Miracle-dz/UniFAR-FTUs huggingface dataset:
Selective Inhibition of BRCA2-Deficient Mammary Tumor Cell Growth by AZD2281 and Cisplatin

Purpose: To assess efficacy of the novel, selective poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor AZD2281 against newly established BRCA2-deficient mouse mammary tumor cell lines and to determine potential synergy between AZD2281 and cisplatin. Experimental Design: We established and thoroughly characterized a panel of clonal cell lines from independent BRCA2-deficient mouse mammary tumors and BRCA2-proficient control tumors. Subsequently, we assessed sensitivity of these lines to conventional cytotoxic drugs and the novel PARP inhibitor AZD2281. Finally, in vitro combination studies were done to investigate interaction between AZD2281 and cisplatin. Results: Genetic, transcriptional, and functional analyses confirmed the successful isolation of BRCA2-deficient and BRCA2-proficient mouse mammary tumor cell lines. Treatment of these cell lines with 11 different anticancer drugs or with γ-irradiation showed that AZD2281, a novel and specific PARP inhibitor, caused the strongest differential growth inhibition of BRCA2-deficient versus BRCA2-proficient mammary tumor cells. Finally, drug combination studies showed synergistic cytotoxicity of AZD2281 and cisplatin against BRCA2-deficient cells but not against BRCA2-proficient control cells. Conclusion: We have successfully established the first set of BRCA2-deficient mammary tumor cell lines, which form an important addition to the existing preclinical models for BRCA-mutated breast cancer. The exquisite sensitivity of these cells to the PARP inhibitor AZD2281, alone or in combination with cisplatin, provides strong support for AZD2281 as a novel targeted therapeutic against BRCA-deficient cancers.
The Emerging Nosocomial Pathogens Cryptosporidium, Escherichia coli 0157: H7, Helicobacter pylori, and Hepatitis C: Epidemiology, Environmental Survival, Efficacy of Disinfection, and Control Measures

Abstract New and emerging infectious diseases pose a threat to public health and may be responsible for nosocomial outbreaks. Cryptosporidium parvum and Escherichia coli are gastrointestina pathogens that have caused nosocomial infections via person-to-person transmission, environmental contamination, or contaminated water or food. Helicobacter pylori has been transmitted via inadequately disinfected endoscopes. Finally, hepatitis C may be acquired by healthcare personnel by percutaneous or mucous membrane exposure to blood or between patients by use of contaminated blood products or via environmental contamination. Rigorous adherence to Standard Precautions, Contact Precautions for patients with infectious diarrhea, disinfection of environmental surfaces, and appropriate disinfection of endoscopes are adequate to prevent nosocomial acquisition of these pathogens.
Implementation of Flexible Work Arrangements for Sustainable Development

Rapid globalization, the Internet-enabled on-demand economy, changing demographics, dynamism and flexibility in the workforce are redefining the landscape of work and inevitably lead to the changes in work arrangements. Flexible work arrangement (FWA) can be defined as a set of benefits provided by employer that lets employees to control over when and where they work outside of the standard arrangement. Although the concept of flexible work arrangements (FWAs) is quite widely analysed by scientific community during past decades, there is a lack of knowledge exploring the impact of flexible work practices on sustainable development. The purpose of this paper is to examine how flexible work arrangements can contribute to sustainable development at different levels of abstraction. Research methodology includes comparative analysis and synthesis of scientific literature, modelling, and empirical research in the form of survey and semi-structured interview. Research revealed that FWAs, when implemented with care and preparation, have a positive influence on sustainability at different levels of abstraction: individual level, company level, and society level. Benefits of flexible work practices turn up through three interconnected domains: economic, environmental, and social. Keywords: flexible work arrangements, sustainability, sustainable development, employees, organization
Quantification of Deep Gray Matter in Preterm Infants at Term-Equivalent Age Using Manual Volumetry of 3-Tesla Magnetic Resonance Images

