Miracle-dz/UniFAR-FTUs huggingface dataset:
Cetuximab in Colon Cancer

In the last decade remarkable progress has been made in the treatment of metastatic colorectal cancer due to the introduction of oxaliplatin and irinotecan in clinical practice. The addition of biological agents seems to offer a chance to further enhance the activity of conventional chemotherapy. Cetuximab, a chimeric mouse-human monoclonal antibody targeting the extracellular domain of the epidermal growth factor receptor (EGFR), has shown low but detectable activity when employed in pretreated patients either as a single agent or in combination with irinotecan. Cetuximab in combination with irinotecan has been registered in the USA and Europe for the treatment of patients with metastatic colorectal cancer expressing the EGFR after failure of prior irinotecan-based cytotoxic therapy. The role of cetuximab in first-line therapy is still investigational. Some phase II trials assessing cetuximab plus chemotherapy demonstrated a high objective response rate and promising results in terms of time to progression and overall survival; data from phase III trials are pending. Further studies are needed to investigate the efficacy of cetuximab in combination with conventional chemotherapy in the adjuvant/neoadjuvant setting and to define criteria for a better selection of patients for this type of treatment.
Cutaneous Toxic Effects of BRAF Inhibitors Alone and in Combination With MEK Inhibitors for Metastatic Melanoma.

IMPORTANCE The cutaneous adverse effects of the BRAF inhibitors vemurafenib and dabrafenib mesylate in the treatment of metastatic melanoma have been well reported. The addition of a MEK inhibitor to a BRAF inhibitor improves the blockade of the mitogen-activated protein kinase pathway. The combination of dabrafenib with the MEK inhibitor trametinib dimethyl sulfoxide (CombiDT therapy) increases response rate and survival compared with a BRAF inhibitor alone. Clinical trials have suggested that CombiDT therapy induces fewer cutaneous toxic effects than a single-agent BRAF inhibitor. To our knowledge, a direct comparison has not been performed before. OBJECTIVE To compare the cutaneous toxic effects of BRAF inhibitor monotherapy and CombiDT therapy in a large cohort of patients. DESIGN, SETTING, AND PARTICIPANTS We performed a retrospective cohort study from September 1, 2009, through November 30, 2013. The study population included 185 Australian patients with unresectable stages IIIC and IV melanoma referred from Crown Princess Mary Cancer Care Centre who underwent review at the Department of Dermatology, Westmead Hospital. Of these, 119 patients received dabrafenib; 36, vemurafenib; and 30, CombiDT therapy. Data analysis were performed in December 2013. MAIN OUTCOMES AND MEASURES Multiple cutaneous adverse effects between BRAF inhibitor monotherapy and CombiDT therapy were identified and compared in a cohort of patients who underwent the same dermatologic assessment. RESULTS The most common cutaneous adverse effects seen in patients receiving the single-agent BRAF inhibitor dabrafenib or vemurafenib included Grover disease (51 patients [42.9%] and 14 [38.9%], respectively [P = .67]), plantar hyperkeratosis (47 [39.5%] and 14 [38.9%], respectively [P = .95]), verrucal keratosis (79 [66.4%] and 26 [72.2%], respectively [P = .51]), and cutaneous squamous cell carcinoma (31 [26.1%] and 13 [36.1%], respectively [P = .54]). Photosensitivity was more common with vemurafenib (14 patients [38.9%]) compared with dabrafenib (1 [0.8%]; P < .001). Compared with dabrafenib, CombiDT therapy showed a higher frequency of folliculitis (12 patients [40.0%] vs. 8 [6.7%]; P < .001) and a significant decrease of cutaneous squamous cell carcinoma (0 vs. 31 [26.1%]; P < .001), verrucal keratosis (0 vs. 79 [66.4%]; P < .001), and Grover disease (0 vs. 51 [42.9%]; P < .001). CONCLUSIONS AND RELEVANCE This study confirms that the prevalence of cutaneous toxic effects differs among vemurafenib, dabrafenib, and CombiDT therapies. Cutaneous squamous cell carcinoma is the most concerning cutaneous toxic effect related to BRAF inhibitor monotherapy that did not appear with CombiDT therapy. Although CombiDT therapy has an improved profile of cutaneous toxic effects, continuous dermatologic assessments should be provided for all patients when receiving these treatments.
Local or Digital Buzz, Global or National Pipelines: Patterns of Knowledge Sourcing in Intelligent Machinery and Digital Content Services in Finland

