The UCSC Genome Browser database: 2024 update.

The UCSC Genome Browser (https://genome.ucsc.edu) is a web-based genomic visualization and analysis tool that serves data to over 7,000 distinct users per day worldwide. It provides annotation data on thousands of genome assemblies, ranging from human to SARS-CoV2. This year, we have introduced new data from the Human Pangenome Reference Consortium and on viral genomes including SARS-CoV2. We have added 1,200 new genomes to our GenArk genome system, increasing the overall diversity of our genomic representation. We have added support for nine new user-contributed track hubs to our public hub system. Additionally, we have released 29 new tracks on the human genome and 11 new tracks on the mouse genome. Collectively, these new features expand both the breadth and depth of the genomic knowledge that we share publicly with users worldwide.

The UCSC Genome Browser database: 2023 update.

The UCSC Genome Browser (https://genome.ucsc.edu) is an omics data consolidator, graphical viewer, and general bioinformatics resource that continues to serve the community as it enters its 23rd year. This year has seen an emphasis in clinical data, with new tracks and an expanded Recommended Track Sets feature on hg38 as well as the addition of a single cell track group. SARS-CoV-2 continues to remain a focus, with regular annotation updates to the browser and continued curation of our phylogenetic sequence placing tool, hgPhyloPlace, whose tree has now reached over 12M sequences. Our GenArk resource has also grown, offering over 2500 hubs and a system for users to request any absent assemblies. We have expanded our bigBarChart display type and created new ways to visualize data via bigRmsk and dynseq display. Displaying custom annotations is now easier due to our chromAlias system which eliminates the requirement for renaming sequence names to the UCSC standard. Users involved in data generation may also be interested in our new tools and trackDb settings which facilitate the creation and display of their custom annotations.

The UCSC Genome Browser database: 2022 update.

The UCSC Genome Browser, https://genome.ucsc.edu, is a graphical viewer for exploring genome annotations. The website provides integrated tools for visualizing, comparing, analyzing, and sharing both publicly available and user-generated genomic datasets. Data highlights this year include a collection of easily accessible public hub assemblies on new organisms, now featuring BLAT alignment and PCR capabilities, and new and updated clinical tracks (gnomAD, DECIPHER, CADD, REVEL). We introduced a new Track Sets feature and enhanced variant displays to aid in the interpretation of clinical data. We also added a tool to rapidly place new SARS-CoV-2 genomes in a global phylogenetic tree enabling researchers to view the context of emerging mutations in our SARS-CoV-2 Genome Browser. Other new software focuses on usability features, including more informative mouseover displays and new fonts.

Expediting the Rehabilitation of Severely Resorbed Ridges Using a Combination of CAD-CAM and Analog Techniques: A Case Report.

With the life expectancy increasing, there is a growing need for prosthetic dental treatments to restore the oral health, function, and quality of life of edentulous patients. Presently, only a few articles are available describing the oral rehabilitation of patients with severely resorbed ridges with milled complete dentures. This clinical case report provides a straightforward protocol consisting of a combination of analog and digital techniques for the rehabilitation of edentulous patients with severely resorbed ridges with milled fixed and removable complete dentures. This technique permits the minimization of the number of appointments, improves patient comfort, allows for the digital archiving of important clinical data, and permits the manufacture of prostheses with improved mechanical properties. These favorable outcomes were achieved by using the patient's existing PMMA complete denture as a custom tray for a final impression with light-bodied Polyvinylsiloxane. Subsequently, the resulting models were digitized, and a digital complete denture was designed and manufactured in an expedited manner using CAD-CAM techniques. Therefore, this case report highlights the potential of CAD/CAM technology to predictably restabilize oral functions and improve patients' quality of life.

Nutrient effects on working memory across the adult lifespan.

