Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictability of human differential gene expression

Significance The identification of genes that are differentially expressed provides a molecular foothold onto biological questions of interest. Whether some genes are more likely to be differentially expressed than others, and to what degree, has never been assessed on a global scale. Here, we reanalyze more than 600 studies and find that knowledge of a gene’s prior probability of differential expression (DE) allows for accurate prediction of DE hit lists, regardless of the biological question. This result suggests redundancy in transcriptomics experiments that both informs gene set interpretation and highlights room for growth within the field. Differential expression (DE) is commonly used to explore molecular mechanisms of biological conditions. While many studies report significant results between their groups of interest, the degree to which results are specific to the question at hand is not generally assessed, potentially leading to inaccurate interpretation. This could be particularly problematic for metaanalysis where replicability across datasets is taken as strong evidence for the existence of a specific, biologically relevant signal, but which instead may arise from recurrence of generic processes. To address this, we developed an approach to predict DE based on an analysis of over 600 studies. A predictor based on empirical prior probability of DE performs very well at this task (mean area under the receiver operating characteristic curve, ∼0.8), indicating that a large fraction of DE hit lists are nonspecific. In contrast, predictors based on attributes such as gene function, mutation rates, or network features perform poorly. Genes associated with sex, the extracellular matrix, the immune system, and stress responses are prominent within the “DE prior. ” In a series of control studies, we show that these patterns reflect shared biology rather than technical artifacts or ascertainment biases. Finally, we demonstrate the application of the DE prior to data interpretation in three use cases: (i) breast cancer subtyping, (ii) single-cell genomics of pancreatic islet cells, and (iii) metaanalysis of lung adenocarcinoma and renal transplant rejection transcriptomics. In all cases, we find hallmarks of generic DE, highlighting the need for nuanced interpretation of gene phenotypic associations.
Trabecular architecture of the great ape and human femoral head

Studies of femoral trabecular structure have shown that the orientation and volume of bone are associated with variation in loading and could be informative about individual joint positioning during locomotion. In this study, we analyse for the first time trabecular bone patterns throughout the femoral head using a whole‐epiphysis approach to investigate how potential trabecular variation in humans and great apes relates to differences in locomotor modes. Trabecular architecture was analysed using microCT scans of Pan troglodytes (n = 20), Gorilla gorilla (n = 14), Pongo sp. (n = 5) and Homo sapiens (n = 12) in medtool 4.1. Our results revealed differences in bone volume fraction (BV/TV) distribution patterns, as well as overall trabecular parameters of the femoral head between great apes and humans. Pan and Gorilla showed two regions of high BV/TV in the femoral head, consistent with hip posture and loading during two discrete locomotor modes: knuckle‐walking and climbing. Most Pongo specimens also displayed two regions of high BV/TV, but these regions were less discrete and there was more variability across the sample. In contrast, Homo showed only one main region of high BV/TV in the femoral head and had the lowest BV/TV, as well as the most anisotropic trabeculae. The Homo trabecular structure is consistent with stereotypical loading with a more extended hip compared with great apes, which is characteristic of modern human bipedalism. Our results suggest that holistic evaluations of femoral head trabecular architecture can reveal previously undetected patterns linked to locomotor behaviour in extant apes and can provide further insight into hip joint loading in fossil hominins and other primates.
LPA1, LPA2, LPA4, and LPA6 receptor expression during mouse brain development

LPA is a small bioactive phospholipid that acts as an extracellular signaling molecule and is involved in cellular processes, including cell proliferation, migration, and differentiation. LPA acts by binding and activating at least six known G protein–coupled receptors: LPA1–6. In recent years, LPA has been suggested to play an important role both in normal neuronal development and under pathological conditions in the nervous system.
Complete mitochondrial genome of Sebastes hubbsi (Scorpaenidae, Scorpaeniformes) from the East Sea, Korea

