Novel risk loci for COVID-19 hospitalization among admixed American populations.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Hibiscus sabdariffa as a Novel Alternative Strategy Against Helicobacter pylori Infection Development to Gastric Cancer.

Most gastric cancers (95%) are related to an initial Helicobacter pylori infection worldwide. Treatments against this pathogen include a mix of antibiotics, antimicrobials, and proton-pump inhibitors. Over time, H. pylori mutated, generating resistance to treatments and making it hard to combat its infection. The purpose of this review is Hibiscus sabdariffa, commonly known as hibiscus, as a potential agent for anti-H. pylori activity. Scientific interest has increased toward plant-derived bioactive compounds, which have the ability to enhance the antibiotic effect and can lead to the development of new drugs, such is the case for H. sabdariffa. In general, studies show that natural products, such as plant-derived bioactive compounds, can be used as alternative treatments from natural origin against the pathogen. The specific action mechanism of these bioactive compounds is still controversial, but it is suggested that they have an anti-inflammatory effect, and they also act as antibiotic coadjutants. Research has been conducted regarding different bioactive compounds such as polyphenols, epicatechins, alkaloids, and caryophyllenes. H. sabdariffa contains several of these compounds; therefore, more studies are needed to establish its effect against H. pylori.

Adalimumab to treat noninfectious pediatric chronic anterior uveitis: a case series.

PURPOSE: Evaluate the response to adalimumab (ADA) in pediatric chronic anterior uveitis (pCAU). METHODS: Retrospective chart review of pCAU patients treated with ADA. Outcomes evaluated included the proportion of patients achieving zero ocular inflammation and discontinuation of topical corticosteroids, visual outcomes, and incidence of uveitis recurrences after ≥ 12 months of prescribing ADA. Incidence and risk factors for developing anti-adalimumab antibodies (AAAs) were also evaluated. RESULTS: Of 27 children aged 11 years, 16 (59%) were Caucasian and 6 (22%) African Americans. Thirteen (48%) patients had idiopathic pCAU, 12 (44%) had juvenile idiopathic arthritis (JIA) related pCAU, and 2 (7%) had tubulointerstitial nephritis and uveitis syndrome. At baseline, African American children had worse visual acuity (p = 0.026). At 1 year, 21 (78%) children achieved zero ocular inflammation (remission). Risk factors associated with non-remission were being African American (20% vs. 94%, p = 0.003) and experiencing ≥ 1 episode of uveitis recurrence (100% vs. 0%, p < 0.001). Six episodes of uveitis recurrence were documented in five children, four of whom were African American. Topical corticosteroids were discontinued in 83% of children, and visual acuity remained stable for 1 year. Twelve children were tested for AAAs due to arthritis or uveitis flare-ups, with five (42%) being positive. No significant factors were associated with the development of AAAs. CONCLUSIONS: We found that ADA is effective in controlling inflammation, reducing the need for topical corticosteroids, and maintaining visual acuity in pCAU. There appears to be racial differences in African American children who had worse baseline disease and poorer outcomes. Studies are necessary to understand better and address these disparities.

Epidemiology and risk factors for the development of cicatrizing conjunctivitis in chronic ocular graft-versus-host disease.

PURPOSE: To evaluate the incidence of chronic cicatrizing conjunctivitis (CCC) and its associated risk factors in the context of chronic ocular graft-vs-host disease (coGVHD). METHODS: A retrospective chart review of individuals diagnosed with coGVHD following hematopoietic stem cell transplantation (HSCT) who were seen at the Bascom Palmer Eye Institute between May 2010 and November 2021 was performed. Data regarding baseline demographic characteristics, systemic co-morbidities, lid margin abnormalities, ocular cicatricial changes, transplant information, immunosuppressive therapy, and GVHD severity assessments were collected. The incidence of cicatricial conjunctivitis was estimated with Kaplan-Meier survival analysis. A Cox regression model was used to assess the contribution of demographic and systemic variables to the development of CCC. RESULTS: 167 individuals were included (53.9 ± 14.7 years old; 60.5 % male). 65 individuals presented with features suggestive of CCC an average of 60.9 ± 53.8 months after HSCT, with 60-month and 120-month incidences of 29.3 % and 48.9 %, respectively. Multivariable analysis demonstrated that age younger than 50 at the time of the first eye visit was associated with a higher chance of CCC development (Hazard Ratio (HR): 2.14, 95 % Confidence Interval (CI): 1.16-3.97, p = 0.02). CONCLUSION: Clinically detected cicatrizing conjunctivitis is an ocular manifestation of coGVHD, with an incidence that increases over time. Younger individuals may be at higher risk for CCC development.

