bluuebunny/crossref_metadata_2025 huggingface dataset:
Antigen‐driven PD‐1+TOX+BHLHE40+ and PD‐1+TOX+EOMES+ T lymphocytes regulate juvenile idiopathic arthritis in situ
Authors: Maschmeyer Patrick , Heinz Gitta Anne , Skopnik Christopher Mark , Lutter Lisanne , Mazzoni Alessio , Heinrich Frederik , von Stuckrad Sae Lim , Wirth Lorenz Elias , Tran Cam Loan , Riedel René , Lehmann Katrin , Sakwa Imme , Cimaz Rolando , Giudici Francesco , Mall Marcus Alexander , Enghard Philipp , Vastert Bas , Chang Hyun‐Dong , Durek Pawel , Annunziato Francesco , van Wijk Femke , Radbruch Andreas , Kallinich Tilmann , Mashreghi Mir‐Farzin
Published: December 2020

T lymphocytes accumulate in inflamed tissues of patients with chronic inflammatory diseases (CIDs) and express pro‐inflammatory cytokines upon re‐stimulation in vitro. Further, a significant genetic linkage to MHC genes suggests that T lymphocytes play an important role in the pathogenesis of CIDs including juvenile idiopathic arthritis (JIA). However, the functions of T lymphocytes in established disease remain elusive. Here we dissect the transcriptional and the clonal heterogeneity of synovial T lymphocytes in JIA patients by single‐cell RNA sequencing combined with T cell receptor profiling on the same cells. We identify clonally expanded subpopulations of T lymphocytes expressing genes reflecting recent activation by antigen in situ. A PD‐1+TOX+EOMES+ population of CD4+ T lymphocytes expressed immune regulatory genes and chemoattractant genes for myeloid cells. A PD‐1+TOX+BHLHE40+ population of CD4+, and a mirror population of CD8+ T lymphocytes expressed genes driving inflammation, and genes supporting B lymphocyte activation in situ. This analysis points out that multiple types of T lymphocytes have to be targeted for therapeutic regeneration of tolerance in arthritis.
Modelling at‐level allodynia after mid‐thoracic contusion in the rat
Authors: Blumenthal Gary H. , Nandakumar Bharadwaj , Schnider Ashley K. , Detloff Megan R. , Ricard Jerome , Bethea John R. , Moxon Karen A.
Published: December 2020

Background

The rat mid‐thoracic contusion model has been used to study at‐level tactile allodynia, a common type of pain that develops after spinal cord injury (SCI). An important advantage of this model is that not all animals develop hypersensitivity. Therefore, it can be used to examine mechanisms that are strictly related to the development of pain‐like behaviour separately from mechanisms related to the injury itself. However, how to separate animals that develop hypersensitivity from those that do not is unclear.

Methods

The aims of the current study were to identify where hypersensitivity and spasticity develop and use this information to identify metrics to separate animals that develop hypersensitivity from those that do not to study differences in their behaviour. To accomplish these aims, a grid was used to localize hypersensitivity on the dorsal trunk relative to thoracic dermatomes and supraspinal responses to tactile stimulation were tallied. These supraspinal responses were used to develop a hypersensitivity score to separate animals that develop hypersensitivity, or pain‐like response to nonpainful stimuli.

Results

Similar to humans, the development of hypersensitivity could occur with the development of spasticity or hyperreflexia. Moreover, the time course and prevalence of hypersensitivity phenotypes (at‐, above‐, or below level) produced by this model were similar to that observed in humans with SCI.

