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1.
Knee ; 48: 257-264, 2024 May 23.
Article En | MEDLINE | ID: mdl-38788308

PURPOSE: To assess the reimplantation rate and predictors of patients requiring second-staged matrix-induced autologous chondrocyte implantation (MACI) reimplantation after initial first stage cartilage biopsy. METHODS: A retrospective review was performed from 2018 to 2022 among patients who underwent only phase I MACI biopsy procedure (biopsy group) or both phase I with transition to phase II implantation of chondrocytes (implantation group) at a single tertiary center. Demographic, qualitative, and quantitative measurements were recorded, and univariate and multivariate regression analysis was performed to assess predictors of ultimately requiring second stage MACI implantation. RESULTS: A total of 71 patients (51% female, age 27.7 ± 10.6 years (range 12-50)) were included in this study. Eventually, 25 of 71 patients (35.2%) experienced persistence of symptoms after initial MACI biopsy and other concomitant procedures, requiring second-stage implantation. Univariate analysis showed the implantation group compared to the biopsy group had a greater lesion size (5.2 cm2 ± 3.3 vs. 3.3 cm2 ± 1.4, p = 0.024), a higher proportion patients ≥ 26 years of age (76% vs. 43%, p = 0.009), a medial femoral condyle lesion more commonly (33% vs 11%, p = 0.005), were more often female (72% vs. 39%, p = 0.008), and had less often soft tissue repair at time of biopsy (32% vs. 61%, p = 0.020). Backward multivariate logistic regression analysis revealed that size of the lesion (OR 1.43, p = 0.031) and age ≥ 26 years old at time of biopsy (OR 3.55, p = 0.042) were independent predictors of not responding to initial surgery and requiring implantation surgery. CONCLUSION: This study found that 35% of patients undergoing MACI phase I biopsy harvest eventually required autologous implantation. Independent risk factors for progressing to implantation after failed initial surgery were larger defect size and older age. LEVEL OF EVIDENCE: III, Cohort Study.

2.
Ann Jt ; 9: 16, 2024.
Article En | MEDLINE | ID: mdl-38694813

Background and Objective: Anterior shoulder dislocations can result in acute glenoid rim fractures that compromise the bony stability of the glenohumeral joint. Adequate fixation of these fractures is required to restore stability, decrease shoulder pain, and facilitate return to activity. The double-row suture bridge is a relatively novel fixation technique, first described in 2009, that accomplishes internal fixation with sufficient stability using an all-arthroscopic technique to restore the glenoid footprint. A 40-year-old female with recurrent anterior shoulder instability in the setting of seizure disorder was found to have a bony Bankart lesion of 25% to 30% with a concomitant superior labral tear. The patient was treated with a double-row bony Bankart bridge and labral repair. At six months follow-up, she has progressed to a full recovery with no recurrence. Methods: A search was conducted in May 2023 in PubMed, EMBASE, and CINAHL with the search terms bony Bankart, bone Bankart, osseous Bankart, acute, bridge, suture bridge, double row. Key Content and Findings: Double-row suture bridge repairs result in improvement in shoulder function as determined by ASES (93.5), QuickDASH (4.5), SANE (95.9), and SF-12 (55.6). The overall recurrence rate of anterior instability after a bony Bankart bridge repair is 8%. When examining the return to prior level of function, 81.4% of patients were able to do so with only 7.9% of patients reporting significant modifications to their activity level. In mid-term results, double row suture bridge demonstrates similar outcomes to other all-arthroscopic fixation methods of bony Bankart injuries. Importantly, bony Bankart bridge remains a viable option for critical glenoid lesions over the 20% cutoff used in other all arthroscopic techniques. Biomechanically, the double-row suture bridge offers distinct benefits over its single-row counterpart including increased compression, reduced displacement, and reduced step-off. Conclusions: Although there is limited data, the studies discussed and the demonstrative case show the potential benefit of all-arthroscopic double-row suture bridge fixation including increased compression, decreased displacement, and a lower complication rate in patients with large bony Bankart lesions traditionally requiring bony augmentation. However, more robust studies are necessary to determine the long-term success of the double-row suture bridge.

