vs BSC) for overall survival was 1.02 (P value by stratified log-rank test, .843). The complete response rate for tipifarnib in this study (8%) was lower than that observed previously, but with a similar median duration of 8 months. The most frequent grade 3 or 4 adverse events were cytopenias in both arms, slightly more infections (39% vs 33%), and febrile neutropenia (16% vs 10%) seen in the tipifarnib arm. The results of this randomized study showed that tipifarnib treatment did not result in an increased survival compared with BSC, including hydroxyurea. This trial was registered at www.clinicaltrials. gov as #NCT00093990.
Use of a new end‐stage kidney disease risk calculator in the Kidney Disease Improving Global Outcomes guideline to evaluate the impact of different living kidney donor candidate assessments

The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends the incorporation of a new risk calculator that quantifies the end‐stage kidney disease (ESKD) risk based on a composite profile of risk factors in living kidney donor candidates (LKDC). We compared the ESKD risk estimates in previously declined versus accepted LKDC to evaluate the predictive capacity and potential impact of this tool.
Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process

Equine infectious anemia virus (EIAV) provides a natural model system by which immunological control of lentivirus infections may be studied. To date, no detailed study addressing in parallel both the humoral and cellular immune responses induced in horses upon infection by EIAV has been conducted. Therefore, we initiated the first comprehensive characterization of the cellular and humoral immune responses during clinical progression from chronic disease to inapparent stages of EIAV infection. Using new analyses of antibody avidity and antibody epitope conformation dependence that had not been previously employed in this system, we observed that the humoral immune response to EIAV required a 6- to 8-month period in which to fully mature. During this time frame, EIAV-specific antibody evolved gradually from a population characterized by low-avidity, nonneutralizing, and predominantly linear epitope specificity to an antibody population with an avidity of moderate to high levels, neutralizing activity, and predominantly conformational epitope specificity. Analyses of the cell-mediated immune response to EIAV revealed CD4+ and CD8+ major histocompatibility complex-restricted, EIAV-specific cytotoxic T-lymphocyte (CTL) activity apparent within 3 to 4 weeks postinfection, temporally correlating with the resolution of the primary viremia. After resolution of the initial viremia, EIAV-specific CTL activity differed greatly among the experimentally infected ponies, with some animals having readily detectable CTL activity while others had little measurable CTL activity. Thus, in contrast to the initial viremia, it appeared that no single immune parameter correlated with the resolution of further viremic episodes. Instead, immune control of EIAV infection during the clinically inapparent stage of infection appears to rely on a complex combination of immune system mechanisms to suppress viral replication that effectively functions only after the immune system has evolved to a fully mature state 6 to 8 months postinfection. These findings strongly imply the necessity for candidate EIAV and other lentivirus vaccines to achieve this immune system maturation for efficacious immunological control of lentivirus challenge.
Impact of primary care management on nursing documentation.

AIM The aim was to investigate whether perceptions of electronic nursing documentation and its performance differed because of primary health care management. BACKGROUND Success in leading people depends on the manager's personality, the context and the people who are led. Close proximity to clinical work, with manager and personnel sharing the same profession, promotes the authority to carry out changes. METHODS This study comprised a postal questionnaire to district nurses and an audit of nursing records from two primary health care organizations, one with a uniprofessional (nursing) organization, and one with multidisciplinary health care centres with general practitioners and/or another profession as managers. RESULTS Uniprofessional nurse management increased district nurses' positive perceptions of nursing documentation but did not affect documentation performance, which was inadequate regardless of management type. CONCLUSIONS Positive perceptions of nursing documentation are bases for further development to a nursing documentation including a holistic view of the patient.
Patient Responses to Ipilimumab, a Novel Immunopotentiator for Metastatic Melanoma: How Different are these From Conventional Treatment Responses?