Conclusion

However, the amount of spared spinal matter in the cord did not explain the development of hypersensitivity, as previously reported. This approach can be used to study the mechanisms underlying the development of hypersensitivity separately from mechanisms related to injury alone.
Understanding Deviations between Spatially Resolved and Homogenized Cathode Models of Lithium‐Ion Batteries
Authors: Schmidt Adrian , Ramani Elvedin , Carraro Thomas , Joos Jochen , Weber André , Kamlah Marc , Ivers-Tiffée Ellen
Published: December 2020

Porous electrode models are essential for inexpensively predicting the performance and lifetime of lithium‐ion batteries. Physics‐based models range from microscopic 3D models, which spatially resolve the microstructural characteristics of all phases in porous electrodes, to reduced and computationally effective models, which do not resolve the microstructure. The homogenized Newman model, also known as the pseudo‐2D (P2D) model, is well established and widely used. However, the necessary simplification shows its weaknesses, especially for high charge and discharge rates, and these lead to significant differences in comparison with the microscopic 3D model. Herein, the validity of the homogenized Newman model is investigated with respect to variations of the microstructural characteristics of a porous cathode. The effects of 1) a homogenized conductive additive; 2) non‐spherical particle geometries; and 3) overlapping particles on charge/discharge curves are analyzed. The result is a better understanding of the validity limits of P2D models. These new insights about the individual influences of the simplifications will be used to improve the homogenized model. The simulation of complex cathode structures, where several homogenization assumptions are violated, shows that the improved homogenized model reaches a very high accuracy, and, thus, overcomes the existing limitations of the P2D model approach.
Hybrid heat sinks for thermal management of passively cooled battery chargers
Authors: Sodhi Gurpreet Singh , Botting Chris , Lau Eric , Palanisamy Muthukumar , Rouhani Mina , Bahrami Majid
Published: December 2020

Battery chargers are an important component in electric and plug‐in hybrid vehicles and various other clean energy systems. The thermal management in battery charger is a crucial aspect that influences its overall performance and cyclic stability. Passive cooling technology using heat sinks is preferred in developing battery chargers due to its reliability, quietness, and efficiency (no parasitic power). In the present work, new hybrid passive heat sinks (HPHS) with various fin geometries, namely inclined interrupted fins, pin fins, and straight interrupted fins, have been developed by adding a phase change material (PCM) layer to passively cooled bare fin heat sinks (BFHS). The developed heat sinks have the same geometric footprint as that of the battery charger, IC650 built by the industrial partner of the project Delta‐Q Technologies. Experimental investigations were carried out to analyze the effects of PCM quantities and continuous (80‐120 W) and intermittent (duty cycle operation) thermal loads on the heating‐cooling performance of the HPHS. Temperature contours obtained using infrared images show that the proposed HPHS provides a more uniform temperature with reduced hot spots compared to BFHS. The heating and cooling performances of straight interrupted fins‐based HPHS were found better for all thermal loads and PCM quantities tested due to their smaller thermal resistance. Increasing the PCM volume fraction from 0.2 to 0.6 improves the load shedding capacity. However, the added thermal resistance requires optimal consideration. While conducting different cyclic operations for inclined interrupted fins‐based HPHS, a maximum overall thermal management ratio of 0.45 was achieved. The proposed HPHS minimizes the temperature fluctuations more effectively while operating at high loads and shorter duty periods. This new passively cooled hybrid heat sink can notably improve the overall performance and reliability of battery chargers during both continuous and intermittent operations.
Comparing single‐phase, non‐Newtonian approaches with experimental results: Validating flume‐scale mud and debris flow in HEC‐RAS
Authors: Gibson S. , Floyd I. , Sánchez A. , Heath R.
Published: December 2020

Post‐fire debris flows and tailing impoundment failures destroy lives and property. These geologic hazards – and other similar processes – fall on a continuum between classic Newtonian flood analyses and geotechnical stability analyses. The US Army Corps of Engineers (USACE) is developing a non‐Newtonian library (DebrisLib) that includes a suite of rheological and clastic approaches to hyper‐concentrated, mudflow and debris flow dynamics. The Hydrologic Engineering Center (HEC) has implemented these non‐Newtonian methods into the widely used, public‐domain open‐channel hydraulics and morphodynamic software, HEC‐RAS (river analysis system). This work presents part of the verification and validation of these non‐Newtonian approaches, applying several rheological equations to published laboratory results high‐concentration flume experiments.

