Multi-omics study reveals different pathogenesis of the generation of skin lesions in SLE and IDLE patients.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies.

Seven-chain adaptive immune receptor repertoire analysis in rheumatoid arthritis reveals novel features associated with disease and clinically relevant phenotypes.

BACKGROUND: In rheumatoid arthritis (RA), the activation of T and B cell clones specific for self-antigens leads to the chronic inflammation of the synovium. Here, we perform an in-depth quantitative analysis of the seven chains that comprise the adaptive immune receptor repertoire (AIRR) in RA. RESULTS: In comparison to controls, we show that RA patients have multiple and strong differences in the B cell receptor repertoire including reduced diversity as well as altered isotype, chain, and segment frequencies. We demonstrate that therapeutic tumor necrosis factor inhibition partially restores this alteration but find a profound difference in the underlying biochemical reactivities between responders and non-responders. Combining the AIRR with HLA typing, we identify the specific T cell receptor repertoire associated with disease risk variants. Integrating these features, we further develop a molecular classifier that shows the utility of the AIRR as a diagnostic tool. CONCLUSIONS: Simultaneous sequencing of the seven chains of the human AIRR reveals novel features associated with the disease and clinically relevant phenotypes, including response to therapy. These findings show the unique potential of AIRR to address precision medicine in immune-related diseases.

Harnessing the Synergy of Fe and Co with Carbon Nanofibers for Enhanced CO2 Hydrogenation Performance.

Amid growing concerns about climate change and energy sustainability, the need to create potent catalysts for the sequestration and conversion of CO2 to value-added chemicals is more critical than ever. This work describes the successful synthesis and profound potential of high-performance nanofiber catalysts, integrating earth-abundant iron (Fe) and cobalt (Co) as well as their alloy counterpart, FeCo, achieved through electrospinning and judicious thermal treatments. Systematic characterization using an array of advanced techniques, including SEM, TGA-DSC, ICP-MS, XRF, EDS, FTIR-ATR, XRD, and Raman spectroscopy, confirmed the integration and homogeneous distribution of Fe/Co elements in nanofibers and provided insights into their catalytic nuance. Impressively, the bimetallic FeCo nanofiber catalyst, thermally treated at 1050 °C, set a benchmark with an unparalleled CO2 conversion rate of 46.47% at atmospheric pressure and a consistent performance over a 55 h testing period at 500 °C. Additionally, this catalyst exhibited prowess in producing high-value hydrocarbons, comprising 8.01% of total products and a significant 31.37% of C2+ species. Our work offers a comprehensive and layered understanding of nanofiber catalysts, delving into their transformations, compositions, and structures under different calcination temperatures. The central themes of metal-carbon interactions, the potential advantages of bimetallic synergies, and the importance of structural defects all converge to define the catalytic performance of these nanofibers. These revelations not only deepen our understanding but also set the stage for future endeavors in designing advanced nanofiber catalysts with bespoke properties tailored for specific applications.

Ionically annealed zwitterionic microgels for bioprinting of cartilaginous constructs.

Foreign body response (FBR) is a pervasive problem for biomaterials used in tissue engineering. Zwitterionic hydrogels have emerged as an effective solution to this problem, due to their ultra-low fouling properties, which enable them to effectively inhibit FBRin vivo. However, no versatile zwitterionic bioink that allows for high resolution extrusion bioprinting of tissue implants has thus far been reported. In this work, we introduce a simple, novel method for producing zwitterionic microgel bioink, using alginate methacrylate (AlgMA) as crosslinker and mechanical fragmentation as a microgel fabrication method. Photocrosslinked hydrogels made of zwitterionic carboxybetaine acrylamide (CBAA) and sulfobetaine methacrylate (SBMA) are mechanically fragmented through meshes with aperture diameters of 50 and 90µm to produce microgel bioink. The bioinks made with both microgel sizes showed excellent rheological properties and were used for high-resolution printing of objects with overhanging features without requiring a support structure or support bath. The AlgMA crosslinker has a dual role, allowing for both primary photocrosslinking of the bulk hydrogel as well as secondary ionic crosslinking of produced microgels, to quickly stabilize the printed construct in a calcium bath and to produce a microporous scaffold. Scaffolds showed ∼20% porosity, and they supported viability and chondrogenesis of encapsulated human primary chondrocytes. Finally, a meniscus model was bioprinted, to demonstrate the bioink's versatility at printing large, cell-laden constructs which are stable for furtherin vitroculture to promote cartilaginous tissue production. This easy and scalable strategy of producing zwitterionic microgel bioink for high resolution extrusion bioprinting allows for direct cell encapsulation in a microporous scaffold and has potential forin vivobiocompatibility due to the zwitterionic nature of the bioink.

