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Abstract Molecular dynamics (MD) simulations produce a substantial volume of high-dimensional data, and traditional methods for analyzing these data pose significant computational demands. Advances in MD simulation analysis combined with deep learning-based approaches have led to the understanding of specific structural changes observed in MD trajectories, including those induced by mutations. In this study, we model the trajectories resulting from MD simulations of the SARS-CoV-2 spike protein-ACE2, specifically the receptor-binding domain (RBD), as interresidue distance maps, and use deep convolutional neural networks to predict the functional impact of point mutations, related to the virus’s infectivity and immunogenicity. Our model was successful in predicting mutant types that increase the affinity of the S protein for human receptors and reduce its immunogenicity, both based on MD trajectories (precision = 0.718; recall = 0.800; $$\hbox {F}_1$$ = 0.757; MCC = 0.488; AUC = 0.800) and their centroids. In an additional analysis, we also obtained a strong positive Pearson’s correlation coefficient equal to 0.776, indicating a significant relationship between the average sigmoid probability for the MD trajectories and binding free energy (BFE) changes. Furthermore, we obtained a coefficient of determination of 0.602. Our 2D-RMSD analysis also corroborated predictions for more infectious and immune-evading mutants and revealed fluctuating regions within the receptor-binding motif (RBM), especially in the $$\beta _{1}^{\prime }/\beta _{2}^{\prime }-C$$ loop. This region presented a significant standard deviation for mutations that enable SARS-CoV-2 to evade the immune response, with RMSD values of 5Å in the simulation. This methodology offers an efficient alternative to identify potential strains of SARS-CoV-2, which may be potentially linked to more infectious and immune-evading mutations. Using clustering and deep learning techniques, our approach leverages information from the ensemble of MD trajectories to recognize a broad spectrum of multiple conformational patterns characteristic of mutant types. This represents a strategic advantage in identifying emerging variants, bypassing the need for long MD simulations. Furthermore, the present work tends to contribute substantially to the field of computational biology and virology, particularly to accelerate the design and optimization of new therapeutic agents and vaccines, offering a proactive stance against the constantly evolving threat of COVID-19 and potential future pandemics.

A whole-school approach to foster competences for democratic culture, described by the Council of Europe's Reference Framework of Competences for Democratic Culture, implies the active involvement of all actors in three areas of school life: teaching and learning, school governance and culture, and co-operation with the community. The European Centre for Modern Languages' project Des environnements d'apprentissage optimisés pour et par les langues vivantes (EOL) similarly assumes that a whole-school approach is essential in the promotion of plurilingual and intercultural education in schools. The article illustrates the EOL project: the core principles of its approach, the tools, materials and examples of practices. The project and its followup activities have proved that setting up language learning friendly environments requires decisions at different levels so as to introduce mechanisms and routines. Considering language education as a key factor for social cohesion, the aim of the article is to answer the question of what schools should do so as to go beyond a one-off, isolated project to unite all stakeholders around a shared language plan for school, which fosters competences for democratic citizenship.

