Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteasome Inhibitors in the Treatment of Multiple Myeloma

The ubiquitin proteasome system is responsible for the degradation of proteins involved in a wide range of cellular processes such as the cell cycle, apoptosis, transcription, cell signalling, immune response and antigen presentation. Protein homeostasis is essential for normal cell growth and inhibition of proteasome function has emerged as a viable strategy for anti-cancer treatment. The first proteasome inhibitor to enter clinical practice, bortezomib, was approved by the Food and Drug Administration as a single agent to treat relapsed/refractory Multiple Myeloma in 2003 and expanded to first-line treatment in combination with melphalan and prednisone in 2008. It is now a routine component of Multiple Myeloma therapy and has had a major impact on expanding treatment options in the last few years. Bortezomib exhibits novel action against Multiple Myeloma by targeting both intracellular mechanisms and interactions within the bone marrow environment. Although it demonstrates significant anti-Myeloma activity when used alone, it has been shown to have even greater benefits when used in combination with conventional and novel chemotherapeutic agents. There are currently over 200 clinical trials ongoing or recently completed examining bortezomib alone and in combination in various stages of disease and treatment. The clinical success of bortezomib has prompted the development of a number of second generation proteasome inhibitors with improved pharmacological properties. In this chapter, we review the development of bortezomib as a novel therapeutic agent in Multiple Myeloma and summarize the key observations from recently completed and ongoing studies on the effect of bortezomib both as a single agent and in combination therapies in the setting of newly diagnosed Multiple Myeloma and for relapsed disease. We also discuss the progress of next generation proteasome inhibitors in the clinic.
Reduced Interferon γ Production and Soluble CD14 Levels in Early Life Predict Recurrent Wheezing by 1 Year of Age

It is unknown whether reduced production of IFNgamma in early life, before any lower respiratory tract illness, is a risk factor for recurrent wheezing in infancy. We followed 238 infants prospectively from birth to 1 year of age. At birth and at 3 months of age, IFNgamma production from polyclonally stimulated peripheral blood mononuclear cells and soluble CD14 (sCD14) levels in plasma were measured. The odds of developing recurrent wheezing (assessed by questionnaire) in the first year of life were up to 4.5 times higher for children in the lowest quartile of IFNgamma production at 3 months (p = 0.0005) and 3.2 times higher for children in the lowest quartile of sCD14 levels at birth (p = 0.004) as compared with children in the other 3 combined quartiles of IFNgamma and sCD14, respectively. Findings were confirmed in the multivariate analysis. IFNgamma production at 3 months and sCD14 levels at birth were correlated (r = 0.188, p = 0.031). Our findings from a longitudinal cohort suggest that impaired IFNgamma production at 3 months and reduced plasma-sCD14 levels at birth significantly increase the risk of developing recurrent wheezing in the first year of life.
On the quest of discovering cultural trails in social media

With the constant increasing reach of the Web and in particular of Social Media, people create and share content that harbors information about habits, norms, preferences and values. Consequently, studying how culture influences users in online social media has increased the interest of several sectors such as the advertising industry, search engines and corporations. As a consequence, anthropological and computational models need to interact and complement each other to better target these new demands. Recently, several studies have analyzed culture from large-scale data but not many took into consideration the cultural models proposed by anthropological theory. By carrying out several experiments on large-scale data from the Web, we propose to combine theoretical concepts of culture with information technology techniques to process, analyze, model and interpret data from the Web. We plan to discover synergies between traditional social studies of culture and those derived from our experiments.
Toughening and functionalization of bioactive ceramic and glass bone scaffolds by biopolymer coatings and infiltration: a review of the last 5 years

Inorganic scaffolds with high interconnected porosity based on bioactive glasses and ceramics are prime candidates for applications in bone tissue engineering. These materials however exhibit relatively low fracture strength and high brittleness. A simple and effective approach to improve the toughness is to combine the basic scaffold structure with polymer coatings or through the formation of interpenetrating polymer-bioactive ceramic microstructures. The polymeric phase can additionally serve as a carrier for growth factors and therapeutic drugs, thus adding biological functionalities. The present paper reviews the state-of-the art in the field of polymer coated and infiltrated bioactive inorganic scaffolds. Based on the notable combination of bioactivity, improved mechanical properties and drug or growth factor delivery capability, this scaffold type is a candidate for bone and osteochondral regeneration strategies. Remaining challenges for the improvement of the materials are discussed and opportunities to broaden the application potential of this scaffold type are also highlighted.
Reproductive health in nomadic communities: challenges of culture and choice.

