Impact of sex differences on the feasibility and safety of distal radial access for coronary procedures: a multicenter prospective observational study.

BACKGROUND: Conventional transradial access in women is associated with a lower success rate and a higher incidence of spasm compared to men. To date, the effect of sex on the performance of distal radial access (DRA) has not been fully elucidated. The aim of this study was to assess the impact of sex on catheterization success and other performance parameters of DRA procedures. METHODS: This is a prospective three-center observational study. From August 2020 to September 2022, data from all consecutive patients who underwent DRA for coronary procedures were collected. RESULTS: A total of 868 procedures were registered and stratified into two groups according to sex: women (n = 258) and men (n = 610). Female patients had less favorable baseline characteristics than male patients in terms of absent or weak pulse (29% vs. 17%; P < 0.001), distal radial diameter (2.2 ±â€…0.3 vs. 2.4 ±â€…0.4 mm; P < 0.001) and proximal radial diameter (2.5 ±â€…0.7 vs. 2.7 ±â€…0.7 mm; P = 0.001). No differences in success rates were found in women compared to men (94.2% vs. 96.6%; P = 0.135), with a higher presence of arterial spasm in women (5.8% vs. 3.0%; P = 0.044). The preprocedural ultrasound evaluation was the only predictor of DRA success [odds ratio = 20.0 (4.739-83.333); P < 0.001]. CONCLUSION: In patients undergoing coronary procedures, the success rate of DRA was high regardless of sex, with a higher incidence of arterial spasm in women.

Enamel fluorosis related with fluoride-containing water ingestion and urinary excretion in schoolchildren.

Background: Natural water sources are considered as the major environmental exposure of fluoride, resulting in increased prevalence of enamel fluorosis. This type of natural exposure should be permanently monitored to avoid the interactions with other non-natural fluoride sources. We evaluated the prevalence of enamel fluorosis in Colombian schoolchildren and its relationship with fluoride-containing water ingestion exposure dose and urinary fluoride excretion. Material and Methods: We included 923 schoolchildren aged 7-12 years residing in eight municipalities in Colombia. Sampling of consumption water was performed in major aquifers used for daily supply. Samples were collected in 98 polyethylene containers and refrigerated until analysis. Water and urine fluoride concentrations were measured using the fluoride selective electrode method. Enamel fluorosis was evaluated using Thylstrup and Ferjerskov Index (TFI). Demographic and anthropometric characteristics were assessed. Besides, other exposures to non-natural fluoride were also evaluated. Logistic regression was applied for multiple analyses. Results: The median fluoride concentration in water and urine samples was 10.5 mg/L and 0.63 mg/L respectively, with the highest value found in Algarrobo-Magdalena, and the lowest value found in Manzanares-Caldas. The overall prevalence of enamel fluorosis was 86.1%, being more frequent the mild codes with TFI-1 to TFI-2. The highest prevalence was found in Margarita-Bolívar and Manzanares-Caldas, and the most severe codes (TFI-5 to TFI-9) were detected in Manzanares-Caldas. The multiple analysis revealed water ingestion exposure dose, urinary excretion, involuntary intake of toothpaste, amount of table salt consumption and sex as significant factors (p< 0.001). Conclusions: The fluoride ingestion exposure dose and its subsequent urinary excretion could be used as estimators of past fluoride exposure, explaining the current prevalence of enamel fluorosis in Colombian schoolchildren. Key words:Fluoride, groundwater ingestion, enamel fluorosis, prevalence, severity.

Degradation behaviour of porous poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) scaffolds in cell culture.

