Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical experience with Liraglutide in 196 patients with type 2 diabetes from a tertiary care center in India

Context: GLP-1 receptor agonists (GLP-1 RA) are unique antidiabetic agents that have the ability to lower blood glucose without causing hypoglycemia, while at the same time promoting weight loss. Information on the efficacy and safety of GLP-1 RA in the Indian diabetic population is limited. Aims: (1) To evaluate the effect of GLP-1 RA, Liraglutide on glycemic control, and weight in obese Indian patients with type 2 diabetes. (2) To study the adverse event profile of Liraglutide in these patients in real-world clinical setting. Settings and Design: Observational study conducted in a tertiary care hospital. Materials and Methods: Liraglutide was prescribed to 196 obese patients with type 2 diabetes who had poor glycemic control on oral medications ± insulin. The initial dose of Liraglutide was 0.6 mg, which was up-titrated to 1.2 mg after 1 week; further up-titration to 1.8 mg was done based on tolerance. Dipeptidyl peptidase-IV (DPP-IV) inhibitors were discontinued and dose of other medications adjusted according to clinical judgment during the study period. Results: Mean age of patients was 49.9 ± 9.6 years. Three month data were available for 175 patients out of a total of 196. At 3 months, glycosylated hemoglobin (HbA1c) was 7.6 ± 0.9% vs. 9.2 ± 1.9% at baseline (P = 0.007) and mean body weight was 96.0 ± 16.5 kg vs. 100.1 ± 17.5 kg at baseline (P < 0.001). Most common adverse events were nausea, burping, and eructation (10%). Conclusion: Liraglutide significantly improves glycemic control with low risk of hypoglycemia and is associated with significant weight loss in obese Indian patients with type 2 diabetes mellitus.
Higher-dimensional categories with finite derivation type

We study convergent (terminating and confluent) presentations of n-categories. Using the notion of polygraph (or computad), we introduce the homotopical property of finite derivation type for n-categories, generalizing the one introduced by Squier for word rewriting systems. We characterize this property by using the notion of critical branching. In particular, we define sufficient conditions for an n-category to have finite derivation type. Through examples, we present several techniques based on derivations of 2-categories to study convergent presentations by 3-polygraphs.
Scavenger Receptor C-type Lectin Binds to the Leukocyte Cell Surface Glycan Lewisx by a Novel Mechanism*

The scavenger receptor C-type lectin (SRCL) is unique in the family of class A scavenger receptors, because in addition to binding sites for oxidized lipoproteins it also contains a C-type carbohydrate-recognition domain (CRD) that interacts with specific glycans. Both human and mouse SRCL are highly specific for the Lewisx trisaccharide, which is commonly found on the surfaces of leukocytes and some tumor cells. Structural analysis of the CRD of mouse SRCL in complex with Lewisx and mutagenesis show the basis for this specificity. The interaction between mouse SRCL and Lewisx is analogous to the way that selectins and DC-SIGN bind to related fucosylated glycans, but the mechanism of the interaction is novel, because it is based on a primary galactose-binding site similar to the binding site in the asialoglycoprotein receptor. Crystals of the human receptor lacking bound calcium ions reveal an alternative conformation in which a glycan ligand would be released during receptor-mediated endocytosis.
Separation of Notch1 Promoted Lineage Commitment and Expansion/Transformation in Developing T Cells

