Miracle-dz/UniFAR-FTUs huggingface dataset:
Biological stimuli responsive drug carriers based on keratin for triggerable drug delivery

A novel drug carrier with dual triggerable release properties based on keratin graft poly(ethylene glycol) (keratin-g-PEG) copolymers is reported. Keratin-g-PEG copolymers with different graft densities are synthesized through thiol–ene click chemistry. Taking advantage of the amphiphilicity and the thiol groups of the graft copolymer, nanoparticles stabilized with PEG chains and keratin as the core, bearing glutathione (GSH) cleavable cross-links, are fabricated in aqueous solutions. The keratin-g-PEG copolymer nanoparticles can serve as excellent carriers for doxorubicin hydrochloride salt (DOX·HCl) with a highest loading capacity of 18.1% (w/w). The release of the loaded DOX is sensitive to the concentration of GSH, especially at a GSH concentration of cellular level. Trypsin can further trigger the release of the loaded DOX in the nanoparticles. In vitro cellular uptake experiments indicate that DOX released from the DOX-loaded keratin-g-PEG nanoparticles can be internalized into the cells efficiently, and the loaded DOX shows a faster release into the nuclei of the cells under higher GSH concentrations. The carriers have promising applications as drug carriers for intracellular drug delivery for cancer therapy.
Cytotoxic, Apoptosis-Inducing Activities, and Molecular Docking of a New Sterol from Bamboo Shoot Skin Phyllostachys heterocycla var. pubescens

Phytochemical screening of nonpolar fractions from the methanol extract of the Bamboo shoot skin Phyllostachys heterocycla var. pubescens resulted in the isolation of a new sterol-glucoside-fatty acid derivative (6’-O-octadeca-8″,11″-dienoyl)-sitosterol-3-O-β-d-glucoside (1), together with six known compounds. The chemical structures of the pure isolated compounds were deduced based on different spectral data. The isolated compounds were assessed to determine their cytotoxic activity, and the results were confirmed by determining their apoptotic activity. Compound 1 was more cytotoxic against the MCF-7 cells (IC50 = 25.8 µM) compared to Fluorouracil (5-FU) (26.98 µM), and it significantly stimulated apoptotic breast cancer cell death with 32.6-fold (16.63% compared to 0.51 for the control) at pre-G1 and G2/M-phase cell cycle arrest and blocked the progression of MCF-7 cells. Additionally, RT-PCR results further confirmed the apoptotic activity of compound 1 by the upregulation of proapoptotic genes (P53; Bax; and caspases 3, 8, and 9) and downregulation of the antiapoptotic genes (BCL2). Finally, the identified compounds, especially 1, were found to have high binding affinity towards both tyrosine-specific protein kinase (TPK) and vascular endothelial growth factor receptor (VEGFR-2) through the molecular docking studies that highlight its mode of action.
A Novel Mixed Methods Approach to Synthesize EDA Data with Behavioral Data to Gain Educational Insight

Whilst investigating student performance in design and arithmetic tasks, as well as during exams, electrodermal activity (EDA)-based sensors have been used in attempts to understand cognitive function and cognitive load. Limitations in the employed approaches include lack of capacity to mark events in the data, and to explain other variables relating to performance outcomes. This paper aims to address these limitations, and to support the utility of wearable EDA sensor technology in educational research settings. These aims are achieved through use of a bespoke time mapping software which identifies key events during task performance and by taking a novel approach to synthesizing EDA data from a qualitative behavioral perspective. A convergent mixed method design is presented whereby the associated implementation follows a two-phase approach. The first phase involves the collection of the required EDA and behavioral data. Phase two outlines a mixed method analysis with two approaches of synthesizing the EDA data with behavioral analyses. There is an optional third phase, which would involve the sequential collection of any additional data to support contextualizing or interpreting the EDA and behavioral data. The inclusion of this phase would turn the method into a complex sequential mixed method design. Through application of the convergent or complex sequential mixed method, valuable insight can be gained into the complexities of individual learning experiences and support clearer inferences being made on the factors relating to performance. These inferences can be used to inform task design and contribute to the improvement of the teaching and learning experience.
Multimodal Data Fusion in Learning Analytics: A Systematic Review

