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In conclusion, the MAPK14 could be a potential biomarker for advanced gastric cancer as well as a pharmacological target, which could improve the survival rate of patients. Protein sources used as supplements of IVF culture media are known to have several implications for the function and stability of embryo culture environment. In fact, they i) transport biologically active molecules ii) chelate heavy metals, iii) regulate media pH, iii) scavenge reactive oxygen species (ROS) and iv) attenuate osmotic stress to which cells are exposed in sub-optimal culture conditions. Instead, their specific relevance to the formulation of cryopreservation solutions used for gamete and embryo cryopreservation remains uncertain. In the present work, we tested the hypothesis that different protein supplements present in cryopreservation solutions, serum or plasma protein solution (PPS), or different concentrations of the same supplement (serum), are associated with different types and/or magnitude of cryopreservation-derived cell damage. To this end, using cryopreservation solutions containing serum or PPS, donated supernumerary human mature oocytes were frozen-thawed by slow freezing and compared with fresh controls. Ultrastructural markers of oocyte quality were adopted as objective measure to assess possible damage from cryopreservation. The study results indicate that the adoption of serum minimises cell damage induced by cryopreservation. Indeed, typical hallmarks of cryodamage in human oocytes, i.e. loss of cortical granules, zona pellucida hardening and above all vacuolization, were largely reduced in oocytes cryopreserved with solutions containing serum, especially if used a higher concentration. This suggest that oocyte cryopreservation still has significant margins of improvement that may derive also from composition of cryopreservation media. Drosophila Larval hematopoiesis takes place at the lymph gland, where myeloid-like progenitors differentiate into Plasmatocytes and Crystal Cells, under regulation of conserved signaling pathways. It has been established that the Notch pathway plays a specific role in Crystal Cell differentiation and maintenance. In mammalian hematopoiesis, the Notch pathway has been proposed to fulfill broader functions, including Hematopoietic Stem Cell maintenance and cell fate decision in progenitors. In this work we describe different roles that Notch plays in the lymph gland. We show that Notch, activated by its ligand Serrate, expressed at the Posterior Signaling Center, is required to restrain Core Progenitor differentiation. We define a novel population of blood cell progenitors that we name Distal Progenitors, where Notch, activated by Serrate expressed in Lineage Specifying Cells at the Medullary Zone/Cortical Zone boundary, regulates a binary decision between Plasmatocyte and Crystal Cell fates. Thus, Notch plays context-specific functions in different blood cell progenitor populations of the Drosophila lymph gland. The process that partitions the nascent vertebrate central nervous system into forebrain, midbrain, hindbrain, and spinal cord after neural induction is of fundamental interest in developmental biology, and is known to be dependent on Wnt/β-catenin signaling at multiple steps. Neural induction specifies neural ectoderm with forebrain character that is subsequently posteriorized by graded Wnt signaling embryological and mutant analyses have shown that progressively higher levels of Wnt signaling induce progressively more posterior fates. However, the mechanistic link between Wnt signaling and the molecular subdivision of the neural ectoderm into distinct domains in the anteroposterior (AP) axis is still not clear. To better understand how Wnt mediates neural AP patterning, we performed a temporal dissection of neural patterning in response to manipulations of Wnt signaling in zebrafish. We show that Wnt-mediated neural patterning in zebrafish can be divided into three phases (I) a primary AP patterning phase, gulation enables a transition to the mes/r1 phase of Wnt-mediated patterning, as it ensures that Wnts expressed in the midbrain and MHB do not suppress midbrain identity, and consequently reinforce formation of the DMB. These findings integrate important temporal elements into our spatial understanding of Wnt-mediated neural patterning and may serve as an important basis for a better understanding of neural patterning defects that have implications in human health. Published by Elsevier Inc.BACKGROUND Different reference change values approaches are widely accepted to interpret the change between two consecutive measured values from the same biological quantity in an individual. Nevertheless, we propose two uncertainty-based models to estimate reference change values which will include all possible variation sources. METHODS The models consisted in 1) estimation of the uncertainty related to each measured value, 2) calculation of the change between these values and its uncertainty, and 3) performing a compatibility study to know if the values are of the same degree of equivalence. Also, results obtained using the proposed models and the classical approaches are shown. RESULTS The primary uncertainty sources corresponded to the within-subject biological, followed by those related to the analytical or pre-analytical phase, and post-analytical, respectively. We observed higher reference change values when our models were applied than those obtained using the classical approaches. CONCLUSIONS The estimation of reference change values using our models could be more realistic than the classical approaches because more identified variation sources were considered. We hope that this study will help and stimulate clinical laboratories to perform uncertainty and reference change values studies, and it allows a greater understanding of these concepts and its application in disease monitoring. Attention comprises a wide set