Machine Learning Applications in Optical Fiber Sensing: A Research Agenda.

The constant monitoring and control of various health, infrastructure, and natural factors have led to the design and development of technological devices in a wide range of fields. This has resulted in the creation of different types of sensors that can be used to monitor and control different environments, such as fire, water, temperature, and movement, among others. These sensors detect anomalies in the input data to the system, allowing alerts to be generated for early risk detection. The advancement of artificial intelligence has led to improved sensor systems and networks, resulting in devices with better performance and more precise results by incorporating various features. The aim of this work is to conduct a bibliometric analysis using the PRISMA 2020 set to identify research trends in the development of machine learning applications in fiber optic sensors. This methodology facilitates the analysis of a dataset comprised of documents obtained from Scopus and Web of Science databases. It enables the evaluation of both the quantity and quality of publications in the study area based on specific criteria, such as trends, key concepts, and advances in concepts over time. The study found that deep learning techniques and fiber Bragg gratings have been extensively researched in infrastructure, with a focus on using fiber optic sensors for structural health monitoring in future research. One of the main limitations is the lack of research on the use of novel materials, such as graphite, for designing fiber optic sensors. One of the main limitations is the lack of research on the use of novel materials, such as graphite, for designing fiber optic sensors. This presents an opportunity for future studies.

Cardiolipin Membranes Promote Cytochrome c Transformation of Polycyclic Aromatic Hydrocarbons and Their In Vivo Metabolites.

The catalytic properties of cytochrome c (Cc) have captured great interest in respect to mitochondrial physiology and apoptosis, and hold potential for novel enzymatic bioremediation systems. Nevertheless, its contribution to the metabolism of environmental toxicants remains unstudied. Human exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with impactful diseases, and animal models have unveiled concerning signs of PAHs' toxicity to mitochondria. In this work, a series of eight PAHs with ionization potentials between 7.2 and 8.1 eV were used to challenge the catalytic ability of Cc and to evaluate the effect of vesicles containing cardiolipin mimicking mitochondrial membranes activating the peroxidase activity of Cc. With moderate levels of H2O2 and at pH 7.0, Cc catalyzed the oxidation of toxic PAHs, such as benzo[a]pyrene, anthracene, and benzo[a]anthracene, and the cardiolipin-containing membranes clearly increased the PAH conversions. Our results also demonstrate for the first time that Cc and Cc-cardiolipin complexes efficiently transformed the PAH metabolites 2-hydroxynaphthalene and 1-hydroxypyrene. In comparison to horseradish peroxidase, Cc was shown to reach more potent oxidizing states and react with PAHs with ionization potentials up to 7.70 eV, including pyrene and acenaphthene. Spectral assays indicated that anthracene binds to Cc, and docking simulations proposed possible binding sites positioning anthracene for oxidation. The results give support to the participation of Cc in the metabolism of PAHs, especially in mitochondria, and encourage further investigation of the molecular interaction between PAHs and Cc.

Geospatial investigations in Colombia reveal variations in the distribution of mood and psychotic disorders.

BACKGROUND: Geographical variations in mood and psychotic disorders have been found in upper-income countries. We looked for geographic variation in these disorders in Colombia, a middle-income country. We analyzed electronic health records from the Clínica San Juan de Dios Manizales (CSJDM), which provides comprehensive mental healthcare for the one million inhabitants of Caldas. METHODS: We constructed a friction surface map of Caldas and used it to calculate the travel-time to the CSJDM for 16,295 patients who had received an initial diagnosis of mood or psychotic disorder. Using a zero-inflated negative binomial regression model, we determined the relationship between travel-time and incidence, stratified by disease severity. We employed spatial scan statistics to look for patient clusters. RESULTS: We show that travel-times (for driving) to the CSJDM are less than 1 h for ~50% of the population and more than 4 h for ~10%. We find a distance-decay relationship for outpatients, but not for inpatients: for every hour increase in travel-time, the number of expected outpatient cases decreases by 20% (RR = 0.80, 95% confidence interval [0.71, 0.89], p = 5.67E-05). We find nine clusters/hotspots of inpatients. CONCLUSIONS: Our results reveal inequities in access to healthcare: many individuals requiring only outpatient treatment may live too far from the CSJDM to access healthcare. Targeting of resources to comprehensively identify severely ill individuals living in the observed hotspots could further address treatment inequities and enable investigations to determine factors generating these hotspots.

