Miracle-dz/UniFAR-FTUs huggingface dataset:
Checkpoint Blockade Toxicity and Immune Homeostasis in the Gastrointestinal Tract

Monoclonal antibodies targeting the regulatory immune “checkpoint” receptors CTLA-4, PD-1, and PD-L1 are now standard therapy for diverse malignancies including melanoma, lung cancer, and renal cell carcinoma. Although effective in many patients and able to induce cures in some, targeting these regulatory pathways has led to a new class of immune-related adverse events. In many respects, these immune toxicities resemble idiopathic autoimmune diseases, such as inflammatory bowel disease, autoimmune hepatitis, rheumatoid arthritis, and vitiligo. Understanding the pathogenesis of these immune toxicities will have implications not only for care of patients receiving checkpoint blockade but may also provide critical insights into autoimmune disease. The gastrointestinal (GI) mucosa is arguably the most complex barrier in the body, host to a diverse commensal microflora and constantly challenged by ingested foreign proteins both of which must be tolerated. At the same time, the GI mucosa must defend against pathogenic microorganisms while maintaining sufficient permeability to absorb nutrients. For these reasons, regulatory cells and receptors are likely to play a central role in maintaining the gut barrier and GI toxicities, such as colitis and hepatitis are indeed among the most common side effects of CTLA-4 blockade and to a lesser extent blockade of PD-1 and PD-L1. High-dose corticosteroids are typically effective for management of both checkpoint colitis and hepatitis, although a fraction of patients will require additional immune suppression such as infliximab. Prompt recognition and treatment of these toxicities is essential to prevent more serious complications.
Effect of nasal triamcinolone acetonide on lower airway inflammatory markers in patients with allergic rhinitis.

BACKGROUND Allergic rhinitis (AR) and asthma are commonly associated, and similar underlying inflammatory processes link both diseases. AR, even in the absence of asthma, is associated with increased levels of exhaled nitric oxide (ENO) and hydrogen peroxide (H(2)O(2)) in exhaled breath condensate, 2 noninvasive markers of lower airway inflammation. OBJECTIVE We sought to evaluate the effect of treatment with the nasal steroid triamcinolone acetonide on ENO and exhaled H(2)O(2) in subjects with AR. METHODS We allocated 23 subjects in a randomized, double-blind, parallel-controlled fashion to 4-week treatment with triamcinolone acetonide (220 microg/d) or matching placebo. RESULTS ENO levels were greater in the subgroup with concomitant asthma (16/23 subjects) and decreased significantly with triamcinolone acetonide treatment in this subgroup of patients in comparison with patients receiving placebo. Breath condensate levels of H(2)O(2) were higher in patients with AR without asthma than in those with asthma but decreased significantly with triamcinolone acetonide treatment in both subgroups. No changes were observed in bronchial hyperresponsiveness, nasal and asthma symptoms, or peak expiratory flow with active treatment or placebo. CONCLUSION We conclude that treatment of AR with triamcinolone acetonide results in decrease of 2 noninvasive markers of lower airway inflammation, ENO and H(2)O(2), supporting that upper and lower airway inflammation should be seen as a continuum in subjects with AR with and without asthma. ENO might be a more specific marker of the lower airway inflammation present in asthma.
Poverty and inequality in the UK: 2009

In this Commentary, we assess the changes to average incomes, inequality and poverty that have occurred since Labour came to power in 1997, with a particular focus on the changes that have occurred in the latest year of data. This analysis is based upon the latest figures from the DWP's Households Below Average Income (HBAI) series, published on 7 May 2009 (Department for Work and Pensions, 2009). The HBAI series takes household income as its measure of living standards, and is derived from the Family Resources Survey, a survey of around 25,000 households in the United Kingdom that asks detailed questions about income from a range of sources.
Light-Induced Chloroplast Differentiation in Soybean Cells in Suspension Culture : Ultrastructural Changes during the Bleaching and Greening Cycles.

