Miracle-dz/UniFAR-FTUs huggingface dataset:
Preparation of Biodegradable Microspheres Containing Repaglinide

The objective of the present study is to prepare and evaluate poly(e-caprolactone) microspheres of repaglinide by using the solvent evaporation technique. The microspheres were prepared with different drug-to-carrier ratios: F1 (1:3), F2 (1:4), F3 (1:5), and F4 (1:6). The microspheres were then evaluated for particle size, SEM, FT-IR study, percentage yield, drug entrapment, stability studies, and for in vitro release kinetics. Scanning electron microscopy (SEM) revealed that microspheres were spherical with a nearly smooth surface morphology. The percentage yield and drug entrapment efÞ ciency were high for all the formulations. Fourier Transform-Infrared spectroscopy (FT-IR) showed that there was no chemical interaction between the drug and the polymer. No appreciable difference was observed in the stability study, in the extent of degradation of the product for 60 days in the microspheres that were stored at various temperatures. The in vitro release study showed that replaglinide release from all the formulations was slow and sustained over 12 h. Application of the in vitro drug release data to various kinetic equations indicated zero order release from repaglinide microspheres. Key words: Biodegradable, microspheres, poly(e-caprolactone), repaglinide.
Epidemiology of infections following haploidentical peripheral blood hematopoietic cell transplantation

The use of T‐cell replete haploidentical hematopoietic cell transplant (haplo‐HCT) has increased substantially since the introduction of post‐transplant cyclophosphamide (PTCy) regimens. Limited data exist concerning infectious complications of haplo‐HCT utilizing mobilized peripheral blood (PB) hematopoietic cells.
Microscopic explanation of the compensation (Meyer-Neldel) rule.

We propose that the Meyer-Neldel compensation rule can be understood as arising naturally for assisted processes in which the energy for the process is much larger than that of a typical excitation. In this case, the total energy is provided by multiple excitations. The prefactor is then proportional to the number of ways of assembling these excitations. This number increases exponentially with the energy for the process, yielding the Meyer-Neldel rule
Are you fiscally fit

ü Consider these best practices in plan design. £ Automatic enrollment and automatic escalation – Auto-enrollment can boost participation to between 86 and 91%. 1 Auto-escalation can improve savings rates; research shows that employees are not likely to opt out at even a high default rate of 5 or 6%. 2 £ Employer match – A match nearly triples the odds of participation.3 £ Plan guardrails – Limiting the number or eliminating loans reinforces your employees’ commitment to long-term planning.
Targeting chromatin defects in selected solid tumors based on oncogene addiction, synthetic lethality and epigenetic antagonism.

Background Although the role of epigenetic abnormalities has been studied for several years in cancer genesis and development, epigenetic-targeting drugs have historically failed to demonstrate efficacy in solid malignancies. However, successful targeting of chromatin remodeling deficiencies, histone writers and histone reader alterations has been achieved very recently using biomarker-driven and mechanism-based approaches. Epigenetic targeting is now one of the most active areas in drug development and could represent novel therapeutic opportunity for up to 25% of all solid tumors. Material and methods We reviewed preclinical and clinical studies that described epigenetic oncogenic addictions, synthetic lethal relationships or epigenetic antagonisms in chromatin regulators. Experimental approaches, their clinical relevance and applicability, as well as corresponding on-going studies are described. Results The most successful approaches that have been clinically validated so far include the targeting of the BRD4-NUT fusion transcript in NUT-midline carcinoma by BET (Bromodomain Extra-Terminal) inhibitors, and the use of EZH2 (Enhancer of Zest Homolog 2) inhibitors in SMARCB1-deficient malignant rhabdoid tumors and SMARCA4-deficient ovarian small cell carcinomas. Clinical validation is still required for other synthetic lethal relationships or epigenetic antagonisms, including those described between EZH2 inhibitors and deficiencies in components of the Polycomb or SWI/SNF chromatin-remodeling complexes (including BAP1, ARID1A and PBRM1 subunits), as well as between the CREBBP and EP300 histone acetylases. Further, interplays between epigenetic modifiers and non-epigenetic cellular processes might be therapeutically exploited, and combinatorial strategies could be envisioned to overcome resistance or to sensitize cells to already approved drugs. Conclusion Epigenetic-targeting drugs have historically failed proving efficacy in solid malignancies when used broadly, but novel mechanism-based approaches in molecularly selected patient populations have facilitated recent successes in proof-of-concept studies in solid tumors. Appropriate clinical trial design and molecular patient selection will be key for the success of epigenetic modifiers in solid tumours.
Evaluation of equine superficial digital flexor tendon lesions