Advanced melanoma has defied treatment advances for several decades. Immunotherapy with high-dose interleukin-2 or interferon-&agr; has been beneficial in some cases, but significant toxicities limit its use. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) signaling switches off T-cell activation and induces immune tolerance. Inhibiting CTLA-4 prolongs the antitumor T-cell response, reversing tolerance. Ipilimumab is a first-in-class anti-CTLA-4 monoclonal antibody, currently under review by the Food and Drug Administration for pretreated melanoma. Ipilimumab has shown durable responses and manageable toxicities in a large phase 3 clinical trial in patients with advanced melanoma. Variable response patterns have been observed, including: (1) response in baseline lesions; (2) a slow, steady decline in tumor burden; (3) response after an increase in tumor burden; and (4) response in index and new lesions accompanied by the appearance of other new lesions. Although responses (1) and (2) may be captured using standard methods, atypical responses (3) and (4) would be classified as progressive disease using conventional assessments. Patients on ipilimumab may have delayed responses or durable stable disease even after apparent disease progression, therefore using new immune-related response criteria is recommended to avoid premature treatment withdrawal. This review compares and contrasts responses to ipilimumab with those after chemotherapy, and discusses treatment implications.
Estimation of Joint Stiffness with a Compliant Load

Joint stiffness defines the dynamic relationship between the position of the joint and the torque acting about it. It consists of two components: intrinsic and reflex stiffness. Many previous studies have investigated joint stiffness in an open-loop environment, because the current algorithm in use is an open-loop algorithm. This paper explores issues related to the estimation of joint stiffness when subjects interact with compliant loads. First, we show analytically how the bias in closed-loop estimates of joint stiffness depends on the properties of the load, the noise power, and length of the estimated impulse response functions (IRF). We then demonstrate with simulations that the open-loop analysis will fail completely for an elastic load but may succeed for an inertial load. We further show that the open-loop analysis can yield unbiased results with an inertial load and document IRF length, signal-to-noise ratio needed, and minimum inertia needed for the analysis to succeed. Thus, by using a load with a properly selected inertia, open-loop analysis can be used under closed-loop conditions.
Health personnel needs and attitudes to rural service in KwaZulu-Natal.

OBJECTIVES To ascertain the urban/rural distribution of health personnel and the opinions of the medical fraternity in KwaZulu-Natal on compulsory rural service for medical practitioners. DESIGN Cross-sectional analysis of geographical distribution of health personnel in KwaZulu-Natal based on 1991/92 South African Medical and Dental Council, South African Nursing Council and Pharmacy Council registration data. Opinion survey by administration of a structured questionnaire to a simple, random sample of private practitioners, academic consultants, postgraduate and undergraduate medical students and key informants in senior health service management in KwaZulu-Natal. RESULTS Peripheral rural areas had health personnel/population ratios higher than or equivalent to those of urban areas, whereas the ratios were 15-40 times lower in deep rural areas. The key finding of the opinion survey was that the majority of all sectors except fifth-year medical students felt that rural service should be compulsory, either post-internship, prior to specialisation or prior to entry into private practice. However, respondents were significantly more likely to agree to rural service that would not affect them personally. The majority (54-87%) of all sectors felt that an option of 'buying out' of rural service should not be permitted. Respondents identified a range of financial, health service, academic, infrastructural and social incentives for rural practice. It is recommended that post-internship rural service be compulsory for a period of 6 months to 1 year provided that academic, health service and infrastructural deficiencies are ameliorated and appropriate financial incentives are provided.
Upregulation of Galectin-9 and PD-L1 Immune Checkpoints Molecules in Patients with Chronic Lymphocytic Leukemia

Background: Deviation of host immune response by engagement of inhibitory receptors is one of the well-known mechanisms of tumor cells for immune evasion and survival. PD-1/PD-L1 and Tim-3/Gal-9 axes are two major pathways in this area which their contribution has been documented in a variety of malignancies. In this study, Gal-9 and PD-L1 expression was investigated in leukemic cells from patients with Chronic Lymphocytic Leukemia (CLL). Methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 25 untreated CLL patients and 15 sex- and age-matched healthy controls. CLL patients were classified into different clinical stages based on the Rai staging system. Total RNA was extracted from all samples and applied for cDNA synthesis. Relative expression of Gal-9 and PD-L1 mRNA was determined by Real-Time PCR using β-actin as a housekeeping gene. Results: Gal-9 and PD-L1 mRNA was significantly more expressed in CLL patients compared to healthy controls (p<0.0001 and p=0.005, respectively). CLL patients in advanced clinical stages showed higher expression of Gal-9 and PD-L1 in comparison to patients in early clinical stages (p<0.0001 and p=0.004, respectively). Conclusion: Our promising results regarding over-expression of Gal-9 and PD-L1 in CLL patients call future complementary studies to more evaluate and confirm these pathways for immunotherapy approaches of this malignancy. Upregulation of both Gal-9 and PD-L1 in CLL patients with advanced clinical stages introduces them as useful prognostic biomarkers for disease progression.
Monocytic HLA‐DR expression in intensive care patients: Interest for prognosis and secondary infection prediction *