OBJECTIVE. Nonhypothesis-based MRI-analysis techniques including deformation-based morphometry and automated tissue segmentation have suggested that preterm infants at term-equivalent age have reduced tissue volume in the basal ganglia and thalami, which is most apparent among infants with supratentorial lesions. The aim of our study was to test this hypothesis by direct measurement of thalamic and lentiform nuclei volumes in preterm infants at term-equivalent age and term-born controls using manual volumetry. DESIGN/METHODS. Forty preterm infants at term-equivalent age (median gestational age: 29.5 weeks; median birth weight: 1.3 kg) and 8 term-born controls were examined using a 3-T Philips (Best, Netherlands) system. T1-weighted volume images and T2-weighted fast-spin echo pseudovolumes were acquired. There was no significant difference in postmenstrual age at image acquisition between the 2 groups. ImageJ 1.34 (National Institutes of Health, Bethesda, MD) was used for manual segmentations. RESULTS. The median thalamic and lentiform nuclei volumes for preterm infants at term-equivalent age were 13.6 and 3.07 cm3, respectively, significantly smaller than term-control volumes of 16.3 and 5.6 cm3, respectively. Ten preterm infants at term-equivalent age had supratentorial lesions (intraventricular hemorrhage, periventricular leukomalacia, or hemorrhagic parenchymal infarction), and the median thalamic and lentiform volumes for this group were 10.4 and 1.7 cm3, respectively. When this group was excluded, the remaining infants who had mild or moderate diffuse excessive high signal intensity in the white matter on T2-weighted images had a smaller, yet significant, volume reduction compared with controls. Tissue volumes were not related to weight and gestational age at birth. CONCLUSIONS. Manual volumetry confirms that preterm infants at term-equivalent age have reduced thalamic and lentiform volumes compared with controls. This was most marked among infants with supratentorial lesions but was also seen among those with nonfocal white matter abnormalities.
Credit Controls as an Escape from the Trilemma. The Bretton Woods Experience

The macroeconomic policy "trilemma" is widely used as a framework to discuss the rationale for capital controls and monetary policy autonomy under the Bretton Woods system (1944-1971). Without denying its usefulness, I highlight two facts at odds with assumptions underlying the "trilemma" argument. First, conflicts between internal and external objectives were uncommon. Second, using quantitative credit controls allowed central banks to disconnect their interest rate from the domestic monetary policy stance. They assigned the interest rate to the external side while managing domestic credit expansion with direct quantitative controls. This paper documents that such mechanism was explicitly considered by contemporary economists and central bankers as a way to escape international financial constraints. In such an environment, capital controls were used to complement credit controls. Interest rate spreads were neither a good measure of capital controls nor of central bank autonomy.
The practical management of chronic hepatitis C infection in Japan - dual therapy of daclatasvir + asunaprevir

ABSTRACT Introduction: Without treatment, many of the 200 million people worldwide with chronic hepatitis C virus (HCV) infection will develop cirrhosis or liver cancer. Japan was the first nation to approve an interferon-free therapy for HCV, and sustained viral response (SVR) rates >90% have been achieved with asunaprevir, a protease inhibitor, plus daclatasvir, an inhibitor of the non-structural 5A (NS5A) protein. Areas covered: This review provides an overview of the results from both clinical trials and real world experience with asunaprevir and daclatasvir therapy focused primarily on Japan. A literature search using the keywords ‘asunaprevir,’ ‘daclatasvir,’ ‘interferon-free therapy,’ and ‘direct-acting antiviral drugs’ was initially used to select relevant literature for inclusion in the review. Expert commentary: While not approved in the United States, dual therapy with asunaprevir plus daclatasvir has already been successfully used in Japan and throughout East Asia to treat many thousands of patients. Pre-existing or treatment-emergent NS5A-Y93 or -L31 resistance-associated variants (RAVs) may lead to viral breakthrough, and alternative therapies should be considered for these patients, but patients who harbor NS5A RAVs only at low frequency are likely to achieve SVR. The therapy has also been shown to be safe and effective with renal dysfunction or liver cirrhosis.
Strengths and Weaknesses of the Consumer Expenditure Survey from a BLS Perspective

ACKNOWLEDGMENTS Thanks are extended to William Hawk and Aylin Kumcu for research assistance in preparing this document, and to Karen Goldenberg, Steve Henderson, Michael Horrigan, John Rogers, and Jay Ryan for comments on an earlier draft. All views expressed in this article are those of the authors and do not necessarily reflect the policies of the U.S. Bureau of Labor Statistics or the views of other staff members. The authors take full responsibility for any errors.
Barriers that impede the adoption of pediatric information technology.

