Miracle-dz/UniFAR-FTUs huggingface dataset:
Energy Expenditure in Older People Hospitalized for an Acute Episode

Weight loss and worsening of nutritional state is a frequent downfall of acute hospitalization in older people. It is usually accepted that acute inflammation is responsible for hypercatabolism. However, several studies suggest, on the contrary, a reduction in resting energy expenditure (REE). This study aimed to obtain a reliable measure of REE and total energy expenditure (TEE) in older patients hospitalized for an acute episode in order to better assess patients’ energy requirements and help understand the mechanisms of weight loss in this situation. Nineteen hospitalized older patients (mean age 83 years) with C-reactive protein (CRP) level >20mg/L were recruited. REE and TEE were measured using gold standard methods of indirect calorimetry and doubly labeled water (DLW), respectively. REE was then compared to data from a previous study on aged volunteers from nursing homes who were free of an acute stressor event. Energy requirements measured by DLW were confirmed at 1.3 × REE. Energy intake covered the needs but did not prevent weight loss in these patients. TEE was not increased in hospitalized patients and was not influenced by inflammation, while the relationship between REE and inflammation was uncertain. Our results suggest that lean mass remains the major determinant of REE in hospitalized older people and that weight loss may not be explained solely by a state of hypercatabolism.
Associations Among Body Mass Index, Cortical Thickness, and Executive Function in Children.

Importance A total of 25.7 million children in the United States are classified as overweight or obese. Obesity is associated with deficits in executive function, which may contribute to poor dietary decision-making. Less is known about the associations between being overweight or obese and brain development. Objective To examine whether body mass index (BMI) is associated with thickness of the cerebral cortex and whether cortical thickness mediates the association between BMI and executive function in children. Design, Setting, and Participants In this cross-sectional study, cortical thickness maps were derived from T1-weighted structural magnetic resonance images of a large, diverse sample of 9 and 10-year-old children from 21 US sites. List sorting, flanker, matrix reasoning, and Wisconsin card sorting tasks were used to assess executive function. Main Outcomes and Measures A 10-fold nested cross-validation general linear model was used to assess mean cortical thickness from BMI across cortical brain regions. Associations between BMI and executive function were explored with Pearson partial correlations. Mediation analysis examined whether mean prefrontal cortex thickness mediated the association between BMI and executive function. Results Among 3190 individuals (mean [SD] age, 10.0 [0.61] years; 1627 [51.0%] male), those with higher BMI exhibited lower cortical thickness. Eighteen cortical regions were significantly inversely associated with BMI. The greatest correlations were observed in the prefrontal cortex. The BMI was inversely correlated with dimensional card sorting (r = -0.088, P < .001), list sorting (r = -0.061, P < .003), and matrix reasoning (r = -0.095, P < .001) but not the flanker task. Mean prefrontal cortex thickness mediated the association between BMI and list sorting (mean [SE] indirect effect, 0.014 [0.008]; 95% CI, 0.001-0.031) but not the matrix reasoning or card sorting task. Conclusions and Relevance These results suggest that BMI is associated with prefrontal cortex development and diminished executive functions, such as working memory.
Tissue-Specific DNA Replication Defects in Drosophila melanogaster Caused by a Meier-Gorlin Syndrome Mutation in Orc4

Meier-Gorlin syndrome (MGS) is a recessive disorder caused by mutations in genes associated with DNA replication. Despite the fact these proteins are essential for replication in every cell, patients with MGS have tissue-specific defects. Meier-Gorlin syndrome is a rare recessive disorder characterized by a number of distinct tissue-specific developmental defects. Genes encoding members of the origin recognition complex (ORC) and additional proteins essential for DNA replication (CDC6, CDT1, GMNN, CDC45, MCM5, and DONSON) are mutated in individuals diagnosed with MGS. The essential role of ORC is to license origins during the G1 phase of the cell cycle, but ORC has also been implicated in several nonreplicative functions. Because of its essential role in DNA replication, ORC is required for every cell division during development. Thus, it is unclear how the Meier-Gorlin syndrome mutations in genes encoding ORC lead to the tissue-specific defects associated with the disease. To begin to address these issues, we used Cas9-mediated genome engineering to generate a Drosophila melanogaster model of individuals carrying a specific Meier-Gorlin syndrome mutation in ORC4 along with control strains. Together these strains provide the first metazoan model for an MGS mutation in which the mutation was engineered at the endogenous locus along with precisely defined control strains. Flies homozygous for the engineered MGS allele reach adulthood, but with several tissue-specific defects. Genetic analysis revealed that this Orc4 allele was a hypomorph. Mutant females were sterile, and phenotypic analyses suggested that defects in DNA replication was an underlying cause. By leveraging the well-studied Drosophila system, we provide evidence that a disease-causing mutation in Orc4 disrupts DNA replication, and we propose that in individuals with MGS defects arise preferentially in tissues with a high-replication demand.
Cancer Treatment Goes Viral: Using Viral Proteins to Induce Tumour-Specific Cell Death

