Miracle-dz/UniFAR-FTUs huggingface dataset:
Densely Distilled Flow-Based Knowledge Transfer in Teacher-Student Framework for Image Classification

We propose a new teacher–student framework (TSF)-based knowledge transfer method, in which knowledge in the form of dense flow across layers is distilled from a pre-trained “teacher” deep neural network (DNN) and transferred to another “student” DNN. In the case of distilled knowledge, multiple overlapped flow-based items of information from the pre-trained teacher DNN are densely extracted across layers. Transference of the densely extracted teacher information is then achieved in the TSF using repetitive sequential training from bottom to top between the teacher and student DNN models. In other words, to efficiently transmit extracted useful teacher information to the student DNN, we perform bottom-up step-by-step transfer of densely distilled knowledge. The performance of the proposed method in terms of image classification accuracy and fast optimization is compared with those of existing TSF-based knowledge transfer methods for application to reliable image datasets, including CIFAR-10, CIFAR-100, MNIST, and SVHN. When the dense flow-based sequential knowledge transfer scheme is employed in the TSF, the trained student ResNet more accurately reflects the rich information of the pre-trained teacher ResNet and exhibits superior accuracy to the existing TSF-based knowledge transfer methods for all benchmark datasets considered in this study.
Monitoring of Pseudorabies in Wild Boar of Germany—A Spatiotemporal Analysis

To evaluate recent developments regarding the epidemiological situation of pseudorabies virus (PRV) infections in wild boar populations in Germany, nationwide serological monitoring was conducted between 2010 and 2015. During this period, a total of 108,748 sera from wild boars were tested for the presence of PRV-specific antibodies using commercial enzyme-linked immunosorbent assays. The overall PRV seroprevalence was estimated at 12.09% for Germany. A significant increase in seroprevalence was observed in recent years indicating both a further spatial spread and strong disease dynamics. For spatiotemporal analysis, data from 1985 to 2009 from previous studies were incorporated. The analysis revealed that PRV infections in wild boar were endemic in all German federal states; the affected area covers at least 48.5% of the German territory. There were marked differences in seroprevalence at district levels as well as in the relative risk (RR) of infection of wild boar throughout Germany. We identified several smaller clusters and one large region, where the RR was two to four times higher as compared to the remaining areas under investigation. Based on the present monitoring intensity and outcome, we provide recommendations with respect to future monitoring efforts concerning PRV infections in wild boar in Germany.
Risk assessment in different Judo techniques for children and adolescent athletes

Judo is a combat sport that involves throwing the opponent onto the back. When being thrown, head biomechanics may be related to head injury risk. This study aimed to assess head injury risks associated with four Judo techniques in children and adolescents with different experience levels. Twenty children (<12 years) and 20 adolescents (≥ 12 years) judoka were recruited. Each group was divided into non-expert and expert. Two inertial sensors were fixed on fallers’ head and torso. Two backward (o-soto-gari and o-uchi-gari) and two forward (ippon-seoi-nage and tai-otoshi) techniques were performed. Peak of linear and angular head acceleration magnitude, impact time duration, neck angle, and the Gadd Severity Index were assessed. Children did not show differences between techniques or experience levels. In contrast, adolescents showed greater linear acceleration peak in o-soto-gari than tai-otoshi (p = 0.03), greater angular acceleration peak in o-soto-gari and o-uchi-gari than ippon-seoi-nage (p < 0.05), and greater neck flexion in o-uchi-gari than ippon-seoi-nage (p = 0.004). Compared to expert adolescents, non-expert adolescents showed greater angular acceleration peak, impact duration, and the Gadd Severity Index in o-soto-gari (p < 0.05) and greater neck extension in o-uchi-gari (p = 0.02). Current results pointed out higher risks for adolescents judoka while being thrown with backward techniques, especially for non-expert participants. This study highlights the need of training athletes in controlling head and neck during back falls from a young age to become expert judoka in adulthood.
Rcf2 revealed in cryo-EM structures of hypoxic isoforms of mature mitochondrial III-IV supercomplexes