The frequencies of mental disorders vary by geographic region. Investigating such variations may lead to more equitable access to mental healthcare and to scientific discoveries that reveal specific localized factors that contribute to the causes of mental illness. This study examined the frequency of three disorders with a major impact on public health ­ schizophrenia, bipolar disorder, and major depressive disorder ­ by analyzing electronic health records from a hospital providing comprehensive mental health care for a large region in Colombia. We show that individuals receiving outpatient care mainly live relatively near the facility. Those receiving inpatient care live throughout the region, but cluster in a few scattered locations. Future research could lead to strategies for more equitable provision of mental healthcare in Colombia and identify environmental or genetic factors that affect the likelihood that someone will develop one of these disorders.

Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?

Lipid membrane nanodomains or lipid rafts are 10-200 nm diameter size cholesterol- and sphingolipid-enriched domains of the plasma membrane, gathering many proteins with different roles. Isolation and characterization of plasma membrane proteins by differential centrifugation and proteomic studies have revealed a remarkable diversity of proteins in these domains. The limited size of the lipid membrane nanodomain challenges the simple possibility that all of them can coexist within the same lipid membrane domain. As caveolin-1, flotillin isoforms and gangliosides are currently used as neuronal lipid membrane nanodomain markers, we first analyzed the structural features of these components forming nanodomains at the plasma membrane since they are relevant for building supramolecular complexes constituted by these molecular signatures. Among the proteins associated with neuronal lipid membrane nanodomains, there are a large number of proteins that play major roles in calcium signaling, such as ionotropic and metabotropic receptors for neurotransmitters, calcium channels, and calcium pumps. This review highlights a large variation between the calcium signaling proteins that have been reported to be associated with isolated caveolin-1 and flotillin-lipid membrane nanodomains. Since these calcium signaling proteins are scattered in different locations of the neuronal plasma membrane, i.e., in presynapses, postsynapses, axonal or dendritic trees, or in the neuronal soma, our analysis suggests that different lipid membrane-domain subtypes should exist in neurons. Furthermore, we conclude that classification of lipid membrane domains by their content in calcium signaling proteins sheds light on the roles of these domains for neuronal activities that are dependent upon the intracellular calcium concentration. Some examples described in this review include the synaptic and metabolic activity, secretion of neurotransmitters and neuromodulators, neuronal excitability (long-term potentiation and long-term depression), axonal and dendritic growth but also neuronal cell survival and death.

Hexa-Histidine, a Peptide with Versatile Applications in the Study of Amyloid-ß(1-42) Molecular Mechanisms of Action.

Amyloid ß (Aß) oligomers are the most neurotoxic forms of Aß, and Aß(1-42) is the prevalent Aß peptide found in the amyloid plaques of Alzheimer's disease patients. Aß(25-35) is the shortest peptide that retains the toxicity of Aß(1-42). Aß oligomers bind to calmodulin (CaM) and calbindin-D28k with dissociation constants in the nanomolar Aß(1-42) concentration range. Aß and histidine-rich proteins have a high affinity for transition metal ions Cu2+, Fe3+ and Zn2+. In this work, we show that the fluorescence of Aß(1-42) HiLyteTM-Fluor555 can be used to monitor hexa-histidine peptide (His6) interaction with Aß(1-42). The formation of His6/Aß(1-42) complexes is also supported by docking results yielded by the MDockPeP Server. Also, we found that micromolar concentrations of His6 block the increase in the fluorescence of Aß(1-42) HiLyteTM-Fluor555 produced by its interaction with the proteins CaM and calbindin-D28k. In addition, we found that the His6-tag provides a high-affinity site for the binding of Aß(1-42) and Aß(25-35) peptides to the human recombinant cytochrome b5 reductase, and sensitizes this enzyme to inhibition by these peptides. In conclusion, our results suggest that a His6-tag could provide a valuable new tool to experimentally direct the action of neurotoxic Aß peptides toward selected cellular targets.

Canine Mammary Cancer: State of the Art and Future Perspectives.