Suspension cultures of SB-P cells of soybean (Glycine max) provide a novel, reproducible, and readily manipulable greening system useful for inducing chloroplast differentiation. The cells are subcultured and grown heterotrophically (3% sucrose) in the dark for at least three successive 14-day periods, subcultured and grown in the dark for 7 days more, and finally placed under white light and grown photoautotrophically. Chlorophyll begins to accumulate by 1 hour of light and continues up to 12 days. The chlorophyll a:chlorophyll b ratio is 3:1. Dark-grown cells contain a small amount of total carotenoids which increase 10-fold during greening. Chloroplast differentiation is strictly light dependent, with photosynthetic pigments accumulating in the light and being lost from cells returned to the dark. In the dark, the chloroplasts dedifferentiate to amyloplasts as the organized thylakoid network is lost and starch accumulates. Under continuous light, the amyloplasts differentiate into mature chloroplasts as the organelle elongates, becomes spanned by several bands of thylakoids, and undergoes grana formation. Chloroplast differentiation in SB-P cells is similar to that in intact angiosperms developing under normal light-dark cycles.
Defining Identity Crimes

The objective of this paper is to report on the definitions of the terms used and in use across different regions for identity crime, namely, identity fraud, identity theft, and identity deception. The purpose is to clarify the meaning of the terms used with a view to gaining a consensus amongst the various stakeholders. This consensus is essential to enable further research. Without consensus measurement and comparisons are meaningless. Our study of identity fraud has an industry-driven research agenda. A grounded theory research methodology is used when interviewing government agencies and private organisation participants. Interviews sought to better understand current information and communications technology (ICT) practitioners’ security and privacy issues with respect to identity fraud perpetrator attacks. We found there to be consensus among stakeholders for the meaning of identity fraud and identity theft but less agreement for identity deception.
What We Know About Environmental Policy: An Inductive Typology of the Research

Environmental performance is a multidimensional concept that is difficult to measure since it concerns either the pollution generated by companies, their energy consumption and their different environmental policies. Academic research has used objective and/or non-objective indicators to measure this performance, dealing with both its managerial and measurement dimensions. This paper provides an inductive typology of the academic work concerning environmental policy through a computerized content analysis of 151 articles from 1992 to 2014 related to the management and measurement of environmental performance. The results highlight four major themes around which the academic research is organized: the relationship between environmental and financial performance, environmental performance under stakeholder engagement and institutional pressures, the strategic management of environmental performance, and increasing awareness of the sustainable development issue. Environmental performance research has evolved from a quantitative towards a more managerial dimension, highlighting the integration of performance within the management of a corporate business strategy.
The utility of implantable loop recorders for diagnosing unexplained syncope in 100 consecutive patients: five-year, single-center experience.

INTRODUCTION The purpose of this study was to retrospectively review the 5-year experience of a university hospital with implantable loop recorders (ILR) for the diagnosis of recurrent, unexplained syncope or presyncope. METHODS One hundred patients with syncope or presyncope of unknown etiology (negative tilt-table test, electrophysiology study and neurologic workup) underwent prolonged monitoring with an ILR from March 2000 to December 2004. All implants were performed using a first-generation (manual activation) or second-generation (manual plus automatic activation) ILR. RESULTS One hundred patients (70 women, 30 men) with a mean age of 68 +/- 18 years received the ILR. Twenty-three patients had coronary artery disease; 2 patients had dilated cardiomyopathy. Ten patients received a first-generation ILR, and 90 patients received a second-generation ILR. After 9 +/- 8 months' follow up, ILR interrogation identified an arrhythmogenic etiology to the syncope/presyncope in 45 patients with 55 events. Eight patients had a diagnosis by ILR less than 2 months from the date of implantation. Twenty-six patients had documented symptomatic bradycardia (asystole, sinus pauses, atrial fibrillation with long pauses); 11 patients had episodes of sinus tachycardia with heart rates of 130 to 140 beats/minute; 2 patients had atrial tachycardia; 5 patients had multiple episodes of nonsustained ventricular tachycardia (NSVT); 1 patient had sustained ventricular tachycardia, and 4 patients had paroxysmal supraventricular tachycardia. All arrhythmias were treated successfully by pacemaker/ICD implantation, radiofrequency catheter ablation and/or medications. One patient had seizure activity, which was detected by ILR as high-frequency noise. Two patients failed to activate their device, as it was a first-generation device. CONCLUSION Five-year experience with the ILR in 100 consecutive patients confirms the utility of this device in the diagnosis of recurrent, infrequent, unexplained syncope or presyncope. It helped diagnose 45% of patients with unexplained syncope with negative electrophysiologic and neurologic workup. Most of these patients had an arrhythmogenic etiology to their syncope. Medical therapy, device therapy, and/or catheter ablation helped successfully treat all patients with an arrhythmogenic etiology detected by ILR.
Circulating kidney injury molecule-1 is a novel diagnostic biomarker for renal dysfunction during long-term adefovir therapy in chronic hepatitis B