Significance As the terminal electron acceptor of our mitochondrial respiratory chains, complex IV drives and regulates oxidative phosphorylation, the process by which most of our ATP is produced. Complex IV forms supercomplexes (SCs) of different stoichiometries with other respiratory proteins, interacting via its subunits with tissue-specific or oxygen level-dependent expression isoforms, suggesting a link between SC assembly and metabolic/disease state. We investigated the effect of complex IV subunit isoform exchange in yeast using cryo-EM and biochemical assays and found no significant differences in overall SC formation, architecture, or catalytic activities. However, our structural work unexpectedly revealed the presence of a Hig1 protein which we propose is a stoichiometric subunit of complex IV, at least when within a SC with complex III. The organization of the mitochondrial electron transport chain proteins into supercomplexes (SCs) is now undisputed; however, their assembly process, or the role of differential expression isoforms, remain to be determined. In Saccharomyces cerevisiae, cytochrome c oxidase (CIV) forms SCs of varying stoichiometry with cytochrome bc1 (CIII). Recent studies have revealed, in normoxic growth conditions, an interface made exclusively by Cox5A, the only yeast respiratory protein that exists as one of two isoforms depending on oxygen levels. Here we present the cryo-EM structures of the III2-IV1 and III2-IV2 SCs containing the hypoxic isoform Cox5B solved at 3.4 and 2.8 Å, respectively. We show that the change of isoform does not affect SC formation or activity, and that SC stoichiometry is dictated by the level of CIII/CIV biosynthesis. Comparison of the CIV5B- and CIV5A-containing SC structures highlighted few differences, found mainly in the region of Cox5. Additional density was revealed in all SCs, independent of the CIV isoform, in a pocket formed by Cox1, Cox3, Cox12, and Cox13, away from the CIII–CIV interface. In the CIV5B-containing hypoxic SCs, this could be confidently assigned to the hypoxia-induced gene 1 (Hig1) type 2 protein Rcf2. With conserved residues in mammalian Hig1 proteins and Cox3/Cox12/Cox13 orthologs, we propose that Hig1 type 2 proteins are stoichiometric subunits of CIV, at least when within a III-IV SC.
The Role of Alternative Lengthening of Telomeres Mechanism in Cancer: Translational and Therapeutic Implications

Telomere maintenance mechanisms (i.e., telomerase activity (TA) and the alternative lengthening of telomere (ALT) mechanism) contribute to tumorigenesis by providing unlimited proliferative capacity to cancer cells. Although the role of either telomere maintenance mechanisms seems to be equivalent in providing a limitless proliferative ability to tumor cells, the contribution of TA and ALT to the clinical outcome of patients may differ prominently. In addition, several strategies have been developed to interfere with TA in cancer, including Imetelstat that has been the first telomerase inhibitor tested in clinical trials. Conversely, the limited information available on the molecular underpinnings of ALT has hindered thus far the development of genuine ALT-targeting agents. Moreover, whether anti-telomerase therapies may be hampered or not by possible adaptive responses is still debatable. Nonetheless, it is plausible hypothesizing that treatment with telomerase inhibitors may exert selective pressure for the emergence of cancer cells that become resistant to treatment by activating the ALT mechanism. This notion, together with the evidence that both telomere maintenance mechanisms may coexist within the same tumor and may distinctly impinge on patients’ outcomes, suggests that ALT may exert an unexpected role in tumor biology that still needs to be fully elucidated.
Behavioral and Electrophysiological Responses of the Fringed Larder Beetle Dermestes frischii to the Smell of a Cadaver at Different Decomposition Stages

A cadaver is colonized by a wide diversity of necrophagous insects. It is well documented that Dipterans are attracted by the volatile organic compounds (VOCs) released by a corpse during the first minutes following death. Coleopterans are known to be attracted by highly decomposed cadavers, but have received less attention regarding the olfaction-based mechanisms underlying these interactions. In the present study, we impregnated gauzes with VOCs collected from each decomposition stage of dead rats: fresh, bloated, active, and advanced decay. We collected the VOCs released by the gauze and confirmed what was previously know from the literature: the decomposition stages are associated with contrasting chemical profiles. We exposed Dermestes frischii Kugelann (Coleoptera: Dermestidae) male and female antennae to the same gauzes and found that stronger electrical responses were recorded when using the smell of the advanced decay stage. Finally, we performed two choices behavioral assays. Females showed no preference for the four decomposition stages, while males were attracted by the smell associated with active and advanced decay stages. These results suggest that specific VOCs released by a decaying body guide necrophagous coleopterans to their feeding site. Whether D. frischii males release pheromones to attract females remains to be tested.
Design of temozolomide-loaded proliposomes and lipid crystal nanoparticles with industrial feasible approaches: comparative assessment of drug loading, entrapment efficiency, and stability at plasma pH

