Miracle-dz/UniFAR-FTUs huggingface dataset:
Current Status and Future Directions of the Immune Checkpoint Inhibitors Ipilimumab, Pembrolizumab, and Nivolumab in Oncology

Objective: To provide the clinician with an update and the current status and future direction of approved immune checkpoint inhibitors (ICIs) in oncology. Data Sources: A PubMed search from January 1, 1966 to March 13, 2015 was performed using the key terms ipilimumab, pembrolizumab, lambrolizumab, nivolumab, immune checkpoint inhibitor, MDX-010, MDX-101, BMS-734016, MK-3475, SCH 900475, MDX-1106, BMS-936558, ONO-4538, CTLA-4, PD-1, or PD-L1 and cancer, oncology, or neoplasm. Additional references were identified from the investigators’ personal files, recent oncology meetings, review articles, clinical guidelines, and package inserts. Study Selection and Data Extraction: All English-language clinical trials assessing the safety and efficacy of ipilimumab, nivolumab, and pembrolizumab in cancer were considered. The PubMed search resulted in 215 trials; 33 met inclusion criteria. A further 28 trials were identified from the above sources; 61 trials from 2005 to 2015 were included. We consolidated and clarified treatment recommendations for the management of immune-related adverse events (irAEs), assessed response criteria, and calculated the clinical utility of leading tumor profiling options. Data Synthesis: Ipilimumab and nivolumab, but not pembrolizumab, have an overall survival (OS) advantage over chemotherapy first line in unresectable/metastatic melanoma. Nivolumab has an OS advantage versus chemotherapy in second-line squamous non-small-cell lung cancer. Data in other settings are promising. Nivolumab and pembrolizumab are better tolerated than ipilimumab. Further validation of response criteria is needed. Tumor profiling to predict clinical benefit is premature but promising. Conclusions: The treatment landscape in oncology is quickly evolving with the advent of ICIs.
Effects of Selenium and Iodine Deficiency on Type I, Type II and Type III Iodothyronine Deiodinases and Circulating Thyroid Hormones in the Rat

The effects of nutritional selenium (Se) deficiency over a period of three generations and of a combined selenium and iodine deficiency on hepatic and cerebrocortical iodothyronine deiodinases and on circulating thyroid hormone levels were examined in the rat. Se deficiency strongly decreased hepatic type I iodothyronine 5'- and 5-deiodinase to 6-13% of that in controls. Iodine depletion had only a marginal decreasing effect on the type I activity. Cerebrocortical type II 5'-deiodinase was decreased in Se-deficient, iodine-replete rats. Its 5-6-fold elevation in iodine-deficient rats was not reversed by additional selenium deficiency. Cortex type III 5-deiodinase was modestly decreased in all groups with insufficient trace element supply. Long-term Se deficiency has only limited effects on serum T4 and T3 levels. Two months of iodine deficiency decreased serum T4 to less than 10% of that in controls, but did not significantly affect serum T3 levels. The strong decrease of hepatic outer- and inner-ring deiodination of T4 in Se deficiency obviously reflects the reduced tissue concentration of the type I deiodinase which was recently identified as a selenoenzyme. The maintenance of increased cerebrocortical type II deiodinase in iodine-depleted animals irrespective of adequate or deficient selenium supply suggests that the type II isoenzyme does not contain selenium in its catalytic site. Further studies are necessary to clarify whether the weak, but repeatedly confirmed decrease of cortex type III deiodinase is the direct effect of Se deficiency or the indirect consequence of the multilevel change in thyroid hormone metabolism. (ABSTRACT TRUNCATED AT 250 WORDS)
The establishing of Chinese medical concepts in Norwegian acupuncture schools: the cultural translation of jingluo (‘circulation tracts’)

