Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling Basins of Attraction for Breast Cancer Using Hopfield Networks

Cancer is a genetic disease for which traditional treatments cause harmful side effects. After two decades of genomics technological breakthroughs, personalized medicine is being used to improve treatment outcomes and mitigate side effects. In mathematical modeling, it has been proposed that cancer matches an attractor in Waddington's epigenetic landscape. The use of Hopfield networks is an attractive modeling approach because it requires neither previous biological knowledge about protein-protein interactions nor kinetic parameters. In this report, Hopfield network modeling was used to analyze bulk RNA-Seq data of paired breast tumor and control samples from 70 patients. We characterized the control and tumor attractors with respect to their size and potential energy and correlated the Euclidean distances between the tumor samples and the control attractor with their corresponding clinical data. In addition, we developed a protocol that outlines the key genes involved in tumor state stability. We found that the tumor basin of attraction is larger than that of the control and that tumor samples are associated with a more substantial negative energy than control samples, which is in agreement with previous reports. Moreover, we found a negative correlation between the Euclidean distances from tumor samples to the control attractor and patient overall survival. The ascending order of each node's density in the weight matrix and the descending order of the number of patients that have the target active only in the tumor sample were the parameters that withdrew more tumor samples from the tumor basin of attraction with fewer gene inhibitions. The combinations of therapeutic targets were specific to each patient. We performed an initial validation through simulation of trastuzumab treatment effects in HER2+ breast cancer samples. For that, we built an energy landscape composed of single-cell and bulk RNA-Seq data from trastuzumab-treated and non-treated HER2+ samples. The trajectory from the non-treated bulk sample toward the treated bulk sample was inferred through the perturbation of differentially expressed genes between these samples. Among them, we characterized key genes involved in the trastuzumab response according to the literature.
Conceptual Closure Elicited by Event Boundary Transitions Affects Commercial Communication Effectiveness

While our experience of the world may appear continuous, recent evidence suggests that our experience is automatically segmented and encoded into long-term memory as a set of discrete events. Event segmentation is an important process in long-term memory encoding with evidence pointing to experiences occurring around event boundaries being better recognized subsequently. Neuroimaging studies have shown increased activity in the hippocampus and other nodes of the default mode network (DMN) when encountering an event boundary. We have previously demonstrated that the steady state topography (SST) measure of brain activity at a left inferior frontal scalp sites is correlated with the strength of long-term memory encoding. More recently, we have noted that event boundaries occurring in naturalistic stimuli such as television advertising trigger a transient drop in activity at the inferior frontal scalp sites, an effect we have termed Conceptual Closure. In this study, SST measures of brain activity were recorded in 50 male participants as they viewed a first-person journey through a 10-room virtual art gallery. We hypothesized that the transition from one room to another would serve as an event boundary which would triggers increased hippocampal and DMN activity while correspondingly decreasing activity in task positive networks in the vicinity of the inferior frontal cortex thus eliciting Conceptual Closure. A permutation test confirmed the hypothesis in that the appearance of the door between gallery rooms was associated with Conceptual Closure in that we observed a significant drop in brain activity at the left hemisphere inferior frontal scalp site at this point in time. Finally, we illustrate the real-world impact of Conceptual Closure by considering the commercial effectiveness of a television advertisement that exhibited Conceptual Closure at points of branding. The television advertisement was broadcast before and after it was re-edited to minimize Conceptual Closure at the time the advertising brand was being featured. Minimizing Conceptual Closure at the time of branding and key message was associated with significant increased commercial effectiveness of the advertisement.
Petrophysical Joint Inversion Applied to Alpine Permafrost Field Sites to Image Subsurface Ice, Water, Air, and Rock Contents

Quantification of ground ice is crucial for understanding permafrost systems and modeling their ongoing degradation. The volumetric ice content is however rarely estimated in permafrost studies, as it is particularly difficult to retrieve. Standard borehole temperature monitoring is unable to provide any ice content estimation, whereas non-invasive geophysical techniques, such as refraction seismic and electrical resistivity measurements can yield information to assess the subsurface ice distribution. Electrical and seismic data are hereby complementary sensitive to the phase change. A petrophysical joint inversion was recently developed to determine volumetric water, air, ice and rock contents from electrical and seismic data using a petrophysical model, but was so far only tested on synthetic data and one proof-of-concept field example. In order to evaluate its applicability on different types of permafrost materials and landforms (bedrock, rock glacier, talus slope), we apply this petrophysical joint inversion scheme to five profiles located in the northwestern Alps. The electrical mixing rule (Archie's second law) was hereby identified as a source of model uncertainty, as it applies only when the electrolytic conduction is the dominating process. We therefore investigate and compare four petrophysical models linking the electrical resistivity with the ground constituents: Archie's law, Archie's law with an additional surface conduction factor, a model considering only surface conduction, and the geometric mean model. In most cases, the three first resistivity relations yield largely comparable results, whose reliability is discussed. The geometric mean model better resolve high ice content, as it is less influenced by the ice-rock ambiguity. We perform a systematic analysis of the regularization parameters and then evaluate our results with validation data including thaw depths and ice contents derived from borehole measurements. Geophysical surveys have generally a lower resolution than borehole data, but have the advantage of providing spatio-temporal information in 2D or 3D. The joint inversion results are in relatively good agreement with the validation data for all sites from ice-poor to ice-rich conditions, when choosing the most adequate resistivity model and porosity initial value. Additional forcing constraints (e.g., porosity range constraint) based on site knowledge can improve the model parameter estimation.
A Novel wx2 Gene of Toxoplasma gondii Inhibits the Parasitic Invasion and Proliferation in vitro and Attenuates Virulence in vivo via Immune Response Modulation

