In the present study, we investigate the post-editese phenomenon, i.e., the unique features that set machine translated post-edited texts apart from human-translated texts. We use two literary texts, namely, the English children's novel by Lewis Carroll Alice’s Adventures in Wonderland (AW) and Paula Hawkins' popular book The Girl on the Train (TGOTT) translated from English into Brazilian-Portuguese to investigate whether the post-editese features can be found on the surface of the post-edited (PE) texts. In addition, we examine how the features found in the PE texts differ from the features encountered in the human-translated (HT) and machine translation (MT) versions of the same source text. Results revealed evidence for post-editese for TGOTT only with PE versions being more similar to the MT output than to the HT texts.

Ribosome profiling and mass spectroscopy have identified canonical and noncanonical translation initiation codons (TICs) that are upstream of the main translation initiation site and used to translate oncogenic proteins. Here, we use a Kozak Similarity Score algorithm to find that nearly all of these TICs have flanking nucleotides closely matching the Kozak sequence. Remarkably, the nucleotides flanking alternative noncanonical TICs are frequently closer to the Kozak sequence than the nucleotides flanking TICs used to translate the gene’s main protein. Of note, the 5’ untranslated region (5‘UTR) of cancer-associated genes with an upstream TIC tend to be significantly longer than the same region in genes not associated with cancer. The presence of a longer than typical 5’UTR increases the likelihood of ribosome binding to upstream noncanonical TICs, and may be a distinguishing feature of a number of genes overexpressed in cancer. Noncanonical TICs that are located in the 5’UTR, although thought disadvantageous and suppressed by evolution, may translate oncogenic proteins because of their flanking nucleotides

According to data from the U.S FDA, the likelihood of a new drug progressing from Phase I clinical trials to market approval is only 8% (DiMasi et al., 2016). Furthermore, a significant attrition rate of 35% occurs during Phase II studies due to the failure to demonstrate clinical efficacy (Arrowsmith, 2011). These statistics underscore the urgent need to reassess the current research and development (R&D) paradigm. To address this challenge, a promising approach called reverse translational pharmacology (RTP) has emerged, aiming to enhance the predictive value of preclinical models used in biomedical research by leveraging animal models that spontaneously develop analogous diseases to humans (Schneider et al., 2018). The rationale behind RTP is that knowledge gained from clinical trials in canines can subsequently inform and guide human clinical trials, leading to improved outcomes for both species. Additionally, this approach capitalizes on the opportunity to stimulate veterinary drug development by leveraging pharmacokinetic (PK), efficacy, and safety data obtained from human clinical studies (Schneider et al., 2018). The application of reverse translational pharmacology holds immense potential for expediting drug development and advancing medical knowledge. By employing animal models that naturally develop diseases akin to those found in humans, researchers can enhance the predictive capacity of preclinical models, thereby mitigating the high attrition rates encountered in later stages of clinical trials. Moreover, the exchange of knowledge and data between human and veterinary medicine engenders a synergistic relationship, fostering progress in both domains (Schneider et al., 2018). As this innovative approach gains momentum, fostering collaborations between basic and clinician scientists, pharmaceutical companies, and veterinary professionals becomes increasingly imperative. By sharing resources, expertise, and findings, we can pave the way for groundbreaking discoveries and the development of safe and efficacious treatments for diverse diseases. Embracing reverse translational pharmacology offers an avenue to redefine the R&D paradigm, bringing us closer to a future where a higher proportion of drugs successfully traverse the arduous path from the laboratory to market approval, ultimately benefiting patients across species. In this brief commentary, we highlight four examples of diseases where reverse translational modeling has been used to support pharmaceutical research, including some applications developed in our research laboratory (SMART Pharmacology) at the Iowa State University College of Veterinary Medicine. In doing so, this report also seeks to provide a brief overview of the heuristic value of computational approaches in comparative research. To further illustrate the value of these in silico approaches, we deliberately chose to employ some features of ChatGPT to produce the present summary (OpenAI. (2023). GPT-3.5 [ChatGPT]. Retrieved from https://openai.com).

Biochirality is evident in the hierarchical relation of molecular and cellular physiology during organism development and aging. Chirality influences the higher levels of biological processes, such as perception, memory and cognition, through intermolecular interactions between DNA, proteins, and lipids. At the molecular level, an organism's aging is the accumulation of macro-molecules with the aberrant composition, chirality, and folding. Cellular aging is driven by the non-physiological phase transitions (PhTs) withing membrane-bound and membrane-less compartments. Genomic instability and protein aging, as the interconnected root-causes of cell and organism aging, share two essential feature – spontaneous nature and accumulation over a lifetime. Consequently, we will analyze the interaction between the enzymatic (Enz) and spontaneous (Sp) post-translational modifications (PTMs^Enz and PTMs ^Sp). Both forms of PTMs significantly contribute to the balance of L- and D-amino acids (L/D-AAs) in organisms, modulating the functions of nervous and immune systems. The most abundant form of PTM - enzymatic phosphorylation is bio-chemically associated with the spontaneous racemization (Rz^Sp). The crass talk of enzymatic phosphorylation and spontaneous racemization, as an essential determinant of protein aging and aggregation, associated with the aberrant autophagy, apoptosis, and cell signaling, is discussed in this review.

Conventional models do not fully explain composition of the solar system – for example, the presence of p-nuclei and post-post-Fe-nuclei remains not yet understood (and is one of the great unresolved puzzles of nuclear astrophysics in general); other puzzles exist. We offer a hypothesis which can explain the appearance of non-native elements in the solar system, and a feasible scenario for its implementation. The hypothesis suggests that a nuclear-fission "event" occurred in the inner part of the solar system at the time currently defined as the birth of the system. Conventional models have never considered fission as a contributing nuclei-production mechanism. Upon examination of the existing models and factual data (presented in volumes of publications but never combined into an aggregate), we identified one plausible scenario by which a fission event (not demolishing the entire solar system) could occur: an encounter with a compact super-dense stellar "fragment" (with specific properties) and its "explosion" in fission-cascades. Such scenario also helps resolve other long-standing puzzles of the solar system. For example, it provides that the fission-produced nuclei subsequently transformed into the material that (eventually) accreted into the "rocky" objects in the system (terrestrial planets, asteroids, etc.) and enriched the pre-existed hydrogen-helium objects (the Sun and the gaseous giants) – this offers an explanation for the planets’ inner position and compositional differences within the predominantly hydrogen-helium rest of the solar system. Other implications also follow.

Connexins are tetraspan transmembrane proteins that form gap junctions and facilitate direct intercellular communication, a critical feature for the development, function and homeostasis of tissues and organs. In addition, a growing number of gap junction-independent functions are being ascribed to these proteins. The connexin gene family is under extensive regulation at the transcriptional and post-transcriptional level, and undergoes numerous modifications at the protein level, including phosphorylation, which ultimately affects their trafficking, stability and function. Here, we summarize these key regulatory events, with emphasis on how these affect their multi-functionality in health and disease.

Huntington’s Disease (HD) is a devastating neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene, for which no disease modifying therapies are currently available. Much of the recent research has focused on developing therapies to directly lower HTT expression, and while promising, these therapies have presented several challenges regarding administration and efficacy. Another promising therapeutic approach is the modulation of HTT post-translational modifications (PTMs) that are dysregulated in disease and have shown to play a key role in HTT toxicity. Among all PTMs, modulation of HTT phosphorylation has been proposed as an attractive therapeutic option due to the possibility of orally administering specific kinase effectors. One of the kinases described to participate in HTT phosphorylation is Protein Kinase CK2. CK2 has recently emerged as a target for the treatment of several neurological and psychiatric disorders, although its role in HD remains controversial. While pharmacological studies in vitro inhibiting CK2 resulted in reduced HTT phosphorylation and increased toxicity, genetic approaches in mouse models of HD have provided beneficial effects. In this review we discuss potential therapeutic approaches related to the manipulation of HTT-PTMs with special emphasis on the role of CK2 as a therapeutic target in HD.

Post-translational modifications (PTMs) represent a cornerstone in the complexity of the proteome, significantly contributing to diversifying protein structure and function. PTMs can significantly influence protein function, stability, localization, and interactions with other molecules. Therefore, it is important when choosing a protein expression system to ensure the precise incorporation of PTMs during protein synthesis, which is paramount for producing biologically active proteins. Cell-free protein synthesis (CFPS) system has emerged as a powerful protein synthesis platform and research toolkit in synthetic biology. The open nature of the system allows the reaction environment to be tailored to any protein of interest to promote specific PTMs, thus allowing for the production of a protein with the desired modifications. This review presents various PTMs achieved in the CFPS systems, providing insights into the current challenges, successes, and future prospects.

The impact of metals bioaccumulation on marine organisms is under investigation. This study was designed to determine the association of oxidative stress in mussels Mytilus galloprovincialis induced by seawater enriched with trace metals with protein synthesis. Mussels were exposed to 40 μg/L Cu, 30 μg/L Hg, or 100 μg/L Cd for 5 and 15 days, and the pollution effect was evaluated by measuring established oxidative biomarkers. The results showed damage on the protein synthesis machine integrity and specifically, on translation factors and ribosomal proteins expression and modifications. Exposure of mussels to all metals caused oxidative damage that was milder in the cases of Cu and Hg, and more pronounced for Cd. However, after prolonged exposure of mussels to Cd (15 days), the effects receded. These changes that perturb protein biosynthesis can serve as a great tool for elucidating the mechanisms of toxicity and could be integrated in biomonitoring programs.

Chikungunya is mosquito born disease that is spread across continents. This research provides valuable insights into the potential functional significance of the hydrophobic tail and cysteine-rich regions in E2 proteins. These findings lay the groundwork for future investigations into the specific roles of the C-terminal domain and post-translational modifications, which could ultimately lead to a better understanding of viral mechanisms and potential therapeutic targets.

During the response of plants to adverse stresses, aquaporin (AQP) plays a prominent role in membrane water transport based on received upstream signals. In addition, they have various physical parts for dealing with environmental stresses. Due to the importance of the AQP gene family, studies have been conducted investigating the function and regulatory system of these genes. However, many of their molecular aspects are still unknown. This study aims to carry out a genomic-wide investigation of the AQP gene family in durum wheat using bioinformatics tools and to investigate the expression patterns of some members in response to salt stress. Our results showed that there are 80 TtAQP genes in durum wheat, which are classified into four main groups based on phylogenetic analysis. Many duplications were observed between the members of the TtAQP gene family, and high diversity in response to post-translational modifications was observed between TtAQP family members. The expression pattern of TtAQP genes disclosed that these genes are primarily upregulated in response to salt stress. Besides, qPCR data revealed that TtAQPs are more induced in delayed responses to salinity stress. Overall, our findings illustrate that TtAQP members are diverse in terms of their structure, regulatory systems and expression levels.

Resilience has been defined as one's competence to maintain a mental health state and overall well-being when undergoing grave stress or facing significant adversities. Numerous resili-ence-investigating research tools were developed over the years, with the Connor-Davidson Re-silience Scale (CD-RISC), a self-rated tool presenting valuable psychometric properties, remaining one of the most prominent. We aimed to translate and validate the brief CD-RISC-10 in a convenient sample of 584 nurses in Greece's secondary and tertiary health care system. We conducted a con-firmatory factor analysis and known-groups validity and estimated the reliability of the CD-RISC-10. Our confirmatory factor analysis revealed that the scale had a unifactorial structure since all the model fit indices were very good. Moreover, the reliability of the CD-RISC-10 was very good since Cronbach's alpha was 0.924 and McDonald's omega was 0.925. Therefore, the Greek version of the CD-RISC-10 confirmed the factor structure of the original one and had very good validity and reliability.

The high flammability and lack of charrability of polystyrene (PS) pose significant limitations on its broader applications. Therefore, there is an urgent need for a straightforward and efficient method for the synthesis of flame-retardant PS, which still poses a considerable challenge. In this study, we present an efficient approach to enhance the flame-retardant properties of PS through direct phosphorylating aromatic C(sp2)-H bonds using commercially available and inexpensive manganese catalyst. A range of phosphonates served as reactive substrates to enable a tunable degree of polymer functionalization. The corresponding phosphorylated PS specimens were determined by means of 1H NMR, 31P NMR, FTIR spectroscopy and GPC. Microscale combustion calorimetry (MCC) tests indicate that this protocol indeed enhances the flame-retardant performance of PS. Moreover, other advantages associated with the incorporation of the phosphonate group have been observed, including improved thermal resistance and wettability. This cost-effective strategy of Mn-catalyzed C-H can also be utilized to directly obtain phosphonate modification of waste foamed PS and styrene acrylonitrile copolymer, providing a new method for the purpose of recycling and upgrading PS plastics.