In regional innovation systems (RIS), there is a need to identify the knowledge bases that firms draw upon and differentiate innovation policies accordingly. From this premise, the main aim of this paper is to compare two Finnish industries, intelligent machinery and digital content services, that draw upon different kinds of knowledge bases. The three main research questions discussed here are as follows: (a) do knowledge sources of the firms representing two different industries with two different knowledge bases differ from each other, and how; (b) how do the knowledge sources differ between different types of RIS and (c) what kind of extra-regional pipelines do the three different cases have? The RIS under scrutiny represent fragmented metropolitan (Helsinki metropolitan area), old industrial (Tampere region) and organizationally thin (South Ostrobothnia) RIS.
The Evolution of Innovation Networks and Spin-off Entrepreneurship: The Case of RAD

Abstract We conducted an in-depth analysis of an Israeli startup, RAD Bynet, founded in 1981, that has intentionally, through the vision of its founder, given rise to 129 other startups employing some 15,000 workers, and created a unique “cloud”. Through a survey of the existing firms, we sought to explore the nature of this ecosystem and to quantify the relationships that exist between the mother company and the enterprises that emerge from it. Our main findings were: (a) social and technological proximity encourages the tendency of the companies to maintain business relationships that probably contribute to knowledge exchange, while technological diversity drives innovation and startup formation; and (b) firms will choose to cooperate on the basis of a shared past and personal proximity relations, as well as technological proximity at a certain level; “viral clouds” of startups like the one we studied can thus intentionally be designed and developed.
A Qualitative Study on the Transfer of Residents Between a Nursing Home and an Emergency Department

Nursing home (NH) residents who have exacerbations of chronic health conditions or new illnesses must generally go the emergency department (ED) for health care, later returning to the nursing home when it is felt that they are no longer require acute care. Transfers between settings of care are referred to as transitions, and research has shown that residents are at risk of experiencing negative health outcomes during these periods. This article reports on a qualitative study of resident transfers between one NH and one ED in Canada. Data were collected using interviews, participant observation, and examination of institutional policies and standard practices. Three themes emerged from the data: (1) work of executing transfers; (2) creating and exchanging resident information; and (3) feelings of guilt but not being responsible about how residents' transfers occurred. Although completion of organization‐specific forms consumed a considerable amount of practitioners' time, they contributed little to resident transfers or to the sharing of information. There is a need for integrated models of care that transcend settings and promote an understanding of the roles and responsibilities of practitioners working along the entire continuum of care.
Root Hairs

Roots hairs are cylindrical extensions of root epidermal cells that are important for acquisition of nutrients, microbe interactions, and plant anchorage. The molecular mechanisms involved in the specification, differentiation, and physiology of root hairs in Arabidopsis are reviewed here. Root hair specification in Arabidopsis is determined by position-dependent signaling and molecular feedback loops causing differential accumulation of a WD-bHLH-Myb transcriptional complex. The initiation of root hairs is dependent on the RHD6 bHLH gene family and auxin to define the site of outgrowth. Root hair elongation relies on polarized cell expansion at the growing tip, which involves multiple integrated processes including cell secretion, endomembrane trafficking, cytoskeletal organization, and cell wall modifications. The study of root hair biology in Arabidopsis has provided a model cell type for insights into many aspects of plant development and cell biology.
Short-term Forecasting Methods Based on the LEI Approach: The Case of the Czech Republic

