Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of lung cancer risk using homology-based emphysema quantification in patients with lung nodules

The purpose of this study was to assess whether homology-based emphysema quantification (HEQ) is significantly associated with lung cancer risk. This retrospective study was approved by our institutional review board. We included 576 patients with lung nodules (317 men and 259 women; age, 66.8 ± 12.3 years), who were selected from a database previously generated for computer-aided diagnosis. Of these, 283 were diagnosed with lung cancer, whereas the remaining 293 showed benign lung nodules. HEQ was performed and percentage of low-attenuation lung area (LAA%) was calculated on the basis of computed tomography scans. Statistical models were constructed to estimate lung cancer risk using logistic regression; sex, age, smoking history (Brinkman index), LAA%, and HEQ were considered independent variables. The following three models were evaluated: the base model (sex, age, and smoking history); the LAA% model (the base model + LAA%); and the HEQ model (the base model + HEQ). Model performance was assessed using receiver operating characteristic analysis and the associated area under the curve (AUC). Differences in AUCs among the models were evaluated using Delong’s test. AUCs of the base, LAA%, and HEQ models were 0.585, 0.593, and 0.622, respectively. HEQ coefficient was statistically significant in the HEQ model (P = 0.00487), but LAA% coefficient was not significant in the LAA% model (P = 0.199). Delong’s test revealed significant difference in AUCs between the LAA% and HEQ models (P = 0.0455). In conclusion, after adjusting for age, sex, and smoking history (Brinkman index), HEQ was significantly associated with lung cancer risk.
PKA at a Cross-Road of Signaling Pathways Involved in the Regulation of Glioblastoma Migration and Invasion by the Neuropeptides VIP and PACAP

Glioblastoma (GBM) remains an incurable disease, mainly due to the high migration and invasion potency of GBM cells inside the brain. PI3K/Akt, Sonic Hedgehog (SHH), and PKA pathways play major regulatory roles in the progression of GBM. The vasoactive intestinal peptide (VIP) family of neuropeptides and their receptors, referred in this article as the “VIP-receptor system”, has been reported to regulate proliferation, differentiation, and migration in a number of tumor cell types and more particularly in GBM cells. These neuropeptides are potent activators of the cAMP/PKA pathway. The present study aimed to investigate the cross-talks between the above cited signaling cascades. Regulation by VIP-related neuropeptides of GBM migration and invasion was evaluated ex vivo in rat brain slices explanted in culture. Effects of different combinations of VIP-related neuropeptides and of pharmacological and siRNA inhibitors of PKA, Akt, and of the SHH/GLI1 pathways were tested on GBM migration rat C6 and human U87 GBM cell lines using the wound-healing technique. Quantification of nuclear GLI1, phospho-Akt, and phospho-PTEN was assessed by western-immunoblotting. The VIP-receptor system agonists VIP and PACAP-38 significantly reduced C6 cells invasion in the rat brain parenchyma ex vivo, and C6 and U87 migration in vitro. A VIP-receptor system antagonist, VIP10-28 increased C6 cell invasion in the rat brain parenchyma ex vivo, and C6 and migration in vitro. These effects on cell migration were abolished by selective inhibitors of the PI3K/Akt and of the SHH pathways. Furthermore, VIP and PACAP-38 reduced the expression of nuclear GLI1 while VIP10-28 increased this expression. Selective inhibitors of Akt and PKA abolished VIP, PACAP-38, and VIP10-28 effects on nuclear GLI1 expression in C6 cells. PACAP-38 induced a time-dependent inhibition of phospho-Akt expression and an increased phosphorylation of PTEN in C6 cells. All together, these data indicate that triggering the VIP-receptor system reduces migration and invasion in GBM cells through a PKA-dependent blockade of the PI3K/Akt and of the SHH/GLI1 pathways. Therefore, the VIP-receptor system displays anti-oncogenic properties in GBM cells and PKA is a central core in this process.
Inverse modelling for predicting both water and nitrate movement in a structured-clay soil (Red Ferrosol)