Toxoplasma gondii (T. gondii) is an obligate intracellular apicomplexan protozoan that can parasitize most warm-blooded animals and cause severe diseases in immunocompromised individuals or fetal abnormalities in pregnant woman. The treatment of toxoplamosis has been limited by effective drugs. Our previous work indicated that the novel gene wx2 of T. gondii may serve as a vaccine antigen candidate. To further investigate the molecular functions of wx2 in highly virulent T. gondii (RH strain), a wx2 gene deletion mutant RH strain (KO-wx2) was established using CRISPR-Cas9. The phynotype of KO-wx2 was analyzed by plaque, invasion, and replication assays in vitro as well as in vivo virulence assays. The results indicated that the targeted deletion of the wx2 gene significantly inhibited in vitro parasite growth and replication in the host cells as well as attenuated parasite virulence in the mouse model. Notably, the percentage of pro-inflammatory factors of interferon gamma (IFN-γ) and interlukin-17A (IL-17A) and anti-inflammatory factor of interlukin-10 (IL-10) in the lymph nodes were upregulated in mice infected with the KO-wx2 strain. Our data suggested that the wx2 gene plays an important role in the process of the parasite’s life cycle and virulence in mice. In addition, it also plays an important role in the host’s immunity reaction, mainly via Th1 and Th17 cellular immunity, not Th2.
Corn Yield and Phosphorus Use Efficiency Response to Phosphorus Rates Associated With Plant Growth Promoting Bacteria

The use of plant growth promoting bacteria (PGPB) that can solubilize phosphorus (P) has shown potential to improve nutrient availability in grass crops such as corn (Zea mays L.) This study was developed to investigate if inoculation with Azospirillum brasilense, Bacillus subtilis or Pseudomonas fluorescens associated with P2O5 rates can improve phosphorus use efficiency (PUE) reflecting on greater corn development and yield. The field trial was set up in a Rhodic Hapludox under no-till system under Savannah conditions, in a completely randomized block design with four replicates. Treatments were tested in a full factorial design and included: (i) five P2O5 rates (0 to 105 kg ha–1) and (ii) four PGPB seed inoculation (Control–without inoculation, A. brasilense, B. subtilis or P. fluorescens). Inoculation was found to increase grain yield by 39.5, 29.1, and 15.9% when B. subtilis was inoculated in the absence of P2O5 rates and associated with 17.5 and 70 kg P2O5 ha–1 and by 34.7% when A. brasilense was inoculated with application of 105 kg P2O5 ha–1. In addition, inoculation with B. subtilis and A. brasilense were found to increase P uptake, benefiting productive components development, leading to an improved PUE, and greater corn grain yield. The results of this study showed positive improvements in P uptake as a result of B. subtilis and A. brasilense inoculation, with an increase of 100.5 and 54.6% on PUE, respectively; while the P. fluorescens inoculation were less evident. Further research should be conducted under biotic or/and abiotic conditions such as attack of pathogens and insects, drought, salinity, water flooding, low and high temperature to better understand the role of PGPB, inoculated alone or in combination as the co-inoculated method.
The Spectrum of Long-Term Behavioral Disturbances and Provided Care After Traumatic Brain Injury