Abstract Background Technological advances based on mobile health (mHealth), the field of digital health (eHealth) aimed at managing health services and care and their concomitant transformations, have become increasingly important in the 21st century. In this context, care for individuals diagnosed with Chronic Non-Communicable Diseases (CNCDs) deserves to be highlighted. The aim of this study is to present the creation, development and implementation of the Telehealth Center of the Federal University of Viçosa (NUTELES - UFV), for the monitoring and management of health care for individuals with Arterial Hypertension (AH) and/or Diabetes Mellitus (DM). Methods This study, carried out in 2022 and 2023, involved 374 patients diagnosed with AH and/or DM in the health micro-region of Viçosa/MG, Brazil, comprising nine municipalities. The research aims to describe the creation, development and implementation of a software (NutelesApp) for the collection, storage, management and analysis of epidemiological research in public health, focusing specifically, on the monitoring and management of health care for individuals with AH and/or DM monitored by Primary Health Care (PHC). The parameters collected and analyzed were obtained through a questionnaire applied to patients, consisting of 70 questions, subdivided into 12 classes of questions. The epidemiological survey data was collected using mobile devices and analyzed using computer techniques based on statistical analysis. Once the field teams had completed their work, the files were transferred to servers for general analysis processing, using estimates of means, prevalence and respective standard errors, calculated using the Statistical Package for Social Science (SPSS) program, which takes into account the planning variables and includes the basic weights resulting from the sampling process. This study was approved by the Human Research Ethics Committee and registered, prior to recruitment, by the Brazilian Registry of Clinical Trials (ReBEC), ID: RBR-45hqzmf (Last approval date: 11/30/2022). Results The information obtained through data collection with subsequent exploratory analysis of epidemiological data using the NutelesApp software suggests that mobile applications intended for the purpose of monitoring and managing healthcare for people with AH and/or DM should address the variables necessary to support a process of understanding the health conditions and/or disease of the individual as a whole and provide short- and long-term learning. Regarding the results of the survey using the software, the variables of 374 people were analyzed. Majority are female (73.2%) and white (43.5%). Most patients are elderly (average 64 years), with blood pressure levels within the normal range for this population, BMI indicates overweight, AC increased risk for cardiovascular events and CC within the recommendation value. All biochemical parameters analyzed were above normal limits. Conclusions The description of the creation and development of the software includes practical examples of its implementation, the results collected and its applicability in real scenarios, presenting determining criteria that can provide assertive and timely interventions for monitoring and managing the health and/or disease parameters of patients with HA and/or DM. In addition, the beneficial consequences of using this application will extend to health units and their respective management, improving the services provided by PHC and enhancing strategies and actions for health promotion and disease prevention.

Summary Background The growing discussion on teacher development focuses on diversified educational skills that promote knowledge and innovation in the teaching, learning and assessment process. With the Covid-19 scenario, this picture of necessary changes has become more evident, demonstrating the need for professional preparation to work in teacher development. The aim of the study was to analyze the effectiveness of teacher development programs for the training of university teachers in the health area, through a systematic review and meta-analysis. Methods The systematic review and meta-analysis were carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved searching five databases - PubMed-Medline, Education Resource Information Center (ERIC), SCOPUS, Embase and Web of Science. The review included randomized clinical trials and cohort studies that addressed the effectiveness of teaching professionalization in the health area for university professors. The quality of the selected studies was assessed based on the evaluation criteria of the Joanna Briggs Institute tool. The random effects meta-analysis method was used to explain the distribution of effects between the studies, using Stata® software (version 11.0) and publication bias was examined by visual inspection of the graphs and Egger's test. Results We included 12 studies in the systematic review and 8 in the meta-analysis. These studies were published between 1984 and 2022 in 14 countries. Significant changes were reported in teachers' behavior to stimulate and encourage students, improvement in the quality of teaching and teaching staff, as well as improvement in skills such as leadership and self-evaluation. Furthermore, the result of the meta-analysis showed that there is evidence of the effectiveness of the positive effects of teacher development programs after their implementation, with this effect being 1.70% and an increase of 4.75 in the effect of these teacher development programs. Conclusion Our study shows that development programs have been implemented in different countries and contexts, all of which have proven to be effective in the short, medium and long term. We recommend that future research focus specifically on the different competencies that have been acquired following the implementation of these programs.

