Miracle-dz/UniFAR-FTUs huggingface dataset:
Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is a critical immunoregulatory molecule (expressed on activated T cells and a subset of regulatory T cells) capable of down-regulating T cell activation. Blockade of CTLA-4 has been shown in animal models to improve the effectiveness of cancer immunotherapy. We thus treated 14 patients with metastatic melanoma by using serial i.v. administration of a fully human anti-CTLA-4 antibody (MDX-010) in conjunction with s.c. vaccination with two modified HLA-A*0201-restricted peptides from the gp100 melanoma-associated antigen, gp100:209–217(210M) and gp100:280–288(288V). This blockade of CTLA-4 induced grade III/IV autoimmune manifestations in six patients (43%), including dermatitis, enterocolitis, hepatitis, and hypophysitis, and mediated objective cancer regression in three patients (21%; two complete and one partial responses). This study establishes CTLA-4 as an important molecule regulating tolerance to “self” antigens in humans and suggests a role for CTLA-4 blockade in breaking tolerance to human cancer antigens for cancer immunotherapy.
Another Chloromyxid Lineage: Molecular Phylogeny and Redescription of Chloromyxum careni from the Asian Horned frog Megophrys nasuta

ABSTRACT. Infection with Chloromyxum careni Mutschmann, 1999 was found in the Asian horned frog Megophrys nasuta from Malaysia and Indonesia. Kidney was the only organ infected. Coelozoic plasmodia up to 300 μm were localized in Bowman's space, embracing the glomerulus from all sides, or rarely in lumina of renal tubules. Plasmodia are polysporic, containing disporic pansporoblasts. Myxospores observed by light microscopy are colorless, variable in shape and size, measuring 6.0–8.5 × 5.0–6.5 μm, composed of two symmetrical valves joined by a meridian suture, containing four pyriform polar capsules 3.0–4.0 × 2.5–3.0 μm and a single sporoplasm. Each valve possesses 14–24 (median 21) fine longitudinal ridges clearly visible only in scanning electron microscopy. Rarely, atypical spores with a markedly pointed posterior pole and only 6–10 surface ridges are present in plasmodia together with typical spores. Both small subunit (SSU) and large subunit (LSU) rRNA gene sequences possess extremely long GU‐rich inserts. In all SSU and LSU rDNA‐based phylogenetic analyses, C. careni clustered as a distinct basal branch to the Myxobolus+Myxidium lieberkuehni clade, out of the marine Chloromyxum clade containing Chloromyxum leydigi, the type species of the genus. These morphological and phylogenetic data suggest erection of a new genus for the C. careni lineage, but we conservatively treat it as a Chloromyxum sensu lato until more information is available.
Voice versus Exit: The Causes and Consequence of Increasing Shareholder Concentration

This conceptual paper investigates the reasons behind the recent increase in corporate engagement by institutional shareholders. Whilst the rise of institutional ownership is nothing new, what has changed is that large economies of scale in the fund management industry have resulted in ownership concentration amongst a relatively small number of very large institutions. This ownership concentration has brought down the cost of engagement while at the same time raising the cost of exit in terms of higher transactions costs (market impact). What has furthermore limited the restricted the ability to exit has been the shift from active to passive funds. Accompanying these institutional trends has been an evolution in the understanding of fiduciary duty towards an understanding that puts greater weight on the inclusion of environmental, social and governance factors. Applying Hirschman’s concepts of Exit and Loyalty to the investment management industry this paper shows that a rising ownership concentration and the growth in passive assets means that for the majority of institutional shareholders, voice is today more practicable than exit. The inability to exit has resulted in an institutional investor community that is both more powerful and compelled to be more involved in corporate affairs.
Who gets the information about genetic testing for cancer risk? The role of race/ethnicity, immigration status, and primary care clinicians

