Retention time and organic loading rate as anaerobic co-digestion key-factors for better digestate valorization practices: C and N dynamics in soils.

The growing use of anaerobic co-digestion (AcoD) in processing organic waste has led to a significant digestate production. To effectively recycle digestate back into soils, it is crucial to understand how operational variables in the AcoD process influence the conversion of organic matter (OM). To address this, a combination of biochemical fractionation and various soil incubation tests were employed to assess the stability of OM in digestates generated from anaerobic continuous reactors fed with a food waste-hay mixture and operating at different hydraulic retention times (HRT) and organic loading rates (OLR). This study revealed that digester performance and operating parameters impacted carbon dynamics in soils. A decrease in the carbon mineralization in soils when increasing the HRT was reported (48 ± 4 % for 70 days compared to 59 ± 1 % for 42 days). Specific HRT and OLR values were found to be linked to carbon accessibility and complexity, confirming that longer HRT lead to higher OM removal and increased complexity in soluble OM, despite minor discrepancies in relative carbon distribution. Furthermore, comparable rates of nitrogen mineralization in soils were observed for all digestates, consistent with the accessibility of nitrogen from the particulate OM. Nevertheless, AcoD converted substrates with the potential to immobilize nitrogen in soils into fast-acting fertilizers. In summary, this study underscores the importance of controlling the AcoD performances to evaluate the suitability of digestates for sustainable agricultural practices.

Intercavity polariton slows down dynamics in strongly coupled cavities.

Band engineering stands as an efficient route to induce strongly correlated quantum many-body phenomena. Besides inspiring analogies among diverse physical fields, tuning on demand the group velocity is highly attractive in photonics because it allows unconventional flows of light. Λ-schemes offer a route to control the propagation of light in a lattice-free configurations, enabling exotic phases such as slow-light and allowing for highly optical non-linear systems. Here, we realize room-temperature intercavity Frenkel polaritons excited across two strongly coupled cavities. We demonstrate the formation of a tuneable heavy-polariton, akin to slow light, appearing in the absence of a periodic in-plane potential. Our photonic architecture based on a simple three-level scheme enables the unique spatial segregation of photons and excitons in different cavities and maintains a balanced degree of mixing between them. This unveils a dynamical competition between many-body scattering processes and the underlying polariton nature which leads to an increased fluorescence lifetime. The intercavity polariton features are further revealed under appropriate resonant pumping, where we observe suppression of the polariton fluorescence intensity.

Photocatalytic Activity of Ag Nanoparticles Deposited on Thermoexfoliated g-C3N4.

The limited access to fresh water and the increased presence of emergent pollutants (EPs) in wastewater has increased the interest in developing strategies for wastewater remediation, including photocatalysis. Graphitic carbon nitride (g-C3N4) is a 2D non-metal material with outstanding properties, such as a 2.7 eV bandgap and physicochemical stability, making it a promising photocatalyst. This work reports the process of obtaining high-surface-area (SA) g-C3N4 using the thermal-exfoliation process and the posterior effect of Ag-nanoparticle loading over the exfoliated g-C3N4 surface. The photocatalytic activity of samples was evaluated through methylene blue (MB) degradation under visible-light radiation and correlated to its physical properties obtained by XRD, TEM, BET, and UV-Vis analyses. Moreover, 74% MB degradation was achieved by exfoliated g-C3N4 compared to its bulk counterpart (55%) in 180 min. Moreover, better photocatalytic performances (94% MB remotion) were registered at low Ag loading, with 5 wt.% as the optimal value. Such an improvement is attributed to the synergetic effect produced by a higher SA and the role of Ag nanoparticles in preventing charge-recombination processes. Based on the results, this work provides a simple and efficient methodology to obtain Ag/g-C3N4 photocatalysts with enhanced photocatalytic performance that is adequate for water remediation under sunlight conditions.