BackgroundFederally Qualified Health Centers (FQHCs) are an essential place for historically underserved patients to access health care, including screening for colorectal cancer (CRC), one of the leading causes of cancer death in the United States. Novel interventions aimed at increasing CRC screening completion rates at FQHCs are crucial. ObjectiveThis study conducts user testing of a digital patient navigation tool, called eNav, designed to support FQHC patients in preparing for, requesting, and completing CRC screening tests. MethodsWe recruited English- and Spanish-speaking patients (N=20) at an FQHC in New York City to user-test the eNav website (2 user tests; n=10 participants per user test). In each user test, participants engaged in a “think aloud” exercise and a qualitative interview to summarize and review their feedback. They also completed a baseline questionnaire gathering data about demographics, technology and internet use, medical history, and health literacy, and completed surveys to assess the website’s acceptability and usability. Based on participant feedback from the first user test, we modified the eNav website for a second round of testing. Then, feedback from the second user test was used to modify and finalize the eNav website. ResultsSurvey results supported the overall usability and acceptability of the website. The average System Usability Scale score for our first user test was 75.25; for the second, it was 75.28. The average Acceptability E-scale score for our first user test was 28.3; for the second, it was 29.2. These scores meet suggested benchmarks for usability and acceptability. During qualitative think-aloud exercises, in both user tests, many participants favorably perceived the website as motivating, interesting, informative, and user-friendly. Respondents also gave suggestions on how to improve the website’s content, usability, accessibility, and appeal. We found that some participants did not have the digital devices or internet access needed to interact with the eNav website at home. ConclusionsBased on participant feedback on the eNav website and reported limitations to digital access across both user tests, we made modifications to the content and design of the website. We also designed alternative methods of engagement with eNav to increase the tool’s usability, accessibility, and impact for patients with diverse needs, including those with limited access to devices or the internet at home. Next, we will test the eNav intervention in a randomized controlled trial to evaluate the efficacy of the eNav website for improving CRC screening uptake among patients treated at FQHCs.

Objective To explore the disparities in community characteristics between the regions with the highest and lowest leg amputation rates. Approach This study used an exploratory method to describe the disparities between community characteristics of these two regions. The study team used several data sources: 1) We used the Dartmouth Atlas Healthcare Map to identify the highest and lowest leg amputation areas. This data was based on leg amputations per 1,000 Medicare enrollees by Hospital referral regions (HRRs) in 2015. 2) We used population estimates and income data from The Census Bureau. 3) We gathered climate, crime index, walk score, bike lanes, and park data from numerous websites. Results Florence, SC has the highest leg amputation rate and Bridgeport, CT has the lowest across the nation. Florence also shows higher cardiovascular disease and diabetes discharge rates. Florence’s population has a slightly higher percentage of persons 65 years and over, a higher percentage of bachelor’s degrees, a higher per capita income, and a lower poverty rate. Florence also has fewer parks, is less walkable or bikeable, and has worse crime. It is worth noting that Bridgeport is close to Yale New Haven Hospital, which has a Limb Preservation Program that could contribute to the region’s extremely low leg amputation rate. Conclusions There are disparities in community characteristics between the regions with the highest and lowest leg amputation rates. Implications Future work needs to investigate the association between community characteristics and leg amputation rates and assess the impact of the Limb Preservation Program.

Abstract Background Epilepsy, a challenging neurological condition, is often present with comorbidities that significantly impact diagnosis and management. In the Pakistani population, where financial limitations and geographical challenges hinder access to advanced diagnostic methods, understanding the genetic underpinnings of epilepsy and its associated conditions becomes crucial. Methods This study investigated four distinct Pakistani families, each presenting with epilepsy and a spectrum of comorbidities, using a combination of whole exome sequencing (WES) and Sanger sequencing. The epileptic patients were prescribed multiple antiseizure medications (ASMs), yet their seizures persist, indicating the challenging nature of ASM-resistant epilepsy. Results Identified genetic variants contributed to a diverse range of clinical phenotypes. In the family 1, which presented with epilepsy, developmental delay (DD), sleep disturbance, and aggressive behavior, a homozygous splice site variant, c.1339–6 C > T, in the COL18A1 gene was detected. The family 2 exhibited epilepsy, intellectual disability (ID), DD, and anxiety phenotypes, a homozygous missense variant, c.344T > A (p. Val115Glu), in the UFSP2 gene was identified. In family 3, which displayed epilepsy, ataxia, ID, DD, and speech impediment, a novel homozygous frameshift variant, c.1926_1941del (p. Tyr643MetfsX2), in the ZFYVE26 gene was found. Lastly, family 4 was presented with epilepsy, ID, DD, deafness, drooling, speech impediment, hypotonia, and a weak cry. A homozygous missense variant, c.1208 C > A (p. Ala403Glu), in the ATP13A2 gene was identified. Conclusion This study highlights the genetic heterogeneity in ASM-resistant epilepsy and comorbidities among Pakistani families, emphasizing the importance of genotype-phenotype correlation and the necessity for expanded genetic testing in complex clinical cases.