Exploring the psychopathological profile of fibromyalgia: insights from the personality assessment inventory and its association with disease impact.

Background: Fibromyalgia (FM) is a complex rheumatic disorder characterized by chronic nociplastic pain and central sensitization. Psychopathological conditions can influence FM symptoms, which worsen their condition. However, not all patients with FM have psychopathological disorders, indicating a heterogeneous population. Objective: To investigate the psychopathological profile and personality disorders in patients with FM and its relationship impact on this disease. Methods: An observational and cross-sectional comparative study was conducted with a sample of 90 women, mean age 48.7 years (SD = 8.12), from Hospital del Mar, Barcelona. The Personality Assessment Inventory (PAI) and the Fibromyalgia Impact Questionnaire (FIQ) were used for assessment. Results: FM patients predominantly exhibited psychopathological profiles resembling affective disorders (37.7%) and Cluster C personality disorders (58.8%). The severity of FM's impact was related to affective disorder symptoms, hypervigilance, derealization, somatization, and Cluster B personality disorder (emotional instability). Different rheumatic symptoms correlated with specific psychopathological patterns. Increased somatic symptoms on the FIQ were related to an unstable and dependent personality, while heightened emotional symptoms on the FIQ were associated with avoidance, borderline traits, and passive-aggressive reactions. Conclusion: Recognizing psychopathological aspects is crucial for managing FM. The PAI is a valuable tool for establishing its psychopathological multidimensional profile, which predominantly shows an affective spectrum conditions and comorbid Cluster C personality disorder, exacerbating the disease's impact.

Five-year results of the very accelerated partial breast irradiation VAPBI phase I-II GEC-ESTRO trial.

BACKGROUND AND PURPOSE: The standard partial breast postoperative treatment for early breast carcinomas with multi-catheter interstitial brachytherapy (MIBT) requires 7-8 fractions in 4-5 days as used in the APBI GEC-ESTRO phase III trial. In 2017 the GEC-ESTRO Breast Cancer Working Group started a Phase I-II trial to study if very accelerated partial breast irradiation (VAPBI) using 3-4 fractions could be equivalent. MATERIAL: 81 patients with low-risk invasive carcinomas underwent high dose rate MIBT. Mean age was 68 (51-90); 33 women received 4 fractions of 6.25 Gy in 2-3 days, and 48 subsequent patients 3 fractions of 7.45 Gy in 2 days, 36 perioperatively and 45 postoperatively. RESULTS: Median follow-up was 62 months, with 5-year actuarial breast recurrence of 3.4 % (two cases). One patient died due to metastasis. Pigmentation changes in the entrance of tubes remained visible only in 12.3 % in long term (skin G1 toxicity). Fibrosis or slight induration (G1) in 22.2 % and G2 in 9.9 %. No case of telangiectasia has been described. Cosmetic outcome is good or excellent in 95 % and fair in 5 %. Four tumors located in the retroareolar area showed nipple retraction. CONCLUSION: VAPBI with MIBT using four fractions of 6.25 Gy or three fractions of 7.45 Gy in two or three days offers good local control, with a 5-year rate of fibrosis G2 similar to the GEC ESTRO phase III trial. VAPBI in two days is a good choice to decrease the total time of treatment, which is beneficial for the patient and reduces the workload.

Assessment of the Effective Sensitivity of SARS-CoV-2 Sample Pooling Based on a Large-Scale Screening Experience: Retrospective Analysis.