Soil physical parameter calculation by inverse modelling provides an indirect way of estimating the unsaturated hydraulic properties of soils. However many measurements are needed to provide sufficient data to determine unknown parameters. The objective of this research was to assess the use of unsaturated water flow and solute transport experiments, in horizontal packed soil columns, to estimate the parameters that govern water flow and solute transport. The derived parameters are then used to predict water infiltration and solute migration in a repacked soil wedge. Horizontal columns packed with Red Ferrosol were used in a nitrate diffusion experiment to estimate either three or six parameters of the van Genuchten–Mualem equation while keeping residual and saturated water content, and saturated hydraulic conductivity fixed to independently measured values. These parameters were calculated using the inverse optimisation routines in Hydrus 1D. Nitrate concentrations measured along the horizontal soil columns were used to independently determine the Langmuir adsorption isotherm. The soil hydraulic properties described by the van Genuchten–Mualem equation, and the NO3– adsorption isotherm, were then used to predict water and NO3– distributions from a point-source in two 3D flow scenarios. The use of horizontal columns of repacked soil and inverse modelling to quantify the soil water retention curve was found to be a simple and effective method for determining soil hydraulic properties of Red Ferrosols. These generated parameters supported subsequent testing of interactive flow and reactive transport processes under dynamic flow conditions.
Telomere Biology and Human Phenotype

Telomeres are nucleoprotein structures that cap the end of each chromosome arm and function to maintain genome stability. The length of telomeres is known to shorten with each cell division and it is well-established that telomere attrition is related to replicative capacity in vitro. Moreover, telomere loss is also correlated with the process of aging in vivo. In this review, we discuss the mechanisms that lead to telomere shortening and summarise telomere homeostasis in humans throughout a lifetime. In addition, we discuss the available evidence that shows that telomere shortening is related to human aging and the onset of age-related disease.
Newly Discovered Occurrences and Gene Tree of the Extracellular Globins and Linker Chains from the Giant Hexagonal Bilayer Hemoglobin in Metazoans

Abstract Multicellular organisms depend on oxygen-carrying proteins to transport oxygen throughout the body; therefore, proteins such as hemoglobins (Hbs), hemocyanins, and hemerythrins are essential for maintenance of tissues and cellular respiration. Vertebrate Hbs are among the most extensively studied proteins; however, much less is known about invertebrate Hbs. Recent studies of hemocyanins and hemerythrins have demonstrated that they have much wider distributions than previously thought, suggesting that oxygen-binding protein diversity is underestimated across metazoans. Hexagonal bilayer hemoglobin (HBL-Hb), a blood pigment found exclusively in annelids, is a polymer comprised up to 144 extracellular globins and 36 linker chains. To further understand the evolutionary history of this protein complex, we explored the diversity of linkers and extracellular globins from HBL-Hbs using in silico approaches on 319 metazoan and one choanoflagellate transcriptomes. We found 559 extracellular globin and 414 linker genes transcribed in 171 species from ten animal phyla with new records in Echinodermata, Hemichordata, Brachiopoda, Mollusca, Nemertea, Bryozoa, Phoronida, Platyhelminthes, and Priapulida. Contrary to previous suggestions that linkers and extracellular globins emerged in the annelid ancestor, our findings indicate that they have putatively emerged before the protostome–deuterostome split. For the first time, we unveiled the comprehensive evolutionary history of metazoan HBL-Hb components, which consists of multiple episodes of gene gains and losses. Moreover, because our study design surveyed linkers and extracellular globins independently, we were able to cross-validate our results, significantly reducing the rate of false positives. We confirmed that the distribution of HBL-Hb components has until now been underestimated among animals.
Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve

Objective To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). Design A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. Setting University hospitals of Leeds and Leicester, UK. Patients 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. Main outcome measures Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. Results All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. Conclusions There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.
The Cell-Cycle Transcriptional Network Generates and Transmits a Pulse of Transcription Once Each Cell Cycle

Multiple studies have suggested the critical roles of cyclin-dependent kinases (CDKs) as well as a transcription factor (TF) network in generating the robust cell-cycle transcriptional program. However, the precise mechanisms by which these components function together in the gene regulatory network remain unclear. Here we show that the TF network can generate and transmit a “pulse” of transcription independently of CDK oscillations. The premature firing of the transcriptional pulse is prevented by early G1 inhibitors, including transcriptional corepressors and the E3 ubiquitin ligase complex APCCdh1. We demonstrate that G1 cyclin-CDKs facilitate the activation and accumulation of TF proteins in S/G2/M phases through inhibiting G1 transcriptional corepressors (Whi5 and Stb1) and APCCdh1, thereby promoting the initiation and propagation of the pulse by the TF network. These findings suggest a unique oscillatory mechanism in which global phase-specific transcription emerges from a pulse-generating network that fires once-and-only-once at the start of the cycle.
Psychosocial factors associated with coping behaviour after inpatient treatment for substance use disorder: a systematic review study protocol

