Survey based assessment of the quality of reporting guidelines of carotid artery stenosis.

BACKGROUND: No evaluation of the quality of different carotid guidelines using validated scales has been performed to date. The present study aims to analyze three carotid stenosis guidelines, apprizing their quality and reporting using validated tools. METHODS: A survey-based assessment of the quality of the European Society for Vascular Surgery (ESVS) 2023, European Stroke Organisation (ESO) 2021, and the Society for Vascular Surgery (SVS) 2021 carotid stenosis guidelines, was performed by 43 vascular surgeons, cardiologists, neurologist or interventional radiologists using two validated appraisal tools for quality and reporting guidelines, the AGREE II instrument and the RIGHT statement. RESULTS: Using the AGREE II tool, the ESVS, SVS, and ESO guidelines had overall quality scores of 87.3%, 79.4%, and 82.9%, respectively (p=0.001) The ESVS and ESO had better scores in the scope and purpose domain, and the SVS in the clarity of presentation domain. In the RIGHT statement, the ESVS, SVS, and ESO guidelines had overall quality scores of 84.0.7%, 74.3%, and 79.0%, respectively (p=0.001). All three guidelines stood out for their methodology for search of evidence and formulating evidence-based recommendations. On the contrary, were negatively evaluated mostly in the cost and resource implications in formulating the recommendations. CONCLUSION: The 2023 ESVS carotid stenosis guideline was the best evaluated among the three guidelines, with scores over 5% higher than the other two guidelines. Efforts should be made by guideline writing committees to take the AGREE II and RIGHT statements into account in the development of future guidelines to produce high-quality recommendations.

Lack of variations in the salamander chytrid fungus, Batrachochytrium salamandrivorans, at its alleged origin: Updating its Japanese distribution with new evidence.

The chytrid fungus Batrachochytrium salamandrivorans [Bsal] is causing declines in the amphibian populations. After a decade of mapping the pathogen in Europe, where it is causing dramatic outbreaks, and North America, where its arrival would affect to the salamander's biodiversity hotspot, little is known about its current status in Asia, from presumably is native. Japan has several species considered as potential carriers, but no regulation is implemented against Bsal spreading. Previous Bsal known presence detected various cases on the Okinawa Island, southwestern Japan. Previous studies on its sister species, B. dendrobatidis presented a high genomic variation in this area and particularly on Cynops ensicauda. Here, we have done the largest monitoring to date in Japan on the Cynops genus, focusing on Okinawa Island and updating its distribution and providing more information to unravel the still unknown origin of Bsal. Interestingly, we have provided revealing facts about different detectability depending on the used molecular techniques and changes in its Japanese distribution. All in all, the Bsal presence in Japan, together with its low variability in the sequenced amplicons, and the lack of apparent mortalities, may indicate that this part of Asia has a high diversity of chytrids.

Validity of Mobility-Based Exposure Assessment of Air Pollution: A Comparative Analysis with Home-Based Exposure Assessment.

Air pollution exposure is typically assessed at the front door where people live in large-scale epidemiological studies, overlooking individuals' daily mobility out-of-home. However, there is limited evidence that incorporating mobility data into personal air pollution assessment improves exposure assessment compared to home-based assessments. This study aimed to compare the agreement between mobility-based and home-based assessments with personal exposure measurements. We measured repeatedly particulate matter (PM2.5) and black carbon (BC) using a sample of 41 older adults in the Netherlands. In total, 104 valid 24 h average personal measurements were collected. Home-based exposures were estimated by combining participants' home locations and temporal-adjusted air pollution maps. Mobility-based estimates of air pollution were computed based on smartphone-based tracking data, temporal-adjusted air pollution maps, indoor-outdoor penetration, and travel mode adjustment. Intraclass correlation coefficients (ICC) revealed that mobility-based estimates significantly improved agreement with personal measurements compared to home-based assessments. For PM2.5, agreement increased by 64% (ICC: 0.39-0.64), and for BC, it increased by 21% (ICC: 0.43-0.52). Our findings suggest that adjusting for indoor-outdoor pollutant ratios in mobility-based assessments can provide more valid estimates of air pollution than the commonly used home-based assessments, with no added value observed from travel mode adjustments.