BACKGROUND: The development of new large-scale saliva pooling detection strategies can significantly enhance testing capacity and frequency for asymptomatic individuals, which is crucial for containing SARS-CoV-2. OBJECTIVE: This study aims to implement and scale-up a SARS-CoV-2 screening method using pooled saliva samples to control the virus in critical areas and assess its effectiveness in detecting asymptomatic infections. METHODS: Between August 2020 and February 2022, our laboratory received a total of 928,357 samples. Participants collected at least 1 mL of saliva using a self-sampling kit and registered their samples via a smartphone app. All samples were directly processed using AutoMate 2550 for preanalytical steps and then transferred to Microlab STAR, managed with the HAMILTON Pooling software for pooling. The standard pool preset size was 20 samples but was adjusted to 5 when the prevalence exceeded 2% in any group. Real-time polymerase chain reaction (RT-PCR) was conducted using the Allplex SARS-CoV-2 Assay until July 2021, followed by the Allplex SARS-CoV-2 FluA/FluB/RSV assay for the remainder of the study period. RESULTS: Of the 928,357 samples received, 887,926 (95.64%) were fully processed into 56,126 pools. Of these pools, 4863 tested positive, detecting 5720 asymptomatic infections. This allowed for a comprehensive analysis of pooling's impact on RT-PCR sensitivity and false-negative rate (FNR), including data on positive samples per pool (PPP). We defined Ctref as the minimum cycle threshold (Ct) of each data set from a sample or pool and compared these Ctref results from pooled samples with those of the individual tests (ΔCtP). We then examined their deviation from the expected offset due to dilution [ΔΔCtP = ΔCtP - log2]. In this work, the ΔCtP and ΔΔCtP were 2.23 versus 3.33 and -0.89 versus 0.23, respectively, comparing global results with results for pools with 1 positive sample per pool. Therefore, depending on the number of genes used in the test and the size of the pool, we can evaluate the FNR and effective sensitivity (1 - FNR) of the test configuration. In our scenario, with a maximum of 20 samples per pool and 3 target genes, statistical observations indicated an effective sensitivity exceeding 99%. From an economic perspective, the focus is on pooling efficiency, measured by the effective number of persons that can be tested with 1 test, referred to as persons per test (PPT). In this study, the global PPT was 8.66, reflecting savings of over 20 million euros (US $22 million) based on our reagent prices. CONCLUSIONS: Our results demonstrate that, as expected, pooling reduces the sensitivity of RT-PCR. However, with the appropriate pool size and the use of multiple target genes, effective sensitivity can remain above 99%. Saliva pooling may be a valuable tool for screening and surveillance in asymptomatic individuals and can aid in controlling SARS-CoV-2 transmission. Further studies are needed to assess the effectiveness of these strategies for SARS-CoV-2 and their application to other microorganisms or biomarkers detected by PCR.

Bridging the gap between ecological succession of fleshy-fruited shrubs and restoration frameworks in semiarid oldfields.

Abandoned agricultural areas (i.e. oldfields) represent an opportunity for natural vegetation recovery, increasing soil carbon sequestration and lessening the impacts of climate change and desertification. Ecological succession in oldfields can be hampered by the harsh conditions of semiarid and arid ecosystems, and hence, restoration actions may be needed in some contexts to reactivate the ecosystem functioning. Fleshy-fruited shrubs are indicators of progression in the ecological succession, which can shift notably across environmental gradients, making difficult to obtain robust conclusions at regional scales. Other poorly studied aspects at such scales (agricultural legacy, structural features and local landscape effects) add to this knowledge gap. Here, we study the species-specific natural colonization patterns of fleshy-fruited shrubs in semiarid oldfields across environmental gradients in the Southeast of the Iberian Peninsula taking into account specific traits of plants. We used Hierarchical Modelling of Species Communities (HMSC) to test the influence of the time since the abandonment and the past land-use history of the oldfields, and the effect of local structural factors, such as the presence of remnant trees and natural patches of vegetation, on the shrub recolonization patterns. We found that altitude and lithology conditioned the structure of shrub communities, allowing the selection of different focal species for making recommendations for restoration. Time since abandonment was not relevant for the colonization process. The persistence of remnant trees in the oldfields showed a positive effect on the occurrence of several shrub species. Close sources of propagules (terrace edges and/or natural vegetation patches) benefited the occurrence of certain species mainly at lower altitudes. Traits of species (growth form, root depth, dispersal mode, fruit length and water content) helped to explain the performance of species along the environmental gradients. We identified the main drivers of natural colonization of fleshy-fruited shrubs in semiarid oldfields across environmental gradients, providing ecological knowledge to guide scientists and practitioners to develop nature-based restoration frameworks. Different management actions are recommended according to the environmental gradient.