Abstract Hybrids of Sebastes hubbsi, considered a valid species, have been found in the ocean. To examine the basic characteristics of mitochondrial DNA, we analysed the complete mitogenome of S. hubbsis using next-generation sequencing. The complete mitogenome was 16,453 bp in length and comprised 13 protein-coding genes (PCGs), 2 rRNAs, 22 tRNAs and 1 control region. The complete mitochondrial DNA had 27.9% A, 26.7% T, 17.2% G and 28.3% C, showing a slight AT bias (54.5%). The start codon of all PCGs was ATG, except COX1 (GTG). The stop codons in the PCGs were mainly TAA, except ND1 and ND3 (TAG), ND4 (AGA) and Cytb (incomplete termination codon, T). The tRNAs had a typical cloverleaf structure, except tRNASer (AGY) which lacked the DHU arm. The complete mitogenome of S. hubbsi can be used for hybridization or on-going speciation studies within allied species in the Scorpaenidae.
Repeated oral dose toxicity study of nickel oxide nanoparticles in Wistar rats: a histological and biochemical perspective

Despite the increasing use of nickel oxide (NiO) nanoparticles (NPs), limited information is available on their toxicological effects. Health consequences of 28 days repeated oral exposure to NiO NPs have not been explored thoroughly. Hence, toxicity investigations were performed after 28‐day daily exposure in albino Wistar rats with NiO NPs following Organization for Economic Co‐operation and Development test guideline 407. Histopathology, biochemical indices including oxidative stress and biodistribution patterns were evaluated to decipher the toxicological impact of NiO NPs. NiO NP characterization by transmission electron microscopy showed an average size of 12.9 (±3.4) nm. Histological studies depicted a prominent impact on the vital organs of the rats. A dose‐dependent rise in both aminotransferase enzyme values was recorded in the homogenates of liver and kidney tissues. A significant decrease in superoxide dismutase activity and increase in catalase activity was noted. Further, a dose‐dependent decrease in reduced glutathione content was recorded in rats, which suggested generation of reactive oxygen species and oxidative stress. Increase in the malondialdehyde levels was observed with an increase in the dose substantiating the antioxidant enzyme activity profiles. Biodistribution studies indicated maximum accumulation of Ni content in liver followed by kidney. Excretion of Ni was predominantly through feces and a little through renal clearance. Our study indicated that NiO NPs adversely alter the biochemical profile of the rats and cause histological damage. Further investigations are warranted to address the mechanism by which physiological path these NiO NPs exhibit their toxic nature in in vivo.
Non-Invasive Measurement of Cardiac Output during Atrial Fibrillation: Comparison between Cardiac Magnetic Resonance Imaging and Inert Gas Rebreathing

Objectives: Atrial fibrillation (AF) is one of the most frequent heart rhythm disorders. It potentially influences cardiac function and its measurement. Cardiac magnetic resonance imaging (CMR) has become the new gold standard for non-invasive assessment of cardiac output (CO). A novel inert gas rebreathing (IGR) device based on the Fick Principle also proved promising in patients in sinus rhythm (SR). The aim of our study was to compare the agreement of non-invasive CO measurements between CMR and IGR in AF patients. Methods: A total of 68 patients, 34 with AF and 34 pair-matched controls in SR, were included. Results: Bland-Altman analysis showed good agreement between both methods, with an average deviation of 0.2 ±1.2 l/min in the AF group versus 0.3 ±1.0 l/min in the SR group (p = 0.77). IGR demonstrated good agreement for CO between 2.0 and 5.4 l/min. However, in hyperdynamic circulatory conditions (CO >5.5 l/min), the increasing disagreement of IGR and CMR measurements reached statistical significance. Conclusions: Non-invasive CO measurements using CMR and IGR are feasible in patients suffering from AF. Good agreement was found between the two methods in an unselected cohort. Hyperdynamic circulatory conditions can lead to significant measurement differences which, however, do not affect the reproducibility of IGR.
Disparities in colorectal cancer screening in New York City: An analysis of the 2014 NYC Community Health Survey

Disparities in colorectal cancer (CRC) screening uptake by race/ethnicity, socioeconomic status, and geography are well documented. We sought to further characterize the relationship between sociodemographic factors and up‐to‐date colonoscopy use in a diverse urban center using the 2014 New York City Community Health Survey (NYCCHS).
Blood-Flow Restriction Resistance Exercise for Older Adults with Knee Osteoarthritis: A Pilot Randomized Clinical Trial