Tendon injuries are commonplace in the equine athlete and are reported to be one of the most prevalent forms of musculoskeletal injuries occurring in horses competing in all disciplines. The superficial digital flexor tendon (SDFT) is the more commonly injured of the flexor tendons, accounting for 75–93% of clinical cases; research suggests that lesions typically occur at the mid-metacarpal level in the ‘core’ or central region of the SDFT. Aims and objectives: The aim of this research was to increase knowledge regarding the susceptibility to injury of specific topographical regions within the SDFT, and to identify any relationship between topographical location and lesion severity to laterality and the equestrian discipline the subjects competed in. Method: Secondary data were ultrasound scans from the forelimb SDFTs of horses (n =100) presenting with primary ‘core’ lesions. Topographical location, percentage distribution of the lesion entirety and the echogenicity of lesions were ascertained and graded.
Title Genomic characterisation of HER 2-positive breast cancer and response to neoadjuvant trastuzumab and chemotherapy-results from the ACOSOG Z 1041 ( Alliance ) trial

Affiliations list 1McDonnell Genome Institute at Washington University School of Medicine, St. Louis, USA; 2Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, USA; 3Siteman Cancer Center, Washington University School of Medicine, St. Louis, USA; 4Department of Genetics, Washington University School of Medicine, St. Louis, USA; 5Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, USA, 6Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, USA; 7Duke University Medical Center, Durham, USA; 8Alliance Statistics and Data Center, Mayo Clinic, Rochester, USA; 9The University of Texas MD Anderson Cancer Center, Houston, USA; 10The University of Texas Southwestern Medical Center, Dallas, USA; 11Mayo Clinic, Rochester, USA; 12Doctors Hospital of Laredo, Laredo, USA; 13Institute for Genomic Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, USA; 14Department of Pediatrics, The Ohio State University College of Medicine, Columbus, USA.
Spontaneous fluctuation correlations in thermal lattice-gas automata.

We construct a 19-bit lattice-gas model which is shown to exhibit spontaneous fluctuation correlations as produced in a thermal fluid system. Thus the lattice gas can be considered in the same sense as a real fluidas a reservoir of excitations with wavelengths and frequencies ranging from the microscopic level to the hydrodynamic scale. In particular the dynamic structure factor obtained from lattice-gas simulations is in agreement with the classical Rayleigh-Brillouin spectrum of real fluids. © 1992 The American Physical Society.
Consumption of ultra-processed foods and body fat during childhood and adolescence: a systematic review

Abstract Objective To review the available literature on the association between consumption of ultra-processed foods and body fat during childhood and adolescence. Design A systematic review was conducted in the PubMed, Web of Science and LILACS databases. Studies that evaluated the association between consumption of ultra-processed food (exposure) and body fat (outcome) during childhood and adolescence were eligible. Subjects Healthy children and adolescents. Results Twenty-six studies that evaluated groups of ultra-processed foods (such as snacks, fast foods, junk foods and convenience foods) or specific ultra-processed foods (soft drinks/sweetened beverages, sweets, chocolate and ready-to-eat cereals) were selected. Most of the studies (n 15) had a cohort design. Consumption was generally evaluated by means of FFQ or food records; and body composition, by means of double indirect methods (bioelectrical impedance analysis and skinfolds). Most of the studies that evaluated consumption of groups of ultra-processed foods and soft drinks/sweetened beverages found positive associations with body fat. Conclusions Our review showed that most studies have found positive associations between consumption of ultra-processed food and body fat during childhood and adolescence. There is a need to use a standardized classification that considers the level of food processing to promote comparability between studies.
A comprehensive genetic profile of phyllodes tumours of the breast detects important mutations, intra‐tumoral genetic heterogeneity and new genetic changes on recurrence