Temperature-dependent photoluminescence down to 77 K of organotin molecular rotors: eco-friendly synthesis, photophysical characterization, X-ray structures, and DFT studies.

Fluorescent organotin compounds are useful in sensing, optoelectronic devices, and in vitro bioimaging. Although in vitro fluorescence bioimaging shows low resolution at room temperature, a better resolution is possible at cryotemperatures. Therefore, the search for new cryoluminescent materials with potential application in high-resolution fluorescence bioimaging remains a great challenge. Herein, we report the cryoluminescence properties of two fluorescent bis-organotin compounds, namely, BisNTHySnBu2 (5) and BisNTHySnPh2 (6), synthesized via microwave irradiation. All compounds were fully characterized using 1H, 13C, and 119Sn NMR spectroscopy, Raman spectroscopy, IR spectroscopy, and HR-MS. The 119Sn δ and 3J(1H,119Sn) of 5 and 6 indicate that two Sn-ligands are chemically and electronically equivalent, as confirmed by cyclic voltammetry. The crystal structure of 6 showed pentacoordinate tin atoms with skeleton ligands. The study of self-assembled monolayers of both Sn-complexes via STM microscopy revealed a similar supramolecular packing in lamella-like patterns, adopting a face-on arrangement, where molecules stay flat lying on HOPG in accordance with the height profile of closely packed monolayers on graphite of about 0.33 nm thickness. However, only the Sn complex 6, which bears phenyls, covers large surface areas. The photophysical properties of bis-organotin compounds were also investigated in solution (room and low temperatures) and in the solid state. Good luminescence properties in solutions with fluorescence quantum yields (Φ) of approximately 35% and 50% were found. Despite this, Φ is quenched in the solid state because of aggregation, as supported by solvent/non solvent fluorescence studies, which is in agreement with STM and AFM investigation.

Deep-learning based analysis of in-vivo confocal microscopy images of the subbasal corneal nerve plexus' inferior whorl in patients with neuropathic corneal pain and dry eye disease.

PURPOSE: To evaluate and compare subbasal corneal nerve parameters of the inferior whorl in patients with dry eye disease (DED), neuropathic corneal pain (NCP), and controls using a novel deep-learning-based algorithm to analyze in-vivo confocal microscopy (IVCM) images. METHODS: Subbasal nerve plexus (SNP) images of the inferior whorl of patients with DED (n = 49, 77 eyes), NCP (n = 14, 24 eyes), and controls (n = 41, 59 eyes) were taken with IVCM and further analyzed using an open-source artificial intelligence (AI)-based algorithm previously developed by our group. This algorithm automatically segments nerves, immune cells, and neuromas in the SNP. The following parameters were compared between groups: nerve area density, average nerve thickness, average nerve segment tortuosity, junction point density, neuroma density, and immune cell density. RESULTS: 160 eyes of 104 patients (63 % females), aged 56.8 ± 15.4 years, were included. The mean nerve area density was significantly lower in the DED (P = 0.012) and NCP (P < 0.001) groups compared to the control group. The junction point density was lower in the NCP group compared with control (P = 0.001) and DED (P = 0.004) groups. The immune cell density was higher in the DED group compared with controls (P < 0.001). CONCLUSIONS: Deep-learning-based analysis of IVCM images of the corneal SNP inferior whorl distinguished a decreased mean nerve area density in patients with DED and NCP compared with controls and an increased immune cell density in patients with oGVHD- and SS-associated DED. These findings suggest that the inferior whorl could be used as landmark to distinguish between patients with DED and NCP.

Effect of COVID-19 on Injury Incidence and Severity in Professional Female Football Players: A Cohort Prospective Study.

