Miracle-dz/UniFAR-FTUs huggingface dataset:
The therapeutic benefits of combined sorafenib and transarterial chemoembolization for advanced hepatocellular carcinoma

Systemic therapy, such as sorafenib, has been used clinically to treat patients with advanced stage or Barcelona Clinic Liver Cancer staging system (BCLC) stage C hepatocellular carcinoma (HCC). The aim of the study was to evaluate the therapeutic benefit of combined sorafenib and transarterial chemoembolization (TACE) in this group of patients.
Influence of curcumin on performance and post-exercise recovery

Abstract Intense exercise, especially involving eccentric contractions, causes muscle damage concomitant with increased reactive oxygen species (ROS), which can lead to increased fatigue and decrements in physical performance. Additionally, inflammatory cytokines and advanced glycation end-products (AGEs) are produced as a result of eccentric exercise and may further lead to decreased exercise performance. Nutritional interventions may provide an avenue to respond to and reduce the symptoms associated with muscle damage. Of recent interest, curcumin, the main constituent in the spice turmeric, has been the focus of various studies considering post-exercise recovery. Curcumin has potent anti-oxidant and anti-inflammatory properties and can reduce the accumulation of AGEs. This review considers the current evidence for curcumin to impact muscle recovery following exercise to improve performance and the potential mechanisms of action. To date, clinical studies have considered the potential role of curcumin to reduce muscular damage following treadmill running (downhill and flat), conventional walking/running, cycling (acute and chronic), single-leg jumping (downhill), and eccentric muscular fitness exercises of the upper and lower body (single- and double-leg). Studies have been conducted in sedentary to highly active men and women, both young and old, with supplementation duration lasting from a single, acute dose to daily dosages for three months. Various curcumin-based interventions have improved self-perceived measures of pain and tenderness, reduced evidence of muscle damage, ameliorated inflammatory markers, increased markers of antioxidant capacity, diminished markers of oxidative stress, reduced markers of AGEs, and attenuated loss in mean power of single-leg sprints. However, these findings have not been consistently reported.
Salmonella Pathogenicity Island 1 (SPI-1): The Evolution and Stabilization of a Core Genomic Type Three Secretion System

Salmonella Pathogenicity Island 1 (SPI-1) encodes a type three secretion system (T3SS), effector proteins, and associated transcription factors that together enable invasion of epithelial cells in animal intestines. The horizontal acquisition of SPI-1 by the common ancestor of all Salmonella is considered a prime example of how gene islands potentiate the emergence of new pathogens with expanded niche ranges. However, the evolutionary history of SPI-1 has attracted little attention. Here, we apply phylogenetic comparisons across the family Enterobacteriaceae to examine the history of SPI-1, improving the resolution of its boundaries and unique architecture by identifying its composite gene modules. SPI-1 is located between the core genes fhlA and mutS, a hotspot for the gain and loss of horizontally acquired genes. Despite the plasticity of this locus, SPI-1 demonstrates stable residency of many tens of millions of years in a host genome, unlike short-lived homologous T3SS and effector islands including Escherichia ETT2, Yersinia YSA, Pantoea PSI-2, Sodalis SSR2, and Chromobacterium CPI-1. SPI-1 employs a unique series of regulatory switches, starting with the dedicated transcription factors HilC and HilD, and flowing through the central SPI-1 regulator HilA. HilA is shared with other T3SS, but HilC and HilD may have their evolutionary origins in Salmonella. The hilA, hilC, and hilD gene promoters are the most AT-rich DNA in SPI-1, placing them under tight control by the transcriptional repressor H-NS. In all Salmonella lineages, these three promoters resist amelioration towards the genomic average, ensuring strong repression by H-NS. Hence, early development of a robust and well-integrated regulatory network may explain the evolutionary stability of SPI-1 compared to T3SS gene islands in other species.
New dehydroabietic acid (DHA) derivatives with anticancer activity against HepG2 cancer cell lines as a potential drug targeting EGFR kinase domain. CoMFA study and virtual ligand-based screening