The aims of this study were to identify genetic changes associated with malignant progression of the fibroepithelial neoplasms, phyllodes tumours of the breast (PTs), and to ascertain whether genetic progression occurs when PTs recur locally. A further aim was to assess whether the genetic data support the classification of these tumours into three subtypes, benign, borderline and malignant. 126 PTs (37 benign, 41 borderline, 48 malignant) were analysed by either array‐CGH or the Illumina Goldengate assay. The large‐scale genetic changes associated with malignant/borderline phenotypes were + 1q, + 5p, + 7, + 8, − 6, − 9p, − 10p and − 13. Cluster analysis of the array‐CGH data supported the division of malignant and borderline PTs into two separate groups, one comprising almost all malignant lesions and the other, benign and borderline tumours. Interstitial deletions of 9p21 that involved the p16INK4a locus were present in many malignant/borderline PTs, and some of these appeared to cause homozygous loss. Loss of expression of p16INK4a was found frequently and this was associated with 9p deletion; we also identified one p16INK4a mutation and evidence of methylation of p16INK4a in malignant PTs. Our evidence shows that inactivation of this gene is important in the development of malignant PTs. In selected PTs, multiple areas of stroma were isolated and analysed separately by array‐CGH. We found considerable intra‐tumoral genetic heterogeneity. Analysis of paired primary and recurrent tumours showed that recurrent tumours often acquired new genetic changes; in particular, benign tumours tended to acquire changes characteristic of the malignant/borderline phenotype. We believe it likely that unfavourable sub‐clones not easily identified by histology account for the unpredictable clinical behaviour of these tumours. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Identification of CXCL13 as a new marker for follicular dendritic cell sarcoma

The homeostatic chemokine CXCL13 is preferentially produced in B‐follicles and is crucial in the lymphoid organ development by attracting B‐lymphocytes that express its selective receptor CXCR5. Follicular dendritic cells (FDCs) have been identified as the main cellular source of this chemokine in lymphoid organs. Recently, genome‐wide approaches have suggested follicular CD4 T‐helper cells (THF) as additional CXCL13 producers in the germinal centre and the neoplastic counterpart of THF (CD4+ tumour T‐cells in angioimmunoblastic T‐cell lymphoma) retains the capability of producing this chemokine. In contrast, no data are available on CXCL13 expression on FDC sarcoma (FDC‐S) cells. By using multiple approaches, we investigated the expression of CXCL13 at mRNA and protein level in reactive and neoplastic FDCs. In reactive lymph nodes and tonsils, CXCL13 protein is mainly expressed by a subset of FDCs in B‐cell follicles. CXCL13 is maintained during FDC transformation, since both dysplastic FDCs from 13 cases of Castleman's disease and neoplastic FDCs from ten cases of FDC‐S strongly and diffusely express this chemokine. This observation was confirmed at mRNA level by using RT‐PCR and in situ hybridization. Of note, no CXCL13 reactivity was observed in a cohort of epithelial and mesenchymal neoplasms potentially mimicking FDC‐S. FDC‐S are commonly associated with a dense intratumoural inflammatory infiltrate and immunohistochemistry showed that these lymphocytes express the CXCL13 receptor CXCR5 and are mainly of mantle zone B‐cell derivation (IgD+ and TCL1+). In conclusion, this study demonstrates that CXCL13 is produced by dysplastic and neoplastic FDCs and can be instrumental in recruiting intratumoural CXCR5+ lymphocytes. In addition to the potential biological relevance of this expression, the use of reagents directed against CXCL13 can be useful to properly identify the origin of spindle cell and epithelioid neoplasms. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Why are MSCs therapeutic? New data: new insight

