Miracle-dz/UniFAR-FTUs huggingface dataset:
Factor XII-Deficient Chicken Plasma as a Useful Target for Screening of Pro- and Anticoagulant Animal Venom Toxins

The sensitivity of vertebrate citrated plasma to pro- and anticoagulant venom or toxins occurs on a microscale level (micrograms). Although it improves responses to agonists, recalcification triggers a relatively fast thrombin formation process in mammalian plasma. As it has a natural factor XII deficiency, the recalcification time (RT) of chicken plasma (CP) is comparatively long [≥ 1800 seconds (s)]. Our objective was to compare the ability of bee venom phospholipase A2 (bvPLA2) to neutralize clot formation induced by an activator of coagulation (the aPTT clot) in recalcified human and chicken plasmas, through rotational thromboelastometry. The strategy used in this study was to find doses of bvPLA2 that were sufficient enough to prolong the clotting time (CT) of these activated plasmas to values within their normal RT range. The CT of CP was prolonged in a dose-dependent manner by bvPLA2, with 17 ± 2.8 ng (n = 6) being sufficient to displace the CT values of the activated samples to ≥ 1800 s. Only amounts up to 380 ± 41 ng (n = 6) of bvPLA2 induced the same effect in activated human plasma samples. In conclusion, the high sensitivity of CP to agonists and rotational thromboelastometry could be useful. For example, during screening procedures for assaying the effects of toxins in several stages of the coagulation pathway, such as clot initiation, formation, stability, strength, or dissolution.
Does experimentally induced pain-related fear influence central and peripheral movement preparation in healthy people and low back pain patients?

Non-specific chronic low back pain (CLBP) is a multifactorial disorder. Pain-related fear and altered movement preparation are considered to be key factors in the chronification process. Interactions between both have been hypothesized, but studies examining the influence of situational fear on movement preparation in low back pain (LBP) are wanting, as well as studies differentiating between recurrent LBP (RLBP) and CLBP. Therefore, this study examined whether experimentally induced pain-related fear influences movement preparation. In healthy controls (n=32), RLBP (n=31) and CLBP (n=30) patients central and peripheral measures of movement preparation were assessed by concurrently measuring trunk muscle anticipatory postural adjustments (APA) with EMG and Contingent Negative Variation (CNV) with EEG during performance of rapid arm movements (RAM). Two conditions were compared, one without (no fear) and one with (fear) possibility of painful stimulation to the back during RAM. Visual analogue scales were used to assess pain-related expectations/fear in both conditions. The experimentally induced fear of pain during movement performance led to an increase in CNV-amplitude, which was similar in all three groups. Concerning APAs no effects of fear were found, but group differences with generally delayed APAs in CLBP compared to controls and RLBP patients were evident. These results suggest that with fear an attentional redirection towards more conscious central movement preparation strategies occurs. Furthermore, differences in movement preparation in RLBP and CLBP patients exist, which could explain why RLBP patients have more recovery capabilities than CLBP.
Molecular and cellular mechanisms of tooth development, homeostasis and repair

ABSTRACT The tooth provides an excellent system for deciphering the molecular mechanisms of organogenesis, and has thus been of longstanding interest to developmental and stem cell biologists studying embryonic morphogenesis and adult tissue renewal. In recent years, analyses of molecular signaling networks, together with new insights into cellular heterogeneity, have greatly improved our knowledge of the dynamic epithelial-mesenchymal interactions that take place during tooth development and homeostasis. Here, we review recent progress in the field of mammalian tooth morphogenesis and also discuss the mechanisms regulating stem cell-based dental tissue homeostasis, regeneration and repair. These exciting findings help to lay a foundation that will ultimately enable the application of fundamental research discoveries toward therapies to improve oral health. Summary: This Review gives an overview of our current understanding of mammalian tooth morphogenesis and discusses recent findings relating to the regulation of stem cell-based dental tissue regeneration and repair.
Disease detection methodologies in relapsed B‐cell acute lymphoblastic leukemia: Opportunities for improvement

