Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling Pharmacokinetic Profiles for Assessment of Anti-Cancer Drug on a Microfluidic System

The pharmacokinetic (PK) properties of drug, which include drug absorption and excretion, play an important role in determining the in vivo pharmaceutical activity. However, current in vitro systems that model PK profiles are often limited by the in vivo-like concentration profile of a drug. Herein, we present a perfused and multi-layered microfluidic chip system to model the PK profile of anti-cancer drug 5-FU in vitro. The chip device contains two layers of culture channels sandwiched by a porous membrane, which allows for drug exposure and diffusion between the two channels. The integration of upper intestine cells (Caco-2) and bottom targeted cells within the device enables the generation of loading and clearance portions of a PK curve under peristaltic flow. Fluorescein as a test molecule was initially used to generate a concentration-time curve, investigating the effects of parameters of flow rate, administration time, and initial concentration on dynamic drug concentration profiles. Furthermore, anti-cancer drug 5-FU was performed to assess its pharmaceutical activity on target cells (human lung adenocarcinoma cells or human pulmonary alveolar epithelial cells) using different drug administration regimens. A dynamic, in vivo-like 5-FU exposure refers to PK profile regimen, led to generate a lower drug concentration (dynamically fluctuate from 0 to 1 μg/mL affected by absorption) compared to the constant exposure. Moreover, the PK profile regimen alleviates the drug-induced cytotoxicity on target cells. These results demonstrate the feasibility of determining the PK profiles using this microfluidic system with in vivo-like drug administration regimens. This established system may provide a powerful platform for the prediction of drug safety and effectiveness in the pharmaceutical research.
EFFECT OF ULTIMATE pH UPON THE WATER‐HOLDING CAPACITY AND TENDERNESS OF MUTTON

SUMMARY— Ultimate pH values in the musculature of sheep ranging from 5.6–7.0 have been obtained by using pre-slaughter injections of epinephrine. A high speed centrifugal method was used to measure the water-holding capacity of raw M. semitendinosus (ST), semimembranosus (SM) and biceps femoris (BF). Results showed a high correlation with ultimate pH. Cooking losses end the amounts of centrifugally expressed juice were determined for the SM and BF cooked for 1 hr at either 65°C or 90°C. Cooking losses at 65°C decreased linearly with increasing pH while the losses at 90°C showed little change up to o raw meat pH of ca. 5.9, then decreased linearly with increasing pH. The amount of juice centrifugally expressed from the cooked meat, which has a high positive correlations with organoleptic juiciness, increased linearly with pH. Tenderness of the cooked SM and BF muscles was measured using o Warner-Bratzler shearing device and an Instron Universal Testing Machine: both gave high objective-subjective correlations. Instron measurements have high negative linear correlations with ultimate pH for both the 65°C and 90°C cooked samples. Hardness of these muscles, cooked at 65°C or 90°C. decreased approximately three-fold as ultimate pH increased from 5.6–6.9. Results obtained using the Warner-Bratzler device showed linear regressions with a significant quadratic component for one muscle at both 65°C and 90°C.
The Use of Varying Levels of Pepsin for Pepsin Digestion Studies with Animal Proteins

Abstract Nine meat and bone meals were digested with a . 002%, . 02%, and . 2% pepsin-HCl solution and six feather meals were digested with . 002%, . 2%, and 2% pepsin-HCl for a 16-hr period. An acid blank value for the meals was determined from digestible nitrogen with . 075 N HC1. The meat and bone meals ranged from 90.03% to 94.09% pepsin digestible nitrogen (PDN) under the standard AOAC (1975) procedure with . 2% pepsin and not subtracting the HC1 digestible nitrogen from the total digestible nitrogen. The same meat and bone meals digested with . 002% pepsin and correcting the value with an acid blank ranged from 60 to 81.95 PDN. Feather meals digested with . 2% pepsin ranged from 66.15 to 79.92 PDN (corrected with acid blank) compared to 12.5 to 34.93 PDN for feather meals digested with . 002% pepsin. The decreased quantity of pepsin-HCl solution increases the sensitivity of the test and increases digestibility difference between the meat and bone and feather meals.
Integrated multi‐omics data analyses for exploring the co‐occurring and mutually exclusive gene alteration events in colorectal cancer