Notch1 signaling is required for T cell development. We have previously demonstrated that expression of a dominant active Notch1 (ICN1) transgene in hematopoietic stem cells (HSCs) leads to thymic-independent development of CD4+CD8+ double-positive (DP) T cells in the bone marrow (BM). To understand the function of Notch1 in early stages of T cell development, we assessed the ability of ICN1 to induce extrathymic T lineage commitment in BM progenitors from mice that varied in their capacity to form a functional pre-T cell receptor (TCR). Whereas mice repopulated with ICN1 transduced HSCs from either recombinase deficient (Rag-2−/−) or Src homology 2 domain–containing leukocyte protein of 76 kD (SLP-76)−/− mice failed to develop DP BM cells, recipients of ICN1-transduced Rag-2−/− progenitors contained two novel BM cell populations indicative of pre-DP T cell development. These novel BM populations are characterized by their expression of CD3ε and pre-Tα mRNA and the surface proteins CD44 and CD25. In contrast, complementation of Rag-2−/− mice with a TCRβ transgene restored ICN1-induced DP development in the BM within 3 wk after BM transfer (BMT). At later time points, this population selectively and consistently gave rise to T cell leukemia. These findings demonstrate that Notch signaling directs T lineage commitment from multipotent progenitor cells; however, both expansion and leukemic transformation of this population are dependent on T cell–specific signals associated with development of DP thymocytes.
Effectiveness and cost-effectiveness of an injury prevention programme for adult male amateur soccer players: design of a cluster-randomised controlled trial

Background and aims Approximately 16% of all sports injuries in the Netherlands are caused by outdoor soccer. A cluster-randomised controlled trial has been designed to investigate the effectiveness and cost-effectiveness of an injury prevention programme (‘The11’) for male amateur soccer players. The injury prevention programme The11, developed with the support of the World Football Association FIFA, aims to reduce the impact of intrinsic injury risk factors in soccer. Methods Teams playing at first-class amateur level in two districts in the Netherlands are participating in the study. Teams in the intervention group were instructed to apply The11 during each practice session throughout the 2009–10 season. All participants of the control group continued their practice sessions as usual. All soccer-related injuries and related costs for each team were systematically reported online by a member of the medical staff. Player exposure to practice sessions and matches was reported weekly by the coaches. Also the use of The11 during the season after the intervention season will be monitored. Discussion Our hypothesis is that integrating the The11 exercises in the warm-up for each practice session is effective in terms of injury incidence, injury severity, healthcare use, and its associated costs and/or absenteeism. Prevention of soccer injuries is expected to be beneficial to adult soccer players, soccer clubs, the Royal Dutch Football Association (KNVB), health insurance companies and society.
Challenges in Virtual Reality Exergame Design

Exercise video games have become increasingly popular due to their potential as tools to increase user motivation to exercise. In recent years we have seen an emergence of consumer level interface devices suitable for use in gaming. While past research has indicated that immersion is a factor in exergame eectiveness, there has been little research investigating the use of immersive interface technologies such as head mounted displays for use in exergames. In this paper we identify and discuss ve major design challenges associated with the use of immersive technologies in exergaming: motion sickness caused by sensory disconnect when using a head mounted display, reliable bodily motion tracking controls, the health and safety concerns of exercising when using immersive technologies, the selection of an appropriate player perspective, and physical feedback latency. We demonstrate a prototype exergame utilising several aordable immersive gaming devices as a case study in overcoming these challenges. The results of a user study we conducted found that our prototype game was largely successful in overcoming these challenges, although further work would lead to improvement and we were able to identify further issues associated with the use of a head mounted display during exercise.
Cancers in the first-degree relatives of children with brain tumours

We used the nationwide Swedish Family-Cancer Database with 2060 childhood brain tumours diagnosed in the period 1958–1996 to analyse the risk of this tumour by parental cancers and in siblings of childhood brain tumour probands. Groups of patients were compared by calculating standardized incidence ratios (SIRs) for brain tumours in offspring. 1.3% of brain tumour patients had a parent with nervous system cancer; SIRs were 2.4 and 1.88 for diagnostic ages < 5 and < 15 years, respectively. The data showed distinct patterns of familial risks for childhood brain tumours, the SIR was 10.26 for brain astrocytoma given a parent with meningioma. Parental colon cancer was associated with offspring ependymoma (SIR 3.70), and parental salivary gland cancers with offspring medulloblastoma (SIR 13.33, but two cases only). SIR for sibling nervous system cancer from childhood brain tumour probands was 3.55 up to age 61. © 2000 Cancer Research Campaign
Phase I Study of the Angiogenesis Inhibitor BIBF 1120 in Patients with Advanced Solid Tumors

