Miracle-dz/UniFAR-FTUs huggingface dataset:
Tolerogenic nanoparticles suppress central nervous system inflammation

Significance Current treatments for autoimmune diseases rely on nonspecific immunosuppression, risking important complications and limiting the long-term use of these approaches for the treatment of chronic human autoimmunity. Thus, there is an unmet need for therapeutic approaches to reestablish immune tolerance in autoimmune disorders in an antigen-specific manner. Here, we describe a nanoliposome (NLP)-based platform for the induction of antigen-specific tolerance via the modulation of signaling by the aryl hydrocarbon receptor. These NLPs suppress disease pathology and pathogenic autoimmunity in preclinical models of multiple sclerosis, providing a candidate antigen-specific therapeutic approach for the management of autoimmune disorders. Therapeutic approaches for the induction of immune tolerance remain an unmet clinical need for the treatment of autoimmune diseases, including multiple sclerosis (MS). Based on its role in the control of the immune response, the ligand-activated transcription factor aryl hydrocarbon receptor (AhR) is a candidate target for novel immunotherapies. Here, we report the development of AhR-activating nanoliposomes (NLPs) to induce antigen-specific tolerance. NLPs loaded with the AhR agonist ITE and a T cell epitope from myelin oligodendrocyte glycoprotein (MOG)35–55 induced tolerogenic dendritic cells and suppressed the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS, in preventive and therapeutic setups. EAE suppression was associated with the expansion of MOG35–55-specific FoxP3+ regulatory T cells (Treg cells) and type 1 regulatory T cells (Tr1 cells), concomitant with a reduction in central nervous system-infiltrating effector T cells (Teff cells). Notably, NLPs induced bystander suppression in the EAE model established in C57BL/6 × SJL F1 mice. Moreover, NLPs ameliorated chronic progressive EAE in nonobese diabetic mice, a model which resembles some aspects of secondary progressive MS. In summary, these studies describe a platform for the therapeutic induction of antigen-specific tolerance in autoimmune diseases.
Hidden Host Mortality from an Introduced Parasitoid: Conventional and Molecular Evaluation of Non-Target Risk

Simple Summary Classical biological control (CBC), i.e., the release of a natural enemy from the pest’s native range, has long been recognized as a viable approach to controlling invasive pests. CBC is considered specific to a given pest and does not come with the environmental risks often associated with broad-spectrum chemical pesticides. However, an exotic natural enemy may pose environmental risks, specifically to native species that are not the target of the biological control program. Some effects of an exotic natural enemy, such as consumption or reproduction, can be measured more readily than others. Our research points out that some of these ‘hidden effects’ can be quite important and merit our attention. We use molecular tools and modeling to help understand the hidden effects both for the target and non-target species. Our model system was an invasive fruit and vegetable pest from Asia, the brown marmorated stink bug (BMSB), Halyomorpha halys, and an exotic parasitoid, Trissolcus japonicus. T. japonicus has become established in North America and could help limit outbreaks of this pest. Unfortunately, it also kills non-target stink bugs with varying degrees of reproductive success, which may have both direct and indirect ecological effects on H. halys and non-target stink bug species. Abstract Hidden trophic interactions are important in understanding food web ecology and evaluating the ecological risks and benefits associated with the introduction of exotic natural enemies in classical biological control programs. Although non-target risk is typically evaluated based on evidence of successful parasitism, parasitoid-induced host mortality not resulting in visible evidence of parasitism (i.e., nonreproductive effects) is often overlooked. The adventive establishment of Trissolcus japonicus, an exotic parasitoid of the introduced stink bug Halyomorpha halys, provides an opportunity to investigate the total impact of this parasitoid on target and non-target hosts in the field. We developed a new methodology to measure nonreproductive effects in this system, involving a species-specific diagnostic PCR assay for T. japonicus. We applied this methodology to field-deployed eggs of four pentatomid species, coupled with traditional rearing techniques. Nonreproductive effects were responsible for the mortality of an additional 5.6% of H. halys eggs due to T. japonicus, and were even more substantial in some of the non-target species (5.4–43.2%). The observed hidden mortality of native non-target species from an introduced parasitoid could change predictions about direct and indirect ecological interactions and the efficacy of biological control of the target pest.
Long-Term SARS-CoV-2 Infection Associated with Viral Dissemination in Different Body Fluids Including Bile in Two Patients with Acute Cholecystitis

