Miracle-dz/UniFAR-FTUs huggingface dataset:
Accuracy of Nodal Positivity in Inadequate Lymphadenectomy in Pancreaticoduodenectomy for Pancreatic Ductal Adenocarcinoma: A Population Study Using the US SEER Database

Objectives: The optimal number of the examined lymph nodes (ELNs) in pancreaticoduodenectomy for pancreatic ductal adenocarcinoma has been widely studied. However, the accuracy of nodal positivity for the patients with inadequate lymphadenectomy is still unclear. The purpose of our study was to determine the accuracy of the number of positive nodes reported for patients with 1–3 positive nodes and the probability that 4 or more nodes could be positive along with tumor size and number of nodes examined. Methods: We obtained data on patients who underwent pancreaticoduodenectomy for resectable pancreatic ductal adenocarcinoma diagnosed during 2004–2013 from the US Surveillance, Epidemiology, and End Results registry. An mathematical model based on Hypergeometric Distribution and Bayes' Theorem was used to estimate the accuracy. Results: Among the 9,945 patients, 55.6% underwent inadequate lymphadenectomy. Of them, 1,842, 6,049, and 2,054 had T1, T2, and T3 stage disease, respectively. The accuracy of the number of observed positive nodes increased as the number of ELNs increased and the tumor size decreased. To rule out the possibility of N2 stage (4 and more positive nodes), there should be at least 13 ELNs for the patients with 1 observed positive lymph node and 14 for the patients with 2. Conclusion: Inadequate lymphadenectomy could result in underestimation of the N stage, and this would have adverse impact on recurrence, efficacy of postoperative treatment, and even overall survival. This model combined with the observed positive lymph nodes, the number of ELNs, and tumor size could provide a more accurate determination of nodal positivity of these patients.
Microalgal Protein Extraction From Chlorella vulgaris FSP-E Using Triphasic Partitioning Technique With Sonication

Green microalgae containing various bioactive compounds and macronutrients such as lipids, carbohydrates, and proteins, have attracted much attention from the global community. Microalgae has the potential to be applied in food industries due to its high protein content, rapid growth rate, and ability to survive in harsh conditions. This study presents a simple yet efficient technique of sonication-assisted triphasic partitioning process, also known as ultrasonic-assisted three phase partitioning (UATPP), for the extraction of proteins from Chlorella vulgaris FSP-E. Comparison studies between three phase partitioning (TPP) and UATPP was conducted to investigate the feasibility of the enhanced technique on proteins extraction. Types of salt, ratio of slurry to t-butanol, salt saturation, sonication frequency, power, irradiation time, and duty cycle as well as biomass loading were studied. UATPP was found to be an improved technique compared to TPP. An optimum separation efficiency and yield of 74.59 ± 0.45 and 56.57 ± 3.70% was obtained, respectively, with the optimized conditions: salt saturation (50%), slurry to t-butanol ratio (1:2), sonication power (100%), irradiation time (10 min), frequency (35 kHz), duty cycle (80%) and biomass loading (0.75 wt%). A scaled-up study was performed to validate the reliability of UATPP for protein extraction. The outcome of the study revealed that UATPP is an attractive approach for downstream processing of microalgae.
Role of PKC and ERK Signaling in Epidermal Blistering and Desmosome Regulation in Pemphigus

Desmosomes reinforce cohesion of epithelial cells at the interface between adjacent cells. They include the cadherin-type adhesion molecules desmoglein 1 (Dsg1) and Dsg3. Pemphigus vulgaris (PV) is an autoimmune disease in which circulating autoantibodies (PV-IgG) targeting Dsg1 and 3 cause characteristic epidermal blister formation. It has been shown that PV-IgG binding induced activation of kinases such as ERK and PKC, and inhibition of these signaling pathways prevented loss of cell cohesion in cell cultures. However, the role of Erk and PKC in blister formation and regulation of desmosome ultrastructure in human skin are unknown. Accordingly, we assessed the role of PKC and ERK signaling pathways in blister formation and regulation of desmosome ultrastructure in human epidermis. Here we performed electron microscopy analyses using human skin explants injected with PV-IgG together with inhibitors for PKC or ERK signaling. Inhibition of PKC was not effective to prevent suprabasal blister formation or ultrastructural alterations of desmosomes. In contrast, inhibition of ERK signaling significantly ameliorated blister formation and decrease in the number of desmosomes whereas shortening and splitting of desmosomes and keratin filament insertion were not different from samples treated with PV-IgG alone. However, apical desmosomes between basal and suprabasal cells remained unaltered when ERK signaling was inhibited. Therefore, our results show that inhibition of ERK but not PKC signaling appears to be effective to ameliorate blistering and alterations of desmosome ultrastructure triggered by PV-IgG in human skin.
Pericytes: Problems and Promises for CNS Repair