A randomized controlled trial of the effectiveness of a one-to-one peer support intervention on resilience, social support, and salivary cortisol in recently diagnosed women with breast cancer.

PURPOSE: Peer support has been suggested as a way to help women diagnosed with breast cancer to better cope with their situation, but studies on its effectiveness have conflicting results. This randomized controlled trial aimed to study the effectiveness of a one-to-one peer support intervention on psychological resilience, social support, and salivary cortisol among breast cancer patients. METHODS: The sample consisted of 121 newly diagnosed women at Onkologikoa Hospital. Patients who were prescribed chemotherapy were randomly assigned to Intervention Group 1 (IG1) or Control Group 1 (CG1). Similarly, those prescribed adjuvant radiotherapy were assigned to IG2 or CG2. Women in IG1 received 8 biweekly social support sessions from volunteer survivors who had successfully overcome breast cancer, while IG2 received 6 biweekly sessions. CG1 and CG2 only received standard care. Resilience, social support, and salivary cortisol were assessed at baseline (T1) and at the end of the intervention (T2). RESULTS: We found a non-significant, yet a small to moderate size increase in resilience from T1 to T2 in IG1 (p = 0.246; dDc = 0.47). Upon regression analysis, we observed that this increase was determined by changes in cortisol (ß = -0.658, p = 00.010), affective support (ß = -0.997, p = 00.014), and emotional support (ß = 0.935, p = 00.008). We also found a significant decrease in resilience levels in CG2 from T1 to T2 (p = 0.003; dDc = 0.88). CONCLUSION: The present study suggests that peer support can exert a protective psychological influence on women diagnosed with breast cancer, and further indicates an exciting avenue for future intervention development in the breast cancer care continuum. TRIAL REGISTRATION: ClinicalTrials.gov NCT05077371.

Proteome allocation is linked to transcriptional regulation through a modularized transcriptome.

It has proved challenging to quantitatively relate the proteome to the transcriptome on a per-gene basis. Recent advances in data analytics have enabled a biologically meaningful modularization of the bacterial transcriptome. We thus investigate whether matched datasets of transcriptomes and proteomes from bacteria under diverse conditions can be modularized in the same way to reveal novel relationships between their compositions. We find that; (1) the modules of the proteome and the transcriptome are comprised of a similar list of gene products, (2) the modules in the proteome often represent combinations of modules from the transcriptome, (3) known transcriptional and post-translational regulation is reflected in differences between two sets of modules, allowing for knowledge-mapping when interpreting module functions, and (4) through statistical modeling, absolute proteome allocation can be inferred from the transcriptome alone. Quantitative and knowledge-based relationships can thus be found at the genome-scale between the proteome and transcriptome in bacteria.

Spino-pelvic parameters and back pain in patients without coronal deformity or history of spinal surgery: A cross-sectional analysis.

BACKGROUND: During the last two decades, there has been a growing interest in spinal sagittal alignment. Most published studies have focused on the role of spinopelvic parameters in patients with adult spinal deformity or in those with previous spinal fusion. OBJECTIVE: The aim of this study was to explore possible association between disability related to back pain and spinopelvic parameters in the absence of coronal deformity or previous spinal surgery. METHODS: In the setting of a larger study involving patients with low back pain (LBP), those without previous surgery or spinal deformity in the coronal plane were selected. A total of 52 patients (mean age 59 years, range 21-86, 23 men and 29 women) were found. The visual analogic scale (VAS) and Oswestry Disability Index questionnaire (ODI) were recorded. Surgimap software was used to measure the sagittal vertical axis (SVA), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), and lumbar lordosis (LL). Statistical analysis was performed with SPSS Statistics software. Pearson or Spearman correlation were the test of choice depending on the specific variables. RESULTS: A statistically significant association was found between SVA and ODI (r 0.59, p< 0.03). Increased pelvic tilt was also associated with more severe disability related to back pain (r 0.48, p< 0.03). PI-LL mismatch showed moderate association with disability and severity of back pain, although this association did not reach statistical significance (r 0.52, p< 0.08). CONCLUSION: Our findings suggest that sagittal misalignment may be related with more severe disability and back pain in patients with minor or null deformity in the coronal plane.

