Miracle-dz/UniFAR-FTUs huggingface dataset:
Evidence for Epigenetic Mechanisms That Silence Both Basal and Immune-Stimulated Transcription of the IL-8 Gene1

It is becoming increasingly clear that epigenetic silencing of gene transcription plays a critical role in the regulation of gene expression in many biological processes. Tight regulation of immunomodulatory substances that are important for the initiation of the inflammatory cascade, such as chemoattractive cytokines, is essential to prevent initiation of unrestrained immune activation. Using the Caco-2 intestinal cell line as a model, we reveal two distinctly different mechanisms by which the gene for the neutrophil chemoattractive cytokine IL-8 is silenced. Nuclear run-on studies, as well as stably transfected reporter and marked minigene constructs, demonstrate that cellular differentiation inhibits immune-activated transcription of the IL-8 gene, a mechanism that is dependent on histone deacetylase activity. Unexpectedly, this silencing mechanism does not involve previously described regulatory elements in the IL-8 promoter but rather cis-acting regions located at a distance from the IL-8 gene locus. Genomic elements distant to the immediate IL-8 locus are also required to silence aberrant basal transcriptional activity of the IL-8 promoter in the absence of immune activation. However, in this case, silencing occurs in a histone deacetylase-independent fashion. These findings were confirmed in transgenic mice in which, in the absence of these elements, aberrant IL-8 gene activity was present primarily in the intestinal tract. Epigenetic silencing of cytokine gene transcription through distant genomic elements is an important level of gene regulation that may be relevant to the pathogenesis of immunologic disease states.
Gender differences in socially responsible consumption. An experimental investigation

ABSTRACT We report on a simple experimental study designed to investigate the different gender attitudes towards socially responsible consumption. We use the Vote-with-the-Wallet Game, (VWG), a version of a repeated multiplayer prisoner’s dilemma that mimics the characteristics of the choice between a conventional and a socially responsible product. More precisely we test the effect of three factors: two different frames and an ex-post redistribution mechanism that transfers resources from purely self-interested consumers to responsible ones. We find that women remain significantly more cooperative (choosing more often the responsible good) when the redistribution mechanism is interrupted and are significantly less satisfied about the behaviour of the other players in that treatment.
Effects of video-feedback interaction training for professional caregivers of children and adults with visual and intellectual disabilities.

BACKGROUND Individuals in group homes may experience poor quality of social interaction with their professional caregivers, limiting their quality of life. The video-based Contact programme may help caregivers to improve their interaction with clients. METHOD Seventy-two caregivers of 12 individuals with visual and intellectual disabilities received a training programme and four individual video-feedback sessions. Quality of interaction was independently measured in an AB-design across subjects with two baseline and three intervention observations, using a time sampling coding system for interactive behaviour as well as a rating for affective mutuality. RESULTS From baseline to intervention, significant increases were found for the frequency with which caregivers confirmed the signals of clients, for the proportion of initiatives taken by clients that were responded to by the caregivers, and the affective mutuality as a quality of the interaction. No significant increase in client responsiveness was observed. Caregivers evaluated the intervention as useful and feasible. CONCLUSIONS The start of the Contact programme coincided with improved quality of interaction between professional caregivers and clients with visual and intellectual disabilities in group homes. Further research is necessary regarding the generalisability, long-term effects and effects on quality of life.
Interferon inducible antiviral MxA is inversely associated with prostate cancer and regulates cell cycle, invasion and Docetaxel induced apoptosis

The interferon inducible Myxovirus (influenza virus) resistance A (MxA) is considered as a key mediator of the interferon‐induced antiviral response. Mx proteins contain the typical GTP‐binding motif and show significant homology to dynamin family of GTPases. Strong interaction of MxA with tubulin suggests that Mx proteins could be involved in mitosis. Studies have shown that MxA inhibit tumor motility/metastasis and virus induced apoptosis. However, the clear association between MxA expression and cancer remains unknown. Meta‐analysis suggested that MxA expression was inversely correlated with prostate cancer (PCa). In this study, we demonstrate the expression MxA in PCa and its functional significance on the cancer phenotype.
The Empirical Sensitivity of the Phillips Curve