A Novel Tendon Injury Model, Induced by Collagenase Administration Combined with a Thermo-Responsive Hydrogel in Rats, Reproduces the Pathogenesis of Human Degenerative Tendinopathy.

Patellar tendinopathy is a common clinical problem, but its underlying pathophysiology remains poorly understood, primarily due to the absence of a representative experimental model. The most widely used method to generate such a model is collagenase injection, although this method possesses limitations. We developed an optimized rat model of patellar tendinopathy via the ultrasound-guided injection of collagenase mixed with a thermo-responsive Pluronic hydrogel into the patellar tendon of sixty male Wistar rats. All analyses were carried out at 3, 7, 14, 30, and 60 days post-injury. We confirmed that our rat model reproduced the pathophysiology observed in human patients through analyses of ultrasonography, histology, immunofluorescence, and biomechanical parameters. Tendons that were injured by the injection of the collagenase-Pluronic mixture exhibited a significant increase in the cross-sectional area (p < 0.01), a high degree of tissue disorganization and hypercellularity, significantly strong neovascularization (p < 0.01), important changes in the levels of types I and III collagen expression, and the organization and presence of intra-tendinous calcifications. Decreases in the maximum rupture force and stiffness were also observed. These results demonstrate that our model replicates the key features observed in human patellar tendinopathy. Collagenase is evenly distributed, as the Pluronic hydrogel prevents its leakage and thus, damage to surrounding tissues. Therefore, this model is valuable for testing new treatments for patellar tendinopathy.

High Levels of Vitamin A in Plant-Based Diets for Gilthead Seabream (Sparus aurata) Juveniles, Effects on Growth, Skeletal Anomalies, Bone Molecular Markers, and Histological Morphology.

Substitution of fish-based ingredients may alter the nutritional profile of the feeds, including the vitamin contents, ultimately leading to unbalanced vitamin supply. Vitamin A plays an essential role in epithelium preservation, cell differentiation, reproduction, and vision. It also intervenes in skeletogenesis through chondrocytes development. Therefore, low levels of vitamin A may cause poor growth and abnormal bone development among other symptoms. Besides, in gilthead seabream excess vitamin A altered bone structure and homeostasis, indicating that an upper level for vitamin A in feeds for this species must be defined. For this purpose, a practical plant-based diet (FM 10% and FO 6%) containing five increasing levels of vitamin A (24,000, 26,000, 27,000, 31,000, and 37,000 IU/kg) supplemented as retinyl acetate was formulated to identify the effects of high levels of vitamin A for gilthead seabream juveniles. The trial was conducted with 450 total fish distributed into 15 tanks, where each diet was tested in triplicates for 70 days. At the end of the trial, samples were taken for analyses of vitamin A-relevant markers. At the end of the trial the high levels of vitamin A supplementation did not cause a reduction in growth, whereas no significant effect was observed for the feed efficiency, specific growth rate, and feed convertion ratio. Although not significant, retinol content in liver showed a tendency to increase with the elevation of dietary vitamin A levels. Although minor, the highest level of vitamin A dietary content (37,000 IU/kg) caused a significant increase in caudal vertebrae partial fusion as well as caudal vertebrae malformations. Increasing dietary vitamin A was related to a reduction in the occurrence of microhemorrhages in the liver and a reduction in the presence of eosinophils associated to the pancreas. Overall, the results of the present study suggested that gilthead seabream juveniles fed a plant-based diet are able to tolerate very high levels of vitamin A supplementation when supplemented as retinyl acetate. Nevertheless, further supplementation should be avoided in order to reduce the prevalence of anomalies affecting the caudal vertebrae.

Interaction between Dietary Vitamin D3 and Vitamin K3 in Gilthead Seabream Larvae (Sparus aurata) in Relation to Growth and Expression of Bone Development-Related Genes.