Mammary cancer is the most frequently diagnosed neoplasia in women and non-spayed female dogs and is one of the leading causes of death in both species. Canines develop spontaneous mammary tumors that share a significant number of biological, clinical, pathological and molecular characteristics with human breast cancers. This review provides a detailed description of the histological, molecular and clinical aspects of mammary cancer in canines; it discusses risk factors and currently available diagnostic and treatment options, as well as remaining challenges and unanswered questions. The incidence of mammary tumors is highly variable and is impacted by biological, pathological, cultural and socioeconomic factors, including hormonal status, breed, advanced age, obesity and diet. Diagnosis is mainly based on histopathology, although several efforts have been made to establish a molecular classification of canine mammary tumors to widen the spectrum of treatment options, which today rely heavily on surgical removal of tumors. Lastly, standardization of clinical study protocols, development of canine-specific biological tools, establishment of adequate dog-specific disease biomarkers and identification of targets for the development of new therapies that could improve survival and have less adverse effects than chemotherapy are among the remaining challenges.

Proposed methodology for designing and developing MOOCs for the deaf community.

Massive Open Online Courses (MOOCs) have become important resources in educational environments worldwide because they have a positive impact on teaching and learning processes. Nevertheless, the way they are designed is crucial to properly address the requirements of special needs people in educational processes. Thus, this paper proposes a methodology for designing and developing MOOCs for Deaf or hard-of-hearing individuals. This exploratory and descriptive study adopted an inclusive education approach based on a literature review and expert consultation. The results highlight the importance of four aspects in MOOC development for these special needs individuals: (i) designing and incorporating elements that meet the needs of Deaf or hard-of-hearing people so that they can use MOOCs effectively; (ii) combining different methodologies and resources; (iii) properly planning and sequencing the design stages; and (iv) using appropriate tools, contents, and times for the process. The findings show that MOOCs should be adequately designed to address the demands of the Deaf community by considering their characteristics and requirements and incorporating current tools, practices, and resources.

Predicting diagnostic conversion from major depressive disorder to bipolar disorder: an EHR based study from Colombia.

Bipolar Disorder (BD) is a severe and chronic disorder characterized by recurrent episodes of depression, mania, and/or hypomania. Most BD patients initially present with depressive symptoms, resulting in a delayed diagnosis of BD and poor clinical outcomes. This study leverages electronic health record (EHR) data from the Clínica San Juan de Dios Manizales in Colombia to identify features predictive of the transition from Major Depressive Disorder (MDD) to BD. Analyzing EHR data from 13,607 patients diagnosed with MDD over 15 years, we identified 1,610 cases of conversion to BD. Using a multivariate Cox regression model, we identified severity of the initial MDD episode, the presence of psychosis and hospitalization at first episode, family history of mood or psychotic disorders, female gender to be predictive of the conversion to BD. Additionally, we observed associations with medication classes (prescriptions of mood stabilizers, antipsychotics, and antidepressants) and clinical features (delusions, suicide attempt, suicidal ideation, use of marijuana and alcohol use/abuse) derived from natural language processing (NLP) of clinical notes. Together, these risk factors predicted BD conversion within five years of the initial MDD diagnosis, with a recall of 72% and a precision of 38%. Our study confirms many previously identified risk factors identified through registry-based studies (such as female gender and psychotic depression at the index MDD episode), and identifies novel ones (specifically, suicidal ideation and suicide attempt extracted from clinical notes). These results simultaneously demonstrate the validity of using EHR data for predicting BD conversion as well as underscore its potential for the identification of novel risk factors and improving early diagnosis.

Smart home adoption factors: A systematic literature review and research agenda.

Smart homes represent the complement of various automation technologies that together make up a network of devices facilitating the daily tasks of residents. These technologies are being studied for their application from different sectors, including the projection of their use to improve energy consumption planning and health care management. However, technology adoption depends on social awareness within the scope of cognitive advantages and innovations compared to perceived risk because although there are multiple benefits, potential users express fears related to the loss of autonomy and security. This study carries out a systematic literature review based on PRISMA in order to analyze research trends and literary evolution in the technological adoption of smart homes, considering the main theories and variables applied by the community. In proposing a research agenda in accordance with the identified gaps and the growing and emerging themes of the object of study, it is worth highlighting the growing interest in the subject, both for the present and its development in the future. Until now, adoption factors have been attributed more to the technological acceptance model and the diffusion of innovation theory, adopting components of the Theory of Planned Behavior; therefore, in several cases, the attributes of different theories are merged to adapt to the needs of each researcher, promoting the creation of empirical and extended models.

Radial astrocyte synchronization modulates the visual system during behavioral-state transitions.