Objectives: To test early measurement of human leukocyte antigen‐DR expression on circulating monocytes (mHLA‐DR) as prognostic marker, and the trend of mHLA‐DR recovery for the prediction of late secondary infection risk in a large intensive care unit population. Design: Prospective, observational study over 16 mos. Setting: Intensive care unit in a tertiary teaching hospital. Inclusion criteria: Simplified Acute Physiology Score II >15, age >18 yrs. Measurements and Main Results: The mHLA‐DR was measured by flow cytometry within the first 3 days and twice a week until discharge. We used a logistic regression model for outcome prediction, and a competing risk approach to test the relationship between mHLA‐DR recovery (log (mHLA‐DR) slope) and incidence of secondary infection. A total of 283 consecutive patients suffering from various pathologies were monitored (Simplified Acute Physiology Score II = 39, Sepsis‐related Organ Failure Assessment of 5 on day 0). Early mHLA‐DR was decreased in the whole population, however, more deeply in sepsis (p < .0001). Low mHLA‐DR was associated with mortality in the whole population (p = .003), as in subgroups (nonseptic, neurologic, and septic), but not when adjusted on Simplified Acute Physiology Score II. In patients with a length of stay of >7 days (n = 70), the lower the slope of mHLA‐DR recovery, the higher the incidence of the first secondary infection (adjusted on early mHLA‐DR, p = .04). Conclusions: For a given severity, mHLA‐DR proved not to a predictive marker of outcome, but a weak trend of mHLA‐DR recovery was associated with an increased risk of secondary infection. Monitoring immune functions through mHLA‐DR in intensive care unit patients therefore could be useful to identify a high risk of secondary infection.
Studies on the increase in cytosolic free calcium induced by epidermal growth factor, serum, and nucleotides in individual A431 cells

The response of cytosolic calcium [Ca2+]i to epidermal growth factor (EGF), fetal calf serum, and nucleotides was determined in individual A431 cells, using the fluorescent probe fura‐2 and quantitative digital video fluorescence microscopy. In the presence of 1 mM external Ca2+, EGF caused a rapid rise in [Ca2+]i, followed by a slower and variable decrease. The cells responded after a lag that varied from 10 to 30 seconds, and there was considerable cell‐to‐cell variation in extent of the rise in [Ca2+]i. A second challenge with EGF gave negative results. No response was obtained in nominally Ca2+‐free medium supplemented with 100 μM EGTA. Somewhat similar results were obtained with fetal calf serum except that a rise in [Ca2+]i was observed both in the presence and absence of external Ca2+. The A431 cells responded to external ATP with a rise in [Ca2+]i in less than 10 seconds, both in Ca2+‐containing and Ca2+‐free media. A coverslip with attached cells was mounted on a small chamber, allowing complete change of medium in 2 seconds. A nearly full response was obtained with only 10 seconds of contact of cells with ATP‐containing medium. After washing out ATP, there was little or no response to a second addition given 100 seconds after the first. However, a second response was obtained when the concentration of agonist was increased 10–20‐fold. These data favor the idea of receptor desensitization. Both homologous and heterologous receptor desensitization was observed. A transient rise in [Ca2+]i was also noted with UTP, while ITP and CTP were inactive.
PU.1 (Sfpi1), a pleiotropic regulator expressed from the first embryonic stages with a crucial function in germinal progenitors

In the adult mammalian testis, spermatogenic differentiation starts from a minute population of spermatogonial stem cells (SSCs). SSCs are generated after birth from the fetal gonocytes, themselves derived from the primordial germ cells (PGCs), which are specified during the first days after implantation. Transcriptome profiling of purified preparations evidenced the preferential accumulation in SSCs of transcripts of PU.1 (Sfpi1), a regulatory gene previously identified in hematopoietic progenitors. In situ immunolabeling and RNA determination showed a complex pattern of expression in the adult testis, first in SSCs and early spermatogonia followed by de novo expression in pachytene spermatocytes. Spermatogenesis in a null mutant (PU.1G/G) was arrested at the prenatal stage, with reduced numbers of gonocytes owing to a defect in proliferation already noticeable at E12.5. Transcripts of several germinal markers, including vasa (Mvh, Ddx4), Oct4 (Pou5f1), Dazl and Taf4b, were detected, whereas stella (PGC7, Dppa3) was not. Germ cells of PU.1G/G newborn testes grafted in nude mice did not initiate the postnatal replicative stage, whereas grafts of their wild-type littermates underwent complete spermatogenesis. During embryonic development, PU.1 transcription was initiated as early as the blastocyst stage, with a generalized expression at E6.5 in the embryonic ectoderm. PU.1 therefore appears to play a determinant role in at least two distinct lineages and, given its wide range of expression, possibly in other stem cells.
Increased sensitivity to protein kinase C activation in aortas of spontaneously hypertensive rats