Multimodal learning analytics (MMLA), which has become increasingly popular, can help provide an accurate understanding of learning processes. However, it is still unclear how multimodal data is integrated into MMLA. By following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, this paper systematically surveys 346 articles on MMLA published during the past three years. For this purpose, we first present a conceptual model for reviewing these articles from three dimensions: data types, learning indicators, and data fusion. Based on this model, we then answer the following questions: 1. What types of data and learning indicators are used in MMLA, together with their relationships; and 2. What are the classifications of the data fusion methods in MMLA. Finally, we point out the key stages in data fusion and the future research direction in MMLA. Our main findings from this review are (a) The data in MMLA are classified into digital data, physical data, physiological data, psychometric data, and environment data; (b) The learning indicators are behavior, cognition, emotion, collaboration, and engagement; (c) The relationships between multimodal data and learning indicators are one-to-one, one-to-any, and many-to-one. The complex relationships between multimodal data and learning indicators are the key for data fusion; (d) The main data fusion methods in MMLA are many-to-one, many-to-many and multiple validations among multimodal data; and (e) Multimodal data fusion can be characterized by the multimodality of data, multi-dimension of indicators, and diversity of methods.
Convolutional Neural Network-Based Humerus Segmentation and Application to Bone Mineral Density Estimation from Chest X-ray Images of Critical Infants

Measuring bone mineral density (BMD) is important for surveying osteopenia in premature infants. However, the clinical availability of dual-energy X-ray absorptiometry (DEXA) for standard BMD measurement is very limited, and it is not a practical technique for critically premature infants. Developing alternative approaches for DEXA might improve clinical care for bone health. This study aimed to measure the BMD of premature infants via routine chest X-rays in the intensive care unit. A convolutional neural network (CNN) for humeral segmentation and quantification of BMD with calibration phantoms (QRM-DEXA) and soft tissue correction were developed. There were 210 X-rays of premature infants evaluated by this system, with an average Dice similarity coefficient value of 97.81% for humeral segmentation. The estimated humerus BMDs (g/cm3; mean ± standard) were 0.32 ± 0.06, 0.37 ± 0.06, and 0.32 ± 0.09, respectively, for the upper, middle, and bottom parts of the left humerus for the enrolled infants. To our knowledge, this is the first pilot study to apply a CNN model to humerus segmentation and to measure BMD in preterm infants. These preliminary results may accelerate the progress of BMD research in critical medicine and assist with nutritional care in premature infants.
Synthesis and in Silico Modelling of the Potential Dual Mechanistic Activity of Small Cationic Peptides Potentiating the Antibiotic Novobiocin against Susceptible and Multi-Drug Resistant Escherichia coli

Cationic antimicrobial peptides have attracted interest, both as antimicrobial agents and for their ability to increase cell permeability to potentiate other antibiotics. However, toxicity to mammalian cells and complexity have hindered development for clinical use. We present the design and synthesis of very short cationic peptides (3–9 residues) with potential dual bacterial membrane permeation and efflux pump inhibition functionality. Peptides were designed based upon in silico similarity to known active peptides and efflux pump inhibitors. A number of these peptides potentiate the activity of the antibiotic novobiocin against susceptible Escherichia coli and restore antibiotic activity against a multi-drug resistant E. coli strain, despite having minimal or no intrinsic antimicrobial activity. Molecular modelling studies, via docking studies and short molecular dynamics simulations, indicate two potential mechanisms of potentiating activity; increasing antibiotic cell permeation via complexation with novobiocin to enable self-promoted uptake, and binding the E. coli RND efflux pump. These peptides demonstrate potential for restoring the activity of hydrophobic drugs.
The Surface Protein Fructose-1, 6 Bisphosphate Aldolase of Klebsiella pneumoniae Serotype K1: Role of Interaction with Neutrophils