Purpose: BIBF 1120 is an oral, potent angiokinase inhibitor targeting receptors of the vascular endothelial growth factors, platelet-derived growth factors, and fibroblast growth factors. This phase I, accelerated titration study assessed the maximum tolerated dose, safety, pharmacokinetics, and pharmacodynamic effects of BIBF 1120. Patients and Methods: Sixty-one patients with advanced cancers received BIBF 1120 in successive cohorts. Twenty-five received 50 to 450 mg once daily and 36 received 150 to 300 mg twice daily in 4-week treatment courses interspersed by 1 week of washout. Dynamic contrast-enhanced magnetic resonance imaging assessed antiangiogenic effect in 42 patients. Results: Most frequent BIBF 1120–related adverse events were mostly mild to moderate (Common Toxicity Criteria grade 1-2) nausea (68.9%), vomiting (45.9%), and diarrhea (44.3%). The majority of dose-limiting adverse events of Common Toxicity Criteria grade 3 or 4 were reversible liver enzyme elevations. The maximum tolerated dose was 250 mg of BIBF 1120 for once and twice daily dosing. BIBF 1120 was absorbed moderately fast (tmax = 1-3 hours at steady state), with no deviation from dose linearity and no decrease of exposure over time. The gMean terminal half-life was from 13 to 19 hours. One complete and two partial responses occurred in patients with renal cell cancer (n = 2) and colorectal cancer (n = 1). Dynamic contrast-enhanced magnetic resonance imaging showed a significant reduction in tumor blood flow in 55% of evaluable patients. Conclusions: BIBF 1120 dosed continuously displayed a favorable safety and pharmacokinetics profile, and first efficacy signals were observed. Twice daily dosing permitted increased drug exposure without additional toxicity. Two hundred milligrams BIBF 1120 twice daily is the recommended dose for phase II monotherapy studies. Clin Cancer Res; 16(1); 311–9
Inhibition of Corticosteroid-Binding Globulin Gene Expression by Glucocorticoids Involves C/EBPβ

Corticosteroid-binding globulin (CBG), a negative acute phase protein produced primarily in the liver, is responsible for the transport of glucocorticoids (GCs). It also modulates the bioavailability of GCs, as only free or unbound steroids are biologically active. Fluctuations in CBG levels therefore can directly affect GC bioavailability. This study investigates the molecular mechanism whereby GCs inhibit the expression of CBG. GCs regulate gene expression via the glucocorticoid receptor (GR), which either directly binds to DNA or acts indirectly via tethering to other DNA-bound transcription factors. Although no GC-response elements (GRE) are present in the Cbg promoter, putative binding sites for C/EBPβ, able to tether to the GR, as well as HNF3α involved in GR signaling, are present. C/EBPβ, but not HNF3α, was identified as an important mediator of DEX-mediated inhibition of Cbg promoter activity by using specific deletion and mutant promoter reporter constructs of Cbg. Furthermore, knockdown of C/EBPβ protein expression reduced DEX-induced repression of CBG mRNA, confirming C/EBPβ’s involvement in GC-mediated CBG repression. Chromatin immunoprecipitation (ChIP) after DEX treatment indicated increased co-recruitment of C/EBPβ and GR to the Cbg promoter, while C/EBPβ knockdown prevented GR recruitment. Together, the results suggest that DEX repression of CBG involves tethering of the GR to C/EBPβ.
c-Src-p38 Mitogen-Activated Protein Kinase Signaling Is Required for Akt Activation in Response to Ionizing Radiation