Exploring the degradation behaviour of biomaterials in a complex in vitro physiological environment can assist in predicting their performance in vivo, yet this aspect remains largely unexplored. In this study, the in vitro degradation over 12 weeks of porous poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) bone scaffolds in human osteoblast (hOB) culture was investigated. The objective was to evaluate how the presence of cells influenced both the degradation behaviour and mechanical stability of these scaffolds. The molecular weight (Mw) of the scaffolds decreased with increasing incubation time and the Mw reduction rate (6.2 ± 0.4 kg mol-1 week-1) was similar to that observed when incubated in phosphate buffered saline (PBS) solution, implying that the scaffolds underwent hydrolytic degradation in hOB culture. The mass of the scaffolds increased by 0.8 ± 0.2 % in the first 4 weeks, attributed to cells attachment and extracellular matrix (ECM) deposition including biomineralisation. During the first 8 weeks, the nominal compressive modulus, E⁎, of the scaffolds remained constant. However, it increased significantly from Week 8 to 12, with increments of 55 % and 42 % in normal and lateral directions, respectively, attributed to the reinforcement effect of cells, ECM and minerals attached on the surface of the scaffold. This study has highlighted, that while the use of PBS in degradation studies is suitable for evaluating Mw changes it cannot predict changes in mechanical properties to PHBV scaffolds in the presence of cells and culture media. Furthermore, the PHBV scaffolds had mechanical stability in cell culture for 12 weeks validating their suitability for tissue engineering applications.

Causal dispositionalism in behaviour genetics.

Causal dispositionalism developed in metaphysics of science offers a useful tool to conceptualize shallow causes in behaviour genetics, in a way such that (a) it accounts for complex aetiology and heterogeneity of effects, and (b) genetic causal contribution can be considered to be explanatory. Genes are thus causal powers that make a difference.

Genetic reanalysis of patients with a difference of sex development carrying the NR5A1/SF-1 variant p.Gly146Ala has discovered other likely disease-causing variations.

NR5A1/SF-1 (Steroidogenic factor-1) variants may cause mild to severe differences of sex development (DSD) or may be found in healthy carriers. The NR5A1/SF-1 c.437G>C/p.Gly146Ala variant is common in individuals with a DSD and has been suggested to act as a susceptibility factor for adrenal disease or cryptorchidism. Since the allele frequency is high in the general population, and the functional testing of the p.Gly146Ala variant revealed inconclusive results, the disease-causing effect of this variant has been questioned. However, a role as a disease modifier is still possible given that oligogenic inheritance has been described in patients with NR5A1/SF-1 variants. Therefore, we performed next generation sequencing (NGS) in 13 DSD individuals harboring the NR5A1/SF-1 p.Gly146Ala variant to search for other DSD-causing variants and clarify the function of this variant for the phenotype of the carriers. Panel and whole-exome sequencing was performed, and data were analyzed with a filtering algorithm for detecting variants in NR5A1- and DSD-related genes. The phenotype of the studied individuals ranged from scrotal hypospadias and ambiguous genitalia in 46,XY DSD to opposite sex in both 46,XY and 46,XX. In nine subjects we identified either a clearly pathogenic DSD gene variant (e.g. in AR) or one to four potentially deleterious variants that likely explain the observed phenotype alone (e.g. in FGFR3, CHD7). Our study shows that most individuals carrying the NR5A1/SF-1 p.Gly146Ala variant, harbor at least one other deleterious gene variant which can explain the DSD phenotype. This finding confirms that the NR5A1/SF-1 p.Gly146Ala variant may not contribute to the pathogenesis of DSD and qualifies as a benign polymorphism. Thus, individuals, in whom the NR5A1/SF-1 p.Gly146Ala gene variant has been identified as the underlying genetic cause for their DSD in the past, should be re-evaluated with a NGS method to reveal the real genetic diagnosis.

Targeting Agents in Biomaterial-Mediated Bone Regeneration.

Bone diseases are a global public concern that affect millions of people. Even though current treatments present high efficacy, they also show several side effects. In this sense, the development of biocompatible nanoparticles and macroscopic scaffolds has been shown to improve bone regeneration while diminishing side effects. In this review, we present a new trend in these materials, reporting several examples of materials that specifically recognize several agents of the bone microenvironment. Briefly, we provide a subtle introduction to the bone microenvironment. Then, the different targeting agents are exposed. Afterward, several examples of nanoparticles and scaffolds modified with these agents are shown. Finally, we provide some future perspectives and conclusions. Overall, this topic presents high potential to create promising translational strategies for the treatment of bone-related diseases. We expect this review to provide a comprehensive description of the incipient state-of-the-art of bone-targeting agents in bone regeneration.