This study identified factors associated with awareness of genetic testing for cancer risk in the US general population. Multiple logistic regression analysis was used to analyze data from the 2000 National Health Interview Survey. The strong predictors were education, race/ethnicity, immigration status, health status, interaction with health professionals, controlling for socioeconomic status, cancer diagnosis, family history of cancer, and perceived personal cancer risk. The substantial lack of awareness of genetic testing among immigrant and ethnic populations warrants further research and tailored educational interventions. Ways to improve quality of patient interactions with non‐genetic clinicians in promoting public knowledge of genetic testing for cancer risk are also worthy of further exploration.
Cytoplasmic localization of DGK&zgr; exerts a protective effect against p53-mediated cytotoxicity

Summary The transcription factor p53 plays a crucial role in coordinating the cellular response to various stresses. Therefore, p53 protein levels and activity need to be kept under tight control. We report here that diacylglycerol kinase &zgr; (DGK&zgr;) binds to p53 and modulates its function both in the cytoplasm and nucleus. DGK&zgr;, a member of the DGK family that metabolizes a lipid second messenger diacylglycerol, localizes primarily to the nucleus in various cell types. Recently, reports have described that excitotoxic stress induces DGK&zgr; nucleocytoplasmic translocation in hippocampal neurons. In the study reported here we found that cytoplasmic DGK&zgr; attenuates p53-mediated cytotoxicity against doxorubicin-induced DNA damage by facilitating cytoplasmic anchoring and degradation of p53 through a ubiquitin–proteasome system. Concomitantly, decreased levels of nuclear DGK&zgr; engender downregulation of p53 transcriptional activity. Consistent with these in vitro cellular experiments, DGK&zgr;-deficient brain exhibits high levels of p53 protein after kainate-induced seizures and even under normal conditions. These findings provide novel insights into the regulation of p53 function and suggest that DGK&zgr; serves as a sentinel to control p53 function both during normal homeostasis and in stress responses.
Long-term societal impacts of conditional cash transfers: Bolsa família a decade in

Conditional Cash Transfers (CCTs) are innovative poverty intervention programs that have been adapted and adopted in dozens of countries around the world. The effectiveness of the programs in the short-term have been established by a number of studies, but they have only recently been around long enough to begin to observe whether they indeed disrupt the inter-generational poverty cycle as claimed. The expected long-term effects are central to the appeal of CCT programs. This empirical study examines the data to determine whether there is evidence that the long-term effects are as apparent as the short-term effects in one of the original adopters, Brazil. The analysis examines municipal level government data using OLS regression and finds evidence that CCTs raised 8 th grade graduation rates and lowered unemployment and birthrates. The conclusion is that, at least in Brazil, CCTs seem to be making headway in changing conditions that often lead to inter-generational poverty cycles.
Mediator subunit 23 overexpression as a novel target for suppressing proliferation and tumorigenesis in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most frequent cancer in the world. However, the molecular mechanisms involved in HCC are still poorly understood. Here, we study the role of mediator subunit 23 (MED23), a component of the Mediator complex, in hepatocarcinogenesis.
Live and Learn: Patient Education Delays the Need to Initiate Renal Replacement Therapy in End-Stage Renal Disease

During a longitudinal study of the quality of life of end-stage renal disease, 204 patients with deteriorating renal function were identified before dialysis or transplantation was required to preserve their lives. These patients were randomly assigned to either an enhanced or a standard education condition. The enhanced education condition consisted of a specially prepared slide-lecture show concerning kidney diseases and their treatment that was delivered by a trained research assistant. The standard education condition consisted of whatever educational procedures were routinely available at the participating hospital. All but six patients have now started treatment by maintenance dialysis. Individuals in the enhanced education condition survived an average of 4.6 months longer than did those in the standard education group without requiring the initiation of renal replacement therapy. This effect could not be attributed to physical differences between the groups, to cohort effects, to delays in contacting the patients, or to when or where they were identified. Possible mechanisms for this effect are discussed.
Complications Associated with Intravenous Midazolam Sedation in Anxious Dental Patients