Abstract Temozolomide is a drug approved for treating glioblastomas, which has 100% oral bioavailability but gets degraded at physiological pH thus having very short half-life and only 20–30% brain bioavailability. Due to its amphiphilic nature, reported nanoformulations exhibits poor drug loading. The objective of this work was to formulate lipid-based drug delivery systems to enhance the brain bioavailability by prolonging the drug release and circulation time of the drug to overcome the limitations of the existing therapies and possible reduction of side effects. The size of the nanocarriers obtained was less than 300 nm and the PDI obtained was less than 0.3. The designed formulation showed higher entrapment efficiency as compared to the other reported nanocarriers of temozolomide. The designed formulations showed prolonged drug release from 12 to 20 h compared to 6 h for the pure drug. About 95% of the pure drug was degraded at plasma pH at the end of 12 h, whereas only 68% and 77% was degraded when entrapped inside the lipid crystal nanoparticles and proliposomes respectively. Further, pharmacokinetic and animal studies can confirm the potential of these for improvement of brain bioavailability.
Extreme Genomic CpG Deficiency in SARS-CoV-2 and Evasion of Host Antiviral Defense

Abstract Wild mammalian species, including bats, constitute the natural reservoir of betacoronavirus (including SARS, MERS, and the deadly SARS-CoV-2). Different hosts or host tissues provide different cellular environments, especially different antiviral and RNA modification activities that can alter RNA modification signatures observed in the viral RNA genome. The zinc finger antiviral protein (ZAP) binds specifically to CpG dinucleotides and recruits other proteins to degrade a variety of viral RNA genomes. Many mammalian RNA viruses have evolved CpG deficiency. Increasing CpG dinucleotides in these low-CpG viral genomes in the presence of ZAP consistently leads to decreased viral replication and virulence. Because ZAP exhibits tissue-specific expression, viruses infecting different tissues are expected to have different CpG signatures, suggesting a means to identify viral tissue-switching events. The author shows that SARS-CoV-2 has the most extreme CpG deficiency in all known betacoronavirus genomes. This suggests that SARS-CoV-2 may have evolved in a new host (or new host tissue) with high ZAP expression. A survey of CpG deficiency in viral genomes identified a virulent canine coronavirus (alphacoronavirus) as possessing the most extreme CpG deficiency, comparable with that observed in SARS-CoV-2. This suggests that the canine tissue infected by the canine coronavirus may provide a cellular environment strongly selecting against CpG. Thus, viral surveys focused on decreasing CpG in viral RNA genomes may provide important clues about the selective environments and viral defenses in the original hosts.
Magnetic resonance imaging and gasless laparoendoscopic single‐site surgery for the diagnosis and management of isolated tubal torsion with a paratubal cyst at 31 weeks of gestation: A case report and literature review

A 30‐year‐old nulliparous woman was transferred under suspicion of acute appendicitis, due to the sudden onset of severe right lower quadrant pain at 31 weeks and 4 days of gestation. Magnetic resonance imaging showed a cystic mass measuring 40 mm in diameter in the right lower abdomen. Because the right ovary without edematous swelling was noted adjacent to the cystic mass, isolated tubal torsion was strongly suspected. Emergency gasless laparoendoscopic single‐site surgery showed isolated torsion of the right fallopian tube with a paratubal cyst. The right ovary was not involved in this torsion. Because the color tone of the distal portion of the fallopian tube did not recover sufficiently after detorsion, right salpingectomy was performed. Postoperatively, the infusion of magnesium sulfate was initiated due to increased uterine contraction and continued until 36 weeks of gestation. At 38 weeks and 1 day of gestation, uneventful vaginal delivery yielded a healthy female infant.
Ageing of Dental Composites Based on Methacrylate Resins—A Critical Review of the Causes and Method of Assessment