BACKGROUND: Earlier statements suggested a negative impact of coronavirus disease 2019 (COVID-19) infection on sports performance and injury risk. With the COVID-19 pandemic under control and the dominance of a less-severe strain of the virus, there is a need to confirm whether these adverse effects still apply to the current situation. HYPOTHESIS: Infected players would have a higher noncontact muscle injury incidence compared with noninfected counterparts. STUDY DESIGN: Cohort observational study. LEVEL OF EVIDENCE: Level 3. METHODS: Seven teams (n = 147 players) competing in the Spanish professional women's football league (Liga F) were prospectively monitored during the 2021-2022 season. Data from noncontact injuries were recorded and classified following the latest consensus statement from the International Olympic Committee. COVID-19 was certified by the medical staff by regular polymerase chain reaction analysis. RESULTS: Ninety-two players suffered at least 1 noncontact muscle injury during the season. Injury incidence during the season was similar in players with COVID-19 (n = 83) and players without infection (5.1 ± 6.7 versus 4.9 ± 10.0 injuries/1000 h of play, respectively; P = 0.90). Players with COVID-19 were not more likely to suffer noncontact injuries compared with those players without infection (R2 = 0.02; odds ratio [OR] 95% confidence interval [95% CI] = 0.36-1.38; P = 0.31). There was no effect of COVID-19 on the days of absence due to injury (R2 = 0.01; OR 95% CI = 1.00-1.01; P = 0.44) or in the classification of the severity of the injury (P = 0.79). CONCLUSION: COVID-19 has no significant effect on noncontact injury incidence and severity in professional female football players. CLINICAL RELEVANCE: Currently, COVID-19 infection does not alter noncontact muscle injury risk in professional football and requires no further attention in terms of injury management. Usual return-to-play protocols apply to COVID-19 considering the particularities of each player since the severity of infection, period of inactivity, and effects on the player's health and performance.

Single-Domain Antibodies as Antibody-Drug Conjugates: From Promise to Practice-A Systematic Review.

BACKGROUND: Antibody-drug conjugates (ADCs) represent potent cancer therapies that deliver highly toxic drugs to tumor cells precisely, thus allowing for targeted treatment and significantly reducing off-target effects. Despite their effectiveness, ADCs can face limitations due to acquired resistance and potential side effects. OBJECTIVES: This study focuses on advances in various ADC components to improve both the efficacy and safety of these agents, and includes the analysis of several novel ADC formats. This work assesses whether the unique features of VHHs-such as their small size, enhanced tissue penetration, stability, and cost-effectiveness-make them a viable alternative to conventional antibodies for ADCs and reviews their current status in ADC development. METHODS: Following PRISMA guidelines, this study focused on VHHs as components of ADCs, examining advancements and prospects from 1 January 2014 to 30 June 2024. Searches were conducted in PubMed, Cochrane Library, ScienceDirect and LILACS using specific terms related to ADCs and single-domain antibodies. Retrieved articles were rigorously evaluated, excluding duplicates and non-qualifying studies. The selected peer-reviewed articles were analyzed for quality and synthesized to highlight advancements, methods, payloads, and future directions in ADC research. RESULTS: VHHs offer significant advantages for drug conjugation over conventional antibodies due to their smaller size and structure, which enhance tissue penetration and enable access to previously inaccessible epitopes. Their superior stability, solubility, and manufacturability facilitate cost-effective production and expand the range of targetable antigens. Additionally, some VHHs can naturally cross the blood-brain barrier or be easily modified to favor their penetration, making them promising for targeting brain tumors and metastases. Although no VHH-drug conjugates (nADC or nanoADC) are currently in the clinical arena, preclinical studies have explored various conjugation methods and linkers. CONCLUSIONS: While ADCs are transforming cancer treatment, their unique mechanisms and associated toxicities challenge traditional views on bioavailability and vary with different tumor types. Severe toxicities, often linked to compound instability, off-target effects, and nonspecific blood cell interactions, highlight the need for better understanding. Conversely, the rapid distribution, tumor penetration, and clearance of VHHs could be advantageous, potentially reducing toxicity by minimizing prolonged exposure. These attributes make single-domain antibodies strong candidates for the next generation of ADCs, potentially enhancing both efficacy and safety.

Analysis of Sports Supplement Consumption of Elite Referees of the Spanish Professional Fotball League.