Co‐occurring and mutually exclusive gene alteration events are helpful for understanding carcinogenesis but systematic screening for such events is quite limited. We conducted pairwise screening tests to identify “hit pairs” in colorectal cancer (CRC) by utilizing the cross‐omics data from The Cancer Genome Atlas (TCGA). Numerous hit pairs involving somatic mutations, copy number variations, and DNA methylation were found to occur nonrandomly in CRC, such as KRAS and HOXB6, SMAD4 and PMEPA1. Based on these hit pairs, we identified 32 synthetic lethal pairs and 7,527 co‐occurring pairs relating to drug response. Our further biological experiments showed that the co‐occurrence of mutant FCGBP and NUDT12 silencing (or mutant TMC3 and RPS6KA6 silencing) with small interfering RNA reduced cell viability. Moreover, novel hit pairs could influence prognosis. The patients who carried concurrent mutations of IRF5 and NEFH, SYNE1 and TTN, or MUC16 and NEFH had worse survival outcomes. Particularly, the presence of mutant SYNE1 and TTN pair not only affects prognosis, but also is related to CRC patients' response to drug treatment. Our “hit pair” genes may provide insights into colorectal carcinogenesis and help open new avenues for CRC therapy.
Risk Factors for Dislodgment of Vaginal Pessaries in Women With Pelvic Organ Prolapse: A Cohort Study

Objective The aim of the study was to evaluate the associated factors associated with pessary dislodgment in women with advanced pelvic organ prolapse (POP). Methods A cohort study with women (N = 98) with advanced POP who chose conservative treatment with ring pessary between December 2016 and 2018 identified by screening. Demographic data, history of POP, urinary, and/or bowel symptoms were collected. A medical visit was scheduled 3 and 6 months after pessary insertion to evaluate symptoms (vaginal discharge, bleeding, pain, discomfort, new-onset urinary, or fecal problems) and any pessary dislodgment. Two groups were created (women who were able to retain the pessary versus who were not able), and univariate and multivariate analysis were performed to look for risk factors for pessary dislodgment. Women who requested to have their pessaries removed during the 6-month follow-up were excluded. Results Ninety-three women included in the study, 78 successfully continued to use the pessary at 6 months, and 15 had pessary dislodgment (16.1%). Demographic characteristics were similar between the treatment group and the control group. After multivariate analysis, women who had their pessaries dislodged presented higher rates of previous surgery (odds ratio = 8.11; 95% confidence interval = 2.09–31.58; P = 0.003) with advanced Pelvic Organ Prolapse Quantification system staging (odds ratio, 13.41; confidence interval, 1.97–91.36; P = 0.008). Conclusions The presence of advanced apical POP and previous POP surgery are risk factors for ring pessary dislodgment. This information should guide physicians for counseling patients before pessary insertion.
Predicting chick body mass by artificial intelligence-based models

The objective of this work was to develop, validate, and compare 190 artificial intelligence-based models for predicting the body mass of chicks from 2 to 21 days of age subjected to different duration and intensities of thermal challenge. The experiment was conducted inside four climate-controlled wind tunnels using 210 chicks. A database containing 840 datasets (from 2 to 21-day-old chicks) - with the variables dry-bulb air temperature, duration of thermal stress (days), chick age (days), and the daily body mass of chicks - was used for network training, validation, and tests of models based on artificial neural networks (ANNs) and neuro-fuzzy networks (NFNs). The ANNs were most accurate in predicting the body mass of chicks from 2 to 21 days of age after they were subjected to the input variables, and they showed an R² of 0.9993 and a standard error of 4.62 g. The ANNs enable the simulation of different scenarios, which can assist in managerial decision-making, and they can be embedded in the heating control systems.
Tobacco Dependence Treatment in Oncology: Initial Patient Clinical Characteristics and Outcomes from Roswell Park Comprehensive Cancer Center