Vitamins D and K are essential fat-soluble nutrients that intervene in bone development processes among other biological functions. The present study is aimed at investigating the potential combined effect of dietary supplementation with vitamin D3 (cholecalciferol) and vitamin K3 (menadione) in gilthead seabream (Sparus aurata) larvae. For that purpose, seabream diets were supplemented with different combinations of vitamin D3/vitamin K3 (mg/kg diet) as follows: 0.00/0, 0.06/70, 0.06/170, 0.13/70, 0.13/170, 0.40/70, and 0.40/170. Feeding gilthead seabream larvae (22 days post hatch) for 21 days with the diets supplemented with 0.06-0.13 mg/kg vitamin D3 and 70 mg/kg vitamin K3 (diets 0.06/70 and 0.13/70) led to the highest larval growth and survival and the highest expression of important biomarkers of both bone development and health, such as bmp2, osx, and mgp, and calcium homeostasis, such as pthrp and casr. However, the increased supplementation with both vitamins at 0.40 mg/kg vitamin D3 and 170 mg/kg vitamin K3 (diet 0.40/170) reduced larval growth and survival, downregulated bmp2 and pthrp expressions, and upregulated osx and mgp, causing an unbalance in the relative expression of these genes. The results of the present study have shown the interaction between vitamin D3 supplementation and vitamin K3 supplementation in larval performance and gene expression related to bone development and calcium homeostasis, denoting the significance of a correct balance between both vitamins in larval diets.

Deciphering the contribution of microbial biomass to the properties of dissolved and particulate organic matter in anaerobic digestates.

The recalcitrant structures either from substrate or microbial biomass contained in digestates after anaerobic digestion (AD) highly influence digestate valorization. To properly assess the microbial biomass contribution to the digested organic matter (OM), a combination of characterization methods and the use of various substrate types in anaerobic continuous reactors was required. The use of totally biodegradable substrates allowed detecting soluble microbial products via fluorescence spectroscopy at emission wavelengths of 420 and 460 nm while the protein-like signature was enhanced by the whey protein. During reactors' operation, a transfer of complex compounds to the dissolved OM from the particulate OM was observed through fluorescence applied on biochemical fractionation. Consequently, the fluorescence complexity index of the dissolved OM increased from 0.59-0.60 to 1.06-1.07, whereas it decreased inversely for the extractable soluble from the particulate OM from 1.16-1.19 to 0.42-0.54. Accordingly, fluorescence regional integration showed differences among reactors based on visual inspection and orthogonal partial latent structures (OPLS) analysis. Similarly, the impact of the substrate type and operation time on the particulate OM was revealed by 13C nuclear magnetic resonance using OPLS, providing a good model (R2X = 0.93 and Q2 = 0.8) with a clear time-trend. A high signal resonated at ∼30 ppm attributed to CH2-groups in the aliphatic chain of lipid-like structure besides carbohydrates intensities at 60-110 ppm distinguished the reactor fed with whey protein from the other, which was mostly biomass related. Indeed, this latter displayed a higher presence of peptidoglycan (δH/C: 1.6-2.0/20-25 ppm) derived from microbial biomass by 1H-13C heteronuclear single-quantum coherence (HSQC) nuclear magnetic resonance. Interestingly, the sample distribution obtained by non-metric multidimensional scaling of bacterial communities resembled the attained using 13C NMR properties, opening new research perspectives. Overall, this study discloses the microbial biomass contribution to digestates composition to improve the OM transformation mechanism knowledge.

Personalized diagnostic approach and indirect quantification of extravasation in human anaphylaxis.