Cell death is a tightly regulated process which can be exploited in cancer treatment to drive the killing of the tumour. Several conventional cancer therapies including chemotherapeutic agents target pathways involved in cell death, yet they often fail due to the lack of selectivity they have for tumour cells over healthy cells. Over the past decade, research has demonstrated the existence of numerous proteins which have an intrinsic tumour-specific toxicity, several of which originate from viruses. These tumour-selective viral proteins, although from distinct backgrounds, have several similar and interesting properties. Though the mechanism(s) of action of these proteins are not fully understood, it is possible that they can manipulate several cell death modes in cancer exemplifying the intricate interplay between these pathways. This review will discuss our current knowledge on the topic and outstanding questions, as well as deliberate the potential for viral proteins to progress into the clinic as successful cancer therapeutics.
Identification of B Cell Epitopes of Blo t 13 Allergen and Cross-Reactivity with Human Adipocytes and Heart Fatty Acid Binding Proteins

Cross-reactivity between allergens and human proteins could have a clinical impact in allergic diseases. Blo t 13 is an allergen from the mite Blomia tropicalis, which belongs to the fatty acid binding protein (FABP) family and has structural homology with human FABPs. This work aimed to map B cell epitopes on Blo t 13 and to identify epitopes involved in cross-reactivity with human heart FABP (FABP3) and adipocyte FABP (FABP4). Sera from 25 patients with house dust mite (HDM) allergy that were sensitized to Blo t 13 were used for testing the reactivity of immunoglobulin E (IgE) and IgG to FABP. The epitope mapping of Blo t 13 was performed using overlapping peptides, and cross-reactivity between Blo t 13 and human FABP was analyzed using human sera and anti-Blo t 13 monoclonal antibodies. IgE antibodies to all FABPs were detected in 14/25 serum samples, and IgG was detected in 25/25 serum samples. The cross-reactivity of Blo t 13 was 42% with FABP3 and 48% with FABP4. Two IgE-binding regions were identified in Blo t 13; one between residues 54 and 72 (the main cross-reacting region) and another between residues 111 to 129. Our results suggest that exposure to the Blo t 13 allergen could induce an auto-reactive response to endogenous FABP in allergic patients sensitized to Blo t 13.
Competitive USB-Powered Hand-Held Potentiostat for POC Applications: An HRP Detection Case

Considerable efforts are made to develop Point-of-Care (POC) diagnostic tests. POC devices have the potential to match or surpass conventional systems regarding time, accuracy, and cost, and they are significantly easier to operate by or close to the patient. This strongly depends on the availability of miniaturized measurement equipment able to provide a fast and sensitive response. This paper presents a low-cost, portable, miniaturized USB-powered potentiostat for electrochemical analysis, which has been designed, fabricated, characterized, and tested against three forms of high-cost commercial equipment. The portable platform has a final size of 10.5 × 5.8 × 2.5 cm, a weight of 41 g, and an approximate manufacturing cost of $85 USD. It includes three main components: the power module which generates a stable voltage and a negative supply, the front-end module that comprises a dual-supply potentiostat, and the back-end module, composed of a microcontroller unit and a LabVIEW-based graphic user interface, granting plug-and-play and easy-to-use operation on any computer. The performance of this prototype was evaluated by detecting chronoamperometrically horseradish peroxidase (HRP), the enzymatic label most widely used in electrochemical biosensors. As will be shown, the miniaturized platform detected HRP at concentrations ranging from 0.01 ng·mL−1 to 1 µg·mL−1, with results comparable to those obtained with the three commercial electrochemical systems.
User Competency and Its Effect of Accounting Information System Implementation