Accurate disease detection is integral to risk stratification in B‐cell acute lymphoblastic leukemia (ALL). The gold standard used to evaluate response in the United States includes morphologic evaluation and minimal residual disease (MRD) testing of aspirated bone marrow (BM) by flow cytometry (FC). This MRD assessment is usually made on a single aspirate sample that is subject to variability in collection techniques and sampling error. Additionally, central nervous system (CNS) assessments for ALL include evaluations of cytopathology and cell counts, which can miss subclinical involvement.
Changes in sleeping energy metabolism and thermoregulation during menstrual cycle

Women with ovulatory menstrual cycles show an increase in body temperature in the luteal phase, compared with follicular phase, particularly during the night. Several, albeit not all, studies reported higher energy expenditure in the luteal phase compared with follicular phase. Q10 of biological reactions lies between 2.0 and 3.0, predicting a 7‐12% increase in energy expenditure when body temperature rises by 1°C. In this study, temperature dependence of energy expenditure was assessed by comparing changes in sleeping energy expenditure and thermoregulation with menstrual cycle in 9 young females. Energy expenditure was measured using a metabolic chamber, in which sleep was recorded polysomnographically, and core body temperature and skin temperature were continuously monitored. Distal‐to‐proximal skin temperature gradient was assessed as an index of heat dissipation. In the luteal phase, a significant increase in average core body temperature (+0.27°C) and energy expenditure (+6.9%) were observed. Heat dissipation was suppressed during the first 2 hr of sleep in the luteal phase, compared with follicular phase. Rise in basal body temperature in the luteal phase was accompanied by increased energy expenditure and suppressed heat dissipation. The 6.9% increase in metabolic rate would require a Q10 of 12.4 to be attributable solely to temperature (+0.27°C), suggesting that energy expenditure in the luteal phase is enhanced through the mechanism, dependent and independent of luteal‐phase rise in body temperature presumably reflects other effects of the sex hormones.
An RNA pseudoknot stimulates HTLV-1 pro-pol programmed −1 ribosomal frameshifting

Programmed −1 ribosomal frameshifts (−1 PRFs) are commonly used by viruses to regulate their enzymatic and structural protein levels. Human T-cell leukemia virus type 1 (HTLV-1) is a carcinogenic retrovirus that uses two independent −1 PRFs to express viral enzymes critical to establishing new HTLV-1 infections. How the cis-acting RNA elements in this viral transcript function to induce frameshifting is unknown. The objective of this work was to conclusively define the 3′ boundary of and the RNA elements within the HTLV-1 pro-pol frameshift site. We hypothesized that the frameshift site structure was a pseudoknot and that its 3′ boundary would be defined by the pseudoknot's 3′ end. To test these hypotheses, the in vitro frameshift efficiencies of three HTLV-1 pro-pol frameshift sites with different 3′ boundaries were quantified. The results indicated that nucleotides included in the longest construct were essential to highly efficient frameshift stimulation. Interestingly, only this construct could form the putative frameshift site pseudoknot. Next, the secondary structure of this frameshift site was determined. The dominant structure was an H-type pseudoknot which, together with the slippery sequence, stimulated frameshifting to 19.4(±0.3)%. The pseudoknot's critical role in frameshift stimulation was directly revealed by examining the impact of structural changes on HTLV-1 pro-pol −1 PRF. As predicted, mutations that occluded pseudoknot formation drastically reduced the frameshift efficiency. These results are significant because they demonstrate that a pseudoknot is important to HTLV-1 pro-pol −1 PRF and define the frameshift site's 3′ boundary.
Development and Survival of MYC-driven Lymphomas Requires MYC-Antagonist MNT to Curb MYC-induced Apoptosis.