Population structure and hybridisation in a population of Hawaiian feral chickens.

Chickens are believed to have inhabited the Hawaiian island of Kauai since the first human migrations around 1200AD, but numbers have peaked since the tropical storms Iniki and Iwa in the 1980s and 1990s that destroyed almost all the chicken coops on the island and released large numbers of domestic chickens into the wild. Previous studies have shown these now feral chickens are an admixed population between Red Junglefowl (RJF) and domestic chickens. Here, using genetic haplotypic data, we estimate the time of the admixture event between the feral population on the island and the RJF to 1981 (1976-1995), coinciding with the timings of storm Iwa and Iniki. Analysis of genetic structure reveals a greater similarity between individuals inhabiting the northern and western part of the island to RJF than individuals from the eastern part of the island. These results point to the possibility of introgression events between feral chickens and the wild chickens in areas surrounding the Koke'e State Park and the Alaka'i plateau, posited as two of the major RJF reservoirs in the island. Furthermore, we have inferred haplotype blocks from pooled data to determine the most plausible source of the feral population. We identify a clear contribution from RJF and layer chickens of the White Leghorn (WL) breed. This work provides independent confirmation of the traditional hypothesis surrounding the origin of the feral populations and draws attention to the possibility of introgression of domestic alleles into the wild reservoir.

DNA Methylation Description of Hippocampus, Cortex, Amygdala, and Blood of Drug-Resistant Temporal Lobe Epilepsy.

Epigenetic changes such as DNA methylation were observed in drug-resistant temporal lobe epilepsy (DR-TLE), a disease that affects 25-30% of epilepsy patients. The main objective is to simultaneously describe DNA methylation patterns associated with DR-TLE in hippocampus, amygdala, surrounding cortex to the epileptogenic zone (SCEZ), and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array was performed in 19 DR-TLE patients and 10 postmortem non-epileptic controls. Overall, 32, 59, and 3210 differentially methylated probes (DMPs) were associated with DR-TLE in the hippocampus, amygdala, and SCEZ, respectively. These DMP-affected genes were involved in neurotrophic and calcium signaling in the hippocampus and voltage-gated channels in SCEZ, among others. One of the hippocampus DMPs (cg26834418 (CHORDC1)) showed a strong blood-brain correlation with BECon and IMAGE-CpG, suggesting that it could be a potential surrogate peripheral biomarker of DR-TLE. Moreover, in three of the top SCEZ's DMPs (SHANK3, SBF1, and MCF2L), methylation status was verified with methylation-specific qPCR. The differentially methylated CpGs were classified in DMRs: 2 in the hippocampus, 12 in the amygdala, and 531 in the SCEZ. We identified genes that had not been associated to DR-TLE so far such as TBX5, EXOC7, and WRHN. The area with more DMPs associated with DR-TLE was the SCEZ, some of them related to voltage-gated channels. The DMPs found in the amygdala were involved in inflammatory processes. We also found a potential surrogate peripheral biomarker of DR-TLE. Thus, these results provide new insights into epigenetic modifications involved in DR-TLE.

The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource.

The NHGRI-EBI GWAS Catalog (www.ebi.ac.uk/gwas) is a FAIR knowledgebase providing detailed, structured, standardised and interoperable genome-wide association study (GWAS) data to >200 000 users per year from academic research, healthcare and industry. The Catalog contains variant-trait associations and supporting metadata for >45 000 published GWAS across >5000 human traits, and >40 000 full P-value summary statistics datasets. Content is curated from publications or acquired via author submission of prepublication summary statistics through a new submission portal and validation tool. GWAS data volume has vastly increased in recent years. We have updated our software to meet this scaling challenge and to enable rapid release of submitted summary statistics. The scope of the repository has expanded to include additional data types of high interest to the community, including sequencing-based GWAS, gene-based analyses and copy number variation analyses. Community outreach has increased the number of shared datasets from under-represented traits, e.g. cancer, and we continue to contribute to awareness of the lack of population diversity in GWAS. Interoperability of the Catalog has been enhanced through links to other resources including the Polygenic Score Catalog and the International Mouse Phenotyping Consortium, refinements to GWAS trait annotation, and the development of a standard format for GWAS data.

