Miracle-dz/UniFAR-FTUs huggingface dataset:
Network controllability-based algorithm to target personalized driver genes for discovering combinatorial drugs of individual patients

Abstract Multiple driver genes in individual patient samples may cause resistance to individual drugs in precision medicine. However, current computational methods have not studied how to fill the gap between personalized driver gene identification and combinatorial drug discovery for individual patients. Here, we developed a novel structural network controllability-based personalized driver genes and combinatorial drug identification algorithm (CPGD), aiming to identify combinatorial drugs for an individual patient by targeting personalized driver genes from network controllability perspective. On two benchmark disease datasets (i.e. breast cancer and lung cancer datasets), performance of CPGD is superior to that of other state-of-the-art driver gene-focus methods in terms of discovery rate among prior-known clinical efficacious combinatorial drugs. Especially on breast cancer dataset, CPGD evaluated synergistic effect of pairwise drug combinations by measuring synergistic effect of their corresponding personalized driver gene modules, which are affected by a given targeting personalized driver gene set of drugs. The results showed that CPGD performs better than existing synergistic combinatorial strategies in identifying clinical efficacious paired combinatorial drugs. Furthermore, CPGD enhanced cancer subtyping by computationally providing personalized side effect signatures for individual patients. In addition, CPGD identified 90 drug combinations candidates from SARS-COV2 dataset as potential drug repurposing candidates for recently spreading COVID-19.
The Effect of Low-Intensity Transcranial Ultrasound Stimulation on Neural Oscillation and Hemodynamics in the Mouse Visual Cortex Depends on Anesthesia Level and Ultrasound Intensity

Objective: Low-intensity transcranial ultrasound stimulation (TUS) can induce motor responses, neural oscillation and hemodynamic responses. Early studies demonstrated that the motor responses evoked by TUS critically depend on anesthesia levels and ultrasound intensity. However, the neural mechanism of how anesthesia levels and ultrasound intensity influence on brain responses during TUS has never been explored yet. To investigate this question, we applied different anesthesia levels and ultrasound intensities on the visual cortex of mouse and observed neural oscillation change and hemodynamic responses during TUS. Methods: low-intensity ultrasound was delivered to mouse visual cortex under different anesthesia levels, and simultaneous recordings for local field potentials (LFPs) and hemodynamic responses were carried out to measure and analyze the changes quantitatively. Results: (i) The change of mean amplitude and mean relative power of sharp wave-ripple (SPW-R) in LFPs induced by TUS decreased as the anesthesia level increased (from awake to 1.5% isoflurane). (ii) The hemodynamic response level induced by TUS decreased as the anesthesia level increased (from awake to1.5% isoflurane). (iii) The coupling strength between neural activities and hemodynamic responses was dependent on anesthesia level. (iv) The neural activities and hemodynamic responses increase as a function of ultrasound intensity. Conclusion: These results support that the neural activities and hemodynamic response of the mouse visual cortex induced by TUS are related to the anesthesia level and ultrasound intensity. Significance: This finding suggests that careful maintenance of anesthesia level and ultrasound intensity is required to acquire accurate LFP and hemodynamic data from samples with TUS.
Land-Use Effect on Olive Groves Pest Prays oleae and on Its Potential Biocontrol Agent Chrysoperla carnea

Simple Summary To rethink the counterproductive effects of the recurrent use of pesticides to control pests, we examine how a conservation biological control approach can promote the necessary conditions for the development of a natural enemy (Chrysoperla carnea) that controls olive moth pest (Prays oleae) in 25 olive groves of the Portuguese Beira Interior region. Our study has the distinctive peculiarity of joining varied technical approaches, since the databases contained information related to the abundance records of both insect populations, the record of olive fruits infestation by the pest, and the information obtained after a geospatial analysis that resulted in landscape metrics. Overall, we corroborated the attraction of C. carnea to the olive moth, highlighted the possible biocontrol potential of C. carnea on this pest, asserted that the promotion of the diversity of land-uses has a significant effect in reducing the abundance of pest, and confirmed that landscapes dominated by olive groves promote the development of P. oleae. The implication of these results is of extreme importance for olive growers since promoting land-uses complexity and heterogeneity surrounding olive groves can reduce the likelihood of suffering pest outbreaks and help to avoid associated economic and environmental problems. Abstract Olive growing has been intensified through the simplification of agricultural landscapes. In order to rethink the environmental drawbacks of these practices, conservation biological control techniques have been examined. In this work, Prays oleae and its natural enemy Chrysoperla carnea were monitored to account for the effects of the amount and diversity of different land-uses. We found that C. carnea showed an attraction to areas with high abundances of P. oleae but this predator did not display any affection by the different land-uses. Inversely, P. oleae abundance was lower in diverse landscapes and higher in simplified ones. Importantly, higher abundances of C. carnea were related to lower infestation levels of P. oleae in the late part of the season. These results corroborate the attraction of C. carnea to the olive moth, highlighting the potential of C. carnea as a biological control agent of this pest, assert that the promotion of land-use diversity can reduce P. oleae and confirm that landscapes dominated by olive groves can promote this pest. The present study aims at contributing to the discussion about the management of agricultural ecosystems by providing farmers with sustainable alternatives that do not have harmful effects on the environment and public health.
Normal thyroid volume in subjects evaluated in a primary ambulatory setting in Liguria.