Deregulated over-expression of MYC is implicated in the development and malignant progression of most (~70%) human tumors. MYC drives cell growth and proliferation but also, at high levels, promotes apoptosis. Here, we report that the proliferative capacity of MYC-driven normal and neoplastic B lymphoid cells depends on MNT, a MYC-related transcriptional repressor. Our genetic data establish that MNT synergises with MYC by suppressing MYC-driven apoptosis and that it does so primarily by reducing the level of pro-apoptotic BIM. In Em-Myc mice, which model the MYC/IGH chromosome translocation in Burkitt's lymphoma, homozygous Mnt deletion greatly reduced lymphoma incidence by enhancing apoptosis and markedly decreasing premalignant B lymphoid cell populations. Strikingly, by inducing Mnt deletion within transplanted fully-malignant Em-Myc lymphoma cells, we significantly extended transplant recipient survival. The dependency of lymphomas on MNT for survival suggests that drugs inhibiting MNT could significantly boost therapy of MYC-driven tumors by enhancing intrinsic MYC-driven apoptosis.
Age Affects Speech Understanding and Multitask Costs

Objectives: We examined the effect of age on speech understanding and multitask costs in the ecologically relevant “Audiovisual True-to-Life Assessment of Auditory Rehabilitation”-paradigm (AVATAR). Design: Twenty-nine normal-hearing middle-aged adults completed AVATAR, which combines an auditory-visual speech-in-noise task with three secondary tasks on auditory localization or visual short-term memory in different dual-, triple-, and quadruple-task combinations. Performance decrements on the secondary tasks were considered to reflect the cognitive resources allocated during listening. Self-reported hearing difficulties were administered via a questionnaire. Results were compared with scores of 35 young normal-hearing adults. Results: Middle-aged adults performed consistently worse than young adults on speech understanding and, in the triple- and quadruple-task combinations only, on secondary task performance. Furthermore, middle-agers reported higher levels of daily listening concentration and more difficulties with speech understanding. Conclusions: This study demonstrated the adverse effect of age on speech-in-noise understanding and the amount of allocated cognitive resources during challenging listening situations realized in AVATAR.
Towards uterus tissue engineering: a comparative study of sheep uterus decellularisation

Abstract Uterus tissue engineering may dismantle limitations in current uterus transplantation protocols. A uterine biomaterial populated with patient-derived cells could potentially serve as a graft to circumvent complicated surgery of live donors, immunosuppressive medication and rejection episodes. Repeated uterine bioengineering studies on rodents have shown promising results using decellularised scaffolds to restore fertility in a partially impaired uterus and now mandate experiments on larger and more human-like animal models. The aim of the presented studies was therefore to establish adequate protocols for scaffold generation and prepare for future in vivo sheep uterus bioengineering experiments. Three decellularisation protocols were developed using vascular perfusion through the uterine artery of whole sheep uteri obtained from slaughterhouse material. Decellularisation solutions used were based on 0.5% sodium dodecyl sulphate (Protocol 1) or 2% sodium deoxycholate (Protocol 2) or with a sequential perfusion of 2% sodium deoxycholate and 1% Triton X-100 (Protocol 3). The scaffolds were examined by histology, extracellular matrix quantification, evaluation of mechanical properties and the ability to support foetal sheep stem cells after recellularisation. We showed that a sheep uterus can successfully be decellularised while maintaining a high integrity of the extracellular components. Uteri perfused with sodium deoxycholate (Protocol 2) were the most favourable treatment in our study based on quantifications. However, all scaffolds supported stem cells for 2 weeks in vitro and showed no cytotoxicity signs. Cells continued to express markers for proliferation and maintained their undifferentiated phenotype. Hence, this study reports three valuable decellularisation protocols for future in vivo sheep uterus bioengineering experiments.
Electrophysiological correlates of action observation treatment in children with cerebral palsy: A pilot study

Action Observation Treatment (AOT) has been shown to be effective in the functional recovery of several clinical populations. However, little is known about the neural underpinnings of the clinical efficacy of AOT in children with Cerebral Palsy (CP). Using electroencephalography (EEG), we recorded µ rhythm desynchronization as an index of sensorimotor cortex modulation during a passive action observation task before and after AOT. The relationship between sensorimotor modulation and clinical outcomes was also assessed. Eight children with CP entered the present randomized controlled crossover pilot study in which the experimental AOT preceded or followed a control Videogame Observation Treatment (VOT). Results provide further evidence of the clinical efficacy of AOT for improving hand motor function in CP, as assessed with the Assisting Hand Assessment (AHA) and Melbourne Assessment of Unilateral Upper Limb Function Scale (MUUL). The novel finding is that AOT increases µ rhythm desynchronization at scalp locations corresponding to the hand representation areas. This effect is associated to functional improvement assessed with the MUUL. These preliminary findings, although referred to as a small sample, suggest that AOT may affect upper limb motor recovery in children with CP and modulate the activation of sensorimotor areas, offering a potential neurophysiological correlate to support the clinical utility of AOT.
Nuclear Export of Cyclin B Mediated by the Nup62 Complex Is Required for Meiotic Initiation in Drosophila Males