Abstract Liver cancer has become the third type of cancer that causes death; this is why the design of new chemotherapeutic drugs against this disease is a major need. With this idea, a series of Dehydroabietic Acid-Based Acylhydrazones have been used to generate a CoMFA model to design new anticancer agents. In this study, we employed a Comparative Molecular Field Analysis studies, we performed those methods on Dehydroabietic Acid-Based Acylhydrazones against HepG2 human cancer cell line. The statistical results are encouraging with Q2 equal to 0.527 and R2 equal to 0.962. The predictive ability of this model was determined using a test set of Dehydroabietic Acid-Based Acylhydrazones that gave an acceptable predictive correlation (R2test) value of 0.614. The developed model guides to design five new molecules with enhanced activity as potential drugs. On the other hand to determine a potential target to these ligands we have established a virtual screening using reverse docking with the most active molecule and 42 antiproliferative targets. Based on the affinity of complex ligand-Target, the intracellular domain of EGFR shows high stability. This suggests that our designed molecules can inhibit the target EGFR which is an important target on targeted therapy of many types of cancer. Communicated by Ramaswamy H. Sarma
Promoting platelets is a therapeutic option to combat severe viral infection of the lung

Jiahuang Qiu, Juan Ma, Shuping Zhang, Jinxiang Han, and Sijin Liu State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China; and Department of Hematology, The First Affiliated Hospital & Shandong Medicinal Biotechnology Center, and University Creative Research Initiatives Center, Shandong First Medical University, Jinan, China
Prognostic significance of an invasive leader cell–derived mutation cluster on chromosome 16q

Intratumoral heterogeneity is defined by subpopulations with varying genotypes and phenotypes. Specialized, highly invasive leader cells and less invasive follower cells are phenotypically distinct subpopulations that cooperate during collective cancer invasion. Because leader cells are a rare subpopulation that would be missed by bulk sequencing, a novel image‐guided genomics platform was used to precisely select this subpopulation. This study identified a novel leader cell mutation signature and tested its ability to predict prognosis in non–small cell lung cancer (NSCLC) patient cohorts.
Controlling Blood Pressure Under Transcranial Doppler Guidance after Endovascular Treatment in Patients with Acute Ischemic Stroke

Objective: This study aimed to control blood pressure (BP) under transcranial Doppler (TCD) guidance in patients with anterior circulation acute ischemic stroke after endovascular treatment (EVT) to reduce the incidence of early neurological deterioration (END) and improve neurological prognosis. Methods: This prospective randomized controlled study included 95 patients who were randomly divided into a TCD-guided BP control (TBC) group and a non-TCD-guided BP control (NBC) group. The patients were monitored by TCD within 72 h after EVT. In the TBC group, BP decreased, BP increased, or intracranial pressure decreased when TCD showed blood flow acceleration, deceleration, or intracranial hypertension respectively. The BP of the NBC group was controlled according to the guidelines. The incidence of END and the prognosis was compared between the 2 groups. Results: TCD identified 18 patients with blood flow acceleration, but the prognosis of the 2 groups was not significantly different. TCD identified 23 patients with blood flow deceleration, and the poor prognosis rate at discharge was lower in the TBC group than in the NBC group (45.5 vs. 91.7%, p = 0.027). TCD identified 34 patients with intracranial hypertension, and the 3-month mortality rate of the TBC group was lower than that of the NBC group (0 vs. 36.8%, p = 0.011). The incidence rates of END and 3-month mortality in the TBC group were lower than those in the NBC group (13.8 vs. 37.5%, p = 0.036; 0 vs. 25.0%, p = 0.012) when TCD parameters were abnormal. Multivariable logistic regression analysis showed that the TBC group (adjusted OR 0.267, 95% CI 0.074–0.955; p = 0.042) was an independent protective factor against the incidence of END when TCD parameters were abnormal. Conclusion: These findings indicated that TCD-guided BP and intracranial pressure control improved the prognosis of patients with blood flow deceleration and intracranial hypertension.
Olive Cake Meal and Bacillus licheniformis Impacted the Growth Performance, Muscle Fatty Acid Content, and Health Status of Broiler Chickens