BACKGROUND Information technology (IT) is a critical but underused component of health care. Many factors contribute to the inconsistent adoption of IT. OBJECTIVE To review the literature to better elucidate barriers that are likely to affect the adoption of IT by pediatric professionals. DATA SOURCES Manuscripts were found using a MEDLINE search combining the terms medicine, information systems, and technology transfer. I also obtained references cited by relevant articles. Finally, I explored the Internet using http://www.google. com and http://www.northernlight. com. STUDY SELECTION Articles discussing barriers or factors affecting the adoption of IT were considered for inclusion. Articles unrelated to clinical IT were excluded. DATA SYNTHESIS A variety of barriers exist that affect the adoption of useful technologies. Situational barriers include challenges imposed by the current national health environment, financial and legal risks associated with technology purchasing and use, and access to technology. The most significant barrier is that pediatric health care practitioners may lack the knowledge or training to use IT effectively. CONCLUSIONS Although some barriers exist that may be challenging to overcome, other barriers, such as the lack of knowledge about the uses of IT, are imminently solvable. Efforts to overcome these barriers should begin in earnest and should include educating stakeholders in the care of children and adolescents, as well as improving the knowledge about various technologies available to support pediatric and adolescent health care.
Cryptotanshinone protects against adriamycin-induced mitochondrial dysfunction in cardiomyocytes

Abstract Context: The serious side effect of Adriamycin (ADR) is cardiomyopathy. Cryptotanshinone (CRY) is widely and safely used as antioxidant with MTD more than 5 mg/g in rats (p.o). Objective: The objective of this study is to study the protection effects of CRY against ADR-induced mitochondrial dysfunction in cardiomyocytes. Materials and methods: The chemical administration lasted for 20 days with an effective dose of CRY (p.o.) at 50 mg/kg in rats. Mitochondrial respiratory chain complex activities, ATP generation, mitochondrial membrane potential (MMP), superoxide anion free radical, oxidative stress-relative enzymes, and mitochondrial biogenesis-relative factors in normal control, ADR (i.p., 1.25 mg/kg), and ADR (i.p., 1.25 mg/kg) + CYP (p.o., 50 mg/kg) groups were detected. Results: 50 mg/kg CRY significantly promoted the energy production of ATP (16.99 ± 2.38 nmol/g Pro) (Pro: Protein) by increasing the complexes activities except II (p > 0.05). After the treatment of CRY, the suppressed MMP was increased while superoxide anion free radical (0.57 ± 0.07/mg Pro) was inhibited markedly. Mitochondrial biogenesis-relative factors PGC-1α, NRF-1, and TFAM were also promoted. Remarkable augmentations of NO, inducible nitric oxide synthase (iNOS), and increased activity of GSH-PX (p < 0.05) were also detected after the treatment of CRY, while no obvious changes on the activity of nitric oxide synthase (cNOS; p > 0.05) were observed. Discussion and conclusion: These results suggest that CRY protects against ADR-induced mitochondrial dysfunction in cardiomyocytes. It could be an ideal potential drug of cardioprotection.
RADFET dosimeters in the belt: The Van Allen Probes on day 365

Van Allen Probes spacecraft VAP-A and -B, launched over a year ago [August 2012], carried 16 pMOS RADFETs into an orbit designed by NASA to probe the heart of the trapped-radiation belts. Nearly 350 days of in situ measurements from the Engineering Radiation Monitor (ERM) (a) demonstrated strong variations of dose rates with time, (b) found a critical correlation between its RADFET dosimeter and Faraday cup data on charged particles, and (c) mapped the belts by measuring variation with orbit altitude. This paper provides update on early results given in [1] along with details and discussion of the RADFET dosimetry analysed.
Microfabricated grooves recapitulate neonatal myocyte connexin43 and N-cadherin expression and localization.