BACKGROUND Ultrasonography (US) is the simplest method of evaluating thyroid volume (TV). The current normal TV in Liguria is not known. The aim of this study was to obtain normative data on TV in Liguria. MATERIALS AND METHODS From 3552 files of endocrine evaluations registered in a primary outpatient setting, we selected 483 files on euthyroid subjects (383 females and 100 males) with a normal echoic pattern on US. The inclusion criterion was the absence of thyroperoxidase autoantibodies and drugs known to interfere with thyroid hormone secretion or metabolism. TV was calculated by means of US. Anthropometric characteristics, smoking habits and the district where subjects lived were registered. RESULTS Less than 50% of patients were not taking any drug. The percentage of obesity was similar in both sexes. TSH levels were similar in males and females. Median TV was 8.0 ml (IQR 6.7 - 9.8 ml) in females and 11.8 ml (9.3 - 15.6 ml) in males (P<0.0001). In females, TV was greater (P=0.01) in smokers than in non-smokers. In both sexes, the right lobe was significantly (P<0.0001) larger in volume than the left. Post-hoc analysis did not show any differences among age-groups in either females or males. In females, but not in males, TV differed significantly (P=0.0002) according to the district of residence. A significant positive correlation was found in both groups between TV and weight, height, BMI and BSA. CONCLUSIONS Reference values of TV in the Ligurian population are now available. TV in the general population could be compared with these normative data.
Changes in Urinary Biomarkers of Organ Damage, Inflammation, Oxidative Stress, and Bone Turnover Following a 3000-m Time Trial

Strenuous exercise induces organ damage, inflammation, and oxidative stress. Currently, to monitor or investigate physiological conditions, blood biomarkers are frequently used. However, blood sampling is perceived to be an invasive method and may induce stress. Therefore, it is necessary to establish a non-invasive assessment method that reflects physiological conditions. In the present study, we aimed to search for useful biomarkers of organ damage, inflammation, oxidative stress, and bone turnover in urine following exercise. Ten male runners participated in this study and performed a 3000-m time trial. We measured biomarkers in urine collected before and immediately after exercise. Renal damage markers such as urea protein, albumin, N-acetyl-β-D-glucosaminidase (NAG), and liver-fatty acid binding protein (L-FABP), and an intestinal damage marker, intestine-fatty acid binding protein (I-FABP), increased following exercise (p < 0.05). However, a muscle damage marker, titin N-terminal fragments, did not change (p > 0.05). Inflammation-related factors (IRFs), such as interleukin (IL)-1β, IL-1 receptor antagonist (IL-1ra), IL-6, complement (C) 5a, myeloperoxidase (MPO), calprotectin, monocyte chemoattractant protein (MCP)-1, and macrophage colony-stimulating factor (M-CSF), increased whereas IRFs such as IL-4 and IL-10 decreased following exercise (p < 0.05). IRFs such as tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-12p40, and interferon (IFN)-γ did not change (p > 0.05). Oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and nitrotyrosine, did not change following exercise (p > 0.05) whereas 8-hydroxy-2′-deoxyguanosine (8-OHdG) decreased (p < 0.05). Bone resorption markers, such as cross-linked N-telopeptide of type I collagen (NTX) and deoxypyridinoline (DPD), did not change following exercise (p > 0.05). These results suggest that organ damage markers and IRFs in urine have the potential to act as non-invasive indicators to evaluate the effects of exercise on organ functions.
Preparation, characterization, and in vitro evaluation of antibacterial sol–gel coated cotton textiles with prolonged release of curcumin

The aim of this study was to develop a textile-based sol–gel release system with antibacterial properties intended for medical applications. Curcumin (a herbal compound extracted from Curcuma longa L.) was embedded in an acid-catalyzed silica xerogel coating on cotton textiles. The release of curcumin was found to be diffusion-controlled, as expressed by the Higuchi and the first-order models. Matrix dissolution release was ruled out by the absence of dissolved silica in the release medium. Results from nitrogen sorption analysis confirmed the presence of mesopores in the xerogel coating, and an increase in both the BET surface area from 1.95 to 2.23 m2 g−1 and in the mesopore volume from 0.003 to 0.004 cm3 g−1 after the sol–gel treatment. Thicker xerogel coatings therefore provided greater porosity for curcumin entrapment, leading to retardation of the diffusion processes and consequently extended release profiles. The treated samples showed better antibacterial properties against Staphylococcus aureus (99% reduction) compared with Escherichia coli (37% reduction). Overall, the developed sol–gel coated textiles demonstrate promising potential for use as wound dressing materials.
Investigating the mitochondrial genomic landscape of Arabidopsis thaliana by long-read sequencing