Few economic concepts have become as em bedded in the calculus of governmental decision making as has the notion of a trade-off between in flation and the full employment of (labour) re sources. While the policy-maker's conversion to the Phillips curve concept is perhaps understand able (since he can be absolved from a failure to attain one of two desirable objectives), the role of the research economist in the specification of an appropriate inflation-unemployment policy has been remarkably passive. The simple theory of the Phillips curve, and its obvious policy implications, were quickly incorporated into the generally ac cepted corpus of macroeconomics. Clearly, if such a trade-off curve exists and is stable, one would expect economic research to be directed toward two issues: (1) determination of the precise economic costs of inflation and unemployment to form bases for an assessment of optimality amongst attainable combinations of inflation and unemployment, and (2) theoretical analyses of various policies designed to shift the trade-off curve to more favourable positions. Surprisingly, very little substantive analytical work has come forward on either count. This is particularly true with respect to the first issue,1 and we are left with
Parenting styles, regimen adherence, and glycemic control in 4- to 10-year-old children with diabetes.

OBJECTIVE To examine relationships among parenting styles, regimen adherence, and glycemic control for preschool and elementary school children who have Type I diabetes. METHODS Parents of 55 children with diabetes completed parenting style and regimen adherence questionnaires. Glycosylated hemoglobin results were collected by chart review. RESULTS Parental warmth was associated with better adherence ratings. Regression analyses showed that parental warmth explained 27% of the variance in adherence ratings. Parental restrictiveness was associated with worse glycemic control in univariate analyses. However, only Black ethnicity, not adherence or parenting variables, predicted glycemic control. Black ethnicity and lower socioeconomic status (SES) were associated with more parental restrictiveness and worse glycemic control. CONCLUSIONS These results suggest that authoritative parenting, characterized by support and affection, may be advantageous for the regimen adherence and glycemic control of school-age and younger children with diabetes. Demographic characteristics are important and require further study in this context.
Clinical importance of follicular lesion of undetermined significance (diagnostic category III according to Bethesda System) diagnosed from Fine-Needle Aspiration Biopsy.

INTRODUCTION Follicular Lesion of Undetermined Significance (FLUS) belongs to the most controversial category of the Bethesda System. The aim of the study was to specify the risk of malignancy in patients with FLUS diagnosis in the material from the Institute of Oncology in Gliwice. This is the first Polish study specifying the risk of malignant neoplasm presence when Fine-Needle Aspiration Biopsy (FNAB) results in a report of diagnostic category III (DC III). MATERIAL AND METHODS Three hundred and ninety-five primary DC III diagnoses from FNABs of the thyroid gland performed from 2010 to 2015 were analysed. Correspondence of DC III with diagnoses from repeated FNABs and histopathology reports was evaluated. RESULTS From 395 DC III patients, 27 were treated surgically for clinical indications, receiving six diagnoses of cancer. Repeat FNAB was performed in 180 cases, and primary diagnosis was confirmed in 41 cases. In the second FNAB there was one diagnosis of "Papillary Thyroid Carcinoma" and one "Suspicious for Papillary Thyroid Carcinoma". From eight patients treated surgically in these series prior cytological cancer diagnosis was confirmed in two cases. Forty-six patients were subjected to third and subsequent FNABs; in one case the diagnosis was "Suspicious for Malignancy". In the analysed material the risk of cancer in patients with FLUS is 2.78%. Taking into account all 56 subsequent FNABs in which the primary diagnosis was confirmed, the risk decreases to 2.43%. CONCLUSIONS The diagnosis of FLUS in the absence of clinical indications is not a basis for surgical treatment.
Critical 23S rRNA interactions for macrolide-dependent ribosome stalling on the ErmCL nascent peptide chain