The application of good governance is an obligation in preparing Local Government Financial Reports. From the results of the audit opinion from the Supreme Audit Agency, there are several findings that explain that not all local governments can prepare financial statements in accordance with the Government Accounting Standards specified. The purpose of this study is to examine the effect of Apparatus Competence (skills and knowledge) on the quality of accounting information systems. This research was conducted at the Regional Government in the city of Banjar Patroman, West Java Province, Indonesia. Data are primary data collected through questionnaires. Data is processed using Partial Least Square. The results of this study indicate that Apparatus Competencies (skills and knowledge) influence the accounting information system. The results of data processing for apparatus skills show that the path coefficient value is 0.063, which explains that for each standard deviation of one point in the skill score will result in an increase in the accounting information system score for the standard deviation of 0.063 points. This means that improving skills will contribute positively to the quality of accounting information systems. The path coefficient for employee knowledge is 0.381, which explains that for every one standard deviation point in the knowledge score will result in an increase in the accounting information system score for the standard deviation of 0.381 points. This means that increasing knowledge will contribute positively to the quality of accounting information systems
Identification of Differentially Expressed Genes Involved in the Molecular Mechanism of Pericarp Elongation and Differences in Sucrose and Starch Accumulation between Vegetable and Grain Pea (Pisum sativum L.)

Pea (Pisum sativum L.), as a major source of plant protein, is becoming one of the major cultivated crop species worldwide. In pea, the pericarp is an important determinant of the morphological characteristics and seed yield. To investigate the molecular mechanism of pericarp elongation as well as sucrose and starch accumulation in the pods of different pea cultivars, we performed transcriptomic analysis of the pericarp of two types of pea cultivar (vegetable pea and grain pea) using RNA-seq. A total of 239.44 Gb of clean sequence data were generated, and were aligned to the reference genome of Pisum sativum L. In the two samples, 1935 differentially expressed genes (DEGs) were identified. Among these DEGs, three antioxidant enzyme superoxide dismutase (SOD) were detected to have higher expression levels in the grain pea pericarps at the pod-elongating stages. Otherwise, five peroxidase (POD)-encoding genes were detected to have lower expression levels in the vegetative pericarps at the development stage of pea pod growth. Furthermore, genes related to starch and sucrose metabolism in the pea pod, such as SUS, INV, FBA, TPI, ADPase, SBE, SSS, and GBSS, were found to be differentially expressed. The RNA-seq data were validated through real-time quantitative RT-PCR of 13 randomly selected genes. Our findings provide the gene expression profile of, as well as differential expression information on, the two pea cultivars, which will lay the foundation for further studies on pod development and nutrition accumulation in the pea and provide valuable information for pea cultivar improvement.
Comparative Assessment of Phenolic Profiles, Cellular Antioxidant and Antiproliferative Activities in Ten Varieties of Sweet Potato (Ipomoea Batatas) Storage Roots

Sweet potato is the sixth most important crop widely cultivated around the world with abundant varieties. Different varieties gain different phenolic profiles which has drawn researchers’ attention for its unique health benefits. Our study evaluated the phenolic profiles, total and cellular antioxidant activities, antiproliferative activities, and cytotoxicity in 10 cultivated varieties of sweet potato in different colours. Among fourteen metabolites detected in our study, hyperoside, ferulic acid and caffeic acid were considered as prominent in SPSRs. According to the principle component analysis, phytochemical composition of HX22, YS15 and YS7 was quite similar. The results also evidenced that purple-fleshed varieties, such as YS43, YZ7 and YY153, have higher total phenolics content and corresponding stronger total antioxidant capacities as well as cellular antiproliferative activities against human liver cancer HepG2 cells than other varieties. The extremely significant correlation between phenolics and total antioxidant activity was also revealed by Pearson correlation analysis (p < 0.05). However, no significant relevance was found between intracellular antioxidant activity and total phenolic content or flesh colour of sweet potatoes.
Frontiers in Microfluidics, a Teaching Resource Review