Abstract Background Patagonian toothfish (Dissostichus eleginoides) is an economically and ecologically important fish species in the family Nototheniidae. Juveniles occupy progressively deeper waters as they mature and grow, and adults have been caught as deep as 2500 m, living on or in just above the southern shelves and slopes around the sub-Antarctic islands of the Southern Ocean. As apex predators, they are a key part of the food web, feeding on a variety of prey, including krill, squid, and other fish. Despite its importance, genomic sequence data, which could be used for more accurate dating of the divergence between Patagonian and Antarctic toothfish, or establish whether it shares adaptations to temperature with fish living in more polar or equatorial climes, has so far been limited. Results A high-quality D. eleginoides genome was generated using a combination of Illumina, PacBio and Omni-C sequencing technologies. To aid the genome annotation, the transcriptome derived from a variety of toothfish tissues was also generated using both short and long read sequencing methods. The final genome assembly was 797.8 Mb with a N50 scaffold length of 3.5 Mb. Approximately 31.7% of the genome consisted of repetitive elements. A total of 35,543 putative protein-coding regions were identified, of which 50% have been functionally annotated. Transcriptomics analysis showed that approximately 64% of the predicted genes (22,617 genes) were found to be expressed in the tissues sampled. Comparative genomics analysis revealed that the anti-freeze glycoprotein (AFGP) locus of D. eleginoides does not contain any AFGP proteins compared to the same locus in the Antarctic toothfish (Dissostichus mawsoni). This is in agreement with previously published results looking at hybridization signals and confirms that Patagonian toothfish do not possess AFGP coding sequences in their genome. Conclusions We have assembled and annotated the Patagonian toothfish genome, which will provide a valuable genetic resource for ecological and evolutionary studies on this and other closely related species.

Machine learning-based drug discovery success depends on molecular representation. Yet traditional molecular fingerprints omit both the protein and pointers back to structural information that would enable better model interpretability. Therefore, we propose LUNA, a Python 3 toolkit that calculates and encodes protein-ligand interactions into new hashed fingerprints inspired by Extended Connectivity FingerPrint (ECFP): EIFP (Extended Interaction FingerPrint), FIFP (Functional Interaction FingerPrint), and Hybrid Interaction FingerPrint (HIFP). LUNA also provides visual strategies to make the fingerprints interpretable. We performed three major experiments exploring the fingerprints' use. First, we trained machine learning models to reproduce DOCK3.7 scores using 1 million docked Dopamine D4 complexes. We found that EIFP-4,096 performed (R2 = 0.61) superior to related molecular and interaction fingerprints. Second, we used LUNA to support interpretable machine learning models. Finally, we demonstrate that interaction fingerprints can accurately identify similarities across molecular complexes that other fingerprints overlook. Hence, we envision LUNA and its interface fingerprints as promising methods for machine learning-based virtual screening campaigns. LUNA is freely available at https://github.com/keiserlab/LUNA.