Emerging Technologies of Three-Dimensional Printing and Mobile Health in COVID-19 Immunity and Regenerative Dentistry.

The ongoing coronavirus disease 2019 (COVID-19) pandemic highlights the importance of developing point-of-care (POC) antibody tests for monitoring the COVID-19 immune response upon viral infection or following vaccination, which requires three key aspects to achieve optimal monitoring, including three-dimensional (3D)-printed POC devices, mobile health (mHealth), and noninvasive sampling. As a critical tissue engineering concept, additive manufacturing (AM, also known as 3D printing) enables accurate control over the dimensional and architectural features of the devices. mHealth refers to the use of portable digital devices, such as smartphones, tablet computers, and fitness and medical wearables, to support health, which facilitates contact tracing, and telehealth consultations during the pandemic. Compared with invasive biosample (blood), saliva is of great importance in the spread and surveillance of COVID-19 as a noninvasive diagnostic method for virus detection and immune status monitoring. However, investigations into 3D-printed POC antibody test and mHealth using noninvasive saliva are relatively limited. Further exploration of 3D-printed antibody POC tests and mHealth applications to monitor antibody production for either disease onset or immune response following vaccination is warranted. This review briefly describes the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and immune response after infection and vaccination, then discusses current widely used binding antibody tests using blood samples and enzyme-linked immunosorbent assays on two-dimensional microplates before focusing upon emerging POC technological platforms, such as field-effect transistor biosensors, lateral flow assay, microfluidics, and AM for fabricating immunoassays, and the possibility of their combination with mHealth. This review proposes that noninvasive biofluid sampling combined with 3D POC antibody tests and mHealth technologies is a promising and novel approach for POC detection and surveillance of SARS-CoV-2 immune response. Furthermore, as key concepts in dentistry, the application of 3D printing and mHealth was also included to facilitate the appreciation of cutting edge techniques in regenerative dentistry. This review highlights the potential of 3D printing and mHealth in both COVID-19 immunity monitoring and regenerative dentistry.

A Comparative Study of Mesoporous Silica and Mesoporous Bioactive Glass Nanoparticles as Non-Viral MicroRNA Vectors for Osteogenesis.

Micro-ribonucleic acid (miRNA)-based therapies show advantages for bone regeneration but need efficient intracellular delivery methods. Inorganic nanoparticles such as mesoporous bioactive glass nanoparticles (MBGN) and mesoporous silica nanoparticles (MSN) have received growing interest in the intracellular delivery of nucleic acids. This study explores the capacity of MBGN and MSN for delivering miRNA to bone marrow mesenchymal stem cells (BMSC) for bone regenerative purposes, with a focus on comparing the two in terms of cell viability, transfection efficiency, and osteogenic actions. Spherical MBGN and MSN with a particle size of ~200 nm and small-sized mesopores were prepared using the sol-gel method, and then the surface was modified with polyethyleneimine for miRNA loading and delivery. The results showed miRNA can be loaded into both nanoparticles within 2 h and was released sustainedly for up to 3 days. Confocal laser scanning microscopy and flow cytometry analysis indicated a high transfection efficiency (>64%) of both nanoparticles without statistical difference. Compared with MSN, MBGN showed stronger activation of alkaline phosphatase and activation of osteocalcin genes. This translated to a greater osteogenic effect of MBGN on BMSC, with Alizarin red staining showing greater mineralization compared with the MSN group. These findings show the potential for MBGN to be used in bone tissue engineering.

Salivary SARS-CoV-2 antibody detection using S1-RBD protein-immobilized 3D melt electrowritten poly(ε-caprolactone) scaffolds.