BACKGROUND: Anaphylaxis is the most acute and life-threatening manifestation of allergic disorders. Currently, there is a need to improve its medical management and increase the understanding of its molecular mechanisms. This study aimed to quantify the extravasation underlying human anaphylactic reactions and propose new theragnostic approaches. METHODS: Molecular determinations were performed in paired serum samples obtained during the acute phase and at baseline from patients presenting with hypersensitivity reactions. These were classified according to their severity as Grades 1, 2 and 3, the two latter being considered anaphylaxis. Tryptase levels were measured by ImmunoCAP, and serum protein concentration was quantified by Bradford assay. Human serum albumin (HSA) and haemoglobin beta subunit (HBB) levels were determined by Western blot and polyacrylamide gel electrophoresis, respectively. RESULTS: A total of 150 patients were included in the study. Of them, 112 had experienced anaphylaxis (83 and 29 with Grade 2 and 3 reactions, respectively). Tryptase diagnostic efficiency substantially improved when considering patients' baseline values (33%-54%) instead of the acute value threshold (21%). Serum protein concentration and HSA significantly decreased in anaphylaxis (p < .0001). HSA levels dropped with the severity of the reaction (6% and 15% for Grade 2 and 3 reactions, respectively). Furthermore, HBB levels increased during the acute phase of all hypersensitivity reactions (p < .0001). CONCLUSIONS: For the first time, the extravasation underlying human anaphylaxis has been evaluated based on the severity of the reaction using HSA and protein concentration measurements. Additionally, our findings propose new diagnostic and potential therapeutic approaches for this pathological event.

Exploring Omega-3's Impact on the Expression of Bone-Related Genes in Meagre (Argyrosomus regius).

Dietary supplementation with Omega-3 fatty acids seems to promote skeletal health. Therefore, their consumption at imbalanced or excessive levels has offered less beneficial or even prejudicial effects. Fish produced in aquaculture regimes are prone to develop abnormal skeletons. Although larval cultures are usually fed with diets supplemented with Omega-3 Long Chain Polyunsaturated fatty acids (LC-PUFAs), the lack of knowledge about the optimal requirements for fatty acids or about their impact on mechanisms that regulate skeletal development has impeded the design of diets that could improve bone formation during larval stages when the majority of skeletal anomalies appear. In this study, Argyrosomus regius larvae were fed different levels of Omega-3s (2.6% and 3.6% DW on diet) compared to a commercial diet. At 28 days after hatching (DAH), their transcriptomes were analyzed to study the modulation exerted in gene expression dynamics during larval development and identify impacted genes that can contribute to skeletal formation. Mainly, both levels of supplementation modulated bone-cell proliferation, the synthesis of bone components such as the extracellular matrix, and molecules involved in the interaction and signaling between bone components or in important cellular processes. The 2.6% level impacted several genes related to cartilage development, denoting a special impact on endochondral ossification, delaying this process. However, the 3.6% level seemed to accelerate this process by enhancing skeletal development. These results offered important insights into the impact of dietary Omega-3 LC-PUFAs on genes involved in the main molecular mechanism and cellular processes involved in skeletal development.

A genome-wide association study of survival in patients with sepsis.

BACKGROUND: Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction and has a high mortality rate in adult intensive care units. Most genetic studies have identified gene variants associated with development and outcomes of sepsis focusing on biological candidates. We conducted the first genome-wide association study (GWAS) of 28-day survival in adult patients with sepsis. METHODS: This study was conducted in two stages. The first stage was performed on 687 European sepsis patients from the GEN-SEP network and 7.5 million imputed variants. Association testing was conducted with Cox regression models, adjusting by sex, age, and the main principal components of genetic variation. A second stage focusing on the prioritized genetic variants was performed on 2,063 ICU sepsis patients (1362 European Americans and 701 African-Americans) from the MESSI study. A meta-analysis of results from the two stages was conducted and significance was established at p < 5.0 × 10-8. Whole-blood transcriptomic, functional annotations, and sensitivity analyses were evaluated on the identified genes and variants. FINDINGS: We identified three independent low-frequency variants associated with reduced 28-day sepsis survival, including a missense variant in SAMD9 (hazard ratio [95% confidence interval] = 1.64 [1.37-6.78], p = 4.92 × 10-8). SAMD9 encodes a possible mediator of the inflammatory response to tissue injury. INTERPRETATION: We performed the first GWAS of 28-day sepsis survival and identified novel variants associated with reduced survival. Larger sample size studies are needed to better assess the genetic effects in sepsis survival and to validate the findings.

