Miracle-dz/UniFAR-FTUs huggingface dataset:
Cross-sectional and longitudinal evaluation of bone mass and quality in children and young adults with juvenile onset systemic lupus erythematosus (JSLE): role of bone mass determinants analyzed by DXA, PQCT and QUS

Introduction Stefano Stagi and Loredana Cavalli contributed equally to the manuscript; Maria Luisa Brandi and Fernanda Falcini contributed equally to the manuscript. There are few prospective data on bone mass and quality in patients with juvenile onset systemic lupus erythematosus (JSLE). There are also few studies analyzing bone mass and quality determinants by using at the same time dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS). Objective The objective of this paper is to evaluate cross-sectionally and longitudinally bone mass and quality determinants in adolescents and young adults with JSLE, and to identify the main predictors of reduced bone mineral density (BMD) and bone quality using these techniques. Methods Fifty-six patients with JSLE (mean age 18.5 ± 5.7 years) entered the study. In all subjects DXA scan at the lumbar spine, radius pQCT and phalangeal QUS were performed the same day. Of these, 46 patients (mean age 23.1 ± 6.2 years) were revaluated with a second DXA, pQCT and QUS. The data obtained were compared with 72 and 80 age- and sex- matched healthy controls. Results At the first evaluation, JSLE patients had a reduced spine BMAD SDS (p < 0.001), and significantly lower levels of TrabBMD (p < 0.0001), SSIp (p < 0.05), AD-SoS and QUS z-score (p < 0.005) but not reduced muscleCSA and CBA values. CortBMD and FatCSA were significantly increased (p < 0.0001). These data were confirmed at longitudinal evaluation regarding spine BMAD SDS (p < 0.001), TrabBMD (p < 0.0001), FatCSA (p < 0.005), AD-SoS (p < 0.001), and QUS z-score (p < 0.005) but not muscle CSA (p ≤ 0.05) and CBA (p < 0.0001). SSIp and CortBMD longitudinal evaluation showed that JSLE patients did not present significant differences in comparison to controls. Conclusions Patients with JSLE have a low bone mass without catch-up growth over time, causing a reduction of peak bone mass with high risk of osteoporosis in early adulthood. To reduce the risk, close monitoring of BMD, better control of disease activity, physical activity and dietary intake of calcium and vitamin D are advocated to ameliorate the loss of bone mass. In patients with proved osteoporosis therapeutic approaches including bisphosphonates should be considered.
Anti-Melanoma Activity of the 9.2.27PE Immunotoxin in Dacarbazine Resistant Cells

We have earlier shown that the 9.2. 27 Pseudomonas Exotoxin A (PE) immunotoxin (IT) efficiently kills melanoma cells through inhibition of protein synthesis followed by some morphologic and biochemical features of apoptosis, a different cell killing mechanism than the one caused by Dacarbazine (DTIC), a chemotherapeutic drug used to treat malignant melanoma. To examine whether induced DTIC resistance also is a determining factor for the effectiveness of 9.2. 27PE IT, we developed a DTIC resistant subline, FEMX-200DR, from the DTIC sensitive cell line FEMX. The cell variants were treated with 9.2. 27PE, an IT binding to the high molecular weight-melanoma associated antigen (HMW-MAA) expressed on most malignant melanoma cells. The IT was equally effective in killing the FEMX-200DR and the FEMX cells, and the cell death was primarily caused by inhibition of protein synthesis. The DNA repair enzyme and apoptotic marker PARP, a substrate of caspase-3, was inactivated, although we observed only a minor activation of caspase-3 and caspase-8, intracellular proteases involved in apoptosis. In addition to being DTIC resistant, the FEMX-200DR cells were also more resistant to apoptosis than the parent cells as a 3 times higher concentration of the apoptotic inducer Staurosporine was needed to obtain IC50. Furthermore, in early passage malignant melanoma cell lines established from lymph node metastases, the 9.2. 27PE caused a time-dependent and dose-dependent decrease in cell viability independent of their DTIC sensitivity. These findings show that the 9.2. 27PE IT efficiently can cause cell death in malignant melanoma cells independent of their level of resistance to apoptosis and DTIC.
The Croonian Lecture, 1976 - Egg cytoplasm and gene control in development

