Miracle-dz/UniFAR-FTUs huggingface dataset:
Lipoproteins Are Critical TLR2 Activating Toxins in Group B Streptococcal Sepsis1

Group B streptococcus (GBS) is the most important cause of neonatal sepsis, which is mediated in part by TLR2. However, GBS components that potently induce cytokines via TLR2 are largely unknown. We found that GBS strains of the same serotype differ in released factors that activate TLR2. Several lines of genetic and biochemical evidence indicated that lipoteichoic acid (LTA), the most widely studied TLR2 agonist in Gram-positive bacteria, was not essential for TLR2 activation. We thus examined the role of GBS lipoproteins in this process by inactivating two genes essential for bacterial lipoprotein (BLP) maturation: the prolipoprotein diacylglyceryl transferase gene (lgt) and the lipoprotein signal peptidase gene (lsp). We found that Lgt modification of the N-terminal sequence called lipobox was not critical for Lsp cleavage of BLPs. In the absence of lgt and lsp, lipoprotein signal peptides were processed by the type I signal peptidase. Importantly, both the Δlgt and the Δlsp mutant were impaired in TLR2 activation. In contrast to released factors, fixed Δlgt and Δlsp GBS cells exhibited normal inflammatory activity indicating that extracellular toxins and cell wall components activate phagocytes through independent pathways. In addition, the Δlgt mutant exhibited increased lethality in a model of neonatal GBS sepsis. Notably, LTA comprised little, if any, inflammatory potency when extracted from Δlgt GBS. In conclusion, mature BLPs, and not LTA, are the major TLR2 activating factors from GBS and significantly contribute to GBS sepsis.
Angiogenic and Fibrinolytic Factors in Blood During the First Half of Pregnancy and Adverse Pregnancy Outcomes

OBJECTIVE: To estimate whether the imbalance of angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and fibrinolytic factors (plasminogen activator inhibitor-2 [PAI-2]) might affect placentation in early pregnancy. METHODS: We studied the associations of maternal soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 concentrations in the first trimester (before 18 weeks of gestation) and soluble fms-like tyrosine kinase-1 and placental growth factor concentrations in the second trimester (18–25 weeks of gestation) with placental function and adverse pregnancy outcomes. This study was embedded in a population-based prospective cohort study. Data were used from 7,519 women. Biomarker concentrations were divided into deciles and evaluated in multivariable linear and logistic regression models. RESULTS: First-trimester high soluble fms-like tyrosine kinase-1 was associated with a 5.2% lower uterine artery index in the second-trimester and a 1.6% higher birth weight (55 g, confidence interval [CI] 15–95). Neither in the first nor in the second trimester were soluble fms-like tyrosine kinase-1 concentrations significantly associated with preeclampsia. First-trimester low placental growth factor was associated with a 6.1% higher uterine artery index and a 3.4% lower birth weight (−115 g, CI −157 to −74). First-trimester low placental growth factor was associated with fetal growth restriction (odds ratio [OR] 2.62, CI 1.68–4.08) and preeclampsia (OR 2.46, CI 1.49–4.08). First-trimester low PAI-2 was associated with a 1.9% higher uterine artery index and a 2.7% lower birth weight (−94 g, CI −136 to −51). First-trimester low PAI-2 was associated with a higher risk of fetal growth restriction (OR 2.22, CI 1.39–3.55). CONCLUSION: First-half-of-pregnancy concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and PAI-2 are associated with uteroplacental vascular resistance, placental weight, and birth weight. Moreover, first-trimester placental growth factor and PAI-2 are associated with an increased risk of adverse pregnancy outcomes. LEVEL OF EVIDENCE: II
Pharmacists' Perceived Barriers to Patient Counseling