Our objective is to alter the surface topography on which cardiac myocytes are grown in culture so that they more closely resemble their in vivo counterparts. Microtextured silicone substrata were made using photolithography and microfabrication techniques and then coated with laminin. Primary cardiac myocytes from newborn rats were plated on microgrooved and nontextured substrata. Myocytes were highly oriented on 5 microm grooves (69.8 +/- 2.0%) and significantly different, p < 0.0001, compared with randomly oriented cells grown on nontextured surfaces (2.9 +/- 0.95%; n = 19). Cells on shallower, 2 microm, grooves were slightly less well oriented (46.9 +/- 4.3%, n = 5, p < 0.001). The lateral spacings of the grooves were altered to examine changes in cell-to-cell contact by confocal immunocytochemistry and quantitative protein analysis. Connexin43 and N-cadherin were distributed around the perimeter of the myocytes plated on 10 x 5 x 5 microgrooved surfaces, similar to the localization found in the neonate. Connexin43 expression in cultures on 5 microm deep grooved substrata was equal to the neonatal heart, whereas it differed in nontextured surfaces. We conclude that it is necessary to combine groove depth (5 microm) and lateral ridge dimensions between grooves (5 microm) in order to recapitulate connexin43 and N-cadherin expression levels and subcellular localization to that of the neonate.
Pyogenic and tuberculous spondylodiskitis (vertebral osteomyelitis) in 80 adult patients.

Bacterial spondylodiskitis--i.e., adjacent vertebral osteomyelitis and diskitis--was studied in 80 adult patients. The infection was due to Mycobacterium tuberculosis in 31 cases (39%) and to pyogenic bacteria in 49 cases (61%). The latter pathogens included gram-negative bacilli in 16 cases (20%), Staphylococcus species in 15 (19%), Streptococcus species in 9 (11%), and Corynebacterium species in 1 (1%); the pathogens in the 8 remaining cases (10%) were not identified. Of the patients with tuberculous spondylodiskitis, 55% came from countries where tuberculosis is endemic (P < .001). Cases due to staphylococci and those due to M. tuberculosis were associated with a high frequency of previous active infection with those respective organisms at any site (47% and 42%, respectively; P < .001) and with a high rate of neurological complications (33% and 32%, respectively; P < .001). Nine patients with pyogenic spondylodiskitis (18%) but only one patient with tuberculous spondylodiskitis (3%) had diabetes mellitus (P < .05). Blood cultures were positive in 23 (56%) of the 41 cases of pyogenic spondylodiskitis due to an identified bacterium. Discovertebral needle biopsy contributed to the bacteriologic diagnosis in 29 (74%) of 39 cases.
The effect of early childhood caries on the quality of life of children and their parents

Objective: To determine the effect the early childhood caries (ECC) has on quality of life (QOL) parameters of both children and their parents. Materials and Methods: A cross-sectional study was carried out in the Department of Pedodontics and Preventive Dentistry, Manipal College of Dental Sciences, Manipal, India. Clinical Setting: The study consisted of 500 children–parent pairs. The study was performed in Manipal and Bhubaneswar (250 children–parent pairs in each group), fulfilling the inclusion requirements of healthy children aged between 3 and 6 years old and children having ECC. The two groups were equally divided as follows: Group I – 250 child–parent pairs (Bhubaneswar) and Group II – 250 child–parent pairs (Manipal and Udupi). Interventions: This was a questionnaire-based study and the parents and their children were provided the questionnaires with various questions on QOL parameters. Questionnaires were validated in the respective local languages. Results: The data collected were analyzed using the SPSS (version 10.0) package. For assessing the internal consistency of the questionnaire, Cronbach's alfa test was used. To find the comparison between groups, Chi square test and “t” test were used. Conclusions: Oral health has a definite effect on the QOL of children. The most affected parameters by ECC were consumption of food and sleep in children, which significantly influence the parents. The questionnaire had good internal consistency in both Kannada and Oriya versions.
Mutants of the Pentose Phosphate Pathway in Aspergillus nidulans