Sensitive detection of immunoglobulin antibodies against SARS-CoV-2 during the COVID-19 pandemic is critical to monitor the adaptive immune response after BNT162b2 mRNA vaccination. Currently employed binding antibody detection tests using 2D microplate-based enzyme-linked immunosorbent assays (ELISA) are limited by the degree of sensitivity. In this study, a 3D antibody test was developed by immobilizing the receptor-binding domain on Spike subunit 1 (S1-RBD) of SARS-CoV-2 onto engineered melt electrowritten (MEW) poly(ε-caprolactone) (PCL) scaffolds (pore: 500 µm, fiber diameter: 17 µm) using carbodiimide crosslinker chemistry. Protein immobilization was confirmed using X-ray photoelectron spectroscopy (XPS) by the presence of peaks corresponding with nitrogen. Self-developed indirect ELISA was performed to assess the functionality of the 3D platform in comparison with a standard 2D tissue culture plate (TCP) system, using whole unstimulated saliva samples from 14 non-vaccinated and 20 vaccinated participants (1- and 3- weeks post-dose 1; 3 days, 1 week and 3 weeks post-dose 2) without prior SARS-CoV-2 infection. The three-dimensional S1-RBD PCL scaffolds, while demonstrating a kinetic trend comparable to 2D TCP, exhibited significantly higher sensitivity and detection levels for all three immunoglobulins assayed (IgG, IgM, and IgA). These novel findings highlight the potential of MEW PCL constructs in the development of improved low-cost, point-of-care, and self-assessing diagnostic platforms for the detection and monitoring of SARS-CoV-2 antibodies.

In vitro evaluation of porous poly(hydroxybutyrate-co-hydroxyvalerate)/akermanite composite scaffolds manufactured using selective laser sintering.

Incorporation of a bioactive mineral filler in a biodegradable polyester scaffold is a promising strategy for scaffold assisted bone tissue engineering (TE). The current study evaluates the in vitro behavior of poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV)/Akermanite (AKM) composite scaffolds manufactured using selective laser sintering (SLS). Exposure of the mineral filler on the surface of the scaffold skeleton was evident from in vitro mineralization in PBS. PHBV scaffolds and solvent cast films served as control samples and all materials showed preferential adsorption of fibronectin compared to serum albumin as well as non-cytotoxic response in human osteoblasts (hOB) at 24 h. hOB culture for up to 21 days revealed that the metabolic activity in PHBV films and scaffolds was significantly higher than that of PHBV/AKM scaffolds within the first two weeks of incubation. Afterwards, the metabolic activity in PHBV/AKM scaffolds exceeded that of the control samples. Confocal imaging showed cell penetration into the porous scaffolds. Significantly higher ALP activity was observed in PHBV/AKM scaffolds at all time points in both basal and osteogenic media. Mineralization during cell culture was observed on all samples with PHBV/AKM scaffolds exhibiting distinctly different mineral morphology. This study has demonstrated that the bioactivity of PHBV SLS scaffolds can be enhanced by incorporating AKM, making this an attractive candidate for bone TE application.

Genomic and gene expression associations to morphology of a sexual ornament in the chicken.

How sexual selection affects the genome ultimately relies on the strength and type of selection, and the genetic architecture of the involved traits. While associating genotype with phenotype often utilizes standard trait morphology, trait representations in morphospace using geometric morphometric approaches receive less focus in this regard. Here, we identify genetic associations to a sexual ornament, the comb, in the chicken system (Gallus gallus). Our approach combined genome-wide genotype and gene expression data (>30k genes) with different aspects of comb morphology in an advanced intercross line (F8) generated by crossing a wild-type Red Junglefowl with a domestic breed of chicken (White Leghorn). In total, 10 quantitative trait loci were found associated to various aspects of comb shape and size, while 1,184 expression QTL were found associated to gene expression patterns, among which 98 had overlapping confidence intervals with those of quantitative trait loci. Our results highlight both known genomic regions confirming previous records of a large effect quantitative trait loci associated to comb size, and novel quantitative trait loci associated to comb shape. Genes were considered candidates affecting comb morphology if they were found within both confidence intervals of the underlying quantitative trait loci and eQTL. Overlaps between quantitative trait loci and genome-wide selective sweeps identified in a previous study revealed that only loci associated to comb size may be experiencing on-going selection under domestication.