3.
Angew Chem Int Ed Engl ; 63(25): e202404018, 2024 Jun 17.
Article En | MEDLINE | ID: mdl-38593269

Biomolecular condensates have emerged as important structures in cellular function and disease, and are thought to form through liquid-liquid phase separation (LLPS). Thorough and efficient in vitro experiments are therefore needed to elucidate the driving forces of protein LLPS and the possibility to modulate it with drugs. Here we present Taylor dispersion-induced phase separation (TDIPS), a method to robustly measure condensation phenomena using a commercially available microfluidic platform. It uses only nanoliters of sample, does not require extrinsic fluorescent labels, and is straightforward to implement. We demonstrate TDIPS by screening the phase behaviour of two proteins that form biomolecular condensates in vivo, PGL-3 and Ddx4. Uniquely accessible to this method, we find an unexpected re-entrant behaviour at very low ionic strength, where LLPS is inhibited for both proteins. TDIPS can also probe the reversibility of assemblies, which was shown for both α-synuclein and for lysozyme, relevant for health and biotechnology, respectively. Finally, we highlight how effective inhibition concentrations and partitioning of LLPS-modifying compounds can be screened highly efficiently.


Biomolecular Condensates , Muramidase , alpha-Synuclein , Muramidase/chemistry , Muramidase/metabolism , Muramidase/isolation & purification , Biomolecular Condensates/chemistry , Biomolecular Condensates/metabolism , alpha-Synuclein/chemistry , alpha-Synuclein/isolation & purification , alpha-Synuclein/metabolism , DEAD-box RNA Helicases/metabolism , DEAD-box RNA Helicases/chemistry , Humans , Phase Separation
5.
J Colloid Interface Sci ; 665: 535-544, 2024 Jul.
Article En | MEDLINE | ID: mdl-38538483

HYPOTHESIS: We hypothesize that pre-assembled lithographic Brownian seven-fold quasi-crystals (QCs) of colloidal tiles at high densities can exhibit a heptatic liquid quasi-crystal (LQC) phase upon release; such heptatic LQCs can undergo heterogeneous dynamics at different length scales, reflecting the underlying symmetry, corrugation, and hierarchy of local sets of tiles. EXPERIMENTS: We design, fabricate, and release a seven-fold QC composed of three differently shaped rhombic tiles using the method of lithographically pre-assembled monolayers (litho-PAMs). High resolution optical microscopy enables spatio-temporal particle tracking of Brownian fluctuations of many tiles in a large area over a long time. We develop an edge-proximity tessellation method for analyzing nearest neighboring particles that can be applied to assemblies and dense systems of complex shapes. FINDINGS: A fluctuating heptatic LQC phase is identified at high tile area fractions. Heterogenous dynamics and order at different length scales indicate diverse, hierarchical motif structures. We show that certain motifs can collectively rotate without any cage breaking, leading to alterations of the local tile-structure reminiscent of phason-flips in atomic QCs; this rotation causes a slow decline in the system's spatial order. We anticipate that edge-proximity tessellation will help elucidate phase transitions of other systems made of diverse building blocks having significant geometrical complexity at multiple length scales.

6.
Arthrosc Tech ; 13(2): 102840, 2024 Feb.
Article En | MEDLINE | ID: mdl-38435260

Batter's Shoulder is a unique injury that may be associated with recurrent microtrauma followed by acute subluxation of the humeral head on the posterior glenoid edge, leading to posterior labral tears. Early identification of this injury is critical, as it may be treated with conservative nonsurgical treatments prior to labral tear onset. If conservative treatment fails and pain persists, surgical options include arthroscopic fixation to reapproximate the posterior labrum to the glenoid and restore capsular tension. Previous studies have shown the benefit of using knotless suture anchors in arthroscopic shoulder fixation. This technical note demonstrates that Batter's Shoulder is a unique injury associated with posterior labral tears of the shoulder and provides a contemporary method of arthroscopic fixation of a posterior labral tear using retensionable knotless all-suture anchors.