Tasks and Experiences of the Prospective, Longitudinal, Multicenter MoMar (Molecular Markers) Study for the Early Detection of Mesothelioma in Individuals Formerly Exposed to Asbestos Using Liquid Biopsies.

Mesothelioma is an aggressive cancer, strongly associated with prior exposure to asbestos. Commonly, tumors are detected at late stages of the disease. Detection at early stages might be meaningful, because therapies might be more effective when the tumor burden is relatively low and the tumor has not spread to distant sites. Circulating biomarkers in blood might be a promising tool to improve the early detection of mesothelioma, but for screening in asymptomatic subjects, candidate biomarkers need to be validated in appropriate studies. This study was conducted to assess the performance of biomarkers in liquid biopsies to detect mesothelioma at early stages. Over a period of 10 years, 2769 volunteers formerly exposed to asbestos were annually examined and liquid biopsies were collected. A follow-up was completed 17 months after the last blood collection. The article provides a detailed overview of our lessons learned and experiences of conducting a prospective, longitudinal, multicenter study. The existing cohort of individuals at risk is highly suitable for the validation of blood-based biomarkers for the early detection of mesothelioma as well as lung cancer.

Assessment of MYC and TERT copy number variations in lung cancer using digital PCR.

OBJECTIVE: Lung cancer is the second most frequent cancer type and the most common cause of cancer-related deaths worldwide. Alteration of gene copy numbers are associated with lung cancer and the determination of copy number variations (CNV) is appropriate for the discrimination between tumor and non-tumor tissue in lung cancer. As telomerase reverse transcriptase (TERT) and v-myc avian myelocytomatosis viral oncogene homolog (MYC) play a role in lung cancer the aims of this study were the verification of our recent results analyzing MYC CNV in tumor and non-tumor tissue of lung cancer patients using an independent study group and the assessment of TERT CNV as an additional marker. RESULTS: TERT and MYC status was analyzed using digital PCR (dPCR) in tumor and adjacent non-tumor tissue samples of 114 lung cancer patients. The difference between tumor and non-tumor samples were statistically significant (p < 0.0001) for TERT and MYC. Using a predefined specificity of 99% a sensitivity of 41% and 51% was observed for TERT and MYC, respectively. For the combination of TERT and MYC the overall sensitivity increased to 60% at 99% specificity. We demonstrated that a combination of markers increases the performance in comparison to individual markers. Additionally, the determination of CNV using dPCR might be an appropriate tool in precision medicine.

FLight Biofabrication Supports Maturation of Articular Cartilage with Anisotropic Properties.

Tissue engineering approaches that recapitulate cartilage biomechanical properties are emerging as promising methods to restore the function of injured or degenerated tissue. However, despite significant progress in this research area, the generation of engineered cartilage constructs akin to native counterparts still represents an unmet challenge. In particular, the inability to accurately reproduce cartilage zonal architecture with different collagen fibril orientations is a significant limitation. The arrangement of the extracellular matrix (ECM) plays a fundamental role in determining the mechanical and biological functions of the tissue. In this study, it is shown that a novel light-based approach, Filamented Light (FLight) biofabrication, can be used to generate highly porous, 3D cell-instructive anisotropic constructs that lead to directional collagen deposition. Using a photoclick-based photoresin optimized for cartilage tissue engineering, a significantly improved maturation of the cartilaginous tissues with zonal architecture and remarkable native-like mechanical properties is demonstrated.

The role of the serotonergic system in atropine's anti-myopic effects.