Acupuncture and other forms of so-called alternative treatments, originating outside the West, have increasingly become an integrated part of the repertoire of medical practices widely used in health care remote from their places of origin. The main aim of this paper is to elucidate the cultural translation of Chinese medical concepts in a Western, acupuncture setting located far from China. Drawing on material from ethnographic fieldwork in acupuncture schools in Norway, this study discusses how concepts used in Chinese acupuncture are taught and interpreted for biomedically oriented students. The paper concentrates on the concept of jingluo (‘circulation tracts’, ‘meridians’) which the schools considered to be vital in order to conduct acupuncture. Similar to several other Chinese medical concepts, jingluo presents claims about the body that significantly differ from biomedical assumptions. The paper adds novel resources and insights to the research concerning medical conceptions, in that it applies the perspective of ‘finitism’ as developed in the field of sociology of knowledge by Barnes, Bloor and Henry (1996) in its analysis. It presents an analysis of five empirical examples demonstrating how a variety of interpretations of jingluo – many of them from different fields and some of them contradictory – were involved in establishing jingluo. Finally, by examining examples of Chinese concepts of the body, the paper seeks to contribute to the wider field of the anthropology of the body as well as to add to our understanding of the ways in which medical pluralism and globalisation of acupuncture unfolds.
Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin.

SCOPE Naturally-occurring chemopreventive agent phenethyl isothiocyanate (PEITC), derived primarily from watercress, has been shown to inhibit cell growth and induce apoptosis in cancer cells. In this study, we examined the potential of PEITC in enhancing cisplatin-induced apoptosis in cervical cancer cells and its mechanisms. METHODS AND RESULTS HeLa cells were exposed to PEITC, cisplatin or both. Pretreatment of cells with PEITC strongly enhanced cisplatin-induced cytotoxicity. PEITC activated the mitogen-activated protein kinases, including c-Jun N-terminal kinase (JNK), extracellular signal-related kinase (ERK), and p38. Caspase-3 activity assay demonstrated that the synergistic induction of apoptosis was significantly attenuated by MEK1/2 inhibitor U0126, but not by JNK or p38 inhibitor, suggesting that ERK activation is responsible for the synergistic effect. We found that NF-κB signaling pathway is not involved in the synergistic effect. Sulforaphane and benzyl isothiocyanate, two other members of the isothiocyanate family, also sensitize HeLa cells to apoptosis induced by cisplatin. Furthermore, we found that the synergistic effect was also observed in cervical cancer C33A and breast cancer MCF-7 cells but not in normal mammary epithelial MCF-10A cells. Finally, we demonstrated that Noxa induction was associated with apoptosis induced by PEITC plus cisplatin. CONCLUSION Taken together, this study shows that PEITC can sensitize cancer cells to apoptosis induced by cisplatin and this effect is mediated through ERK activation, suggesting the potential of PEITC to be used as an adjuvant with cisplatin in combination therapeutic treatments.
Sarcoplasmic reticulum Ca2+ uptake and thapsigargin sensitivity in permeabilized rabbit and rat ventricular myocytes.

Ca2+ uptake by the sarcoplasmic reticulum (SR) and free [Ca2+] were measured simultaneously with indo 1 and a Ca(2+)-selective minielectrode in suspensions of permeabilized rabbit or rat ventricular myocytes (approximately 10 mg/mL protein). In the presence of 25 mumol/L ruthenium red and 10 mmol/L oxalate, the Km for Ca2+ uptake by the SR was approximately 250 nmol/L in rabbit and rat ventricular myocytes. The maximal Ca2+ uptake rate was 2.4 times higher in rat than in rabbit. Addition of 5 nmol thapsigargin (TG) per milligram cell protein abolished Ca2+ uptake completely in both species. The [TG] necessary for a half-maximal reduction of the uptake rate (K1/2) was 55 pmol/mg cell protein for rabbit and 390 pmol/mg cell protein for rat. Assuming that the number of pump sites is two times the concentration of TG necessary to inhibit half of the Ca2+ pump activity (ie, the TG affinity is very high), the density of pump sites is 7.7 mumol/kg wet wt for rabbit and 54.6 mumol/kg wet wt for rat. Despite a fivefold decrease of the Ca2+ uptake rate by a submaximal [TG], the permeabilized myocytes were still able to lower the free [Ca2+] to < 150 nmol/L from a peak value > 10 mumol/L. The relative inhibition of Ca2+ uptake by TG did not depend on the free [Ca2+]. Addition of more than 5 nmol TG per milligram cell protein abolished Ca2+ uptake by the SR completely in < 15 seconds and reduced the uptake rate by 95% in 5 seconds. (ABSTRACT TRUNCATED AT 250 WORDS)
Electoral Systems, Corruption and Satisfaction with Democracy