AbstractThe aim of this study was to evaluate serum kidney injury molecule-1 (KIM-1) as a new diagnostic marker of renal dysfunction in chronic hepatitis B (CHB) patients receiving long-term adefovir dipivoxil (ADV) treatment.We retrospectively enrolled 85 patients treated with ADV and 85 patients treated with entecavir (ETV) monotherapy, for at least 6 months. The 2 groups were matched for baseline age (± 5 years), sex, and estimated glomerular filtration rate (eGFR). Serum creatinine, cystatin C, and KIM-1 concentrations were measured, and eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine–cystatin C equation, at baseline and last follow-up.eGFR decreased by 10–20% from baseline in 11/85 (14.1%) patients, 20–30% in 5/85 (5.9%), and ≥ 30% in 2/85 (2.4%) patients treated with ADV. Serum KIM-1 was more significantly increased after ADV treatment 86.53 (10.20–355.40) pg/mL than ETV treatment 61.54 (10.53–200.56) pg/mL (P < 0.01). Furthermore, serum KIM-1 was positively correlated with serum cystatin C (r = 0.47; P < 0.001) and negatively correlated with eGFR (r = -0.46; P < 0.001). The area under the receiver operating characteristic curve (AUC-ROC) of serum KIM-1 for identifying renal dysfunction in all enrolled patients was 0.94 (95% confidence interval [95% CI], 0.87 to 1.02; P < 0.001), while the AUC-ROC of serum creatinine was only 0.82 (95% CI, 0.60 to 1.03; P < 0.01). Serum KIM-1 is a promising new diagnostic biomarker of renal dysfunction during long-term ADV therapy for CHB patients.
An Explanation for Accounting Income Smoothing

It is widely believed that corporate managers often engage in income smoothing, taking actions to dampen fluctuations in their firms' publicly reported net income. One reason given for this is that managers think that investors pay more for a firm with a smoother income stream. (See Ronen and Sadan [1981].) While there have been many empirical studies attempting to document whether or not income smoothing actually occurs, there has been little exploration of why a manager might rationally want to smooth his firm's income. Explaining why smoothing might be observed, and how it can result in an increased stock price, is the focus of this paper. In two recent studies, Lambert [1984] and Dye [1988] demonstrate, in agency settings, that a risk-averse manager who is precluded from borrowing and lending in the capital markets has an incentive to smooth his firm's reported income. In this paper, in contrast, it is shown that within a market setting an incentive exists for a manager to smooth income that is independent of either risk aversion or restricted access to capital markets. The market setting is also useful in that it allows for the analysis of the effect of income smoothing on stock prices. It is shown here that if a manager can choose which of two periods to recognize certain income, he may prefer the choice that is expected to
Menopause and the skin