Microvascular complications are often associated with slow and progressive damage of various organs. Pericytes are multi-functional mural cells of the microcirculation that control blood flow, vascular permeability and homeostasis. Whereas accumulating evidence suggests that these cells are also implicated in a variety of diseases, pericytes represent promising targets that can be manipulated for therapeutic gain. Here, we review the role of pericytes in angiogenesis, blood-brain barrier (BBB) function, neuroinflammation, tissue fibrosis, axon regeneration failure, and neurodegeneration. In addition, we outline strategies altering pericyte behavior to point out problems and promises for axon regeneration and central nervous system (CNS) repair following injury or disease.
Biocontrol of the Major Plant Pathogen Ralstonia solanacearum in Irrigation Water and Host Plants by Novel Waterborne Lytic Bacteriophages

Three new lytic bacteriophages were found to effectively control the pathogen Ralstonia solanacearum, a quarantine bacterium in many countries, and causative agent of bacterial wilt, one of the most important vascular plant diseases. Bacterial wilt management has been carried out with fluctuating effects, suggesting the need to find alternative treatments. In this work, three lytic phages were isolated from environmental water from geographically distant regions in Spain. They proved to specifically infect a collection of R. solanacearum strains, and some of the closely related pathogenic species Ralstonia pseudosolanacearum, without affecting non-target environmental bacteria, and were able to lyze the pathogen populations within a wide range of conditions comprising environmental values of water temperatures, pH, salinity, and lack of aeration found in storage tanks. The three bacteriophages displayed high efficiency in controlling R. solanacearum, with reductions of the bacterial populations of several orders of magnitude in just a few hours, and proved to be able to survive in freshwater for months at environmental temperatures keeping activity on R. solanacearum, pointing out their suitability for field application through irrigation. Concerning their biocontrol potential, they were effective in reducing high populations of the pathogen in environmental water, and bacterial wilt incidence in planta by watering with either one phage or their combinations in assays with more than 300 plants. This is the first report on effective R. solanacearum biocontrol by applying single or combined bacteriophages through irrigation water in conditions mimicking those of the natural settings. The three phages belong to the Podoviridae family and are members of the T7likevirus genus. They are the first isolated phages from river water with activity against R. solanacearum, showing the longest persistence in natural water reported until now for phages with biocontrol potential, and consistently being able to control the disease in the host plant under environmental conditions. Consequently, the use of these bacteriophages for the prevention and/or biocontrol of the bacterial wilt disease caused by R. solanacearum has been patented. Evidence provided reveals the suitability of these waterborne phages to be effectively considered as a valuable strategy within the frame of sustainable integrated management programs.
The Contribution of Functional Traits to the Breeding Progress of Central-European Winter Wheat Under Differing Crop Management Intensities

Wheat yields in many of the main producing European countries stagnate since about 20 years. Hence, it is of high interest, to analyze breeding progress in terms of yield and how associated traits changed. Therefore, a set of 42 cultivars (released between 1966 and 2012) was selected and yield as well as functional traits defined by the Monteith and Moss equation were evaluated under three levels of management intensity. The Monteith Moss equation thereby calculates grain yield as the product of incident photosynthetically active radiation, fraction of intercepted radiation, radiation use efficiency, and harvest index. The field trial was performed in a high yielding environment in Northern Germany in two seasons (2016–2017 and 2017–2018) with very contrasting rainfall rates. The three differing managements were: intensive (high N + pesticides), semi-intensive (high N − pesticides), and extensive (low N − pesticides). The results indicate that the stagnation of wheat yields in Central-Europe is not caused by a diminishing effect of breeding on yield potential. This equally applies to suboptimal growing conditions like extensified crop management and restricted water supply. Nearly all functional sub-traits showed a parallel progress but coefficients of determination of relationships between traits and year of variety release are decreasing along the hierarchy of yield formation. One exception is radiation interception which did not show a stable linear increase during breeding history. In recent years, biomass is getting more important in comparison to harvest index. Values of harvest index are slowly approaching theoretical maxima and correlations with grain yield are decreasing.
Impact of a High Protein Intake on the Plasma Metabolome in Elderly Males: 10 Week Randomized Dietary Intervention