The muscarinic cholinergic antagonist atropine is the most widely used pharmacological treatment for the visual disorder myopia (short-sightedness), the leading cause of low-vision worldwide. This study sought to better define the mechanism by which atropine inhibits myopic growth. Although classified as a muscarinic-cholinergic antagonist, atropine has been found to bind and modulate the activity of several non-cholinergic systems (e.g., serotonin). Thus, this study investigated whether the serotonergic system could underly atropine's anti-myopic effects. Using a chick model of myopia, we report that atropine's growth-inhibitory effects can be attenuated by pharmacological stimulation of the serotonin system. This may suggest that atropine can slow the development of myopia through inhibiting serotonergic receptor activity. We also observed that pharmacological antagonism of serotonergic receptors inhibits the development of experimental myopia in a dose-dependent manner, further demonstrating that modulation of serotonergic receptor activity can alter ocular growth rates. Finally, we found that neither experimental myopia, nor atropine treatment, induced a significant change in retinal serotonergic output (i.e., synthesis, transport, release and catabolism). This may suggest that, although myopic growth can be inhibited through modulation of serotonergic receptor activity (by atropine or serotonergic antagonists), this does not require a change in serotonin levels. These findings regarding a serotonergic mechanism for atropine may have significant ramifications for the treatment of human myopia. This includes assessing the use of atropine in patients who are also undergoing treatment to upregulate serotonergic signaling (e.g., serotonergic anti-depressants).

Medication Adherence in Patients with Hematologic Malignancies Who Are Hematopoietic Stem Cell Transplantation Survivors: A Qualitative Study.

Medication adherence is critical for optimal health outcomes in patients with hematologic malignancies who have undergone allogeneic hematopoietic stem cell transplants (HSCT). However, this population struggles with medication nonadherence. Research that comprehensively describes the complex patient- and medication-related factors which impact medication adherence in this population is lacking. Hence, we used semistructured qualitative interviews to explore the diverse and complex factors contributing to medication adherence in HSCT recipients. We conducted 30 in-depth interviews with patients who were more than 180 days post-allogeneic HSCT at the Dana-Farber Cancer Institute. The interviews explored the physical, social, psychological, and sociodemographic factors that facilitate or discourage adherence to the post-transplantation medication regimen. Interviews were audio-recorded, transcribed, and coded using NVivo software. Two themes emerged that characterized the barriers patients face with their medication regimen. Patients reported factors outside of their control, such as managing multiple pharmacies, health insurance difficulties, and dosage timing, as significant barriers to medication adherence. Patients also reported barriers within their control, such as familial responsibilities. Important facilitators for medication adherence included caregiver and clinician support, previous experience managing a medication regimen, and tools that aid pill organization and timing. Furthermore, patients reported that although medication side effects and quantity of pills did not directly impact medication adherence, it increased their psychological distress. Facilitators and barriers to medication adherence can be physical, psychological, organizational, and social. There are many aspects of medication regimens that significantly increase patient distress. Hence, supportive interventions to improve medication adherence in patients undergoing HSCT may need to incorporate strategies to manage medication side effects and skills to improve psychological well-being and social support.

Zwitterionic Granular Hydrogel for Cartilage Tissue Engineering.

Zwitterionic hydrogels have high potential for cartilage tissue engineering due to their ultra-hydrophilicity, nonimmunogenicity, and superior antifouling properties. However, their application in this field has been limited so far, due to the lack of injectable zwitterionic hydrogels that allow for encapsulation of cells in a biocompatible manner. Herein, a novel strategy is developed to engineer cartilage employing zwitterionic granular hydrogels that are injectable, self-healing, in situ crosslinkable and allow for direct encapsulation of cells with biocompatibility. The granular hydrogel is produced by mechanical fragmentation of bulk photocrosslinked hydrogels made of zwitterionic carboxybetaine acrylamide (CBAA), or a mixture of CBAA and zwitterionic sulfobetaine methacrylate (SBMA). The produced microgels are enzymatically crosslinkable using horseradish peroxidase, to quickly stabilize the construct, resulting in a microporous hydrogel. Encapsulated human primary chondrocytes are highly viable and able to proliferate, migrate, and produce cartilaginous extracellular matrix (ECM) in the zwitterionic granular hydrogel. It is also shown that by increasing hydrogel porosity and incorporation of SBMA, cell proliferation and ECM secretion are further improved. This strategy is a simple and scalable method, which has high potential for expanding the versatility and application of zwitterionic hydrogels for diverse tissue engineering applications.