Adult marrow‐derived mesenchymal stem cells (MSCs) are able to differentiate into bone, cartilage, muscle, marrow stroma, tendon–ligament, fat and other connective tissues. The questions can be asked, what do MSCs do naturally and where is the MSC niche? New insight and clinical experience suggest that MSCs are naturally found as perivascular cells, summarily referred to as pericytes, which are released at sites of injury, where they secrete large quantities of bioactive factors that are both immunomodulatory and trophic. The trophic activity inhibits ischaemia‐caused apoptosis and scarring while stimulating angiogenesis and the mitosis of tissue intrinsic progenitor cells. The immunomodulation inhibits lymphocyte surveillance of the injured tissue, thus preventing autoimmunity, and allows allogeneic MSCs to be used in a variety of clinical situations. Thus, a new, enlightened era of experimentation and clinical trials has been initiated with xenogenic and allogeneic MSCs. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Intraoperative salvage does not affect expression of markers for erythrophagocytosis

Dear Sir, Red cell salvage is an effective blood conservation strategy that reduces the need for allogeneic blood transfusion by about 30% (Carless et al., 2006) and is commonly implemented in cardiac, orthopaedic and transplant operations that involve high blood loss. Despite its introduction over 20 years ago, autologous transfusion and cell salvage remain poorly investigated and tested. It has been suggested that high suction pressures in extracorporeal circuitry, such as cardiopulmonary bypass and haemodialysis machines, can inflict sub-lethal, mechanical damage to erythrocytes, which might predispose them to phagocytosis by macrophages (Yazer et al., 2008; Polaschegg, 2009). Erythrocytes expressing surface markers for consumption are phagocytosed predominantly by splenic macrophages in humans. Aberrant or excessive uptake of red blood cells can have deleterious consequences. Hod et al. (2010) demonstrated an iron-mediated, pro-inflammatory mechanism of injury that ensues as a result of excessive red cell uptake. In order to be taken up by macrophages, erythrocytes modulate expression of surface markers that signal senescence or damage. The nature of these signals has not been completely elucidated, but candidate molecules include CD47, sialic acid and phospatidylserine. CD47 may act as either a ‘don’t eat me’ signal (Oldenborg et al., 2000), its expression decaying with age (Stewart et al., 2005), or alternatively undergoing a conformational change to act as an ‘eat me’ signal after cell damage (Burger et al., 2012). Sialic acids are neuraminic acid derivatives, which exist on the termini of glycan chains of all mammalian membranes. They are thought to be lost with age and treatment with neuraminidase, an enzyme that removes sialic acids, has been reported to result in rapid erythrocyte uptake (Durocher et al., 1975; Bratosin et al., 1995). Phosphatidylserine is maintained on the inner cell membrane of healthy cells but is translocated to the outer surface in cells undergoing apoptosis (Wlodkowic et al., 2012). In this study we compared the expression of surface markers (α-2,3 and α-2,6 linked sialic acids, CD47 and phosphatidylserine) on native and salvaged red blood cells that may mediate interactions with macrophages. Patients listed to undergo either total hip replacement or coronary artery bypass grafting were recruited. Inclusion
Toward Reproducible Three-Dimensional Microstructure Analysis of Granular Materials and Complex Suspensions