Glial cells support the function of neurons. Recent evidence shows that astrocytes are also involved in brain computations. To explore whether and how their excitable nature affects brain computations and motor behaviors, we used two-photon Ca2+ imaging of zebrafish larvae expressing GCaMP in both neurons and radial astrocytes (RAs). We found that in the optic tectum, RAs synchronize their Ca2+ transients immediately after the end of an escape behavior. Using optogenetics, ablations, and a genetically encoded norepinephrine sensor, we observed that RA synchronous Ca2+ events are mediated by the locus coeruleus (LC)-norepinephrine circuit. RA synchronization did not induce direct excitation or inhibition of tectal neurons. Nevertheless, it modulated the direction selectivity and the long-distance functional correlations among neurons. This mechanism supports freezing behavior following a switch to an alerted state. These results show that LC-mediated neuro-glial interactions modulate the visual system during transitions between behavioral states.

Creating Value in Non-Profit Sports Organizations: An Analysis of the DART Model and Its Performance Implications.

This study aims to analyze the impact of value creation and cocreation, as measured by the dialogue, access, risk assessment, and transparency (DART) model, on the performance of non-profit sports organizations (NPSOs). To assess this impact, the authors analyzed data collected from sports and administration managers of NPSOs, specifically Colombian amateur soccer clubs. The study used partial-least-squares structural-equation modeling (PLS-SEM) with constructs of the reflexive-formative type. The results indicate that value creation has a positive impact on the performance of NPSOs through the mediating effect of value cocreation. Despite the limitations of this study, including the limited research on the relationship between value creation and cocreation and NPSO performance in Colombia, the findings contribute to the understanding of the mediating effect of cocreation. The authors found that cocreation mainly affects the sport, customers/members, communication and image, finance, and organization dimensions of NPSOs in developing countries. This study draws attention to the potential benefits of cocreation for NPSOs and emphasizes the importance of creating value in this context. The study concludes that further studies on the constructs proposed in this research would help to understand the phenomenon of innovation and its impact on NPSOs. Overall, this study provides valuable insights for managers and policymakers in NPSOs-especially in developing countries-on the importance of value cocreation in improving their performance.

Carbohydrate quality, fecal microbiota and cardiometabolic health in older adults: a cohort study.

The impact of carbohydrate quality, measured by the carbohydrate quality index (CQI), on gut microbiota and health has been scarcely investigated. The aim of this study was to cross-sectionally and longitudinally explore the relationships between CQI, fecal microbiota, and cardiometabolic risk factors in an elderly Mediterranean population at high cardiovascular risk. At baseline and 1-year, CQI was assessed from food frequency questionnaires data, cardiometabolic risk factors were measured, and fecal microbiota profiled from 16S sequencing. Multivariable-adjusted linear regression models were fitted to assess the associations between tertiles of baseline CQI, fecal microbiota, and cardiometabolic risk factors at baseline, and between tertiles of 1-year change in CQI, 1-year change in fecal microbiota and cardiometabolic risk factors. Cross-sectionally, higher CQI was positively associated with Shannon alpha diversity index, and abundance of genera Faecalibacterium and Christensenellaceae R7 group, and negatively associated with the abundance of Odoribacter, and uncultured Rhodospirillales genera. Some of these genera were associated with higher glycated hemoglobin and lower body mass index. In addition, we observed a positive association between CQI, and some pathways related with the metabolism of butyrate precursors and plants-origin molecules. Longitudinally, 1-year improvement in CQI was associated with a concurrent increase in the abundance of genera Butyrivibrio. Increased abundance of this genera was associated with 1-year improvement in insulin status. These observations suggest that a better quality of carbohydrate intake is associated with improved metabolic health, and this improvement could be modulated by greater alpha diversity and abundance of specific genera linked to beneficial metabolic outcomes.

SARS-COV-2 specific t-cells in patients with thyroid disorders related to COVID-19 are enriched in the thyroid and acquire a tissue-resident memory phenotype.