OBJECTIVE: To identify the nutrients that influence the performance of working memory, which is greatly affected as age progresses. METHOD: A total of 1646 healthy adults between 21 and 80 years old participated in the study. The daily consumption of 64 nutrients was examined using a food frequency questionnaire that assessed food intake during the previous year. Working memory was measured in the verbal and spatial domains using a computerized task. We examined which nutrients influence working memory across the entire adult lifespan and whether the influence of any of these nutrients on working memory is moderated by individuals' ages. RESULTS: Working memory, across the entire adult lifespan, benefits from the intake of cholesterol, alcohol, gamma- and delta-tocopherol, vitamin B6, and palmitoleic, oleic, alpha linoleic and linoleic acids. Moderator analyses revealed that fats, energy, lactose and sodium negatively influenced working memory in middle-aged and older adults, whereas vitamin D and vitamin C had positive effects on memory beyond 70 years of age. CONCLUSION: Nutrients have the ability to positively or negatively affect working memory, which varies as a function of age.

Gene Identification in Inflammatory Bowel Disease via a Machine Learning Approach.

Inflammatory bowel disease (IBD) is an illness with increasing prevalence, particularly in emerging countries, which can have a substantial impact on the quality of life of the patient. The illness is rather heterogeneous with different evolution among patients. A machine learning approach is followed in this paper to identify potential genes that are related to IBD. This is done by following a Monte Carlo simulation approach. In total, 23 different machine learning techniques were tested (in addition to a base level obtained using artificial neural networks). The best model identified 74 genes selected by the algorithm as being potentially involved in IBD. IBD seems to be a polygenic illness, in which environmental factors might play an important role. Following a machine learning approach, it was possible to obtain a classification accuracy of 84.2% differentiating between patients with IBD and control cases in a large cohort of 2490 total cases. The sensitivity and specificity of the model were 82.6% and 84.4%, respectively. It was also possible to distinguish between the two main types of IBD: (1) Crohn's disease and (2) ulcerative colitis.

Minimally Invasive Laminate Veneer Therapy for Maxillary Central Incisors.

Minimally invasive dentistry is a considered process that requires the clinician to be prepared with the ideal sequence and the tools needed. This report describes a well-planned ultraconservative approach using only two ceramic laminate veneers for the maxillary central incisors to significantly improve the patient's overall smile. A 30-year-old female presented with the chief complaints of having diastemas between the central and lateral incisors as well as incisal wear. Diagnostic wax-up and mock-up were performed, and the patient approved the minimally invasive treatment with veneers only for central incisors. A reduction guide aided the conservative tooth preparations, and hand-crafted feldspathic veneers were bonded under total isolation with a rubber dam. The two final conservative veneers significantly improved the smile and fulfilled the patient's expectations. Following proper planning and sequencing, predictable outcomes were obtained and fulfilled the patient's esthetic demands. Minimally invasive restorative dentistry with only two single veneers can impact the entire smile frame. Overtreatment in the esthetic zone is unnecessary to meet a patient's esthetic expectations.

Soft Tissue Grafting Procedures before Restorations in the Esthetic Zone: A Minimally Invasive Interdisciplinary Case Report.

An esthetically pleasing smile is a valuable aspect of physical appearance and plays a significant role in social interaction. Achieving the perfect balance between extraoral and intraoral tissues is essential for a harmonious and attractive smile. However, certain intraoral deficiencies, such as non-carious cervical lesions and gingival recession, can severely compromise the overall aesthetics, particularly in the anterior zone. Addressing such conditions requires careful planning and meticulous execution of both surgical and restorative procedures. This interdisciplinary clinical report presents a complex case of a patient with esthetic complaints related to asymmetric anterior gingival architecture and severely discolored and eroded maxillary anterior teeth. The patient was treated using a combination of minimally invasive ceramic veneers and plastic mucogingival surgery, resulting in a successful outcome. The report emphasizes the potential of this approach in achieving optimal esthetic results in challenging cases, highlighting the importance of an interdisciplinary team approach in achieving a harmonious balance between dental and soft tissue aesthetics.

A mini review on the main challenges of implementing mechanical biological treatment plants for municipal solid waste in the Latin America region: Learning from the experiences of developed countries.