Identification and quantification of chimeric sequencing reads in a highly multiplexed RAD-seq protocol.

Highly multiplexed approaches have become common in genomic studies. They have improved the cost-effectiveness of genotyping hundreds of individuals using combinatorially barcoded adapters. These strategies, however, can potentially misassigned reads to incorrect samples. Here, we used a modified quaddRAD protocol to analyse the occurrence of index hopping and PCR chimeras in a series of experiments with up to 100 multiplexed samples per sequencing lane (639 samples in total). We created two types of sequencing libraries: four libraries of type A, where PCRs were run on individual samples before multiplexing, and three libraries of type B, where PCRs were run on pooled samples. We used fixed pairs of inner barcodes to identify chimeric reads. Type B libraries show a higher percentage of misassigned reads (1.15%) than type A libraries (0.65%). We also quantify the commonly undetectable chimeric sequences that occur whenever multiplexed groups of samples with different outer barcodes are sequenced together on a single flow cell. Our results suggest that these types of chimeric sequences represent up to 1.56% and 1.29% of reads in type A and B libraries, respectively. We also show that increasing the number of mismatches allowed for barcode rescue to above 2 dramatically increases the number of recovered chimeric reads. We provide recommendations for developing highly multiplexed RAD-seq protocols and analysing the resulting data to minimize the generation of chimeric sequences, allowing their quantification and a finer control on the number of PCR cycles necessary to generate enough input DNA for library preparation.

Surface Modification of Pure Zinc by Acid Etching: Accelerating the Corrosion Rate and Enhancing Biocompatibility and Antibacterial Characteristics.

Zinc (Zn) has recently been identified as an auspicious biodegradable metal for medical implants and devices due to its tunable mechanical properties and good biocompatibility. However, the slow corrosion rate of Zn in a physiological environment does not meet the requirements for biodegradable implants, hindering its clinical translation. The present study aimed to accelerate the corrosion rate of pure Zn by utilizing acid etching to roughen the surface and increase the substrate surface area. The effects of acid etching on surface morphology, surface roughness, tensile properties, hardness, electrochemical corrosion and degradation behavior, cytocompatibility, direct cell attachment, and biofilm formation were investigated. Interestingly, acid-treated Zn showed an exceptionally high rate of corrosion (∼226-125 µm/year) compared to untreated Zn (∼62 µm/year), attributed to the increased surface roughness (Ra ∼ 1.12 µm) of acid-etched samples. Immersion tests in Hank's solution revealed that acid etching accelerated the degradation rate of Zn samples. In vitro, MC3T3-E1 cell lines in 50 and 25% conditioned media extracts of treated samples showed good cytocompatibility. Reduced bacterial adhesion, biofilm formation, and dispersion were observed for Staphylococci aureus biofilms cultured on acid-etched pure Zn substrates. These results suggest that the surface modification of biodegradable pure Zn metals by acid etching markedly increases the translation potential of zinc for various biomedical applications.

Microbial Communities in Volcanic Glacier Ecosystems.

Glaciers constitute a polyextremophilic environment characterized by low temperatures, high solar radiation, a lack of nutrients, and low water availability. However, glaciers located in volcanic regions have special characteristics, since the volcanic foci provide them with heat and nutrients that allow the growth of microbial communities highly adapted to this environment. Most of the studies on these glacial ecosystems have been carried out in volcanic environments in the northern hemisphere, including Iceland and the Pacific Northwest. To better know, the microbial diversity of the underexplored glacial ecosystems and to check what their specific characteristics were, we studied the structure of bacterial communities living in volcanic glaciers in Deception Island, Antarctica, and in the Kamchatka peninsula. In addition to geographic coordinates, many other glacier environmental factors (like volcanic activity, altitude, temperature, pH, or ice chemical composition) that can influence the diversity and distribution of microbial communities were considered in this study. Finally, using their taxonomic assignments, an attempt was made to compare how different or similar are the biogeochemical cycles in which these microbiomes are involved.