BACKGROUND: SARS-CoV-2 infections have been associated with the onset of thyroid disorders like classic subacute thyroiditis (SAT) or atypical SAT upon severe COVID disease (COV-A-SAT). Little is known about thyroid anti-viral immune responses. OBJECTIVES: To define the role of T-cells in COV-A-SAT. METHODS: T-cells from COV-A-SAT patients were analyzed by multi-dimensional flow cytometry, UMAP and DiffusionMap dimensionality reduction and FlowSOM clustering. T-cells from COVID-naïve healthy donors, patients with autoimmune thyroiditis (ATD) and with SAT following COVID vaccination were analyzed as controls. T-cells were analyzed four and eight months post-infection in peripheral blood and in thyroid specimen obtained by ultrasound-guided fine needle aspiration. SARS-COV2-specific T-cells were identified by cytokine production induced by SARS-COV2-derived peptides and with COVID peptide-loaded HLA multimers after HLA haplotyping. RESULTS: COV-A-SAT was associated with HLA-DRB1*13 and HLA-B*57. COV-A-SAT patients contained activated Th1- and cytotoxic CD4+ and CD8+ effector cells four months post-infection, which acquired a quiescent memory phenotype after eight months. Anti-SARS-CoV-2-specific T-cell responses were readily detectable in peripheral blood four months post-infection, but were reduced after eight months. CD4+ and CD8+ tissue-resident memory cells (TRM) were present in the thyroid, and circulating CXCR3+T-cells identified as their putative precursors. SARS-CoV-2-specific T-cells were enriched in the thyroid, and acquired a TRM phenotype eight months post-infection. CONCLUSIONS: The association of COV-A-SAT with specific HLA haplotypes suggests a genetic predisposition and a key role for T-cells. COV-A-SAT is characterized by a prolonged systemic anti-viral effector T-cell response and the late generation of COVID-specific TRM in the thyroid target tissue.

Technology acceptance factors of e-commerce among young people: An integration of the technology acceptance model and theory of planned behavior.

This study aims to examine the factors involved in the technological acceptance of e-commerce among young university students. The research is focused on the articulation between the Technology Acceptance Model (TAM) and the Theory of Planned Behavior (TPB) by collecting secondary data and conducting a survey with 376 young university students, validated by using structural equations (SEM). The predominant factors and variables involved in the adoption of e-commerce by young university students in Medellín were identified. The results show that the attitude towards usage has a positive effect on usage intention because people consider a website to be useful and trust builds regarding usage intention, which will enable to make the transaction in an easier and safer way. In conclusion, perceived usefulness comes before attitude towards usage, and thus the main direct antecedent of the intention to use e-commerce is established.

University Dropout Model for Developing Countries: A Colombian Context Approach.

University dropout is a problem that has raised great concern in institutions of higher education. For this reason, academic institutions need to study the phenomenon and come up with alternatives that contribute to the improvement of students' individual commitments. The aim is to examine the dimensions influencing the decision of university students to drop out. A quantitative approach study was carried out, based on a cross-sectional exploratory-descriptive field design, in which 372 students participated. According to the participants, one of the dimensions that influence the decision to leave the university is the support of the institutions to the continuity of the motivation processes to the student body, since the easy access to the credits is greater than the scholarships granted, which coincides with the financing restrictions of university students in developing countries. In conclusion, it is observed that the communication between managers, teachers, and students is a key factor in the processes of academic retention as a strategy to combat the phenomenon of university desertion.

Influence of environmental awareness on the willingness to pay for green products: an analysis under the application of the theory of planned behavior in the Peruvian market.

Introduction: This paper aimed to build a predictive model through an empirical study to examine the influence of environmental awareness (EA) on attitude (ATT) and perceived behavioral control (PBC), as well as to determine the influence of the three variables of the theory of planned behavior (TPB) on willingness to pay (WP) for green products in the Peruvian market. Methods: A total of 405 Peruvian consumers were surveyed. Most of them were between the ages of 18 and 30 and single. To test the hypotheses, partial least squares (PLS-SEM) were used using the SamrtPls4 software. The results show the significant positive effect of EA on ATT and PBC. The positive and significant effect of ATT, SN, and PBC on WP was also tested A total of 405 Peruvian consumers were surveyed. Most of them were between 18 and 30 years old and single. To test the hypotheses, partial least squares (PLS-SEM) was used using SamrtPls4 software. Results: The results show the positive and significant effect of AD on ATT and PBC. The positive and significant effect of ATT, SN and PBC on WP was also tested. Discussion: The research provides antecedents that allow evaluation of the possibility that companies and governments adjust the dissemination strategies and related public policies regarding the impact of environmentally responsible behavior in order to contribute to the development of environmental awareness as a variable that promotes the disposition of consumers to pay for environmentally friendly products.