This paper is aimed at developing short-term forecasting methods based on the LEI (leading economic indicators) approach. We use a set of econometric models (PCA, SURE) that provide estimates of GDP growth for the Czech economy for a co-incident quarter and a few quarters ahead. These models exploit monthly or quarterly indicators such as business surveys, financial or labour market indicators, monetary aggregates, interest rates and spreads, etc. that become available before the release of data on GDP growth itself. Our tests show that the LEIs provide relatively accurate forecasts of GDP fluctuations in the short run.
Learning to learn from failures: the impact of operating experience on railroad accident responses

Failures are difficult to learn from, and organizations unable to learn may continue to fail. This study reconciles conflicting theoretical predictions regarding whether organizations are able to learn from failure, by examining the moderating role of knowledge gained through an organization’s operating experience. The study also forwards the possibility that generalist and specialist organizations systematically differ at this process. Hypotheses are tested on a panel of railroad companies. These tests provide strong support for the role of operating experience, and partial support for differences across generalists and specialists. Contributions to organizational learning theory and related literatures are discussed.
Evaluation of the sustainable tourism potential of a protected area for landscape planning: a case study of the ancient city of Pompeipolis in Kastamonu

From ancient civilisations to the present, the underground and aboveground sites at Pompeipolis have reflected the social, economic, and cultural characteristics of the surrounding region and been a marker of its archaeological and natural heritage. This area should be passed on to future generations of humanity; to promote the protection of this site, promotional activities should be planned that use it in the best way. In this study, I evaluate the potential for the caretakers of the ancient city of Pompeipolis within Kastamonu to establish modern conservation approaches, balance its conservation and use within the framework of cultural tourism, and determine problem areas and opportunities. This framework is intended to establish a continuity of forward-looking tourism. In the context of the Kastamonu archaeological sites and the data obtained from studies conducted in the immediate vicinity, and by evaluating research studies and the literature, I will demonstrate the problems and opportunities that may be encountered while preserving the original character of the area. This will ensure its protection, balance, and sustainability, as well as conducting landscape design and developing tourism activities in the area.
Public Pension Funds and Operating Budgets: A Tale of Three States

This article provides a normative framework for understanding the important link between public pension fund management and government operating budgets. Three aspects of pension fund management are discussed that have a significant impact on the operating budget: pension contribution, investment strategy, and the funding of pension liabilities. Three cases concerning West Virginia, New Jersey, and New York City are discussed to illustrate these three important aspects. The normative framework and the case studies demonstrate two important principles in prudently managing public pension funds: ensuring intergenerational equity and protecting the long-term health of government budgets.
Physicians’ Insurance Limits and Malpractice Payments: Evidence from Texas Closed Claims, 1990–2003

Physicians’ insuring practices influence their incentives to take care when treating patients, their risk of making out‐of‐pocket payments in malpractice cases, and the adequacy of compensation available to injured patients. Yet these practices and their effects have rarely been studied. Using Texas Department of Insurance data on 9,525 paid malpractice claims against physicians that closed in 1990–2003, we provide the first systematic evidence on levels of coverage purchased by physicians with paid liability claims and how those levels affect out‐of‐pocket payments and patient compensation. We find that these physicians carried much less insurance than is conventionally believed, that their real primary limits declined steadily over time, that policy limits often act as effective caps on recovery, and that personal contributions by physicians to close claims were rare. Our findings call into question a number of common assumptions about the relationship between physicians' insuring practices and the medical malpractice liability system.
Effect of acute and subchronic nicotine treatment on cortical acetylcholine release and on nicotinic receptors in rats and guinea‐pigs

