Miracle-dz/UniFAR-FTUs huggingface dataset:
Biosimilars: Practical Considerations for Pharmacists

Objective: To review the scientific and regulatory aspects of biosimilar development and practical considerations for the use of biosimilars that are relevant to pharmacists. Data Sources: Literature searches of PubMed and congress abstracts for publications pertaining to biosimilars were conducted from January 2016 to January 2017. Individual drug company web pages and governmental, regulatory, and other agency websites were also reviewed. Study Selection/Data Extraction: Published articles, regulatory guidelines, and other sources covering biologic/biosimilar development and approval, reporting results of biosimilar studies or survey research, and/or identifying biosimilars in development or approved for use in Europe or the United States were reviewed and included. Data Synthesis: Biologic therapies have revolutionized the treatment of serious diseases, including hematological or autoimmune disorders and cancers. A biosimilar is highly similar to a licensed biologic (ie, reference or originator) and has no clinically meaningful differences in safety, purity, and potency. Unlike small-molecule drugs, biologics are large, complex proteins that cannot be exactly replicated, so the concept of a generic equivalent cannot be applied to biologics. Regulatory agencies have provided a framework for biosimilar approval, but there are many practical considerations for pharmacists, including interchangeability, substitution, naming, indication extrapolation, product labeling, therapeutic drug monitoring, manufacturer attributes, logistics of product use, and reimbursement. Conclusions: Pharmacists will play a key role in managing the introduction of biosimilars into health care systems. Understanding the principles of biosimilar development and evolving regulatory guidelines relevant to their use will allow pharmacists to make informed decisions regarding formulary inclusion and educate patients and other health care providers about biosimilars.
Essays in Islamic Finance

8 Chapter 1: Introduction . 10 1. Motivation of study . 10 2. Rationale and objectives . 12 3. Thesis organisation . 14 4. Description of thesis and findings . 15 4.1 Has the prohibition of ribā an-nasi’ah hindered the economic development of the Muslim world? 15 4.2 Can an interest-free credit facility be more efficient than a usurious payday loan? 18 4.3 Reinforcing resilience of the financial architecture with default-free collateralised loan . 20 5. Contributions . 22 5.1 Has the prohibition of ribā an-nasi’ah hindered the economic development of the Muslim world? 22 5.2 Can an interest-free credit facility be more efficient than a usurious payday loan? 23 5.3 Reinforcing resilience of the financial architecture with default-free collateralised loan . 23 Chapter 2: Has the Prohibition of Ribā An-Nasi’ah Hindered Economic Development of the Muslim World . 25
Transaction Logic Programming

An extension of predicate logic, called Transaction Logic, is proposed, which accounts in a clean and declarative fashion for the phenomenon of state changes in logic programs and databases. Transaction Logic has a natural model theory and a sound and complete proof theory, but unlike many other logics, it allows users to program transactions. The semantics leads naturally to features whose amalgamation in a single logic has proved elusive in the past. These features include both hypothetical and committed updates, dynamic constraints on transaction execution, non-determinism, and bulk updates. Finally, Transaction Logic holds promise as a logical model of hitherto non-logical phenomena, including so-called procedural knowledge in AI, and the behavior of object-oriented databases, especially methods with side eeects. This paper presents the semantics of Transaction Logic coupled with a sound and complete proof theory for a Horn-like subset of the logic.
Effects of Teacher Autonomy Support and Students' Autonomous Motivation on Learning in Physical Education

This study applied self-determination theory to investigate the effects of students' autonomous motivation and their perceptions of teacher autonomy support on need satisfaction adjustment, learning achievement, and cardiorespiratory fitness over a 4-month personal conditioning unit. Participants were 253 urban adolescents (121 girls and 132 boys, ages = 12–14 years). Based on a series of multiple regression analyses, perceived autonomy support by teachers significantly predicted students' need satisfaction adjustment and led to learning achievement, especially for students who were not autonomously motivated to learn in physical education. In turn, being more autonomous was directly associated with cardiorespiratory fitness enhancement. The findings suggest that shifts in teaching approaches toward providing more support for students' autonomy and active involvement hold promise for enhancing learning.
Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner

Background— Oxidative stress plays a causal role in vascular injury in diabetes mellitus, but the mechanisms and targets remain poorly understood. Methods and Results— Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite (ONOO−) or high glucose significantly inhibited both basal and insulin-stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Furthermore, protein kinase B/Akt inhibition induced by ONOO− or high glucose and apoptosis triggered by high glucose could be abolished by transfection of PTEN-specific small interfering RNA, suggesting that PTEN mediated the Akt inhibition by ONOO−. In addition, exposure of human umbilical vein endothelial cells to ONOO− or high glucose remarkably increased Ser428 phosphorylation of LKB1, a tumor suppressor. Interestingly, the ONOO−-enhanced PTEN phosphorylation and Akt inhibition can be blocked by LKB1-specific small interfering RNA. Consistently, LKB1 phosphorylated PTEN at Ser380/Thr382/383 in vitro, suggesting that LKB1 might act as an upstream kinase for PTEN. Compared with nondiabetic mice, the levels of PTEN, LKB1-Ser428 phosphorylation, and 3-nitrotyrosine (a biomarker of ONOO−) were significantly increased in the aortas of streptozotocin-induced diabetic mice, which was in parallel with a reduction in Akt-Ser473 phosphorylation and an increase in apoptosis. Furthermore, administration of PTEN-specific small interfering RNA suppressed diabetes-enhanced apoptosis and Akt inhibition. Finally, treatment with Tempol, a superoxide dismutase mimetic, and insulin, both of which reduced the ONOO− formation, markedly reduced diabetes-enhanced LKB1-Ser428 phosphorylation, PTEN, and apoptosis in the endothelium of mouse aortas. Conclusion— We conclude that hyperglycemia triggers apoptosis by inhibiting Akt signaling via ONOO−-mediated LKB1-dependent PTEN activation.
A structural model of wealth, obesity and health in the UK

Based on a household health production framework, this paper exploits the combination of socioeconomic, health and nutrition information from the UK National Diet and Nutrition Survey to analyze the endogenous relationship among wealth, nutrition, weight and the final health outcomes. Results show that higher wealth determines lower weight and better health as expected, but through a better diet rather than extra exercise or lower calorie consumption.
Assessment and therapeutic choice in septic arthritis of the hip in an intravenous drug abuser: case report at 14 years follow-up and review of literature.

INTRODUCTION Osteoarticular infections are found frequently in drug addicted individuals, representing one of the main reasons for their hospitalization. Through inoculation, the pathogenic agents can enter the individual's system directly through the skin or parenterally, transmitted, that is, through syringes and other objects used during such practice. In these particular conditions, or when the medical history is vague, a warranted suspicion and the execution of targeted research can help in the diagnosis of high-risk patients such as addicts. DISCUSSION With this paper, the Authors are presenting a case of septic arthritis in the hip joint, in a drug addicted patient with the habit of injecting narcotics into the femoral vein, in correspondence of the anatomical region known as the triangle of Scarpa. Following an examination of the bacterial culture samples taken by arthrocentesis, the S. Aureus infection was identified and a targeted antibiotic therapy (coxacillin and aminoglycosides) was prescribed. After one year, with clinical examination and medical scans resulting negative for infection, there was a remaining deformity of the femoral head and, therefore, a total hip arthroplasty (THA) was performed. The 14 year post-operative clinical examination and medical scan check-up showed a complete articular functionality and recovery of normal daily and work related activities.
Does Public Service TV and the Intensity of the Political Information Environment Matter?