Our study aimed to investigate the kinetics of SARS-CoV-2 RNA in bile and in different body fluids of two SARS-CoV-2 positive patients with acute cholecystitis by innovative droplet digital PCR (ddPCR) assays. For each patient, nasopharyngeal- and rectal swabs, bile, urine, and plasma samples were collected at different time points for SARS-CoV-2 RNA quantification by two ddPCR assays. For both patients, ddPCR revealed persistent and prolonged detection of viral RNA in the nasopharyngeal swab despite triple-negative or single-positive results by qRT-PCR. In Patient 1, SARS-CoV-2 RNA dropped more rapidly in bile and rectal-swab and declined slowly in nasopharyngeal swab and plasma, becoming undetectable in all compartments 97 days after symptoms started. Conversely, in patient 2, SARS-CoV-2 RNA was detected, even if at low copies, in all body samples (with the exception of urine) up to 75 days after the onset of symptoms. This study highlights that SARS-CoV-2 RNA can persist for a prolonged time in respiratory samples and in several biological samples despite negativity to qRT-PCR, supporting SARS-CoV-2’s ability to provoke persistent and disseminated infection and therefore to contribute to extra-pulmonary clinical manifestations.
A U-Net Based Approach for Automating Tribological Experiments

Tribological experiments (i.e., characterizing the friction and wear behavior of materials) are crucial for determining their potential areas of application. Automating such tests could hence help speed up the development of novel materials and coatings. Here, we utilize convolutional neural networks (CNNs) to automate a common experimental setup whereby an endoscopic camera was used to measure the contact area between a rubber sample and a spherical counterpart. Instead of manually determining the contact area, our approach utilizes a U-Net-like CNN architecture to automate this task, creating a much more efficient and versatile experimental setup. Using a 5× random permutation cross validation as well as additional sanity checks, we show that we approached human-level performance. To ensure a flexible and mobile setup, we implemented the method on an NVIDIA Jetson AGX Xavier development kit where we achieved ~18 frames per second by employing mixed-precision training.
Debt-Related Financial Hardship and Health

Recent research shows personal financial debt is an important socioeconomic determinant of health, but the mechanisms through which it operates are not well understood. This article uses data from a mixed-methods study to explore how changes in spending and behavior that result from debt have salient health consequences in a cross-sectional sample of Boston area adults (n = 286). Findings show that a large majority of respondents had skipped medical care, housing payments, or consumer purchases at least once because of their debt. Controlling for multiple sociodemographic characteristics, each of these measures of debt-related behavior change was associated with worse self-rated health, and higher depressive symptoms, anxiety, and perceived stress. In models including all three measures, skipped medical care was associated with worse health across all outcomes, while skipped consumer purchases were associated with higher perceived stress and depression. These findings suggest that altered spending and care-seeking behaviors are potential pathways through which financial debt can negatively affect health and suggest areas in need of additional research.
Evaluation of Molecular Serotyping Assays for Shigella flexneri Directly on Stool Samples

Shigella flexneri is prevalent worldwide and is the most common Shigella species in many countries. At least 19 S. flexneri serotypes exist, and serotype information is important for epidemiologic and vaccine development purposes. ABSTRACT Shigella flexneri is prevalent worldwide and is the most common Shigella species in many countries. At least 19 S. flexneri serotypes exist, and serotype information is important for epidemiologic and vaccine development purposes. We evaluated the performance of real-time PCR assays for O-antigen modification genes to identify the major serotypes on isolates and direct stool samples. The assays were formulated into two multiplex panels: one panel included gtrII, gtrV, gtrX, oac, and wzx6 to identify S. flexneri serotypes 2a, 2b, 3a, 5a, 5b, 6, and X, and the other panel included ipaH, gtrI, gtrIc, and gtrIV to confirm Shigella detection and further identify S. flexneri serotypes 1a, 1b, 1d, 3b, 4a, 4b, 7a, and 7b. We first evaluated 283 Shigella isolates, and PCR serotyping demonstrated 97.0% (95% confidence interval, 93.0% to 99.0%) sensitivity and 99.9% (99.9% to 100%) specificity compared to conventional serotyping. The assays then were utilized on direct stool specimens. A quantitative detection algorithm was developed with a validation set of 174 Shigella culture-positive stool samples and further tested with a derivation set of 164 samples. The PCR serotyping on stool achieved 93% (89% to 96%) sensitivity and 99% (99% to 100%) specificity compared to serotyping. Most discrepancies were genotypic-phenotypic discordance, not genotypic failure. These real-time PCR assays provide an efficient and novel tool for S. flexneri serotype identification.
IGF2R-initiated proton rechanneling dictates an anti-inflammatory property in macrophages