Plant mitochondrial genomes have distinctive features compared to those of animals; namely, they are large and divergent, with sizes ranging from hundreds of thousands of to a few million bases. Recombination among repetitive regions is thought to produce similar structures that differ slightly, known as “multipartite structures,” which contribute to different phenotypes. Although many reference plant mitochondrial genomes represent almost all the genes in mitochondria, the full spectrum of their structures remains largely unknown. The emergence of long-read sequencing technology is expected to yield this landscape; however, many studies aimed to assemble only one representative circular genome, because properly understanding multipartite structures using existing assemblers is not feasible. To elucidate multipartite structures, we leveraged the information in existing reference genomes and classified long reads according to their corresponding structures. We developed a method that exploits two classic algorithms, partial order alignment (POA) and the hidden Markov model (HMM) to construct a sensitive read classifier. This method enables us to represent a set of reads as a POA graph and analyze it using the HMM. We can then calculate the likelihood of a read occurring in a given cluster, resulting in an iterative clustering algorithm. For synthetic data, our proposed method reliably detected one variation site out of 9,000-bp synthetic long reads with a 15% sequencing-error rate and produced accurate clustering. It was also capable of clustering long reads from six very similar sequences containing only slight differences. For real data, we assembled putative multipartite structures of mitochondrial genomes of Arabidopsis thaliana from nine accessions sequenced using PacBio Sequel. The results indicated that there are recurrent and strain-specific structures in A. thaliana mitochondrial genomes.
Extensive linkage and genetic coupling of song and preference loci underlying rapid speciation in Laupala crickets.

In nature, closely related species commonly display divergent mating behaviors, suggesting a central role for such traits in the origin of species. Elucidating the genetic basis of divergence in these traits is necessary to understand the evolutionary process leading to reproductive barriers and speciation. The rapidly speciating Hawaiian crickets of the genus Laupala provides an ideal system for dissecting the genetic basis of mating behavior divergence. In Laupala, closely related species differ markedly in male song pulse rate and female preference for pulse rate. These behaviors play an important role in determining mating patterns. Previous studies identified a genetic architecture consisting of numerous small to moderate effect loci causing interspecific differences in pulse rate and preference, including colocalizing pulse rate and preference QTL on linkage group one (LG1). To further interrogate these QTL, we conduct a fine mapping study using high-density SNP linkage maps. With improved statistical power and map resolution, we provide robust evidence for genetic coupling between song and preference, along with two additional pulse rate QTL on LG1, revealing a more resolved picture of the genetic architecture underlying mating behavior divergence. Our sequence-based genetic map, along with dramatically narrowed QTL confidence intervals, allowed us to annotate genes within the QTL regions and identify several exciting candidate genes underlying variation in pulse rate and preference divergence. Such knowledge suggests potential molecular mechanisms underlying the evolution of behavioral barriers.
Factors supporting the implementation of integrated care between physical and mental health services: an integrative review

ABSTRACT In Australia and internationally there is a strong policy commitment to the redesign of health services toward integrated physical and mental health care. When executed well, integrated care has been demonstrated to improve the access to, clinical outcomes from, and quality of care while reducing overtreatment and duplication. Despite the demonstrated effectiveness and promise of integrated care, exactly how integrated care is best achieved remains less clear. The aim of this review study was to identify factors that support the implementation of integrated care between physical and mental health services. An integrative review was conducted following the framework developed by Whittemore and Knafl, with quantitative and qualitative evidence systematically considered. To identify studies, Medline, PubMed, PsychINFO, CINAHL were searched for the period from 2003 to 2018, and reference lists of included studies and review articles were examined. Nineteen studies were included. Synthesis of study findings identified seven key factors supporting the implementation of integrated care between physical and mental health services: (a) adequate resourcing, (b) shared values, (c) effective communication, (d) information technology (IT) infrastructure, (e) flexible administrative organizations, (f) role clarity and accountability, and (g) staff engagement and training. There was little theoretical development in included studies, with little insight into the contextual factors or underlying mechanism required to support the implementation of integrated care initiatives. This review identified a set of inter-related barriers and facilitators which, if addressed, can improve the implementation and sustainability of truly integrated care.
Hypoxia-induced mitochondrial abnormalities in cells of the placenta