Viruses feature an evolutionary shaped minimal genome that is obligately dependent on the cellular transcription and translation machinery for propagation. To suppress host cell immune responses and ensure efficient replication, viruses employ numerous tactics to favor viral gene expression and protein synthesis. This necessitates a carefully balanced network of virus- and host-encoded components, of which the RNA-based regulatory mechanisms have emerged as particularly interesting albeit insufficiently studied, especially in unicellular organisms. Here, recent advances that further our understanding of RNA-based translation regulation, mainly through post-transcriptional chemical modification of ribonucleosides, codon usage, and (virus-encoded) transfer RNAs, will be discussed in the context of viral infection.

Brain plasticity is induced by learning during wakefulness and is consolidated during sleep. But the molecular mechanisms involved are poorly understood and their relation to experience-dependent changes in brain activity remains to be clarified. Localized mRNA translation is im-portant for the structural changes at synapses supporting brain plasticity consolidation. Sleep has been shown activate the translation mTOR pathway, via phosphorylation of 4E-BPs, during brain plasticity, but whether this activation is specific to synapses is not known. We investigated this question using acute exposure of rats to an enriched environment (EE). We measured brain activity with EEGs and 4E-BPs phosphorylation at cortical and cerebellar synapses with Western Blot. Sleep significantly increased the conversion of 4E-BPs to its hyperphosphorylated form at synapses, especially after EE exposure. EE exposure increased oscillations in the alpha band dur-ing active exploration and in the theta to beta (4-30Hz) range, as well as spindle density, during NREM sleep. Theta activity during exploration and NREM spindle frequency predicted changes in 4E-BPs hyperphosphorylation at synapses. Our results provide a link between EEG and mo-lecular markers of plasticity across wake and sleep.

Statistical machine translation (SMT) which was the dominant paradigm in machine translation (MT) research for nearly three decades has recently been superseded by the end-to-end deep learning approaches to MT. Although deep neural models produce state-of-the-art results in many translation tasks, they are found to under-perform on resource-poor scenarios. Despite some success, none of the present-day benchmarks that have tried to overcome this problem can be regarded as a universal solution to the problem of translation of many low-resource languages. In this work, we investigate the performance of phrase-based SMT (PB-SMT) and NMT on two rarely-tested low-resource language-pairs, English-to-Tamil and Hindi-to-Tamil, taking a specialised data domain (software localisation) into consideration. This paper demonstrates our findings including the identification of several issues of the current neural approaches to low-resource domain-specific text translation and rankings of our MT systems via a social media platform-based human evaluation scheme.

When using computer-aided translation systems in a typical, professional translation workflow, there are several stages at which there is room for improvement. The SCATE (Smart Computer-Aided Translation Environment) project investigated several of these aspects, both from a human-computer interaction point of view, as well as from a purely technological side. This paper describes the SCATE research with respect to improved fuzzy matching, parallel treebanks, the integration of translation memories with machine translation, quality estimation, terminology extraction from comparable texts, the use of speech recognition in the translation process, and human computer interaction and interface design for the professional translation environment. For each of these topics, we describe the experiments we performed and the conclusions drawn, providing an overview of the highlights of the entire SCATE project.

This article is a tribute to Lewis Wolpert on the occasion of the recent 50th anniversary of the publication of his article ‘Positional Information and the Spatial Pattern of Differentiation’. This tribute relates to another of his ideas: his early ‘Progress Zone’ timing model for limb development. Recent evidence is reviewed that a mechanism sharing features with this model patterns the main body axis in early vertebrate development. This tribute celebrates the golden era of Developmental Biology.

The lexical-semantic issues in translating food taste adjectives into Chinese are examined in this article. Chinese food has a wide variety of colorful flavors. Correctly interpreting the adjectives that describe how food tastes is crucial. With tasty, simple-to-digest meals, it promotes and popu-larizes Chinese cuisine. Because, eating light, low-fat meals is crucial in today's world. Yet, due to poor translation and unclear menus, Chinese restaurants in CIS nations, particularly in Uzbeki-stan, are unpopular with customers. The biggest mistakes in Chinese restaurant menu are related to the incorrect translation of the taste adjectives of the food. This article aims to identify the most erroneously translated Chinese adjectives, analyze them linguistically, and determine the cause of translation errors. The translation ability of 60 Chinese language translators with HSK 4 level is analyzed on the basis of experiment. Recommendations for solving the problem studied in this ar-ticle have been developed.

Subjectivity has been an inherent issue in the conventional Fugl-Meyer assessment, which has been the focus of recognition research in several studies. This paper continues our previous work on a recognition method of finger movement impairment levels using EMG. In contrast to our previous work, this paper provided a better recognition result with an improved experimental setting, such as higher sampling frequency and number of EMG channels. A large number of patients was recruited to provide a reliable recognition performance. This paper employed two data processing mechanisms, inter-subject cross-validation (ISCV) and data-scaled inter-subject cross-validation (DS-ISCV), resulting in two evaluation methods. The employed machine-learning algorithms are SVM, random forest (RF), and multi-layer perceptron (MLP). The highest average recall score across impairment levels of 0.73 was achieved by MLP_ISCV in the spherical grasp task. Subsequently, the highest average recall score of non-majority classes of 0.72 was achieved by the SVM_DS-ISCV in the mass extension task. The cross-validation result showed that the proposed method effectively handled the imbalanced dataset without being biased toward the majority class. The proposed method demonstrated the potential to assist doctors in clarifying the finger movement impairment level.

Different bacterial species have dramatically different generation times, from 20-30 minutes in Escherichia coli to about two weeks in Mycobacterium leprae. The translation machinery in a cell needs to synthesize all proteins for a new cell in each generation. The three subprocesses of translation, i.e., initiation, elongation, and termination, are expected to be under stronger selection pressure to optimize in short-generation bacteria (SGB) such as Vibrio natriegens than in the long-generation Mycobacterium leprae. The initiation efficiency depends on the start codon decoded by the initiation tRNA, the optimal Shine-Dalgarno (SD) decoded by the anti-SD (aSD) sequence on small subunit rRNA, and the secondary structure that may embed the initiation signals and prevent them from being decoded. The elongation efficiency depends on the tRNA pool and codon usage. The termination efficiency in bacteria depends mainly on the nature of the stop codon and the nucleotide immediately downstream of the stop codon. By contrasting SGB with long-generation bacteria (LGB), we predict that 1) SGB to have more ribosome RNA operons to produce ribosomes, and more tRNA genes for carrying amino acid to ribosomes, 2) SGB to have a higher percentage of genes using AUG as start codon and UAA as stop codon than LGB, 3) SGB to exhibit better codon and anticodon adaptation than LGB, and 4) SGB to have weaker secondary structure near translation initiation signals than LGB. These differences between SGB and LGB should be more pronounced in highly expressed genes than lowly expressed genes. We present empirical evidence in support of these predictions.

A Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown aetiology under growing interest now in view of the increasingly recognized post-COVID syndrome as a new entity with similar clinical presentation. We performed the first cross-sectional study of ME/CFS in community population in Russia and then described and compared some clinical and pathophysiological characteristics of ME/CFS and post-COVID syndrome as neuroimmune disorders. Of the cohort of 76 individuals who suggested themselves suffering from ME/CFS 56 subsequently were confirmed as having CFS/ME according to ≥1 of the 4 most commonly used case definition. Of the cohort of 14 individuals with post-COVID-19 syndrome 14 met diagnostic criteria for ME/CFS. The prevalence of clinically expressed and subclinical anxiety and depression in ME / CFS and post-COVID ME/CFS did not differ significantly from that in healthy individuals. Severity of anxiety / depressive symptoms did not correlate with the severity of fatigue neigther in ME / CFS nor in post-COVID ME/CFS, but the positive correlation was found between the severity of fatigue and 20 other symptoms of ME / CFS related to the domains of “post-exertional exhaustion”, “immune dysfunction”, “sleep disturbances”, "dysfunction of the autonomic nervous system", "neurological sensory / motor disorders" and "pain syndromes". Immunological abnormalities were identified in 12/12 patients with ME / CFS according to the results of laboratory testing. The prevalence of postural orthostatic tachycardia assessed by the active standing test was 37.5% in ME / CFS and 75.0% in post-COVID ME/CFS (the latter was higher than in healthy controls, p = 0.02) There was a more pronounced increase in heart rate starting from the 6th minute of the test in post-COVID ME/CFS compared with the control group. Assessment of the functional characteristics of microcirculation by laser doppler flowmetry revealed obvious and very similar changes in ME/CFS and post-COVID ME/CFS compared to the healthy controls. The identified pattern corresponded to the hyperemic form of microcirculation disorders, usually observed in acute inflammatory processes or in deficiency of systemic vasoconstriction influences.

Generative large language models (LLMs), e.g., ChatGPT, have demonstrated remarkable proficiency across several NLP tasks such as machine translation, question answering, text summarization, and natural language understanding. Recent research has shown that utilizing ChatGPT for assessing the quality of machine translation (MT) achieves state-of-the-art performance at the system level but performs poorly at the segment level. To further improve the performance of LLMs on MT quality assessment, we conducted an investigation into several prompting methods. Our results indicate that by combining Chain-of-Thoughts and Error Analysis, a new prompting method called Error Analysis Prompting, LLMs like ChatGPT can \textit{generate human-like MT evaluations at both the system and segment level}. Additionally, we discovered some limitations of ChatGPT as an MT evaluator, such as unstable scoring and biases when provided with multiple translations in a single query. Our findings aim to provide a preliminary experience for appropriately evaluating translation quality on ChatGPT while offering a variety of tricks in designing prompts for in-context learning. We anticipate that this report will shed new light on advancing the field of translation evaluation with LLMs by enhancing both the accuracy and reliability of metrics. The project can be found at https://github.com/Coldmist-Lu/ErrorAnalysis_Prompt.

BACKGROUNDː The so-called Low Cardiac Output Syndrome (LCOS) is one of the most common complications in pediatric patients with congenital heart disease undergoing corrective surgery. LCOS requires high concentrations of inotropes to support cardiac contractility and improve cardiac output, allowing for a better systemic perfusion. To date, serum lactate concentrations and central venous oxygen saturation (ScVO2) are the most commonly used perfusion markers, but they are not completely reliable to identify a state of global tissue hypoxia. The study aims to evaluate whether the venoarterial carbon dioxide difference/arterial-venous oxygen difference ratio [P(v-a)CO2/C(a-v)O2] can be a good index to predict the development of LCOS in the aforemen-tioned patients, so as to treat it promptly. METHODSː This study followed a population of 98 children undergoing corrective cardiac surgery from June 2018 to October 2020 at the Department of Cardiac Surgery of University Hospital Inte-grated Trust and their subsequent admission at the Postoperative Cardiothoracic Surgery Intensive Care Unit. During the study, central arterial and venous blood gas analysis were carried out before and after cardiopulmonary bypass (CPB) (pre-CPB and post-CPB), at admission to intensive care unit, before and after extubation and at any time of instability or modification of the patient’s clinical and therapeutic conditions. RESULTSː The data analysis shows that 46.9% of the children developed a LCOS (in line with the current literature) but that there is no statistically significant association between the P(v-a)CO2/C(a-v)O2 ratio and LCOS onset. Despite the limits of statistical significance, however, a 31% increase in the ratio emerged from the pre-CPB phase to the post-CPB phase when LCOS is present. CONCLUSIONSː This study confirms a statistically significant association between the most used markers in adult patients (serum lactate concentration, ScVO2 and oxygen extraction ratio-ERO2) measured in the pre-CPB phase and the incidence of LCOS onset, especially in patients with he-modynamic instability before surgery.

Over the years, machine learning has emerged as a tool for automated translation and has been studied relentlessly for decades. RBMT, SMT, and NMT models have been used to achieve machine translation and the results have drastically improved from when research in this field first began. Although a few general-purpose translators such as Google Translate or Microsoft Translator have accurate translations compared to that of a human translator, many pieces of text containing highly technical terms or homonyms are often mistranslated completely. When considering the necessity and importance of translating technical patents from different domains, accuracy in translation is not something that can be compromised. This motivates the need to improve the performance of machine translation further. The scope of this paper covers three open-source machine translation models for the purpose of patent documentation translation from English to Japanese, evaluates their performance on patent data, and proposes a methodology that enabled us to improve one of the model’s BLEU score by 41.22%, achieving a BLEU score of 46.18.

One of the most pivotal challenges that learners may face, during foreign language learning, is building a reliable lexicon. Insufficient vocabulary knowledge may put serious obstacles in the foreign language learning process. Thus, students need to equip themselves with different strategies to cope with these difficulties. Translation equivalence (TE) is one of these strategies. Since the success or failure of any vocabulary learning strategy depends on two main factors: developing the learners’ vocabulary knowledge and the extent of difficulty or ease with which the learner acquires new words, this research aims at investigating the impact of this strategy on EFL learners’ vocabulary knowledge and word learnability. 258 Tunisian 9^th graders participated in this project. Two vocabulary recognition tests, one using translation equivalence and the other using only-English strategies, were used to test the hypotheses. Different statistical tests and techniques were employed to analyze data. Findings showed that TE has a positive impact on learners’ vocabulary knowledge and revealed that students, at this level of proficiency, learn vocabulary through translation better than any other strategy using only English.