The influence of political ideology on clinical trial knowledge, invitation, and participation among adults in the United States.

BACKGROUND: Clinical trials remain a critical component of medical innovation. Evidence suggests that individuals' political ideologies may impact their health behaviors. However, there is a paucity of literature examining the relationship between political ideologies and clinical trial knowledge and participation. METHODS: Study data were derived from Health Information National Trends Survey 5 Cycle 4 (n = 3300), which was conducted from February to June 2020. We used participants' characteristics to estimate the prevalence of clinical trial knowledge and participation. We used multivariable logistic regressions to investigate whether political ideology had a significant impact on clinical trial knowledge and participation. Jack-knife replicate weights were applied for population-level estimates. RESULTS: Most participants were White (64.2%), earned above US$50,000 (62.4%), and lived in urban areas (88.0%). About 59.2% reported having some knowledge of clinical trials, and only 8.9% had ever been invited to participate in clinical trials. A total of 37.0%, 29.5%, and 33.5% of the population endorsed moderate, liberal, and conservative political viewpoints respectively. In the adjusted logistic regression analysis, compared to conservatives, liberals (adjusted odds ratio, 1.92; 95% confidence interval, 1.31-2.80) and moderates (adjusted odds ratio, 1.43; 95% confidence interval, 1.09-1.88) had significantly greater odds of having knowledge of clinical trials. Also, liberals had higher odds of receiving invitations to participate in clinical trials (odds ratio, 1.76; 95% confidence interval, 1.08-2.85; p = 0.023) and greater odds of trial participation (odds ratio, 3.90; 95% confidence interval, 1.47-10.33; p = 0.007) compared to moderates. CONCLUSIONS: The mechanism underlying the higher rates of clinical trial invitations to liberals is unclear and requires further comprehensive investigation. Similarly, further qualitative studies are needed to understand the attributes that promote knowledge and increased likelihood of clinical trial participation among liberals. This will provide crucial insight to help design interventions that further involve conservatives and moderates in clinical trials and scientific enterprise.

Paediatric fractures of carpal bones other than the scaphoid.

OBJECTIVES: Fractures of carpal bones other than the scaphoid are rare in children. The aim of this study was to analyze results and identify risk factors for an unfavorable outcome. MATERIAL AND METHODS: Children and adolescents up to the age of 16 years who sustained a carpal fracture other than in the scaphoid between 2004 and 2021 were reviewed in this single-center retrospective study. RESULTS: In a series of 209 children and adolescents with carpal fractures, 22 had fractures other than the scaphoid. Mean age was 13 years (range 8-16) years, with a total of 41 fractures, with highest incidences for the capitate (10), trapezium (6), triquetrum (4) and pisiform (4). Twenty-nine of these 41 fractures were missed on initial X-ray. Non-displaced fractures were treated with a short arm spica cast including the thumb. Four patients were operated on for displacement fracture or carpometacarpal subluxation. All fractures united, and patients returned to full activities. At the final consultation at a median 14 months (range 6-89) post-injury, all patients with non-displaced fractures were free of symptoms, with excellent Mayo Wrist Scores (MWS). However, three patients with operated trapezium fractures developed early radiological signs of osteoarthritis, two of them with residual pain and MWS rated only good. CONCLUSION: Non-displaced pediatric carpal fractures treated by forearm cast have excellent prognosis. Fractures of the trapezium with displacement or first carpometacarpal subluxation incur a risk of osteoarthritis despite anatomical reduction and internal fixation.

Endoscopic third ventriculostomy with choroid plexus cauterization: predictors of long-term success and comparison with shunt placement for primary treatment of infant hydrocephalus.