7.
Chem Sci ; 15(7): 2528-2544, 2024 Feb 14.
Article En | MEDLINE | ID: mdl-38362440

Amyloid fibrils of proteins such as α-synuclein are a hallmark of neurodegenerative diseases and much research has focused on their kinetics and mechanisms of formation. The question as to the thermodynamic stability of such structures has received much less attention. Here, we newly utilize the principle of transient incomplete separation of species in laminar flow in combination with chemical depolymerization for the quantification of amyloid fibril stability. The relative concentrations of fibrils and monomer at equilibrium are determined through an in situ separation of these species based on their different diffusivity inside a microfluidic capillary. The method is highly sample economical, using much less than a microliter of sample per data point and its only requirement is the presence of aromatic residues (W, Y) because of its label-free nature, which makes it widely applicable. Using this method, we investigate the differences in thermodynamic stability between different fibril polymorphs of α-synuclein and quantify these differences for the first time. Importantly, we show that fibril formation can be under kinetic or thermodynamic control and that a change in solution conditions can both stabilise and destabilise amyloid fibrils. Taken together, our results establish the thermodynamic stability as a well-defined and key parameter that can contribute towards a better understanding of the physiological roles of amyloid fibril polymorphism.

8.
Ann Rheum Dis ; 83(5): 556-563, 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38331589

OBJECTIVES: We aimed to cluster patients with rheumatoid arthritis (RA) based on comorbidities and then examine the association between these clusters and RA disease activity and mortality. METHODS: In this population-based study, residents of an eight-county region with prevalent RA on 1 January 2015 were identified. Patients were followed for vital status until death, last contact or 31 December 2021. Diagnostic codes for 5 years before the prevalence date were used to define 55 comorbidities. Latent class analysis was used to cluster patients based on comorbidity patterns. Standardised mortality ratios were used to assess mortality. RESULTS: A total of 1643 patients with prevalent RA (72% female; 94% white; median age 64 years, median RA duration 7 years) were studied. Four clusters were identified. Cluster 1 (n=686) included patients with few comorbidities, and cluster 4 (n=134) included older patients with 10 or more comorbidities. Cluster 2 (n=200) included patients with five or more comorbidities and high prevalences of depression and obesity, while cluster 3 (n=623) included the remainder. RA disease activity and survival differed across the clusters, with cluster 1 demonstrating more remission and mortality comparable to the general population. CONCLUSIONS: More than 40% of patients with prevalent RA did not experience worse mortality than their peers without RA. The cluster with the worst prognosis (<10% of patients with prevalent RA) was older, had more comorbidities and had less disease-modifying antirheumatic drug and biological use compared with the other clusters. Comorbidity patterns may hold the key to moving beyond a one-size-fits-all perspective of RA prognosis.


Antirheumatic Agents , Arthritis, Rheumatoid , Humans , Female , Middle Aged , Male , Comorbidity , Arthritis, Rheumatoid/drug therapy , Prognosis , Antirheumatic Agents/therapeutic use , Obesity/epidemiology , Prevalence
9.
Biomedicines ; 12(1)2024 Jan 12.
Article En | MEDLINE | ID: mdl-38255274

The gut microbiome and its associated metabolites are integral to the maintenance of gut integrity and function. There is increasing evidence that its alteration, referred to as dysbiosis, is involved in the development of a systemic conditions such as cardiovascular disease (e.g., systemic hypertension, atherosclerosis). Pulmonary hypertension (PH) is a condition characterised by progressive remodelling and vasoconstriction of the pulmonary circulation, ultimately leading to right ventricular failure and premature mortality if untreated. Initial studies have suggested a possible association between dysbiosis of the microbiome and the development of PH. The aim of this article is to review the current experimental and clinical data with respect to the potential interaction between the gut microbiome and the pathophysiology of pulmonary hypertension. It will also highlight possible new therapeutic targets that may provide future therapies.