of processes such as phasic alertness, orienting, executive control, and the executive (i.e., detecting infrequent targets) and arousal (i.e., sustaining a fast reaction) vigilance components. Importantly, the effects of transcranial direct current stimulation (tDCS) over attentional functioning have been mostly addressed by measuring these processes separately and by delivering offline tDCS with low precision over the stimulation region. In the current study, we examined the effects of online High-Definition tDCS (HD-tDCS) over the behavioral and electrophysiological functioning of attentional and vigilance components. Participants (N = 92) were randomly assigned to one of three stimulation groups right dorsolateral prefrontal cortex stimulation, right posterior parietal cortex (PPC) stimulation, and sham. All of them performed - in combination with the HD-tDCS protocol - an attentional networks task (ANTI-Vea) suitable to measure the executive and arousal components of vigilance along with three typical attentional functions phasic alertness, orienting, and executive control. In addition, EEG was registered at the baseline and at the post-stimulation period. We observed that, regardless the stimulation region, online HD-tDCS (a) reduced phasic alertness (p = .008), but did not modulated the orienting and executive control functioning; and (b) mitigated the executive vigilance decrement (p = .011), but did not modulated arousal vigilance across time-on-task. Interestingly, only HD-tDCS over PPC reduced considerably the increment of alpha power observed across time-on-task (p = .009). The current study provides further evidence for both an empirical dissociation between vigilance components and the cortical regions underlying attentional processes. We highlight the advantages of using online HD-tDCS to examine the stimulation effects on attentional and vigilance functioning. The Tear Film Lipid Layer (TFLL) covering the surface of the aqueous film at human cornea forms a first barrier between the eye and environment. Its alterations are related to dry eye disease. TFLL is formed by a complex mixture of lipids, with an excess of nonpolar components and a minor fraction of polar molecules. Its thickness is up to 160 nm, hence a multilayer-like structure of TFLL is assumed. However, details of TFLL organization are mostly unavailable in vivo due to the dynamic nature of the human tear film. To overcome this issue, we employ a minimalistic in vitro lipid model of TFLL. We study its biophysical characteristics by using a combination of the Langmuir trough with fluorescence microscopy. The model consists of two-component polar-nonpolar lipid films with a varying component ratio spread on the aqueous subphase at physiologically relevant temperature. We demonstrate that the model lipid mixture undergoes substantial structural reorganization as a function of lateral pressure and polar to nonpolar lipid ratio. In particular, the film is one-molecule-thick and homogenous under low lateral pressure. Upon compression, it transforms into a multilayer structure with inhomogeneities in the form of polar-nonpolar lipid assemblies. Based on this model, we hypothesize that TFLL in vivo has a duplex polar-nonpolar structure and it contains numerous mixed lipid aggregates formed because of film restructuring. These findings, despite the simplified character of the model, seem relevant for TFLL physiology as well as for understanding pathological conditions related to the lipids of the tear film. V.p63 is expressed from two promoters and produces two N-terminal isoforms, TAp63 and ΔNp63. Alternative splicing creates three C-terminal isoforms p63α/β/δ whereas alternative polyadenylation in coding sequence (CDS-APA) creates two more C-terminal isoforms p63γ/ε. While several transcription factors have been identified to differentially regulate the N-terminal p63 isoforms, it is unclear how the C-terminal p63 isoforms are regulated. Thus, we determined whether PABPN1, a key regulator of APA, may differentially regulate the C-terminal p63 isoforms. We found that PABPN1 deficiency increases p63γ mRNA through CDS-APA. We also found that PABPN1 is necessary for p63α translation by modulating the binding of translation initiation factors (eIF4E and eIF4G) to p63α mRNA. Moreover, we found that the p53 family, especially p63α, regulates PABPN1 transcription, suggesting that the mutual regulation between p63 and PABPN1 forms a feedback loop. Furthermore, we demonstrated that PABPN1 deficiency inhibits cell growth, which can be rescued by ectopic ΔNp63α. Finally, we showed that PABPN1 controls the terminal differentiation of HaCaT keratinocytes by modulating ΔNp63α expression. Taken together, our findings suggest that PABPN1 is a key regulator of the C-terminal p63 isoforms through CDS-APA and mRNA translation and that the p63-PABPN1 loop modulates p63 activity and the APA landscape. Although deep learning algorithms have shown expert-level performance, previous efforts were mostly binary classifications of limited disorders. We trained an algorithm with 220,680 images of 174 disorders and validated using Edinburgh (1,300 images; 10 disorders) and SNU dataset (2,201 images; 134 disorders). The algorithm could accurately predict malignancy, suggest primary treatment options, render multi-class classification among 134 disorders and improve the performance of medical professionals. The AUCs for malignancy detection were 0.928±0.002 (Edinburgh) and 0.937±0.004 (SNU). The AUCs of primary treatment suggestion (SNU) were 0.828±0.012, 0.885±0.006, 0.885±0.006 and 0.918±0.006 for steroids, antibiotics, antivirals and antifungals. For multi-class classification, the mean Top-1/Top-5 accuracies were 56.7±1.6%/92.0±1.1% (Edinburgh) and 44.8±1.2%/78.1±0.3% (SNU). With the assistance of our algorithm, the sensitivity and specificity of 47 clinicians (21 dermatologists and 26 dermatology residents) for malignancy prediction (SNU; 240 images) improved by 12.