This article is concerned with how a fertilized egg develops into a complete individual. In nearly all animal species (the main exceptions being mammals), fertilized eggs develop entirely independently of their mother. Commonly, eggs are surrounded by layers of materials such as membranes, jelly layers, or a shell, which isolate the egg and developing embryo from their environment. Embryos remain inside these coverings until they hatch as a mobile, free-living larva capable of feeding itself. Such a stage is usually reached only a few days or even hours after fertilization. During this time, development appears to take place without any chemical or physical instructions from the embryo’s environment. Development involves the formation of hundreds or thousands of cells from a single fertilized egg cell, as well as the conversion of yolk, a food-reserve, into the numerous different kinds of proteins which make up the cells of a complete larva. The question of how a superficially structureless egg converts itself, in a relatively short time, into a complex and highly organized structure has interested scientists since the time of Aristotle, 2000 years ago. However, specific concepts or explanations of early development were not well formulated until the eighteenth century. In 1779, for example, Bonnet made the explicit proposal that in each egg is a miniature embryo which itself contains an ovary with eggs, each of which themselves contain miniatures with ovaries, and eggs, and so on - the so-called doctrine of ‘emboitement’. Even Bonnet did not believe this doctrine in its strict sense, which would demand, as Bonnet’s own calculations showed, that Eve would have had 27 million embryos in her ovary. Throughout the nineteenth century there was extensive discussion of the relative merits of epigenesis and preformation. † In the later part of the nineteenth century, there arose the concept of neopreformation, according to which the preformed components of a fertilized egg were thought of as molecules and not morphological structures. For example, Lankester (1877) stated that: ‘Though the substance of a cell may appear homogeneous under the most powerful microscope, excepting for the fine granular matter suspended in it, it is quite possible, indeed certain, that it may contain, already formed and individualised, various kinds of physiological molecules. The visible process of segregation is only the sequel of a differentiation already established, and not visible. ’ This concept of the existence of determinant molecules in eggs may be taken as the point of departure for the present article. A concise account of early theories of development is included in Davidson’s (1968) book, and a history of embryology has been published by Needham (1934) and Oppenheimer (1955).
Induction of endothelial cell apoptosis by the binding of anti-endothelial cell antibodies to Hsp60 in vasculitis-associated systemic autoimmune diseases.

OBJECTIVE Anti-endothelial cell antibodies (AECAs), which recognize a number of endothelial antigens, are seen in patients with systemic autoimmune diseases, more often in the presence of vasculitis than in its absence. Some AECAs induce apoptosis of endothelial cells (ECs), but their target antigens remain unknown. The aim of this study was to determine whether Hsp60 is a target antigen and whether AECAs induce apoptosis in ECs. METHODS Two-dimensional electrophoresis and conventional Western blotting techniques were used to characterize AECA targets. Hsp60 reactivity was determined by enzyme-linked immunosorbent assay. RESULTS Hsp60 was shown to be targeted by a proportion of AECAs. The level of reactivity was higher in patients with systemic autoimmune disease and vasculitis than in those without vasculitis and in patients with systemic lupus erythematosus than in patients with other systemic autoimmune diseases. Hsp60 was expressed on the plasma membrane of heat-stressed ECs, and this followed Hsp60 messenger RNA transcription, confinement of the protein to the cytoplasm, and translocation of the protein to the surface. Shedding of Hsp60 from ECs was induced by stress and resulted in the binding of soluble Hsp60 to the surface of ECs, particularly stressed ECs. Apoptosis of ECs was triggered by anti-Hsp60-containing AECA-positive sera and was inhibited by preincubation of the ECs with recombinant Hsp60. CONCLUSION Our data support the notion that Hsp60 is an important target for AECAs and that such an interaction contributes to pathogenic effects, especially in vasculitis-associated systemic autoimmune disease.
Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population