Aim This prospective study was designed to establish the nature, frequency and sequelae of complications arising in patients receiving dental treatment under intravenous midazolam sedation. Methods All patients attending the Sedation Department at Newcastle Dental Hospital for intravenous sedation over a six-month period were audited. A standardised data-collection pro forma was designed in order to collect data relating to the patient, the sedation episode, the dental treatment and any complications arising. The published standard used in this study states that the incidence of complications should be no more than 8%. Results Four hundred and one patients were included. The mean dose of midazolam administered was 7.6 mg with a mean titration rate of 0.9 mg/min. Complications were reported in 12 patients (3%), 11 of which were minor and one moderate. All complications were managed successfully within the department with no lasting sequelae. Treatment was completed in 382 (95.7%) patients, with failure to complete treatment in 17 (4.3%) patients due to disinhibition (1), poor cooperation (10), and the sedation wearing off (6). Conclusion The standard was met because complications arising were infrequent (3%) and predominantly minor in nature. Complications were managed conservatively and effectively, with all patients being discharged home the same day with no lasting sequelae. The study demonstrates that intravenous midazolam provides a safe sedation technique, suitable for adult dental patients in primary care, when administered by trained personnel on carefully selected patients and in accordance with nationally agreed protocols and guidelines.
Remediation of Benzo[a]pyrene and Chrysene-Contaminated Soil with Industrial Hemp (Cannabis sativa)

ABSTRACT The phytoremediation, with industrial hemp (Cannabis sativa), of a Hawaiian silty clay soil contaminated with two polycyclic aromatic hydrocarbons (PAHs), chrysene and benzo[a]pyrene, was studied. Hemp showed a very high tolerance to the contaminants. The growth rates of hemp, compared with control, in soils fortified with chrysene and benzo[a]pyrene at concentrations of each varying from 25 to 200 μg/g were consistently above 100%. The plants grew from seed for 45 days in soil fortified with PAHs at concentrations of 25, 50, and 75 μg/g. Controls were pots with contaminated soil but no plant. PAHs levels were significantly reduced in all pots (control and seeded pots), except for one set at a high concentration of chrysene, which may be due to uneven spiking. A time course study over 28 days was done to monitor changes of microbial count and levels of chrysene. Little changes were observed for the total microbial count in the soil, and the concentration of chrysene in the soil decreased slightly in the pots containing plants. However, the chrysene levels in those pots were consistently lower than those in the pots without plants.
Giardiasis in the Adult Population of Dakshina Kannada District of South India

A 10-year study of Giardia intestinalis infections in adults was conducted in the Dakshina Kannada District of Karnataka State, South India. Coproparasitological investigations were made on 10000 stool specimens collected from selected patients. The infection rate was 37.1% with a male disease rate of 91.4%. The highest incidence rate was recorded in the age group 15–26 years. A possible reason for this preponderance of giardiasis in these males, is discussed. The optimum time for transmission appeared to be during the warmer months of the year (May to October) which coincided with the greatest amount of rainfall. The most common symptoms were abdominal discomfort, flatulence, diarrhoea, weight loss and anorexia. The predominating symptoms in our series varied with socio-economic level. There appeared to be some correlation between the clinical manifestations and the immune status of the individual.
MITF is a critical regulator of the carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) in malignant melanoma

The multifunctional Ig‐like carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1) is neo‐expressed in the majority of malignant melanoma lesions. CEACAM1 acts as a driver of tumor cell invasion, and its expression correlates with poor patient prognosis. Despite its importance in melanoma progression, how CEACAM1 expression is regulated is largely unknown. Here, we show that CEACAM1 expression in melanoma cell lines and melanoma tissue strongly correlates with that of the microphthalmia‐associated transcription factor (MITF), a key regulator of melanoma proliferation and invasiveness. MITF is revealed as a direct and positive regulator for CEACAM1 expression via binding to an M‐box motif located in the CEACAM1 promoter. Taken together, our study provides novel insights into the regulation of CEACAM1 expression and suggests an MITF‐CEACAM1 axis as a potential determinant of melanoma progression.
The impact of managed care on substance abuse treatment services.