Women live one‐third of their lives in the post‐menopausal state. Significant hormonal alterations occur at the time of menopause, leading to a range of physiological disorders affecting multiple organ systems in the body. The effects of menopause on the skin have been underresearched. Many skin changes occur at the time of menopause and the cutaneous effects of hormone replacement therapy are significant. Menopausal changes in hormones may alter the biomechanical properties of the skin and certain disorders are more common in menopausal women, such as lichen sclerosus, atrophic vulvovaginitis, flushing and dysaesthetic vulvodynia. Hair and oral changes may also be associated. As the average life expectancy increases, dermatologists need to be familiar with skin diseases affecting women in this age group.
Fatigue Properties Of Nodular Cast Irons Alloyed By Si, Mo And Cu

Abstract In recent years, the research of nodular cast iron has been focused on increasing fatigue resistence. In the paper, two types of alloyed nodular cast irons have been investigated – SiMo-nodular cast iron alloyed by 4% of silicon and 1% of molybdenum and SiCu-nodular cast iron alloyed by 4% of silicon and 1.5% of copper. SiMo-nodular cast iron is suitable for high-temperature applications, for example the exhaust manifolds of the combustion engines. SiCu-nodular cast iron is used in various components of tribotechnical units. These components are often loaded by fatigue. The mechanical and fatigue behaviour of both nodular cast iron types has been studied by means of tensile test, impact bending test, hardness test and fatigue tests. Fatigue tests were realised at low frequency cyclic push-pull loading up to 10 million cycles. The relationship between the amplitude of stress and number of cycles to failure was investigated and the fatigue strength was determined. Mechanical and fatigue properties of both nodular cast iron types are correlated with the microstructure of specimens.
Optimization and Performance Analysis of a Massively Parallel Dynamic Programming Algorithm for Rna Secondary Structure Prediction

An optimized and parallelized form of a dynamic pro gramming algorithm capable of generating optimal and suboptimal RNA secondary structures is pre sented. Implementation of this algorithm on a MasPar MP-2 with 16K processors is shown to perform ex tremely well for very large nucleic acid sequences such as HIV (AIDS) and Rhinovirus (common cold). These sequences are, respectively, 9,128 and 7,208 nu cleotides in length. By taking advantage of the parallel nature of MasPar and also optimizing the communica tion requirements the implementation essentially re duced the algorithm from order O(n3) to 0(n 2). This reduction in complexity enables us to fold large RNA sequences in reasonable amounts of time. This capa bility has proven to be a valuable tool in studying the molecular structure and biological function of mole cules this large.
Maternal MTHFR 677C>T is a risk factor for congenital heart defects: effect modification by periconceptional folate supplementation.

AIMS Periconceptional folate supplementation prevents neural tube defects and possibly congenital heart defects (CHD) as well. The search for candidate genes involved in the folate metabolism includes the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism. We studied the association between MTHFR 677C > T variants and CHD risk. The interaction with periconceptional folate supplementation was also investigated. METHODS AND RESULTS A case-control study and a family-based transmission disequilibrium test (TDT) were conducted to explore this association. In 133 triads, the TDT revealed no association of the fetal 677T allele with the development of a heart defect. In 158 mothers with a CHD-affected child, the maternal MTHFR 677CT and TT genotypes in combination with no use of periconceptional folate supplements were associated with, respectively, a three-fold (OR 3.3 95% CI 1.46-7.32) and six-fold (OR 6.3 95% CI 2.32-17.27) increased risk for conotruncal heart defects in offspring. In a case-only study, the interaction between periconceptional folate supplementation and maternal MTHFR genotype was significant (P = 0.012). CONCLUSION The maternal MTHFR 677C > T variants are a risk factor for CHD in offspring, confined to conotruncal heart defects. A gene-environment interaction between maternal MTFHR 677CT and TT genotypes with periconceptional folate supplementation was observed. These findings provide a mechanism of the protective role of folate and support the thesis that periconceptional folate supplementation might prevent CHD.
RBP1 Recruits Both Histone Deacetylase-Dependent and -Independent Repression Activities to Retinoblastoma Family Proteins