Hypermucoviscosity phenotypic Klebsiella pneumoniae (HV-Kp) serotype K1 is the predominant pathogen of a pyogenic liver abscess, an emerging infectious disease that often complicates septic metastatic syndrome in diabetic patients with poor sugar control. HV-Kpisolates were more resistant to neutrophil phagocytosis than non-HV-Kpisolates because of different pathogen-associated molecular patterns. The protein expression of HV-Kp after interaction with neutrophils is unclear. We studied KP-M1 (HV phenotype; serotype K1), DT-X (an acapsularmutant strain of KP-M1), and E. coli (ATCC 25922) with the model of Kp-infected neutrophils, using a comparative proteomic approach. One the identified protein, namely fructose-1, 6-bisphosphate aldolase (FBA), was found to be distributed in the KP-M1 after infecting neutrophils. Cell fractionation experiments showed that FBA is localized both to the cytoplasm and the outer membrane. Flow cytometry demonstrated that outer membrane-localized FBA was surface-accessible to FBA-specific antibody. The fba gene expression was enhanced in high glucose concentrations, which leads to increasing bacterial resistance to neutrophils phagocytosis and killing. The KP-M1 after FBA inhibitors and FBA-specific antibody treatment showed a significant reduction in bacterial resistance to neutrophils phagocytosis and killing, respectively, compared to KP-M1 without treatment. FBA is a highly conserved surface-exposed protein that is required for optimal interaction of HV-Kp to neutrophils.
Temperature-Dependent Raman Spectroscopic Study of the Double Molybdate KBi(MoO4)2

In situ high-temperature Raman spectra of polycrystalline KBi(MoO4)2 were recorded from room temperature to 1073 K. Thermal stability of the monoclinic KBi(MoO4)2 was examined by temperature-dependent XRD. The monoclinic phase transformed into the scheelite tetragonal structure at 833 K, and then to the monoclinic phase at 773 K. Quantum chemistry ab initio calculation was performed to simulate the Raman spectra of the structure of KBi(MoO4)2 high-temperature melt. The experimental Raman band at 1023 K was deconvoluted into seven Gaussian peaks, and the calculated results were in good agreement with the experimental data. Therefore, the vibrational modes of Raman peaks of molten KBi(MoO4)2 were assigned. It was confirmed that the isolated structure of [Bi(MoO4)2]− monomer, consisting of Mo6+ centers and Bi3+ sub-centers connected by edge-sharing, mainly exists in the melt of KBi(MoO4)2.
Increase in HIV incidence in women exposed to rape

Objective: To determine the incidence of HIV acquisition in women postrape compared with a cohort of women who had not been raped. Design: A prospective cohort study. Methods: The Rape Impact Cohort Evaluation study based in Durban, South Africa, enrolled women aged 16–40 years from postrape care services, and a control group of women from Primary Healthcare services. Women who were HIV negative at baseline (441 in the rape-exposed group and 578 in the control group) were followed for 12–36 months with assessments every 3 months in the first year and every 6 months thereafter. Multivariable Cox regression models adjusted for baseline and time varying covariates were used to investigate the effect of rape exposure on HIV incidence over follow-up. Results: Eighty-six women acquired HIV during 1605.5 total person-years of follow-up, with an incident rate of 6.6 per 100 person-years [95% confidence interval (CI): 4.8–9.1] among the rape exposed group and 4.7 per 100 person-years (95% CI: 3.5–6.2) among control group. After controlling for confounders (age, previous trauma, social support, perceived stress, multiple partners and transactional sex with a casual partner), women exposed to rape had a 60% increased risk of acquiring HIV [adjusted hazard ratio: 1.59 (95% CI: 1.01–2.48)] compared with those not exposed. Survival analysis showed difference in HIV incident occurred after month 9. Conclusion: Rape is a long-term risk factor for HIV acquisition. Rape survivors need both immediate and long-term HIV prevention and care.
A Case of Persistent Diarrhea in a Man with the Molecular Detection of Various Campylobacter species and the First Isolation of candidatus Campylobacter infans