Background: The central channel of the nuclear pore complex plays an important role in the selective transport of proteins between the nucleus and cytoplasm. Previous studies have demonstrated that the depletion of the Nup62 complex, constructing the nuclear pore channel in premeiotic Drosophila cells, resulted in the absence of meiotic cells. We attempted to understand the mechanism underlying the cell cycle arrest before meiosis. Methods: We induced dsRNAs against the nucleoporin mRNAs using the Gal4/UAS system in Drosophila. Results: The cell cycle of the Nup62-depleted cells was arrested before meiosis without CDK1 activation. The ectopic over-expression of CycB, but not constitutively active CDK1, resulted in partial rescue from the arrest. CycB continued to exist in the nuclei of Nup62-depleted cells and cells depleted of exportin encoded by emb. Protein complexes containing CycB, Emb, and Nup62 were observed in premeiotic spermatocytes. CycB, which had temporally entered the nucleus, was associated with Emb, and the complex was transported back to the cytoplasm through the central channel, interacting with the Nup62 complex. Conclusion: We proposed that CycB is exported with Emb through the channel interacting with the Nup62 complex before the onset of meiosis. The nuclear export ensures the modification and formation of sufficient CycB-CDK1 in the cytoplasm.
A systematic review and meta-analysis

Background: This systematic review and meta-analysis were performed to evaluate kidney function in patients with sepsisassociated acute kidney injury (SA-AKI) on alkaline phosphatase (AP) therapy. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched electronically from inception until May 4, 2019 and randomized controlled studies assessing AP treatment in patients with SA-AKI were included. Pool analyses with fixed effects or random effects models calculated pooled mean, standard deviation, and odds ratio (OR) with 95% confidence interval (CI). Results:Four randomized controlled trials involving AP therapy for 392 patients with SA-AKI were included. AP had a positive effect on endogenous creatinine clearance (ECC) in patients with SA-AKI at day 14 (random effects: mean difference=10.56, 95% CI= 2.27–18.84, P= .01) and day 28 (random effects: mean difference=14.30, 95% CI=6.27–22.33, P= .0005). All-cause mortality at day 28 (fixed effects: OR=0.62, 95% CI=0.40–0.97, P= .04) and day 90 (fixed effects: OR=0.61, 95% CI=0.39–0.96, P= .03) improved. Plasma creatinine level (fixed effects: mean difference= 76.83, 95% CI= 146.92 to 6.74, P= .03) and biomarkers level (random effects: mean difference= 6.57, 95% CI= 10.74 to 2.40, P< .00001) also improved in the therapy group compared with placebo. Conclusion: In patients with SA-AKI, AP showed a relatively late protective effect by improving ECC at days 7, 14, and 28. ECC level improved when patients received AP dose of 0.212mg/kg. Mortality improved at days 28 and 90, respectively, when patients received AP dose of 1.6mg/kg. Levels of overall AKI biomarkers were improved in short term. Abbreviations: AKI = acute kidney injury, AP = alkaline phosphatase, BiAP = bovine intestinal phosphatase, DAMP = dangerassociated molecular patterns, ECC = endogenous creatinine clearance, eGFR = estimated glomerular filtration rate, GFR = glomerular filtration rate, GST = glutathione S-transferase, IL-18 = interleukin 18, IQR = interquartile range, KIM-1 = kidney injury molecule 1, LPS = lipopolysaccharide, MD =mean difference, NGAL = neutrophil gelatinase-associated lipocalin, OR = odds ratio, PAMP = pathogen-associated molecular patterns, RCT = randomized controlled trial, ROB = risk of bias, RRT = renal replacement therapy, SA-AKI = sepsis-associated acute kidney injury, SD = standard deviation.
Automated Skeletal Classification with Lateral Cephalometry Based on Artificial Intelligence