In recent years, a number of studies have suggested a positive linkage between public service broadcasting and public knowledge about current affairs. Most studies are, however, based on aggregate, cross-sectional data. On the individual level they fall short of establishing any causal linkage between TV news exposure and public knowledge. In addition, studies which investigate whether the intensity of the political information environment matters for learning effects from watching TV news, are missing. Against this background, this study compares knowledge effects from watching public service and commercial TV news in three contexts that vary in the intensity of the political information environment: a national election campaign, a European parliamentary election campaign and a non-election period. Among other things, the results show stronger knowledge effects from watching public service than commercial TV news.
Binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main genetic variants of human alpha 1-acid glycoprotein: evidence for drug-binding differences between the variants and for the presence of two separate drug-binding sites on alpha 1-acid glycop

Human alpha 1-acid glycoprotein (AAG), a plasma drug transport protein, has three main genetic variants, the A variant and the F1 and S variants, which are encoded by two different genes. The binding of disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone to the two main gene products of AAG-the A variant and a mixture of the F1 and S variants (60% F1 and 40% S)-separated by chromatography from native commercial AAG, a mixture of almost equal proportions of the F1, S and A variants, was studied by equilibrium dialysis. A selective binding of disopyramide and methadone to the A variant and a preferential binding of dipyridamole to the F1S variant mixture were found. Lignocaine and chlorpromazine had a slight preference for binding to the A variant and to the F1S mixture, respectively, but progesterone showed no selectivity with regard to any of the variants of AAG. The differences in drug-binding demonstrated between the A variant and the F1S mixture confirmed those of a previous study, in which a selective binding of imipramine to the A variant and of warfarin and mifepristone to the F1S mixture have been found. These results indicate specific drug transport roles for each AAG variant, according to its separate genetic origin. The results of control binding experiments performed with (unfractionated) commercial AAG and the series of tested ligands concurred with that for the separate AAG variants, with respect to the proportion of the A variant (27%) and that of the F1 and S variants (73%) in the commercial protein. In addition, disopyramide, methadone, dipyridamole, chlorpromazine, lignocaine and progesterone were used in equilibrium dialysis displacement experiments to study interactions on binding sites labelled with imipramine for the A variant and with warfarin for the F1S variant mixture. The four latter ligands were found to competitively inhibit the binding of warfarin to the F1S variant mixture and all of them that of imipramine to the A variant. The ligands association constants to each AAG variant obtained from such inhibitory experiments were comparable to those determined in the direct binding studies. As the stochlometry of the interactions of the A variant and the F1S variants, respectively, with their specific ligands was approximately one (1), it was concluded that these ligands bind to each of these variants via a single common binding site. These results indicate that the AAG molecule would have for its ligands at least two separate binding sites, showing different specificity and localization, and not one site, as it is generally assumed. The possible pharmacological and clinical consequences of the binding results with the separate AAG variants are discussed.
Cholesterol-induced mammary tumorigenesis is enhanced by adiponectin deficiency: role of LDL receptor upregulation

Adiponectin is an adipokine that can suppress the proliferation of various human carcinoma cells. Although its anti-tumor activities have been suggested by many clinical investigations and animal studies, the underlying mechanisms are not fully characterized. In MMTV-polyomavirus middle T antigen (MMTV-PyVT) transgenic mice models, reduced- or complete loss-of-adiponectin expression promotes mammary tumor development. The present study demonstrated that while tumor development in control MMTV-PyVT mice is associated with a progressively decreased circulating cholesterol concentration, adiponectin deficient MMTV-PyVT mice showed significantly elevated total- and low density lipoprotein (LDL)-cholesterol levels. Cholesterol contents in tumors derived from adiponectin deficient mice were dramatically augmented. High fat high cholesterol diet further accelerated the tumor development in adiponectin deficient PyVT mice. The protein levels of LDL receptor (LDLR) were found to be upregulated in adiponectin-deficient tumor cells. In human breast carcinoma cells, treatment with LDL-cholesterol or overexpressing LDLR elevates nuclear beta-catenin activity and facilitates tumor cell proliferation. On the other hand, adiponectin decreased LDLR protein expression in breast cancer cells and inhibited LDL-cholesterol-induced tumor cell proliferation. Both in vivo and in vitro evidence demonstrated a stimulatory effect of adiponectin on autophagy process, which mediated the down-regulation of LDLR. Adiponectin-induced reduction of LDLR was blocked by treatment with a specific inhibitor of autophagy, 3-methyladenine. In conclusion, the study demonstrates that adiponectin elicits tumor suppressive effects by modulating cholesterol homeostasis and LDLR expression in breast cancer cells, which is at least in part attributed to its role in promoting autophagic flux.
On the numerical inversion of Laplace transforms: comparison of three new methods on characteristic problems from applications