The paper reviews the environmental factors affecting ageing processes, and the degradation of resins, filler, and the filler-matrix interface. It discusses the current methods of testing materials in vitro. A review of literature was conducted with the main sources being PubMed. ScienceDirect, Mendeley, and Google Scholar were used as other resources. Studies were selected based on relevance, with a preference given to recent research. The ageing process is an inherent element of the use of resin composites in the oral environment, which is very complex and changes dynamically. The hydrolysis of dental resins is accelerated by some substances (enzymes, acids). Bonds formed between coupling agent and inorganic filler are prone to hydrolysis. Methods for prediction of long-term behaviour are not included in composite standards. Given the very complex chemical composition of the oral environment, ageing tests based on water can only provide a limited view of the clinical performance of biomaterial. Systems that can reproduce dynamic changes in stress (thermal cycling, fatigue tests) are better able to mimic clinical conditions and could be extremely valuable in predicting dental composite clinical performance. It is essential to identify procedure to determine the ageing process of dental materials.
Differences in behavior between surface and cave Astyanax mexicanus may be mediated by changes in catecholamine signaling

Astyanax mexicanus is a teleost fish that is in the process of allopatric speciation. Ancestral Astyanax are found in surface rivers and derived blind forms are found in cave systems. Adaptation to life in nutrient poor caves without predation includes the evolution of enhanced food seeking behaviors and loss of defensive responses. These behavioral adaptations may be mediated by changes in catecholaminergic control systems in the brain. We examined the distribution of tyrosine hydroxylase, a conserved precursor for the synthesis of the catecholamines dopamine and noradrenaline, in the brains of surface and cave Astyanax using immunohistochemistry. We found differences in tyrosine hydroxylase staining in regions that are associated with nonvisual sensory perception, motor control, endocrine release, and attention. These differences included significant increases in the diameters of tyrosine hydroxylase immunoreactive soma in cave Astyanax in the olfactory bulb, basal telencephalon, preoptic nuclei, ventral thalamus, posterior tuberculum, and locus coeruleus. These increases in modulation by dopamine and noradrenaline likely indicate changes in behavioral control that underlie adaptations to the cave environment.
The Relationship of IL-8 and IL-10 Myokines and Performance in Male Marathon Runners Presenting Exercise-Induced Bronchoconstriction

At present, it is unclear which exercise-induced factors, such as myokines, could diminish the negative impact of the reduction in pulmonary function imposed by the exercise in question. In this study, we aim to evaluate the prevalence of exercise-induced bronchoconstriction (EIB) and also to investigate the effect of myokines in the performance of marathon runners presenting EIB or not. Thirty-eight male recreational marathon runners (age 38.8 [33–44], height 175.7 [172.0–180.3]; weight 74.7 [69.3–81.6]) participated in this study, and through spirometry tests, a prevalence of 23.6% of EIB was found, which is in agreement with the literature. The volunteers who tested positive to EIB (EIB+) presented lower maximum aerobic capacity compared to those who tested negative (EIB−) (EIB+ 44.02 [39.56–47.02] and EIB− 47.62 [44.11–51.18] p = 0.03). The comparison of plasma levels of IL-1β (EIB+ p = 0.296, EIB− p = 0.176, EIB+ vs. EIB− baseline p = 0.190 immediately after p = 0.106), IL-4 (undetectable), IL-6 (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.301 immediately after p = 0.614), IL-8 (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.110 immediately after p = 0.453), IL-10 (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.424 immediately after p = 0.876) and TNF-α (EIB+ p = 0.003, EIB− p ≤ 0.001, EIB+ vs. EIB− baseline p = 0.141 immediately after p = 0.898) were similar in both groups 24 h before and immediately after the marathon. However, negative correlations were found between the marathon finishing time and the levels of IL-8 (r = −0.81, p = 0.022), and IL-10 (r = −0.97, p ≤ 0.001) immediately after completing the marathon. In conclusion, for the first time, it is shown that the myokines IL-8 and IL-10 are related to improvement of the performance of marathon runners presenting EIB.
Characterization of the SIM-A9 cell line as a model of activated microglia in the context of neuropathic pain