Behavioral impairments are linked to neuroinflammation in mice with Cerebral Cavernous Malformation disease.

Background: Cerebral Cavernous Malformations (CCMs) are neurovascular abnormalities in the central nervous system (CNS) caused by loss of function mutations in KRIT1 (CCM1), CCM2, or PDCD10 (CCM3) genes. One of the most common symptoms in CCM patients is associated with motor disability, weakness, seizures, stress, and anxiety, and the extent of the symptom or symptoms may be due to the location of the lesion within the CNS or whether multiple lesions are present. Previous studies have primarily focused on understanding the pathology of CCM using animal models. However, more research has yet to explore the potential impact of CCM lesions on behavioral deficits in animal models, including effects on short-term and long-term memory, motor coordination, and function. Methods: We used the accelerating RotaRod test to assess motor and coordination deficits. We also used the open field test to assess locomotor activity and pathology-related behavior and Pavlovian fear conditioning to assess short-and long-term memory deficits. Our behavioral studies were complemented by proteomics, histology, immunofluorescence, and imaging techniques. We found that neuroinflammation is crucial in behavioral deficits in male and female mice with neurovascular CCM lesions (Slco1c1-iCreERT2; Pdcd10 fl/fl ; Pdcd10 BECKO ). Results: Functional behavior tests in male and female Pdcd10 BECKO mice revealed that CCM lesions cause sudden motor coordination deficits associated with the manifestation of profound neuroinflammatory lesions. Our findings indicate that maturation of CCM lesions in Pdcd10 BECKO mice also experienced a significant change in short- and long-term memory compared to their littermate controls, Pdcd10 fl/fl mice. Proteomic experiments reveal that as CCM lesions mature, there is an increase in pathways associated with inflammation, coagulation, and angiogenesis, and a decrease in pathways associated with learning and plasticity. Therefore, our study shows that Pdcd10 BECKO mice display a wide range of behavioral deficits due to significant lesion formation in their central nervous system and that signaling pathways associated with neuroinflammation and learning impact behavioral outcomes. Conclusions: Our study found that CCM animal models exhibited behavioral impairments such as decreased motor coordination and amnesia. These impairments were associated with the maturation of CCM lesions that displayed a neuroinflammatory pattern.

A small-molecule microtubule-stabilizing agent safely reduces Aß plaque and tau pathology in transgenic mouse models of Alzheimer's disease.

INTRODUCTION: Intraneuronal inclusions composed of tau protein are found in Alzheimer's disease (AD) and other tauopathies. Tau normally binds microtubules (MTs), and its disengagement from MTs and misfolding in AD is thought to result in MT abnormalities. We previously identified triazolopyrimidine-containing MT-stabilizing compounds that provided benefit in AD mouse models and herein describe the characterization and efficacy testing of an optimized candidate, CNDR-51997. METHODS: CNDR-51997 underwent pharmacokinetic, pharmacodynamic, safety pharmacology, and mouse tolerability testing. In addition, the compound was examined for efficacy in 5XFAD amyloid beta (Aß) plaque mice and PS19 tauopathy mice. RESULTS: CNDR-51997 significantly reduced Aß plaques in 5XFAD mice and tau pathology in PS19 mice, with the latter also showing attenuated axonal dystrophy and gliosis. CNDR-51997 was well tolerated at doses that exceeded efficacy doses, with a good safety pharmacology profile. DISCUSSION: CNDR-51997 may be a candidate for advancement as a potential therapeutic agent for AD and/or other tauopathies. Highlights There is evidence of microtubule alterations (MT) in Alzheimer's disease (AD) brain and in mouse models of AD pathology. Intermittent dosing with an optimized, brain-penetrant MT-stabilizing small-molecule, CNDR-51997, reduced both Aß plaque and tau inclusion pathology in established mouse models of AD. CNDR-51997 attenuated axonal dystrophy and gliosis in a tauopathy mouse model, with a strong trend toward reduced hippocampal neuron loss. CNDR-51997 is well tolerated in mice at doses that are meaningfully greater than required for efficacy in AD mouse models, and the compound has a good safety pharmacology profile.