BACKGROUND: Sports supplements (SSs) are widely used among team sport athletes; however, evidence supporting the use of SSs among football referees at the elite level is scarce. The aim of the present study was to analyze the consumption of SSs among referees with respect to their level of competition and referee type (main referees (MRs) vs. assistant referees (ARs)). METHODS: A total of 106 football referees participated in this study, with 46.2% from the First Spanish Division and 53.8% from the Second Spanish Division, representing 84.13% of the total number of referees. Each participant completed a validated questionnaire about SS consumption, with the SSs classified according to the Australian Institute of Sport (AIS) ABCD system: Group A has strong evidence for enhancing athlete health and performance, Group B shows potential benefits but needs more evidence, Group C has inconclusive evidence against use, and Group D includes prohibited substances. RESULTS: A total of 84.0% of the MRs and ARs reported the consumption of at least one SS. Differences were found only in the consumption of medical supplements between division (p = 0.016) and type of referee (p = 0.041), though no significant differences were found among the remaining AIS SS categories (p > 0.05). Sport performance (49.6%), Internet (41.0%), and dietitian-nutritionists (31.7%) were the primary reason for SS consumption, purchase location, and source of information, respectively. The most frequently consumed SS were whey protein (45.3%), followed by creatine (33.0%), sport bars and sports drinks (28.3%), and caffeine (19.8%). CONCLUSIONS: MRs and ARs reported a high prevalence of dietary supplement (SS) consumption, with significant differences between division and referee type observed only in medical supplement consumption.

Damage in a large systemic lupus erythematosus cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER) with emphasis on the cardiovascular system: a longitudinal analysis.

OBJECTIVE: To assess organ damage, with emphasis on the cardiovascular system, over the different stages of the disease in a large SLE cohort. METHODS: Multicentre, longitudinal study of a cohort of 4219 patients with SLE enrolled in the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We longitudinally analysed SDI (globally and for each domain) over time only in the 1274 patients whose dates of damage events had been recorded. RESULTS: During the first year after diagnosis of SLE, 20% of the 1274 patients presented with new damage manifestations. At years 2 and 3, new damage was recorded in 11% and 9% of patients. The annual percentage of patients with new damage after year 5 decreased to 5%. In the first year with the disease, most damage was accumulated in the musculoskeletal, neuropsychiatric and renal systems; in later stages, most damage was in the musculoskeletal, ocular and cardiovascular systems. Considering 'cerebrovascular accident' and 'claudication for 6 months' as cardiovascular items, the cardiovascular system was the second most affected system during the early stages of SLE, with 19% of the patients who presented with damage affected at first year after diagnosis. During the late stages, 20-25% of the patients presenting with new damage did so in this modified cardiovascular domain of the SDI. CONCLUSIONS: New damage occurs mainly during the first year following diagnosis of SLE. Cardiovascular damage is relevant in both the early and the late stages of the disease. Strategies to prevent cardiovascular damage should be implemented early after diagnosis of SLE.

Deceleration Capacity During Directional Change as a Time-Efficient (Ecological) Prescreening of Hip Adductor Force Status in Amateur Soccer Players.

ABSTRACT: Miralles-Iborra, A, Del Coso, J, De Los Ríos-Calonge, J, Elvira, JLL, Barbado, D, Urban, T, and Moreno-Pérez, V. Deceleration capacity during directional change as a time-efficient (ecological) prescreening of hip adductor force status in amateur soccer players. J Strength Cond Res XX(X): 000-000, 2024-Reduced isometric adductor muscle strength has been identified as a modifiable risk factor contributing to injury in soccer players. However, the measurement of hip adductor muscle strength is habitually laboratory-based, with isolated hip movements that do not reflect soccer-specific movements that induce groin injury during match play. This study aimed to determine the usefulness of deceleration capacity during a change of direction (COD) as a time-efficient (ecological) prescreening of hip adductor force status in soccer players. Nineteen amateur soccer players completed unilateral isometric hip adductor strength assessments and a 180° COD test. Isometric hip strength assessment included the maximum peak torque (PT) and maximum rate of torque development (RTDmax) relative to players' body mass. Players' deceleration capacity during the COD test was determined for each leg through maximum deceleration normalized to the linear momentum. A linear regression analysis was performed to associate isometric hip strength variables with the deceleration capacity during the COD test at each leg. There was not a statistically significant association between deceleration capacity and hip isometric maximum PT of the dominant and nondominant legs (r ≤ 0.14, p > 0.05). Nevertheless, a moderate association was found between deceleration capacity and RTDmax for both legs (r ≥ 0.58, p < 0.05). The optimal linear regression model suggests that measuring deceleration capacity during a directional change test could explain RTDmax by 33 and 43% for the dominant and nondominant legs, respectively. During a 180° COD test, the deceleration capacity captured through GPS-accelerometer device was limited as a prescreening tool to evaluate hip adductor force status in soccer players.