Resident microglia of the central nervous system are being increasingly recognized as key players in diseases such as neuropathic pain. Biochemical and behavioral studies in neuropathic pain rodent models have documented compelling evidence of the critical role of ATP mediated-P2X4R-brain-derived neurotrophic factor (BDNF) signaling pathway in the initiation and maintenance of pain hypersensitivity, a feature driving neuropathic pain-related behavior. The goal of this study was to develop and characterize an in vitro cell line model of activated microglia that can be subsequently utilized for screening neuropathic pain therapeutics. In the present study, we characterized the SIM-A9 microglia cell line for key molecules in the P2X4R-BDNF signaling axis using a combination of biochemical techniques and developed an ATP-activated SIM-A9 microglia model. We present three novel findings: first, SIM-A9 cells expressed P2X4R and BDNF proteins, second, ATP, but not LPS, was cytocompatible with SIM-A9 cells and third, exposure of cells to optimized ATP concentrations for defined periods increased intracellular expression of Iba1 and BDNF proteins. Increased Iba1 levels confirmed microglia activation and increased BDNF expression confirmed ATP-mediated stimulation of the P2X4R signaling pathway. We propose that this ATP-activated SIM-A9 cell line model system can be utilized for screening both small- as well as macro-molecular neuropathic pain therapeutics targeting BDNF and/or P2X4R knockdown.
Feeding brown fat: dietary phytochemicals targeting non-shivering thermogenesis to control body weight

Excessive adipose accumulation, which is the main driver for the development of secondary metabolic complications, has reached epidemic proportions and combined pharmaceutical, educational and nutritional approaches are required to reverse the current rise in global obesity prevalence rates. Brown adipose tissue (BAT) is a unique organ able to dissipate energy and thus a promising target to enhance BMR to counteract a positive energy balance. In addition, active BAT might support body weight maintenance after weight loss to prevent/reduce relapse. Natural products deliver valuable bioactive compounds that have historically helped to alleviate disease symptoms. Interest in recent years has focused on identifying nutritional constituents that are able to induce BAT activity and thereby enhance energy expenditure. This review provides a summary of selected dietary phytochemicals, including isoflavones, catechins, stilbenes, the flavonoids quercetin, luteolin and resveratrol as well as the alkaloids berberine and capsaicin. Most of the discussed phytochemicals act through distinct molecular pathways e.g. sympathetic nerve activation, AMP-kinase signalling, SIRT1 activity or stimulation of oestrogen receptors. Thus, it might be possible to utilise this multitude of pathways to co-activate BAT using a fine-tuned combination of foods or combined nutritional supplements.
Biosensors Platform Based on Chitosan/AuNPs/Phthalocyanine Composite Films for the Electrochemical Detection of Catechol. The Role of the Surface Structure

Biosensor platforms consisting of layer by layer films combining materials with different functionalities have been developed and used to obtain improved catechol biosensors. Tyrosinase (Tyr) or laccase (Lac) were deposited onto LbL films formed by layers of a cationic linker (chitosan, CHI) alternating with layers of anionic electrocatalytic materials (sulfonated copper phthalocyanine, CuPcS or gold nanoparticles, AuNP). Films with different layer structures were successfully formed. Characterization of surface roughness and porosity was carried out using AFM. Electrochemical responses towards catechol showed that the LbL composites efficiently improved the electron transfer path between Tyr or Lac and the electrode surface, producing an increase in the intensity over the response in the absence of the LbL platform. LbL structures with higher roughness and pore size facilitated the diffusion of catechol, resulting in lower LODs. The [(CHI)-(AuNP)-(CHI)-(CuPcS)]2-Tyr showed an LOD of 8.55∙10−4 μM, which was one order of magnitude lower than the 9.55·10−3 µM obtained with [(CHI)-(CuPcS)-(CHI)-(AuNP)]2-Tyr, and two orders of magnitude lower than the obtained with other nanostructured platforms. It can be concluded that the combination of adequate materials with complementary activity and the control of the structure of the platform is an excellent strategy to obtain biosensors with improved performances.