Choline supplementation in early life improves and low levels of choline can impair outcomes in a mouse model of Alzheimer's disease.

Maternal choline supplementation (MCS) improves cognition in Alzheimer's disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.

A retrospective study of deep learning generalization across two centers and multiple models of X-ray devices using COVID-19 chest-X rays.

Generalization of deep learning (DL) algorithms is critical for the secure implementation of computer-aided diagnosis systems in clinical practice. However, broad generalization remains to be a challenge in machine learning. This research aims to identify and study potential factors that can affect the internal validation and generalization of DL networks, namely the institution where the images come from, the image processing applied by the X-ray device, and the type of response function of the X-ray device. For these purposes, a pre-trained convolutional neural network (CNN) (VGG16) was trained three times for classifying COVID-19 and control chest radiographs with the same hyperparameters, but using different combinations of data acquired in two institutions by three different X-ray device manufacturers. Regarding internal validation, the addition of images from an external institution to the training set did not modify the algorithm's internal performance, however, the inclusion of images acquired by a device from a different manufacturer decreased the performance up to 8% (p < 0.05). In contrast, generalization across institutions and X-ray devices with the same type of response function was achieved. Nonetheless, generalization was not observed across devices with different types of response function. This factor was the key impediment to achieving broad generalization in our research, followed by the device's image-processing and the inter-institutional differences, which both reduced generalization performance to 18.9% (p < 0.05), and 9.8% (p < 0.05), respectively. Finally, clustering analysis with features extracted by the CNN was performed, revealing a substantial dependence of feature values extracted by the pre-trained CNN on the X-ray device which acquired the images.

COVID-19 vaccine hesitancy prevalence in Mexico: A systematic review and metanalysis.

Background: Vaccine hesitancy (VH) is a recognized threat to public health that undermines efforts to mitigate disease burden. This study aims to gather available evidence regarding COVID-19 VH in Mexico, estimate the prevalence of VH, and its determinants to inform policymaking in this country. Methods: Following PRISMA guidelines, a systematic review of the MEDLINE literature, articles that estimated the prevalence of COVID-19 VH in Mexico were included in the analysis to obtain a pooled estimate. We used a binomial-normal model for meta-analysis of proportions (i.e., generalized linear mixed model) to perform the metanalysis. We then performed a narrative review of COVID-19 VH in Mexican subpopulations. Results: Seven studies met inclusion criteria. We estimated a pooled prevalence of COVID-19 VH of 16 % (95 % CI: 11-23 %) in Mexico. We found an association between VH and demographic characteristics, intrinsic vaccine factors, and beliefs. Subgroup analyses from specific studies suggested that patients with clinical conditions such as breast cancer or rheumatologic diseases had a higher prevalence of VH. Conclusions: VH is a highly complex and dynamic phenomenon in Mexico. Characterizing and understanding COVID-19 vaccine hesitancy in the Mexican population helps target future policy interventions to mitigate the spread and impact of infectious diseases. The implications of VH differ among groups that may be at higher risk of severe disease, underscoring the importance of prompt research among these groups as well as targeted interventions to address VH.

Ambient Environment and the Epidemiology of Preterm Birth.

Preterm birth (PTB) is associated with substantial mortality and morbidity. We describe environmental factors that may influence PTB risks. We focus on exposures associated with an individual's ambient environment, such as air pollutants, water contaminants, extreme heat, and proximities to point sources (oil/gas development or waste sites) and greenspace. These exposures may further vary by other PTB risk factors such as social constructs and stress. Future examinations of risks associated with ambient environment exposures would benefit from consideration toward multiple exposures - the exposome - and factors that modify risk including variations associated with the structural genome, epigenome, social stressors, and diet.

Proteome profiling identifies a link between the mitochondrial pathways and host-microbial sensor ELMO1 following Salmonella infection.