Article history: Received on: 25/11/2013 Revised on: 19/12/2013 Accepted on: 24/01/2014 Available online: 30/01/2014 The aim of this study was to investigate the prevalence and nature of patient counseling barriers as perceived by pharmacists. The data was collected by adding a question about the existence and nature of counseling barriers, if they exist, to the standard patient counseling form used by pharmacists. The prevalence of counseling barriers was 12.5%. The major counseling barrier was counseling the caregiver instead of the patient (27.8%), followed by low level of education, lack of privacy, lack of interest/time and partial consciousness of the patient (16.7% each) and hearing impairment (11.1%). Finally gender and delay of discharge order were the least reported (5.26% each). This study recommends that a special counseling protocol should be implemented for patients with low level of education and partial hearing impairment and that a proper setting for counseling and strict implementation of policies should be provided by the institution.
Ginsenoside Rg1 and Aluminum Hydroxide Synergistically Promote Immune Responses to Ovalbumin in BALB/c Mice

ABSTRACT The combined adjuvant effect of ginsenoside Rg1 and aluminum hydroxide (alum) on immune responses to ovalbumin (OVA) in mice was investigated. BALB/c mice were subcutaneously (s.c.) inoculated twice with OVA alone or in combination with Rg1, alum, or Rg1 plus alum. Samples were collected 2 weeks after the boosting for the measurement of anti-OVA immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-γ) and interleukin-5 (IL-5) produced in singular splenocyte cultures. Delayed-type hypersensitivity (DTH) responses were measured in mice immunized as described above. After 10 days, the mice were injected s.c. with OVA at the footpads. Thereafter, the thickness of the footpads was measured once daily for 5 days. The results indicated that alum enhanced mainly Th2 (IgG1 and IL-5) responses (P < 0.05), while Rg1 enhanced both Th1 (IgG1 and IL-5) and Th2 (IgG2a, IFN-γ, and DTH) responses (P < 0.05). The highest immune responses were found in the mice injected with OVA solution containing both alum and Rg1. In addition, the hemolytic activity of Rg1 was much lower than that of Quil A. Therefore, Rg1 deserves further studies in order to tailor desired immune responses when a mixed Th1/Th2 immune response is needed.
Natural Burial: Traditional - Secular Spiritualities and Funeral Innovation

Preface 1. Funeral Forms, Life-styles and Death-styles 2. Varied Sites and Changing Rites 3. Options and Motivations: What People Say 4. Self-Gift, Soil, and Society 5. Spirituality, Theology, Self and Sense of Place Notes Bibliography Index.
The impact of multiuser diversity on space-time block coding

In this letter, analytic performance results are derived for space-time block coding paired with multiuser diversity. We consider a scenario in which K active data users, each of which is potentially equipped with multiple antenna elements, are served by a multi-antenna element base station (BS). We focus on the downlink channel, where a space-time block coding scheme is employed and assume that channel quality information is reported to the BS by all users on a per frame basis. Using a scoring function at the BS, time resources are allocated to the user with the best instantaneous effective signal-to-noise ratio (SNR), facilitating a multiuser diversity mechanism. Using order statistics, we compute histograms and cumulative distribution functions of the effective SNR at the space-time combiner output and assess the interaction between multiuser diversity obtained via scheduling and spatial diversity obtained via the space-time code.
Chk1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition

In Xenopus embryos, cell cycle elongation and degradation of Cdc25A (a Cdk2 Tyr15 phosphatase) occur naturally at the midblastula transition (MBT), at which time a physiological DNA replication checkpoint is thought to be activated by the exponentially increased nucleo‐cytoplasmic ratio. Here we show that the checkpoint kinase Chk1, but not Cds1 (Chk2), is activated transiently at the MBT in a maternal/zygotic gene product‐regulated manner and is essential for cell cycle elongation and Cdc25A degradation at this transition. A constitutively active form of Chk1 can phosphorylate Cdc25A in vitro and can target it rapidly for degradation in pre‐MBT embryos. Intriguingly, for this degradation, however, Cdc25A also requires a prior Chk1‐independent phosphorylation at Ser73. Ectopically expressed human Cdc25A can be degraded in the same way as Xenopus Cdc25A. Finally, Cdc25A degradation at the MBT is a prerequisite for cell viability at later stages. Thus, the physiological replication checkpoint is activated transiently at the MBT by developmental cues, and activated Chk1, only together with an unknown kinase, targets Cdc25A for degradation to ensure later development.
Corticotropin‐Releasing Factor Stimulates Catecholamine Release in Hypothalamus and Prefrontal Cortex in Freely Moving Rats as Assessed by Microdialysis