1 The effect of acute and chronic (16 days) administration of nicotine on cortical acetylcholine (ACh) release, gross behaviour and brain nicotinic binding sites was investigated in rats and guinea‐pigs. 2 The drug, injected either subcutaneously (0.45‐0.90 mg kg−1) or intracerebroventricularly (1, 3 and 5 μg) increased the cortical ACh release, in a dose‐dependent manner, through mecamylamine‐sensitive receptors for 1–2 h in both species. 3 Chronic treatment significantly increased basal ACh release in the rat and slightly lowered it in the guinea‐pig, but the response to a challenging dose of nicotine was proportionally maintained in both species. 4 The number of nicotinic receptors was four times higher in the rat than in the guinea‐pig and was not dependent on the radioligand used ([3H]‐nicotine or [3H]‐ACh, in the presence of atropine) to determine this. The nicotinic binding sites showed an apparent increase in chronically treated rats but no change in guinea‐pigs. 5 Tolerance to the inhibitory effect of the drug, assessed with the T maze test, was found in the rat. No apparent change in gross behaviour was detected in the guinea‐pig. 6 It is concluded that chronic nicotine treatment causes evident tolerance to its inhibitory effect on behaviour in the rat, but no adaptation to its excitatory properties on the cholinergic brain structures in rats and guinea‐pigs.
Testing for Seasonal Unit Roots in Monthly Panels of Time Series

We consider the problem of testing for seasonal unit roots in monthly panel data. To this aim, we generalize the quarterly CHEGY test to the monthly case. This parametric test is contrasted with a new nonparametric test, which is the panel counterpart to the univariate RURS test that relies on counting extrema in time series. All methods are applied to an empirical data set on tourism in Austrian provinces. The power properties of the tests are evaluated in simulation experiments that are tuned to the tourism data.
Induction of Neutralizing Antibodies against Diphtheria Toxin by Priming with Recombinant Mycobacterium bovis BCG Expressing CRM197, a Mutant Diphtheria Toxin

ABSTRACT BCG, the attenuated strain of Mycobacterium bovis, has been widely used as a vaccine against tuberculosis and is thus an important candidate as a live carrier for multiple antigens. With the aim of developing a recombinant BCG (rBCG) vaccine against diphtheria, pertussis, and tetanus (DPT), we analyzed the potential of CRM197, a mutated nontoxic derivative of diphtheria toxin, as the recombinant antigen for a BCG-based vaccine against diphtheria. Expression of CRM197 in rBCG was achieved usingEscherichia coli-mycobacterium shuttle vectors under the control of pBlaF*, an upregulated β-lactamase promoter from Mycobacterium fortuitum. Immunization of mice with rBCG-CRM197 elicited an anti-diphtheria toxoid antibody response, but the sera of immunized mice were not able to neutralize diphtheria toxin (DTx) activity. On the other hand, a subimmunizing dose of the conventional diphtheria-tetanus vaccine, administered in order to mimic an infection, showed that rBCG-CRM197 was able to prime the induction of a humoral response within shorter periods. Interestingly, the antibodies produced showed neutralizing activity only when the vaccines had been given as a mixture in combination with rBCG expressing tetanus toxin fragment C (FC), suggesting an adjuvant effect of rBCG-FC on the immune response induced by rBCG-CRM197. Isotype analysis of the anti-diphtheria toxoid antibodies induced by the combined vaccines, but not rBCG-CRM197alone, showed an immunoglobulin G1-dominant profile, as did the conventional vaccine. Our results show that rBCG expressing CRM197 can elicit a neutralizing humoral response and encourage further studies on the development of a DPT vaccine with rBCG.
Developers, non‐linearity and asymmetry in the development cycle

Summary There is some evidence of cyclical non‐linearities in the property market but the analytical techniques used to identify them provide no insight into their source or nature. Studies of other sectors of the economy suggest that a primary cause of non‐linearities is the differential response of agents to the same shocks at different stages of the business cycle. Developers are key agents in the property sector and their behaviour may vary between different stages of the development cycle. Computer‐based behavioural modelling is used formally to imitate alternative strategies developers might adopt to formulate profit expectations and, hence, to make development decisions. When developers use current costs and values to determine their expectations the effects of property market price signals are delayed but not exaggerated. When developers’ expectations are conditioned by past experience, the effects of price signals are both delayed and exaggerated. The results of the latter strategy are more marke.
Composition of Photosystem II Antenna in Light-Harvesting Complex II Antisense Tobacco Plants at Varying Irradiances