Simple Summary The extraction of oils from olives usually results in large quantities of olive cake meal (OCM), which has a high nutritional value. The OCM is used successfully in livestock and poultry feeding, but due to the high fiber content, alternative methods of treating OCM must be considered. To increase the efficiency of OCM in broiler chickens’ diet, it can be mixed with suitable microorganisms with beneficial effects. Hence, the current study investigated the influence of OCM and Bacillus licheniformis (BL) on the growth, nutrient utilization, blood chemistry, and muscle fatty acid profile of broilers. Birds were divided into six experimental groups (control, OCM (2%), OCM (4%), BL, OCM (2%)/BL, and OCM (4%)/BL groups). The results revealed that the inclusion of BL with OCM diets improved the fat utilization and, accordingly, increased the growth, nutrient utilization, and antioxidative response in broilers. Abstract Olive cake meal (OCM) is characterized by its high nutritional value and is used as an alternative source of protein and fats in poultry diets. However, due to the high percentage of fiber in OCM, beneficial bacteria cells are used to improve the digestion rates. Therefore, the influence of OCM and Bacillus licheniformis (BL) on the growth, nutrient utilization, blood chemistry, and muscle fatty acid profile of broilers was exclusively examined in this study. Three hundred and sixty birds were randomly divided into six experimental groups (6 replicates/10 birds each): Control, OCM (2%), OCM (4%), BL, OCM (2%)/BL, and OCM (4%)/BL groups. Although feed intake was not meaningfully influenced by dietary treatments, weight gain was enhanced and feed conversion ratio was reduced (p < 0.05). The abdominal fat was lowered in broilers fed OCM (2%), OCM (4%), OCM (2%)/BL, and OCM (4%)/BL diets without a difference to those fed BL only (p < 0.05). Interestingly, blood total protein, albumin, Newcastle disease (ND) titer, and high-density lipoprotein (HDL) cholesterol were significantly increased, while total cholesterol was decreased by the mixture of OCM and BL (p < 0.05). Muscle oleic and linoleic acids, as well as vitamin E, increased significantly in broilers fed both OCM (4%) and BL, while linolenic acid increased in all groups except those fed BL and control diets (p < 0.05). Liver malondialdehyde (MDA) was decreased by feeding BL or both OCM at 2% or 4% and BL (p < 0.05). In conclusion, the inclusion of BL to OCM diets resulted in improved fat utilization and, accordingly, enhanced growth, nutrient utilization, and antioxidative response in broilers. Based on the obtained results, it is recommended to use BL to improve the nutritional value of OCM and to increase the feed utilization of OCM by broilers.
COVID‐19: searching for clues among other respiratory viruses