The success of Toxoplasma gondii (intracellular parasite) host cell invasion relies on the apical complex, a specialized microtubule cytoskeleton structure associated with secretory organelles. The genome encodes three isoforms of both α- and β-tubulin which are altered by specific post-translational modifications (PTMs), changing the biochemical/biophysical proprieties of microtubules, and modulating their interaction with associated proteins. Tubulin PTMs are a powerful and evolutionarily conserved mechanism to generate tubulin diversity, forming a biochemical ‘tubulin code’ that can be ‘read’ by microtubule-interacting factors. The T. gondii tubulin PTMs are: α-tubulin acetylation, α-tubulin detyrosination, Δ5α-tubulin, Δ2α-tubulin, α- and β-tubulin polyglutamylation, and α- and α-tubulin methylation. Tubulin glutamylation is a key candidate to assist microtubule remodeling in Toxoplasma, being involved in the regulation of microtubule stability, dynamics, interaction with motor proteins, and severing enzymes. The correct balance of tubulin glutamylation is achieved by the coordinated action of polyglutamylases and deglutamylating enzymes. In this work we will review and discuss the current knowledge on T. gondii tubulin glutamylation. By in silico identification of mammalian protein orthologs we explored and updated the identification of putative proteins related to glutamylation, contributing to a better understanding of the role of tubulin glutamylation in T. gondii.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

In post-COVID-19 syndrome, clinical presentation of the nerve fiber dysfunction plays an important role. The possibility of autoantigen cross-mimicry of coronavirus infection and the peripheral nervous system need to be investigated. The bioinformatic analysis was applied to search for possible common protein sequences located in the immunological epitopes. Among the autoantigens of the human nervous system, fibroblast growth factor receptor protein 3, myelin protein P0, myelin protein P2, sodium channel protein type 9, alpha protein subunit, plexin-D1 protein and ubiquitin-carboxyl-terminal hydrolase protein of the L1 isoenzyme were selected. The “Alignmentaj” program was created. The UniProt database, Protein Data Bank and AlphaFold databases were used. The analysis of protein sequence similarities of spike glycoproteins in human coronaviruses revealed common pentapeptides of the MERS-CoV-2 virus with the fibroblast growth factor receptor 3 and myelin protein P2. Among seasonal coronaviruses, common peptide sequences were identified in HCoV-HKU-1 virus with sodium channel protein type 9 subunit alpha and Plexin-D1, HCoV-OС43 with Plexin-D1, as well as HCoV-NL63 with Plexin-D1 and Ubiquitin carboxyl-terminal hydrolase isozyme L1. The data obtained make it possible to identify new potential targets for the development of autoimmune reactions that occur against the background of the activity of highly pathogenic and seasonal coronaviruses.

Pharmacogenomics may improve patient care by guiding drug selection and dosing, however this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe co-morbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV, and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using literature, a list of pharmacogenes vital in disposition of the top 20 drugs was constructed leading to drug-gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants and statins were frequently prescribed cholesterol lowering drugs. HIV was reported in 20.3% of the study participants with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.

Studies over the past three years have substantially expanded the involvements of eIF3 in mRNA translation. It now appears that this multi-subunit complex is involved in every possible form of mRNA translation, controlling every step of protein synthesis from initiation to elongation, termination and quality control in positive as well as negative fashion. Through the study of eIF3, we are beginning to appreciate protein synthesis as a highly integrated process coordinating protein production with protein folding, subcellular targeting, and degradation. At the same time, eIF3 subunits appear to have specific functions that probably vary between different tissues and individual cells. Considering the broad functions of eIF3 in protein homeostasis, it comes as little surprise that eIF3 is increasingly implicated in major human diseases and first attempts at therapeutically targeting eIF3 have been undertaken. Much remains to be learned, however, about subunit- and tissue-specific functions of eIF3 in protein synthesis and disease and their regulation by environmental conditions and posttranslational modifications.

The investigation of membrane proteins, key constituents of cells, is hampered by the difficulty and complexity of their in vitro synthesis, of unpredictable yield. Cell-free synthesis is herein employed to unravel the impact of the expression construct on gene transcription and translation, without the complex regulatory mechanisms of cellular systems. Through the systematic design of plasmids in the immediacy of the start of the target gene, it was possible to identify translation initiation and the conformation of mRNA as the main factors governing the cell-free expression efficiency of the human voltage dependent anion channel (VDAC), a relevant membrane protein in drug-based therapy. A simple translation initiation model was developed to quantitatively assess the expression potential for the designed constructs. A scoring function is proposed that quantifies the feasibility of formation of the translation initiation complex through the ribosome-mRNA hybridization energy and the accessibility of the mRNA segment binding to the ribosome. The scoring function enables to optimize plasmid sequences and semi-quantitatively predict protein expression efficiencies. This scoring function is publicly available as webservice XenoExpressO at rna.tbi.univie.ac.at.

Exploiting the linguistic knowledge of the source language for neural machine translation (NMT) has recently achieved impressive performance on many large-scale language pairs. However, since the Turkish→English machine translation task is low-resource and the source-side Turkish is morphologically-rich, there are limited resources of bilingual corpora and linguistic information available to further improve the NMT performance. Focusing on the above issues, we propose a multi-source NMT approach that models the word feature in parallel to external linguistic features by using two separate encoders to explicitly incorporate linguistic knowledge into the NMT model. We extend the word embedding layer of the knowledge-based encoder to accommodate for each word’s linguistic annotations in the context. Moreover, we share all parameters across encoders to enhance the representation ability of the NMT model on the source language. Experimental results show that our proposed approach achieves substantial improvements of up to 2.4 and 1.1 BLEU scores in Turkish→English and English→Turkish machine translation tasks, respectively, which points to a promising way to utilize the source-side linguistic knowledge for the low-resource NMT.

Circular RNAs (circRNAs) are covalently closed RNAs that are present in all eukaryotes tested. CircRNAs are less abundantly expressed than mRNAs. Recent RNAseq analyses indicate that more than 800,000 circRNA isoforms exist in humans, which is more than twice the number of currently known mRNA isoforms. CircRNAs are generated through backsplicing that depends on pre-mRNA structures, which are influenced by intronic elements, for example primate-specific Alu elements, leading to species-specific circRNAs. CircRNAs are mostly cytosolic, stable and influence cells by sequestering miRNAs and RNA-binding proteins. We review the increasing evidence that circRNAs are translated into proteins using several cap-independent translational mechanisms, that include internal ribosomal entry sites, N6-methyladenosine RNA modification, adenosine to inosine RNA editing and interaction with the eIF4A3 component of the exon junction complex. CircRNA are translated under conditions that favor cap-independent translation, notably in cancer. CircRNA-encoded proteins are shorter than mRNA-encoded proteins and overall have a high propensity for phase separation. In summary, circRNA encoded proteins are translated under particular cellular conditions and contribute to proteome diversity and pathophysiology.

The Transformer architecture, while adept at capturing context through self-attention, falls short in encapsulating complex syntactic structures effectively. Addressing this gap, we introduce the Linguistic Structure through Graphical Interpretation with BERT (LSGIB) approach in Machine Translation (MT) frameworks. Combining the strengths of Graph Attention Network (GAT) and BERT, LSGIB intricately captures syntactic dependencies as explicit knowledge from the source language. This enhances the source language representation and aids in more accurate target language generation. Our empirical analysis leverages gold-standard syntax-annotated sentences and employs a Quality Estimation (QE) model. This approach enables us to assess translation improvements in terms of syntactic accuracy, extending beyond traditional BLEU score metrics. The LSGIB model demonstrates superior translation quality across diverse MT tasks, maintaining robust BLEU scores. Our study delves into the optimal sentence lengths benefiting from LSGIB and identifies which syntactic dependencies are more precisely captured. We observe that GAT's ability to learn specific dependency relations directly influences the translation quality of sentences with those relations. Additionally, we discover that incorporating syntactic structure into BERT's intermediate and lower layers offers a novel approach to modeling linguistic structure in source sentences.

Insulin-degrading enzyme (IDE) is a highly conserved metalloprotease mainly localized in the cytosol. Although IDE can degrade insulin and some other low molecular weight substrates efficiently, its ubiquitous expression suggests additional functions supported by experimental findings, such as a role in stress responses, cellular protein homeostasis. Translation of full-length (Met1) IDE transcripts has reported to result in targeting to mitochondria but the role of IDE in this compartment is unknown. To obtain initial leads on the function of IDE in mitochondria, here we used a proximity biotinylation approach to identify proteins interacting with wild-type and protease-dead IDE targeted to the mitochondrial matrix. We find that mitochondrial IDE interacts strongly with mitochondrial ribosomes as well as with proteins of the respiratory chain. The mitochondrial interactomes of wild type and mutant IDE are highly similar and do not reveal any proteolytic IDE substrates. We speculate that IDE could adopt similar functions in mitochondria as in the cytosol, acting as a chaperone and contributing to protein homeostasis and stress responses.

Abstract: COVID-19 Long Haulers, an estimated 3% to 12% of people infected globally with coronavirus having latter devasting symptoms 12 weeks after the initial infection is on the rise. We conducted a collaborative study with the long covid patient organization in Greece in order to estimate the prevalence, symptoms and problems that adult long haulers experience and then propose a management plan for these patients. Symptoms were obtained from 208 patients using unstructured qualitative free text entries in an anonymized online questionnaire. The majority of respondents (68.8%) were not hospitalized and had been diagnosed more than six months ago with lingering symptoms (66,8%). Eighteen different symptoms (fatigue, tachycardia, shortness of breath, parosmia etc) were mentioned in both hospitalized and community patients. Interestingly, patients with initial mild symptoms suffer from the same persistent symptoms as those who were hospitalized. Awareness of long covid sequelae seems to be low even among medical doctors. Treatment options incorporating targeted rehabilitation programs are either not available or still excluded from the management plan of long covid patients. Since long COVID is a multi-systemic entity, we propose a holistic interventional approach using a multidisciplinary medical team in order to securely and effectively diagnose and treat these specific patients. Academic and medical community must collaborate with long covid patients’ organizations so as to provide personalized medicine.

Background: Post COVID-19 syndrome or Long Covid (LC) is a novel fluctuating condition with a protracted course in some patients. Specialist LC services have been operational in the UK since 2020 and deal with a high caseload of patients. Aims: To evaluate long-term outcomes in patients discharged from a community-based LC specialist service. Methods: A service evaluation study that included patients who were well engaged in the services [completed the standard Patient Reported Outcome Measures (PROMs) and received intervention from clinician(s)] and had been discharged for at least 3 months from the service. They consented to the study and completed standard PROMs: COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), EQ-5D-5L, and National Institute for Health and Care Excellence (NICE) criteria for Myalgia Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS). Results: Out of 460 patients contacted, 112 (average of 37.6 months since infection and 9.8 months post-discharge) completed the PROMs. 90.2% patients continued to experience LC symptoms and disability and had not returned to their pre-COVID health status. The average EQ-5D-5L index score was 0.53 (SD 0.29) highlighting a significant disability and that LC had become a long-term condition (LTC) in majority of patients who responded to the survey. 43% patients met the criteria for suspected ME/CFS. Conclusion: A proportion of LC patients develop Persistent Long Covid (PLC) consistent with a LTC and had a significant overlap with ME/CFS.

This study aimed to translate and validate the Genomic Nursing Concept Inventory (GNCI) in Greek, analyze the genomic knowledge of nurses in Crete, Greece, and explore potential factors that could affect it. This cross-sectional study included 324 nurses from public hospitals and primary care units between July and December 2022. The GNCI is a 31-item questionnaire that evaluates genomic nursing concepts, but it has not been translated and validated in Greek. The translation process included independent forward translations, reconciliation, and back-translation. To evaluate internal consistency, Cronbach’s alpha was used, and Confirmatory Factor Analysis (CFA) was conducted to determine the fit of the model. Multiple linear regression analysis was performed to examine the associations between the demographic variables and GNCI scores. The internal consistency of the GNCI was acceptable (Cronbach’s alpha= 0.622). The CFA indicated that the one-factor model had an adequate fit (SRMR = 0.076, CD = 0.677, CFI = 0.744). The mean GNCI score was moderate (0.35±0.14). Regression analysis suggested that only gender could affect GNCI scores, with female nurses scoring higher than male nurses (p>0.001). In conclusion, the Greek version of the GNCI is a reliable tool for assessing genomic knowledge among Greek nurses.

To investigate the differences in cadium (Cd) uptake and translocation among edible rapes and select suitable rape varieties for safe production, a field experiment was carried out with 25 varieties of edible rapes on a farmland polluted with Cd in the central souothern part of Hunan Province. The growing characteristics and Cd contents in rape tissues were measured, and the amount of Cd removed was calculated. The results showed that the growth of 25 rape varieties was not inhibited without withering or inconsistent changes in leaf and so on. The Cd contents in stem-leaf and root of rapes were in the range 0.05-0.26mg·kg-1 and 0.04-0.26mg·kg-1, respectively. Basing on BCF, the stem-leaf showed a greater capacity for Cd transport than root. And the total Cd removed by rape were 0.002-0.016 mg·plant-1. Except for plant height, BCF of soil available Cd from soil to stem-leaf, TCF of Cd from root to stem-leaf and Cd taken away by rape, there was no significant difference among edible rape varieties. Although Cd contents in stem-leaf of 25 rape varieties does not exceed the national safety standards, planting “Lvjin 1”, “Guanyou Qingjing” and “Guanyou brassica” not only reduced soil pollution but also allowed the production of safe leafy rape.