10.
Arthritis Care Res (Hoboken) ; 76(5): 616-626, 2024 May.
Article En | MEDLINE | ID: mdl-38148547

OBJECTIVE: Juvenile localized scleroderma (jLS) is a chronic autoimmune disease commonly associated with poor outcomes, including contractures, hemiatrophy, uveitis, and seizures. Despite improvements in treatment, >25% of patients with jLS have functional impairment. To improve patient evaluation, our workgroup developed the Localized scleroderma Total Severity Scale (LoTSS), an overall disease severity measure. METHODS: LoTSS was developed as a weighted measure by a consensus process involving literature review, surveys, case vignettes, and multicriteria decision analysis. Feasibility was assessed in larger Childhood Arthritis and Rheumatology Research Alliance groups. Construct validity with physician assessment and inter-rater reliability was assessed using case vignettes. Additional evaluation was performed in a prospective patient cohort initiating treatment. RESULTS: LoTSS severity items were organized into modules that reflect jLS disease patterns, with modules for skin, extracutaneous, and craniofacial manifestations. Construct validity of LoTSS was supported by a strong positive correlation with the Physician Global Assessment (PGA) of severity and damage and weak positive correlation with PGA-Activity, as expected. LoTSS was responsive, with a small effect size identified. Moderate-to-excellent inter-rater reliability was demonstrated. LoTSS was able to discriminate between patient subsets, with higher scores identified in those with greater disease burden and functional limitation. CONCLUSION: We developed a new LS measure for assessing cutaneous and extracutaneous severity and have shown it to be reliable, valid, and responsive. LoTSS is the first measure that assesses and scores all the major extracutaneous manifestations in LS. Our findings suggest LoTSS could aid assessment and management of patients and facilitate outcome evaluation in treatment studies.


Scleroderma, Localized , Scleroderma, Systemic , Severity of Illness Index , Humans , Scleroderma, Localized/diagnosis , Scleroderma, Localized/physiopathology , Scleroderma, Localized/complications , Female , Male , Child , Reproducibility of Results , Adolescent , Feasibility Studies , Prospective Studies , Consensus , Observer Variation
11.
Arthroscopy ; 2023 Dec 25.
Article En | MEDLINE | ID: mdl-38151167

PURPOSE: To systematically review the literature and report the outcomes of various surgical treatments for reverse Hill-Sachs lesions (RHSL) in the setting of posterior shoulder instability. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. All studies assessing outcomes of surgical treatment of RHSL from inception to January 2023 were identified in PubMed, Embase, and Cochrane Library. Inclusion criteria consisted of studies reporting outcomes, minimum mean 1-year follow-up, and minimum Level IV evidence. Outcomes were assessed using Forest plots with random effects models using R software. RESULTS: A total of 29 studies consisting of 291 patients were included with a mean age of 42 years (range 16-88 years), 87% male gender, and mean follow-up of 4.5 years. The mean size of impacted or affected cartilage was 35%, and time from injury to surgery was mean 15 weeks. Nearly all studies were Level IV evidence, and quality of studies was low. Random effect models were performed, and data are presented as range. A low incidence of instability was noted for all surgical techniques with good patient-reported outcome measures. Most studies reported outcomes of the modified McLaughlin procedure (13 studies, 126 patients) with overall Constant-Murley Score of 65 to 92. Trends were seen towards better Constant-Murley Score and external rotation with a shorter delay between injury, and when arthroscopic and joint preserving treatments were performed. CONCLUSIONS: This systematic review showed low rates of instability recurrence, reproducible range of motion, and favorable patient-reported outcome measures were reported following all treatments for RHSLs with posterior instability. There was a significant association between better outcomes and a shorter delay between injury and surgery. The level of evidence is limited, given the small and retrospective studies which can be explained by the rarity of these injuries. LEVEL OF EVIDENCE: Level IV; systematic review of Level IV or better investigations.