Most of the municipal solid waste (MSW) generated in the Latin America (LATAM) region is currently disposed of in landfills and dumpsites, which results in many negative environmental impacts. Mechanical biological treatment (MBT) is a strategy that combines the mechanical separation of recoverable materials with the biological stabilization of organic matter. MBT plants have proven to be a good alternative for the management of MSW and have been successfully implemented in developed countries for more than 30 years. However, the efficient introduction of these facilities in developing countries, such as those in the LATAM region, requires further feasibility studies. Therefore, this mini review seeks to offer significant insights into the main challenges that must be overcome to facilitate the implementation and operation of MBT plants, considering the unique technological, sociocultural, economic and political context of the LATAM region, through a comparison of the reported experiences of MBT plants in more developed countries with those in the LATAM region. The analysis herein indicates that key actions for the successful operation of MBT plants in the LATAM region include both the implementation of source separation as well as selective collection practices. Moreover, this work shows that other factors, like the establishment of valorization markets with safe working conditions for informal collectors, the development of intermunicipal cooperation schemes and the enforcement of strong regulatory frameworks for waste disposal specifications, are important contextual factors that have allowed the efficient operation of MBT plants in developed countries. Although the implementation of many of these practices will be challenging, such measures are necessary to increase the sustainability of MSW treatment practices in the LATAM region.

Variant interpretation: UCSC Genome Browser Recommended Track Sets.

The UCSC Genome Browser has been an important tool for genomics and clinical genetics since the sequence of the human genome was first released in 2000. As it has grown in scope to display more types of data it has also grown more complicated. The data, which are dispersed at many locations worldwide, are collected into one view on the Browser, where the graphical interface presents the data in one location. This supports the expertise of the researcher to interpret variants in the genome. Because the analysis of single nucleotide variants and copy number variants require interpretation of data at very different genomic scales, different data resources are required. We present here several Recommended Track Sets designed to facilitate the interpretation of variants in the clinic, offering quick access to datasets relevant to the appropriate scale.

2,5-Dimethylfuran Production by Catalytic Hydrogenation of 5-Hydroxymethylfurfural Using Ni Supported on Al2O3-TiO2-ZrO2 Prepared by Sol-Gel Method: The Effect of Hydrogen Donors.

5-Hydroxymethylfurfural (5-HMF) has been described as one of the 12 key platform molecules derived from biomass by the US Department of Energy, and its hydrogenation reaction produces versatile liquid biofuels such as 2,5-dimethylfuran (2,5-DMF). Catalytic hydrogenation from 5-HMF to 2,5-DMF was thoroughly studied on the metal nickel catalysts supported on Al2O3-TiO2-ZrO2 (Ni/ATZ) mixed oxides using isopropanol and formic acid (FA) as hydrogen donors to find the best conditions of the reaction and hydrogen donor. The influence of metal content (wt%), Ni particle size (nm), Nickel Ni0, Ni0/NiO and NiO species, metal active sites and acid-based sites on the catalyst surface, and the effect of the hydrogen donor (isopropanol and formic acid) were systematically studied. The structural characteristics of the materials were studied using different physicochemical methods, including N2 physisorption, XRD, Raman, DRS UV-Vis, FT-IR, SEM, FT-IR Pyad, H2-TPD, CO2-TPD, H2-TPR, TEM and XPS. Second-generation 2,5-DMF biofuel and 5-HMF conversion by-products were analyzed and elucidated using 1H NMR. It was found that the Ni0NiO/ATZ3WI catalyst synthesized by the impregnation method (WI) generated a good synergistic effect between the species, showing the best catalytic hydrogenation of 5-HMF to 2,5-DMF using formic acid as a hydrogen donor for 24 h of reaction and temperature of 210 °C with 20 bar pressure of Argon (Ar).

Diagnostic Mock-Up as a Surgical Reduction Guide for Crown Lengthening: Technique Description and Case Report.

