Miracle-dz/UniFAR-FTUs huggingface dataset:
Biosimilars: Hope and concern

As patents of the first introduced biologic therapeutics in oncology have begun to expire, competing pharmaceutical companies are allowed to produce and market the same protein as the original agent. These products are called biosimilars. Upon patent expiration, biosimilars would hopefully be a cheaper alternative to the original agent and that is the main reason for their existence. Although the financial aspect is similar to generics, the complex nature of these products generates the need for a distinct regulatory environment. Biosimilars are produced by DNA technology in bacteria, plant cells, or animal cells, while generics are produced by chemical synthesis. Details in the process of synthesis, selection of the microorganism, protein extraction, purification and manufacturing, affect the precise nature of the end product. Monoclonal antibodies are large proteins with four polypeptide chains and interact variably with each other and with the environment. It is important for payors to realize that biosimilars are different from generics; therefore, they need to develop different set of rules for approving, registering, and dispensing biosimilars. Regulators ought to respect the physicians’ request for non-interchangeability and facilitate in any possible way of traceability. Such regulations along with a rigorous pharmacovigilance program will satisfy the concerns for true equivalence in activity and long-term safety. This is the only way to accumulate over time reliable safety information for new biosimilars. In conclusion, the wish born by the medical community and the society for a more affordable health system triggers the emergence of biosimilars, which could meet that goal if properly regulated.
Correction: Relation between Financial Market Structure and the Real Economy: Comparison between Clustering Methods

We quantify the amount of information filtered by different hierarchical clustering methods on correlations between stock returns comparing the clustering structure with the underlying industrial activity classification. We apply, for the first time to financial data, a novel hierarchical clustering approach, the Directed Bubble Hierarchical Tree and we compare it with other methods including the Linkage and k-medoids. By taking the industrial sector classification of stocks as a benchmark partition, we evaluate how the different methods retrieve this classification. The results show that the Directed Bubble Hierarchical Tree can outperform other methods, being able to retrieve more information with fewer clusters. Moreover, we show that the economic information is hidden at different levels of the hierarchical structures depending on the clustering method. The dynamical analysis on a rolling window also reveals that the different methods show different degrees of sensitivity to events affecting financial markets, like crises. These results can be of interest for all the applications of clustering methods to portfolio optimization and risk hedging.
Digital Ecodynamics in Small Firms: Using Information Technology to Compete

Today, digital technologies and content are integrated into almost all aspects of business and society. However, the Internet and related digital technologies continuously evolve, and businesses are hard pressed to fully utilize technology-related opportunities. The technologies in themselves do not necessarily provide business advantages but must be combined and coordinated with other firm resources to address business problems in innovative ways (Bharadwaj 2000; Mata et al. 1995). Used imaginatively, digital technology can “rapidly create new sources of competitive advantage, and concatenate a series of temporary advantages over time” (Tanriverdi et al. 2010, p. 822). Technology investments can spur innovation and increase competitiveness. Some firms use digital technologies (in particular, information technology or IT) to drive their business strategies, facilitating innovation and creating business value. As business activities are digitized or performed electronically, firms can share information with, and respond flexibly to, suppliers and customers; they can reduce cycle times, control quality, and improve customer satisfaction (Barua et al. 2004). Digital technology, along with other management, organizational, and environmental resources, can create business value (Barua et al. 2004; Bharadwaj 2000; Mata et al. 1995). It enables complementary strategic, operational and tactical initiatives (Sambamurthy and Zmud 2000).
Haemophilia and joint disease: pathophysiology, evaluation, and management