The host EnguLfment and cell MOtility protein 1 (ELMO1) is a cytosolic microbial sensor that facilitates bacterial sensing, internalization, clearance, and inflammatory responses. We have shown previously that ELMO1 binds bacterial effector proteins, including pathogenic effectors from Salmonella and controls host innate immune signaling. To understand the ELMO1-regulated host pathways, we have performed liquid chromatography Multinotch MS3-Tandem Mass Tag (TMT) multiplexed proteomics to determine the global quantification of proteins regulated by ELMO1 in macrophages during Salmonella infection. Comparative proteome analysis of control and ELMO1-depleted murine J774 macrophages after Salmonella infection quantified more than 7000 proteins with a notable enrichment in mitochondrial-related proteins. Gene ontology enrichment analysis revealed 19 upregulated and 11 downregulated proteins exclusive to ELMO1-depleted cells during infection, belonging to mitochondrial functions, metabolism, vesicle transport, and the immune system. By assessing the cellular energetics via Seahorse analysis, we found that Salmonella infection alters mitochondrial metabolism, shifting it from oxidative phosphorylation to glycolysis. Importantly, these metabolic changes are significantly influenced by the depletion of ELMO1. Furthermore, ELMO1 depletion resulted in a decreased ATP rate index following Salmonella infection, indicating its importance in counteracting the effects of Salmonella on immunometabolism. Among the proteins involved in mitochondrial pathways, mitochondrial fission protein DRP1 was significantly upregulated in ELMO1-depleted cells and in ELMO1-KO mice intestine following Salmonella infection. Pharmacological Inhibition of DRP1 revealed the link of the ELMO1-DRP1 pathway in regulating the pro-inflammatory cytokine TNF-α following infection. The role of ELMO1 has been further characterized by a proteome profile of ELMO1-depleted macrophage infected with SifA mutant and showed the involvement of ELMO1-SifA on mitochondrial function, metabolism and host immune/defense responses. Collectively, these findings unveil a novel role for ELMO1 in modulating mitochondrial functions, potentially pivotal in modulating inflammatory responses. Significance Statement: Host microbial sensing is critical in infection and inflammation. Among these sensors, ELMO1 has emerged as a key regulator, finely tuning innate immune signaling and discriminating between pathogenic and non-pathogenic bacteria through interactions with microbial effectors like SifA of Salmonella . In this study, we employed Multinotch MS3-Tandem Mass Tag (TMT) multiplexed proteomics to determine the proteome alterations mediated by ELMO1 in macrophages following WT and SifA mutant Salmonella infection. Our findings highlight a substantial enrichment of host proteins associated with metabolic pathways and mitochondrial functions. Notably, we validated the mitochondrial fission protein DRP1 that is upregulated in ELMO1-depleted macrophages and in ELMO1 knockout mice intestine after infection. Furthermore, we demonstrated that Salmonella -induced changes in cellular energetics are influenced by the presence of ELMO1. This work shed light on a possible novel link between mitochondrial dynamics and microbial sensing in modulating immune responses.

Understanding Anxiety in Cervical Dystonia: An Imaging Study.

BACKGROUND: Anxiety may precede motor symptoms in cervical dystonia (CD) and is associated with an earlier onset of dystonia. Our understanding of anxiety in CD is inadequate. OBJECTIVE: To investigate brain networks associated with anxiety in CD. METHODS: Twenty-six subjects with idiopathic CD underwent MRI Brain without contrast. Correlational tractography was derived using Diffusion MRI connectometry. Quantitative Anisotropy (QA) was used in deterministic diffusion fiber tracking. Correlational tractography was then used to correlate QA with State-Trait Anxiety Inventory (STAI) state (STAI-S) and trait (STAI-T) subscales. RESULTS: Connectometry analysis showed direct correlation between state anxiety and QA in tracts from amygdala to thalamus/ pulvinar bilaterally, and trait anxiety and QA in tracts from amygdala to motor cortex, sensorimotor cortex and parietal association area bilaterally (FDR ≤0.05). CONCLUSION: Our efforts to map anxiety to brain networks in CD highlight the role of the amygdala in the pathophysiology of anxiety in CD.