Background and Objectives: The report describes a technique using a diagnostic mock-up as a crown-lengthening surgical guide to improve the gingival architecture. Materials and Methods: The patient's primary concern was improving her smile due to her "gummy smile" and short clinical crowns. After clinical evaluation, surgical crown lengthening accompanied by maxillary central full-coverage single-unit prostheses and lateral incisor veneers was recommended. The diagnostic mock-up was placed in the patient's maxillary anterior region and used as a soft tissue reduction guide for the gingivectomy. Once the planned gingival architecture was achieved, a flap was reflected to proceed with ostectomy in order to obtain an appropriate alveolar bone crest level using the overlay. After six months, all-ceramic crowns and porcelain veneers were provided as permanent restorations. Results: A diagnostic mock-up fabricated with a putty guide directly from the diagnostic wax-up can be an adequate surgical guide for crown-lengthening procedures. The diagnostic wax-up was used to fabricate the diagnostic mock-up. These results suggested that it can be used as a crown-lengthening surgical guide to modify the gingival architecture. Several advantages of the overlay used in the aesthetic complex case include: (1) providing a preview of potential restorative outcomes, (2) allowing for the appropriate positioning of gingival margins and the desired alveolar bone crest level for the crown-lengthening procedure, and (3) serving as a provisional restoration after surgery. Conclusions: The use of a diagnostic mock-up, which was based on a diagnostic wax-up, as the surgical guide resulted in successful crown lengthening and provisional restorations. Thus, a diagnostic overlay can be a viable option as a surgical guide for crown lengthening.

Modelling the PSI response in general anesthesia.

In anesthesia automation, one of the main important issues is the availability of a reliable measurement of the depth of consciousness level (hypnosis) of the patient. According to this value, the hypnotic drug dosage can be adequately calculated. One of the most studied hypnosis indexes is the bispectral index (BIS). In this article we analyzed an alternative called patient state index (PSI). The objectives of this study are, first, to validate the accuracy of the PSI describing the hypnosis level during the maintenance phase of general anesthesia, by comparing with the BIS and, second, to model the relationship between propofol infusion rate and PSI values, obtained from a SEDLine monitor. For this, real data from patients undergoing general anesthesia simultaneously monitored with both BIS and PSI signals was used. Results obtained are interesting for a correct interpretation of PSI signal in clinical practice.

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice.

The prevalence of inflammatory diseases is increasing in modern urban societies. Inflammation increases risk of stress-related pathology; consequently, immunoregulatory or antiinflammatory approaches may protect against negative stress-related outcomes. We show that stress disrupts the homeostatic relationship between the microbiota and the host, resulting in exaggerated inflammation. Repeated immunization with a heat-killed preparation of Mycobacterium vaccae, an immunoregulatory environmental microorganism, reduced subordinate, flight, and avoiding behavioral responses to a dominant aggressor in a murine model of chronic psychosocial stress when tested 1-2 wk following the final immunization. Furthermore, immunization with M. vaccae prevented stress-induced spontaneous colitis and, in stressed mice, induced anxiolytic or fear-reducing effects as measured on the elevated plus-maze, despite stress-induced gut microbiota changes characteristic of gut infection and colitis. Immunization with M. vaccae also prevented stress-induced aggravation of colitis in a model of inflammatory bowel disease. Depletion of regulatory T cells negated protective effects of immunization with M. vaccae on stress-induced colitis and anxiety-like or fear behaviors. These data provide a framework for developing microbiome- and immunoregulation-based strategies for prevention of stress-related pathologies.

Pediatric asthma treatment: What to do when international guideline recommendations do not agree.