OBJECTIVE: Endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) can avoid ventriculoperitoneal shunt (VPS) dependence in very young hydrocephalic children, although long-term success as a primary treatment in North America has not been previously reported. Moreover, optimal age at surgery, impact of preoperative ventriculomegaly, and relationship to prior cerebrospinal fluid (CSF) diversion remain poorly defined. The authors compared ETV/CPC and VPS placement for averting reoperation, and they evaluated preoperative predictors for reoperation and shunt placement after ETV/CPC. METHODS: All patients under 12 months of age who underwent initial hydrocephalus treatment via ETV/CPC or VPS placement at Boston Children's Hospital between December 2008 and August 2021 were reviewed. Analyses included Cox regression for independent outcome predictors, and both Kaplan-Meier and log-rank rank tests for time-to-event outcomes. Cutoff values for age and preoperative frontal and occipital horn ratio (FOHR) were determined with receiver operating characteristic curve analysis and Youden's J index. RESULTS: In total, 348 children (150 females) were included with principal etiologies of posthemorrhagic hydrocephalus (26.7%), myelomeningocele (20.1%), and aqueduct stenosis (17.0%). Of these, 266 (76.4%) underwent ETV/CPC and 82 (23.6%) underwent VPS placement. Treatment choice largely reflected surgeon preferences before practice shifted toward endoscopy, with endoscopy not considered for > 70% of initial VPS cases. ETV/CPC patients trended toward fewer reoperations, and Kaplan-Meier analysis estimated that 59% of patients would achieve long-term shunt freedom through 11 years (median 42 months of actual follow-up). Among all patients, corrected age < 2.5 months (p < 0.001), prior temporizing CSF diversion (p = 0.003), and excess intraoperative bleeding (p < 0.001) independently predicted reoperation. Among ETV/CPC patients, corrected age < 2.5 months (p = 0.031), prior CSF diversion (p = 0.001), preoperative FOHR > 0.613 (p = 0.011), and excessive intraoperative bleeding (p = 0.001) independently predicted ultimate conversion to VPS. The actual VPS insertion rates remained low in patients who were ≥ 2.5 months old at ETV/CPC either with prior CSF diversion (2/10 [20.0%]) or without prior CSF diversion (24/123 [19.5%]); however, the actual VPS insertion rates increased in patients who were < 2.5 months old at ETV/CPC with prior CSF diversion (19/26 [73.1%]) or without prior CSF diversion (44/107 [41.1%]). CONCLUSIONS: ETV/CPC successfully treated hydrocephalus in most patients younger than 1 year irrespective of etiology, averting observed shunt dependence in 80% of patients ≥ 2.5 months of age regardless of prior CSF diversion and in 59% of those < 2.5 months of age without prior CSF diversion. For infants aged < 2.5 months with prior CSF diversion, particularly those with severe ventriculomegaly, ETV/CPC was unlikely to succeed unless safely delayed.

Nutritional, textural and sensory properties of lasagna dough containing air yam, a non-conventional edible plant.

The incorporation of non-conventional edible plants into gluten-free food products shows potential and the ability to increase nutritional properties. Therefore, the aim of this study was to develop a gluten-free air yam-based lasagna dough and to evaluate the nutritional, textural, and sensory properties. First, the air yam flour was obtained by drying the tubers at 55 °C for 16 h and then, mixed with the water and egg powder, it constituted the lasagna dough. The nutritional composition and bioaccessible mineral content of air yam flour and lasagna dough were evaluated, as well as the texture, microbiological and sensory properties of the lasagna dough. The results indicated that air yam flour and the lasagna dough had high dietary fiber contents, 17.1% and 9.4%, respectively. Additionally, the low-fat content found means that the lasagna dough can be considered both gluten-free and fat-free. The most bioaccessible mineral present was K in both air yam flour and lasagna dough. In sensory analysis, the lasagna dough containing air yam showed an intermediate acceptability in relation to two already commercialized lasagna doughs. This study shows an application to this group of plants that are still little explored, allowing the development to consumers and industries.

Climate change alters slug abundance but not herbivory in a temperate grassland.

Climate change will significantly impact the world's ecosystems, in part by altering species interactions and ecological processes, such as herbivory and plant community dynamics, which may impact forage quality and ecosystem production. Yet relatively few field experimental manipulations assessing all of these parameters have been performed to date. To help fill this knowledge gap, we evaluated the effects of increased temperature (+3°C day and night, year-round) and precipitation (+30% of mean annual rainfall) on slug herbivory and abundance and plant community dynamics biweekly in a pasture located in central Kentucky, U.S.A. Warming increased slug abundance once during the winter, likely due to improving conditions for foraging, whereas warming reduced slug abundance at times in late spring, mid-summer, and early fall (from 62-95% reduction depending on month). We found that warming and increased precipitation did not significantly modify slug herbivory at our site, despite altering slug abundance and affecting plant community composition and forage quality. Climate change will alter seasonal patterns of slug abundance through both direct effects on slug biology and indirect effects mediated by changes in the plant community, suggesting that pasture management practices may have to adapt.