Despite the importance of smoking cessation to cancer care treatment, historically, few cancer centers have provided treatment for tobacco dependence. To address this gap, the National Cancer Institute (NCI) launched the Cancer Center Cessation Initiative (C3i). As part of this effort, this study examined implementation outcomes in a cohort of cancer survivors (CSs) who smoked cigarettes in the first year of an ongoing process to develop and implement a robust Tobacco Treatment Service at Roswell Park Comprehensive Cancer Center. We provide a comprehensive description of the new tobacco use assessment and referral process, and of the characteristics of cancer survivors who agreed to treatment including traditional tobacco-related psychosocial and cancer treatment-related characteristics and novel characteristics such as delay discounting rates. We also examine characteristic differences among those who agreed to treatment between those who attended and those who did not attend treatment. As the new tobacco assessment was implemented, the number of referrals increased dramatically. The mean number of treatment sessions attended was 4.45 (SD = 2.98) and the six-month point prevalence intention to treat abstinence rate among those who attended was 22.7%. However, only 6.4% agreed to treatment and 4% attended at least one treatment session. A large proportion of cancer survivors who agreed to treatment were women, of older age, of lower socioeconomic status (SES), and who had high levels of depressive symptomology. The findings demonstrate that the implementation of system changes can significantly improve the identification of cancer survivors who use tobacco and are referred to tobacco use treatment. Among those who attend, treatment is effective. However, the findings also suggest that a systematic assessment of barriers to engagement is needed and that cancer survivors may benefit from additional treatment tailoring. We present plans to address these implementation challenges. Systematic electronic medical record (EMR)-sourced referral to tobacco treatment is a powerful tool for reaching cancer survivors who smoke, but more research is needed to determine how to enhance engagement and tailor treatment processes.
Factors influencing adult female oviposition in the citrus leafminer Phyllocnistis citrella

1 The citrus leafminer (CLM) Phyllocnistis citrella Stainton (Lepidoptera: Gracillariidae) is a serious pest in most citrus‐growing regions of the world. The influence of leaf length, citrus species or variety, leaf colour tone and temperature on CLM oviposition was studied from field observations and laboratory experiments. The spatial distribution of eggs on leaves was also examined. Field data were obtained from 1100 samples collected in eastern Spain for 7 years.
The Architectural Dynamics of the Bacterial Flagellar Motor Switch

The rotary bacterial flagellar motor is remarkable in biochemistry for its highly synchronized operation and amplification during switching of rotation sense. The motor is part of the flagellar basal body, a complex multi-protein assembly. Sensory and energy transduction depends on a core of six proteins that are adapted in different species to adjust torque and produce diverse switches. Motor response to chemotactic and environmental stimuli is driven by interactions of the core with small signal proteins. The initial protein interactions are propagated across a multi-subunit cytoplasmic ring to switch torque. Torque reversal triggers structural transitions in the flagellar filament to change motile behavior. Subtle variations in the core components invert or block switch operation. The mechanics of the flagellar switch have been studied with multiple approaches, from protein dynamics to single molecule and cell biophysics. The architecture, driven by recent advances in electron cryo-microscopy, is available for several species. Computational methods have correlated structure with genetic and biochemical databases. The design principles underlying the basis of switch ultra-sensitivity and its dependence on motor torque remain elusive, but tantalizing clues have emerged. This review aims to consolidate recent knowledge into a unified platform that can inspire new research strategies.
Heartwood in relation to age and growth rate in Pinus sylvestris L. in Scandinavia

Summary Knowledge about the transformation of sapwood into heartwood contributes to the understanding of the nature of pine trees and should be considered prior to the conversion of sawlogs to produce timber of prescribed properties and optimal revenue. In this study, heartwood formation was ascribed to the joint effect of ageing and growth rate. Observations of heart- and sapwood in 1656 trees and sawlogs of Scots pine (Pinus sylvestris L.), sampled throughout Scandinavia, were analysed using mixed models. The most important finding was expressed in the pine heartwood age rule: heartwood age equals the square root of cambial age less three, to the second power. This global formula was valid irrespective of environmental factors and location within the tree, and described 93 per cent of the variance in the sample. Transition rate increases from 0.6 rings a ‐1 at 50 years to 0.8 rings a‐1 at 200 years. The spatial amount of heartwood might be influenced by the silviculture through the annual ring width pattern. For samples missing sapwood, e.g. archaeological wood, the results might be combined with dendrochronology in specimen dating. When the diameter and the heartwood diameter of sawlogs were known, the mean annual ring width could be estimated with a standard deviation of 0.5 mm a ‐1 . The simplicity, consistency and high correlation of the pine heartwood age rule confirms the importance of age as the main factor in heartwood formation.
Protein-tyrosine Phosphatase α, RPTPα, Is a Helicobacter pylori VacA Receptor*