Abstract The nascent peptide exit tunnel has recently been identified as a functional region of ribosomes contributing to translation regulation and co-translational protein folding. Inducible expression of the erm resistance genes depends on ribosome stalling at specific codons of an upstream open reading frame in the presence of an exit tunnel-bound macrolide antibiotic. The molecular basis for this translation arrest is still not fully understood. Here, we used a nucleotide analog interference approach to unravel important functional groups on 23S rRNA residues in the ribosomal exit tunnel for ribosome stalling on the ErmC leader peptide. By replacing single nucleobase functional groups or even single atoms we were able to demonstrate the importance of A2062, A2503 and U2586 for drug-dependent ribosome stalling. Our data show that the universally conserved A2062 and A2503 are capable of forming a non-Watson–Crick base pair that is critical for sensing and transmitting the stalling signal from the exit tunnel back to the peptidyl transferase center of the ribosome. The nucleobases of A2062, A2503 as well as U2586 do not contribute significantly to the overall mechanism of protein biosynthesis, yet their elaborate role for co-translational monitoring of nascent peptide chains inside the exit tunnel can explain their evolutionary conservation.
Resistance to sunitinib in renal clear cell carcinoma results from sequestration in lysosomes and inhibition of the autophagic flux

Metastatic renal cell carcinomas (mRCC) are highly vascularized tumors that are a paradigm for the treatment with antiangiogenesis drugs targeting the vascular endothelial growth factor (VEGF) pathway. The available drugs increase the time to progression but are not curative and the patients eventually relapse. In this study we have focused our attention on the molecular mechanisms leading to resistance to sunitinib, the first line treatment of mRCC. Because of the anarchic vascularization of tumors the core of mRCC tumors receives only suboptimal concentrations of the drug. To mimic this in vivo situation, which is encountered in a neoadjuvant setting, we exposed sunitinib-sensitive mRCC cells to concentrations of sunitinib below the concentration of the drug that gives 50% inhibition of cell proliferation (IC50). At these concentrations, sunitinib accumulated in lysosomes, which downregulated the activity of the lysosomal protease CTSB (cathepsin B) and led to incomplete autophagic flux. Amino acid deprivation initiates autophagy enhanced sunitinib resistance through the amplification of autolysosome formation. Sunitinib stimulated the expression of ABCB1 (ATP-binding cassette, sub-family B [MDR/TAP], member 1), which participates in the accumulation of the drug in autolysosomes and favor its cellular efflux. Inhibition of this transporter by elacridar or the permeabilization of lysosome membranes with Leu-Leu-O-methyl (LLOM) resensitized mRCC cells that were resistant to concentrations of sunitinib superior to the IC50. Proteasome inhibitors also induced the death of resistant cells suggesting that the ubiquitin-proteasome system compensates inhibition of autophagy to maintain a cellular homeostasis. Based on our results we propose a new therapeutic approach combining sunitinib with molecules that prevent lysosomal accumulation or inhibit the proteasome.
Depression in patients with HIV infection.

The epidemiology, clinical features, and drug treatment of depression in HIV-infected patients are discussed. The lifetime prevalence of depression in patients infected with HIV has been estimated at 22-45%. The signs and symptoms of depression are similar in HIV-infected and noninfected patients, but patients with HIV infection may more frequently have sleep and appetite disturbances. Diagnosis should focus on affective or cognitive depression symptoms that reflect mood state alone. Patients with a history of depression, homosexual men, women, and i.v. drug abusers are among HIV-infected individuals who may be at increased risk for depression. Depression may alter the course of HIV infection by impairing immune function or influencing behavior. Depression my contribute to nonadherence to therapy. Antidepressant therapy is effective in most HIV-positive patients with major depression. Tricyclic antidepressants (TCAs) have produced response rates as high as 89%, but their usefulness has been limited by adverse effects. Selective serotonin-reuptake inhibitors and other non-TCAs have also demonstrated efficacy and are generally better tolerated. Psychostimulants have improved mood, cognition, and energy level, and androgens have been used for their anabolic effects. The systemic concentrations of antidepressants may be altered by coadministered drugs that affect their cytochrome P-450 isoenzyme-mediated metabolism; in turn, the metabolism and toxicity of certain antiretrovirals may be affected by antidepressants. Guidelines on the treatment of depression in the general population may be applied to patients with HIV infection. Depressive disorders are prevalent among patients with HIV infection but often respond to a variety of treatments.
India and the United States: Accidental or Inevitable Antagonists?