Mutants of the pentose phosphate pathway have been isolated in Aspergillus nidulans. These fail to grow on a variety of carbohydrates that are catabolized through the pentose phosphate pathway. They also grow poorly on nitrate and nitrite as sole nitrogen sources. The pentose phosphate pathway mutations have been assigned to two unlinked genes. Mutants with lesions in the pppB locus have reduced activities of four enzymes of the pentose phosphate pathway, of glucose-phosphate isomerase, and of mannitol-1-phosphate dehydrogenase. pppA− mutants have elevated activities of these same enzymes except for transaldolase, for which they have much reduced activity. Both classes of mutants accumulate sedoheptulose-7-phosphate to an extent that is increased considerably when nitrate is present in the medium. Nitrate does not cause an increase in accumulation of sedoheptulose-7-phosphate in double mutants which, in addition to the pppA1 mutation, carry a mutation that leads to the lack of nitrate reductase activity. These last results suggest that nitrate stimulates the flux through the oxidative pentose phosphate pathway, but that this stimulation depends upon the metabolism of nitrate.
Effect of calcification on in vivo mechanical response of rabbit arteries to balloon dilation.

BACKGROUND Atherosclerosis has been associated with loss of artery wall distensibility in human cadavers and in experimental animal models, giving it the lay term "hardening of the arteries. " METHODS AND RESULTS To assess the effect of calcification on arterial distensibility, balloon pressure and volume were recorded during dilation of calcified aortas in Watanabe heritable hyperlipidemic (WHHL) rabbits in vivo. Calcification was induced by dietary supplements of cholesterol, vitamin D2, and calcium. Balloon pressure, volume, and time signals were acquired at high frequency with controls for temperature and balloon inflation rate. Resistance to balloon dilation was minimal in control rabbit aortas (delta Vmax = 5.0 +/- 3.5 microliters) and in excised nonatherosclerotic human coronary arteries, and it was small in aortas from cholesterol-fed rabbits (12.3 +/- 8 microliters), even when lipid levels were markedly elevated by a high cholesterol diet (611 +/- 347 mg/dl). With dietary cholesterol, vitamin D2, and calcium supplements, WHHL rabbits developed mild hypercalcemia (15 +/- 1.9 mg/dl), hypercholesterolemia (1,100 +/- 633 mg/dl), moderate-to-marked aortic calcification, and high resistance to balloon dilation (38 +/- 27) comparable to that seen in angioplasty patients. CONCLUSIONS It is concluded that experimentally induced calcification decreases the distensibility of the rabbit aorta in vivo and that it yields to balloon dilation by plastic deformation closely resembling that seen in balloon angioplasty of human coronary arteries. These findings suggest that calcification contributes to arterial "hardening" associated with atherosclerosis.
Social work within a medical setting: an ethnographic study of a hospital social work team

This thesis reports on an ethnography of a hospital social work team in Wales. The aim of this study was to explore the nature of the statutory social work role within hospitals, to examine how hospital social workers do their work, and to shed light on how social work fits into the hospital context. My findings indicate that hospital social workers face constant pressure from managers and clinicians to expedite patient discharges, and exclude almost all other tasks from their role. Their daily work is a sequence of bureaucratic tasks, focused on management of the failing body, often to the exclusion of considering the wider social or psychological needs of the patient. Drawing on the work of Bauman, I argue that the bureaucratic and managerial systems in which hospital social workers operate produce dehumanising practices and distance decision makers from the human consequences and moral dimensions of their decisions. Even within these systems, however, some levels of discretion are maintained and hospital social workers use their discretion in a variety of ways. The hospital social workers in this study consistently expressed values derived from anti-discriminatory practice and, despite the constraints they encountered, were able to perform work that showed a concern for social justice, human rights and empowerment at the individual’s level. Thus, I argue that hospital social work in the UK is driven by liberal, rather than radical values, and is largely unconcerned with addressing wider issues of structure, social disadvantage and oppression. The hospital social work role involves the co- ordination of knowledge provided by clinical professions, which must then be processed to match the needs of the patient to the services that are available. Social workers are outsiders within the hospital setting and there is a considerable amount of distrust between them and the clinical professionals, which occasionally manifests in open conflict. I draw on Goffman’s dramaturgical insights to analyse how social workers manage their position within the hospital and draw on his theory of frame analysis to understand the way conflicts arise. Hospital social workers maintain a distinct identity within the hospital that is tied to their liberal values. I argue that their practices can be interpreted both as arising from the zeitgeist of liquid modernity and as adapting to the human need brought about by liquid modernity. I suggest that social work must either pursue individual liberation further, following the liberal values currently underpinning these hospital social workers’ practice, or adopt a more radical or critical approach in seeking to influence government policies around social care.