This is a literature teaching resource review for biologically inspired microfluidics courses or exploring the diverse applications of microfluidics. The structure is around key papers and model organisms. While courses gradually change over time, a focus remains on understanding how microfluidics has developed as well as what it can and cannot do for researchers. As a primary starting point, we cover micro-fluid mechanics principles and microfabrication of devices. A variety of applications are discussed using model prokaryotic and eukaryotic organisms from the set of bacteria (Escherichia coli), trypanosomes (Trypanosoma brucei), yeast (Saccharomyces cerevisiae), slime molds (Physarum polycephalum), worms (Caenorhabditis elegans), flies (Drosophila melangoster), plants (Arabidopsis thaliana), and mouse immune cells (Mus musculus). Other engineering and biochemical methods discussed include biomimetics, organ on a chip, inkjet, droplet microfluidics, biotic games, and diagnostics. While we have not yet reached the end-all lab on a chip, microfluidics can still be used effectively for specific applications.
Combing the Cancer Genome for Novel Kinase Drivers and New Therapeutic Targets

Protein kinases are critical regulators of signaling cascades that control cellular proliferation, growth, survival, metabolism, migration, and invasion. Deregulation of kinase activity can lead to aberrant regulation of biological processes and to the onset of diseases, including cancer. In this review, we focus on oncogenic kinases and the signaling pathways they regulate that underpin tumor development. We highlight genomic biomarker-based precision medicine intervention strategies that match kinase inhibitors alone or in combination to mutationally activated kinase drivers, as well as progress towards implementation of these treatment strategies in the clinic. We also discuss the challenges for identification of novel protein kinase cancer drivers in the genomic era.
Antibody Structure and Function: The Basis for Engineering Therapeutics

Antibodies and antibody-derived macromolecules have established themselves as the mainstay in protein-based therapeutic molecules (biologics). Our knowledge of the structure–function relationships of antibodies provides a platform for protein engineering that has been exploited to generate a wide range of biologics for a host of therapeutic indications. In this review, our basic understanding of the antibody structure is described along with how that knowledge has leveraged the engineering of antibody and antibody-related therapeutics having the appropriate antigen affinity, effector function, and biophysical properties. The platforms examined include the development of antibodies, antibody fragments, bispecific antibody, and antibody fusion products, whose efficacy and manufacturability can be improved via humanization, affinity modulation, and stability enhancement. We also review the design and selection of binding arms, and avidity modulation. Different strategies of preparing bispecific and multispecific molecules for an array of therapeutic applications are included.
Physicochemical and morphological transformations of chitosan nanoparticles across the gastrointestinal tract and cellular toxicity in an in vitro model of the small intestinal epithelium.

Nanoscale chitosan materials exhibit nano-specific properties that make them useful in agri-food and biomedical applications. Chitosan nanoparticles (Chnps) are being explored as nanocarrier platforms to increase oral bioavailability of drugs and nutraceuticals, but little is known of their fate and transformations in the gastrointestinal tract (GIT), or of their potential toxicity. Here, the fate in the GIT of Chnps, soluble starch-coated Chnps (SS-Chnps), and bulk chitosan powder (Chp) and their cytotoxicity, were assessed using a simulated digestion and a cellular model of the small intestinal epithelium. Physico-chemical characterization revealed dissolution of Chp, but not of Chnps or SS-Chnps, during the gastric phase of digestion, stability of the starch coating of SS-Chnps in the oral and gastric phases, and agglomeration of all materials during the small intestinal phase. A slight but significant (10%, p<0.01) increase in cytotoxicity (LDH release) was observed with exposure to digested Chnps, but not Chp or SS-Chnps.
Antibodies to citrullinated peptides in serum and saliva in patients with rheumatoid arthritis and their association to periodontitis.