A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is encoded by a major autoimmunity gene and is a known inhibitor of T cell receptor (TCR) signaling and drug target for cancer immunotherapy. However, little is known about PTPN22 posttranslational regulation. Here, we characterize a phosphorylation site at Ser325 situated C terminal to the catalytic domain of PTPN22 and its roles in altering protein function. In human T cells, Ser325 is phosphorylated by glycogen synthase kinase-3 (GSK3) following TCR stimulation, which promotes its TCR-inhibitory activity. Signaling through the major TCR-dependent pathway under PTPN22 control was enhanced by CRISPR/Cas9-mediated suppression of Ser325 phosphorylation and inhibited by mimicking it via glutamic acid substitution. Global phospho-mass spectrometry showed Ser325 phosphorylation state alters downstream transcriptional activity through enrichment of Swi3p, Rsc8p, and Moira domain binding proteins, and next-generation sequencing revealed it differentially regulates the expression of chemokines and T cell activation pathways. Moreover, in vitro kinetic data suggest the modulation of activity depends on a cellular context. Finally, we begin to address the structural and mechanistic basis for the influence of Ser325 phosphorylation on the protein's properties by deuterium exchange mass spectrometry and NMR spectroscopy. In conclusion, this study explores the function of a novel phosphorylation site of PTPN22 that is involved in complex regulation of TCR signaling and provides details that might inform the future development of allosteric modulators of PTPN22.

Do we all do the same things? Applicability of daily activities at the intersection of demographics.

OBJECTIVE: To evaluate the extent to which demographic factors-and their intersections-influence the applicability of items assessing activities of daily living (ADLs) in a sample of older adults. METHOD: Participants' (n = 44,713) Functional Activities Questionnaire (FAQ) scores from a multicenter database were evaluated to see how participant and collateral demographics, contextual, and clinical characteristics impacted ADL nonapplicability (NA). Collateral, contextual, and clinical characteristics were matched in those with and without NA. The effect of participant demographics and their interactions on NA responses were modeled with logistic regression. RESULTS: At least one FAQ item (most commonly bill payment, taxes, playing games, and meal preparation) was rated as NA in up to one third of participants across ethnoracial groups. Dementia staging had the largest impact on NA, followed by participant demographics. In a matched sample, logistic models revealed that participant demographics, in particular sex, best predicted NA. However, meaningful interactions with ethnoracial group were noted for bill payment, taxes, meal preparation, and game engagement, suggesting that demographic intersections (e.g., younger vs. older Latinxs) meaningfully predict whether a given ADL was applicable to an individual participant. CONCLUSIONS: Neuropsychology is predicated on accurate assessments of both cognition and daily functioning and, in an increasingly diverse aging population, there should be careful consideration of demographic factors, their interactions, and historical contexts that drive day-to-day demands. This study establishes limitations of existing measures and paths forward for creating fair measures of functioning in older adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predicting Injuries in Elite Female Football Players With Global-Positioning-System and Multiomics Data.

PURPOSE: Injury prevention is a crucial aspect of sports, particularly in high-performance settings such as elite female football. This study aimed to develop an injury prediction model that incorporates clinical, Global-Positioning-System (GPS), and multiomics (genomics and metabolomics) data to better understand the factors associated with injury in elite female football players. METHODS: We designed a prospective cohort study over 2 seasons (2019-20 and 2021-22) of noncontact injuries in 24 elite female players in the Spanish Premiership competition. We used GPS data to determine external workload, genomic data to capture genetic susceptibility, and metabolomic data to measure internal workload. RESULTS: Forty noncontact injuries were recorded, the most frequent of which were muscle (63%) and ligament (20%) injuries. The baseline risk model included fat mass and the random effect of the player. Six genetic polymorphisms located at the DCN, ADAMTS5, ESRRB, VEGFA, and MMP1 genes were associated with injuries after adjusting for player load (P < .05). The genetic score created with these 6 variants determined groups of players with different profile risks (P = 3.1 × 10-4). Three metabolites (alanine, serotonin, and 5-hydroxy-tryptophan) correlated with injuries. The model comprising baseline variables, genetic score, and player load showed the best prediction capacity (C-index: .74). CONCLUSIONS: Our model could allow efficient, personalized interventions based on an athlete's vulnerability. However, we emphasize the necessity for further research in female athletes with an emphasis on validation studies involving other teams and individuals. By expanding the scope of our research and incorporating diverse populations, we can bolster the generalizability and robustness of our proposed model.