Objective To investigate whether baseline systolic blood pressure variability was a risk factor for stroke, cardiovascular mortality or cardiac events during the Syst-Eur trial. Design The Syst-Eur study was a randomized, double-blind, placebo-controlled trial, powered to detect differences in stroke rate between participants on active antihypertensive treatment and placebo. Systolic blood pressure variability measurements were made on 744 participants at the start of the trial. Systolic blood pressure variability was calculated over three time frames: 24 h, daytime and night-time. The placebo and active treatment subgroups were analysed separately using an intention-to-treat principle, adjusting for confounding factors using a multiple Cox regression model. Participants An elderly hypertensive European population. Main outcome measures Stroke, cardiac events (fatal and non-fatal heart failure, fatal and non-fatal myocardial infarction and sudden death) and cardiovascular mortality (death attributed to stroke, heart failure, myocardial infarction, sudden death, pulmonary embolus, peripheral vascular disease and aortic dissection). Results The risk of stroke increased by 80% (95% confidence interval: 17–176%) for every 5 mmHg increase in night-time systolic blood pressure variability in the placebo group. Risk of cardiovascular mortality and cardiac events was not significantly altered. Daytime variability readings did not predict outcome. Antihypertensive treatment did not affect systolic blood pressure variability over the median 4.4-year follow-up. Conclusion In the placebo group, but not the active treatment group, increased night-time systolic blood pressure variability on admission to the Syst-Eur trial was an independent risk factor for stroke during the trial.
EXTREME OBESITY IS ASSOCIATED WITH SUICIDAL BEHAVIOR AND SUICIDE ATTEMPTS IN ADULTS: RESULTS OF A POPULATION‐BASED REPRESENTATIVE SAMPLE

A number of studies have revealed that the number of completed suicides decreases with increasing body mass index (BMI). However, only few studies have evaluated the association between suicidal behavior, suicide attempts, and the various BMI categories. The aim of this study was to determine whether obesity is positively associated with increased suicide attempts and suicidal behavior with consideration of gender differences.
Do Palestinian workers' remittances from Israel matter for the Palestinian economy?

This paper studies the impact of Palestinian workers' remittances from Israel on Palestinian economic growth using quarterly data over the period 2000-2016. Stationary and cointegration tests as well as a vector error correction model are applied for such purpose. Cointegration tests provide evidence of a long-run positive equilibrium relationship between remittances and output growth. Results also indicate that remittances have influence on Palestinian economic development at both short- and long-run level. https://doi.org/10.24897/acn.64. 68.179
The mediating role of the nurse-patient dyad bonding in bringing about patient satisfaction.

AIM This article is a report on a Synergy Model-guided correlational study of the direct and indirect relations of nurse-characteristics and patient characteristics to patient satisfaction, as mediated by nurse-patient dyad bonding. BACKGROUND Findings from previous studies have revealed that interventions alone do not fully account for patient outcomes, and that the effect of interventions on outcomes is mediated by factors such as interpersonal communication. The characteristics of the nurse and the patient synergize during their interaction, forming nurse-patient dyad bonding that affects patient satisfaction. Patient satisfaction is regarded as a critical part of the quality outcomes in healthcare. METHOD A total of 210 nurse-patient dyadic interactions were observed using the Nurse-Patient Bonding Instrument. Nurse characteristics and patient characteristics were gathered through observation, interview and chart review. Data were collected in 2008 from four hospitals in the Philippines. RESULTS Path analysis revealed that the patient characteristic of predictability had both direct effect and indirect effects on patient satisfaction, and that the nurse characteristic of facilitation of learning had an indirect effect on patient satisfaction. Nurse-patient dyad bonding mediated the relations between patient predictability and patient satisfaction, and nurse facilitation of learning and patient satisfaction. CONCLUSION The nurse and the patient both have a role to play in forming a therapeutic dyadic relationship that brings about the desired outcome. Further research on the formation and development of nurse-patient dyads in other settings and with other patient outcomes is recommended.
Structural basis for recognition of intron branchpoint RNA by yeast Msl5 and selective effects of interfacial mutations on splicing of yeast pre-mRNAs