The respiratory tract requires robust immune defenses because of its constant exposure to antigens—air pollutants, allergens and microbes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the respiratory virus that causes coronavirus disease 2019 (COVID-19), poses a challenge to our immune system in the infected lungs as well as globally in the prevention of its spread. Following the declaration of pandemic status by the World Health Organization, researchers worldwide have been called to arms to develop diagnostic tools, treatments and prophylactic vaccines to combat the COVID-19 outbreak. There has been an increasingly rapid stream of information made immediately accessible online at an unprecedented rate, and this information provides a description of the pandemic in real time. Many key questions about COVID-19, however, remain unanswered because this virus is a new human pathogen and because there is a significant time lag from an individual becoming infected, to then becoming symptomatic, to seeking care and finally being confirmed and reported. In mid-January, there were only 41 laboratory-confirmed cases, and now there are over 1 915 000 confirmed cases. New diagnoses will always precede recovery (or death) by days to weeks, meaning that what we see in real time is merely the tip of the iceberg. Regional differences in case reporting and number of people tested, and the skewing of those cases being reported toward those with greater severity have made it difficult to predict the outbreak dynamics and determine effective prevention measures (e.g. mortality rate, transmissibility). To fill the knowledge gap as we increase our knowledge of SARSCoV-2, outbreak measures have also largely been based on knowledge of similar respiratory viruses. In this trending Virtual Issue of Immunology & Cell Biology, we present a series of reviews and original articles that highlight key defense mechanisms employed against various respiratory viruses, with an emphasis on influenza. We hope this collection will provide clues for improving immunity to SARS-CoV-2, and preventing severe and lifethreatening complications resulting from COVID-19. Innate immune cells, such as airway macrophages and dendritic cells, form part of the first line of defense in the respiratory tract. Previous infections or vaccinations support the development of specific adaptive immunity including mucosal antibodies and tissue-resident memory T cells, which join the innate immune system in the frontline defenses. This issue pulls together aspects of innate and adaptive defenses as depicted in Figure 1 to better understand our immune defenses against respiratory viruses. Sensing by the innate immune system via pathogen recognition receptors is critical to establish protective immunity against respiratory viruses. Mifsud et al. (1 in Figure 1) demonstrated that the Toll-like receptor 2 agonist,
Spatiotemporally precise optogenetic activation of sensory neurons in freely walking Drosophila

Previous work has characterized how walking Drosophila coordinate the movements of individual limbs (DeAngelis et al., 2019). To understand the circuit basis of this coordination, one must characterize how sensory feedback from each limb affects walking behavior. However, it has remained difficult to manipulate neural activity in individual limbs of freely moving animals. Here, we demonstrate a simple method for optogenetic stimulation with body side-, body segment-, and limb-specificity that does not require real-time tracking. Instead, we activate at random, precise locations in time and space and use post hoc analysis to determine behavioral responses to specific activations. Using this method, we have characterized limb coordination and walking behavior in response to transient activation of mechanosensitive bristle neurons and sweet-sensing chemoreceptor neurons. Our findings reveal that activating these neurons has opposite effects on turning, and that activations in different limbs and body regions produce distinct behaviors.
MIMU/Odometer Fusion with State Constraints for Vehicle Positioning during BeiDou Signal Outage: Testing and Results

With the rapid development of autonomous vehicles, the demand for reliable positioning results is urgent. Currently, the ground vehicles heavily depend on the Global Navigation Satellite System (GNSS) and the Inertial Navigation System (INS) providing reliable and continuous navigation solutions. In dense urban areas, especially narrow streets with tall buildings, the GNSS signals are possibly blocked by the surrounding tall buildings, and under this condition, the geometry distribution of the in-view satellites is very poor, and the None-Line-Of-Sight (NLOS) and Multipath (MP) heavily affects the positioning accuracy. Further, the INS positioning errors will quickly diverge over time without the GNSS correction. Aiming at improving the position accuracy under signal challenging environment, in this paper, we developed an MIMU(Micro Inertial Measurement Unit)/Odometer integration system with vehicle state constraints (MO-C) for improving the vehicle positioning accuracy without GNSS. MIMU/Odometer integration model and the constrained measurements are given in detail. Several field tests were carried out for evaluating and assessing the MO-C system. The experiments were divided into two parts, firstly, field testing with data post-processing and real-time processing was carried out for fully assessing the performance of the MO-C system. Secondly, the MO-C was implemented in the BeiDou Satellite Navigation System (BDS)/integrated navigation system (INS) for evaluating the MO-C performance during the BDS signal outage. The MIMU standalone positioning accuracy was compared with that from the MIMU/Odometer integration (MO), MO-C and MIMU with constraints (M-C) for assessing the Odometer, and the influence of the constraint on the positioning errors reduction. The results showed that the latitude and longitude errors could be suppressed with Odometer assisting, and the height errors were suppressed while the state constraints were included.
Différences ethniques et saisonnières du statut en vitamine D chez les étudiants au Québec : une étude de cohorte