Corruption has been recognized as a detrimental factor of the citizens’ satisfaction with the way democracy works in their country and their confidence with political institutions. On the contrary, the direct impact of the institutional context on political support is less clear and previous studies present contradictory results. However, from a recent literature emerges that the institutional context plays a role in mediating the impact that the performance of the government authorities have on political support. This paper aims to analyze if and how the restraints posited by the electoral systems on political corruption affect the citizens’ satisfaction with democracy. The main argument advanced is that those characteristics of the electoral systems that help to constrain corruption among elected officials, strengthening the relation of accountability with the voters and favoring the monitoring by the opposition parties, weaken the negative effects of corruption on the level of political support expressed by citizens. Differently from previous studies that took into account the institutional context along the traditional distinction between majoritarian and proportional/consensual democracies, this paper focuses on specific aspects of the electoral system, such as the district magnitude, the ballot structure, the electoral formula and the level of vote-seats disproportionality. Several research hypotheses on the effect of corruption on political support conditional on the features of the electoral system are tested through a comparative multilevel design on a sample of 34 countries taken from the Module 2 of the CSES data. Results confirm that, even though there is not an electoral system that outperform the others, those features that reduce incentives of politicians to cultivate personal vote and extract rent from their position weaken the negative impact of perceived corruption on satisfaction with democracy.
Poor insight into memory impairment in patients with Huntington disease.

BACKGROUND AND PURPOSE Patients suffering from Huntington disease (HD) have been shown to present with poor self-awareness of a variety of symptoms. The study aimed to assess the self-awareness of memory impairment in HD in comparison to advanced Parkinson disease (PD), mild PD and cervical dystonia. MATERIAL AND METHODS Self-awareness was tested in 23 patients with HD by comparing patient and caregiver ratings in reference to clinical control groups (25 patients with advanced PD, 21 with mild PD and 20 with cervical dystonia). Self-awareness was tested using the Self Rating Scale of Memory Functions, which was administered to both the patients and the caregivers. Neuropsychological assessment addressed general cognitive status (Mini-Mental State Examination), verbal learning (Auditory Verbal Learning Test, 15-word list) and mood (Montgomery-Asberg Depression Rating Scale). RESULTS Patients with HD significantly underestimated their memory dysfunction. Underestimation of memory deficit correlated with disease duration and disease severity in HD. CONCLUSIONS Huntington disease patients underestimate memory dysfunction. These results add to the previous reports on poor insight in HD in other domains and suggest that anosognosia in HD, albeit usually rather mild, may be a generalized phenomenon.
Activation in Macrophages Proinflammatory Responses during TLR Lipin-1 Integrates Lipid Synthesis with

Lipin-1 is a Mg 2+ -dependent phosphatidic acid phosphatase involved in the de novo synthesis of phospholipids and triglycerides. Using macrophages from lipin-1–deﬁcient animals and human macrophages deﬁcient in the enzyme, we show in this work that this phosphatase acts as a proinﬂammatory mediator during TLR signaling and during the development of in vivo inﬂammatory processes. After TLR4 stimulation lipin-1–deﬁcient macrophages showed a decreased production of diacylglycerol and activation of MAPKs and AP-1. Consequently, the generation of proinﬂammatory cytokines like IL-6, IL-12, IL-23, or enzymes like inducible NO synthase and cyclooxygenase 2, was reduced. In addition, animals lacking lipin-1 had a faster recovery from endotoxin administration concomitant with a reduced production of harmful molecules in spleen and liver. These ﬁndings demonstrate an unanticipated role for lipin-1 as a mediator of macrophage proinﬂammatory activation and support a critical link between lipid biosynthesis and systemic inﬂammatory responses. The Journal of Immunology , 2014, 193: 000–000.
Intubating conditions and onset of neuromuscular block of rocuronium (Org 9426); a comparison with suxamethonium