A systematic review of trends in photobiomodulation in dentistry between 2018 and 2022: advances and investigative agenda.

Background: Photobiomodulation (PBM) involves laser therapy utilized in medical sciences to modulate biological processes acting as a palliative and immune response-enhancing treatment. This study conducts a comprehensive bibliometric analysis to explore current trends in PBM-related scientific production, encompassing publications, citations, impact, keywords and clusters. Additionally, it aims to predict future research trends in this domain. Methods: The data for this quantitative and qualitative bibliometric analysis were obtained from 608 scientific documents retrieved in November 2022, with 123 sourced from Web of Science and 485 from Scopus, Utilizing Excel, the data was processed in Excel to extract essencial information. Productivity and impact were evaluated for eligibility, and VOSviewer aided in determining associativity for the bibliometric analysis. Results: The findings of this study demostrate that the scientific production related to PBM adheres to a growth power law, exhibiting characteristics of both exponential and linear phases. Notably, recent research trends emphasize critical concepts such as laser therapy, orthodontics, and dental pulp stem cells. Particularly significant is the burgeoning interest in utilizing PBM within dentistry as a complementary alternative to existing protocols. Conclusions: PBM stands as a promising laser therapy within medical applications. Through a detailed bibliometric analysis, this study underscores the increasing significance of PBM, especially within the realm of dental treatments. These insights offer a glimpse into the evolving landscape of PBM research and provide valuable guidance for potential future directions of study.

Biochemical and Biophysical Characterization of the Caveolin-2 Interaction with Membranes and Analysis of the Protein Structural Alteration by the Presence of Cholesterol.

Caveolin-2 is a protein suitable for the study of interactions of caveolins with other proteins and lipids present in caveolar lipid rafts. Caveolin-2 has a lower tendency to associate with high molecular weight oligomers than caveolin-1, facilitating the study of its structural modulation upon association with other proteins or lipids. In this paper, we have successfully expressed and purified recombinant human caveolin-2 using E. coli. The structural changes of caveolin-2 upon interaction with a lipid bilayer of liposomes were characterized using bioinformatic prediction models, circular dichroism, differential scanning calorimetry, and fluorescence techniques. Our data support that caveolin-2 binds and alters cholesterol-rich domains in the membranes through a CARC domain, a type of cholesterol-interacting domain in its sequence. The far UV-CD spectra support that the purified protein keeps its folding properties but undergoes a change in its secondary structure in the presence of lipids that correlates with the acquisition of a more stable conformation, as shown by differential scanning calorimetry experiments. Fluorescence experiments using egg yolk lecithin large unilamellar vesicles loaded with 1,6-diphenylhexatriene confirmed that caveolin-2 adsorbs to the membrane but only penetrates the core of the phospholipid bilayer if vesicles are supplemented with 30% of cholesterol. Our study sheds light on the caveolin-2 interaction with lipids. In addition, we propose that purified recombinant caveolin-2 can provide a new tool to study protein-lipid interactions within caveolae.

Formation and evolution of C-C, C-O, C[double bond, length as m-dash]O and C-N bonds in chemical reactions of prebiotic interest.

A series of prebiotic chemical reactions yielding the precursor building blocks of amino acids, proteins and carbohydrates, starting solely from HCN and water is studied here. We closely follow the formation and evolution of the pivotal C-C, C-O, C[double bond, length as m-dash]O, and C-N bonds, which dictate the chemistry of the molecules of life. In many cases, formation of these bonds is set in motion by proton transfers in which individual water molecules act as catalysts so that water atoms end up in the products. Our results indicate that the prebiotic formation of carbon dioxide, formaldehyde, formic acid, formaldimine, glycolaldehyde, glycine, glycolonitrile, and oxazole derivatives, among others, are best described as highly nonsynchronous concerted single step processes. Nonetheless, for all reactions involving double proton transfer, the formation and breaking of O-H bonds around a particular O atom occur in a synchronous fashion, apparently independently from other primitive processes. For the most part, the first process to initiate seems to be the double proton transfer in the reactions where they are present, then bond breaking/formation around the reactive carbon in the carbonyl group and finally rupture of the C-N bonds in the appropriate cases, which are the most reluctant to break. Remarkably, within the limitations of our non-dynamical computational model, the wide ranges of temperature and pressure in which these reactions occur, downplay the problematic determination of the exact constraints on the early Earth.