A man with a well-controlled HIV infection, previously diagnosed with lymphogranuloma venereum and treated for Hodgkin’s lymphoma, was suffering from chronic diarrhea. He travelled to Indonesia in the month prior to the start of complaints. Over a 15-month period, sequences related to Campylobacter troglodytis/upsaliensis, C. pinnepediorum/mucosalis/concisus and C. hominis were detected by 16S rRNA qPCR-based assays in various stool samples and in a colon biopsy. Culture revealed the first isolation of “candidatus Campylobacter infans”, a species identified recently by molecular methods only. The patient was treated with azithromycin, ciprofloxacin and tetracycline. To identify potential continuous exposure of the patient to Campylobacter, stool samples of the partner and the cat of the patient were analyzed and C. pinnepediorum/mucosalis/concisus and C. helveticus, respectively, were detected. The diversity in detected species in this immunocompromised patient with a lack of repeatedly consistent findings resulted in the conclusion that not any of the Campylobacter species was the primary cause of the clinical condition. This study shows the challenges in detection and interpretation of diagnostic results regarding Campylobacter.
Cardiometabolic Risk Factor in Obese and Normal Weight Individuals in Community Dwelling Men

The aim of this study was to investigate the cardiometabolic risk factors (CRFs) in community dwelling men based on a combination of body mass index (BMI) and waist circumference (WC). This cross-sectional study was based on 867 males between the ages of 20 and 71 years. Subjects were categorized into 4 groups by BMI and WC (Group 1, BMI < 25 kg/m2 and WC < 90 cm; Group 2, BMI < 25 kg/m2 and WC > 90 cm; Group 3, BMI > 25 kg/m2 and WC < 90 cm; and Group 4 BMI > 25 kg/m2 and WC > 90 cm). The proportion of subjects with a normal weight with high WC was 3.2%. Among normal weight men with the high range of WC, significantly high Odds ratios (ORs) and 95% CI were found for hypertriglyceridemia (3.8, 1.8–8.2) and high blood glucose (3.2, 1.5–6.9). The probability that the general obesity group (Group 3) had one CRF was around twice that of the reference group (Group 1) (1.9 to 2.1 times), but Group 2 had probability more than 4 times higher (4.3 to 4.6 times). In community dwelling adult men, normal weight with high waist circumference was associated with the highest cardiometabolic risk. In conclusion, follow-up screening of those with high WC may be necessary to detect and prevent cardiometabolic diseases, particularly for men with a normal weight.
Prediction of lymph node metastases using pre-treatment PET radiomics of the primary tumour in esophageal adenocarcinoma: an external validation study.

OBJECTIVES To improve clinical lymph node staging (cN-stage) in esophageal adenocarcinoma by developing and externally validating three prediction models; one with clinical variables only, one with positron emission tomography (PET) radiomics only, and a combined clinical and radiomics model. METHODS Consecutive patients with fluorodeoxyglucose (FDG) avid tumours treated with neo-adjuvant therapy between 2010 and 2016 in two international centres (n = 130 and n = 60, respectively) were included. Four clinical variables (age, gender, clinical T-stage and tumour regression grade) and PET radiomics from the primary tumour were used for model development. Diagnostic accuracy, area under curve (AUC), discrimination and calibration were calculated for each model. The prognostic significance was also assessed. RESULTS The incidence of lymph node metastases was 58% in both cohorts. The AUCs of the clinical, radiomics and combined models were 0.79, 0.69 and 0.82 in the developmental cohort, and 0.65, 0.63 and 0.69 in the external validation cohort, with good calibration demonstrated. The AUC of current cN-stage in development and validation cohorts was 0.60 and 0.66, respectively. For overall survival, the combined clinical and radiomics model achieved the best discrimination performance in the external validation cohort (X2 = 6.08, df = 1, p = 0.01). CONCLUSION Accurate diagnosis of lymph node metastases is crucial for prognosis and guiding treatment decisions. Despite finding improved predictive performance in the development cohort, the models using PET radiomics derived from the primary tumour were not fully replicated in an external validation cohort. ADVANCES IN KNOWLEDGE This international study attempted to externally validate a new prediction model for lymph node metastases using PET radiomics. A model combining clinical variables and PET radiomics improved discrimination of lymph node metastases, but these results were not externally replicated.
Preclinical Models for Studying the Impact of Macrophages on Cancer Cachexia