The intubating conditions and neuromuscular blocking profile following 600 μg ˙ kg‐1 rocuronium (Org 9426) have been investigated in patients under various experimental conditions. They were compared with conditions following 1.5 mg ˙ kg‐1 suxamethonium, preceded by a precurarising dose (10 mg) of gallamine, and with those in a control group in the absence of a muscle relaxant. Rocuronium produced good to excellent intubating conditions at 60 as well as at 90 s after administration, even though there was only a partial blockade of the adductor pollicis muscle. Intubating conditions following suxamethonium were comparable with those after rocuronium. Half of the control patients could not be intubated. The clinical duration and the recovery time of 600 μg ˙ kg‐1 of rocuronium were 24(4) and 9(3) min (mean(s.d.)), respectively. Rocuronium may have a major advantage over existing non‐depolarising muscle relaxants due to the early presence of excellent intubating conditions. The results indicate that rocuronium may replace suxamethonium in procedures in which rapid sequence induction is required.
A critical assessment of transaction cost theory and governance of public services with special reference to water and sanitation

This paper aims to provide a critical assessment of Oliver Williamson’s work on the choice between public and private governance by focusing on his central proposition that public governance should be considered as an organisation of last resort when all else fails. Our primary argument is that Williamson’s work on public governance reflects an underdeveloped framework, mostly focusing on sovereign administration, and is not suitable for application to a host of other public services. It has the potential to corroborate any governance form that limits the usefulness of transaction cost theory (TCT) as an instrument of analysis and prediction. Although Williamson characterises TCT as an empirical success story, our application of it to the public–private dilemma for the water and sanitation sector finds very little historical and contemporary validity in this view.
New therapeutic options in systemic treatment of advanced cutaneous melanoma

Introduction: For many years systemic treatment of advanced/metastatic melanoma has been based on chemotherapy or immunotherapy. However, even very toxic regimens (e.g., polychemotherapy, bio-chemotherapy or immunotherapy with HD-IL-2) despite increased response rates as compared with standard dacarbazine monotherapy have not improved patients' outcomes. Over the last two decades, a huge effort, made in order to determine the molecular and immunological mechanisms responsible for biology of melanoma led to development of novel targeted agents. Areas covered: The aim of this article is to summarize data on novel targeted agents used for treatment of metastatic melanoma. The authors searched PubMed, EMBASE and abstracts from ASCO, ESMO, AACR congresses for Phase II/III clinical studies evaluating novel immunomodulating agents and kinase inhibitors in melanoma patients. Expert opinion: Elucidation of the crucial role of MAPK pathway and BRAF kinase mutations in particular has led to development of specific small molecule kinase inhibitors (vemurafenib, dabrafenib, trametinib), and new insight into molecular mechanisms responsible for immune response and tolerance resulted in development of immunomodulatory agents (ipilimumab, anti-PD1, anti-PD-L1). The introduction of novel drugs has changed the natural history of melanoma. However, it has also generated new clinical challenges that have to be resolved as soon as possible.
One-Hertz transcranial magnetic stimulation over the frontal eye field induces lasting inhibition of saccade triggering

The aim of the study was to examine the effect of low-frequency repetitive transcranial magnetic stimulation on saccade triggering. In five participants, a train of 600 pulses with a frequency of 1 Hz was applied over the right frontal eye field and – as control condition – over the vertex. After repetitive transcranial magnetic stimulation application, oculomotor performance was evaluated with an overlap paradigm. The results show that the repetitive transcranial magnetic stimulation effect was specific for frontal eye field stimulation. Saccade latencies were found to be increased bilaterally for several minutes after the stimulation, and the time course of recovery was different for the ipsilateral and contralateral sides. The results are discussed in the light of possible local and remote repetitive transcranial magnetic stimulation effects on the oculomotor network.
Organizational Commitment: Teachers' Perceptions in Turkey Örgütsel Adanmişlik: Türkiyedeki Öğretmenlerin Algilari