The Akt and mitogen-activated protein kinase (MAPK) pathways have been implicated in tumor cell survival and contribute to radiation resistance. However, the molecular basis for link between MAPK and Akt in cell survival response to radiation is unclear. Here, we show that c-Src-Rac1-p38 MAPK pathway signals Akt activation and cell survival in response to radiation. Ionizing radiation triggered Thr308 and Ser473 phosphorylation of Akt. Exposure of cells to radiation also induced p38 MAPK and c-Jun NH2-terminal kinase activations. Inhibition of c-Jun NH2-terminal kinase suppressed radiation-induced cell death, whereas inhibition of p38 MAPK effectively increased sensitivity to radiation. Interestingly, inhibition of p38 MAPK completely attenuated radiation-induced Ser473 phosphorylation of Akt but did not affect Thr308 phosphorylation. Conversely, overexpression of p38 MAPK enhanced Ser473 phosphorylation of Akt in response to radiation. In addition, inhibition of p38 MAPK failed to alter phosphoinositide 3-kinase and phosphoinositide-dependent protein kinase activities. Ectopic expression of RacN17, dominant-negative form of Rac1, inhibited p38 MAPK activation and Ser473 phosphorylation of Akt. Following exposure to radiation, c-Src was selectively activated among Src family tyrosine kinases. Inhibition of c-Src attenuated Rac1 and p38 MAPK activations and Ser473 phosphorylation of Akt. Our results support the notion that the c-Src-Rac1-p38 MAPK pathway is required for activation of Akt in response to radiation and plays a cytoprotective role against radiation in human cancer cells. (Mol Cancer Res 2008;6(12):1872–80)
Explicature and semantics.

According to the relevance-theoretic account, identifying what is communicated explicitly by an utterance (its explicature) involves several pragmatic processes: disambiguation, saturation of indexical elements, the recovery of unarticulated constituents and ad hoc concept construction, both of the latter being free from any linguistic indication. This is at odds with a current philosophical position according to which contextual contributions to the proposition expressed are confined to the processes of disambiguation and saturation; this view necessitates positing a number of hidden (unarticulated) indexicals in the logical form of linguistic expressions. The arguments for the two positions are assessed.
Size Dependent Kinetics of Gold Nanorods in EPR Mediated Tumor Delivery

Gold nanorods (AuNR) have been intensively used in nanomedicine for cancer diagnostics and therapy, due to their excellent plasmonic photothermal properties. Tuning the size and aspect ratio of AuNR tailors the localized surface plasmon resonance (LSPR) in the NIR spectrum at which biological tissues are transparent, thus enables specific and effective treatment. The AuNR extravasates into tumor interstitium through enhanced permeation and retention (EPR) effect. Efficient AuNR based cancer therapy requires efficient AuNR tumor delivery. However, the size of AuNR can dramatically affect its blood circulation and tumor accumulation. Here we proposed for the first time a systematic framework to investigate the size-dependent kinetics of AuNRs during EPR mediated tumor delivery. By using 64Cu-labeled AuNRs with positron emission tomography (PET) and kinetic modeling, the in vivo uptake and kinetics of 64Cu-AuNR during its blood circulation, tumor accumulation and elimination were studied both in vitro and in vivo. The results of different sized AuNRs were compared and the optimum size of AuNR was suggested for EPR mediated tumor delivery. Our study provides a better understanding of the in vivo behavior of AuNR, which can help future design of nanomaterials for cancer imaging and therapy.
Protein Kinase C- e Transgenic Mice: A Unique Model for Metastatic Squamous Cell Carcinoma 1

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the most common forms of human skin cancer. BCC is slow growing and mostly localized, whereas SCC metastasizes to the regional lymph nodes and subsequently to distal organs. In murine skin carcinogenesis models for SCC, the incidence of metastasis is very low. We report here that FVB/N transgenic mice, which overexpress ( ; 18-fold) epitope-tagged protein kinase C- e (T7-PKC e ) protein in the epidermis provide a unique murine model system for highly malignant/metastatic SCC. Skin tumors were developed by the initiation-promotion protocol (initiation with 100 nmol 7,12-dimethyl-benz[ a ]anthracene; promotion with 5 nmol 12- O - tetradecanoylphorbol-13-acetate twice weekly). T7-PKC e transgenic mice showed 92% suppression of papilloma development compared with wild- type littermates after 23 weeks of tumor promotion. However, within 15–20 weeks of 12- O -tetradecanoylphorbol-13-acetate promotion, 40% of T7-PKC e mice developed at least one carcinoma compared with 7% of the wild-type mice. All carcinomas from T7-PKC e mice appeared without prior papilloma formation. Interestingly, 7,12-dimethyl-benz[ a ]anthra- cene alone resulted in the development of squamous cell carcinomas in 22% of T7-PKC e mice, whereas wild-type littermates developed no tumors. Histopathological analysis of tumors from multiple T7-PKC e mice revealed moderately differentiated SCC invading the dermal region with neoplasia appearing to originate and invade from the hair follicle. Carcinomas of T7-PKC e mice rapidly metastasized to regional lymph nodes within 3 weeks of appearance. In wild-type mice, the grade of the invading tumors, originating from interfollicular epidermis, was pathologically categorized as well-differentiated SCC and remained localized to the dermis. The T7-PKC e transgenic mice may provide a rapid and unique in vivo model to investigate metastatic SCC.
Global Income Inequality A review