Introduction: Behavioral disturbances are found in 50–60% of traumatic brain injury (TBI) survivors with an enormous impact on daily functioning and level of recovery. However, whether typical profiles can be distinguished and how these relate to provided care is unclear. The purpose of this study is to specify the characteristics of behavioral disturbances in patients with various severity of TBI and the impact on functional outcome. Furthermore, the pathways of care after hospital discharge for patients and their care givers are analyzed. Methods: We performed a retrospective cohort study comprising 226 patients with mild TBI (mTBI; n = 107) and moderate-to-severe TBI (mod/sevTBI; n = 119) treated at the outpatient clinic and/or rehabilitation center of our university hospital between 2010 and 2015. Inclusion criteria were: behavioral disturbances as determined with the Differential Outcome Scale and age ≥16 years. Functional outcome was determined by the Glasgow Outcome Scale Extended and return to work (RTW) at six months to one year post-injury. Behavioral impairments and pathway of care were derived from medical files and scored according to predefined criteria. Results: Overall 24% of patients showed serious behavioral disturbances; three times higher in mod/sevTBI (35%) compared to mTBI (13%). mTBI patients mostly showed irritation (82%) and anger (49%), while mod/sevTBI patients mostly showed irritation (65%) and disinhibition (55%). Most (92%) patients returned home, half of the patients did not RTW. Deficits in judgment and decision-making increased risk of no RTW 10-fold. One in ten patients was (temporarily) admitted to a nursing home or psychiatric institution. 13% Of caregivers received support for dealing with impairments of patients and 13% of the mTBI and 17% of the mod/sevTBI patients experienced relational problems. Conclusions: The spectrum of behavioral disturbances differs between TBI severity categories and serious behavioral disturbances are present in a quarter of patients. Only half of the patients resumed work regardless of severity of injury suggesting that particularly the presence and not the severity of long-term behavioral disturbances interferes with RTW. Most patients returned home despite these behavioral disturbances. These findings underline the importance of early identification and appropriate treatment of behavioral disturbances in TBI patients.
Prevalence, Virulence Characterization, AMR Pattern and Genetic Relatedness of Vibrio parahaemolyticus Isolates From Retail Seafood of Kerala, India

Vibrio parahaemolyticus, a halophilic bacterium often found in the marine or estuarine environment is a well-known enteropathogen responsible for foodborne outbreaks associated with seafood. The pathogenic strains of V. parahaemolyticus are marked by the presence of thermostable direct hemoylsin (tdh) and/or TDH related hemolysin (trh) genes. This study aimed to investigate the prevalence and characteristics of potentially pathogenic V. parahaemolyticus in selected retail markets of Cochin, Kerala, along the south-western coast of the Indian subcontinent. One hundred samples collected from 10 retail markets were analyzed for the presence of pathogenic isolates of V. parahaemolyticus. Out of the 721 presumptive isolates, 648 were confirmed to be V. parahaemolyticus by toxR gene amplification, among which 29 were Kanagawa phenomenon (KP) positive. Among these potentially pathogenic isolates, 17 possessed the tdh gene whereas none of them had the trh gene. The faint amplification bands produced during the amplification of tdh gene from two isolates was confirmed by sequencing. Multiplex O serotyping identified O1 serotype as the most prevalent serotype among the 29 potentially pathogenic isolates. Further, studies on the pandemic nature of these isolates revealed that 14 of the 29 were positive for the PGS-PCR, whereas all the isolates were negative for GS-PCR and HU-α PCR. The antibiogram of the isolates revealed that three isolates had significant Multiple Antibiotic Resistance (MAR) index of 0.2 or above. Pathogenic isolates resistant to second, third and fourth generation Cephalosporins were found to be present in the seafood studied. The molecular fingerprinting studies using ERIC-PCR, and PFGE revealed that three of these isolates shared close genetic similarities with the clinical strains. The environmental and seafood isolates that produced faint amplification bands during the amplification of tdh gene suggests that the tdh gene often goes undetected in environmental isolates. The conventional methods used to identify the pathogenic V. parahaemolyticus would be good for clinical isolates, but a more elaborate method is recommended for the detection of tdh gene in environmental isolates. This is the first comprehensive study on pathogenic V. parahaemolyticus in Kerala, India and demonstrates for the first time, the isolation of potentially pathogenic V. parahaemolyticus, carrying tdh gene from seafood collected from retail markets in Kerala.
Colder Ambient Temperatures Influence Acute Onset Canine Intervertebral Disc Extrusion

Canine intervertebral disc disease is one of the most common neurologic conditions in veterinary medicine but the influence of environmental factors thereon has not been fully investigated. Subjectively, there has been the impression of increased admissions of acute spinal cord injuries due to intervertebral disc extrusion during periods of colder temperatures. In the present retrospective study, the different weather conditions (temperature, precipitation, sunshine, humidity, and atmospheric pressure) during the acute onset of clinical signs and a lag period of 3 days prior to the occurrence of symptoms were analyzed. One-hundred-and-one client owned dogs from the meteorological region of the Lake Geneva were presented to two referral centers during the 6-year (2007–2012) study period. Chondrodystrophic dogs represented 65.3% of our population, with the French Bulldog (19.8%) and Dachshund (17.8%) being the most common breeds. Multivariable logistic regression analysis identified an increased occurrence of intervertebral disc disease during colder temperatures. Our results are congruent with those of human studies which have shown that lower ambient temperatures are associated with more pain and increased risk for muscle injuries. The interplay of endogenous (breed, anatomical characteristics) and exogenous (environmental) factors should be addressed in a larger cohort study.
Poor Motor Performance – Do Peers Matter? Examining the Role of Peer Relations in the Context of the Environmental Stress Hypothesis