Abstract: In vivo microdialysis was used to measure changes in extracellular concentrations of catecholamines and indoleamines in freely moving rats in response to administration of corticotropin‐releasing factor (CRF). Dialysis probes were placed stereotaxically in either the medial hypothalamus or the medial prefrontal cortex. We used a repeated‐measures design in which each rat received artificial CSF or one dose of CRF 3–4 h apart, and each subject was retested with the same treatments in the reverse order 5–7 days later. With the dialysis probe in the hypothalamus, intracerebroventricular administration of CRF (17 or 330 pmol) dose‐dependently increased dialysate concentrations of norepinephrine (NE), dopamine (DA), and all their measurable catabolites except normetanephrine. The effects on NE were substantially greater than those on DA. Dialysate concentrations of serotonin could not be measured reliably, but those of its catabolite, 5‐hydroxyindoleacetic acid, were also elevated. Concentrations of NE and DA were elevated within the first one or two (20 min) collection periods, with a peak response at ∼ 1–2 h. Dialysate concentrations of catecholamines and metabolites normally returned to baseline within 3 h. Similar data were obtained with dialysis probes in the medial prefrontal cortex after intracerebroventricular administration of 17 or 167 pmol of CRF, except that the increases in DA exceeded those of NE in this region. Intraperitoneal administration of CRF (1 nmol) similarly elevated dialysate concentrations of NE, DA, 5‐hydroxyindoleacetic acid, and all catecholamine catabolites except normetanephrine in both medial hypothalamus and medial prefrontal cortex. These results support earlier neurochemical data suggesting that CRF administered both centrally and peripherally stimulates the release of both DA and NE in the brain.
East Germany overtakes West Germany: recent trends in order-specific fertility dynamics

Some 20 years after unification, the contrast between East and West Germany provides a unique natural experiment for studying the persistence of communist-era family patterns, the effects of economic change, and the complexities of the process of fertility postponement. After unification, fertility rates plummeted in the former East Germany to record low levels. The number of births per year fell 60 percent. The period total fertility rate (TFR) reached a low of 0.8. Since the middle of the 1990s, however, period fertility rates have been rising in East Germany, in contrast to the nearly constant rates seen in the West. By 2008, the TFR of East Germany had overtaken that of the West. In this paper, we explore why fertility in the East is higher than in West Germany, despite the severe economic situation in the East, whether the East German TFR will increase even further in the future, and whether the West German rate will remain at the constantly low level that has prevailed since the 1970s. This article seeks to shed some light on these questions by (a) giving an account of the persisting East-West differences in attitudes towards and constraints on childbearing, (b) conducting an order-specific fertility analysis of recent fertility trends, and (c) projecting completed fertility for the recent East and West German cohorts. In addition to using the Human Fertility Database, we draw upon Perinatal Statistics, which enable us to conduct an order-specific fertility analysis. This new data source allows us to calculate a tempo-corrected TFR for East and West Germany, which has not been available previously.
Exploring anchoring effect and the moderating role of repeated anchor in electronic commerce

Most of the anchoring studies conduct the experiments following two-stage experimental design in which a comparative judgement is followed by an absolute estimate. However, this design is impractical in many situations, especially in online auction environments where consumers cannot be asked to make comparisons before they make estimates. This study suggests and validates an alternative experimental design where no comparison process is needed to induce anchoring bias. Moreover, we postulate that repeated occurrence of anchoring points affect the strength of the anchoring effect on participants' price estimates. Two experiments were conducted to investigate the anchoring effect in both two-stage and one-stage designs. The results showed that the anchoring effect was robust under two-stage design, and repeated occurrence of the anchor did not reinforce the anchoring effect. Moreover, people's price estimates are susceptible to the anchoring effect even when they were not asked to make a comparative judgement before they determine the final estimate. However, the anchoring effect can be further consolidated when the anchor appears three times rather than once. Experimental design introduced in study 2 provides a promising website design direction and we suggest that high anchors should be embedded in a web page repeatedly to influence the buyers' value estimates to produce a premium.
Spiritual Turning Points and Perceived Control over the Life Course