OBJECTIVE To examine the impact of managed care on the number and types of services offered by substance abuse treatment (SAT) facilities. Both the number and types of services offered are important factors to analyze, as research shows that a broad range of services increases treatment effectiveness. DATA SOURCES The 2000 National Survey of Substance Abuse Treatment Services (NSSATS), which is designed to collect data on service offerings and other characteristics of SAT facilities in the United States. These data are merged with data from the 2002 Area Resource File (ARF), a county-specific database containing information on population and managed care activity. We use data on 10,513 facilities, virtually a census of all SAT facilities. STUDY DESIGN We estimate the impact of managed care (MC) on the number and types of services offered by SAT facilities using instrumental variables (IV) techniques that account for possible endogeneity between facilities' involvement in MC and service offerings. Due to limitations of the NSSATS data, MC and specific services are modeled as binary variables. PRINCIPAL FINDINGS We find that managed care causes SAT facilities to offer, on average, approximately two fewer services. This effect is concentrated primarily in medical testing services (i.e., tests for TB, HIV/AIDs, and STDs). We also find that MC increases the likelihood of offering substance abuse assessment and relapse prevention groups, but decreases the likelihood of offering outcome follow-up. CONCLUSION Our findings raise policy concerns that managed care may reduce treatment effectiveness by limiting the range of services offered to meet patient needs. Further, reduced onsite medical testing may contribute to the spread of infectious diseases that pose important public health concerns.
PUVA‐bath photochemotherapy (PUVA‐soak therapy) of recalcitrant dermatoses of the palms and soles

PUVA‐bath therapy has proven to avoid many side effects associated with oral 8‐methoxypsoralen (8‐MOP) treatment. In order to investigate the effectiveness of topical PUVA‐bath therapy (PUVA‐soak therapy) on chronic palmoplantar dermatoses, 30 patients with plaque‐type psoriasis, pustular psoriasis, endogenous eczema, dyshidrotic eczema and hyperkeratotic dermatitis of the palms and soles were treated over 8 weeks with PUVA‐soak using 8‐MOP. No additional treatment except skin moisturising cream such as unguentum emulsificans aquosum was used during the study period. The single UVA‐doses applied ranged from 0.3 to 3.0 J/cm2 (mean single dose of 1.8 J/cm2), with a mean cumulative dose of 48.6 J/cm2 per patient. Altogether 26 of 30 patients responded well within 8 weeks of treatment with 63% of all patients showing a complete remission and 23% showing considerable improvement, as shown by flattening of plaques, decreased scaling and erythema, as well as decreased vesicle and pustule formation. The condition responding best to our therapy was palmoplantar psoriasis followed by atopic eczema. Hyperkeratotic dermatitis displayed the poorest responding rates in this study. Unwanted side effects such as erythema, pain, blistering or patchy hyperpigmentation were not observed in any of the patients. We conclude that PUVA‐soak therapy can be highly efficient in the treatment of palmoplantar dermatoses, especially in the management of palmoplantar psoriasis.
Transient response assessment of vector PI current controllers in renewable energy applications

Grid codes force generation units based on renewable sources to act similarly to conventional power plants: when a fault is detected, they must remain connected and support the grid. To fulfill these requirements, the transient response of the current controllers is critical. This paper applies a recently proposed methodology which assesses and optimizes the transient response of proportional-resonant controllers (PR) to a different type of linear regulators: the vector proportional-integral (VPI) controllers. This methodology is based on the study of the error signal roots: both reference tracking and disturbance rejection abilities should be considered for proper gain tuning. This work proves that VPI controllers lead to longer settling times and bigger overshoot than PR controllers for high sampling frequencies. However, as the sampling frequency decreases, the transient response of both controllers presents more similarities. A three-phase voltage source converter prototype has been implemented. Experimental results provide a direct comparison between the transient behavior of VPI and PR controllers in different conditions: a +90° phase-angle jump in the current reference and a `type C' voltage sag at the point of common coupling.
Interdependence between Monetary Policy and Stock Liquidity: A Panel VAR Approach