In patients with haemophilia, regular replacement therapy with clotting factor concentrates (prophylaxis) is effective in preventing recurrent bleeding episodes into joints and muscles. However, despite this success, intra-articular and intramuscular bleeding is still a major clinical manifestation of the disease. Bleeding most commonly occurs in the knees, elbows, and ankles, and is often evident from early childhood. The pathogenesis of haemophilic arthropathy is multifactorial, with changes occurring in the synovium, bone, cartilage, and blood vessels. Recurrent joint bleeding causes synovial proliferation and inflammation (haemophilic synovitis) that contribute to end-stage degeneration (haemophilic arthropathy); with pain and limitation of motion severely affecting patients’ quality of life. If joint bleeding is not treated adequately, it tends to recur, resulting in a vicious cycle that must be broken to prevent the development of chronic synovitis and degenerative arthritis. Effective prevention and management of haemophilic arthropathy includes the use of early, aggressive prophylaxis with factor replacement therapies, as well as elective procedures, including restorative physical therapy, analgesia, aspiration, synovectomy, and orthopaedic surgery. Optimal treatment of patients with haemophilia requires a multidisciplinary team comprising a haematologist, physiotherapist, orthopaedic practitioner, rehabilitation physician, occupational therapist, psychologist, social workers, and nurses.
Comparison of paclitaxel- and sirolimus-eluting stents in everyday clinical practice: the SORT OUT II randomized trial.

CONTEXT Approval of drug-eluting coronary stents was based on results of relatively small trials of selected patients; however, in routine practice, stents are used in a broader spectrum of patients. OBJECTIVE To compare the first 2 commercially available drug-eluting stents-sirolimus-eluting and paclitaxel-eluting-for prevention of symptom-driven clinical end points, using a study design reflecting everyday clinical practice. DESIGN, SETTING, AND PATIENTS Randomized, blinded trial conducted August 2004 to January 2006 at 5 university hospitals in Denmark. Patients were 2098 men and women (mean [SD] age, 63.6 [10.8] years) treated with percutaneous coronary intervention (PCI) and randomized to receive either sirolimus-eluting (n = 1065) or paclitaxel-eluting (n = 1033) stents. Indications for PCI included ST-segment elevation myocardial infarction (STEMI), non-STEMI or unstable angina pectoris, and stable angina. MAIN OUTCOME MEASURES The primary end point was a composite clinical end point of major adverse cardiac events, defined as either cardiac death, acute myocardial infarction, target lesion revascularization, or target vessel revascularization. Secondary end points included individual components of the composite end point, all-cause mortality, and stent thrombosis. RESULTS The sirolimus- and the paclitaxel-eluting stent groups did not differ significantly in major adverse cardiac events (98 [9.3%] vs 114 [11.2%]; hazard ratio, 0.83 [95% confidence interval, 0.63-1.08]; P = .16) or in any of the secondary end points. The stent thrombosis rates were 27 (2.5%) and 30 (2.9%) (hazard ratio, 0.87 [95% confidence interval, 0.52-1.46]; P = .60), respectively. CONCLUSION In this practical randomized trial, there were no significant differences in clinical outcomes between patients receiving sirolimus- and paclitaxel-eluting stents. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00388934.
Career Thoughts Inventory: A Review and Critique.

Numerous career interest measures are available. Information on one such career inventory, the Career Thoughts Inventory (CTI) is presented here. The instrument is a self-administered assessment and intervention tool designed to provide a measure of dysfunctional thinking in career problem solving and decision making. The inventory is intended for use by high school and college students who are choosing a field of study, an occupation, or employment; it can also be used by working adults who are considering a career change or reentering the labor market. Te CTI was standardized on a sample of 571 adults, 595 college students, and 396 high school students. The test yields information on three construct scores: decision making confusion, commitment anxiety, and external conflict. It consists of 48 negative statements and takes between 7 and 15 minutes to fill out. Scoring can be carried out in 5 minutes or less. The test booklet is a combintir:n of the inventory, the answer form, and the profile form. Scoring is simple, but it is recommended that confirmation of test results in a clinical interview be made. An accompanying workbook offers exercises, checklists, and diagrams to assist the test taker in interpreting scores. Appropriate procedures were used to establish validity in terms of content, construct, and concurrent aspects of the instrument. (RJM) ******************************************************************************** Reproductions supplied by EDRS are the best that can be made from the original document. ******************************************************************************** Career Thoughts Inventory: A Review and Critique
PASDJO: quantifying password strength perceptions with an online game