Introduction Impaired utero-placental perfusion is a well-known feature of early preeclampsia and is associated with placental hypoxia and oxidative stress. Although aberrations at the level of the mitochondrion have been implicated in PE pathophysiology, whether or not hypoxia-induced mitochondrial abnormalities contribute to placental oxidative stress is unknown. Methods We explored whether abnormalities in mitochondrial metabolism contribute to hypoxia-induced placental oxidative stress by using both healthy term placentae as well as a trophoblast cell line (BeWo cells) exposed to hypoxia. Furthermore, we explored the therapeutic potential of the antioxidants MitoQ and quercetin in preventing hypoxia-induced placental oxidative stress. Results Both in placental explants as well as BeWo cells, hypoxia resulted in reductions in mitochondrial content, decreased abundance of key molecules involved in the electron transport chain and increased expression and activity of glycolytic enzymes. Furthermore, expression levels of key regulators of mitochondrial biogenesis were decreased while the abundance of constituents of the mitophagy, autophagy and mitochondrial fission machinery was increased in response to hypoxia. In addition, placental hypoxia was associated with increased oxidative stress, inflammation, and apoptosis. Moreover, experiments with MitoQ revealed that hypoxia-induced reactive oxygen species originated from the mitochondria in the trophoblasts. Discussion This study is the first to demonstrate that placental hypoxia is associated with mitochondrial-generated reactive oxygen species and significant alterations in the molecular pathways controlling mitochondrial content and function. Furthermore, our data indicate that targeting mitochondrial oxidative stress may have therapeutic benefit in the management of pathologies related to placental hypoxia.
Morphological Characterization of the In Vitro Mycorrhizae Formed between Four Terfezia Species (Pezizaceae) with Cistus salviifolius and Cistus ladanifer—Towards Desert Truffles Production in Acid Soils

Terfezia species are obligate symbiotic partners of several xerophytic host plants, mainly belonging to the Cistaceae. Yet, their mycorrhizal associations with members of the genus Cistus remain poorly characterized and their potential application in desert truffle cultivation remains unexplored. This work provides the first anatomic descriptions of the mycorrhizae formed in vitro by four Terfezia species (i.e., T. arenaria; T. extremadurensis; T. fanfani, T. pini) with C. ladanifer and C. salviifolius, two of the most widespread and common Cistus species in acidic soils. All the tested associations resulted in the formation of ectomycorrhizae with well-developed Hartig net, but with a varying degree of mantle development. Our results also demonstrate that all the experimented Terfezia-Cistus combinations expressed high mycorrhization rates. Moreover, the present work shows that C. salviifolius and C. ladanifer are suitable plant hosts for Terfezia species, including some that are, to date, known to be only associated with annual herbs or tree species. This new evidence might aid in broadening the number of situations whereby Terfezia spp. can be cultivated in acid soils.
Well Placement Optimization Using a Particle Swarm Optimization Algorithm, a Novel Approach

Optimal well placement is a crucial step in reservoir development process. The key points in such an optimization process are using a fast function evaluation tool and development of an efficient optimization algorithm. This study presents an approach that uses particle swarm optimization algorithm in conjunction with streamline simulation to determine the optimum well locations within a reservoir, regarding a modified net present value as the objective. Performance of this algorithm was investigated through several different examples, and compared to that of genetic algorithm (GA) and simulated annealing (SA) methods. It was observed that particle swarm optimization algorithm outperformed both SA and GA in terms of efficiency and accuracy.
Changes in Disruptive Behavior Mediated by Social Competency: Testing the STARS Theory of Change in a Randomized Sample of Elementary Students

Objective: We tested the hypothesis that the positive impact of STARS (Self-Management Training and Regulation Strategy) participation on disruptive classroom behavior was mediated by improvements in teacher-perceived self-control, social competency, and student–teacher relationships. Method: Using a classroom block randomized design in six urban schools, we relied on the responses of 42 teachers who screened 762 fourth- and fifth-grade students to identify 108 students (x¯ age = 10.3 years, range: 8.8–11.8 years) with elevated levels of teacher-rated disruptive behavior. These students were randomly placed in either the STARS (n = 60) or a control condition (n = 48). Results: Controlling for pretest differences, a path model revealed that STARS students experienced significant changes in posttest assessments of disruptive classroom behavior (d = .46) as well as significant changes in the key program targets of perceived autonomy, social competence, and student–teacher relations. Increases in social competence—a core STARS program target—appear to fully mediate posttest changes in disruptive classroom behavior. Conclusions: Findings indicate that providing social competence training, using structured and formative feedback sessions, and providing increased opportunities for struggling students to practice skills leads to improvements in challenging classroom behaviors.