High protein diets may improve the maintenance of skeletal muscle mass in the elderly, although it remains less clear what broader impact such diets have on whole body metabolic regulation in the elderly. Non-targeted polar metabolomics analysis using HILIC HPLC-MS was used to profile the circulating plasma metabolome of elderly men (n = 31; 74.7 ± 4.0 years) who were randomized to consume for 10 weeks a diet designed to achieve either protein (RDA; 0.8·g−1·kg−1) or that doubled this recommend intake (2RDA; 1.6.g.kg−1). A limited number of plasma metabolites (n = 24) were significantly differentially regulated by the diet. These included markers of protein anabolism, which increased by the 2RDA diet, including; urea, creatine, and glutarylcarnitine. Whilst in response to the RDA diet; glutamine, glutamic acid, and proline were increased, relative to the 2RDA diet (p < 0.05). Metaboanalyst identified six major metabolic pathways to be influenced by the quantity of protein intake, most notably the arginine and proline pathways. Doubling of the recommended protein intake in older males over 10 weeks exerted only a limited impact on circulating metabolites, as determined by LC-MS. This metabolomic response was almost entirely due to increased circulating abundances of metabolites potentially indicative of altered protein anabolism, without evidence of impact on pathways for metabolic health. Trial Registration: This trial was registered on 3rd March 2016 at the Australia New Zealand Clinical Trial Registry (www.anzctr.org.au) at ACTRN 12616000310460.
IDLDA: An Improved Diffusion Model for Predicting LncRNA–Disease Associations

It has been demonstrated that long non-coding RNAs (lncRNAs) play important roles in a variety of biological processes associated with human diseases. However, the identification of lncRNA–disease associations by experimental methods is time-consuming and labor-intensive. Computational methods provide an effective strategy to predict more potential lncRNA–disease associations to some degree. Based on the hypothesis that phenotypically similar diseases are often associated with functionally similar lncRNAs and vice versa, we developed an improved diffusion model to predict potential lncRNA–disease associations (IDLDA). As a result, our model performed well in the global and local cross-validations, which indicated that IDLDA had a great performance in predicting novel associations. Case studies of colon cancer, breast cancer, and gastric cancer were also implemented, all lncRNAs which ranked top 10 in both databases were verified by databases and related literature. The results showed that IDLDA might play a key role in biomedical research.
The Development and Validation of a Dehumanization Measure Within Romantic Relationships

Despite the emergence of research into interpersonal dehumanization, there has been little by way of empirical investigation of the phenomenon within the context of romantic relationships. To address this, we introduce and validate the Dehumanization in Romantic Relationships Scale (DIRRS), a self-report measure of dehumanization perpetration and targeting within close relationships. In Study 1 (N = 1251, M age = 25.35, SD = 6.03), confirmatory factor analysis revealed that the dimensionality of interpersonal dehumanization may be more nuanced than first thought. Specifically, a four factor first-order structure [comprised of factors that relate to denials of human uniqueness (i.e., immature and unrefined) and human nature (i.e., exploitable and emotionless) was found to be the best fit to the data]. These results were replicated on a different sample in Study 2 (N = 847, M age = 23.40, SD = 6.43)—in addition to the assessment of criterion-related validity. Study 3 (N = 328, M age = 23.40, SD = 6.43) cross-validated the criterion-related validity reported in Study 2, and in addition, highlights that dehumanization is also associated with emotional and physical abuse. This research extends theory on interpersonal dehumanization and provides an empirically validated measure to reliably assess the occurrence of dehumanization within romantic relationships.
Dexamethasone Causes Hypertension in Rats Even Under Chemical Blockade of Peripheral Sympathetic Nerves

Synthetic glucocorticoids (GCs) are widely used to treat inflammatory conditions. However, chronic use of GCs can lead to hypertension. The cause of this undesired side effect remains unclear. Previously, we developed an in vivo rat model to study the mechanisms underlying hypertension induced by the chronic administration of the potent synthetic GC, dexamethasone (DEX) and found that the catecholamine biosynthetic pathway plays an important role. In the current study, we used this model to investigate the role of the adrenal medulla, renal nerves, and other peripheral sympathetic nerves in DEX-induced hypertension. After 5 days of baseline telemetric recording of mean arterial pressure (MAP) and heart rate (HR), rats were subjected to one of the following treatments: renal denervation (RDNX), adrenal medullectomy (ADMX), 6-hydroxydopamine (6-OHDA, 20 mg/kg, i.p.) to induce chemical sympathectomy, or a combination of ADMX and 6-OHDA. On day 11, the animals received vehicle (VEH) or DEX in drinking water for 7 days, with the latter causing an increase in MAP in control animals. ADMX and RDNX by themselves exacerbated the pressor effect of DEX. In the chemical sympathectomy group, DEX still caused a rise in MAP but the response was lower (ΔMAP of 6-OHDA/DEX < VEH/DEX, p = 0.039). However, when ΔMAP was normalized to day 10, 6-OHDA + DEX did not show any difference from VEH + DEX, certainly not an increase as observed in DEX + ADMX or RDNX groups. This indicates that sympathetic nerves do not modulate the pressor effect of DEX. TH mRNA levels increased in the adrenal medulla in both VEH/DEX (p = 0.009) and 6-OHDA/DEX (p = 0.031) groups. In the 6-OHDA group, DEX also increased plasma levels of norepinephrine (NE) (p = 0.016). Our results suggest that the activation of catecholamine synthetic pathway could be involved in the pressor response to DEX in animals even under chemical sympathectomy with 6-OHDA.
Biological Sex: A Potential Moderator of Physical Activity Efficacy on Brain Health