Users often fail to create strong passwords. Besides lack of motivation, another possible explanation are misconceptions about the factors that contribute to password strength. Such misconceptions play an important role for the design of feedback systems during password selection. In this paper, we present an online game that helps quantifying the perception of password strength. Players score points by rating the strength of passwords accurately under time pressure. We analyzed the usage logs from the first four months after rollout. We found that users underestimate passphrases by 1.4 points on a 5-point strength scale, while their other ratings are fairly consistent with our estimates. Although we used a different methodology, we were able to corroborate related findings and narrow down the features that users think contribute to password strength. We highlight how the data collected through PASDJO can help designing better password feedback and boost user experience during account creation.
Physiological modes of action of toxic chemicals in the nematode Acrobeloides nanus

To gain a better understanding of the mechanisms through which a chemical exerts toxicity, a deeper insight is needed regarding the physiological processes that take place during a toxic stress. This issue can have important benefits for risk assessment, because it can contribute to a better interpretation of toxicity data. Here, we study the physiological mode of action of three different compounds (cadmium, carbendazim, and pentachlorobenzene) with an experimental data–based approach using whole life‐cycle toxicity data from the nematode Acrobeloides nanus. We use a process–based model, based on the dynamic energy budget theory, to study the fluxes of energy related to physiological processes and their variation throughout the life cycle. With this approach, we unravel the physiological modes of action based on resource allocation, and we model the effects of the different modes of action at the population level. The mode of action of carbendazim was through a decrease in assimilation, with an additional effect on the production of reactive oxygen species (ROS). Cadmium increased the costs of growth, with an extra effect on ROS production, and pentachlorobenzene decreased assimilation. We compared the present results with those of previous studies using the nematode Caenorhabditis elegans, and we found that the modes of action for the three compounds differed from those found in A. nanus, showing that the life‐history characteristics of each organism have a clear influence on the resulting modes of action. This highlights the importance of the interactions between a chemical and the biological characteristics of the organism in determination of the resulting physiological modes of action.
Do tonic and burst TMS modulate the lemniscal and extralemniscal system differentially?

Introduction: Tinnitus is an auditory phantom percept related to tonic and burst hyperactivity of the auditory system. Two parallel pathways supply auditory information to the cerebral cortex: the tonotopically organised lemniscal system, and the non-tonotopic extralemniscal system, firing in tonic mode and burst mode respectively. Transcranial magnetic stimulation (TMS) is a non-invasive method capable of modulating activity of the human cortex, by delivering tonic or burst stimuli. Burst stimulation is shown to be more powerful in activating the cerebral cortex than tonic stimulation and bursts may activate neurons that are not activated by tonic stimulations. Methods: The effect of both tonic and burst TMS in 14 placebo-negative patients presenting narrow band/white noise tinnitus were analysed. Results: Our TMS results show that narrow band/white noise tinnitus is better suppressed with burst TMS in comparison to tonic TMS, t(13)=6.4, p=. 000. For pure tone tinnitus no difference is found between burst or tonic TMS, t(13)=. 3, ns. Discussion: Based on the hypothesis that white noise is the result of hyperactivity in the non-tonotopic system and pure tone tinnitus of the tonotopic system, we suggest that burst stimulation modulates the extralemniscal system and lemniscal system and tonic stimulation only the lemniscal system.
Model Clouds over Oceans as Seen from Space: Comparison with HIRS/2 and MSU Radiances