Three frequently used methods for numerically inverting Laplace transforms are tested on complicated transforms taken from the literature. The first method is a straightforward application of the trapezoidal rule to Bromwich's integral. The second method, developed by Weeks [22], integrates Bromwich's integral by using Laguerre polynomials. The third method, devised by Talbot [18], deforms Bromwich's contour so that the integrand of Bromwich's integral is small at the beginning and end of the contour. These methods are also applied to joint Laplace-Fourier transform problems. All three methods give satisfactory results; Talbot's, however, has an accurate method for choosing required parameters.
A Dirty Model for Multiple Sparse Regression

The task of sparse linear regression consists of finding an unknown sparse vector from linear measurements. Solving this task even under “high-dimensional” settings, where the number of samples is fewer than the number of variables, is now known to be possible via methods such as the LASSO. We consider the multiple sparse linear regression problem, where the task consists of recovering several related sparse vectors at once. A simple approach to this task would involve solving independent sparse linear regression problems, but a natural question is whether one can reduce the overall number of samples required by leveraging partial sharing of the support sets, or nonzero patterns, of the signal vectors. A line of recent research has studied the use of ℓ1/ℓq norm block-regularizations with q > 1 for such problems. However, depending on the level of sharing, these could actually perform worse in sample complexity when compared to solving each problem independently. We present a new “adaptive” method for multiple sparse linear regression that can leverage support and parameter overlap when it exists, but not pay a penalty when it does not. We show how to achieve this using a very simple idea: decompose the parameters into two components and regularize these differently. We show, theoretically and empirically, that our method strictly and noticeably outperforms both ℓ1 or ℓ1/ℓq methods, over the entire range of possible overlaps (except at boundary cases, where we match the best method), even under high-dimensional scaling.
A first approach to tactile texture recognition

Tactile texture recognition seems to be a very important research area with various interesting applications which include medical, geological and autonomous mobile robotics; despite the great amount of tasks that biological beings solve using the sense of touch, not much work is done in this area (except for pressure-related sensing), and there are only a few papers in literature that uses dynamic tactile sensing strategies, i.e. the kind of exploration that we and the biological beings use to recognize a texture. In this paper we present a system for tactile texture recognition, using sound-understanding techniques. We develop a sensing "pen" with an electret piezoelectric microphone, covered by a rugged material. The pen is rubbed over the material that we want to identify, the sound produced is segmented, the FFT is obtained and the result is introduced to a learning vector quantization technique (LVQ). We explore 18 common materials which includes surfaces from glass to a real human beard. We achieve more than 93% of recognition over the 18 textures, and when the system makes an error it gives a similar texture as result.
Synthesis of 2’-(5-Chloro-2-Hydroxybenzylidene) Benzenesulfanohydrazide Schiff Base and its Anti- Ulcer Activity in Ethanol-Induced Gastric Mucosal Lesions in Rats