The aortic muscle of spontaneously hypertensive (SHR) and normotensive control (WKY) rats was stimulated with phorbol esters and the contractile response was measured as isometric tension. Phorbol esters are known activators of protein kinase C. The aortas of SHR were characterized by the following distinct alterations in the response to phorbol myristate acetate: (1) increased sensitivity: half-maximal force was achieved at 62 ± 6 nmol/1 phorbol myristate acetate in SHR and 105 ± 8 nmol/l in WKY; (2) increased contractility: the maximal force developed by phorbol myristate acetate was greater in SHR aortas (1.9 ± 0.3 versus 1.6 ± 0.2 g in WKY) compared with the decreased contractility generated with noradrenaline and high levels of potassium; (3) decreased dependency on extracellular calcium for half-maximal tension: in the presence of 3 μmol/l phorbol myristate acetate 50% of maximal force was attained at 21 ± 8 μmol/1 extracellular calcium compared with 49 ± 9 μmol/l in WKY; (4) diminished relaxation in response to excess extracellular calcium: phorbol myristate acetate-precontracted WKY aortas began to relax when calcium was raised above 4 mmol/l in the bath and relaxation reached 51% at 8–10 mmol/l. Relaxation was almost absent in SHR (3–7%). Hence, there is an abnormality in the response to protein kinase C activation by phorbol esters in SHR vascular smooth muscle. Intracellular calcium appears to be involved. Studies of protein kinase C will prove important in understanding vascular smooth muscle function in normal and abnormal states.
The Relations Among Relatedness Needs, Subjective Well-Being, and Depression of Korean Elderly

The first part of the study examined what the relatedness needs Korean elderly have in close relationships (spouse, children, friends) are. The most salient needs were “love and care” for spouse and “contact and often meeting” for children and friends. The second part of the study assessed the relations among the difference between expectation and satisfaction of relatedness needs, subjective well-being, and depression of Korean elderly. Regression analyses showed that the difference between expectation and satisfaction of relatedness needs for spouse and children significantly predicted subjective well-being and depression. Finally, gender differences are discussed in terms of the patriarchal culture of Korean society.
Composition of Lipids in Elasmobranch Electric Organ and Acetylcholine Receptor Membranes

Abstract: The composition of phospholipids from electric organ and from membranes enriched in acetylcholine receptors (AChRs) is analyzed in three elasmobranch fish (Torpedo marmorata, Torpedo californica, and Discopyge tschudii). Irrespective of their purity, AChR‐containing membranes are similar to electric organ in lipid and fatty acid composition. The following characteristics are common to the three species: (a) Choline, ethanolamine, and serine glycerophospholipids account for 80–90% of the phospholipids. (b) Their major fatty acid constituents are monoenes, saturates, and long‐chain (n‐3) polyenes (especially docosahexaenoate). (c) A large proportion of (he ethanolamine glycerophospholipids (30–50%) is made up by plasmenylethanolamine, which contains fewer polyenes than phosphatidylethanolamine per mole of lipid. (d) Poly‐phosphoinositides represent 20–30% of the inositides of electric organ, (e) Phosphatidylinositol and phosphatidate have large proportions of 20‐and 22‐carbon polyenes. (f) Diphosphatidylglycerol and triacylglycerols are rich in oleate but also contain long‐chain polyenes. (g) Sphingo‐myelin has monoenes and saturates ranging from 14 to 26 carbons. Species‐related variations are observed (a) in the ratios between some phospholipid classes and subclasses and (b) in the relative abundance of the major polyunsatu‐rated acyl chains of phospholipids. Despite these differences, the average unsaturation and length of fatty acids in major phospholipid classes are similar for the three species.