Abstract Radiation observations are a key element in the evaluation of the 40-yr reanalysis at the European Centre for Medium-Range Weather Forecasts. This paper uses the High-Resolution Infrared Radiation Sounder/2 (HIRS/2) and Microwave Sounding Unit (MSU) observations on board the National Oceanic and Atmospheric Administration satellites, to assess the characteristics of the cloud fields produced by the forecasting system over midlatitude and tropical oceans. Infrared and microwave radiation have different sensitivities to clouds and are therefore complementary. Observed and model-generated radiances, as well as HIRS/2-derived cloud parameters, are compared. The model clouds are shown to be well distributed, with realistic seasonal cycles. However, deficiencies are identified and discussed: the cloud radiative impact may be too low in the midlatitudes, the frequency of occurrence of high clouds is overestimated in the intertropical convergence zone, and the stratocumulus off the west coast of the cont.
Mapping the Various Meanings of Social Innovation: Towards a Differentiated Understanding of an Emerging Concept

With a growing and especially fragmented body of literature on social innovations, the demand for categorizing the field increases. This study analyzes the current use of the concept social innovation. Following a systematic conceptual literature review methodology, the authors reviewed articles and books. The elements were then grouped in coherent categories. The authors found seven categories of social innovation that are linked to a distinct understanding of the concept. After presenting the categories and major themes which are discussed within each category, the different categories are set in context with each other. Subsequently, the authors discuss how the most prominent conceptualizations meet the criteria of concept clarity. Finally, the authors point to some aspects that are necessary in the future in order to strengthen the clarity of the social innovation concept.
Deletion mutations in the dystrophin gene of Saudi patients with Duchenne and Becker muscular dystrophy.

OBJECTIVE The deletion in the dystrophin gene has been reported for many ethnic groups, but until now the mutations in this gene have not been thoroughly investigated in Saudi patients with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). We examined the deletion pattern in the dystrophin gene of the Saudi patients applying multiplex-polymerase chain reaction (PCR). The aim of this study is to describe the outcome of our initial effort to identify mutations in the dystrophin gene in a representative group of Saudi patients with DMD and BMD. METHODS Genomic deoxyribose nucleic acid was isolated from 41 patients with DMD and BMD (27 patients confirmed by muscle biopsy and 14 patients with clinical suspicion), 3 patients with limb girdle muscular dystrophy, 12 male relatives of the patients, and 5 healthy Saudi volunteers. A total of 25 exons around the deletion prone regions (hot spots) of the dystrophin gene were amplified. The study was carried out at the King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia between 2000 and 2002. RESULTS The deletion of one or more exons was found in 21 of 27 DMD and BMD patients confirmed by muscle biopsy. The deletion in the gene was detected in 5 of 14 patients with DMD diagnosis, but not confirmed by dystrophin staining of muscle biopsy. No deletion in the dystrophin gene was detected in control Saudi volunteers, the limb girdle dystrophy patients, and the relatives of patients, as expected. CONCLUSION The present study suggests that intragenic dystrophin gene deletions occur with the same frequency in Saudi patients compared with other ethnic groups. The PCR-based deletion analysis provides a reasonable first step in the diagnostic care of Saudi patients who may be afflicted with DMD and BMD.
Dynamic Determinants of Longevity and Exceptional Health

It is well known from epidemiology that values of indices describing physiological state in a given age may influence human morbidity and mortality risks. Studies of connection between aging and life span suggest a possibility that dynamic properties of age trajectories of the physiological indices could also be important contributors to morbidity and mortality risks. In this paper we use data on longitudinal changes in body mass index, diastolic blood pressure, pulse pressure, pulse rate, blood glucose, hematocrit, and serum cholesterol in the Framingham Heart Study participants, to investigate this possibility in depth. We found that some of the variables describing individual dynamics of the age-associated changes in physiological indices influence human longevity and exceptional health more substantially than the variables describing physiological state. These newly identified variables are promising targets for prevention aiming to postpone onsets of common elderly diseases and increase longevity.
Expression in Multigene Families. Analysis of Chloroplast and Mitochondrial Proteases1