Helicobacter pylori vacuolating cytotoxin, VacA, induces vacuolation, mitochondrial damage, cytochrome c release, and apoptosis of gastric epithelial cells. To detect gastric proteins that serve as VacA receptors, we used VacA co-immunoprecipitation techniques following biotinylation of the cell surface and identified p250, a receptor-like protein-tyrosine phosphatase β (RPTPβ) as a VacA-binding protein (Yahiro, K., Niidome, T., Kimura, M., Hatakeyama, T., Aoyagi, H., Kurazono, H., Imagawa, K., Wada, A., Moss, J., and Hirayama, T. (1999) J. Biol. Chem. 274, 36693–36699). VacA causes vacuolation of G401 cells, a human kidney tumor cell line, although they do not express RPTPβ. By co-immunoprecipitation with VacA, we identified p140 as a potential receptor in those cells. p140 purified by chromatography on a peanut agglutinin affinity matrix contained internal amino acid sequences of RGEENTDYVNASFIDGYRQK and AEGILDVFQTVK, which are identical to those in RPTPα. The peptide mass fingerprinting of p140 by time of flight-MS analysis also supported this identification. Treatment of G401 cells with RPTPα-morpholino antisense oligonucleotide before exposure to toxin inhibited vacuolation. These data suggest that RPTPα acts as a receptor for VacA in G401 cells. Thus, two receptor tyrosine phosphatases, RPTPα and RPTPβ, serve as VacA receptors.
Comparison of health-related habits and metabolic syndrome risk factors according to obesity type in Korean postmenopausal women.

OBJECTIVE This study aimed to investigate the differences in health-related habits, metabolic syndrome risk factors, and related diseases prevalence according to obesity type in postmenopausal women. METHODS This cross-sectional study used a data set of 1,443 postmenopausal women who were 40 years or older (range = 45-80, mean = 64.10) from the 2016 Korean National Health and Nutrition Examination Survey VII-1. The participants were classified into normal group (body mass index [BMI] <25 kg/m, waist circumference (WC) <85 cm), BMI obesity group (BMI ≥25 kg/m, WC <85 cm), abdominal obesity group (BMI <25 kg/m, WC ≥85 cm), and BMI and abdominal obesity group (BMI ≥25 kg/m, WC ≥85 cm). To compare health-related habits and metabolic syndrome risk factors according to obesity type, a chi-square test and t test were performed. The relationship between obesity and metabolic syndrome was assessed using a logistic regression analysis of adjusted demographic and women's health covariates. RESULTS The abdominal obesity group had a significantly longer sedentary time per day (524.31 min), a higher activity restriction rate (25.0%), and a lower nutrition labeling recognition rate (3.6%) than the other groups (P < 0.001). The occurrence of metabolic syndrome was the highest in the BMI and abdominal obesity group (66.1%), followed by the abdominal obesity group (59.3%). Compared with the normal group, the prevalence of metabolic syndrome was significantly higher in the BMI obesity group (adjusted odds ratio [OR] = 2.23, 95% CI = 1.15-4.31), abdominal obesity group (adjusted OR = 7.33, 95% CI = 4.38-12.25), and the BMI and abdominal obesity group (adjusted OR = 12.44, 95% CI = 8.78-17.62). CONCLUSIONS In postmenopausal women, the abdominal obesity group was associated with a high prevalence of metabolic syndrome and related diseases. Therefore, to reduce abdominal obesity in postmenopausal women, it is necessary to correct long sedentary time, high activity restriction rate, and low nutritional labeling recognition rate identified as health-related habits of the abdominal obesity group.
Homing behaviour facilitates subtle genetic differentiation among river populations of Alosa sapidissima : microsatellites and mtDNA

Significant but subtle differentiation was detected for both microsatellite DNA and mitochondrial DNA among four populations of American shad Alosa sapidissima. The data indicate that straying among rivers is sufficient to permit only marginal population differentiation in this species, but suggest that individual river populations should be managed as distinct stocks. Comparison of the Hudson and Columbia populations, the latter derived from the former over 100 years ago, revealed only a slight reduction in microsatellite DNA variation for the founded population but halving of mitochondrial DNA, consistent with the haploid maternal inheritance of the latter marker. The depleted and endangered James River (Virginia) population and two other Atlantic coast populations exhibited similar levels of microsatellite DNA variation, but mtDNA diversity in the James River was marginally lower than in other Atlantic populations, again consistent with the low effective population size of mtDNA.
Caracterização física e físico-química de diferentes formulações de doce de goiaba (Psidium guajava L.) da cultivar Pedro Sato