Saccharomyces cerevisiae Msl5 orchestrates spliceosome assembly by binding the intron branchpoint sequence 5′-UACUAAC and, with its heterodimer partner protein Mud2, establishing cross intron-bridging interactions with the U1 snRNP at the 5′ splice site. Here we define the central Msl5 KH-QUA2 domain as sufficient for branchpoint RNA recognition. The 1.8 Å crystal structure of Msl5-(KH-QUA2) bound to the branchpoint highlights an extensive network of direct and water-mediated protein–RNA and intra-RNA atomic contacts at the interface that illuminate how Msl5 recognizes each nucleobase of the UACUAAC element. The Msl5 structure rationalizes a large body of mutational data and inspires new functional studies herein, which reveal how perturbations of the Msl5·RNA interface impede the splicing of specific yeast pre-mRNAs. We also identify interfacial mutations in Msl5 that bypass the essentiality of Sub2, a DExD-box ATPase implicated in displacing Msl5 from the branchpoint in exchange for the U2 snRNP. These studies establish an atomic resolution framework for understanding splice site selection and early spliceosome dynamics.
Locating Affordable Housing: The Legal System's Misallocation of Subsidized Housing Incentives

The primary goal of subsidized housing policy in the United States is to increase access to affordable housing for low-income households. Yet data show that states disproportionately award low-income housing tax credits to finance the development of projects in neighborhoods where there is already a relatively high number of housing units available at similar rent levels. Through a fifty-state study of state housing agency allocation rules, this Article evaluates the legal apparatus that facilitates this “misallocation problem. ” I find that approximately seventy-five percent of states fail to make the provision of below-market rents a threshold requirement of receiving an award of low-income housing tax credits. As a result, locational choices often are dictated by private developers who are incentivized to develop where land is cheapest. I argue that states should revise their allocation rules to ensure that, as a default, tax credits are awarded to projects that offer at least a ten percent rent advantage as compared to the local private market. The Article considers challenges to this proposal related to lack of state housing agency autonomy, federal framework limitations, land costs, and local political opposition and, in each case, offers a variety of responses.
Modulated Binding of SATB1, a Matrix Attachment Region Protein, to the AT-Rich Sequence Flanking the Major Breakpoint Region of BCL2

ABSTRACT The t(14,18) chromosomal translocation that occurs in human follicular lymphoma constitutively activates the BCL2 gene and disrupts control of apoptosis. Interestingly, 70% of the t(14,18) translocations are confined to three 15-bp clusters positioned within a 150-bp region (major breakpoint region or [MBR]) in the untranslated portion of terminal exon 3. We analyzed DNA-protein interactions in the MBR, as these may play some role in targeting the translocation to this region. An 87-bp segment (87MBR) immediately 3′ to breakpoint cluster 3 was essential for DNA-protein interaction monitored with mobility shift assays. We further delineated a core binding region within 87MBR: a 33-bp, very AT-rich sequence highly conserved between the human and mouse BCL2 gene (37MBR). We have purified and identified one of the core factors as the matrix attachment region (MAR) binding protein, SATB1, which is known to bind to AT-rich sequences with a high propensity to unwind. Additional factors in nuclear extracts, which we have not yet characterized further, increased SATB1 affinity for the 37MBR target four- to fivefold. Specific binding activity within 37MBR displayed cell cycle regulation in Jurkat T cells, while levels of SATB1 remained constant throughout the cell cycle. Finally, we demonstrated in vivo binding of SATB1 to the MBR, strongly suggesting the BCL2 major breakpoint region is a MAR. We discuss the potential consequences of our observations for both MBR fragility and regulatory function.
The Impact of Terrorism on the Economic Growth: An Empirical Study of Pakistan 1