Recent advancements in neural language models, particularly attention-based architectures like the Transformer, have substantially surpassed traditional methods in various natural language processing tasks. These models adeptly generate nuanced token representations by considering contextual relations within a sequence. However, augmenting these models with explicit syntactic knowledge, such as part of speech tags, has been found to remarkably bolster their effectiveness, especially under constrained data scenarios. This study introduces the Linguistic Enhanced Transformer (LET), which integrates multiple syntactic features, showing a notable increase in translation accuracy, evidenced by an improvement of up to 1.99 BLEU points on subsets of the WMT '14 English-German dataset. Furthermore, this paper demonstrates that enriching BERT models with syntax-aware embeddings enhances their performance on several GLUE benchmark tasks.

This manuscript addresses the phenomenon of masked priming in bilingual individuals. We employed a lexical decision task with masked translation priming, which serves as a valuable tool for elucidating the orthographic and lexical processes involved in the initial stages of reading. Our study builds upon previous research conducted on monolingual masked priming, which consistently demonstrates shifts in the response time (RT) distributions when comparing related and unrelated primes. Within the framework of a diffusion model, we implemented two theoretical positions. First, we posited that translation priming operates at the orthographic level, resulting in enhanced efficiency during the encoding process. Second, we explored the possibility that translation priming operates at the semantic level, influencing the accumulation of evidence during the lexical decision task. Our findings indicate that translation priming elicits outcomes similar to those observed in monolingual priming paradigms. Specifically, we observed that translation priming facilitation is manifested as shifts in the RT distributions. We interpret these findings as suggesting that the benefits derived from the encoding process are not specific to the accessed lexicon following brief stimulus presentation.

Similarly to his special theory of relativity, Einstein's special principle of relativity extends beyond the limits currently known to it. Up to now, the principle has not been suspected to have the potential to translate laws. However, the principle holds an inherent capacity to translate physical laws and, in so doing, speeds up our understanding and control of physical reality. Such a translation of laws leads to the faster discovery of other laws, such as the Laws of Electronic Motion, characterizing the motion of electrons around the atomic nucleus, and the Third Law of Biological Resistance, facilitating the successful control of drug resistance in medicine. The ability of the special principle of relativity to translate laws shines forth once the said principle is duly interpreted. This interpretation exposes a parallelism between experimental frames of reference and justifies the applicability of the laws of one frame of reference in other parallel frames of reference. This process opens the door to our faster discovery of the laws governing a multiplicity of frames parallel to a frame we already know the laws of. In practice, the interpretation of Einstein's special principle of relativity speeds up our understanding of the workings of physical reality and strengthens our capacity to subdue matter.

Malnutrition in children is a global health problem, particularly in developing countries. The effects of an insufficient supply of nutrients on body composition and physiological functions may have implications for drug disposition and ultimately affect the clinical outcome in this vulnerable population. Physiologically based pharmacokinetic (PBPK) modeling can be used to predict the effect of malnutrition as it links physiological changes to pharmacokinetic (PK) consequences. However, the absence of detailed information on body composition and the limited availability of controlled clinical trials in malnourished children complicates the establishment and evaluation of a generic PBPK model in this population. In this manuscript we describe the creation of physiologically-based bridge to a malnourished pediatric population, by combining information on a) the differences in body composition between healthy and malnourished adults and b) the differences in physiology between healthy adults and children. Model performance was confirmed using clinical reference data. This study presents a physiologically-based translational framework for prediction of drug disposition in malnourished children. The model is readily applicable for dose recommendation strategies to address the urgent medicinal needs of this vulnerable population.

Cyclin dependent kinase 1 (CDK1) has been primarily identified as a key cell cycle regulator in both mitosis and meiosis. Recently, an extramitotic function of CDK1 emerged when evidence was found that CDK1 is involved in many cellular events that are essential for cell proliferation and survival. In this review we summarize the involvement of active CDK1 in the initiation and elongation steps of protein synthesis in eukaryotes. During its activation CDK1 influences the initiation of protein synthesis, promotes the activity of specific translational initiation factors and affects the functioning of a subset of elongation factors. Our review provides insights into gene expression regulation during the transcriptionally silent cell cycle/M-phase and describes quantitative and qualitative translational changes based on the extramitotic role of the cell cycle master regulator CDK1, to optimize temporal synthesis of proteins to sustain division-related processes: mitosis and cytokinesis.

The cellular stress response corresponds to the molecular changes that cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression, at transcriptional and post-transcriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support translation of specific mRNAs. One of the major mechanisms involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Importantly, cellular mRNA IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents an update of the reported ITAFs regulating cellular mRNA translation and of the different mechanisms allowing them to control translation initiation in specific conditions. The impact of ITAFs on coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.

The aim was to identify if surface electromyography (sEMG) parameters are indicative of post-activation potentiation (PAP)/post-activation performance enhancement (PAPE), in terms of twitch potentiation and voluntary performance. Three databases were used in March 2024, with the following inclusion criteria: (a) original research, assessed in healthy human adults, (b) sEMG parameters were measured. The exclusion criteria were: (a) studies with no PAP/PAPE-protocol, (b) non-randomized control trials. The following data were extracted: study characteristics/demographics, PAP/PAPE-protocols, sEMG parameters, twitch/performance outcomes, and study findings. A modified physiotherapy evidence database (PEDro) scale was used for quality assessment. Fifteen randomized controlled trials (RCTs), with a total of 199 subjects were included. The M-wave amplitude (combined with a twitch torque outcome) was shown to generally be indicative of PAP. The sEMG amplitude (in some muscles) were found to be indicative of PAPE during ballistic movements, while a small decrease in the MdF (in certain muscles) were shown to reflect PAPE. Changes in the Hmax/Mmax ratio were found to contribute (temporally) to PAP, while the H-reflex amplitude was shown to be neither indicative of PAP nor PAPE. This review provides preliminarily findings suggesting that certain sEMG parameters could be indicative of PAP/PAPE. However, future research is warranted.

Post-ovulatory aging (POA) is an inevitable factor during some assisted reproduction technology procedures, and results in poor fertilization rates and impaired embryo development. This study used RNA sequencing analysis and experimental validation to study the similarities and differences between in vivo- and in vitro-matured porcine oocytes before and after POA. Differentially expressed genes (DEGs) between fresh in vivo-matured oocyte (F_vivo) and aged in vivo-matured oocyte(A_vivo) and DEGs between fresh in vitro-matured oocyte (F_vitro) and aged in vitro-matured oocyte(A_vitro) were intersected to explore the co-effects of POA. It was found that "organelles", especially "mitochondria", were significantly enriched GO terms. The expression of genes related to the “electron transport chain” and “cell redox homeostasis” pathways related to mitochondrial function significantly showed low expression patterns in both A_vivo and A_vitro groups. WGCNA analysis to explore gene expression modules specific to A_vivo. Trait-modules association analysis showed that the red modules were most associated with in vivo aging. There are a total of 959 genes in the red module, which are mainly enriched in “RNA binding”, “mRNA metabolic process”, etc. GO terms, and “spliceosome” and “nucleotide excision repair” pathways. DNAJC7, IK, and DDX18 were at the hub of the gene regulatory network. And these genes were all expressed higher in A_vivo. In summary, POA affects the organelle function of oocytes. A_vivo oocytes have some unique gene expression patterns. These genes may be potential anti-aging targets. This study helps us understand the detailed mechanism of POA and provides strategies for researching oocyte aging.

Background: Patients with burn scars often suffer from a ‘vicious cycle’ in which their skin becomes dry and pruritus. This greatly reduces patients' quality of life, but there is no well-known mechanism yet, and the development of drugs for effective treatment is necessary. Objective: This study evaluated the efficacy and safety of cosmetic formulation containing arginine glutamate ion pair (named as RE:pair) on epidermal barrier function and reducing pruritus. Materials and Methods: A total of 20 patients [15 male and 5 female; average age 48.35 ± 13.13 years] participated in evaluating the effectiveness of using the RE:pair formula topically twice daily for up to 4 weeks after burn pruritus. Treatment efficacy was evaluated by Numerical Rating Scale (NRS) for itching and pain, transepidermal water loss (TEWL), skin hydration, Vancouver Scar Scale (VSS) evaluation, and the patient’s overall satisfaction. Results: This formula was well-tolerated, with significant relief of NRS for itching and pain score after 2nd weeks and 4th weeks of application (p < 0.05). The itching score was high in some patients, and overall, it decreased significantly after 4 weeks compared to before application. Also, the personal pain score decreased after 4th weeks. Overall TEWL showed 35 % improvement after 4th week, and 52 % improvement was confirmed in arms and 19 % in legs. The overall improvement effect of skin hydration was also 45 % (p = 0.0012), and the improvement effect was 40 % (p = 0.0371) in areas including arms and 54 % (p = 0.0313) in areas including legs. All patient satisfactory evaluations were "excellent". Conclusions: RE:pair formula was safe and effective in improving skin barrier and itch relief, and if further studies are conducted, it can be used as an excellent topical treatment for post-burn scar that strengthens the skin barrier.

Open pit mining is a common activity in the Yucatan peninsula for the extraction of limestone. This mining is known under the generic name of quarries, and regionally as sascaberas (sascab=white soil in Mayan language). These areas are characterized by the total removal of the natural vegetation cover and soil in order to have access to the calcareous material. The present study shows the composition and structure of the vegetation in five quarries after approximately ten years of abandonment, and the conserved vegetation near to each one of the quarries in southeastern Quintana Roo. Using a canonical correspondence analysis (CCA), the distribution of the species was determined in relation to the edaphic variables: soil depth, percentage of organic matter (OM), cationic exchange capacity (CEC), pH and texture. 26 families, 46 genera and 50 species were recorded in the quarries and 25 families, 45 genera and 47 species were recorded in the conserved areas. The dominant species in the quarries belong to the families Poaceae, Fabaceae, Rubiaceae and Anacardiaceae. The quarries with higher values of OM (1.63%), CEC (24.05 Cmol/kg), depth (11 cm) and sand percentage (31.33%) include the following species like Lysiloma latisiliquum, Metopium brownei and Bursera simaruba which are commonly found in secondary forests. On the other hand, quarries with lower values of OM (0.39%), CEC (16.58 Cmol/kg) and depth (5.02), and higher percentage of silt (42.44%) were dominated by herbaceous species belonging to the Poaceae family and by Borreria verticillata, which are typical in disturbed areas of southeastern Mexico. In all cases, the pH was slightly alkaline due to the content of calcium carbonate (CaCO3), characteristic of the soils of the region. The edaphic variables are significantly correlated with the development and distribution of vegetation, and with the structure of the communities.

Codon bias analysis of SARS-CoV-2 reveals suboptimal adaptation for translation in human cells it infects. The detailed examination of the codons preferentially used by SARS-CoV-2 shows a strong preference for LysAAA, GlnCAA, GluGAA, and Arg AGA infrequently used in human genes. In the absence of an adapted tRNA pool, efficient decoding of these codons requires a 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2) modification at the U34 wobble position of the corresponding tRNAs (tLysUUU; tGlnUUG; tGluUUC; tArgUCU). The optimal translation of SARS-CoV-2 open reading frames (ORFs) may therefore require several adjustments to the host's translation machinery, enabling the highly biased viral genome to achieve a more favorable "Ready-to-Translate" state in human cells. Experimental approaches based on LC-MS/MS quantification of tRNA modifications and on alteration of enzymatic tRNA modification pathways provide strong evidence to support the hypothesis that SARS-CoV-2 induces U34 tRNA modifications and relies on these modifications for its lifecycle. The conclusions emphasize the need for future studies on the evolution of SARS-CoV-2 codon bias and its ability to alter the host tRNA pool through the manipulation of RNA modifications.

Traditional African vegetables (TAV) are an important component of an ecologically sustainable approach to addressing food and nutrition security in Africa (countries?). This review aims to identify the scope of the knowledge translation literature that exists across multiple aspects of the TAV value chain and to identify gaps in knowledge translation research. A scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) was conducted. The Population, Concept, and Context (PCC) framework was used to guide the development of inclusion and exclusion criteria for this review. Web of Science, Scopus, Science direct and ABI/Inform databases were searched to identify relevant studies which were then screened using the Covidence online software to select studies and extract information for analysis and reporting. A total of 182 studies/articles were selected and examined. The most significant knowledge documented about TAVs is their vast genetic diversity contributing to their rich nutritional and medicinal properties, their ability to withstand harsh environmental conditions such as drought, pests, and diseases as well as the effects of various post-handling techniques on nutrient content of TAVs with the production phase of TAVs value chain being the most studied. This review found that although there is a breadth of knowledge created about TAVs, there is still little documentation of transferring and utilizing of this knowledge across the TAVs value chain. This review identified that more research is needed to document strategies and practices for the transfer and utilisation of knowledge to ensure it is utilized to enhance nutritional outcomes across Africa.