The aim of the current study was to investigate pathways of the Environmental Stress Hypothesis concerning the role of peer relations in the context of poor motor skills. First, we examined (1) the mediating role of peer problems in the association between motor performance in daily activities and internalizing problems as a main pathway of the Environmental Stress Hypothesis. Furthermore, we explored the role of (2) children’s popularity as a mediator and (3) best friendship quality as a moderator path of the effect of motor performance on both peer problems and internalizing problems. The non-clinical sample of the present study consisted of 189 children (48.6% females) aged 9–11 years (Mage = 9.69, SDage = 0.46). Parents reported on their child’s motor performance in daily activities by completing the Developmental Coordination Disorder Questionnaire. The Strengths and Difficulties Questionnaire was used to assess peer problems as well as internalizing problems. The Self Description Questionnaire provided a measure of children’s self-reported popularity. The Friendship Quality Questionnaire was used to investigate children’s best friendship quality. Results of a structural equation model suggest that peer problems fully mediated the association between the motor performance in daily activities and both popularity and internalizing problems. However, no evidence for the mediating effect of popularity in the association between peer problems and internalizing problems was found. Further, best friendship quality had a non-significant moderating effect on the relation between peer problems and internalizing problems. The mediating role of peer problems highlights the importance of peer relations in the motor performance of daily activities. Schools and psychomotor interventions were suggested as practical implications to support children with poor motor performance in their relationship with their peers and to improve their motor performance in daily activities.
Astrocytes and Microglia as Major Players of Myelin Production in Normal and Pathological Conditions

Myelination is an essential process that consists of the ensheathment of axons by myelin. In the central nervous system (CNS), myelin is synthesized by oligodendrocytes. The proliferation, migration, and differentiation of oligodendrocyte precursor cells constitute a prerequisite before mature oligodendrocytes extend their processes around the axons and progressively generate a multilamellar lipidic sheath. Although myelination is predominately driven by oligodendrocytes, the other glial cells including astrocytes and microglia, also contribute to this process. The present review is an update of the most recent emerging mechanisms involving astrocyte and microglia in myelin production. The contribution of these cells will be first described during developmental myelination that occurs in the early postnatal period and is critical for the proper development of cognition and behavior. Then, we will report the novel findings regarding the beneficial or deleterious effects of astroglia and microglia, which respectively promote or impair the endogenous capacity of oligodendrocyte progenitor cells (OPCs) to induce spontaneous remyelination after myelin loss. Acute delineation of astrocyte and microglia activities and cross-talk should uncover the way towards novel therapeutic perspectives aimed at recovering proper myelination during development or at breaking down the barriers impeding the regeneration of the damaged myelin that occurs in CNS demyelinating diseases.
Using Biosecurity Measures to Combat Respiratory Disease in Cattle: The Norwegian Control Program for Bovine Respiratory Syncytial Virus and Bovine Coronavirus

Bovine respiratory disease (BRD) cause important health problems in all cattle husbandry systems. It contributes substantially to the use of antimicrobial substances and compromises animal welfare and the sustainability of the cattle industry. The existing preventive measures of BRD focus at the individual animal or herd level and include vaccination, mass treatment with antimicrobials and improvement of the animal's environment and general health status. Despite progress in our understanding of disease mechanism and technological development, the current preventive measures are not sufficiently effective. Thus, there is a need for alternative, sustainable strategies to combat the disease. Some of the primary infectious agents in the BRD complex are viruses that are easily transmitted between herds such as bovine respiratory syncytial virus (BRSV) and bovine coronavirus (BCoV). This conceptual analysis presents arguments for combatting BRD through improved external biosecurity in the cattle herds. As an example of a population-based approach to the control of BRD, the Norwegian BRSV/BCoV control-program is presented. The program is voluntary and launched by the national cattle industry. The core principle is classification of herds based on antibody testing and subsequent prevention of virus-introduction through improved biosecurity measures. Measures include external herd biosecurity barriers and regulations in the organization of animal trade to reduce direct and indirect transmission of virus. Improved biosecurity in a large proportion of herds will lead to a considerable effect at the population level. Positive herds are believed to gain freedom by time if new introduction is avoided. Vaccination is not used as part of the program. Dissemination of information to producers and veterinarians is essential. We believe that reducing the incidence of BRD in cattle is essential and will lead to reduced antimicrobial usage while at the same time improving animal health, welfare and production. Alternative approaches to the traditional control measures are needed.