The proteolytic machinery of chloroplasts and mitochondria in Arabidopsis consists primarily of three families of ATP-dependent proteases, Clp, Lon, and FtsH, and one family of ATP-independent proteases, DegP. However, the functional significance of the multiplicity of their genes is not clear. To test whether expression of specific isomers could be differently affected by growth conditions, we analyzed transcript abundance following short-term exposure to different environmental stimuli, using 70-mer oligonucleotide arrays. This analysis revealed variability in the response to high light and different temperatures within members of each family. Thirty out of the 41 tested genes were up-regulated in response to high light, including both chloroplast and mitochondrial isozymes, whereas only six and five genes responded to either high or low temperature, respectively. The extent of response was variable, ranging from 2- to 20-fold increase in the steady-state levels. Absolute transcript levels of the tested genes, compiled from one-channel arrays, were also variable. In general, transcripts encoding mitochondrial isozymes were accumulated to a lower level than chloroplastic ones. Within the FtsH family, transcript abundance of most genes correlated with the severity of mutant phenotypes in the relevant genes. This correlation was also evident at the protein level. Analysis of FtsH isozymes revealed that FtsH2 was the most abundant species, followed by FtsH5 and 8, with FtsH1 being accumulated to only 10% of FtsH2 level. These results suggest that, unlike previous expectations, the relative importance of different chloroplast protease isozymes, evidenced by mutant phenotypes at least in the FtsH family, is determined by their abundance, and not necessarily by different specific functions or specialized expression under certain conditions.
Genetic effects on transpiration, canopy conductance, stomatal sensitivity to vapour pressure deficit, and cavitation resistance in loblolly pine

Physiological uniformity and genetic effects on canopy‐level gas‐exchange and hydraulic function could impact loblolly pine (Pinus taeda L.) plantation sustainability and ecosystem dynamics under projected changes in climate. Over a 1‐year period, we examined genetic effects on mean and maximum mid‐day canopy conductance (Gs, Gsmax) and transpiration (E, max‐E) within a juvenile loblolly pine plantation composed of ‘genotypes’ (e.g. different genetic entries) from each of the three different genetic groups (clones, full‐sibs, open‐pollinated). We also compared reference canopy conductance (Gs−ref or Gs at a vapour pressure deficit (D) = 1 kPa), maximum E (Emax) in response to D, stomatal sensitivity to D, specific hydraulic conductivity (ks), and cavitation resistance among genotypes. Based on genetic and physiological principles, we hypothesized that (1) within genotypes, physiological uniformity will increase as inherent genetic diversity decreases and (2) genotypes with greater ks and higher canopy‐level gas‐exchange rates will be more sensitive to increases in D, and more susceptible to loss of ks. In our results, high‐ and low‐genetic diversity genotypes showed no differences in E and Gs uniformity over time. However, E and max‐E were significantly different among genotypes, and genotypes showed significant seasonal variability in Gs and Gsmax. Additionally, there were significant differences in Emax, Gs−ref, Gs sensitivity to D, and the pressure at which 50% loss of ks occurs (P50) among individual genotypes. We found no relationship between mean hydraulic conductivity parameters and overall Gs−ref or Gs sensitivity. However, the genotype full embolism point (P88) and loss of ks rate (LCrate) both showed a significant positive relationship with genotype Gs−ref during the spring, indicating that genotypes with higher Gs were less resistant to cavitation. Overall, genetic effects on canopy‐level gas‐exchange and cavitation resistance were significant, implying that physiological differences among genotypes might affect stand water use, carbon gain, drought tolerance, and hydrologic processes. Contrary to our expectations, uniformity in physiological process rates did not increase as inherent genetic diversity decreased, suggesting that clonal genotypes exhibit high physiological plasticity under plantation conditions. Lastly, our results imply that genotypes with higher spring‐time gas‐exchange rates may be more susceptible to catastrophic loss of ks. With changes in climate expected to continue, physiological differences among genotypes may affect loblolly pine plantation carbon and water cycling. Copyright © 2011 John Wiley & Sons, Ltd.