Recent evidence indicates that spirituality and religion are associated with both physical and psychological health. Because a belief that rewards are largely determined by external forces tends to be detrimental to mental health, the idea that God can be equated with such an external force seems contradictory to the proven benefits of religion and spirituality. The purpose of this article is to examine changes in perceived control in the context of spiritual turning points as uncovered in the narrative histories of 30 elderly people. We propose that for many people who derive benefits from religion or spirituality, God may act as a mediator, in the sense that trusting in God provides personal control. In addition to creating a model of God-mediated control, the study's findings suggest a relationship between recall for type of control during a spiritual turning point and the interpretation of that turning point in late life.
Central nervous system involvement by multiple myeloma: A multi‐institutional retrospective study of 172 patients in daily clinical practice

The multicenter retrospective study conducted in 38 centers from 20 countries including 172 adult patients with CNS MM aimed to describe the clinical and pathological characteristics and outcomes of patients with multiple myeloma (MM) involving the central nervous system (CNS). Univariate and multivariate analyses were performed to identify prognostic factors for survival. The median time from MM diagnosis to CNS MM diagnosis was 3 years. Thirty‐eight patients (22%) were diagnosed with CNS involvement at the time of initial MM diagnosis and 134 (78%) at relapse/progression. Upon diagnosis of CNS MM, 97% patients received initial therapy for CNS disease, of which 76% received systemic therapy, 36% radiotherapy and 32% intrathecal therapy. After a median follow‐up of 3.5 years, the median overall survival (OS) from the onset of CNS involvement for the entire group was 7 months. Untreated and treated patients had median OS of 2 and 8 months, respectively (P < 0.001). At least one previous line of therapy for MM before the diagnosis of CNS disease and >1 cytogenetic abnormality detected by FISH were independently associated with worse OS. The median OS for patients with 0, 1 and 2 of these risk factors were 25 months, 5.5 months and 2 months, respectively (P < 0.001). Neurological manifestations, not considered chemotherapy‐related, observed at any time after initial diagnosis of MM should raise a suspicion of CNS involvement. Although prognosis is generally poor, the survival of previously untreated patients and patients with favorable cytogenetic profile might be prolonged due to systemic treatment and/or radiotherapy. Am. J. Hematol. 91:575–580, 2016. © 2016 Wiley Periodicals, Inc.
Comparison of dna cleavage induced by etoposide and doxorubicin in two human small‐cell lung cancer lines with different sensitivities to topoisomerase ii inhibitors

In an attempt to clarify the role of drug‐induced proteinassociated DNA breaks (i.e., DNA topoisomerase II‐mediated DNA cleavage) in the cytotoxic activity of doxorubicin and etoposide, their cellular effects were compared in 2 human small‐cell lung cancer (SCLC) lines, characterized by differential sensitivity to DNA topoisomerase II inhibitors. These drugs were selected for comparative studies since they are among the most effective agents in the treatment of SCLC. H146 and N592 cell lines were obtained from pleural effusion and bone‐marrow aspirate of pretreated patients, respectively. Both cell lines grew as floating aggregates with similar doubling times (30 and 33 hr for N592 and H146 cells, respectively). Although, immediately after 1 hr exposure to equitoxic drug levels, the extent of DNA cleavage produced by doxorubicin was markedly lower than that produced by etoposide, DNA lesions produced by doxorubicin persisted and even increased following drug removal. In contrast, an almost complete disappearance of etoposide‐Induced DNA breaks was noted 1 hr after drug removal. Resealing of strand breaks was faster in N592 than in H146 cells. These findings suggest that reversal of these lesions plays a major role in cell survival rather than the occurrence of DNA breaks immediately following drug exposure. This observation is consistent with the view that inhibition of DNA re‐ligation rather than stimulation of DNA cleavage is the critical step for drug action. The different response of these cell lines to cytotoxic action of the topoisomerase inhibitors is associated with a differential drug effect on DNA integrity (detected as DNA double‐strand breaks and DNA‐protein cross‐links). However DNA lesions were comparable when cells were exposed to equitoxic drug levels. The observation that etoposide‐induced DNA breaks were similar in isolated nuclei from both cell lines suggests that drug‐target interaction is modulated in a different manner in the intact cell. As indicated by doxorubicin uptake and retention, cellular drug pharmacokinetics do not account for the different drug response of the studied SCLC lines, presumably reflecting a different extent of DNA break formation and/or a different cytotoxic consequence of DNA damage.
The significance of squamous differentiation in endometrial carcinoma. Data from a gynecologic oncology group study