This article examines the relationship between monetary policy and individual stock liquidity in an order-driven emerging stock market like India. This study considers stocks listed in National Stock Exchange of India (NSE) and continuously traded from April 2002 to March 2015. Considering the multiple dimensions of liquidity, this study uses five different liquidity proxies to capture the various facets of liquidity such as trading activity, price impact and transaction cost. An array of macroeconomic and firm-specific control variables are used while analysing the liquidity and monetary policy relationship. Econometric methods like panel vector autoregressive (VAR)–Granger causality test, impulse response functions and variance decomposition analysis have been employed to carry out this analysis. The empirical findings suggest that monetary policy significantly Granger-causes stock liquidity, and the expansionary monetary policy characterised by low interest rate and higher money supply is positively associated with individual stock liquidity in India. The impact of monetary policy on liquidity of individual stocks is more prominent during financial crisis. The findings of the present study have certain theoretical as well as practical implications. The market participants in equity market can improve the forecasting of liquidity of their investment portfolio by employing monetary policy along with individual asset’s characteristics. Regulators and policymakers may consider the cross-sectional relationship between stock liquidity and monetary policy as an important source of information for policy formulation and implementation. JEL Classification: E44, E51, G12
Estrogen Selectively Promotes the Differentiation of Dendritic Cells with Characteristics of Langerhans Cells1

The steroid hormone estrogen regulates the differentiation, survival, or function of diverse immune cells. Previously, we found that physiological amounts of 17β-estradiol act via estrogen receptors (ER) to promote the GM-CSF-mediated differentiation of dendritic cells (DC) from murine bone marrow progenitors in ex vivo cultures. Of the two major subsets of CD11c+ DC that develop in these cultures, estrogen is preferentially required for the differentiation of a CD11bintLy6C− population, although it also promotes increased numbers of a CD11bhighLy6C+ population. Although both DC subsets express ERα, only the CD11bhighLy6C+ DC express ERβ, perhaps providing a foundation for the differential regulation of these two DC types by estrogen. The two DC populations exhibit distinct phenotypes in terms of capacity for costimulatory molecule and MHC expression, and Ag internalization, which predict functional differences. The CD11bintLy6C− population shows the greatest increase in MHC and CD86 expression after LPS activation. Most notably, the estrogen-dependent CD11bintLy6C− DC express langerin (CD207) and contain Birbeck granules characteristic of Langerhans cells. These data show that estrogen promotes a DC population with the unique features of epidermal Langerhans cells and suggest that differentiation of Langerhans cells in vivo will be dependent upon local estrogen levels and ER-mediated signaling events in skin.
Lactulose-Mannitol Intestinal Permeability Test: A Useful Screening Test for Adult Coeliac Disease

The aim of this study was to determine the value of the lactulose-mannitol intestinal permeability test in screening the general adult population for unrecognized enteropathy and latent coeliac disease. Subjects with positive serology (identified by screening carried out by the Belfast MONICA Project) along with controls were followed-up after 3 years and classified as having transient serology, persistent serology or coeliac disease. A 5-h urine collection was performed following the ingestion of 5 g lactulose, 2 g mannitol and glucose as an osmotic filler. Urinary concentrations of lactulose and mannitol were measured by enzymatic analysis. Percentage lactulose excretion (%LE) (0·94 versus 0·31, P < 0·001) and lactulose-mannitol excretion ratio (LMER) (0·12 versus 0·02, P < 0·001) were significantly higher in screening-detected coeliac disease subjects compared with MONICA controls. The sensitivity of the permeability test was 87% in the screening situation compared with 81% in the clinical situation. In subjects with persistent and transient serology the LMER did not differ significantly from that of controls. The lactulose-mannitol test is a useful test for screening the general adult population for coeliac disease. Subjects with persistent and transient serology did not differ from MONICA controls and are unlikely to have latent coeliac disease.