12.
Food Res Int ; 172: 113080, 2023 10.
Article En | MEDLINE | ID: mdl-37689860

The integration of intramuscular fat-or marbling-into cultured meat will be critical for meat texture, mouthfeel, flavor, and thus consumer appeal. However, culturing muscle tissue with marbling is challenging since myocytes and adipocytes have different media and scaffold requirements for optimal growth and differentiation. Here, we present an approach to engineer multicomponent tissue using myogenic and adipogenic microtissues. The key innovation in our approach is the engineering of myogenic and adipogenic microtissues using scaffolds with customized physical properties; we use these microtissues as building blocks that spontaneously adhere to produce multicomponent tissue, or marbled cultured meat. Myocytes are grown and differentiated on gelatin nanofiber scaffolds with aligned topology that mimic the aligned structure of skeletal muscle and promotes the formation of myotubes in both primary rabbit skeletal muscle and murine C2C12 cells. Pre-adipocytes are cultured and differentiated on edible gelatin microbead scaffolds, which are customized to have a physiologically-relevant stiffness, and promote lipid accumulation in both primary rabbit and murine 3T3-L1 pre-adipocytes. After harvesting and stacking the individual myogenic and adipogenic microtissues, we find that the resultant multicomponent tissues adhere into intact structures within 6-12 h in culture. The resultant multicomponent 3D tissue constructs show behavior of a solid material with a Young's modulus of âˆ¼ 2 ± 0.4 kPa and an ultimate tensile strength of âˆ¼ 23 ± 7 kPa without the use of additional crosslinkers. Using this approach, we generate marbled cultured meat with âˆ¼ mm to âˆ¼ cm thickness, which has a protein content of âˆ¼ 4 ± 2 g/100 g that is comparable to a conventionally produced Wagyu steak with a protein content of âˆ¼ 9 ± 4 g/100 g. We show the translatability of this layer-by-layer assembly approach for microtissues across primary rabbit cells, murine cell lines, as well as for gelatin and plant-based scaffolds, which demonstrates a strategy to generate edible marbled meats derived from different species and scaffold materials.


Gelatin , Muscle Fibers, Skeletal , Animals , Mice , Rabbits , Cell Differentiation , Meat , Muscle, Skeletal
13.
IUCrJ ; 10(Pt 6): 678-693, 2023 Nov 01.
Article En | MEDLINE | ID: mdl-37727961

Fixed targets are a popular form of sample-delivery system used in serial crystallography at synchrotron and X-ray free-electron laser sources. They offer a wide range of sample-preparation options and are generally easy to use. The supports are typically made from silicon, quartz or polymer. Of these, currently, only silicon offers the ability to perform an aperture-aligned data collection where crystals are loaded into cavities in precise locations and sequentially rastered through, in step with the X-ray pulses. The polymer-based fixed targets have lacked the precision fabrication to enable this data-collection strategy and have been limited to directed-raster scans with crystals randomly distributed across the polymer surface. Here, the fabrication and first results from a new polymer-based fixed target, the micro-structured polymer fixed targets (MISP chips), are presented. MISP chips, like those made from silicon, have a precise array of cavities and fiducial markers. They consist of a structured polymer membrane and a stabilization frame. Crystals can be loaded into the cavities and the excess crystallization solution removed through apertures at their base. The fiducial markers allow for a rapid calculation of the aperture locations. The chips have a low X-ray background and, since they are optically transparent, also allow for an a priori analysis of crystal locations. This location mapping could, ultimately, optimize hit rates towards 100%. A black version of the MISP chip was produced to reduce light contamination for optical-pump/X-ray probe experiments. A study of the loading properties of the chips reveals that these types of fixed targets are best optimized for crystals of the order of 25 µm, but quality data can be collected from crystals as small as 5 µm. With the development of these chips, it has been proved that polymer-based fixed targets can be made with the precision required for aperture-alignment-based data-collection strategies. Further work can now be directed towards more cost-effective mass fabrication to make their use more sustainable for serial crystallography facilities and users.

14.
Nat Chem ; 15(9): 1306-1316, 2023 09.
Article En | MEDLINE | ID: mdl-37337111

Protein liquid-liquid phase separation can lead to disease-related amyloid fibril formation. The mechanisms of conversion of monomeric protein into condensate droplets and of the latter into fibrils remain elusive. Here, using mass photometry, we demonstrate that the Parkinson's disease-related protein, α-synuclein, can form dynamic nanoscale clusters at physiologically relevant, sub-saturated concentrations. Nanoclusters nucleate in bulk solution and promote amyloid fibril formation of the dilute-phase monomers upon ageing. Their formation is instantaneous, even under conditions where macroscopic assemblies appear only after several days. The slow growth of the nanoclusters can be attributed to a kinetic barrier, probably due to an interfacial penalty from the charged C terminus of α-synuclein. Our findings reveal that α-synuclein phase separation occurs at much wider ranges of solution conditions than reported so far. Importantly, we establish mass photometry as a promising methodology to detect and quantify nanoscale precursors of phase separation. We also demonstrate its general applicability by probing the existence of nanoclusters of a non-amyloidogenic protein, Ddx4n1.