Tumor necrosis factor α (TNF-α) is a multifunctional cytokine protein acknowledged as a vital mediator in cell differentiation, proliferation, and survival. Additionally, TNF-α is a crucial component of the host’s defense by mediating inflammatory and immune responses against various aggressive agents, including viruses, bacteria parasites, and tumors. However, excessive production can be detrimental to the body and is also implicated in developing several inflammatory and immune-mediated disorders. Therefore, there is great interest in studying its role and its modulation, in various diseases, both in in vitro, in vivo, and in silico experiments. In this review, we evaluated the structures of proteins related to TNF-α available in public databases. In addition, we described the main antibodies blocking this cytokine and its applications and commented on the potential of naturally produced binding molecules, such as TNF-α-binding proteins produced by ticks. We also discuss the role of structural bioinformatics techniques in understanding the mechanisms of chronic inflammatory diseases related to TNF-α. We hope that the data presented in this review will be useful for studies that aim to better understand the mechanisms of the interactions of TNF-α with other proteins and will lead to new drugs or treatments.

The reduced usage of inorganic fertilizers is needed to avoid various undesirable impacts. This study aimed to assess whether partial reduction of inorganic fertilizers with the use of organic fertilizers can maintain nutrient adequacy and yield of maize. The research was conducted in Juwiring, Klaten, Central Java from August 2021 - March 2022 designed in a Completely Randomized Group Design with seven fertilizer combination treatments, namely ¼ NPK + 1 organic fertilizer, ½ NPK + 1 organic fertilizer, ¾ NPK + 1 organic fertilizer, ¾ NPK + ¾ organic fertilizer, and two comparison treatments namely no fertilizer and standard NPK (350 kg ha-1, SP36 150 kg ha-1, KCl 75 kg ha-1) repeated three times. The parameters observed were N-total soil and tissue, P-available soil, K-available available P and soil CEC, P and K levels of plant tissue. Organic fertilizer of 10 t ha-1 was applied a week before planting. The application of ½ NPK of the standard dose + 1 organic fertilizer showed higher N-total soil, P-available, and K-available as well as higher corn yield than the standard NPK treatment with the results of cob weight (22.52 g), cob weight without cob (13.92 g), cob length (21.47 g), and cob diameter (4.55 g) against the standard NPK treatment. The use of organic fertilizers needs to be done to maintain the sustainability of natural resources. ABSTRAK Pengurangan penggunaan pupuk anorganik perlu dilakukan untuk menghindari berbagai dampak yang tidak diharapkan. Penelitian bertujuan untuk mengkaji apakah pengurangan sebagian pupuk anorganik dengan pupuk organik mampu menjaga kecukupan hara dan hasil jagung. Penelitian dilaksanakan di Juwiring, Klaten, Jawa Tengah sejak Agustus 2021 – Maret 2022 menggunakan Rancangan Acak Kelompok Lengkap dengan tujuh perlakuan kombinasi pupuk yaitu: ¼ NPK + 1 pupuk organik, ½ NPK + 1 pupuk organik, ¾ NPK + 1 pupuk organik(E), 1 NPK + 1 pupuk organik, ¾ NPK + ¼ pupuk organik, ¾ NPK + ½ pupuk organik, ¾ NPK + ¾ pupuk organik, dua perlakuan pembanding yaitu tanpa pupuk serta NPK standar (350 kg ha-1, SP36 150 kg ha-1, KCl 75 kg ha-1) yang diulang 3 kali. Parameter pengamatan yaitu N-total tanah dan jaringan, P-tersedia tanah, K-Tersedia tanah dan KTK tanah, serta kadar P dan K jaringan tanaman. Pupuk organik 10 t ha-1 diberikan seminggu sebelum tanam. Aplikasi ½ NPK dari dosis standar + 1 pupuk organik menunjukkan N-total, P-tersedia, dan K-tersedia tanah serta hasil jagung yang lebih tinggi dari perlakuan NPK standar dengan hasil berat tongkol berkelobot (22,52 g), berat tongkol tanpa kelobot (13,92 g), panjang tongkol (21,47 g), dan diameter tongkol (4,55 g) terhadap perlakuan NPK standar. Penggunaan pupuk organik perlu dilakukan untuk menjaga keberlanjutan sumberdaya alam.