Introduction Much is known about factors associated with coping with abstinence from substance use. The planned systematic review aims to summarise available studies exploring the change in psychosocial factors associated with coping after long-term (≥3 months) inpatient treatment for substance use disorder (SUD). Examples of psychosocial factors of interest are social support, housing, activity (eg, employment and education) mental health and quality of life. Coping behaviour can be understood as responses or actions taken in a stressful situation, particularly how psychosocial factors affect a person’s coping behaviour with abstinence from substances in everyday life (characterised as a stressful situation). Methods and analysis A set of text words were developed based on the population (people with SUD), exposure (long-term inpatient SUD treatment), outcome (psychosocial factors) and study design (prospective cohort studies) of interest. A systematic search will be conducted in eight electronic databases: Campbell Collaboration Library, Cochrane Library, EMBASE, Epistemonikos, Medline, PsychINFO, Social Sciences Citation Index and SocINDEX. The titles and abstracts will be screened for relevance before a pre-piloted data collection form will be used to evaluate eligibility and extract data from the search results. The planned review will include peer-reviewed study reports published in English or Scandinavian language. Ethics and dissemination The target group, people with SUD, might be considered as vulnerable. Based on this, the population will be the group of interest in the planned systematic review of studies that have already been conducted. Patients and the general public will not be involved in the development of this systematic review. The results will be summarised in a study report and submitted to a peer-reviewed international journal. Additionally, results will be disseminated in the mass media and at international research conferences. PROSPERO registration number CRD42018087408.
Drop Jump Asymmetry is Associated with Reduced Sprint and Change-of-Direction Speed Performance in Adult Female Soccer Players

Studies that examine the effects of inter-limb asymmetry on measures of physical performance are scarce, especially in adult female populations. The aim of the present study was to establish the relationship between inter-limb asymmetry and speed and change-of-direction speed (CODS) in adult female soccer players. Sixteen adult players performed a preseason test battery consisting of unilateral countermovement jump (CMJ), unilateral drop jump (DJ), 10 m, 30 m, and 505 CODS tests. Inter-limb asymmetry was calculated using a standard percentage difference equation for jump and CODS tests, and Pearson’s r correlations were used to establish a relationship between asymmetry and physical performance as well as asymmetry scores themselves across tests. Jump-height asymmetry from the CMJ (8.65%) and DJ (9.16%) tests were significantly greater (p < 0.05) than asymmetry during the 505 test (2.39%). CMJ-height asymmetry showed no association with speed or CODS. However, DJ asymmetries were significantly associated with slower 10 m (r = 0.52; p < 0.05), 30 m (r = 0.58; p < 0.05), and 505 (r = 0.52–0.66; p < 0.05) performance. No significant relationships were present between asymmetry scores across tests. These findings suggest that the DJ is a useful test for detecting existent between-limb asymmetry that might in turn be detrimental to speed and CODS performance. Furthermore, the lack of relationships present between different asymmetry scores indicates the individual nature of asymmetry and precludes the use of a single test for the assessment of inter-limb differences.
Unraveling Morphophysiological and Biochemical Responses of Triticum aestivum L. to Extreme pH: Coordinated Actions of Antioxidant Defense and Glyoxalase Systems

Soil pH, either low (acidity) or high (alkalinity), is one of the major constraints that affect many biochemical and biological processes within the cell. The present study was carried out to understand the oxidative damage and antioxidant defense in wheat (Triticum aestivum L. cv. BARI Gom-25) grown under different pH regimes. Eight-day-old seedlings were exposed to growing media with different pH levels (4.0, 5.5, 7.0, and 8.5). Seedlings grown in pH 4.0 and in pH 8.5 showed reductions in biomass, water, and chlorophyll contents; whereas plants grown at pH 7.0 (neutral) exhibited a better performance. Extremely acidic (pH 4.0) and/or strongly alkaline (pH 8.5)-stress also increased oxidative damage in wheat by excess reactive oxygen species (ROS) generation and methylglyoxal (MG) production, which increased lipid peroxidation and disrupted the redox state. In contrary, the lowest oxidative damage was observed at a neutral condition, followed by a strong acidic condition (pH 5.5), which was mainly attributed to the better performance of the antioxidant defense and glyoxalase systems. Interestingly, seedlings grown at pH 5.5 showed a significant increase in morphophysiological attributes compared with extreme acidic (pH 4.0)- and strong alkaline (pH 8.5)-stress treatments, which indicates the tolerance of wheat to the acidic condition.
Feeding intolerance alters the gut microbiota of preterm infants