Polyploidy, a prevalent event in plant evolution, drives phenotypic diversification and speciation. While transcriptional changes and regulation in polyploids have been extensively studied, the translational level impact remains largely unexplored. To address this gap, we conducted a com-parative transcriptomic and translatomic analysis of cotton leaves from allopolyploid species G. hirsutum (AD1) and G. barbadense (AD2) relative to their model A-genome and D-genome diploid progenitors. Our data revealed that while allopolyploidization significantly affects the transcrip-tional landscape, its impact on translation was relatively modest, evidenced by a narrower ex-pression range and fewer expression changes in ribosome-protected fragments than in mRNA levels. Allopolyploid-specific changes commonly identified in both AD1 and AD2 were observed in 7,393 genes at either transcriptional or translational levels. Interestingly, the majority of translational changes exhibited concordant down-regulation in both ribosome-protected fragments and mRNA, particularly associated with terpenoid synthesis and metabolism. Regarding translational efficiency (TE), at least one-fifth of cotton genes exhibit translational level regulation, with a general trend of more down-regulation than up-regulation of TE. The magnitude of translational regulation was slightly reduced in allopolyploids compared to diploids, and allopolyploidy tends to have a more profound impact on genes and functional associations with ultra-low TE. Moreover, we demonstrated a reduced extent of homeolog expression biases during translation compared to transcription. In conclusion, our study provides insights into the regulatory consequences of allopolyploidy post-transcription, contributing to a comprehensive understanding of regulatory mechanisms of duplicated gene expression evolution.

Optoacoustic imaging is an emerging technology that holds great promise for improving general clinical practice since it offers a unique combination of optical absorption contrast, high resolution, and high penetration depth. This combination of factors provides a distinct advantage over alternative imaging modalities in oncology, cardiology, dermatology, or endocrinology among other medical fields. Optoacoustic technology affords the medical practitioner the possibility of visualizing light-absorbing biomolecules like water, lipids, oxy/deoxy hemoglobin, or melanin in deep tissue with relatively cheap and small form factor instruments, without the need of contrast agents or ionizing radiation. Moreover, exogenous fluorescent contrast agents like indocyanine green or methylene blue can also be observed. Driven by its potential for new applications in the clinic, the field has experienced intense changes in the last 20 years. Continuous technological advancements in instrumentation, image formation methods, or acquisition geometries, have led to the development of numerous clinical devices also motivating the creation of several startup companies that aim to translate the technology from the lab to the clinic. Thus, the question arises: how far are we from clinical adoption? In this article, we aim to shed light on such question by reviewing the clinical studies that have been performed in the last 10 years. Our intention is to go beyond the classical review format by providing a brief general overview of the steps that new imaging methods undergo on their journey from the lab to clinical adoption. Then we examine the progress that optoacoustic technology has made on such a journey.

The gene translation system possesses inherent complexity in distinguishing codons with degeneracy through repertoires of aminoacyl-tRNAs in the ribosome. Implementation of inosine nucleoside at the anticodon wobble-position in certain tRNAs, especially in eukaryotes, might be arisen to establish complex decoding systems. This report introduces the novel concept of “decoding tables”, which serve as concise summaries of codon-anticodon pairings provided in codon table-like format. Utilizing tRNA genome database information and a procedure based on compiled tRNA studies, the tRNA repertoire and the use of wobble pairings can be depicted for any organisms. The decoding table sheds light on the use of wobble pairings across diverse organisms.

Low-resource languages often face the problem of insufficient data, which leads to poor quality in machine translation. One approach to address this issue is data augmentation. Data augmentation involves creating new data by transforming existing data through methods such as flipping, cropping, rotating, and adding noise. Traditionally, pseudo-parallel corpora are generated by randomly replacing words in low-resource language machine translation. However, this method can introduce ambiguity as the same word may have different meanings in different contexts. This study proposes a new approach for low-resource language machine translation, which involves generating pseudo-parallel corpora by replacing phrases. The performance of this approach is compared with other data augmentation methods, and it is observed that combining it with other data augmentation methods further improves performance. To enhance the robustness of the model, R-Drop regularization is also used. R-Drop is an effective method for improving the quality of machine translation. The proposed method was tested on Chinese-Kazakh (Latin script) translation tasks, resulting in performance improvements of 4.99 and 7.7 for Chinese-to-Kazakh and Kazakh-to-Chinese translations, respectively.

Hypoxia — reduction in oxygen availability—plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OG dioxyenases in the control of gene expression in response to hypoxia and their relevance to human cancers.

We tested the hypothesis that concatemers of ancestral tRNAs gave rise to the 16S ribosomal RNA. We built an ancestral sequence of proto-tRNAs that showed a significant identity of 51.69% and a percentage of structural identity of 0.941 with the 16S ribosomal molecule. We also propose a hypothesis for the emergence of translation.

The vertebrate anterior-posterior (A-P = craniocaudal) axis is evidently made by a timing mechanism. Evidence has accumulated that tentatively identifies the A-P timer as being or involving Hox temporal collinearity. Here, I focus on the two current competing models based on this premise. Common features and points of dissent are examined and a common model is distilled from what remains. This is an attempt to make sense of the literature.

The tremendous diversity and complexity of proteins invariably results in protein misfolding, to which cells have evolved numerous mechanisms of mitigating. Degrading misfolded proteins is perhaps the most intuitive strategy, but also critical to managing proteostasis are the elaborate mechanisms of translational control. Attenuated rates of translation ameliorate protein misfolding by downregulating the flux of new protein and conserving ATP. Loss of translational control, particularly in neurons, constitutes a major proteostatic dysfunction capable of causing or exacerbating neurodegeneration, while interventions aimed at downregulating protein synthesis are generally neuroprotective. In this review, I examine the critical neuronal signaling networks employed to control translation with an emphasis on current research. This includes the Unfolded Protein Response (UPR), the mitochondrial UPR (mtUPR), mTORC1 signaling, and stress granule formation.

Previous studies suggested that trauma-focused cognitive behavior therapy (TF-CBT) is effective in reducing symptoms of post-traumatic stress disorder (PTSD) and depression in children and adolescents. However, the effects of app-assisted TF-CBT-based interventions in psychiatric clinics compared to treatment-as-usual (TAU) are under-explored. The purpose of this study was to reveal the added value of the app-assisted TF-CBT-based intervention as an add-on to TAU. The digitalized measures of the Child and Adolescent Trauma Screen (CATS), The Adolescent Dissociative Experience Scale (A-DES), Short Moods and Feelings Questionnaire (SMFQ), PTSD Checklist (PCL-5), and Children's Post-Traumatic Cognitions Inventory (CPTCI) were applied at baseline and post-treatment. The app-assisted TF-CBT-based group participants started with higher levels of negative alterations in cognition and mood compared to TAU participants but at post-treatment, no significant differences were observed between the app-assisted TF-CBT and TAU groups. Within the app-assisted TF-CBT group, post-treatment scores were significantly lower in post-traumatic stress symptoms, intrusion symptoms, alterations in arousal and reactivity, overall post-traumatic cognitions, and belief in being "a fragile person in a scary world”. Within the TAU group, post-treatment scores were notably lower just in dissociation and intrusion symptoms. The study suggests that app-assisted TF-CBT-based intervention can be effective in addressing specific trauma-related symptoms. The findings imply the necessity for screening for traumatic experiences, incorporating trauma-informed care, implementation of TF-CBT into treatment protocols, utilization of app-assisted interventions, tailoring interventions to individual needs, and comprehensive assessment and monitoring of treatment progress.

Background: This study aimed to examine the course of Depression and anxiety in COVID-19 survivors with a psychiatric history compared with those without a psychiatric history. Methods: A web-based cross-sectional survey for COVID-19 survivors was conducted from July to September 2021. 6016 COVID-19 survivors, the accuracy of whose responses was determined to be assured, were included in analyses. Exposures included psychiatric history and time since COVID-19 infection, and the main outcomes and measures included severity of depression and anxiety, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. Results: Mean severity of PHQ-9 and GAD-7 were significantly higher in participants with a psychiatric history than in those without a psychiatric history. Two-way analysis of covariance for PHQ-9 showed a significant main effect of the presence of psychiatric history and a significant interaction effect of psychiatric history × time since infection. Two-way analysis of covariance for the GAD-7 score revealed a significant main effect of the presence of psychiatric history and time since COVID-19 infection and the interaction effect of these factors. Conclusions: The course of depression and anxiety was more severe in COVID-19 survivors with a psychiatric history than in those without a psychiatric history.

Recent advancements in neural machine translation (NMT) offer promising potential for generating cross-language clinical natural language processing (NLP) resources. There is a pressing need to be able to foster the development of clinical NLP tools that extract key clinical entities in a comparable way for a multitude of medical application scenarios, hindered by lack of multilingual annotated data. This study explores the efficacy of using NMT and annotation projection techniques with expert in the loop validation to develop named entity recognition (NER) systems for an under resourced target language (Catalan) by leveraging Spanish clinical corpora annotated by domain experts. We employed a state-of-the-art NMT system to translate three clinical case corpora. The translated annotations were then projected onto the target language texts and subsequently validated and corrected by clinical domain experts. The efficacy of the resulting NER systems was evaluated against manually annotated test sets in the target language. Our findings indicate that this approach not only facilitates the generation of high-quality training data for the target language (Catalan) but also demonstrates the potential to extend this methodology to other languages, thereby enhancing multilingual clinical NLP resource development. The generated corpora and components are publicly accessible, providing potentially a valuable resource for further research and application in multilingual clinical settings: https://zenodo.org/doi/10.5281/zenodo.13133124.

Regulation at the level of translation plays an essential role in modulating gene expression. Given the importance of knowledge about translationally active mRNAs as an indicator of translation efficiency, it is crucial for researchers to have at their disposal organised sources of functional information on translation - plant translatomic maps similar to transcription maps. The development of a general experimental and computational methodology for constructing translatome maps is essential to address this challenge. In this manuscript, we discuss what researchers can do to design plant translatome maps, namely, we review: (i) experimental methods to obtain translationally active mRNA fractions, considering their advantages and limitations; (ii) additional methodological approaches to obtain complete pools of translationally active mRNAs; (iii) sequencing methods to qualitatively and quantitatively assess different mRNA fractions; and (iv) multivariate analyses of sequencing results by bioinformatics methods, including metrics for assessing mRNA translational activity.

The Pandemic in 2019 forced a digital adaptation with direct consequences on all educational stakeholders. On behalf of teachers and trainers, while many regarded these changes with some scepticism, others embraced the opportunity to integrate technology into their teaching methods and as learning resources. As translation trainers, it is essential to follow and understand the translation market. Thus, the exponential changes that digital technology has brought to this sector over the years impose constant shifts in teaching and learning methods and resources. In fact, translators require vast competencies, amongst which is the flexibility to adapt. In translation training Project-Based Learning (PBL) has been established as an essential teaching and learning method, as it has proven to foster the development of competencies as it simulates the translator's work environment. Thus, the need to adapt new strategies reinforced PBL and its benefits. PBL, however, similar to a freelance translator, places the student in the centre of the learning process, where self-regulation becomes essential, as it is necessary to analyse the market/situation and be flexible enough to adapt to the context accordingly. As of 2018-2019, technical translation courses at ISCAP have implemented PBL as their main teaching and learning method. At the same time, a study on student self-regulation began. The purpose was to understand student perception on their own self-regulation competence and its development or lack thereof after one year of PBL. Results indicate that PBL is seen as a useful simulation of the translation labour market and that it does enhance many essential competences, amongst which is student self-regulation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that caused the COVID-19 pandemic still able to infect the population in many countries. The Omicron strain is the most mutated variant of SARS-CoV-2. The high transmissibility of the strain and the ability to evade immunity require a priority study of its properties in order to quickly create effective means of preventing it. The present work is devoted to the study of in silico interaction of piRNAs with the genome of the SARS-CoV-2 (gRNA) in order to identify endogenous piRNAs and propose synthetic piRNAs with high antiviral activity for drug development. The studies were carried out using proven bioinformatic methods of interaction of the entire SARS-CoV-2 genome with more than eight million piRNAs. Binding sites (BSs) of piRNAs in the 5'UTR were located with overlapping nucleotide sequences called clusters of BSs. Several clusters of BSs were found in the nsp3, nsp7, RNA-dependent RNA polymerase, endoRNAse, S surface glycoprotein, ORF7a and nucleocapsid. 16 synthetic piRNAs have been proposed that interact with gRNA with free binding energy from -170 kJ/mol to -175 kJ/mol, which can be used to create drugs that suppress the reproduction of SARS-CoV-2.