The shelf life of preserves can be extended by the use of preservatives and other combined preservation methods. The objective of the present study was to verify the effects of potassium sorbate and citric acid concentrations and the pulp:sugar ratio on the physical and physicochemical characteristics of guava preserve formulations. A complete 23 factorial design was used with 3 central points. Linear models were fitted to describe the responses as a function of the significant factors. The results showed that the potassium sorbate concentration had little effect on the responses analysed, except for the pH. The pulp/sugar ratio and the citric acid concentration are the most relevant variables to this process. The citric acid concentration and the pulp:sugar ratio must be increased to obtain firm preserves and greater yield.
Protective Effect of Angiotensin 1–7 on Sarcopenia Induced by Chronic Liver Disease in Mice

Sarcopenia associated with chronic liver disease (CLD) is one of the more common extrahepatic features in patients with these pathologies. Among the cellular alterations observed in the muscle tissue under CLD is the decline in the muscle strength and function, as well as the increased fatigue. Morphological changes, such as a decrease in the fiber diameter and transition in the fiber type, are also reported. At the molecular level, sarcopenia for CLD is characterized by: (i) a decrease in the sarcomeric protein, such as myosin heavy chain (MHC); (ii) an increase in the ubiquitin–proteasome system markers, such as atrogin-1/MAFbx1 and MuRF-1/TRIM63; (iii) an increase in autophagy markers, such as LC3II/LC3I ratio. Among the regulators of muscle mass is the renin-angiotensin system (RAS). The non-classical axis of RAS includes the Angiotensin 1–7 [Ang-(1-7)] peptide and its receptor Mas, which in skeletal muscle has anti-atrophic effect in models of muscle wasting induced by immobilization, lipopolysaccharide, myostatin or angiotensin II. In this paper, we evaluated the effect of Ang-(1-7) on the sarcopenia by CLD in a murine model induced by the 5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) hepatotoxin administered through diet. Our results show that Ang-(1-7) administration prevented the decline of the function and strength of muscle and increased the fatigue detected in the DDC-fed mice. Besides, we observed that the decreased fiber diameter and MHC levels, as well as the transition of fiber types, were all abolished by Ang-(1-7) in mice fed with DDC. Finally, Ang-(1-7) can decrease the atrogin-1 and MuRF-1 expression as well as the autophagy marker in mice treated with DDC. Together, our data support the protective role of Ang-(1-7) on the sarcopenia by CLD in mice.
Tumor Necrosis Factor-α-induced IKK Phosphorylation of NF-κB p65 on Serine 536 Is Mediated through the TRAF2, TRAF5, and TAK1 Signaling Pathway*

The activation of NF-κB has been shown to be regulated by multiple phosphorylations of IκBs and the NF-κB p65 subunit. Here, we characterized the intracellular signaling pathway leading to phosphorylation of p65 on Ser-536 using a novel anti-phospho-p65 (Ser-536) antibody. The Ser-536 of endogenous p65 was rapidly phosphorylated in response to a wide variety of NF-κB stimulants including TNF-α in the cytoplasm and rapidly dephosphorylated in the nucleus. The TNF-α-but not IL-1β-induced Ser-536 phosphorylation was severely impaired in murine embryonic fibroblasts derived from traf2-/-traf5-/- mice. Bay 11-7082, an inhibitor of IκB phosphorylation, inhibited the TNF-α-induced phosphorylation in vivo. In addition, overexpression of TGF-β-activated kinase 1 (TAK1), IKKα and IKKβ stimulated the phosphorylation, and their dominant negative mutants blocked the TNF-α-induced phosphorylation. Moreover, small interfering RNAs (siRNAs) against TAK1, IKKα and IKKβ blocked the phosphorylation of endogenous p65. On the other hand, calyculin-A, a protein phosphatase inhibitor, blocked the dephosphorylation in the nucleus in vivo. These results indicate that similar signaling pathways were utilized for the phosphorylations of IκBα and p65, which further support the idea that both IκB and NF-κB are substrates for the IKK complex in the activation of NF-κB.