Parkinson Disease , alpha-Synuclein , Humans , alpha-Synuclein/metabolism , Amyloid/metabolism , Parkinson Disease/metabolism
15.
J Epidemiol Community Health ; 77(9): 565-570, 2023 09.
Article En | MEDLINE | ID: mdl-37353312

BACKGROUND: The NHS Diabetes Prevention Programme (DPP) in England is a behavioural intervention for preventing type 2 diabetes mellitus (T2DM) among people with non-diabetic hyperglycaemia (NDH). How this programme affects inequalities by age, sex, limiting illnesses or disability, ethnicity or deprivation is not known. METHODS: We used multinomial and binary logistic regression models to compare whether the population with NDH at different stages of the programme are representative of the population with NDH: stages include (1) prevalence of NDH (using survey data from UK Household Longitudinal Study (n=794) and Health Survey for England (n=1383)); (2) identification in primary care and offer of programme (using administrative data from the National Diabetes Audit (n=1 267 350)) and (3) programme participation (using programme provider records (n=98 024)). RESULTS: Predicted probabilities drawn from the regressions with demographics as each outcome and dataset identifier as predictors showed that younger adults (aged under 40) (4% of the population with NDH (95% CI 2.4% to 6.5%)) and older adults (aged 80 and above) (12% (95% CI 9.5% to 14.2%)) were slightly under-represented among programme participants (2% (95% CI 1.8% to 2.2%) and 8% (95% CI 7.8% to 8.2%) of programme participants, respectively). People living in deprived areas were under-represented in eight sessions (14% (95% CI 13.7% to 14.4%) vs 20% (95% CI 16.4% to 23.6%) in the general population). Ethnic minorities were over-represented among offers (35% (95% CI 35.1% to 35.6%) vs 13% (95% CI 9.1% to 16.4%) in general population), though the proportion dropped at the programme completion stage (19% (95% CI 18.5% to 19.5%)). CONCLUSION: The DPP has the potential to reduce ethnic inequalities, but may widen socioeconomic, age and limiting illness or disability-related inequalities in T2DM. While ethnic minority groups are over-represented at the identification and offer stages, efforts are required to support completion of the programme. Programme providers should target under-represented groups to ensure equitable access and narrow inequalities in T2DM.


Diabetes Mellitus, Type 2 , Humans , Aged , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/prevention & control , Ethnicity , Longitudinal Studies , Minority Groups , England/epidemiology
16.
Sci Adv ; 9(26): eadh3715, 2023 Jun 28.
Article En | MEDLINE | ID: mdl-37379378

While much attention has been given to jamming of granular and colloidal particles having monomodal size distributions, jamming of systems having more complex size distributions remains an interesting direction. We create concentrated, disordered binary mixtures of size-fractionated nanoscale and microscale oil-in-water emulsions, which are stabilized by the same common ionic surfactant, and measure the optical transport properties, microscale droplet dynamics, and mechanical shear rheological properties of these mixtures over a wide range of relative and total droplet volume fractions. Simple effective medium theories do not explain all of our observations. Instead, we show that our measurements are consistent with more complex collective behavior in extremely bidisperse systems, involving an effective continuous phase that governs nanodroplet jamming, as well as depletion attractions between microscale droplets induced by nanoscale droplets.