Specific activation of IGF2R inhibits inflammatory diseases via induction of anti-inflammatory macrophages. Metabolic traits of macrophages can be rewired by insulin-like growth factor 2 (IGF2); however, how IGF2 modulates macrophage cellular dynamics and functionality remains unclear. We demonstrate that IGF2 exhibits dual and opposing roles in controlling inflammatory phenotypes in macrophages by regulating glucose metabolism, relying on the dominant activation of the IGF2 receptor (IGF2R) by low-dose IGF2 (L-IGF2) and IGF1R by high-dose IGF2. IGF2R activation leads to proton rechanneling to the mitochondrial intermembrane space and enables sustained oxidative phosphorylation. Mechanistically, L-IGF2 induces nucleus translocation of IGF2R that promotes Dnmt3a-mediated DNA methylation by activating GSK3α/β and subsequently impairs expression of vacuolar-type H+-ATPase (v-ATPase). This sequestrated assembly of v-ATPase inhibits the channeling of protons to lysosomes and leads to their rechanneling to mitochondria. An IGF2R-specific IGF2 mutant induces only the anti-inflammatory response and inhibits colitis progression. Together, our findings highlight a previously unidentified role of IGF2R activation in dictating anti-inflammatory macrophages.
Stakeholder Development of an Online Program to Track Arthritis‐Related Patient‐Reported Outcomes Longitudinally: Live Yes! INSIGHTS

Patient‐reported outcome measures (PROMs) are increasingly used in clinical settings but may not provide benefits to patients outside of health encounters. The Arthritis Foundation’s Live Yes! Network provides an opportunity for PROM use by individuals and the network that assists individuals with managing their arthritis between encounters. Our objective was to develop a patient‐reported outcomes platform for the network, Live Yes! INSIGHTS, using mixed methods and extensive stakeholder input.
Age and Outcomes in Hip Arthroscopy for Femoroacetabular Impingement: A Comparison Across 3 Age Groups

Background: Limited evidence exists concerning the effect of age on hip arthroscopy outcomes for femoroacetabular impingement (FAI). Purpose/Hypothesis: The purpose was to investigate patient-reported outcomes (PROs) and clinical failure rates across various age groups in patients undergoing hip arthroscopy for FAI. We hypothesized that older patients would experience lower improvements in PROs and higher clinical failure rates. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 109 of 130 eligible consecutive patients underwent hip arthroscopy for FAI with a minimum 5-year follow-up. Patients were stratified into 3 groups for comparison (ages 15-34, 35-50, and 51-75 years). Clinical survival rates to revision surgery or total hip arthroplasty (THA) were determined by Kaplan-Meier analysis, and PROs were assessed using analysis of variance. Regression analysis was used to determine factors associated with clinical failure and ΔPROs from baseline to 5 years. Results: The 5-year survival-to-revision rate was 71% (survival time, 69.2 months; 95% CI, 62.8 to 75.5 months). A significant difference in survival to THA was found between groups (P = .030). Being in the older group versus the young and middle-aged groups predicted increased risk of THA conversion (hazard ratio, 5.7; 95% CI, 1.1 to 28.6; P = .035). Overall modified Harris Hip Score (mHHS) and Nonarthritic Hip Score (NAHS) improved from baseline to 5 years (mHHS, P < .001; NAHS, P < .001). Body mass index (mHHS: beta, −1.2; 95% CI, −2.2 to −0.3; P = .013; NAHS: beta, −1.6; 95% CI, −2.6 to −0.5; P = .005) and baseline PROs (mHHS: beta, −0.8; 95% CI, −1.1 to −0.4; P < .001; NAHS: beta, −0.7; 95% CI, −1.1 to −0.4; P < .001) were predictive of 5-year ΔPROs. A decrease was seen in minimal clinically important difference rates in middle-aged (P = .011) and old (P = .030) groups from 6-month to 5-year outcomes. Conclusion: Although hip arthroscopy for FAI yielded improvements in PROs regardless of age, middle-aged and older patients experienced greater declines in clinical outcomes over time than younger patients. Older patients remain good candidates for arthroscopy despite a greater risk for conversion to THA.
The impact of temperature on the water isotope (2H/1H, 17O/16O, 18O/16O) fractionation upon transport through a low-density polyethylene membrane