The notion that there is a one to one mapping from genotype to phenotype was overturned a long time ago. Along with genotype and environment, ‘non-genetic changes’ orchestrated by altered RNA and protein molecules also guide the development of phenotype. The idea that there is a route through which changes in phenotype can lead to changes in genotype impinges on several phenomena of molecular, developmental, evolutionary and applied interest. Phenotypic changes that do not alter the underlying DNA sequence have been studied across model systems (eg: DNA and histone modifications, RNA editing, prion formation) and are known to play an important role in short term adaptation. However, because of their transient nature and unstable inheritance, the role of such changes in long term evolution has remained controversial. I classify and review three ways in which non-genetic changes can influence genotype and impact cellular fitness across generations, with an emphasis on the enticing idea that they may act as stepping stones for genetic adaptation. I focus on work from microbial systems and attempt to highlight recent experiments and models that bear on this idea. Overall, I review evidence which suggests that non-genetic changes can impact phenotype via their influence on the genotype, and thus play a role in evolutionary change.

A dogma is normally considered as a principle or a belief accepted as an indisputable truth by some individuals and/or groups. Theoretically there can be no dogmas in science, but it has been demonstrated that scientific thought operates by conceptual changes. A dogma therefore can be understood as a concept present at the heart of some contemporary research programmes that need to be altered to overcome paradigms. Here we argue that two ideas relating to emergence of the biological system research need to be re-evaluated. First, is the idea that research programmes about the emergence of the biological system are the same as those of the origin of cells. Cells are strikingly important biological entities, hard core concepts for the entire field of biology. The emergence of the biological system happened much earlier than the origin of cells and thus the First Universal Common Ancestor (FUCA) should be viewed as a great-grandfather to the Last Universal Cellular Ancestor (LUCA); i.e. the latter is the first cellular life form. Second, RNA-world theories are the focus of mainstream research programmes for the origin of life stricto sensu. In the RNA-world view, self-replication of nucleic acids is seen as one of the most relevant events in the pre-biotic world. Without denying the relevance of self-replication, we argue here that the most germane event which occurred in the pre-biotic world was the crosstalk between nucleic acids and peptides. When these two macromolecules started to interact, the singularity that aggregated the complexity required to produce life emerged. Thus, comprehension of the early origins of the translation machinery and the assembly of the genetic code is key. Therefore, the relevance of cell theory and self-replication should be re-evaluated as well as the concept of life itself.

Musyakalah is one of the Arabic linguistic styles included under the category of majaz. This style is commonly used in Al-Quran. The Indonesian translation of Al-Quran is a case where many of the figures of speech are translated literally, thereby causing serious semantic problems. Thus, the research problem of this is formulated with the following questions: 1) How many musyakalah ayahs are there in Al-Quran?; 2) How are the musyakalah ayahs translated, literally (harfiyya) or interpretatively (tafsiriyya)?; 3) How many ayahs are translated literally and how many are translated interpretatively?; and 4) Which translated musyakalah ayahs have the potential to raise semantic and theological problems? The corpus in this research consists of all musyakalah ayahs in Al-Quran and their translation to Indonesian published by the Department of Religious Affairs of Indonesia. The research adopted a descriptive-semantic method. The findings of this research are: 1) There are only eleven ayahs in Al-Quran using musyakalah style, namely: Alhasyr ayah 19, Ali Imran ayah 54, Annaml ayah 50, Alanfal ayah 30, Asysyura ayah 40, Albaqarah ayah 15, Almaidah 116, Aljatsiah ayah 34, Attaubah ayah 79, Annisa ayah 142, and Albaqarah 194; 2) The musyakalah ayahs translated literally are: Aljatsiah 34, Almaidah 116, Asysura 40, Annaml 50, and Alhasyr 19, whereas the musyakalah ayahs translated interpretatively are Albaqarah 194, Annisa 142, Attaubah 79, Albaqarah 15, Alanfal 30, and Ali Imran 54; 3) Of the eleven musyakalah ayahs, only Alhasyr ayah 19 that is translated correctly and does not have the potential of creating misinterpretation. Meanwhile, the interpretation of the other four ayahs can potentially cause misinterpretation or are against the basic principles of Islam. The six remaining ayahs are translated interpretatively and thus do not have the potential to be misinterpreted; 4) The findings suggest that musyakalah ayahs are more appropriately translated interpretatively. Therefore, the following is recommended: 1) Considering the different characteristics of Arabic and Indonesian languages, studies on Al-Quran translation into Indonesian should continuously be carried out; 2) In order to avoid misinterpretation, it is better that the translation of musyakalah ayahs uses tafsiriyya (interpretative) approach; 3) The harfiyya (literal) and tafsiriyya (interpretative) approaches should be developed for other styles beside musyakalah..

Direct and indirect effects after mine operations cease must ideally be subject to perpetual monitoring routines in order to detect possible risks or avoid adverse effects on the surrounding ecosystems at an early stage. In this contribution, mining subsidence lakes created inside the nature reserve Kirchheller Heide and Hilsfeld Forest are subjected to analysis for a long-term monitoring scheme. For this purpose, we employ high-resolution unmanned aerial system (UAS)-based multispectral and thermal mapping tools to provide a fast, non-invasive and multitemporal environmental monitoring method. Specifically, we propose to monitor vegetation evolution through multispectral analysis, biotypes identification using machine learning algorithms, and water surface extent detection, together with their thermal behavior. The aim of this contribution is to present the proposed workflow and first results to establish a baseline for future analyses and subsequent surveys for longterm multi-temporal monitoring

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital and probably appeared during biogenesis four billion years ago. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and protein molecules, drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: tRNAs, aaRS, mRNAs, and ribosomes. When assembled in the right order, the translation machine created biosynthetic polypeptides, a process that transferred information from mRNAs to proteins. This was the beginning of the prebiotic information age. The molecular attraction between tRNA and amino acids led to different stages of the translation machines and the genetic code. tRNA is an ancient molecule that designed and built mRNA for storing the information of its cognate amino acid. Each mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional. The origin of the genetic code is enigmatic; herein we propose an evolutionary explanation: the demand for a wide range of specific enzymes in the peptide/RNA world was the main selective pressure for the origin of information-directed protein synthesis. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and the adaptive theory. These three theories are compatible with our coevolution model of the translation machines and the genetic code. We suggest biosynthetic pathways as the origin of the specific translation machines which provided the framework for the origin of the genetic code. During translation, the genetic code developed in three stages coincident with the refinement of the translation machines: GNC code developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to understand the prebiotic information system better, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the translation might have worked in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. Using AnyLogic software we were able to simulate and visualize the entire evolution of the translation machines and the genetic code. The results indicate that the emergence of the information age from the peptide/RNA world was a watershed event in the origin of life about four billion years ago.

The Late Heavy Bombardment Period (4.1 to 3.8 billion years ago) of heightened impact cratering activity on young Earth is likely the driving force for the origin of life. During the Eoarchean, asteroids such as carbonaceous chondrites delivered the building blocks of life and water to early Earth. Asteroid collisions created innumerable hydrothermal crater lakes in the Eoarchean crust which inadvertently became the perfect cradle for prebiotic chemistry. These hydrothermal crater lakes were filled with cosmic water and the building blocks of life. forming a thick prebiotic soup. The unique combination of exogenous delivery of extraterrestrial building blocks of life, and the endogenous biosynthesis in hydrothermal impact crater lakes very likely gave rise to life. A new symbiotic model for the origin of life within the hydrothermal crater lakes is here proposed. In this scenario, life arose around four billion years ago through five hierarchical stages of increasing molecular complexity: cosmic, geologic, chemical, information, and biological. During the prebiotic synthesis, membranes first appeared in the hydrothermal crater lakes, followed by the simultaneous origin of RNA and protein molecules, creating the RNA/protein world. These proteins were noncoded protein enzymes that facilitated chemical reactions. RNA molecules formed in the hydrothermal crater basin by polymerization of the nucleotides on the montmorillonite mineral substrate. Similarly, the initial synthesis of abiotic protein enzymes was mediated by the condensation of amino acids on pyrite surfaces. The regular wet-dry cycles within the crater lakes assisted further concentration, condensation, and polymerization of the RNAs and proteins. Lipid membranes randomly encapsulated amino acids, RNA, and protein molecules from the prebiotic soup to initiate a molecular symbiosis inside the protocells, this led to the hierarchical emergence of several cell components. As the role of protein enzymes became essential for catalytic process in the RNA/protein world, Darwinian selection from noncoded to coded protein synthesis led to translation systems and the genetic code, heralding the information stage. In this stage, the biochemical pathways suggest the successive emergence of translation machineries such as tRNAs, aaRS, mRNAs, and of ribosomes for protein synthesis. The molecular attraction between tRNA and amino acid led to the emergence of translation machinery and the genetic code. tRNA is an ancient molecule that created mRNA for the purpose of storing amino acid information like a digital strip. Each mRNA strand became the storage device for genetic information that encoded the amino acid sequences in triplet nucleotides. As information became available in the digital languages of the codon within mRNA, biosynthesis became less random and more organized and directional. The original translation machinery was simpler before the emergence of the ribosome than that of today. We review three main concepts on the origin and evolution of the genetic code: the stereochemical theory, the coevolution theory, and adaptive theory. We believe that these three theories are not mutually exclusive, but are compatible with our coevolution model of translations machines and the genetic code. We suggest biosynthetic pathways as the origin of the translation machine that provided the framework for the origin of the genetic code. During translation, the genetic code developed in three stages coincident with the refinement of the translation machinery: GNC code with four codons and four amino acids during interactions of pre-tRNA/pre-aaRS /pre-mRNA, SNS code consisting of 16 codons and 10 amino acids appeared during the tRNA/aaRS/mRNA interaction, and finally the universal genetic code evolved with the emergence of the tRNA/aaRS/mRNA/ribosome machine. The universal code consists of 64 codons and 20 amino acids, with a redundancy that minimizes errors in translation. To address the question of the origin of the biological information system in the RNA/protein world, we converted letter codons into numerical codons in the Universal Genetic Code Table. We developed a software called CATI (Codon-Amino Acid-Translator-Imitator) to translate randomly chosen numerical codons into corresponding amino acids and vice versa, gaining insight into how translation might have worked in the RNA/protein world. We simulated the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. We used AnyLogic software to simulate and visualize the evolution of the translation machines and the genetic code. We conclude that the emergence of the information age from the RNA/protein world was a watershed event in the origin of life about four billion years ago.

Cotton (Gossypium spp.) is the most important fibre crop worldwide. Black root rot and Fusarium wilt are two major diseases of cotton caused by soil-borne Berkeleyomyces rouxiae and Fusarium oxysporum f. sp. vasinfectum (Fov), respectively. Phenotyping plant symptoms caused by soil-borne pathogens has always been a challenge. To increase the uniformity of infection, we adapted a seedling screening method that directly uses liquid cultures to inoculate the plant roots and the soil. Four isolates each of B. rouxiae and Fov were collected from cotton fields in Australia and were characterised for virulence on cotton under controlled plant growth conditions. While the identity of all four B. rouxiae isolates were confirmed by multi-loci sequencing, only two of them were found to be pathogenic on cotton, suggesting variability in the ability of isolates of this species to cause disease. The four Fov isolates were phylogenetically clustered together with the other Australian Fov isolates and displayed both external and internal symptoms characteristic of Fusarium wilt on cotton plants. Furthermore, the isolates appeared to induce varied levels of plant disease severity indicating differences in their virulence on cotton. To contrast the virulence of the Fov isolates, four putatively non-pathogenic Fusarium oxysporum (Fo) isolates collected from cotton seedlings exhibiting atypical wilt symptoms were assessed for their ability to colonise cotton host. Despite the absence of Secreted In Xylem genes (SIX6, SIX11, SIX13 and SIX14) characteristic of Fov, all four Fo isolates retained the ability to colonise cotton and induce wilt symptoms. This suggests that slightly virulent strains of Fo may contribute to the overall occurrence of Fusarium wilt in cotton fields. Findings from this study will allow better distinction to be made between plant pathogens and endophytes and allow fungal effectors underpinning pathogenicity to be explored.

It was thought until the 1990s that the eukaryotic translation machinery was unable to translate a circular RNA. However internal ribosome entry sites (IRESs) and m⁶A-induced ribosome engagement sites (MIRESs) were discovered, promoting 5’end-independent translation initiation. Today a new family of so-called “non-coding” circular RNAs (circRNAs) has emerged, revealing the pivotal role of 5’end-independent translation. CircRNAs have a strong impact on translational control via their sponge function, and form a new mRNA family as they are translated into proteins with pathophysiological roles. While there is no more doubt about translation of covalently closed circRNA, the linearity of canonical mRNA is only theoretical: it has been shown for more than thirty years that polysomes exhibit a circular form and mRNA functional circularization has been demonstrated in the 1990s by the interaction of initiation factor eIF4G with poly(A) binding protein. More recently, additional mechanisms of 3’-5’ interaction have been reported, including m⁶A modification. Functional circularization enhances translation via ribosome recycling and acceleration of the translation initiation rate. This update of covalently and non-covalently circular mRNA translation landscape shows that RNA circular shape might be the rule for translation with an important impact on disease development and biotechnological applications.