Lateral cephalometry has been widely used for skeletal classification in orthodontic diagnosis and treatment planning. However, this conventional system, requiring manual tracing of individual landmarks, contains possible errors of inter- and intravariability and is highly time-consuming. This study aims to provide an accurate and robust skeletal diagnostic system by incorporating a convolutional neural network (CNN) into a 1-step, end-to-end diagnostic system with lateral cephalograms. A multimodal CNN model was constructed on the basis of 5,890 lateral cephalograms and demographic data as an input. The model was optimized with transfer learning and data augmentation techniques. Diagnostic performance was evaluated with statistical analysis. The proposed system exhibited >90% sensitivity, specificity, and accuracy for vertical and sagittal skeletal diagnosis. Clinical performance of the vertical classification showed the highest accuracy at 96.40 (95% CI, 93.06 to 98.39; model III). The receiver operating characteristic curve and the area under the curve both demonstrated the excellent performance of the system, with a mean area under the curve >95%. The heat maps of cephalograms were also provided for deeper understanding of the quality of the learned model by visually representing the region of the cephalogram that is most informative in distinguishing skeletal classes. In addition, we present broad applicability of this system through subtasks. The proposed CNN-incorporated system showed potential for skeletal orthodontic diagnosis without the need for intermediary steps requiring complicated diagnostic procedures.
Sugar, amino acid and inorganic ion profiling of the honeydew from different hemipteran species feeding on Abies alba and Picea abies

Several hemipteran species feed on the phloem sap of plants and produce large amounts of honeydew that is collected by bees to produce honeydew honey. Therefore, it is important to know whether it is predominantly the hemipteran species or the host plant to influence the honeydew composition. This is particularly relevant for those botanical and zoological species from which the majority of honeydew honey originates. To investigate this issue, honeydew from two Cinara species located on Abies alba as well as from two Cinara and two Physokermes species located on Picea abies were collected. Phloem exudates of the host plants were also analyzed. Honeydew of all species contained different proportions of hexoses, sucrose, melezitose, erlose, and further di- and trisaccharides, whereas the phloem exudates of the host trees contained no trisaccharides. Moreover, the proportions of sugars differed significantly between hemipteran species feeding on the same tree species. Sucrose hydrolysis and oligosaccharide formation was shown in whole-body homogenates of aphids. The type of the produced oligosaccharides in the aphid-extracts correlated with the oligosaccharide composition in the honeydew of the different aphid species. The total contents of amino acids and inorganic ions in the honeydew were much lower than the sugar content. Glutamine and glutamate were predominant amino acids in the honeydew of all six hemipteran species and also in the phloem exudates of both tree species. Potassium was the dominant inorganic ion in all honeydew samples and also in the phloem exudate. Statistical analyses reveal that the sugar composition of honeydew is determined more by the hemipteran species than by the host plant. Consequently, it can be assumed that the sugar composition of honeydew honey is also more influenced by the hemipteran species than by the host tree.
A Wearable Electrocardiogram Telemonitoring System for Atrial Fibrillation Detection

In this paper we proposed a wearable electrocardiogram (ECG) telemonitoring system for atrial fibrillation (AF) detection based on a smartphone and cloud computing. A wearable ECG patch was designed to collect ECG signals and send the signals to an Android smartphone via Bluetooth. An Android APP was developed to display the ECG waveforms in real time and transmit every 30 s ECG data to a remote cloud server. A machine learning (CatBoost)-based ECG classification method was proposed to detect AF in the cloud server. In case of detected AF, the cloud server pushed the ECG data and classification results to the web browser of a doctor. Finally, the Android APP displayed the doctor’s diagnosis for the ECG signals. Experimental results showed the proposed CatBoost classifier trained with 17 selected features achieved an overall F1 score of 0.92 on the test set (n = 7270). The proposed wearable ECG monitoring system may potentially be useful for long-term ECG telemonitoring for AF detection.