t he relationship between India and the United States has been, sad to say, more often one of a tagonism than of friendship. If relations are to improve, we must understand how deep seated that antagonism is. An "accidental" antagonism is almost by definition easily resolved by the actions of persons of good will. Difficulties arose, this view runs, because of it-might-have-been-otherwise events-Richard Nixon's getting upset by his treatment in Delhi when he was at the nadir of his political career after his defeat in the 1962 California gubernatorial election, Krishna Menon's particularly irritating manners, and the like. Small matters that have been blown out of proportion can quickly be brought back into perspective once sensible politicians and officials set to work. "Inevitable" antagonisms, on the other hand, implydthat the conflict is more deep seated, and that solutions will be beyond the capacity of the particular governments but must await a changed situation. The dissolving of the antagonism will occur when long-term changes occur, and solutions emerge. In this view-which I share (though perhaps not in the extreme form presented here for the purposes of stimulating discussion)-there are fundamental divergences of interests and world-view that keep India and the United States apart and explain the surface-level, often trivial, disagreements and conflictual policies. There are many layers to the India-U.S. relationship, which I somewhat arbitrarily examine from three angles: geopolitical, economic, and sociocultural/personal. My strategy of exploration is archaeological: I consider the surface layers first and proceed to deeper, more fundamental ones.
Clinical and immunological manifestations in 134 Puerto Rican patients with systemic lupus erythematosus

To gain a better understanding of systemic lupus erythematosus (SLE) in Puerto Ricans we studied the clinical and serologic manifestations in a cohort of 134 patients. The female to male ratio was 18: 1. Mean age at diagnosis was 32 12 y. The mean duration of disease and follow-up were 7.4 6.0 and 5.8 6.0 years respectively. Mortality was 3%. Photosensitivity (76.9%) and malar rash (71.9%) were the most common clinical manifestations. Arthritis was observed in 67.5% of patients. Anemia was seen in 67.2% of patients, but only 12.7% had autoimmune hemolytic anemia. Leukopenia (41.8%) and lymphopenia (64.9%) were also common. Serositis was observed in only 28%. Severe kidney damage such as nephrotic syndrome (14.2%) or renal failure (4%) was infrequent. Cardiovascular (12.7%) and neurologic (9.0%) manifestations were also uncommon. Antinuclear antibodies (ANA) were detected in 93.3%, anti-dsDNA antibodies in 54.5%, anti-Ro antibodies in 30.1% and anti-La antibodies in 14.2%. Low C3 and low C4 were observed in 38.3% and 35.7% respectively. This study suggests that Puerto Ricans with SLE present a mild form of disease predominantly manifested by cutaneous, musculoskeletal and hematologic involvement, but low prevalence of major organ damage and low mortality.
An effcient induction motor drive method with a regenerative power storage system driven by an optimal torque

When the motor speed is reduced by using a regenerative brake, the mechanical energy of rotation can be converted to the regenerative electric energy. In order to improve the efficiency of the motor drive systems, the regenerative power is charged and discharged by power storage systems (PSS). Moreover, optimal regenerative and acceleration torque of the motor should be discussed in order to maximize the regenerative electric energy and to minimize the required energy for acceleration. This paper presents an effective robust control method of a regenerative power storage system (PSS) and a design methodology of an optimal acceleration torque in order to achieve an efficient induction motor drive system. The PSS, treated in this paper, consists of an electrolytic capacitor and a bi-directional DC-DC chopper. At first, it will be shown that the PSS can be represented by a quite general second order differential equation. For this model, a robust control method will be proposed. Secondary, an optimal acceleration torque will be derived by means of variational method. The effectiveness of the proposed methods are illustrated by some simulations and experiments.
Spread through air spaces is a predictive factor of recurrence and a prognostic factor in stage I lung adenocarcinoma.