Youth sexuality is a critical determinant of reproductive health particularly in developing countries. Access to family planning services safe motherhood prevention and treatment of sexually-transmitted infections (STIs) including HIV and AIDS and the elimination of gender violence would improve the lives of the poor and spur economic and social development. Nomadic communities reproductive health is a critical issue. The lifestyle of moving from place to place for subsistence seems to deprive these communities of basic services. This trend has been complicated by remoteness physical distance to health services high levels of illiteracy and local beliefs and practices. On the other hand HIV incidence among pastoral communities appears to be relatively low; Talle relates this to the cultural identity of the Maasai. Although the Maasai value multiple sexual partners and engage in large sex networks their sexual morals are not loose and their sexual interactions are regulated by a strict morality of prescribed sexual partners according to age-set and kinship affiliation. It seems that in most countries reproductive health practices and needs of nomadic communities are not well understood due to limited information. It was against this background that African Medical Research Foundation (AMREF) implemented a programme targeting young nomads from 2006 to 2010. This article shares some insights and experiences from the programme and discusses some important challenges and issues related to nomadic reproductive health. (excerpt)
Update on the use of abdominal and thoracic endografts for treating aortic aneurysms

ABSTRACT Endovascular abdominal and thoracic aneurysm repair has heralded a paradigm shift in the management of abdominal and thoracic aortic aneurysms. Randomized controlled trials have suggested superior short-term and equivalent long-term outcomes of endovascular repair compared with open surgery. Existing endografts have undergone several modifications to meet anatomic challenges and improve patient results. In the past, endovascular repair has been limited to infrarenal abdominal aortic aneurysms and isolated thoracic aortic aneurysms. The advent of fenestrated and branched endografts have made endovascular repair of thoracoabdominal and juxtarenal aneurysms possible. Continued evolution of endograft technology will maximize the benefit and minimize complications in patients with a range of aneurysmal disease.
Application of MEMS technology and engineering in medicine: a new paradigm for facial muscle reanimation

Translational research may lead to development of micro-electromechanical system-based devices to treat muscle and nerve dysfunctions whose current treatments are inadequate and, at best, palliative. This paper discusses the development of engineered microsystems as a treatment option for palsies of the seventh cranial nerve and the potential application of these devices as a platform technology for treatment of other nervous dysfunctions. The engineering techniques for electrical and chemical stimulation of denervated muscle are discussed along with current caveats from clinical and engineering standpoints. As opposed to current treatments, miniaturized implants offer the possibility of the reduced toxicity and increased specificity of direct drug delivery. As with the increased miniaturization of other technologies, engineering of these increasingly small implantable microsystems holds great promise for the future development of yet smaller, even nanoscale, implantable devices.
Assistive technologies in caring for the oldest old: a review of current practice and future directions

Our aging populations have led to concern as to whether existing care provision will cope with the predicted future demand. The oldest old (those over 85 years) are a particular challenge; they are the fastest growing sector of our population and have high rates of comorbidity and cognitive impairment. Assistive technologies provide one possible solution to promote independence for older individuals, but are often underutilized in routine care. In this perspective, we consider how assistive technology can support the future care of the oldest old. First, we summarize the evidence on the health of the oldest old and their current use of assistive technology with a review on the evidence to date on the effectiveness, and potential benefits, of assistive technology. We then discuss the ethical issues associated with the use of assistive technology in this population and, finally, identify key directions for future research and service development in this field.
Composition and anti-insect activity of essential oils from Tagetes L. species (Asteraceae, Helenieae) on Ceratitis capitata Wiedemann and Triatoma infestans Klug.

Essential oils from four species of the genus Tagetes L. (Asteraceae, Helenieae) collected in Tucumán province, Argentina, were evaluated for their chemical composition, toxicity, and olfactory activity on Mediterranean fruit fly Ceratitis capitata Wiedemann adults and for repellent properties on Triatoma infestans (Klug) (Chagas disease vector). Yields of essential oils range from 0.2 to 0.8% (v/w). The same main constituents among Tagetes minuta L. , Tagestes rupestris Cabrera, and Tagetes terniflora Kunth, (cis-trans)-ocimenes, (cis-trans)-tagetones, and (cis-trans)-ocimenones showed important differences in their relative compositions. Tagetes filifolia Lag. was characterized by the recognized phenylpropanoids methylchavicol and trans-anethole as the main components. LD(50) was ≤20 μg/insect in topical bioassays. T. rupestris was the most toxic to C. capitata females, whereas the other oils presented similar toxicities against males and females. Tagetes rupestris oil attracted both sexes of C. capitata at 5 μg, whereas T. minuta showed opposite activities between males (attractant) and females (repellent). Oils from T. minuta and T. filifolia were the most repellent to T. infestans. The results suggest that compositions of essential oils influence their insecticidal and olfactory properties. The essential oils from Tagetes species show an important potential as infochemical agents on insects' behaviors. This study highlights the chemical variability of essential oils as a source of variation of anti-insect properties.
Taming aspects