Purpose: To study the anti-ulcer activity of 2’-(5-Chloro-2-hydroxybenzylidene) benzenesulfanohydrazide Schiff base against ethanol-induced gastric mucosal lesions in rats. Methods: 2’-(5-Chloro-2-hydroxybenzylidene) benzenesulfano-hydrazide (Cl-BzSO-HAP) was synthesized, and structurally characterized by elemental analysis, FT-IR, 1 H-NMR and C-NMR. Its preventive activity against ulcer induced by absolute ethanol in Sprague-Dawley rats were studied in vivo. Twenty four Sprague Dawley (SD) rats (12 males and 12 females) were assigned equally into 4 groups (n = 6), including negative control and positive control groups. The third group received a low oral dose of the compound (50 mg/kg) while the fourth group was administered a high oral dose (100 mg/kg). The degree of gastric lesion formation was assessed. Prior to dosing, the animals were fasted overnight. Results: Cl-BzSO-HAP showed significant preventive activity against ulcer induced by absolute ethanol. Oral administration of the compound (both low and high doses) prior to ethanol administration inhibited gastric lesion formation by 88.0 and 94.9 %, respectively, compared to 82.7 % for the positive control, cimetidine. Conclusion: Extensive gastric necrosis in rats induced by absolute ethanol was prevented by administration of Cl-BzSO-HAP resulting in reduced or total absence of lesions. Keywords: Benzenesulfanohydrazone, Schiff base, Gastric ulcer, Histology.
Light Direction from Shad(ow)ed Random Gaussian Surfaces

Three human observers estimated the illumination direction for samples of random Gaussian surfaces illuminated by a collimated beam from random directions. These stimuli appear as ‘texture’ due to shading and shadowing (the surface on the microscale was Lambertian of uniform albedo; thus texture appears only through shading and shadowing). We found that observers were able to estimate the azimuth of the source with remarkable accuracy. In the shading regime (no shadows) the observers committed 180° azimuth errors with 50% probability, whereas in the shadow-dominated regime they were able to avoid this convex/concave confusion to a large extent. They evidently relied on second-order statistics in the shading regime and used an unidentified first-order cue in the shadow regime. The elevations of the source were also estimated with remarkable precision. We attribute this to the statistical homogeneity of the sample which can apparently be exploited by the observers. Likely cues are the fraction of shadowed surface, average intensity and rms contrast. The ability of human observers to estimate the illumination direction from surface texture no doubt contributes to the ability to estimate the light field in scenes, which is a prerequisite to the photometric parsing of scenes (shape from shading, and so forth).
Families’ Priorities Regarding Hospital-to-Home Transitions for Children With Medical Complexity

BACKGROUND: National health care policy recommends that patients and families be actively involved in discharge planning. Although children with medical complexity (CMC) account for more than half of pediatric readmissions, scalable, family-centered methods to effectively engage families of CMC in discharge planning are lacking. We aimed to systematically examine the scope of preferences, priorities, and goals of parents of CMC regarding planning for hospital-to-home transitions and to ascertain health care providers’ perceptions of families’ transitional care goals and needs. METHODS: We conducted semistructured interviews with parents and health care providers at a tertiary care hospital. Interviews were continued until thematic saturation was reached. Interviews were audio recorded, transcribed verbatim, and analyzed to identify emergent themes via a general inductive approach. RESULTS: Thirty-nine in-depth interviews were conducted, including 23 with family caregivers of CMC and 16 with health care providers. Families’ priorities, preferences, and goals for hospital-to-home transitions aligned with 7 domains: effective engagement with health care providers, respect for families’ discharge readiness, care coordination, timely and efficient discharge processes, pain and symptom control, self-efficacy to support recovery and ongoing child development, and normalization and routine. These domains also emerged in interviews with health care providers, although there were minor differences in themes discussed. CONCLUSIONS: Although CMC have diverse transitional care needs, their families’ priorities, preferences, and goals aligned with 7 domains that bridged their hospital admission with reestablishment of a home routine. This research provides essential foundational data to engage families in discharge planning, guiding the operationalization of national health policy recommendations.