Terrorism has negatively affected growth and development and has forced an intense economic burden on Pakistan. The general loss of self-assurance in economy and high defense and security expenditures leads to economic distortions which further affects the economic growth and instability in the country. This study analyzes empirically the long and short-run impact of terrorism on the economic growth of Pakistan during 1980-2016 and suggests suitable policy measures to control the problems arising from the terrorism. The results of Auto Regressive Distributed Lag (ARDL) approach to co-integration reveals a long-term relationship among economic growth and independent variables during this period. The ARDL results reveal that terrorism is one of the main hurdles in the way of economic growth in Pakistan. Trade openness, human capital is the supporting factors in boosting economic growth. The results of Error Correction Mechanism (ECM) indicate that even in the short-run terrorism can deteriorate the economic growth of Pakistan. The negative impact of terrorism on the economy is proved beyond doubt from the findings of the study, thus, the study suggest that government should focus more on the basic causes of domestic terrorism and should emphasize on the awareness programs. The government should also focus on the reduction in the income inequality among the citizens as it is considered one of the key reasons to upsurge the terrorist activities among the deprived classes in the society.
Risk Factors for Vaginal Mesh Exposure After Mesh-Augmented Anterior Repair: A Retrospective Cohort Study

Objectives The aim of this study is to identify risk factors for vaginal mesh exposure after mesh-augmented repair of anterior prolapse. Methods We performed a retrospective cohort study of all patients who had mesh-augmented anterior repair by 1 surgeon between January 2007 and February 2012. Data were extracted from medical records. The primary outcome was the rate of anterior or apical vaginal mesh exposure. Both univariate and multivariate analyses were performed. Results A total of 201 subjects were included. The mean (SD) follow-up was 14.3 (12.4) months. All cases were done using a type 1 macroporous monofilament polypropylene mesh. The overall mesh exposure rate was 8.5% (17/201). Univariate analysis showed a statistically significant positive association between exposure rates and the following risk factors: lower body mass index (BMI) (P = 0.016), menopause in combination with the use of hormone replacement therapy (P = 0.023), midline sagittal vaginal incision (compared with distal transverse incision) (P = 0.026), concurrent total hysterectomy (P < 0.001), surgery time (P = 0.002), and worse apical prolapse at baseline (P = 0.007). After multivariate analysis using logistic regression, only BMI (P < 0.001) and concomitant total hysterectomy (odds ratio, 48; P < 0.001) remained relevant. The exposure rate was 23.5% (16/68) when concomitant hysterectomy was performed compared with 0.8% (1/133) when no hysterectomy was done. Exposure rates stratified by BMI class were 12.9% (8/62) for BMI less than 25 kg/m2, 9.5% (8/84) for BMI of 25 to 29.9 kg/m2, 3.1% (1/32) for BMI of 30 to 34.9 kg/m2, and 0% (0/23) for BMI greater than or equal to 35 kg/m2. Conclusions Concomitant total hysterectomy is an independent risk factor for mesh exposure after mesh-augmented anterior repair, whereas BMI may negatively correlate with exposure rates.
cDNA Cloning and Expression of the Xenopus Homologue of the Neural Adhesion Molecule, Contactin (F3/F11)

Abstract Contactin (F3/F11) is an immunoglobulin superfamily cell surface glycoprotein predominantly expressed in the nervous system. To examine the structure and tissue distribution of Xenopus contactin, a cDNA clone was isolated based on the amino acid sequences conserved among chicken and mammalian contactin proteins. The conceptual translate of the cDNA consists of 1005 amino acid residues that have 70% identity to those of chicken and mammalian contactin. Northern blot hybridization using a labeled cDNA fragment revealed specific expression of 6.5 kb mRNA in the brain. Monoclonal and polyclonal antibodies prepared to the recombinant Xenopus contactin peptides detected a single 135 kD band on Western blots of the brain and spinal cord extracts. Differential extraction and phosphatidylinositol-specific phospholipase C (PI-PLC) digestion experiments showed that the immunoreactive 135 kD proteins bind, at least in part, to the membrane by GPI anchor. On brain tissue sections, strong contactin immunoreactivities were detected on nerve fibers of a subset of cerebral and cerebellar neurons. These results suggest that the basic structure and tissue distribution of Xenopus contactin are similar to those in other vertebrates.