Aspect-oriented programming languages support the modular definition of crosscutting abstractions. In most languages, this is achieved through pointcuts, which provide a means for quantifying over execution events in order to implicitly trigger advice. Notably, an advice is more than a simple event handler because of its ability to override the underlying computation. Unrestricted quantification and arbitrary advice computation are powerful but dangerous. In this talk we look at a number of approaches to tame aspects in order to retain their benefits without sacrificing important software engineering properties, like modular reasoning, separate development, type soundness, and controlled interferences. Specifically, we report on our work in scoping, interfaces, types, and effects: scoping We have proposed scoping strategies [8], which extend the work of Dutchyn et al. [2], and have been successfully applied to distribution [10] and access control [13-15]; execution levels [3, 9], which avoid infinite regression and computational interference between aspects, and have been applied to compose dynamic analyses aspects [11]; and membranes [4, 12], which allow more flexible topological scoping and local weaving customization. interfaces We recently developed the notion of Join Point Interfaces [1], which builds upon Steimann et al. [6], recovering sound type checking and retaining flexibility thanks to generic interfaces and controlled global quantification. types and effects We provide a typed embedding of aspects in Haskell, which statically ensures that pointcut/advice bindings are type safe; in addition, the use of monads makes it possible to statically control interferences and effects of aspects [4, 7]. Finding the right balance between power and control is a delicate and still open question, especially when aiming at simplicity of usage. We believe further work is needed to address this crucial challenge for the principled adoption of aspects.
Thyroid surgery for treatment of Graves’ disease complicated by ophthalmopathy: a comprehensive review

Graves’ disease (GD) is an autoimmune disorder in which antibodies directed against thyroid-stimulating hormone receptors leads to thyrotoxicosis. Graves’ ophthalmopathy, a condition that occurs in up to half of GD patients, is a cause of significant morbidity and is potentially vision threatening. Three treatment options are equally effective for uncomplicated GD and these include thyroid surgery (thyroidectomy), radioactive iodine thyroid ablation and antithyroid drugs. However, recent practice surveys suggest that surgery is the least favored GD treatment. When GD is complicated by moderate-to-severe Graves’ ophthalmopathy, antithyroid drugs and surgery are recommended by current guidelines, and again the preference for thyroid surgery in these cases has remained low. This report aims to review current published data regarding thyroidectomy as a treatment for GD, and in particular, we focus on the effects of thyroidectomy on Graves’ ophthalmopathy development and progression.
Modeling improved syllabification algorithm for Amharic

In this paper, a rule-based automatic syllabification Algorithm for Amharic language using linguistic implementation notions is designed following the Maximal Onset and Sonority Hierarchy principles. Amharic is a syllabic language in which every grapheme represents consonant-vowel assimilation. However, while reading a text in Amharic, all the CV syllables are not uttered as expected and hence the syllables in the text are not the CV sequence seen in the grapheme sequence. Epenthesis and gemination are also major challenges in Amharic grapheme-to-phoneme conversion because of the failure of Amharic orthography to show epenthetic vowel and geminated consonants. This limits the performance of many Amharic speech systems (such as Text-To-Speech and Automatic Speech Recognition) and other natural language applications. After a thorough study of the syllable structure, identification of linguistic syllabification rules and a survey of the relevant literature, a set of rules were identified and used to design a syllabification algorithm. The system was implemented and tested. The experiment was conducted using carefully selected Amharic words. The system exhibited a 98.1% word accuracy rate with very high sensitivity to epenthesis.
Physician order entry: a mixed blessing to pharmacy?

Objective. The Alberta Cancer Board (ACB) Pharmacy conducted a timing study to determine how electronic prescription ordering impacts the workload in pharmacy in comparison to the current paper system. The objective was to compare the mean time required to review orders generated by an electronic physician order entry system to the existing paper method, and to determine whether such an implementation would decrease pharmacist intervention rates. Methods. Self-reporting and measurement by stopwatch timing were used to record the timing data on the prescription order review process on all outpatient parenteral chemotherapy orders for adults handled within the ACB’s two main tertiary centres for the month of June. The primary endpoint measured was mean pharmacist order review time for manual and electronic orders. The secondary endpoint measured was pharmacist intervention rate for manual and electronic orders. Results. Among all 836 chemotherapy orders reviewed, the mean pharmacist order review time was increased by 5.15 min with the implementation of an electronic order entry system. A total of 62 pharmacist interventions were recorded in the study. The pharmacist intervention rate was 7.14% for the electronic orders and 7.47% for the manual paper orders. Conclusions. The study showed that the implementation of an electronic physician order entry system has significant impacts on pharmacy workload without providing significant reductions in pharmacist intervention rates.
Lung involvement and drug-induced lung disease in patients with rheumatoid arthritis