OBJECTIVES Spread through air spaces (STAS) is considered a prognosticator related to local recurrence. We assessed the prognostic impact of spread through air spaces and local recurrence in stage I lung adenocarcinoma. METHODS From July 2004 to November 2014, 877 lung cancer patients underwent surgery, of whom 318 with pathological stage I adenocarcinoma were reviewed. We investigated the characteristics of spread through air spaces and analysed the relationship between spread through air spaces and prognosis. RESULTS The median follow-up was 30 months. Of the 318 patients, 47 (14.8%) had spread through air spaces. The patients with spread through air spaces were associated with male sex (P < 0.001), smoking (P < 0.001), solid nodules (P < 0.001), stage IB disease (P = 0.006), epidermal growth factor receptor mutation negativity (P < 0.001), and lymphovascular (P < 0.001) and pleural invasion (P = 0.001). Among the preoperative findings, spread through air spaces was significantly related to solid nodules on computed tomography. Local recurrence occurred in 11 of 47 (23.4%) cases with spread through air spaces and 10 of 271 (3.7%) cases without spread through air spaces (P < 0.01). Univariate analysis showed that the overall 5-year survival rates were 62.7 and 91.1% in cases with and without spread through air spaces, respectively (P < 0.01), and the recurrence-free 5-year survival rates were 54.4 and 87.8% in cases with and without spread through air spaces, respectively (P < 0.01). Multivariate analysis confirmed spread through air spaces as a significant prognosticator for overall survival and a predictive factor for recurrence after surgery. CONCLUSIONS Among stage I lung adenocarcinoma patients, spread through air spaces was found frequently in the invasive cases and was closely related to poor prognosis and recurrence.
Relationship of depression, disability, and quality of life in Parkinson's disease: a hospital-based case-control study.

BACKGROUND Depression, anxiety, cognitive impairment, sleep disturbances are common neuropsychiatric manifestations in Parkinson's disease (PD). AIMS To compare the prevalence and severity of depression in PD with a group of patients with other chronic medical illnesses and ascertain the relationship of depression with disability and quality of life in PD. SETTINGS AND DESIGN Hospital-based prospective case-control study. PATIENTS AND METHODS Forty-six PD patients and 30 non-PD controls having chronic medical conditions were studied. All were assessed by Beck Depression Inventory (BDI) and Montgomery Asberg Depression Rating Scale (MADRS), World Health Organization Disability Assessment Schedule (WHODAS II) and World Health Organization Quality of Life Scale-Brief Version (WHOQOL-Bref). Statistical Analysis Used : SPSS Version 13.0 was used for analysis which included descriptive tests, independent t test, chi-square test, Fisher's exact test, and Pearson's correlation coefficient. Results : The prevalence of depression was higher and more severe in PD than controls (MADRS: 54.3% vs 23.3%, P<0.01; BDI 49.9% vs 23.4%, P<0.05). PD patients had significantly greater overall disability than controls (36.8±19.4 vs 15.1±15.4; P<0.001), and the difference was observed in all six domains of WHODAS II. CONCLUSIONS PD patients had inferior quality of life than controls in all four spheres of WHOQOL-Bref. In PD, depression correlated positively with various domains of disability (P<0.001) and negatively with quality of life (P<0.001). In summary, the prevalence and severity of depression is significantly higher in PD than can be explained by chronic illness. Depression plays an important role in determining the disability and quality of life.
Social determinants of mixed feeding behavior among HIV-infected mothers in Jos, Nigeria

Abstract Mixed feeding confers excess risk of mother-to-child transmission (MTCT) of HIV compared with exclusive breastfeeding and exclusive formula feeding. We undertook a qualitative and quantitative cross-sectional survey to identify the social determinants of mixed feeding among a subset of the 469 HIV-infected women enrolled in a MTCT prevention program in Jos, Nigeria. Formula was provided free-of-cost. Of the 91 participants, 68 (75%) exclusively formula fed, 7 (8%) exclusively breastfed, and 16 (18%) practiced mixed feeding. Of the mixed feeding women, seven primarily formula fed and nine primarily breastfed. Women who primarily formula fed described family pressure as the reason for mixed feeding, while women who primarily breastfed reported insufficient breast milk. In a multivariate analysis, lack of partner support of the feeding decision predicted mixed feeding behavior (OR: 4.2; 95% CI: 1.2–14.9; p=0.03). Disclosure of HIV status was significantly correlated (p<0.001) with partner support. HIV prevention interventions aimed at reducing mixed feeding should encourage supportive partner relationships that facilitate disclosure of HIV status. Attention should also be made to the differing pressures faced by women attempting to exclusively breast feed and exclusively formula feed.