The vertebrate anterior-posterior (A-P) body axis arises due to time space translation (TST). BMP dependent Hox temporal collinearity in early embryonic mesoderm generates the initial vertebrate axial pattern because the Hox codes associated with sequential times are frozen sequentially by BMP inhibiting signals from the embryonic organiser or node. There are three reasons why it is now opportune to review TST. 1/ It has become clear that this mechanism is highly relevant for current and emergent directions in medicine. Making a particular tailored stem cell or culturing a specific organoid in vitro both depend on it. 2/ This unexpected and perhaps unlikely sounding mechanism has recently been thoroughly validated. 8 recent primary publications from 6 major groups confirm that TST is the mechanism for primary axial patterning in the 4 best investigated vertebrate embryos. 3/ Its mechanism is now becoming clear. Previous publications propose it involves Hox regulation of cell movement during gastrulation or sequential stabilisation of Hox codes by anti BMP as above. Neither of these processes works alone but together they amount to a very convincing mechanism.

Contrary to optical images, Synthetic Aperture Radar (SAR) images are in different electromagnetic spectrum where the human visual system is not accustomed to. Thus, with more and more SAR applications, the demand for enhanced high-quality SAR images has increased considerably. However, high-quality SAR images entail high costs due to the limitations of current SAR devices and their image processing resources. To improve the quality of SAR images and to reduce the costs of their generation, we propose a Dialectical Generative Adversarial Network (Dialectical GAN) to generate high-quality SAR images. This method is based on the analysis of hierarchical SAR information and the “dialectical” structure of GAN frameworks. As a demonstration, a typical example will be shown where a low-resolution SAR image (e.g., a Sentinel-1 image) with large ground coverage is translated into a high-resolution SAR image (e.g., a TerraSAR-X image). Three traditional algorithms are compared, and a new algorithm is proposed based on a network framework by combining conditional WGAN-GP (Wasserstein Generative Adversarial Network - Gradient Penalty) loss functions and Spatial Gram matrices under the rule of dialectics. Experimental results show that the SAR image translation works very well when we compare the results of our proposed method with the selected traditional methods.

This study presents a French translation and validation of the Durand Adaptive Psychopathic Traits Questionnaire (DAPTQ), an instrument for assessing adaptive traits known to correlate with the psychopathic personality. Bilingual (French and English) individuals from France and Canada (N = 141, 52% in France, M_age = 29.73, SD = 9.09) completed both versions of the DAPTQ (French and English), alongside measurements of perceived stress, trait anxiety, authentic leadership and creativity. Correlation between the DAPTQ total and subscales across versions showed strong associations (r = .84 to .96). The DAPTQ – French version also demonstrated good internal consistency (α = .87), convergent validity, and concurrent validity. These findings support the cross-cultural equivalence of the DAPTQ and therefore its effectiveness as a valid assessment method of adaptive traits.

Premortem clinical diagnoses and postmortem autopsy findings do not match throughout history. These clinicopathological discrepancies are expected to be raised during the coronavirus disease 2019 (COVID-19) pandemic due to increased pressure on healthcare. At the same time, autopsies and clinicopathological discrepancies accurately display the quality of the healthcare system. To assess that, we examined the relevant works of literature according to the PRISMA-based protocol. As discrepancy rate changes in the correlation to the length of stay in the hospital, we also checked whether studies with patients from the intensive care unit (ICU) differed in discrepancies significantly. We found overall risk differences pretty much alike in "pre-COVID" and "during the pandemic" groups of studies. Based on that, we concluded that healthcare quality did not drop significantly during the pandemic. Be it as it may, the pandemic exposed some shortcomings in mortem healthcare regarding consensus to the autopsy, organ retention, burial, and the postponed burial or the digitalization of post mortem healthcare. All of these issues should be addressed in the future.

The embryonic epicardium originates from the proepicardium, an extracardiac primordium constituted by a cluster of mesothelial cells. In early embryos, the embryonic epicardium is characterized by a squamous cell epithelium resting on the myocardium surface. Subsequently, it invades the subepicardial space and thereafter the embryonic myocardium by means of epithelial-mesenchymal transition. Within the myocardium, epicardial-derived cells present multilineage potential, later differentiating into smooth muscle cells and contributing both to coronary vasculature and cardiac fibroblasts in the mature heart. Over the last decades, we have progressively increased our understanding of those cellular and molecular mechanisms driving proepicardial/embryonic epicardium formation. This study provides a state-of-the-art review of the transcriptional and emerging post-transcriptional mechanisms involved in the formation and differentiation of the embryonic epicardium.

Background: Whilst lack of concentration is a known symptom of anaemia, its association with post-stroke dementia is unclear. Methods: We used data from a UK regional stroke register. To be eligible, patient must have survived to discharge and had anaemia by WHO criteria. Dementia status and other prevalent co-morbidities were assessed using ICD-10 codes. Patients were followed till May 2015 (mean follow-up 3.7 years, total person years = 27,769). Hazard Ratio for incident dementia was calculated using Cox-proportional hazards model controlling for potential confounders. Fine and Gray model was additionally constructed using mortality as the competing risk. Results: A total of 7,454 stroke patients were included with mean age (SD) of 75.9(12.3) years (50.2% men). Those with anaemia were older, has higher disability and co-morbidity burden prior to stroke. We observed a large amount of variation in the dementia incidence rates over time and that the hazard ratio increased every year. The significant association between anaemia and dementia incidence was lost after controlling for pre-stroke Modified Rankin score (HR1.17(0.97,1.40)). With every 20g/dL increase in Hb was associated with a significant reduction in the risk of dementia after adjustment for age, sex, stroke factors and disability but lost significance after adjustment for vascular risk factors. Competing risk analyses showed similar results. Conclusion: Whilst we found no evidence of anaemia as a risk factor for post-stroke dementia, the findings may be limited by potential under recognition of post stroke dementia.

The Sars-Cov-2 pandemic led to several needed containing measures that conditioned the onset of depressive, anxiety and post-traumatic stress symptoms in population. These symptoms, espe-cially if not diagnosed and treated, can also occur in patients undergoing surgery with high im-pact on people’s lives, like hysterectomy. To evaluate the post-surgical distress and anx-ious-depressive symptoms following hysterectomy for benign disease focusing on the impact of COVID-19 pandemic. The prospective observational cohort study included patients undergoing hysterectomy for benign disease. Psychologic evaluation through social-demographic question-naires was obtained before surgery (T1), postoperatively (T2), and 3 months after surgery (T3). The HADS (Hospital Anxiety and Depression Scale) was used to evaluate anxious-depressive symptoms and the PCL-5 (Post-traumatic Stress Disorder Checklist for DSM-5) compared the on-set of post-surgical distress and anxiety and depressive symptoms. The pre-COVID-19 pan-demic period was compared to the post-COVID-19 pandemic phase. Patients treated after COVID-19 pandemic showed higher depressive symptoms rate compared to those treated before (p-value=0.02); conversely, pre-COVID-19 patients were more prone to develop a PTSD (p-value=0.04). A significative association between the occurrence PTSD and anxiety-depressive symptoms registered at T2 a (p-value=0.007) and T3 (p-value

Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; chronic, low grade inflammatory response; immune dysregulation and defective immune response; reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal dysregulation, mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; as well as cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers or their link to etiopathogenetic mechanisms, and the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on main LC symptomatology in the frame of the epidemiological and pathogenetic aspects of the syndrome, and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven by recruitment of brain stress systems. However, AUD differs among the sexes: men are more likely to develop AUD, but women progress from casual to binge drinking and heavy alcohol use more quickly. The central amygdala (CeA) is a hub of stress and anxiety, with corticotropin releasing factor (CRF)-CRF1 receptor and GABAergic signaling dysregulation occurring in alcohol dependent male rodents. However, we recently showed that GABAergic synapses in female rats are less sensitive to the acute effects of ethanol. Here, we used patch clamp electrophysiology to examine the effects of alcohol dependence on the CRF-modulation of rat CeA GABAergic transmission of both sexes. We found that GABAergic synapses of naïve female rats were unresponsive to CRF application compared males, although alcohol dependence induced a similar CRF responsivity in both sexes. In situ hybridization revealed that females had less CeA neurons containing mRNA for the CRF1 receptor (Crhr1) than males, but in dependence, the percentage of Crhr1-expressing neurons in females increased, unlike males. Overall, our data provide evidence for sexually dimorphic CeA CRF system effects on GABAergic synapses in dependence.

For disciplines like biological science, security, and the medical field, link prediction is a popular research area. To demonstrate the link prediction many methods have been proposed. Some of them that have been demonstrated through this review paper are TransE, Complex, DistMult, and DensE models. Each model defines link prediction with different perceptions. We argue that the practical performance potential of these methods, having similar parameter values, using the fine-tuning technique to evaluate their reliability and reproducibility of results. We describe those methods and experiments; provide theoretical proofs and experimental examples, demonstrating how current link prediction methods work in such settings. We use the standard evaluation metrics for testing the model's ability.

Bacteria participate in a wide diversity of symbiotic associations with eukaryotic hosts that require precise interactions for bacterial recognition and persistence. Most commonly, host-associated bacteria interfere with host gene expression to modulate the immune response to the infection. However, many of these bacteria also interfere with host cellular differentiation pathways to create a hospitable niche, resulting in the formation of novel cell types, tissues, and organs. In both of these situations, bacterial symbionts must interact with eukaryotic regulatory pathways. Here, we detail what is known about how bacterial symbionts, from pathogens to mutualists, control host cellular differentiation across the central dogma, from epigenetic chromatin modifications, to transcription and mRNA processing, to translation and protein modifications. We identify four main trends from this survey. First, mechanisms for controlling host gene expression appear to evolve from symbionts co-opting cross-talk between host signalling pathways. Second, symbiont regulatory capacity is constrained by the processes that drive reductive genome evolution in host-associated bacteria. Third, the regulatory mechanisms symbionts exhibit correlate with the cost/benefit nature of the association. And, fourth symbiont mechanisms for interacting with host genetic regulatory elements are not bound by native bacterial capabilities. Using this knowledge, we explore how the ubiquitous intracellular Wolbachia symbiont of arthropods and nematodes may modulate host cellular differentiation to manipulate host reproduction. Our survey of the literature on how infection alters gene expression in Wolbachia and its hosts revealed that, despite their intermediate-sized genomes, different strains appear capable of a wide diversity of regulatory manipulations. Given this and Wolbachia’s diversity of phenotypes and eukaryotic-like proteins, we expect that many symbiont-induced host differentiation mechanisms will be discovered in this system.

Mammalian genomes encode tens of thousands of long-noncoding RNAs (lncRNAs), which are capable of interactions with DNA, RNA and protein molecules, thereby enabling a variety of transcriptional and post-transcriptional regulatory activities. Strikingly, about 40% of lncRNAs are expressed specifically in the brain in precisely regulated temporal and spatial expression patterns. In stark contrast to the highly conserved repertoire of protein-coding genes, thousands of new lncRNAs have appeared during primate nervous system evolution with hundreds of human-specific lncRNAs. Their evolvable nature and the myriad of potential functions make lncRNAs ideal candidates for drivers of human brain evolution. The human brain displays the largest relative volume of any animal species and the most remarkable cognitive abilities. In addition to brain size, structural reorganization and adaptive changes represent crucial hallmarks of human brain evolution. LncRNAs are increasingly reported to be involved in neurodevelopmental processes including proliferation, neurite outgrowth and synaptogenesis, as well as in neuroplasticity, suggested to underlie human brain evolution. Hence, evolutionary human brain adaptations are proposed to be essentially driven by lncRNAs, which will be discussed in this review.

The existence of a common ancestor to all living organisms in Earth is a necessary corollary of Darwin idea of common ancestry. The Last Universal Common Ancestor (LUCA) has been normally considered as the ancestor of cellular organisms that originated the three domains of life: Bacteria, Archaea and Eukarya. Recent studies about the nature of LUCA indicate that this first organism should present hundreds of genes and a complex metabolism. Trying to bring another of Darwin ideas into the origins of life discussion, we went back into the prebiotic chemistry trying to understand how LUCA could be originated under gradualist assumptions. Along this line of reasoning, it became clear to us that the definition of another ancestral should be of particular relevance to the understanding about the emergence of biological systems. Together with the view of biology as a language for chemical translation, on which proteins are encoded into nucleic acids polymers, we glimpse a point in the deep past on which this Translation mechanism could have taken place. Thus, we propose the emergence of this process shared by all biological systems as a point of interest and propose the existence of this pre-cellular entity named FUCA, as the First Universal Common Ancestor. FUCA was born in the very instant on which RNA-world replicators started to be capable to catalyze the bonding of amino acids into oligopeptides. FUCA has been considered mature when the translation system apparatus has been assembled together with the establishment of a primeval, possibly error-prone genetic code. This is FUCA, the earliest ancestor of LUCA’s lineage.