Interstitial lung disease (ILD) is a common extra-articular manifestation of rheumatoid arthritis (RA) and a significant cause of morbidity and mortality. Usual interstitial pneumonia and nonspecific interstitial pneumonia seem to be the most frequent patterns in RA patients with ILD, although the proportion of patients with usual interstitial pneumonia is higher than among patients with other systemic rheumatic autoimmune diseases. RA patients with ILD most frequently present with chronic symptoms of cough and dyspnea when climbing stairs or walking uphill. A physical examination may reveal inhalatory crackles and a pulmonary function test demonstrates restrictive physiology, often with reduced diffusing capacity. High-resolution computed tomography is generally sufficient to confirm a diagnosis of ILD, although a minority of cases may require a surgical lung biopsy. Conventional disease-modifying antirheumatic drugs such as methotrexate (MTX) or leflunomide (LEF) and biological agents such as TNF-blocking agents or rituximab may trigger or aggravate ILD in RA patients, and infections may contribute to increased mortality in such patients. LEF should not be used in patients with a history of MTX pneumonitis. The prevalence of interstitial pneumonia among RA patients treated with anti-TNF agents ranges from 0.5 to 3%; however, as the evidence that anti-TNF increases or decreases the risk of ILD is controversial, it is not clear whether this indicates more severe RA requiring biological therapy or the effect of exposure to potentially toxic drugs such as MTX or LEF. The development of treatment-related ILD is a paradoxical adverse event, and patients should be warned about this rare but serious complication of biological or disease-modifying antirheumatic drug therapy.
EyeRing: a finger-worn input device for seamless interactions with our surroundings

Finger-worn interfaces remain a vastly unexplored space for user interfaces, despite the fact that our fingers and hands are naturally used for referencing and interacting with the environment. In this paper we present design guidelines and implementation of a finger-worn I/O device, the EyeRing, which leverages the universal and natural gesture of pointing. We present use cases of EyeRing for both visually impaired and sighted people. We discuss initial reactions from visually impaired users which suggest that EyeRing may indeed offer a more seamless solution for dealing with their immediate surroundings than the solutions they currently use. We also report on a user study that demonstrates how EyeRing reduces effort and disruption to a sighted user. We conclude that this highly promising form factor offers both audiences enhanced, seamless interaction with information related to objects in the environment.
MOOCs and the funnel of participation

Massive Online Open Courses (MOOCs) are growing substantially in numbers, and also in interest from the educational community. MOOCs offer particular challenges for what is becoming accepted as mainstream practice in learning analytics. Partly for this reason, and partly because of the relative newness of MOOCs as a widespread phenomenon, there is not yet a substantial body of literature on the learning analytics of MOOCs. However, one clear finding is that drop-out/non-completion rates are substantially higher than in more traditional education. This paper explores these issues, and introduces the metaphor of a 'funnel of participation' to reconceptualise the steep drop-off in activity, and the pattern of steeply unequal participation, which appear to be characteristic of MOOCs and similar learning environments. Empirical data to support this funnel of participation are presented from three online learning sites: iSpot (observations of nature), Cloudworks ('a place to share, find and discuss learning and teaching ideas and experiences'), and openED 2.0, a MOOC on business and management that ran between 2010--2012. Implications of the funnel for MOOCs, formal education, and learning analytics practice are discussed.
Systematic Literature Review of the Epidemiology of Nongenetic Forms of Hypogonadism in Adult Males

This study summarizes the literature on the prevalence, incidence, and proportion of patients receiving treatment for male hypogonadism and a systematic literature search was performed for articles published in the last 20 years. Of the 97 studies identified, 96 examined the prevalence, 2 examined the incidence, and 4 examined the proportion of males with hypogonadism patients receiving treatment. Based on studies conducted in Europe and USA, the prevalence of hypogonadism in the general population ranged from 2.1% to 12.8% of middle-aged to older men, with an estimated incidence of 12 new cases per 1,000 person-years. Prevalence was higher among patients with comorbid conditions, such as type 2 diabetes mellitus and obesity. Approximately 10–12% of men with hypogonadism were receiving testosterone treatment. This literature review suggests that there is potentially a significant burden of hypogonadism in the general population. Burden seems to increase with age and in the presence of certain disease conditions. Data suggests that many hypogonadal men who may benefit from testosterone replacement are not receiving treatment. This may be the result of underdiagnosis of the disease, lack of awareness by patients or physicians, irregularities surrounding the diagnostic criteria, and deficiency of long-term safety studies.