Return of genomic results does not motivate intent to participate in research for all: Perspectives across 22 countries.

PURPOSE: The aim of this study was to determine how attitudes toward the return of genomic research results vary internationally. METHODS: We analyzed the "Your DNA, Your Say" online survey of public perspectives on genomic data sharing including responses from 36,268 individuals across 22 low-, middle-, and high-income countries, and these were gathered in 15 languages. We analyzed how participants responded when asked whether return of results (RoR) would motivate their decision to donate DNA or health data. We examined variation across the study countries and compared the responses of participants from other countries with those from the United States, which has been the subject of the majority of research on return of genomic results to date. RESULTS: There was substantial variation in the extent to which respondents reported being influenced by RoR. However, only respondents from Russia were more influenced than those from the United States, and respondents from 20 countries had lower odds of being partially or wholly influenced than those from the United States. CONCLUSION: There is substantial international variation in the extent to which the RoR may motivate people's intent to donate DNA or health data. The United States may not be a clear indicator of global attitudes. Participants' preferences for return of genomic results globally should be considered.

Sequencing-based genome-wide association studies reporting standards.

Genome sequencing has recently become a viable genotyping technology for use in genome-wide association studies (GWASs), offering the potential to analyze a broader range of genome-wide variation, including rare variants. To survey current standards, we assessed the content and quality of reporting of statistical methods, analyses, results, and datasets in 167 exome- or genome-wide-sequencing-based GWAS publications published from 2014 to 2020; 81% of publications included tests of aggregate association across multiple variants, with multiple test models frequently used. We observed a lack of standardized terms and incomplete reporting of datasets, particularly for variants analyzed in aggregate tests. We also find a lower frequency of sharing of summary statistics compared with array-based GWASs. Reporting standards and increased data sharing are required to ensure sequencing-based association study data are findable, interoperable, accessible, and reusable (FAIR). To support that, we recommend adopting the standard terminology of sequencing-based GWAS (seqGWAS). Further, we recommend that single-variant analyses be reported following the same standards and conventions as standard array-based GWASs and be shared in the GWAS Catalog. We also provide initial recommended standards for aggregate analyses metadata and summary statistics.

Finite element analysis of the performance of additively manufactured scaffolds for scapholunate ligament reconstruction.

Rupture of the scapholunate interosseous ligament can cause the dissociation of scaphoid and lunate bones, resulting in impaired wrist function. Current treatments (e.g., tendon-based surgical reconstruction, screw-based fixation, fusion, or carpectomy) may restore wrist stability, but do not address regeneration of the ruptured ligament, and may result in wrist functional limitations and osteoarthritis. Recently a novel multiphasic bone-ligament-bone scaffold was proposed, which aims to reconstruct the ruptured ligament, and which can be 3D-printed using medical-grade polycaprolactone. This scaffold is composed of a central ligament-scaffold section and features a bone attachment terminal at either end. Since the ligament-scaffold is the primary load bearing structure during physiological wrist motion, its geometry, mechanical properties, and the surgical placement of the scaffold are critical for performance optimisation. This study presents a patient-specific computational biomechanical evaluation of the effect of scaffold length, and positioning of the bone attachment sites. Through segmentation and image processing of medical image data for natural wrist motion, detailed 3D geometries as well as patient-specific physiological wrist motion could be derived. This data formed the input for detailed finite element analysis, enabling computational of scaffold stress and strain distributions, which are key predictors of scaffold structural integrity. The computational analysis demonstrated that longer scaffolds present reduced peak scaffold stresses and a more homogeneous stress state compared to shorter scaffolds. Furthermore, it was found that scaffolds attached at proximal sites experience lower stresses than those attached at distal sites. However, scaffold length, rather than bone terminal location, most strongly influences peak stress. For each scaffold terminal placement configuration, a basic metric was computed indicative of bone fracture risk. This metric was the minimum distance from the bone surface to the internal scaffold bone terminal. Analysis of this minimum bone thickness data confirmed further optimisation of terminal locations is warranted.