Amorphous TiO2nano-coating on stainless steel to improve its biological response.

This study delves into the potential of amorphous titanium oxide (aTiO2) nano-coating to enhance various critical aspects of non-Ti-based metallic orthopedic implants. These implants, such as medical-grade stainless steel (SS), are widely used for orthopedic devices that demand high strength and durability. The aTiO2nano-coating, deposited via magnetron sputtering, is a unique attempt to improve the osteogenesis, the inflammatory response, and to reduce bacterial colonization on SS substrates. The study characterized the nanocoated surfaces (SS-a TiO2) in topography, roughness, wettability, and chemical composition. Comparative samples included uncoated SS and sandblasted/acid-etched Ti substrates (Ti). The biological effects were assessed using human mesenchymal stem cells (MSCs) and primary murine macrophages. Bacterial tests were carried out with two aerobic pathogens (S. aureusandS. epidermidis) and an anaerobic bacterial consortium representing an oral dental biofilm. Results from this study provide strong evidence of the positive effects of the aTiO2nano-coating on SS surfaces. The coating enhanced MSC osteoblastic differentiation and exhibited a response similar to that observed on Ti surfaces. Macrophages cultured on aTiO2nano-coating and Ti surfaces showed comparable anti-inflammatory phenotypes. Most significantly, a reduction in bacterial colonization across tested species was observed compared to uncoated SS substrates, further supporting the potential of aTiO2nano-coating in biomedical applications. The findings underscore the potential of magnetron-sputtering deposition of aTiO2nano-coating on non-Ti metallic surfaces such as medical-grade SS as a viable strategy to enhance osteoinductive factors and decrease pathogenic bacterial adhesion. This could significantly improve the performance of metallic-based biomedical devices beyond titanium.

Non-immune hydrops fetalis is associated with bi-allelic pathogenic variants in the MYB Binding Protein 1a (MYBBP1A) gene.

Non-immune hydrops fetalis (NIHF) is a rare entity characterized by excessive accumulation of fluid within the fetal extravascular compartments and body cavities. Here we present two intrauterine fetal demises with NIHF presenting with oligohydramnios, cystic hygroma, pleural effusion, and generalized hydrops with predominance of subcutaneous edema. The fetuses also presented with ascites, severe and precocious IUGR and skeletal anomalies. Whole exome sequencing was applied in order to screen for a possible genetic cause. The results identified biallelic variants in MYBBP1A in both fetuses. A previous report described another case with a similar phenotype having compound heterozygous variants in the same gene. The protein encoded by MYBBP1A is involved in several cellular processes including the synthesis of ribosomal DNA, the response to nucleolar stress, and tumor suppression. Our functional protein analysis through immunohistochemistry indicates that MYBBP1A is a gene expressed during fetal stages. Altogether, we concluded that MYBBP1A is associated with the development of hydrops fetalis. More cases and further studies are necessary to understand the role of this gene and the mechanism associated with NIHF.

Validation of the Spanish Childhood Trauma Questionnaire-Short Form in adolescents with suicide attempts.

Background: Child maltreatment is associated with a higher probability of mental disorders and suicidal behavior in adolescence. Therefore, accurate psychometric instruments are essential to assess this. Objective: To validate the Spanish version of the Childhood Trauma Questionnaire-Short Form (CTQ-SF) in adolescents with suicide attempts. Methods: Multisite cohort study of 208 adolescents with suicide attempts using data from the following scales: Mini International Neuropsychiatric Interview (MINI), Columbia Suicide Severity Rating Scale (C-SSRS), Patient Health Questionnaire (PHQ-9), and CTQ-SF. Statistical analysis: CTQ-SF scores analyzed by descriptive statistics. Internal consistency: McDonald's omega and Cronbach's alpha. Concurrent validity with PHQ-9 and C-SSRS scores: Spearman correlation coefficient. Structural validity: Confirmatory factor analysis. Results: Floor and ceiling effects: Physical abuse and neglect as well as sexual abuse demonstrated high floor effects (50.0, 35.1, and 61.1% of adolescents, respectively). No ceiling effects were found. The CTQ-SF had excellent internal consistency (McDonald's omega = 0.94), as did the majority of its subscales (Cronbach's alpha 0.925-0.831) except for physical neglect (0.624). Its concurrent validity was modest, and the emotional neglect subscale had the lowest Spearman correlation coefficients (0.067-0.244). Confirmatory factor analysis: Compared with alternative factor structures, the original CTQ-SF model (correlated 5-factor) exhibited a better fit [S-B χ 2 = 676.653, p < 0; RMSEA (90% CI = 0.076-0.097) = 0.087; SRMR = 0.078; CFI = 0.980; TLI = 0.978]. Conclusion: The Spanish CTQ-SF is a reliable, valid instrument for assessing traumatic experiences in adolescents at high risk of suicide. It appears appropriate for use in routine clinical practice to monitor maltreatment in this group.