ABSTRACT In the present study we investigated the isotope effects associated with water loss from closed low-density polyethylene (LDPE) bottles via diffusion at temperatures between 4 and 60 °C. While at low temperatures (4 and 10 °C) no substantial diffusional loss of water was observed within storage time, a pronounced loss was found for the experiments at room temperature and 60 °C. The latter was associated with a substantial increase in δ 18O, δ 17O, and δ 2Η values, and a decrease in the deuterium excess. The magnitude of the isotope effects essentially depended on the extent of water evaporation from the closed bottles through the LDPE membrane.
The Class III Peroxidase gene OsPrx30, Transcriptionally Modulated by the AT-hook Protein OsATH1, Mediates Rice Bacterial Blight-induced ROS Accumulation.

Class III peroxidases (CIII Prxs) play critical roles in plant immunity by scavenging reactive oxygen species (ROS). However, the functions of CIII Prxs in rice (Oryza sativa L.) immunity are largely unexplored. Here, we report a Prx precursor, OsPrx30, that is responsive to the bacterial blight Xanthomonas oryzae pv. oryzae (Xoo). OsPrx30 was primarily expressed in rice roots, leaves, and stems, and its protein product was mainly localized at the endoplasmic reticulum. Overexpression of OsPrx30 enhanced the plant's susceptibility to Xoo by maintaining a high level of peroxidase (POD) activity and reducing the content of H2 O2 , while depletion of OsPrx30 had the opposite effects. Furthermore, we identified an AT-hook transcription factor, OsATH1, that specifically bound to the OsPrx30 promoter. As observed in plants overexpressing OsPrx30, depletion of OsATH1 enhanced susceptibility to Xoo. Finally, we demonstrated that depletion of OsATH1 increased histone H3 acetylation at the AT-rich region of the OsPrx30 promoter. Taken together, these results reveal a mechanism underlying the POD-induced natural resistance to bacterial diseases and suggest a model for transcription regulation of Prx genes in rice. This article is protected by copyright. All rights reserved.
Changes in Matrix Components in the Developing Human Meniscus

Background: Treatment of meniscal tears is necessary to maintain the long-term health of the knee joint. Morphological elements, particularly vascularity, that play an important role in meniscal healing are known to change during skeletal development. Purpose: To quantitatively evaluate meniscal vascularity, cellularity, collagen, and proteoglycan content by age and location during skeletal development. Study Design: Descriptive laboratory study. Methods: Medial and lateral menisci from 14 male and 7 female cadavers aged 1 month to 11 years were collected and evaluated. For each meniscus, histologic and immunohistologic techniques were used to establish the ratio of the area of proteoglycan (safranin O) positivity to the total area (proteoglycan ratio), collagen type I and type II immunostaining positivity, number of blood vessels, and cell density. These features were evaluated over the entire meniscus and also separately in 5 circumferential segments: anterior root, anterior horn, body, posterior horn, and posterior root. Additionally, cell density and number of blood vessels were examined in 3 radial regions: inner, middle, and periphery. Results: Age was associated with a decrease in meniscal vessel count and cell density, while the proteoglycan ratio increased with skeletal maturity. Differences in vessel counts, cellular density, and proteoglycan ratio in different anatomic segments as well as in the inner, middle, and peripheral regions of the developing menisci were also observed. Collagen immunostaining results were inconsistent and not analyzed. Conclusion: The cellularity and vascularity of the developing meniscus decrease with age and the proteoglycan content increases with age. All of these parameters are influenced by location within the meniscus. Clinical Relevance: Age and location differences in meniscal morphology, particularly in the number of blood vessels, are expected to influence meniscal healing.
Prognostic impact of short-term ambulatory blood pressure variability for microvascular and macrovascular outcomes in patients with type 2 diabetes: the Rio de Janeiro Type 2 Diabetes Cohort Study