Squamous differentiation is identified in about 25% of endometrial adenocarcinomas (AC). Its significance has been the subject of debate for decades, and it has been reported that the prognosis of adenoacanthoma (AA) is better than, the same as, and worse than that of AC. Part of this confusion has resulted from semantic differences relating to the use of AA and adenosquamous carcinoma (AS). To investigate the prognostic importance of squamous differentiation in endometrial carcinomas and compare the prognostic utility of two classification systems, 456 women were studied who had typical AC and 175 women who had typical AC containing areas of squamous differentiation (AC + SQ) and who had been entered in a Gynecologic Oncology Group protocol of Stage I and II endometrial adenocarcinoma. Assessment of histologic grade and depth of invasion was done both by the pathologist at the member institution and at a second highly structured review. Differentiation of the squamous component of endometrial carcinomas was found to parallel that of the glandular component in most tumors. The biologic behavior of endometrial carcinomas with squamous elements was similar, but not identical, to that of typical AC. Although the frequency of nodal metastasis was similar for both AC and AC + SQ, the presence of squamous elements was associated with an increased probability of survival. Division of AC + SQ by depth of myometrial invasion and by architectural grade of the glandular component provided useful prognostic information that was superior to that resulting simply from division of AC + SQ into AA or AS. The authors recommend that these terms be replaced by “adenocarcinoma with squamous differentiation” and that the pathologist provide information on the architectural grade and depth of myometrial invasion to guide the gynecologist in determining appropriate therapy. Cancer 68:2293–2302, 1991.
Isoprene Responses and Functions in Plants Challenged by Environmental Pressures Associated to Climate Change

The functional reasons for isoprene emission are still a matter of hot debate. It was hypothesized that isoprene biosynthesis evolved as an ancestral mechanism in plants adapted to high water availability, to cope with transient and recurrent oxidative stresses during their water-to-land transition. There is a tight association between isoprene emission and species hygrophily, suggesting that isoprene emission may be a favorable trait to cope with occasional exposure to stresses in mesic environments. The suite of morpho-anatomical traits does not allow a conservative water use in hygrophilic mesophytes challenged by the environmental pressures imposed or exacerbated by drought and heat stress. There is evidence that in stressed plants the biosynthesis of isoprene is uncoupled from photosynthesis. Because the biosynthesis of isoprene is costly, the great investment of carbon and energy into isoprene must have relevant functional reasons. Isoprene is effective in preserving the integrity of thylakoid membranes, not only through direct interaction with their lipid acyl chains, but also by up-regulating proteins associated with photosynthetic complexes and enhancing the biosynthesis of relevant membrane components, such as mono- and di-galactosyl-diacyl glycerols and unsaturated fatty acids. Isoprene may additionally protect photosynthetic membranes by scavenging reactive oxygen species. Here we explore the mode of actions and the potential significance of isoprene in the response of hygrophilic plants when challenged by severe stress conditions associated to rapid climate change in temperate climates, with special emphasis to the concomitant effect of drought and heat. We suggest that isoprene emission may be not a good estimate for its biosynthesis and concentration in severely droughted leaves, being the internal concentration of isoprene the important trait for stress protection.