Lack of sun exposure is a major risk factor of vitamin D deficiency, which is more pronounced in countries of high latitudes and in black people. Serum concentrations of vitamin D, intrinsic and extrinsic factors, which may influence vitamin D status, were measured 3 times (fall 2010, winter and summer 2011) in a sample of volunteer students living in Quebec City. A total of 65 participants including 29 Africans students and 36 Quebecers students completed the study. Vitamin D concentrations changed over the seasons. They are particularly low among African participants. Vitamin D concentrations were significantly correlated with race, body mass index (BMI), and seasons. The low vitamin D status of students in Quebec City and particularly among Africans students is a public health concern that should be explored further.
Sexual attraction modulates interpersonal distance and approach-avoidance movements towards virtual agents in males

How does sexual attraction alter social interaction behavior? We examined the influence of sexual orientation on locomotor approach-avoidance behavior and interpersonal distance. We immersed androphilic and gynophilic male subjects into a virtual environment and presented various male and female virtual persons. In the first experiment, subjects took a step forward (approach) or backward (avoidance) in response to the sex of the virtual person. We measured reaction time, peak velocity, and step size, and obtained ratings of sexual attractiveness in every trial. In the second experiment, subjects had to approach the virtual person as if they were to engage in a social interaction. Here, we analyzed interpersonal distance and peak velocity of the approaches. Our results suggest that sexual attraction facilitates the approach response and reduces the preferred interpersonal distance. We discuss our findings in terms of proxemics, current findings in sex research, and the applicability of our novel task in other fields of psychological research.
Therapeutic drug monitoring of adalimumab in RA: no predictive value of adalimumab serum levels and anti-adalimumab antibodies for prediction of response to the next bDMARD

Background After adalimumab treatment failure, tumour necrosis factor inhibition (TNFi) and non-TNFi biological disease-modifying anti-rheumatic drugs (bDMARDs) are equally viable options on a group level as subsequent treatment in rheumatoid arthritis (RA) based on the current best evidence synthesis. However, preliminary data suggest that anti-adalimumab antibodies (anti-drug antibodies, ADA) and adalimumab serum levels (ADL) during treatment predict response to a TNFi as subsequent treatment. Objective To validate the association of presence of ADA and/or low ADL with response to a subsequent TNFi bDMARD or non-TNFi bDMARD. Sub-analyses were performed for primary and secondary non-responders. Methods A diagnostic test accuracy retrospective cohort study was done in consenting RA patients who discontinued adalimumab after >3 months of treatment due to inefficacy and started another bDMARD. Inclusion criteria included the availability of (random timed) serum samples between ≥8 weeks after start and ≤2 weeks after discontinuation of adalimumab, and clinical outcome measurements Disease Activity Score in 28 joints - C-reactive protein (DAS28-CRP) between 3 to 6 months after treatment switch. Test characteristics for EULAR (European League Against Rheumatism) good response (DAS28-CRP based) after treatment with the next (non-)TNFi bDMARD were assessed using area under the receiver operating characteristic and sensitivity/specificity. Results 137 patients were included. ADA presence was not predictive for response in switchers to a TNFi (sensitivity/specificity 18%/75%) or a non-TNFi (sensitivity/specificity 33%/70%). The same was true for ADL levels in patients that switched to a TNFi (sensitivity/specificity 50%/52%) and patients that switched to a non-TNFi (sensitivity/specificity 32%/69%). Predictive value of ADA and ADL were similar for both primary and secondary non-responders to adalimumab. Conclusions In contrast to earlier research, we could not find predictive value for response to a second TNFi or non-TNFi for either ADA or random timed ADL.