17.
Sci Rep ; 13(1): 5360, 2023 04 01.
Article En | MEDLINE | ID: mdl-37005480

Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as ACPA-positive (ACPA+) or ACPA-negative (ACPA-), respectively. In this study, we aimed to elucidate a broader range of serological autoantibodies that could further explain immunological differences between patients with ACPA+ RA and ACPA- RA. On serum collected from adult patients with ACPA+ RA (n = 32), ACPA- RA (n = 30), and matched healthy controls (n = 30), we used a highly multiplex autoantibody profiling assay to screen for over 1600 IgG autoantibodies that target full-length, correctly folded, native human proteins. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA- RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies with significantly higher abundances in ACPA+ RA patients and ACPA- RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons; this provides further evidence of immunological differences between these two RA subgroups despite sharing similar symptoms. On the other hand, we identified 30 and 25 autoantibodies with lower abundances in ACPA+ RA and ACPA- RA, respectively, of which 8 autoantibodies were common in both comparisons; we report for the first time that the depletion of certain autoantibodies may be linked to this autoimmune disease. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with Clinical Disease Activity Index, but associate differently depending on patients' ACPA status. In all, we present candidate autoantibody biomarker signatures associated with ACPA status and disease activity in RA, providing a promising avenue for patient stratification and diagnostics.


Arthritis, Rheumatoid , Autoantibodies , Adult , Humans , Anti-Citrullinated Protein Antibodies
18.
Phys Rev E ; 107(2-1): 024605, 2023 Feb.
Article En | MEDLINE | ID: mdl-36932564

The unjamming of elastic concentrated nanoemulsions into viscous dilute nanoemulsions, through dilution with the continuous phase, offers interesting opportunities for a pulsed-field gradient (PFG) NMR, particularly if the nanoemulsion is designed to take advantage of the nuclear specificity offered by NMR. Here, we make and study size-fractionated oil-in-water nanoemulsions using a perfluorinated copolymer silicone oil that is highly insoluble in the aqueous continuous phase. By studying these nanoemulsions using ^{19}F stimulated-echo PFG-NMR, we avoid any contribution from the aqueous continuous phase, which contains a nonfluorinated ionic surfactant. We find a dramatic change in the ^{19}F PFG-NMR decays at high field-gradient strengths as the droplet volume fraction, ϕ, is lowered through dilution. At high ϕ, observed decays as a function of field-gradient strength exhibit decay-to-plateau behavior indicating the jamming of nanodroplets, which contain ^{19}F probe molecules, in an elastic material reminiscent of a nanoporous solid. In contrast, at lower ϕ, only a simple decay is observed, indicating that the nanodroplets have unjammed and can diffuse over much larger distances. Through a comparison with bulk mechanical rheometry, we show that this dramatic change coincides with the loss of low-frequency shear elasticity of the nanoemulsion.

19.
Phys Chem Chem Phys ; 25(21): 14700-14710, 2023 May 31.
Article En | MEDLINE | ID: mdl-36806848

Minimal understanding of the formation mechanism and structure of polydopamine (pDA) and its natural analogue, eumelanin, impedes the practical application of these versatile polymers and limits our knowledge of the origin of melanoma. The lack of conclusive structural evidence stems from the insolubility of these materials, which has spawned significantly diverse suggestions of pDA's structure in the literature. We discovered that pDA is soluble in certain ionic liquids. Using these ionic liquids (ILs) as solvents, we present an experimental methodology to solvate pDA, enabling us to identify pDA's chemical structure. The resolved pDA structure consists of self-assembled supramolecular aggregates that contribute to the increasing complexity of the polymer. The underlying molecular energetics of pDA solvation and a macroscopic picture of the disruption of the aggregates using IL solvents have been investigated, along with studies of the aggregation mechanism in water.

20.
Phys Rev E ; 107(1-2): 015101, 2023 Jan.
Article En | MEDLINE | ID: mdl-36797864

We experimentally investigate the microfluidic flow of oil-in-water nanoemulsions in aqueous sodium dodecyl sulfate (SDS) solutions having different concentrations and injection flow rates. A coaxial microfluidic device is employed to explore the behavior of nanoemulsion threads in these sheathing SDS solutions. Using two high-speed cameras, which simultaneously capture both top and side views, we reveal a variety of flow phenomena, ranging from simple core-annular flow to complex flows, such as gravitational, inertial, and buckling thread flows. By analyzing these complex flows, we develop a methodology that elucidates the relationship of core-annular and gravitational flows at low flow rates. Further, we examine the off-axis displacements and bending of core threads at large flow rates, and we study the buckling dynamics of nanoemulsion threads subjected to osmotic stresses caused by large SDS concentrations in the sheathing fluid.

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