Studies reveal that there is a strong relationship between organizational commitment and staff performance. Organizational commitment is defined as psychological commitment of staff to their organization and addressed as affective, continuance and normative commitment dimensions. This study purposes to discover teachers' perceptions on policies on organizational success, loyalty to the organization, keep working for their organization, organizational values and fate/future of their organizations. This qualitatively study was carried out with 20 teachers from 10 different schools in Istanbul with an interview technique. Results reveal that teachers' perceptions on policies on organizational success, loyalty to the organization, keep working for their organization, organizational values and fate/future of their organizations are low and negative. These results show that there is not healthy organizational culture in the schools of that sample. Therefore, it is recommended that some administrative steps be taken to increase teachers' commitments for achieving success at schools. OZ: Arastirmalar, orgutsel adanmislik ve calisanlarin performanslari arasinda kuvvetli bir iliskinin varligini ortaya koymaktadirlar. Orgutsel adanmislik, calisanlarin orgute psikolojik olarak baglanmasi olarak tanimlamakta ve duygusal, devamlilik ve normatif baglilik olmak uzere uc boyutta ele alinmaktadir. Bu calisma ile ogretmenlerin kurumlarinin orgutsel basarisina dair politikalarina, orgutlerine bagliliklarina, ayni kurumda calismaya devam etme isteklerine, orgutlerinin degerlerine ve orgutlerinin gelecegi konularindaki bagliliklarina dair algilarinin ortaya cikarilmasini amaclamaktadir. Nitel olarak yurutulen bu calisma, Istanbul, Kadikoy ilcesinde gorev yapan 20 ogretmenle gorusmeler yontemiyle gerceklestirilmistir. Arastirma sonuclari ogretmenlerin kurumlarinin orgutsel basarisina dair politikalari, kurumlarina bagliliklari, orgutlerinin degerlerine ve orgutlerinin gelecegine dair baglilik algilarinin dusuk ve olumsuz oldugunu ortaya koymustur. Bu sonuclar arastirmanin yurutuldugu okullarda saglikli bir orgutsel kulturun bulunmadigini ortaya koymaktadir. Bu nedenle okullarda basarinin yakalanabilmesi icin ogretmenlerin orgutlerine bagliliklarinin artirilmasi yonunde yonetsel bazi adimlarin atilmasi gerektigi onerilmektedir. Anahtar sozcukler: Orgut, orgutsel adanmislik, ogretmenler, yoneticiler.
The impact of middle school agricultural education programs as perceived by Georgia middle school principals

The purpose of this study was to determine Georgia middle school principal’s perceptions of agricultural education. According to the 10 x 15 Long Range Goal for Agricultural Education, “By 2015 there will be in operation 10,000 quality agricultural education programs serving students through an integrated model of classroom/laboratory instruction, experiential learning, and leadership and personal skill development” (National FFA Organization, a, 2009). Installing middle school agricultural education programs is one avenue to potentially meet this goal (Rayfield & Croom, 2007). The likelihood of having a quality agricultural education program is increased when administrative support is present (Kalme & Dyer, 2000). This quantitative study examines seventy-four Georgia middle school principals that have agricultural education programs at their school to determine their perception of agricultural education. Conclusions include principals have a perceived knowledge of agricultural education, principals perceive that agricultural education has a positive impact on student grades and test scores in math and science, and principals perceive that agricultural education has a positive impact on student leadership. The researcher recommends that the study should be duplicated individually in other states and collectively across the nation; research should be conducted to compare how principals without agricultural education programs perceive agricultural education; principals should be educated on the duties of a FFA advisor and the parts of agricultural education; principals should be educated on the benefits of agricultural education; and research should be conducted to compare principals perception of agricultural education’s impact on student leadership to other student leadership organization’s impact on students leadership.
Job Satisfaction in Academia: Why Are Some Faculty Members Happier Than Others?

Abstract In studying the correlates of job satisfaction among political science faculty we confirm some findings from other disciplines, such as the relationship between institutional type and satisfaction. We demonstrate that those working in top-ranked departments or in private institutions tend to have higher levels of satisfaction with their jobs and with their contributions to the profession. Both job satisfaction and professional satisfaction tend to be highest among full professors; and greater productivity in terms of publishing is independently linked to greater levels of professional satisfaction. In contrast, comparatively higher undergraduate teaching loads undermine professional satisfaction. We also determine that men and women do not differ systematically from one another in their satisfaction levels. We do, however, document significantly lower levels of satisfaction among racial minorities in political science departments. In exploring this finding, we uncover reports of discrimination and dramatic differences in levels of collegiality experienced by different subgroups of faculty members. Experiences with discrimination undermine job satisfaction and are more frequently reported by women than men and are more common among minority faculty than nonminorities.