The number of older people worldwide living with cognitive impairment and neurodegenerative diseases is growing at an unprecedented rate. Despite accumulating evidence that engaging in physical activity is a promising primary behavioral strategy to delay or avert the deleterious effects of aging on brain health, a large degree of variation exists in study findings. Thus, before physical activity and exercise can be prescribed as “medicine” for promoting brain health, it is imperative to understand how different biological factors can attenuate or amplify the effects of physical activity on cognition at the individual level. In this review article, we briefly discuss the current state of the literature, examining the relationship between physical activity and brain health in older adults and we present the argument that biological sex is a potent moderator of this relationship. Additionally, we highlight some of the potential neurobiological mechanisms underlying this sex difference for this relatively new and rapidly expanding line of research.
DeepNEU: Artificially Induced Stem Cell (aiPSC) and Differentiated Skeletal Muscle Cell (aiSkMC) Simulations of Infantile Onset POMPE Disease (IOPD) for Potential Biomarker Identification and Drug Discovery

Infantile onset Pompe disease (IOPD) is a rare and lethal genetic disorder caused by the deletion of the acid alpha-glucosidase (GAA) gene. This gene encodes an essential lysosomal enzyme that converts glycogen to glucose. While enzyme replacement therapy helps some, our understanding of disease pathophysiology is limited. In this project we develop computer simulated stem cells (aiPSC) and differentiated skeletal muscle cells (aiSkMC) to empower IOPD research and drug discovery. Our Artificial Intelligence (AI) platform, DeepNEU v3.6 was used to generate aiPSC and aiSkMC simulations with and without GAA expression. These simulations were validated using peer reviewed results from the recent literature. Once the aiSkMC simulations (IOPD and WT) were validated they were used to evaluate calcium homeostasis and mitochondrial function in IOPD. Lastly, we used aiSkMC IOPD simulations to identify known and novel biomarkers and potential therapeutic targets. The aiSkMC simulations of IOPD correctly predicted genotypic and phenotypic features that were reported in recent literature. The probability that these features were accurately predicted by chance alone using the binomial test is 0.0025. The aiSkMC IOPD simulation correctly identified L-type calcium channels (VDCC) as a biomarker and confirmed the positive effects of calcium channel blockade (CCB) on calcium homeostasis and mitochondrial function. These published data were extended by the aiSkMC simulations to identify calpain(s) as a novel potential biomarker and therapeutic target for IOPD. This is the first time that computer simulations of iPSC and differentiated skeletal muscle cells have been used to study IOPD. The simulations are robust and accurate based on available published literature. We also demonstrated that the IOPD simulations can be used for potential biomarker identification leading to targeted drug discovery. We will continue to explore the potential for calpain inhibitors with and without CCB as effective therapy for IOPD.
Arsenic Species in Cordyceps sinensis and Its Potential Health Risks

High arsenic residues make Cordyceps sinensis a concern in China. Arsenic toxicity is related to its species. Many studies have evaluated the toxicity of total arsenic, but few have studied its species. In this study, the species of arsenic in C. sinensis and its potential health risk were investigated. SEC-HPLC-ICP-MS was used to analysis of arsenic in C. sinensis and unknown arsenic (uAs) was discovered. Additionally, arsenic in C. sinensis was mainly found in alkali-soluble proteins. The trend of arsenic transformation indicated that unknown arsenic in C. sinensis may be converted into free inorganic arsenic, which enhanced toxicity. The result of risk assessment indicated that there were potential health risks of uAs. Hereon, we proposed recommendations for the use of C. sinensis and regulatory recommendations for arsenic standards. This study contributed to the toxicity reveal, safety evaluation, and risk assessment of arsenic in C. sinensis.
Upon Repeated Reflection: Consequences of Frequent Exposure to the Cognitive Reflection Test for Mechanical Turk Participants

Participants from public participant panels, such as Amazon Mechanical Turk, are shared across many labs and participate in many studies during their panel tenure. Here, I demonstrate direct and indirect downstream consequences of frequent exposure in three studies (N1−3 = 3, 660), focusing on the cognitive reflection test (CRT), one of the most frequently used cognitive measures in online research. Study 1 explored several variants of the signature bat-and-ball item in samples recruited from Mechanical Turk. Panel tenure was shown to impact responses to both the original and merely similar items. Solution rates were not found to be higher than in a commercial online panel with less exposure to the CRT (Qualtrics panels, n = 1, 238). In Study 2, an alternative test with transformed numeric values showed higher correlations with validation measures than the original test. Finally, Study 3 investigated sources of item familiarity and measured performance on novel lure items.