Comparative analysis of eleven SARS-CoV-2 immunoassays and neutralisation data: time to enhance standardisation and correlation of protection.

BACKGROUND: To infer a reliable SARS-CoV-2 antibody protection level from a serological test, an appropriate quantitative threshold and solid equivalence across serological tests are needed. Additionally, tests should show a solid correlation with neutralising assays and with the protection observed in large population cohorts even against emerging variants. OBJECTIVES: We studied convalescent and vaccinated populations using 11 commercial antibody assays. Results were compared to evaluate discrepancies across tests. Neutralisation capacity was measured in a subset of the samples with a lentiviral-based assay. METHODS: Serum from convalescent (n = 121) and vaccinated individuals (n = 471, 260 with Comirnaty, 110 with Spikevax, and 96 with Vaxzevria) was assessed using 11 different assays, including two from Abbott, Euroimmun, Liaison, Roche, and Vircell, and one from Siemens. A spike protein-lentiviral vector with a fluorescent reporter was used for neutralisation assay of serum from convalescent (n = 26) and vaccinated (n = 39) individuals. RESULTS: Positivity ranged between 81.3 and 94.3% after infection and 99.4 and 99.7% after vaccination, depending on the assay. Both cohorts showed a high level of qualitative agreement across tests (Fleiss' kappa = 0.598 and 0.719 for convalescent and vaccinated respectively). Spikevax vaccine recipients showed the highest level of antibodies in all tests. Effectiveness of each test predicting SARS-CoV-2 neutralising capacity depended on assay type and target, with CLIA and anti-S being more effective than ELISA and anti-N assays, respectively. CONCLUSIONS: High-throughput immunoassays are good predictors of neutralising capacity. Updated targets and better standardisation would be required to find an effective correlate of protection, especially to account for antibodies against new variants.

AI-MARRVEL - A Knowledge-Driven AI System for Diagnosing Mendelian Disorders.

BACKGROUND: Diagnosing genetic disorders requires extensive manual curation and interpretation of candidate variants, a labor-intensive task even for trained geneticists. Although artificial intelligence (AI) shows promise in aiding these diagnoses, existing AI tools have only achieved moderate success for primary diagnosis. METHODS: AI-MARRVEL (AIM) uses a random-forest machine-learning classifier trained on over 3.5 million variants from thousands of diagnosed cases. AIM additionally incorporates expert-engineered features into training to recapitulate the intricate decision-making processes in molecular diagnosis. The online version of AIM is available at https://ai.marrvel.org. To evaluate AIM, we benchmarked it with diagnosed patients from three independent cohorts. RESULTS: AIM improved the rate of accurate genetic diagnosis, doubling the number of solved cases as compared with benchmarked methods, across three distinct real-world cohorts. To better identify diagnosable cases from the unsolved pools accumulated over time, we designed a confidence metric on which AIM achieved a precision rate of 98% and identified 57% of diagnosable cases out of a collection of 871 cases. Furthermore, AIM's performance improved after being fine-tuned for targeted settings including recessive disorders and trio analysis. Finally, AIM demonstrated potential for novel disease gene discovery by correctly predicting two newly reported disease genes from the Undiagnosed Diseases Network. CONCLUSIONS: AIM achieved superior accuracy compared with existing methods for genetic diagnosis. We anticipate that this tool may aid in primary diagnosis, reanalysis of unsolved cases, and the discovery of novel disease genes. (Funded by the NIH Common Fund and others.).