Plants with genes coding for chlorophyll a/b-binding proteins of light-harvesting complex II (LHCII) in antisense orientation (Lhcb) that are characterized by severely reduced Lhcb transcript levels (below 10% of wild type) do not show a bleached phenotype due to a specific loss of the polypeptide. To produce such a phenotype, a conceptually different antisense approach was tested with a dual-functional transcript encoding the gene for hygromycin phosphotransferase and the transit sequence of Lhcb1–2 in the antisense orientation. Using increasing concentrations of hygromycin, transformants with Lhcb steady-state levels as low as 9% of wild type were regenerated and grown in a growth chamber. Together with Lhcb antisense plants obtained in an earlier study, these antisense plants were analyzed biochemically for their photosystem II (PSII) antenna composition under varying light conditions. All antisense plants showed a characteristic low-irradiance-induced increase of their PSII antenna size as determined by higher chlorophyll concentrations, an increased content of LHCII, and a constant chlorophyll b-to-lutein ratio in comparison with control plants. One to 5% of the total Lhcb transcript amount was sufficient to allow unrestricted formation of the PSII antenna at low irradiance, suggesting that LHCII biogenesis is not controlled primarily by transcription.
Not Reporting a Profit: Constructing a Non‐Profit Organisation

Public sector reformers advocate contracting‐out as a means of improving cost‐effectiveness. In the health sector, market‐based contracts with for‐profit organisations can reduce equity of access and divert public funds to private gain. Such issues have prompted policy makers to seek alternative contracting strategies. This paper examines a primary health care policy whereby government contracts with private non‐profit organisations to increase efficiency and meet World Health Organisation ideals. The study found that the policy's implementation has not achieved these aims when for‐profit providers masquerade as non‐profit organisations. The implication is that governments may find it more effective to manage for structural diversity than mandate homogenisation.
Issue Representation in Neighborhood Organizations: Questing for Democracy at the Grassroots

In this era of government reinvention and devolution, some have expressed interest in applying that logic to the local level by including neighborhood associations among the mechanisms for delivering urban services. However, if decision-making authority were to be decentralized to a greater extent, there is the possibility that the decisions of these organizational participants might not be reflective of the group they are supposed to represent. This article seeks to examine the issue representation ability of neighborhood associations. Using a unique neighborhood-level dataset from Indianapolis, this analysis reveals how representative the organization’s activities are in terms of the issues that are of most importance to residents (other participants and non-participants). In addition, the article presents and tests a model to explain differences in the levels of representation. The findings raise concerns with the wisdom of such devolution as well as highlight the environmental and organizational characteristics that influence issue representation.
Investigating innovation management practices in Iranian organizations

The aim of this study is threefold. First to explore the extent to which innovation practices and activities are implemented in Iranian organizations. Second, given special conditions of Iran to find out what factors currently form the main drivers and barriers to innovation in Iranian organizations. Third, to survey if there is any relationship between innovation practices and organizational performance of Iranian organizations mainly based on a descriptive analysis. Based on the review of literature of innovation practices, drivers and barriers of successful implementation to innovation practices were identified. Through a self-administered questionnaire which was collected from 87 Iranian organizations the extent of innovation practices implementation and their rankings in the surveyed organizations were determined. Analysis of data and the obtained results revealed that opening of new domestic target groups is the most frequently practice of innovation. Also, customer centricity and organizational structure and bureaucratic and excessive administrative regulations were ranked as the main driver and barrier of innovation implementation respectively. Finally, the result of chi-square test showed that the implementation of innovation practices is positively and significantly related to organizational performance of Iranian organizations.
Long Run Money Neutrality: The Case of Guatemala

The Fisher and Seater (1993) methodology is used to test for the long run neutrality of money in Guatemala, 1950-2001. Real GDP, real per capita GDP, and the money measures, M1 and M2, are integrated of order one [I (l)]. Given these orders of integration, the Fisher-Seater neutrality test can be applied. The evidence suggests that M1 and M2 are neutral with respect to real GDP. Furthermore, the test indicates that M1, but not M2, is neutral with respect to real per capita GDP as well.