In a pilot randomized clinical trial, participants aged ≥60 years (n = 35) with physical limitations and symptomatic knee osteoarthritis (OA) were randomized to 12 weeks of lower-body low-load resistance training with blood-flow restriction (BFR) or moderate-intensity resistance training (MIRT) to evaluate changes in muscle strength, pain, and physical function. Four exercises were performed three times per week to volitional fatigue using 20% and 60% of one repetition maximum (1RM). Study outcomes included knee extensor strength, gait speed, Short Physical Performance Battery (SPPB) performance, and pain via the Western Ontario and McMaster Universities OA Index (WOMAC). Per established guidance for pilot studies, primary analyses for the trial focused on safety, feasibility, and effect sizes/95% confidence intervals of dependent outcomes to inform a fully-powered trial. Across three speeds of movement, the pre- to post-training change in maximal isokinetic peak torque was 9.96 (5.76, 14.16) Nm while the mean difference between groups (BFR relative to MIRT) was −1.87 (−10.96, 7.23) Nm. Most other directionally favored MIRT, though more spontaneous reports of knee pain were observed (n = 14) compared to BFR (n = 3). BFR may have lower efficacy than MIRT in this context—though a fully-powered trial is needed to definitively address this hypothesis.
Sweetened Beverages Consumption and Pancreatic Cancer: A Meta-Analysis

Abstract No study has summarized earlier findings on the association of sweetened beverages (SBs) consumption and risk of Pancreatic Cancer (PC). This systematic review and meta-analysis was conducted to systematically review available observational studies that examined the association of SB consumption with risk of PC. Relevant papers published up to December 2017 were searched through PubMed, MEDLINE, SCOPUS, EMBASE, and Google Scholar databases, using relevant keywords. Cohort and case–control studies that examined the association of SB with PC in adults were included. Overall, 5 cohort studies with 2,041,689 participants (58.68% female, 41.32% male) and 4 case–control studies [enrolled 1,496 cases with PC (55.82% male, 44.18% female) and 3,179 controls (53.32% male, 46.68% female)] were included. Combining effect sizes from cohort studies, we found no significant association between SB consumption and risk of PC (RR: 1.06; 95% CI: 0.87–1.29). Although, stratification by the study location, follow-up duration, exposure and outcome assessment method, and adjustment for physical activity and race/ethnicity removed between-study heterogeneity, it did not affect the association. We found that 50 g/d increment in SB consumption was not linearly associated with risk of PC (RR: 1.00, 95% CI: 0.96, 1.04). No significant nonlinear association was also reached (P-nonlinearity = 0.13). In addition, pooling effect sizes from case–control studies, we did not find significant association between SB consumption and risk of PC (RR: 1.11; 95% CI: 0.92–1.35). We did not find any significant association between SB consumption and risk of PC. Additional studies are required to shed light on this issue.
Structure of glycerol dehydrogenase (GldA) from Escherichia coli.

Escherichia coli (strain K-12, substrain MG1655) glycerol dehydrogenase (GldA) is required to catalyze the first step in fermentative glycerol metabolism. The protein was expressed and purified to homogeneity using a simple combination of heat-shock and chromatographic methods. The high yield of the protein (∼250 mg per litre of culture) allows large-scale production for potential industrial applications. Purified GldA exhibited a homogeneous tetrameric state (∼161 kDa) in solution and relatively high thermostability (Tm = 65.6°C). Sitting-drop sparse-matrix screens were used for protein crystallization. An optimized condition with ammonium sulfate (2 M) provided crystals suitable for diffraction, and a binary structure containing glycerol in the active site was solved at 2.8 Å resolution. Each GldA monomer consists of nine β-strands, thirteen α-helices, two 310-helices and several loops organized into two domains, the N- and C-terminal domains; the active site is located in a deep cleft between the two domains. The N-terminal domain contains a classic Rossmann fold for NAD+ binding. The O1 and O2 atoms of glycerol serve as ligands for the tetrahedrally coordinated Zn2+ ion. The orientation of the glycerol within the active site is mainly stabilized by van der Waals and electrostatic interactions with the benzyl ring of Phe245. Computer modeling suggests that the glycerol molecule is sandwiched by the Zn2+ and NAD+ ions. Based on this, the mechanism for the relaxed substrate specificity of this enzyme is also discussed.
High dietary saturated fat intake accentuates obesity risk associated with the fat mass and obesity-associated gene in adults.