The evolution of release factors catalyzing the hydrolysis of the final peptidyl-tRNA bond and the release of the polypeptide from the ribosome has been a longstanding paradox. While the components of the translation apparatus are generally well-conserved across extant life, structurally-unrelated release factor peptidyl hydrolases (RF-PHs) emerged in the stems of the bacterial and archaeo-eukaryotic lineages. We analyze the diversification of RF-PH domains within the broader evolutionary framework of the translation apparatus. Thus, we reconstruct the possible state of translation termination in the Last Universal Common Ancestor with possible tRNA-like terminators. Further, evolutionary trajectories of the several auxiliary release factors in ribosome quality control (RQC) and rescue pathways point to multiple independent solutions to this problem and frequent transfers between superkingdoms including the recently-characterized ArfT, which is more widely-distributed across life than previously appreciated. The eukaryotic RQC system was pieced together from components with disparate provenance, which include the long-sought Vms1/ANKZF1 RF-PH of bacterial origin. We also uncover an under-appreciated evolutionary driver of innovation in rescue pathways: effectors deployed in biological conflicts that target the ribosome. At least three rescue pathways (centered on the prfH/RFH, baeRF-1, and C12orf65 RF-PH domains), were likely innovated in response to such conflicts.

Chikungunya virus is a re-emerging mosquito-borne alphavirus. Outbreaks are unpredictable and explosive in nature. Fever, arthralgia, and rash are common symptoms during the acute phase. Diagnostic tests are required to differentiate chikungunya virus from other co-circulating arboviruses, as symptoms can overlap, causing a dilemma for clinicians. Arthritis is observed during the sub-acute and chronic phases, which can flare up, resulting in increased morbidity that adversely affects activities of daily living. During the 2019 chikungunya epidemic in Thailand, cases surged in Bangkok in the last quarter of the year. Here, we demonstrate the chronic sequelae of post-chikungunya arthritis in one of our patients 1 year after the initial infection. An inflammatory process involving edema, erythema, and tenderness to palpation of her fingers' flexor surfaces was observed, with positive chikungunya IgG and negative IgM tests and antigen. The condition produced stiffness in the patient’s fingers and limited their range of motion, adversely affecting daily living activities. Resolution of symptoms was observed with a short course of an anti-inflammatory agent. More research is required to determine whether sanctuaries enable chikungunya virus to evade the host immune response and remain latent, flaring up months later and triggering an inflammatory response that causes post-chikungunya arthritis.

Introduction: Urological conditions significantly impact global health, with increasing demand for urologists in both developed and developing countries. Disparities in access to surgical care between high-income countries (HICs) and low- and middle-income countries (LMICs) are evident. Despite advancements in urology, LMIC training programs often follow outdated curricula and traditional methods. Methodology: A comprehensive search strategy identified urology training programs in LMICs using the EduRank website, Google searches, and PubMed. Data were collected from literature, official documents, and online resources, focusing on variables such as program duration, research requirements, and resident salaries. Results: The analysis revealed significant variability in program structures and requirements across LMICs. Residency training durations ranged from 4 to 6 years, with inconsistent research obligations and resident salaries averaging $12,857 annually, with a range from 5,412 to 18,174$. Fellowship opportunities were limited, with only a small number of programs achieving international accreditation. Conclusion: The study highlights substantial disparities in urology training between HICs and LMICs. There is an urgent need for standardized and locally tailored training frameworks to enhance the quality of urology education in LMICs. Future research should focus on developing strategies to improve training opportunities, ensuring equitable access to advanced urological care and education globally.

BACKGROUND This study investigated the association of postprandial plasma glucose (PPG) with cancer mortality using a general cohort of US adults. METHODS This cohort study included 14,860 US adults who attended the third National Health and Nutrition Examination Survey from 1988 to 1994, with mortality being followed up to December 31, 2019. The experimental exposures were levels of plasma glucose, including PPG with a fasting time of 0-3.9 h (PPG_0-3.9h) and 4-7.9 h (PPG_4-7.9h), plasma glucose with a fasting time ≥ 8 h (PG_fasting), and plasma glucose at 2 h after oral glucose tolerance test (PG_2hOGTT). Plasma glucose-associated cancer mortality risk was assessed using Cox proportional hazards models. RESULTS A 1-natural-log-unit increase in PPG_4-7.9h was associated with a higher multivariate-adjusted risk for cancer mortality [hazard ratio (HR), 3.24; 95% confidence interval (CI), 1.50-7.00]. However, PPG_0-3.9h, PG_fasting, PG_2hOGTT, hemoglobin A_1c, and insulin were not significantly associated with cancer mortality. The positive association of PPG_4-7.9h with cancer mortality remained in those without a prior diagnosis of cancer. CONCLUSIONS High PPG_4-7.9h is associated with a higher cancer mortality risk in US adults. Lowering PPG_4-7.9h may reduce cancer mortality.

Breast Angiosarcoma is a rare malignancy, accounting less than 1% of all soft tissue. It comprises primitive and secondary subtypes, such as radiogenic breast angiosarcoma (RAS). Despite the multimodal treatment, angiosarcomas represent an incurable disease for many patients and represent a cause of substantial deterioration of their quality of life. Surgery represents the cornerstone in the management, but high recurrence rates are reported. Electrochemotherapy (ECT) is practicable locoregional treatment in patients with advanced angiosarcoma, in a multimodal therapeutic strategy. ECT palliative benefit includes optimal patient compliance, good local hemostasis control, and local responses. Considering that only 22 cases are described in literature, we reported a rare case of RAS treated with ECT, after a multidisciplinary approach including Next Generation Sequencing (NGS). A literature review about the feasibility of ECT in RAS management was also performed.

Objectives: To examine the long term impact of COVID-19 on sleep patterns and development of sleep disorders. Methods: Using the centralized Massachusetts General Brigham (MGB) Research Patient Data Registry (RPDR), SARS-CoV2 positive patients were surveyed about their sleep patterns before and after the viral infection. Information related to co-morbid conditions and medications were obtained through chart review. Results: Two hundred and forty five completed surverys were analysed. Average age was 53.3 ± 16.3 years, and participants were predominantly Non-Hispanic White (84.1%) and female (74.3%). Average BMI (kg/m2) was 29.9 ± 6.9, and a greater proportion was non-smokers (63.2%). After COVID-19, there was an increase in the percentage of participants reporting difficulty initiating (31 ± 46% vs. 39 ± 49%, P=0.01), and maintaining sleep (43 ± 49% vs. 57 ± 49%, P<0.001), and use of sleep aids (24 ± 43% vs. 30 ± 45% P=0.003) with an incidence rate of 24.3%, 37.4%, and 12.3% respectively. In addition, there was an increase in daytime fatigue and the need for napping (58 ± 49% vs. 36 ± 48%, P <0.0001) with an incidence of 8% and 23% respectively. The sleep symptoms persisted beyond 12 months among 28% of the participants and were predominantly seen among women. Conclusions: Infection with SARS-CoV2 has negative effects on sleep, and a significant proportion of adults experience insomnia and daytime sleepiness beyond 12 months after recovering from the initial infection.

Despite the relative scarcity of studies focusing on pharmacotherapy in aphasia, there is evidence in the literature indicating that remediation of language disorders via pharmaceutical agents could be a promising aphasia treatment option. Among the various agents used to treat chronic aphasic deficits, cholinergic drugs have provided interesting results. In the current review, we focused on published reports investigating the impact of acetylcholine on language and further cognitive disturbances. It has been suggested that acetylcholine plays an important role in neuroplasticity and is related to several aspects of cognition, such as memory and attention. Moreover, cholinergic input is diffused to a wide network of cortical areas, which have been associated with language sub-processes. This could be a possible explanation for the positive reported outcomes of cholinergic drugs in aphasia recovery, and specifically in distinct language processes, such as naming and comprehension, as well as overall communication competence. However, evidence with regard to functional alterations in specific brain areas after pharmacotherapy is rather limited. Finally, despite the positive results derived from the relevant studies, cholinergic pharmacotherapy treatment in post-stroke aphasia has not been widely implemented. The present review aims to provide an overview of the existing literature in cholinergic pharmacotherapy interventions in post-stroke aphasia, following an integrated approach by converging evidence from neuroanatomy, neurophysiology, and neuropsychology.

Our understanding of Alzheimer’s disease (AD) pathogenesis has developed with several hypotheses over the last 40 years, including the Amyloid and Tau hypotheses, respectively. More recently, the p53 protein, well-known as ‘the guardian of the genome,’ has gained attention for its role in the early evolution of AD. This is due to p53’s central role in the control of oxidative stress and potential involvement in both Amyloid and Tau pathways. p53 is commonly regulated by post-translational modifications (PTMs), which affect its conformation, increasing its capacity to adopt multiple structural and functional states, including those that can influence several processes in AD. The following review will explore the impact of p53 post-translational modifications (PTMs) on its function and consequential involvement in AD pathogenesis.

Abstract Objectives To assess the causes and risk factors of posttraumatic stress disorder (PTSD) in adult asylum seekers and refugees. To explore whether the causes and risk factors of PTSD, between male and female adult refugees/ asylum seekers is different. Study design Systematic review of current literature. Data Sources PubMed, Web of Science, Scopus and Google Scholar up until February 2019 Method A structured systematic search was conducted in the relevant databases. Papers were excluded, if they failed to meet the inclusion and exclusion criteria. Afterwards, a qualitative assessment was performed on the selected papers. Results 12 Studies were included for the final analysis. All papers were either case studies/report or cross sectional studies. The number of traumatic events experienced by refugees/asylum seekers, is the most frequently reported pre-migration causes for PTSD development. Whilst acculturative stress, is the most common post migration stressor. There were mixed reports, regarding the causes of PTSD between both genders of refugees/asylum seekers. Conclusion This reviews’ findings, have potential clinical application into helping clinicians, to risk stratify refugees/asylum seekers for PTSD development and thus aid in embarking on earlier intervention measures. However, more rigorous research similar to this one, is needed for it to be implemented into clinical practice.

Public key encryption methods are often used to create a digital signature, and where Bob has a public key and a private key. In order to prove his identity, he will encrypt something related to the message with his private key, and which can then be checked with his public key. The main current methods of public-key encryption include RSA and ECC (Elliptic Curve Cryptography), and which involve computationally difficult operations. But these operations have not been proven to be hard in an era of quantum computers. One well-known hard problem is the solving of quadratic equations with $m$ equations with $n$ variables. This is a known NP-hard problem, even in a world of quantum computers. These can be used as post-quantum signature schemes and which involve multivariate equations. In order to understand these methods, this paper outlines a simple example of implementing the oil and vinegar method, and where we have a number of unknown oil variables and a number of known vinegar variables, and where the vinegar variables help convert the hard problem into an easy one.

Localized protein translation occurs through trafficking of mRNAs and protein translation machineries to different compartments of the cell, leading to rapid on-site synthesis of proteins in response to signaling cues. The spatiotemporally precise nature of the local translation process necessitates continual developments of technologies reviewed herein to visualize and map biomolecular components and the translation process with better spatial and temporal resolution, and with fewer artifacts. We also discuss approaches to control local translation, which can serve as a design paradigm for subcellular genetic devices for eukaryotic synthetic biology.

Genetic factors influence medication response (pharmacogenetics), affecting the pharmacody-namics and pharmacokinetics of many medicaments used in clinical care. The ability of medica-tions to cross the blood-brain barrier (BBB) represents a critical putative factor in the effectiveness and tolerability of various central nervous system (CNS) medications at a pharmacokinetic (dosing) level. Pharmacogenetics has the potential to personalise medicine to a greater extent than has been possible, with the potential to help reduce heuristic delays to effective tolerable pharmacotherapy. Here, we critically examine and summarise the evidence, particularly for ABCB1 polymorphisms associated with various CNS medications. These transporters appear to have a role in BBB pharmacogenetics. We identify some of the most promising variants for clinical translation while spotlighting the complexities of the involved systems and limitations of the current empirical literature.

As large language models (LLMs) continue to advance, evaluating their comprehensive capabilities becomes significant for their application in various fields. This research study comprehensively evaluates the language, vision, speech, and multimodal capabilities of GPT-4o. The study employs standardized exam questions, reasoning tasks, and translation assessments to assess the model's language capability. Additionally, GPT-4o's vision and speech capabilities are tested through image classification and object recognition tasks, as well as accent classification. The multimodal evaluation assesses the model's performance in integrating visual and linguistic data. Our findings reveal that GPT-4o demonstrates high accuracy and efficiency across multiple domains in language and reasoning capabilities, excelling in tasks that require few-shot learning. GPT-4o also provides notable improvements in multimodal tasks compared to its predecessors. However, the model shows variability and faces limitations in handling complex and ambiguous inputs, particularly in audio and vision capabilities. This paper highlights the need for more comprehensive benchmarks and robust evaluation frameworks, encompassing qualitative assessments involving human judgment as well as error analysis. Future work should focus on expanding datasets, investigating prompt-based assessment, and enhancing few-shot learning techniques to test the model's practical applicability and performance in real-world scenarios.