OBJECTIVES A connection between prevalence of rheumatoid arthritis (RA) and periodontitis has been reported. The hypothesis for this association involves increased citrullination in the oral mucosa in patients with periodontitis. Whether ongoing periodontitis has an effect on IgA antibodies to citrullinated peptides (ACPA) in saliva is unknown. We studied IgA ACPA in saliva and serum and their relation to periodontitis and smoking in a population-based elderly RA cohort. METHODS A population-based cohort of patients with RA ≥61 years of age (n=132) was examined by rheumatologists and a dental hygienist. Analyses of IgG ACPA in serum and IgA ACPA in serum and saliva were performed. The presence of ACPA was compared in patients with RA with and without periodontitis. RESULTS IgA ACPA in serum occurred in 35% of RA patients with periodontitis and in 43% of RA patients without periodontitis (p=0.740). IgG ACPA in serum was found in 66% of RA patients with periodontitis, and in 69% without periodontitis (p=0.740). IgA ACPA in saliva occurred in 20% with periodontitis and 55% without periodontitis (p=0.062). A logistic regression analysis adjusting for age, gender and smoking gave an odds ratio (OR) of 0.456 (95% CI=0.183-1.137, p=0.092) for saliva IgA ACPA positive individuals to have periodontitis. CONCLUSIONS IgA ACPA in serum or saliva was not more common in RA patients with periodontitis. This implies that local production of ACPA by the oral mucosa is not enhanced by periodontal inflammation, in patients with established RA.
Stumbling prediction based on plantar pressure distribution.

BACKGROUND Stumbles are common accidents that can result in falls and serious injuries, particularly in the workplace where back and forth movements are involved and in offices where high heels are imperative. Currently, the characteristics of plantar pressure during a stumble and the differences between stumbling and a normal gait remain unclear. OBJECTIVE This paper is aimed at providing insights into the feasibility of the data mining technique for interventions in stumble-related occupational safety issues. METHODS The characteristics of plantar pressure distribution during stumbling and normal gait were analyzed by using the power spectrum density (PSD) and the Support Vector Machine (SVM). The PSD, a novel pattern recognition feature, was used to mathematically describe the image signal. The SVM, a powerful data mining technique, was used as the classifier to recognize a stumble. Dynamic plantar pressures were measured from twelve healthy participants as they walked. RESULTS The plantar pressures of the stumbling gaits had significantly different patterns compared to the normal ones, from either a qualitative or quantitative perspective. The mean recognition accuracy of the proposed method reached 96.7% . CONCLUSIONS This study helps better understand stumbles and provides a theoretical basis for stumble-related occupational injuries. In addition, the stumble is the precursor of a fall and the research on stumble recognition would be of value to predict and provide warnings of falls and to design anti-fall devices for potential victims.
Management of Acute Severe Colitis in the Era of Biologicals and Small Molecules

Acute severe ulcerative colitis (ASUC) is a medical emergency which occurs in about 20%–30% of patients with ulcerative colitis during their lifetime, and does carry a mortality risk of 1%. The management of inflammatory bowel diseases has evolved with changes in objective patient monitoring, as well as the availability of new treatment options with the development of new biological and small molecules; however, data is limited regarding their use in the context of ASUC. This review aims to discuss the emerging data regarding biologicals and small molecules therapies in the context of ASUC.
Structural evidence for the critical role of the prion protein hydrophobic region in forming an infectious prion

Prion or PrPSc is the proteinaceous infectious agent causing prion diseases in various mammalian species. Despite decades of research, the structural basis for PrPSc formation and prion infectivity remains elusive. To understand the role of the hydrophobic region in forming infectious prion at the molecular level, we report X-ray crystal structures of mouse (Mo) prion protein (PrP) (residues 89–230) in complex with a nanobody (Nb484). Using the recombinant prion propagation system, we show that the binding of Nb484 to the hydrophobic region of MoPrP efficiently inhibits the propagation of proteinase K resistant PrPSc and prion infectivity. In addition, when added to cultured mouse brain slices in high concentrations, Nb484 exhibits no neurotoxicity, which is drastically different from other neurotoxic anti-PrP antibodies, suggesting that the Nb484 can be a potential therapeutic agent against prion disease. In summary, our data provides the first structure-function evidence supporting a crucial role of the hydrophobic region of PrP in forming an infectious prion.