Global inequality is a relatively recent topic. It was not until the early 1980s that the first calculations of inequality across world citizens were done.1 This is because in order to calculate global inequality, one needs to have data on (within-) national income distributions for most of the countries in the world, or at least for most of the populous and rich countries. But it is only from the earlyto mid-1980s that such data became available for China,2 the Soviet Union and its constituent republics and large parts of Africa. Before we move to an analysis of global inequality, however, it is useful to set the stage by delineating what topics we shall be concerned with and what not. This is necessary precisely because of the relative underdevelopment of the topic, reflected in the fact that the same or similar terms are often used in the literature to mean different things. We need to distinguish between inequality among countries’ mean incomes (inter-country inequality or Concept 1 inequality as dubbed by Milanovic, 2005), inequality among countries’ mean incomes weighted by countries’ populations (Concept 2 inequality), and inequality between world individuals (global or Concept 3 inequality). Concept 1 inequality deals with convergence and divergence of countries’ incomes, and although at first this line of work was couched in inequality terms (see Baumol, 1986), most of the later work used cross-
A Compact Model for Double-Gate Heterojunction Tunnel FETs

A compact model for generic heterojunction tunnel FETs (H-TFET) is developed to simulate H-TFET formed by different source/body material systems. The model is based on the device electrostatic potentials obtained from the solution of Poisson's equation. After deriving the potential profile, the tunneling distance from the source to the channel is calculated by matching the boundary conditions between the two materials. The drain current, terminal charges, and capacitance are derived based on the electrostatics dictated by the tunneling distance. To improve the accuracy for lightly doped source H-TFET in p-type devices, the effect of source depletion is also included. The model has been implemented in a circuit simulator without convergence program. It has also been extensively verified by TCAD simulations and published data to show its validity.
Association between Dioxin and Diabetes Mellitus in an Endemic Area of Exposure in Taiwan

Abstract Dioxin has been recognized as an environmental endocrine disruptor, but epidemiology studies of its effects on type 2 diabetes mellitus (DM) found inconsistent results, especially in men. Therefore, we conducted a study in Taiwan to evaluate the association between exposure to dioxin and DM. We recruited participants in an area where the residents were exposed to dioxin released from a factory. Using 20 and 64 pg WHO98-TEQDF/g lipid as the cut-offs, we categorized participants into 3 groups according to the level of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in the serum. We defined DM as a fasting plasma glucose level more than 126 mg/dl or an existing diagnosis. Of the 2898 participants, 425 patients of DM were identified, and we observed positive associations between dioxin and DM. After adjusting for age and body mass index (BMI), we found that a high serum dioxin level was an independent risk factor for DM (adjusted odds ratio [AOR] associated with 20–63 pg WHO98-TEQDF/g lipid = 2.1, 95% confidence interval [95% CI] 1.5–2.9; AOR for ≥64 pg WHO98-TEQDF/g lipid = 3.2, 95% CI 2.1–4.8). The findings are compatible with those in previous studies of PCDD/Fs. When we stratified the participants by sex, the serum dioxin level remained an independent risk factor for DM in both men and women. Exposure to dioxin is a risk factor for DM, independent of age and BMI in both men and women. Therefore, screening and intervention programs should be considered in endemic areas of exposure to dioxin.