A Mixed-Reality Tele-Operation Method for High-Level Control of a Legged-Manipulator Robot.

In recent years, legged (quadruped) robots have been subject of technological study and continuous development. These robots have a leading role in applications that require high mobility skills in complex terrain, as is the case of Search and Rescue (SAR). These robots stand out for their ability to adapt to different terrains, overcome obstacles and move within unstructured environments. Most of the implementations recently developed are focused on data collecting with sensors, such as lidar or cameras. This work seeks to integrate a 6DoF arm manipulator to the quadruped robot ARTU-R (A1 Rescue Tasks UPM Robot) by Unitree to perform manipulation tasks in SAR environments. The main contribution of this work is focused on the High-level control of the robotic set (Legged + Manipulator) using Mixed-Reality (MR). An optimization phase of the robotic set workspace has been previously developed in Matlab for the implementation, as well as a simulation phase in Gazebo to verify the dynamic functionality of the set in reconstructed environments. The first and second generation of Hololens glasses have been used and contrasted with a conventional interface to develop the MR control part of the proposed method. Manipulations of first aid equipment have been carried out to evaluate the proposed method. The main results show that the proposed method allows better control of the robotic set than conventional interfaces, improving the operator efficiency in performing robotic handling tasks and increasing confidence in decision-making. On the other hand, Hololens 2 showed a better user experience concerning graphics and latency time.

Injury epidemiology in the men’s and women’s Spanish rollerhockey league: a descriptive study / Epidemiología lesional en la liga española de hockey patines masculina yfemenina: un estudio descriptivo

The purpose of the present study is to describe the injury patterns among male and female athletes of the Spanish Rink hockey league. A cross-sectional study was performed, concerning the time-loss injuries (the athlete is prevented to participate in a training session / game because of the injury registered by the medical staff of every team. 137 athletes were included (98 male, age 26.7 ± 5.9 years; 39 female, age 23.3 ± 4.6 years). Ninety-four time-loss injuries were recorded, being the most frequent the muscle injury (38 episodes, 40.4%), especially the ones affecting the adductor longus muscle (23 episodes, 60,5% of the muscle injuries). The majority of the registered injuries were classified as mild (1-7 days of time-loss) but the and the median return-to-play was 19.4 ± 29.6 days. Eight episodes of reinjury were described (8.5% of total injuries) and 2 injuries required surgical treatment (2.1% of total injuries). Concerning female athletes, we can highlight a increased number of ligament injuries in the lower limbs compared with male athletes and the absence of tendinopathies causing time-loss. The knee injuries were the injuries with a higher return-to-play in goalkeepers. The present study is the first to describe the injury patterns among rink hockey elite athletes and must set a starting point to study and prevent injuries in this sport.(AU)

El propósito del presente estudio es describir los patrones lesionales durante una temporada de los deportistas de la máxima competición masculina y femenina de Hockey Patines en España. Se realizó un estudio descriptivo de las lesiones con baja deportiva (el/la deportista no puede participar como mínimo en un entrenamiento o partido debido a la lesión) recogidas por los equipos biomédicos de cada equipo. Se estudiaron 137 deportistas (98 hombres, con una media de edad de 26,7 ± 5,9 años y 39 mujeres con una media de edad de 23,3 ± 4,6 años) Se recogieron un total de 94 lesiones con baja deportiva, siendo las más frecuentes las lesiones musculares (38 episodios, 40,4% de las lesiones totales), en especial del músculo aductor largo (23 episodios, 60,5% de las lesiones musculares). La mayoría de lesiones registradas fueron leves (1-7 días de baja deportiva) aunque el tiempo medio de baja fue de 19,4 ± 29,6 días. Se recogieron 8 episodios de relesión (8,5% de las lesiones totales) y 2 lesiones que precisaron tratamiento quirúrgico (2,1% de las lesiones totales). Al estudiar a las deportistas femeninas destaca que presentaron un mayor número de lesiones ligamentosas de extremidades inferiores en comparaciones con los varones y no se describió ningún episodio de tendinopatía.Al estudiar las lesiones específicas de los porteros/as se evidenció que las lesiones que causaban más baja deportiva eran las lesiones de rodilla. El presente estudio es el primero en describir las lesiones en jugadores/as de primer nivel de hockey patines y debe marcar un punto de partida para el estudio y prevención de las lesiones en este deporte.(AU)