BACKGROUND: There was a need for a solid asthma guideline in Mexico to update and unify asthma management. Because high-quality asthma guidelines exist worldwide, in which the latest evidence on asthma management is summarized, the ADAPTE approach allows for the development of a national asthma guideline based on evidence from already existing guidelines, adapted to national needs. OBJECTIVE: To fuse evidence from the best asthma guidelines and adapt it to local needs with the ADAPTE approach. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) II asthma guidelines were evaluated by a core group to select 3 primary guidelines. For each step of asthma management, clinical questions were formulated and replied according to (1) evidence in the primary guidelines, (2) safety, (3) Cost, and (4) patient preference. The Guidelines Development Group, composed of a broad range of experts from medical specialties, primary care physicians, and methodologists, adjusted the draft questions and replies in several rounds of a Delphi process and 3 face-to-face meetings, taking into account the reality of the situation in Mexico. We present the results of the pediatric asthma treatment part. RESULTS: Selected primary guidelines are from the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN), Global Initiative for Asthma (GINA), and Spanish Guidelines on the Management of Asthma (GEMA) 2015, with 2016 updates. Recommendations or suggestions were made for asthma treatment in Mexico. In this article, the detailed analysis of the evidence present in the BTS/SIGN, GINA, and GEMA sections on the (non) pharmacologic treatment of pediatric asthma, education, and devices are presented for 2 age groups: children 5 years or younger and children 6 to 11 years old with asthma. CONCLUSION: For the pediatric treatment and patient education sections, applying the AGREE II and Delphi methods is useful to develop a scientifically sustained document, adjusted to the Mexican situation, as is the Mexican Guideline on Asthma.

A randomized controlled trial: branched-chain amino acid levels and glucose metabolism in patients with obesity and sleep apnea.

There is evidence that changes in branched-chain amino acid (BCAA) levels may correlate with the efficacy of therapeutic interventions for affecting improvement in metabolic control. The objective of this study was to evaluate whether serum concentrations of BCAAs (leucine, isoleucine, valine) could mediate in insulin sensitivity and glucose tolerance after continuous positive airway pressure (CPAP) treatment in patients with obstructive sleep apnea (OSA). A prospective randomized controlled trial of OSA patients with morbid obesity was conducted. Eighty patients were randomized into two groups: 38 received conservative treatment and 42 received CPAP treatment for 12 weeks. Plasma levels of BCAA, glucose tolerance and insulin resistance were evaluated at baseline and after treatment. After treatment, significant decreases of leucine levels were observed in both groups when compared with baseline levels (P < 0.005). With respect to patients with normal glucose tolerance (NGT), patients with impaired glucose tolerance (IGT) had higher baseline levels of isoleucine (78 ± 16 versus 70 ± 13 µmol L-1 , P = 0.014) and valine (286 ± 36 versus 268 ± 41 µmol L-1 , P = 0.049), respectively. Changes in levels of leucine and isoleucine after treatment were related negatively to changes in fasting plasma glucose and glycosylated haemoglobin values only in the conservative group (P < 0.05). In summary, we found that the treatment with CPAP for 12 weeks caused similar changes in circulating BCAAs concentrations to conservative treatment and a differential metabolic response of CPAP and conservative treatment was observed between the relationship of BCAAs and glucose homeostasis. Additional studies are needed to determine the interplay between branched-chain amino acids and glucose metabolism in patients with sleep apnea.

The effect of progressive muscle relaxation on daily cortisol secretion.

Abbreviated progressive muscle relaxation (APMR) is a much used stress-management technique. Its efficacy relevant to placebo control is already established in the literature and the primary aim of the present study was to ascertain whether its proven impact on psychological stress measures is matched by a decrease in prevailing levels of the stress-associated hormone cortisol, using accurate and robust measurement based on multiple sampling of full diurnal cortisol secretion profiles. First-year university students can face significant stress in adjustment to academic demands and immersion in a novel social network and provided a convenient study population. One hundred and one first-year students completed APMR with prevailing stress levels assessed a week before and after intervention. Both cortisol and self-report measures were significantly reduced post-intervention by 8% and 10%, respectively. The efficacy of the intervention was independent of, and not modulated by neuroticism, gender, age and smoking status. We also demonstrated that cortisol reduction was unlikely to have been a consequence of adaptation to any initial cortisol elevation prompted by the challenge of the demanding saliva collection protocol. We conclude that the efficacy of APMR in this population extends to reduction in biologically expressed stress levels as well as levels based solely on self-report.

Venous Thromboembolism Risk and Adherence to Pharmacological Thromboprophylaxis in Hospitalized Patients in Uruguay: First Nationwide Study.