Abstract Focused ion beam nanotomography (FIB-nt) is a novel method for high resolution three-dimensional (3D) imaging. In this investigation we assess the methodological parameters related to image acquisition and data processing that are critical for obtaining reproducible microstructural results from granular materials and from complex suspensions. For this purpose three case studies are performed: (1) The precision of FIB-nt is evaluated by analyzing a reference sample with nanospheres. Due to the implementation of an automated correction procedure, drift phenomena can be removed largely from the FIB data. However, at high magnifications remaining drift components can induce problems for 3D-shape reconstructions. (2) Correct object recognition from densely packed microstructures requires specific algorithms for splitting of agglomerated particles. To establish quantitative criteria for the correct degree of splitting, a parametric study with dry portland cement is performed. It is shown that splitting with a k-value of 0.6 leads to accurate results. (3) Finally, the reproducibility of the entire cryo-FIB analysis is investigated for high pressure frozen cement suspensions. Reproducible analyses can be obtained if the magnification is adapted to the particle size. At low magnifications the small particles and their surface area are underestimated. At high magnifications representativity is questioned because local inhomogeneities can become dominant.
Comparison of CpG island hypermethylation and repetitive DNA hypomethylation in premalignant stages of gastric cancer, stratified for Helicobacter pylori infection

CpG island hypermethylation and genomic DNA hypomethylation are found not only in gastric cancers but also in associated premalignant lesions. Helicobacter pylori infection induces aberrant CpG island hypermethylation in gastric mucosae. However, little is known about the relationship between H. pylori infection and aberrant methylation in premalignant lesions. The present study characterized methylation changes in a subset of genes and repetitive DNA elements (ALU, LINE‐1, SAT2) and examined their relationship with H. pylori infection in premalignant lesions of gastric cancers. We performed MethyLight analysis of 25 genes and SAT2 and COBRA analysis of ALU and LINE‐1 in 212 gastric tissue samples. H. pylori infection was closely associated with enhanced hypermethylation of CpG island loci in chronic gastritis samples, but this association was not found among intestinal metaplasias, gastric adenomas and gastric cancers. The number of methylated genes was greater in intestinal metaplasia and gastric adenoma samples than in chronic gastritis samples, regardless of H. pylori infection. Methylation of repetitive DNA elements in gastric lesions generally decreased with progression of the gastric lesion along the multistep carcinogenesis. No difference was noted in the number of methylated genes in chronic gastritis or intestinal metaplasia between gastric cancer patients and non‐cancer subjects. In conclusion, we found that there was no enhanced CpG island hypermethylation in gastric cancer and premalignant lesions in association with H. pylori infection and our findings suggest that CpG island hypermethylation and repetitive DNA hypomethylation are enhanced with progression of the gastric lesion through the multistep carcinogenesis, regardless of the status of H. pylori infection. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Prognostic relevance of DNA copy number changes in colorectal cancer

In a study of 109 colorectal cancers, DNA copy number aberrations were identified by comparative genomic hybridization using a DNA microarray covering the entire genome at an average interval of less than 1 Mbase. Four patterns were revealed by unsupervised clustering analysis, one of them associated with significantly better prognosis than the others. This group contained tumours with short, dispersed, and relatively few regions of copy number gain or loss. The good prognosis of this group was not attributable to the presence of tumours showing microsatellite instability (MSI‐H). Supervised methods were employed to determine those genomic regions where copy number alterations correlate significantly with multiple indices of aggressive growth (lymphatic spread, recurrence, and early death). Multivariate analysis identified DNA copy number loss at 18q12.2, harbouring a single gene, BRUNOL4 that encodes the Bruno‐like 4 splicing factor, as an independent prognostic indicator. The data show that the different patterns of DNA copy number alterations in primary tumours reveal prognostic information and can aid identification of novel prognosis‐associated genes. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Demonstration of neutral atom trapping with microwaves.

We demonstrate trapping of neutral Cs atoms by the magnetic dipole force due to a microwave field. The trap is formed in a spherical microwave cavity tuned near the ground state hyperfine transition (9.193 GHz). With a microwave power of 83 W, the trap is [approx]0.1 mK deep. It is loaded with Cs atoms laser cooled to [approx]4 [mu]K. We observed oscillatory motion of atoms in the trap at frequencies of 1--3 Hz. This type of trap has certain advantages for achieving the conditions for Bose-Einstein condensation in hydrogen or the alkalis, because it can confine atoms predominantly in the lowest energy spin state.