Non-destructive classification of unlabeled cells: Combining an automated benchtop magnetic resonance scanner and artificial intelligence.

In order to treat degenerative diseases, the importance of advanced therapy medicinal products has increased in recent years. The newly developed treatment strategies require a rethinking of the appropriate analytical methods. Current standards are missing the complete and sterile analysis of the product of interest to make the drug manufacturing effort worthwhile. They only consider partial areas of the sample or product while also irreversibly damaging the investigated specimen. Two-dimensional T1 / T2 MR relaxometry meets these requirements and is therefore a promising in-process control during the manufacturing and classification process of cell-based treatments. In this study a tabletop MR scanner was used to perform two-dimensional MR relaxometry. Throughput was increased by developing an automation platform based on a low-cost robotic arm, resulting in the acquisition of a large dataset of cell-based measurements. Two-dimensional inverse Laplace transformation was used for post-processing, followed by data classification performed with support vector machines (SVM) as well as optimized artificial neural networks (ANN). The trained networks were able to distinguish non-differentiated from differentiated MSCs with a prediction accuracy of 85%. To increase versatility, an ANN was trained on 354 independent, biological replicates distributed across ten different cell lines, resulting in a prediction accuracy of up to 98% depending on data composition. The present study provides a proof of principle for the application of T1 / T2 relaxometry as a non-destructive cell classification method. It does not require labeling of cells and can perform whole mount analysis of each sample. Since all measurements can be performed under sterile conditions, it can be used as an in-process control for cellular differentiation. This distinguishes it from other characterization techniques, as most are destructive or require some type of cell labeling. These advantages highlight the technique's potential for preclinical screening of patient-specific cell-based transplants and drugs.

External validation of the R2eD AVM scoring system to assess rupture risk in pediatric AVM patients.

OBJECTIVE: The assessment of hemorrhagic risk is of central importance in the management of pediatric brain arteriovenous malformations (AVMs). A recently published scoring system, the R2eD AVM (race, exclusive deep location or not, AVM size < 3 or ≥ 3, venous drainage exclusively deep or not, and monoarterial feeding or >1 arterial feeders) considers patient race and AVM location, size, venous drainage, and arterial supply and was successfully externally validated for use in adults to predict the risk of AVM hemorrhagic presentation. In this study the authors sought to externally validate the R2eD AVM score for prediction of hemorrhagic risk in the pediatric AVM population. METHODS: A pediatric database at Boston Children's Hospital was retrospectively reviewed for all patients with a diagnosis of intracranial AVM. Exclusion criteria included age > 21 years, multiple AVMs, and incomplete clinical/radiographic data. Demographic data and R2eD AVM score calculations were collected for all patients. Univariate binary logistic regression and multivariate stepwise backward elimination models were used to determine factors associated with hemorrhagic presentation. RESULTS: A total of 212 AVMs were identified in 212 patients with vascular anomalies from 1995 to 2021, and 144 patients met the inclusion criteria (74 [51.4%] male, 111 [77.1%] White), of whom 87 (60.4%) patients presented with rupture and 122 (84.7%) underwent resection. The mean age at surgery was 12 years (range 3 months to 20 years). The R2eD AVM scoring system was applied to each patient. The score components of size < 3 cm and exclusive deep venous drainage were significantly associated with rupture risk (p < 0.05). The complete model for the R2eD AVM score had an area under the curve of 0.671 (95% CI 0.586-0.757). CONCLUSIONS: This study demonstrated poor external validity of the R2eD AVM score in predicting pediatric AVM rupture risk. The results suggest that future studies are warranted to determine a better scoring method to capture pediatric rupture risk, given the significant differences in clinical presentation in pediatric compared with adult AVM patients.

Application of Fuzzy Composite Programming in a Questionnaire as a Methodological Test to Study the Effect of Reservoir Management on Social Interests-A Survey Based on Two Case Studies in Southern Germany.