Pericarditis efusivo-constrictiva recidivante tras COVID-19 / Recurrent Pericarditis After Covid-19

Paciente con artritis reumatoide que tiene COVID-19 con debut de pericaditis recidivante, diagnóstico diferencial.(AU)

Patient with rheumatoid arthritis who has Covid-19 with recurrent pericaditis debut, differential diagnosis.(AU)

Specificity and Breadth of the Neutralizing Antibody Response to a Live-Attenuated Tetravalent Dengue Vaccine.

BACKGROUND: An effective dengue vaccine should ideally induce broadly neutralizing antibody (nAb) responses against all 4 dengue virus (DENV) serotypes. METHODS: We characterized the specificity and breadth of the nAb response to TAK-003, a live-attenuated tetravalent dengue vaccine, in serum samples from phase 2 and 3 clinical trials. RESULTS: Microneutralization tests using postvaccination serum showed comparable neutralization against diverse DENV-1-4 genotypes. Reporter virus particle neutralization assays after depletion of anti-DENV-2 nAbs demonstrated that the nAb response to DENV-1, -3, and -4 comprises both type-specific (TS) and cross-reactive (CR) nAbs. CONCLUSIONS: Therefore, TAK-003 induces broad tetravalent TS and CR nAb responses.

Medical Theatre as an Innovative Pedagogical Strategy in Medical Simulation.

Medical education has overshadowed the importance for interpersonal abilities in modern medicine practice. In this work, we report an innovative strategy to teach, practice, and evaluate communication and empathy abilities, based on medical theater. This approach was based on interdisciplinary effort between Medicine, Performing Arts, and Bioethics Faculty. Development and first pilot experience results are here reported. A multidisciplinary team was established with the objective to structure the methodology where simulated clinical consultations were performed: two interviews took place, each with one medical student as physician and one performing arts student as simulated patient. Thirty students and 7 Faculty members participated as spectators. Students received immediate feedback and they qualitatively evaluated the global experience. We conclude that medical theater methodology is a developmental strategy that could promote integral acquisition of communication competences. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01551-8.

Somatic Hypermutation and Framework Mutations of Variable Region Contribute to Anti-Zika Virus-Specific Monoclonal Antibody Binding and Function.

Zika virus (ZIKV) is a global public health concern due to its ability to cause congenital Zika syndrome and lack of approved vaccine, therapeutic, or other control measures. We discovered eight novel rabbit monoclonal antibodies (MAbs) that bind to distinct ZIKV envelope protein epitopes. The majority of the MAbs were ZIKV specific and targeted the lateral ridge of the envelope (E) protein domain III, while the MAb with the highest neutralizing activity recognized a putative quaternary epitope spanning E protein domains I and III. One of the non-neutralizing MAbs specifically recognized ZIKV precursor membrane protein (prM). Somatic hypermutation of immunoglobulin variable regions increases antibody affinity maturation and triggers antibody class switching. Negative correlations were observed between the somatic hypermutation rate of the immunoglobulin heavy-chain variable region and antibody binding parameters such as equilibrium dissociation constant, dissociation constant, and half-maximal effective concentration value of MAb binding to ZIKV virus-like particles. Complementarity-determining regions recognize the antigen epitopes and are scaffolded by canonical framework regions. Reversion of framework region amino acids to the rabbit germ line sequence decreased anti-ZIKV MAb binding activity of some MAbs. Thus, antibody affinity maturation, including somatic hypermutation and framework region mutations, contributed to the binding and function of these anti-ZIKV MAbs. IMPORTANCE ZIKV is a global health concern against which no vaccine or therapeutics are available. We characterized eight novel rabbit monoclonal antibodies recognizing ZIKV envelope and prM proteins and studied the relationship between somatic hypermutation of complementarity-determining regions, framework regions, mutations, antibody specificity, binding, and neutralizing activity. The results contribute to understanding structural features and somatic mutation pathways by which potent Zika virus-neutralizing antibodies can evolve, including the role of antibody framework regions.