Cancer‐associated cachexia is defined by loss of weight and muscle mass, and by the potential loss of adipose tissue accompanied by insulin resistance and increased resting energy expenditure. Cachexia is most prevalent in pancreatic cancer, the third leading cause of cancer‐related deaths. While various factors interact to induce cachexia, the precise mechanisms underlying this clinical condition are not fully understood. Clinically relevant animal models of cachexia are needed given the lack of standard diagnostic methods or treatments for this condition. Described in this article are in vitro and in vivo models used to study the role of macrophages in the induction of cachexia in pancreatic cancer. Included are procedures for isolating and culturing bone marrow−derived macrophages, harvesting tumor‐ and macrophage‐derived conditioned medium, and studying the effect of conditioned medium on C2C12 myotubes. Also described are procedures involving the use of an orthotopic model of pancreatic cancer, including a method for examining skeletal muscle atrophy in this model. © 2020 Wiley Periodicals LLC.
M1 muscarinic acetylcholine receptor‐mediated inhibition of GABA release from striatal medium spiny neurons onto cholinergic interneurons

Acetylcholine (ACh) modulates neurotransmitter release in the central nervous system. Although GABAergic transmission onto the striatal cholinergic interneurons (ChIN) is modulated by dopamine receptors, cholinergic modulation of the same synapse is still unknown. In the present study, modulatory roles of ACh in the GABAergic transmission from striatal medium spiny neurons (MSNs) onto ChIN were investigated using optogenetics and whole‐cell patch‐clamp technique in juvenile and young‐adult mice brain slices. GABAA receptor‐mediated inhibitory postsynaptic currents (IPSCs) were evoked by focal electrical‐ or blue‐light stimulation. Bath application of carbachol, a muscarinic ACh receptor agonist, suppressed the amplitude of IPSCs in a concentration‐dependent manner in both age groups. A choline esterase inhibitor, physostigmine, also suppressed the amplitude of IPSCs. In the presence of a membrane permeable M1 muscarine receptor antagonist, pirenzepine, carbachol‐induced suppression of IPSCs was antagonized, whereas a M2 muscarine receptor antagonist, a M4 receptor antagonist, or a membrane impermeable M1 receptor antagonist did not antagonize carbachol‐induced suppression of IPSCs. Retrograde cannabinoid cascade via cannabinoid receptor 1 was not involved in carbachol‐induced inhibition. Furthermore, carbachol did not affect amplitude of inward currents induced by puff application of GABA, whereas coefficient of variation of IPSCs was significantly increased by carbachol. These results suggest that activation of presynaptic M1 muscarine receptors located on the GABAergic terminals including intracellular organelle of MSNs inhibits GABA release onto ChIN.
Similar foraging energetics of two sympatric albatrosses despite contrasting life histories and wind-mediated foraging strategies

ABSTRACT Understanding the environmental and behavioral factors that influence how organisms maintain energy balance can inform us about their potential resiliency to rapid environmental changes. Flexibility in maintaining energy balance is particularly important to long-lived, central-place foraging seabirds that are constrained when locating food for offspring in a dynamic ocean environment. To understand the role of environmental interactions, behavioral flexibility and morphological constraints on energy balance, we used doubly labeled water to measure the at-sea daily energy expenditure (DEE) of two sympatrically breeding seabirds, Campbell (Thalassarche impavida) and grey-headed (Thalassarche chrysostoma) albatrosses. We found that species and sexes had similar foraging costs, but DEE varied between years for both species and sexes during early chick rearing in two consecutive seasons. For both species, greater DEE was positively associated with larger proportional mass gain, lower mean wind speeds during water take-offs, greater proportions of strong tailwinds (>12 m s−1), and younger chick age. Greater proportional mass gains were marginally more costly in male albatrosses that already have higher wing loading. DEE was higher during flights with a greater proportion of strong headwinds for grey-headed albatrosses only. Poleward winds are forecasted to intensify over the next century, which may increase DEE for grey-headed albatrosses that heavily use this region during early chick rearing. Female Campbell albatrosses may be negatively affected by forecasted slackening winds at lower latitudes due to an expected greater reliance on less energy efficient sit-and-wait foraging strategies. Behavioral plasticity associated with environmental variation may influence future population responses to climate change of both species. Highlighted Article: Related albatrosses have similar guard-stage foraging costs despite life history and foraging strategy differences; however, lighter forecasted wind in endemic albatross ranges may increase take-off costs and increase sit-and-wait strategies.