ABSTRACT Retinoblastoma (RB) tumor suppressor family proteins block cell proliferation in part by repressing certain E2F-specific promoters. Both histone deacetylase (HDAC)-dependent and -independent repression activities are associated with the RB “pocket. ” The mechanism by which these two repression functions occupy the pocket is unknown. A known RB-binding protein, RBP1, was previously found by our group to be an active corepressor which, if overexpressed, represses E2F-mediated transcription via its association with the pocket. We show here that RBP1 contains two repression domains, one of which binds all three known HDACs and represses them in an HDAC-dependent manner while the other domain functions independently of the HDACs. Thus, RB family members repress transcription by recruiting RBP1 to the pocket. RBP1, in turn, serves as a bridging molecule to recruit HDACs and, in addition, provides a second HDAC-independent repression function.
High dose CHOP: A phase II study of initial treatment in aggressive non-Hodgkin lymphoma. Cancer and Leukemia Group B 9351

Cyclophosphamide and doxorubicin, two important drugs in the treatment of lymphoma, exhibit a relationship between dose and fractional cell kill, and because of their toxicity profiles, they are candidates for significant dose escalation. We performed a phase II trial to determine the response rate, toxicity, and feasibility of escalated doses of both drugs as part of high dose CHOP in diffuse aggressive lymphoma. Patients who had advanced, previously untreated diffuse aggressive lymphomas (IWF E-H) and an International Prognostic Index of intermediate to high risk were eligible. Treatment was cyclophosphamide 2 gm/m2/day intravenously on Days 1 and 2 (total cycle dose 4 gm/m2), doxorubicin 35 mg/m2/day as a continuous infusion on Days 1 and 2 (total 70 mg/m2), vincristine 1.4 mg/m2 (maximum 2 mg) on Day 1 and prednisone 100 mg/day orally on Days 1 – 5 repeated every 3 weeks for a total of four cycles. G-CSF, prophylactic antibiotics, and mesna were provided. A total of 99 patients were enrolled; 98 received therapy. Major toxicities were Grade 4 neutropenia and thrombocytopenia occurring in 97% and 92%, respectively. Serious infections occurred in 53%. Treatment-related mortality was 2%. The overall response rate is 85%, and two-year failure free and overall survival are 39% and 64%, respectively. Persistent or relapsed lymphoma was the overwhelming cause of death. Six patients have developed AML or MDS. In view of the substantial toxicity accompanying high dose CHOP, the observed outcome suggests that its efficacy is not sufficient to make further study feasible.
Differential fertility, intergenerational occupational mobility, and change in the occupational distribution: Some elementary interrelationships

Abstract Relationships between differential fertility, intergenerational mobility, and change in the occupational distribution are formalized in a vector equation. Analysis of implications of differential fertility and intergenerational mobility patterns for change in the occupational distribution is possible in terms of components of the equations. While a process of intergenerational mobility is, by itself, “equilibrium-seeking” (in the sense of the “Formal Theory of Social Mobility”), it is seen that, when differential fertility is taken into account, the inter-generational change process is, in general, neither “equilibrium-seeking” nor “equilibrium-maintaining. ” Intergenerational mobility directly attributable to differential fertility and change in the occupational distribution may be separated from mobility attributable to “competition” or to other factors. The extent of latter type of mobility is seen to be relatively stable from country to country, whereas the extent of mobility due to differenti.
The Informational Content of Distant-Delivery Futures Contracts

Futures markets have two main goals: price discovery and risk management. Because management decisions often have to be made on a time horizon longer than the time until expiration of the nearby futures contract, it is important to determine how well distant-delivery futures contracts are able to assist in price discovery. We focus on soybean and live cattle distant-delivery futures contracts and test for the informational value added to nearby contracts. Two tests for information value provide partially conflicting results due to the different information measures employed. If being able to predict the price trend is sufficient, then we find some information value in distantdelivery futures contracts, while if accurate point estimates of future spot prices are desired the results are negative. Surprisingly, we do not find the expected dichotomy between the storable (soybeans) and non-storable (cattle) commodities.