Admixture Mapping of Sepsis in European Individuals With African Ancestries.

Sepsis is a severe systemic inflammatory response to infections that is accompanied by organ dysfunction. Although the ancestral genetic background is a relevant factor for sepsis susceptibility, there is a lack of studies using the genetic singularities of a recently admixed population to identify loci involved in sepsis susceptibility. Here we aimed to discover new sepsis loci by completing the first admixture mapping study of sepsis in Canary Islanders, leveraging their distinctive genetic makeup as a mixture of Europeans and African ancestries. We used a case-control approach and inferred local ancestry blocks from genome-wide data from 113,414 polymorphisms genotyped in 343 patients with sepsis and 410 unrelated controls, all ascertained for grandparental origin in the Canary Islands (Spain). Deviations in local ancestries between cases and controls were tested using logistic regressions, followed by fine-mapping analyses based on imputed genotypes, in silico functional assessments, and gene expression analysis centered on the region of interest. The admixture mapping analysis detected that local European ancestry in a locus spanning 1.2 megabases of chromosome 8p23.1 was associated with sepsis (lowest p = 1.37 × 10-4; Odds Ratio [OR] = 0.51; 95%CI = 0.40-0.66). Fine-mapping studies prioritized the variant rs13249564 within intron 1 of MFHAS1 gene associated with sepsis (p = 9.94 × 10-4; OR = 0.65; 95%CI = 0.50-0.84). Functional and gene expression analyses focused on 8p23.1 allowed us to identify alternative genes with possible biological plausibility such as defensins, which are well-known effector molecules of innate immunity. By completing the first admixture mapping study of sepsis, our results revealed a new genetic locus (8p23.1) harboring a number of genes with plausible implications in sepsis susceptibility.

Machine learning-optimized Combinatorial MRI scale (COMRISv2) correlates highly with cognitive and physical disability scales in Multiple Sclerosis patients.

Composite MRI scales of central nervous system tissue destruction correlate stronger with clinical outcomes than their individual components in multiple sclerosis (MS) patients. Using machine learning (ML), we previously developed Combinatorial MRI scale (COMRISv1) solely from semi-quantitative (semi-qMRI) biomarkers. Here, we asked how much better COMRISv2 might become with the inclusion of quantitative (qMRI) volumetric features and employment of more powerful ML algorithm. The prospectively acquired MS patients, divided into training (n = 172) and validation (n = 83) cohorts underwent brain MRI imaging and clinical evaluation. Neurological examination was transcribed to NeurEx™ App that automatically computes disability scales. qMRI features were computed by lesion-TOADS algorithm. Modified random forest pipeline selected biomarkers for optimal model(s) in the training cohort. COMRISv2 models validated moderate correlation with cognitive disability [Spearman Rho = 0.674; Lin's concordance coefficient (CCC) = 0.458; p < 0.001] and strong correlations with physical disability (Spearman Rho = 0.830-0.852; CCC = 0.789-0.823; p < 0.001). The NeurEx led to the strongest COMRISv2 model. Addition of qMRI features enhanced performance only of cognitive disability model, likely because semi-qMRI biomarkers measure infratentorial injury with greater accuracy. COMRISv2 models predict most granular clinical scales in MS with remarkable criterion validity, expanding scientific utilization of cohorts with missing clinical data.