To understand the concerns, approvals and disapprovals of expert opinions about managerial issues from around reservoirs this study uses the approach of Fuzzy Composite Programming (FCP) in direct questionnaires to parameterize and rate a set of indicators with statements about managerial issues concerning societal implications by the responding experts. The personal ratings get summarized in four different layers and converted into one final numerical value which will be in the range of 0 as the absolute disapproval of the indicators and 1 as the absolute approval of the indicators. The FCP approach thereby rates the individual indicator, secondly the indicator category, thirdly the compensational factor and fourthly the dimensions of sustainability. This facilitates a rapid comparison of results of rather complicated sets of pre-set indicators in topics reaching from legal issues to societal concerns in one final numerical value to identify crucial topics and start open debates. This study was carried out as a methodological test at two water reservoirs in southern Germany. The results show a general possibility of using a rather retrospect methodology towards current ratings of experts in the field of reservoir management. 10 respondents answered the FCP questionnaires, 5 at each study site. The scores of the calculation showed a higher level of positive connection in the case of the Schwarzenbachtalsperre (SBT) with a score of 0.77, compared to a score of 0.54 in the case of the Franconian Lake District (FLD). Apart from the pure numerical scores, FCP can show conflicting issues and possible compromise solutions between the different stakeholders, in/based on the individual ratings. The findings could help reach a more sustainable management of water resources that includes all stakeholders, by pointing out debatable implications.

Engineering Inflammation-Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering.

Articular cartilage defects caused by traumatic injury rarely heal spontaneously and predispose into post-traumatic osteoarthritis. In the current autologous cell-based treatments the regenerative process is often hampered by the poor regenerative capacity of adult cells and the inflammatory state of the injured joint. The lack of ideal treatment options for cartilage injuries motivated the authors to tissue engineer a cartilage tissue which would be more resistant to inflammation. A clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 knockout of TGF-ß-activated kinase 1 (TAK1) gene in polydactyly chondrocytes provides multivalent protection against the signals that activate the pro-inflammatory and catabolic NF-κB pathway. The TAK1-KO chondrocytes encapsulate into a hyaluronan hydrogel deposit copious cartilage extracellular matrix proteins and facilitate integration onto native cartilage, even under proinflammatory conditions. Furthermore, when implanted in vivo, compared to WT fewer pro-inflammatory M1 macrophages invade the cartilage, likely due to the lower levels of cytokines secreted by the TAK1-KO polydactyly chondrocytes. The engineered cartilage thus represents a new paradigm-shift for the creation of more potent and functional tissues for use in regenerative medicine.

Fractal analysis of healthy and diseased vasculature in pediatric Moyamoya disease.

BACKGROUND AND PURPOSE: Fractal dimension is an objective metric for the notion of structural complexity. We sought to investigate differences in structural complexity between healthy and affected territories of cerebral vasculature in moyamoya, as well as associated scalp vasculature and native transdural collaterals in patients with moyamoya by comparing their respective fractal dimensions. METHODS: Our cohort consisted of 15 transdural collaterals from 12 patients with unilateral anterior circulation moyamoya. Frames of distal arterial vasculature from internal and external carotid angiograms were selected then automatically segmented and also manually annotated by a cerebrovascular surgeon. In the affected hemisphere, the region with transdural collateral supply was compared to the contralateral region. The resulting skeletonized angiograms were analyzed for their fractal dimensions. RESULTS: We found the average fractal dimension (Df) of the moyamoya-side ICA was 1.82 with slightly different means for the anteroposterial (AP) and lateral views (mean = 1.82; mean = 1.81). The overall mean for healthy cerebral vasculature was also found to be 1.82 (AP: mean = 1.83; lateral: mean = 1.81). Mean Df of native transdural collaterals was found to be 1.82 (AP: mean = 1.83; lateral: mean = 1.81). The mean Df difference between autosegmented and manually segmented images was 0.013. CONCLUSION: In accordance with the clinical understanding of moyamoya disease, the distal arterial structural complexity is not affected in moyamoya, and is maintained by transdural collaterals formed by vasculogenesis. Autosegmentation of cerebral vasculature is also shown to be accurate when compared to manual segmentation.