INTRODUCTION: Venous thromboembolism (VTE) is a serious, frequent, and preventable medical complication in hospitalized patients. Although the efficacy of prophylaxis (pharmacological and/or mechanical) has been demonstrated, compliance with prophylaxis is poor at international and national levels. AIM: To determine the indication and use of pharmacological thromboprophylaxis in hospitalized patients in Uruguay. METHODS: An observational, descriptive, cross-sectional, multicentre study involving 31 nationwide healthcare facilities was conducted. Baseline characteristics associated with hospital admission, the percentage of the population with an indication for thromboprophylaxis, and the percentage of patients receiving pharmacological thromboprophylaxis were assessed. The VTE risk was determined using the Padua score for medical patients; the Caprini score for surgical patients; the Royal College of Obstetricians and Gynaecologists (RCOG) guidelines for pregnant-postpartum patients. RESULTS: 1925 patients were included, representing 26% of hospitalized patients in Uruguay. 71.9% of all patients were at risk of VTE. Of all patients at risk of VTE, 58.6% received pharmacological thromboprophylaxis. The reasons for not receiving thromboprophylaxis were prescribing omissions in 16.1% of cases, contraindication in 15.9% and 9.4% of patients were already anticoagulated for other reasons. Overall, just 68% of patients were "protected" against VTE. Recommendations of major thromboprophylaxis guidelines were followed in 70.1% of patients at risk. CONCLUSIONS: Despite the progress made in adherence to thromboprophylaxis indications, nonadherence remains a problem, affecting one in six patients at risk of VTE in Uruguay.

Epigenetic Signatures in Hypertension.

Clear epigenetic signatures were found in hypertensive and pre-hypertensive patients using DNA methylation data and neural networks in a classification algorithm. It is shown how by selecting an appropriate subset of CpGs it is possible to achieve a mean accuracy classification of 86% for distinguishing control and hypertensive (and pre-hypertensive) patients using only 2239 CpGs. Furthermore, it is also possible to obtain a statistically comparable model achieving an 83% mean accuracy using only 22 CpGs. Both of these approaches represent a substantial improvement over using the entire amount of available CpGs, which resulted in the neural network not generating accurate classifications. An optimization approach is followed to select the CpGs to be used as the base for a model distinguishing between hypertensive and pre-hypertensive individuals. It is shown that it is possible to find methylation signatures using machine learning techniques, which can be applied to distinguish between control (healthy) individuals, pre-hypertensive individuals and hypertensive individuals, illustrating an associated epigenetic impact. Identifying epigenetic signatures might lead to more targeted treatments for patients in the future.

An immediate implant approach to replace failing maxillary anterior dentition due to orthodontically induced severe root resorption.

Incomplete orthodontic therapy can lead to severe root resorption, resulting in mobile and non-restorable teeth. This clinical report presents the diagnosis, treatment planning and oral rehabilitation of a young woman with failing dentition in the anterior maxilla due to orthodontically induced root resorption. The patient's chief complaint was mobile maxillary anterior teeth 2 years after discontinuing orthodontic treatment. Radiographic and clinical evaluations revealed a missing right first premolar and left premolars and grade III mobility from the right canine to the left lateral incisor. Due to a hopeless prognosis, extraction of the maxillary anterior teeth was planned, followed by grafting procedures. Four implants were immediately placed in the fresh sockets of the canine and central sites, and a removable provisional appliance was delivered to contour the soft tissues involved. The final restorations consisted of two three-unit layered zirconia implant-supported fixed dental prostheses. Well-planned immediate implant therapy and zirconia restorations can successfully replace mobile teeth with severe root resorption caused by external surface resorption from incomplete orthodontic treatment. Combining grafting procedures during implant placement can replace hard tissue lost due to extractions, whereas provisional restorations can re-establish optimal tissue architecture in the aesthetic zone. The present case offers insight into effective strategies for treating non-compliant or uncooperative patients with failing dentition due to orthodontically induced root resorption.