Feeding intolerance (FI) is a common disease in preterm infants, often causing a delay in individual development. Gut microbiota play an important role in nutrient absorption and metabolism of preterm infants. To date, few studies have focused on the community composition of gut microbiota of preterm infants with feeding intolerance. In this study, we collected fecal samples from 41 preterm infants diagnosed with feeding intolerance and 29 preterm infants without feeding intolerance, at three specific times during the development and prevalence of feeding intolerance (after birth, when feeding intolerance was diagnosed, after feeding intolerance was gone), from different hospitals for 16S rRNA gene sequencing. The gut microbiota community composition of preterm infants diagnosed with feeding intolerance was significantly different from that of preterm infants without feeding intolerance. At the time when feeding intolerance was diagnosed, the relative abundance of Klebsiella in preterm infants with feeding intolerance increased significantly, and was significantly higher than that of the preterm infants without feeding intolerance. After feeding intolerance was cured, the relative abundance of Klebsiella significantly decreased in the infants diagnosed with feeding intolerance, while the relative abundance of Klebsiella in preterm infants without feeding intolerance was not significantly altered during the development and prevalence of feeding intolerance. Furthermore, we verified that Klebsiella was effective in the diagnosis of feeding intolerance (AUC = 1) in preterm infants, suggesting that Klebsiella is a potential diagnostic biomarker for feeding intolerance.
Ultrastructural and histochemical study of previtellogenic oogenesis in the desert lizard Scincus mitranus (Squamata, Sauropsida)

The structure of the granulosa in reptilian sauropsids varies between groups. We investigated the follicle development in the desert lizard Scincus mitranus. In the germinal bed, oogonia, and primary oocytes were identified and found to be interspersed between the epithelial cells. Previtellogenesis was divided into three stages: early, transitional, and late previtellogenic stages. During the early previtellogenic stage (diplotene), the oocyte is invested by small epithelia cells that formed a complete single layer, which may be considered as a young follicle. The transitional previtellogenic stage was marked by proliferation and differentiation of the granulosa layer from a homogenous layer consisting of only small cells to a heterogeneous layer containing three cell types: small, intermediate, and large cells. The late previtellogenic stage was marked by high‐synthetic activity of large cells and the initiation of cytoplasmic bridges between large granulosa cells and the oocyte. Small cells were the only type of granulosa cells that underwent division. Thus, these cells may be stem cells for the granulosa cell population and may develop into intermediate and subsequently large cells. The intermediate cells may be precursors of large cells, as suggested by their ultrastructure. The ultrastructure of the large granulosa was indicative of their high synthetic activity. Histochemical analysis indicated the presence of cholesterol and phospholipids in the cytoplasm of large cells, the zona pellucida, among the microvilli, in the bridges region, and in the cortical region of the oocyte cytoplasm. These materials may be transferred from large cells into the oocyte through cytoplasmic bridges and provide nutritive function to large cells rather than functioning in steroidogenesis or vitellogenesis.
Insulator‐based dielectrophoresis combined with the isomotive AC electric field and applied to single cell analysis

We developed an insulator‐based dielectrophoretic (iDEP) creek‐gap device that enables the isomotive movement of cells and that is suitable for determining their DEP properties. In the iDEP creek‐gap device, a pair of planar insulators forming a single fan‐shaped channel allows the induction of the isomotive iDEP force on cells. Hence, the cells’ behavior is characterized by straight motion at constant velocity in the longitudinal direction of the channel. Operation of the device was demonstrated using human breast epithelial cells (MCF10A) by applying an AC voltage of Vpp = 34 V peak‐to‐peak and frequencies of 200 kHz and 50 MHz to the device. Subsequently, the magnitude of DEP forces and the real part of the ClausiusMossotti (CM) factor, Re(β), were deduced from the measured cell velocity. The values of Re(β) were 0.14 ± 0.01 for the frequency of 200 kHz and −0.12 ± 0.01 for 50 MHz. These results demonstrated that the DEP properties of the cells could be extracted over a wide field frequency range. Therefore, the proposed iDEP creek‐gap device was found to be applicable to cell analysis.