Bacterial nanocellulose (BC) has attracted significant attention across a wide array of applications due to its distinctive characteristics. Recently, there has been increasing interest in leveraging waste biomass to improve sustainability in BC biogenesis processes. This study focuses on optimizing the citrus pulp waste (CPW) medium to enhance BC production using Komagataeibacter sucrofermentans. The screening of initial medium pH, yeast extract, CPW sugar and inoculum concentrations was conducted using the Plackett–Burman design, with BC yield (mgDW/gCPW) as the model response. The significant parameters, i.e., CPW sugars and yeast extract concentrations, were optimized using response surface methodology, employing a five-level, two-factor central composite design. The optimized CPW-based growth medium resulted in a final yield of 66.7 ± 5.1 mgDW/gCPW, representing a 14-fold increase compared to non-optimized conditions (4.3 ± 0.4 mgBC/gCPW). Material characterization analysis indicated that the produced BC showed high thermal stability (30% mass retained at 600 °C) and a crystallinity index value of 71%. Additionally, to enhance process sustainability, spent baker’s yeast hydrolysate (BYH) was assessed as a substitute for yeast extract, leading to a final BC titer of 9.3 ± 0.6 g/L.

Atrial fibrillation (AF) is a common cardiac arrhythmia that poses a significant risk of stroke and thromboembolic events. Anticoagulation therapy is essential for preventing stroke in patients with AF. An increasing number of people of all ages, including cardiac patients, approach physical activity as both a leisure-time exercise and a competitive sport. Therefore, patients at risk of AF are increasingly allowed to practice sports activities. Management of oral anticoagulant therapy (OAT) in these patients is extremely challenging because of the need to balance the risks and benefits of medications, considering both hemorrhagic (in case of trauma) and ischemic complications when the drugs are avoided. Official recommendations are limited for these patients and forbid sports that increase the risk of trauma and consequent bleeding in most cases. These recommendations are strongly influenced by the “traditional” management of OAT, which mainly involves coumarin derivatives. Non-vitamin K antagonist direct oral anticoagulants (DOACs), with their more favorable pharmacokinetic–pharmacodynamic profile than that of coumarin derivatives, may represent an opportunity to modify the approach to sports activity in patients with AF and indications for OAT. This study aimed to review the use of anticoagulants in athletes with AF, highlight their efficacy and safety, and provide practical considerations regarding their management.

BACKGROUND: Few data on the management of acute phase of traumatic spinal cord injury (tSCI) in patients suffering polytrauma are available. As the therapeutic choices in the first hours may have a deep impact on outcome of tSCI patients, we conducted an international survey investigating this topic. METHODS: The survey was composed of 29 items. The main endpoints of the survey were to examine: (1) the hemodynamic and respiratory management, (2) the coagulation management, (3) the timing of magnetic resonance imaging (MRI) and spinal surgery, (4) the use of corticosteroid therapy, (5) the role of intraspinal pressure (ISP)/spinal cord perfusion pressure (SCPP) monitoring and (6) the utilization of therapeutic hypothermia. RESULTS: There were 171 respondents from 139 centers worldwide. A target mean arterial pressure (MAP) target of 80-90 mmHg was chosen in almost half of the cases [n = 84 (49.1%)]. A temporary reduction in the target MAP, for the time strictly necessary to achieve bleeding control in polytrauma, was accepted by most respondents [n = 100 (58.5%)]. Sixty-one respondents (35.7%) considered acceptable a hemoglobin (Hb) level of 7 g/dl in tSCI polytraumatized patients. An arterial partial pressure of oxygen (PaO2) of 80-100 mmHg [n = 94 (55%)] and an arterial partial pressure of carbon dioxide (PaCO2) of 35-40 mmHg [n = 130 (76%)] were chosen in most cases. A little more than half of respondents considered safe a platelet (PLT) count > 100.000/mm3 [n = 99 (57.9%)] and prothrombin time (PT)/activated partial thromboplastin time (aPTT)