Supplemental Digital Content is available in the text Objective: To evaluate the prognostic importance of short-term blood pressure variability (BPV) for the occurrence of macrovascular and microvascular complications in individuals with type 2 diabetes. Methods: Six hundred and forty patients had 24-h ambulatory BP monitoring performed at baseline and were followed-up over a median of 11.2 years. Daytime, night-time and 24-h SBP and DBPV parameters (standard deviations and variation coefficients) were calculated. Multivariate Cox analysis, adjusted for risk factors and mean BPs, examined the associations between BPV and the occurrence of microvascular (retinopathy, microalbuminuria, renal function deterioration, peripheral neuropathy) and macrovascular complications [total cardiovascular events (CVEs), major adverse CVEs [MACEs]), and cardiovascular and all-cause mortalities. Improvements in risk discrimination were assessed by the C-statistic and Integrated Discrimination Improvement (IDI) index. Results: During follow-up, 186 patients had a CVE (150 MACEs), and 237 patients died (107 from cardiovascular diseases); 155 newly developed or worsened diabetic retinopathy, 200 achieved the renal composite outcome (124 newly developed microalbuminuria and 102 deteriorated renal function), and 170 newly developed or worsened peripheral neuropathy. Daytime DBPV was the best predictor for all cardiovascular outcomes and mortality, with hazard ratios (for increments of 1SD) ranging from 1.27 (95% CI 1.09–1.48) for all-cause mortality to 1.55 (1.29–1.85) for MACEs, and it improved cardiovascular risk discrimination (with increases in C-statistic of up to 0.026, and IDIs of up to 22.8%). No BPV parameter predicted any microvascular outcome. Conclusion: Short-term BPV, particularly daytime DBPV, predicts future development of macrovascular complications and mortality and improves cardiovascular risk discrimination in patients with diabetes.
Etude des propriétés électroniques des boîtes quantiques InAs/InP par spectroscopie de défauts profonds (DLTS) pour des applications optoélectroniques

Ce travail porte sur une etude des proprietes electroniques des boites quantiques InAs/InP, qui est un systeme tres prometteur pour les telecommunications. Ces nanoparticules sont etudiees pour differentes tailles, densite et dopage. Dans le premier chapitre, nous decrivons l’interet du systeme InAs/InP pour les applications optoelectroniques. Nous presentons la technique de croissance et quelques exemples d’applications de ces boites quantiques. Nous donnons une description generale complete des processus d’emission susceptible d’exister dans ces structures. Dans le deuxieme chapitre, nous presentons les methodologies de caracterisation electrique mises en jeu, en insistant sur la complementarite de deux techniques d’analyse : la spectroscopie transitoire des defauts profonds et la mesure C(V). Dans le troisieme chapitre, nous etudions ces boites quantiques avec la technique C(V) pour aboutir a une analyse qualitative et quantitative des profils N(W) des echantillons. Une etude de ce profil en fonction de la temperature nous permet de determiner les types d’emission qui dominent dans nos structures. L’effet du fort dopage de la couche matrice, ainsi que la densite de boites est discute. Dans le quatrieme chapitre, une etude DLTS menee sur l’ensemble des echantillons disponibles montre plusieurs defauts relies au controle de la croissance et de la qualite des interfaces. En outre, une etude plus approfondie nous permet d’extraire la reponse electrique des boites quantiques ainsi que leurs etats electroniques s et p existants.
MODELLING EMISSIONS FROM CARS

Exhaust emissions, HC, CO and NOX are identified as being more variable than fuel consumption, and therefore more difficult to model. The causes of variability in both source and measurement are described. The emissions rates and their coefficients of variation are depicted on joint axes of power and speed which allow explanation of the terms in 5 models of the lumped parameter type. Four cars have been selected to test the models. The performance of the models in 'closed loop' tests tends to improve with increasing complexity. Generally, emissions are predicted with 2 to 5 times the errors experienced in the prediction of fuel consumption with a given level of model. For the covering abstract of the conference, see TRIS 452099. (TRRL)