Fat mass and obesity-associated (FTO) is the strongest genetic determinant of obesity identified to date. Dietary fat is a key environmental factor that may interact with genotype to affect risk of obesity and metabolic syndrome (MetS). This study investigated associations among FTO rs9939609, obesity measures, and MetS phenotypes in adults and determined potential modulation by dietary fat intake at baseline and after a 7.5-y follow-up when MetS cases and controls were selected. FTO rs9939609 genotype, biochemical, dietary, and lifestyle measurements were determined in the LIPGENE-SU.VI. MAX study (n = 1754). FTO rs9939609 A allele carriers had a higher risk of being overweight or obese [OR = 1.66 (95% CI: 1.07, 2.57); P = 0.02] and of having a larger abdominal circumference [OR = 1.42 (95% CI: 1.01, 1.99); P = 0.04] compared with the TT homozygotes. These associations were independent of physical activity and energy intake and were maintained over the follow-up period, particularly in the MetS individuals. High dietary SFA intake (≥ 15.5% energy) and a low dietary PUFA:SFA intake ratio (<0.38) further accentuated the risk of having a BMI ≥ 25 kg/m(2) and being abdominally obese. Non-risk allele carriers appeared to be unresponsive to dietary SFA intake or to the dietary PUFA:SFA intake ratio with respect to obesity measures. In conclusion, FTO rs9939609 was associated with obesity measures, especially in those with the MetS, which was further exacerbated by high dietary SFA intake at baseline and 7.5 y later. These data indicate important novel modulation of genetic risk by dietary fat exposure in individuals with increased cardiometabolic risk.
Computer Simulations of Continuous Flow Peritoneal Dialysis Using the 3-Pore Model—A First Experience

Background: Continuous flow peritoneal dialysis (CFPD) is performed using a continuous flux of dialysis fluid via double or dual-lumen PD catheters, allowing a higher dialysate flow rate (DFR) than conventional treatments. While small clinical studies have revealed greatly improved clearances using CFPD, the inability to predict ultrafiltration (UF) may confer a risk of potentially harmful overfill. Here we performed physiological studies of CFPD in silico using the extended 3-pore model. Method: A 9-h CFPD session was simulated for: slow (dialysate to plasma creatinine [D/P crea] < 0.6), fast (D/P crea > 0.8) and average (0.6 ≤ D/P crea ≤ 0.8) transporters using 1.36%, 2.27%, or 3.86% glucose solutions. To avoid overfill, we applied a practical equation, based on the principle of mass-balance, to predict the UF rate during CFPD treatment. Results: Increasing DFR > 100 mL/min evoked substantial increments in small- and middle-molecule clearances, being 2 – 5 times higher compared with a 4-h continuous ambulatory PD (CAPD) exchange, with improvements typically being smaller for average and slow transporters. Improved UF rates, exceeding 10 mL/min, were achieved for all transport types. The β2-microglobulin clearance was strongly dependent on the UF rate and increased between 60% and 130% as a function of DFR. Lastly, we tested novel intermittent-continuous regimes as an alternative strategy to prevent overfill, being effective for 1.36% and 2.27%, but not for 3.86% glucose. Conclusion: While we find substantial increments in solute and water clearance with CFPD, previous studies have shown similar improvements using high-volume tidal automated PD (APD). Lastly, the current in silico results need confirmation by studies in vivo.
Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells

Accidental radiation exposure that is due to a nuclear accident or terrorism using radioactive materials has severe detrimental effects on human health, and it can manifest as acute radiation syndrome depending on the dose and distribution of the radiation. Therefore, the development of radiation countermeasure agents is urgently needed to protect humans against radiation injury. Besides nuclear DNA, the mitochondria are important targets of ionizing radiation (IR) because these organelles generate reactive oxygen species (ROS). Recently, we revealed that mitochondrial ROS‐activated cell signaling is associated with IR‐induced tumor formation. Here, we investigated the effectiveness of ascorbic acid and epicatechin (EC) in scavenging ROS as radiation countermeasure agents by using human cells and mouse. Preradiation and postradiation treatments with EC mitigate ROS‐mediated mitochondrial damage, IR‐induced oxidative stress responses including reduction of superoxide dismutase activity, and elevated nuclear factor erythroid 2–related factor 2 expression, and they improve human fibroblast survival. As well as in vitro, EC mitigated ROS‐mediated mitochondrial damage after exposure to IR in vivo in mouse platelets. Furthermore, oral administration of EC significantly enhanced the recovery of mouse hematopoietic cells from radiation injury in vivo. In summary, EC is a potentially viable countermeasure agent that is immediately effective against accidental IR exposure by targeting mitochondria‐mediated oxidative stress. —Shimura, T. , Koyama, M. , Aono, D. , Kunugita, N. Epicatechin as a promising agent to countermeasure radiation exposure by mitigating mitochondrial damage in human fibroblasts and mouse hematopoietic cells. FASEB J. 33, 6867–6876 (2019). www.fasebj. org
The complete mitochondrial genome of a fishfly, Dysmicohermes ingens (Chandler) (Megaloptera: Corydalidae: Chauliodinae)

Abstract The complete mt genome of a fishfly species, Dysmicohermes ingens (Megaloptera: Corydalidae: Chauliodinae), was sequenced. The 16,271 bp long genome has the standard metazoan complement of 37 genes and an A+T-rich region, in the insect ancestral genome arrangement. All protein coding genes (PCGs) initiate with ATN except that cox1 initiates with CGA and nad1 initiates with TTG. This is the first report that cox1 uses CGA as the start codon in Neuropterida. The control region occupying 1495 bp is comparatively simple, with no conserved blocks or long tandem repeats.
The Effect of Cytochalasans on the Actin Cytoskeleton of Eukaryotic Cells and Preliminary Structure–Activity Relationships

In our ongoing search for new bioactive fungal metabolites, two new cytochalasans were isolated from stromata of the hypoxylaceous ascomycete Hypoxylon fragiforme. Their structures were elucidated via high-resolution mass spectrometry (HR-MS) and nuclear magnetic resonance (NMR) spectroscopy. Together with 23 additional cytochalasans isolated from ascomata and mycelial cultures of different Ascomycota, they were tested on their ability to disrupt the actin cytoskeleton of mammal cells in a preliminary structure–activity relationship study. Out of all structural features, the presence of hydroxyl group at the C7 and C18 residues, as well as their stereochemistry, were determined as important factors affecting the potential to disrupt the actin cytoskeleton. Moreover, reversibility of the actin disrupting effects was tested, revealing no direct correlations between potency and reversibility in the tested compound group. Since the diverse bioactivity of cytochalasans is interesting for various applications in eukaryotes, the exact effect on eukaryotic cells will need to be determined, e.g., by follow-up studies involving medicinal chemistry and by inclusion of additional natural cytochalasans. The results are also discussed in relation to previous studies in the literature, including a recent report on the anti-Biofilm activities of essentially the same panel of compounds against the pathogenic bacterium, Staphylococcus aureus.
Loss of Independence After Operative Management of Femoral Neck Fractures

Objectives: The FAITH trial evaluated effects of sliding hip screws versus cancellous screws in femoral neck fracture patients. Using FAITH trial data, we quantified changes in living status, use of aids, and investigated factors associated with living and walking independently 12 months after fracture. Methods: We conducted a descriptive analysis to quantify patients' changes in living status, use of aids, and used multivariable Cox regression analyses to determine factors associated with living and walking independently after fracture. Results: Of patients who lived independently before hip fracture, 3.07% (50–80 years old) and 19.81% (>80 years old) were institutionalized 12 months after injury. Of patients who were walking independently before injury, 33.62% (50–80 years old) and 69.34% (>80 years old) required a walking aid 12 months after injury. Factors associated with higher chances of living independently included the following: being between 50 and 80 years, having a class I American Society of Anesthesiologists classification, not using a walking aid before fracture, being a nonsmoker or former smoker, and having an acceptable quality of implant placement. Factors associated with higher chances of walking without an aid included the following: being between 50 and 80 years, having a class I American Society of Anesthesiologists classification, living independently before fracture, being a nonsmoker or former smoker, having an undisplaced fracture, and not requiring revision surgery. Conclusions: Femoral neck fracture patients suffer great losses of independence. Identifying factors associated with living and walking independently after hip fracture may help surgeons better identify which patients are at risk and optimize care of patients with this injury. Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.