This study tested the linear Bingham model as well as the turbulent and Bagnold quadratic terms of the O'Brien equation. HEC‐RAS also includes the non‐linear Herschel–Bulkley (HB) approach, which quantifies shear‐thickening or shear‐thinning processes. The study used these non‐Newtonian models in HEC‐RAS to simulate 10 of Parsons et al.’s (2001) flume experiments, which measured the snout and plug velocity of fluids with high solid concentrations (Cv = 68–74%) and a broad range of material gradations (d50 = 0.05–1 mm, d15 = 0.006–0.1 mm). The experiments also measured and back‐calculated Bingham and HB parameters of the materials, finding HB powers between 0.45 and 1.25 (i.e. fluids that are dilatant, pseudo‐plastic and visco‐plastic).

The rheological models incorporated into DebrisLib and implemented in HEC‐RAS reproduce experimental data well for most experiments. The Bingham model generated a plug velocity root‐mean‐square error (RMSE) of 0.21 m/s using standard flow parameters and Parsons et al.’s calibrated parameters, a substantial improvement over the unmodified shallow water flow equations (RMSE 0.77 m/s). Experiments with strong snout effects tended to generate higher residuals, especially in the snout velocity. The RMSE associated with the O'Brien equation was larger with the Parsons et al. fit parameters, but similar (0.23 m/s) with measured parameters. The turbulent parameter was the largest (often the dominant) parameter in most O'Brien simulations, with the dispersive stress only proving significant for the coarsest material. DebrisLib had to use a modified version of the dispersive term to simulate these concentrations. Both the 2D depth‐averaged shallow water equation (SWE) and diffusion wave equation were used to simulate the experiments. The best results were obtained with the SWE with horizontal mixing.
Stable isotope dynamics of groundwater interactions with Ganges river
Authors: Das Prerona , Mukherjee Abhijit , Hussain Syed Aaquib , Jamal Md. Shahid , Das Kousik , Shaw Ashok , Layek Mrinal K. , Sengupta Probal
Published: December 2020

Groundwater depletion has been an emerging crisis in recent years, especially in highly urbanized areas as a result of unregulated exploitation, thus leaving behind an insufficient volume of usable freshwater. Presently Ganges river basin, the sixth largest prolific fluvial system and sustaining a huge population in South Asia, is witnessed to face (i) aquifer vulnerability through surface waterborne pollutant and (ii) groundwater stress due to summer drying of river as a result of indiscriminate groundwater abstraction. The present study focuses on a detailed sub‐hourly to seasonally varying interaction study and flux quantification between river Ganges and groundwater in the Indian subcontinent which is one of the first documentations done on a drying perennial river system that feeds an enormous population. Contributing parameters to the total discharge of a river at its middle course on both temporal and spatial scale is estimated through three‐component hydrograph separation and end‐member mixing analysis using high‐resolution water isotope (δ18O and δ2H) and electrical conductivity data. Results from this model report groundwater discharge in river to be the highest in pre‐monsoon, that is, 30%, whereas, during post‐monsoon the contribution lowers to 25%; on the contrary, during peak monsoon, the flow direction reverses thus recharging the groundwater which is also justified using annual piezometric hydrographs of both river water and groundwater. River water‐groundwater interaction also shows quantitative variability depending on river morphometry. The current study also provides insight on aquifer vulnerability as a result of pollutant mixing through interaction and plausible attempts towards groundwater management. The present study is one of the first in South Asian countries that provides temporally and spatially variable detailed quantification of baseflow and estimates contributing parameters to the river for a drying mega fluvial system.
Angular optimization for cancer identification with circularly polarized light
Authors: Nishizawa Nozomi , Al‐Qadi Bassam , Kuchimaru Takahiro
Published: December 2020

Depolarization of circularly polarized light scattered from biological tissues depends on structural changes in cell nuclei, which can provide valuable information for differentiating cancer tissues concealed in healthy tissues. In this study, we experimentally verified the possibility of cancer identification using scattering of circularly polarized light. We investigated the polarization of light scattered from a sliced biological tissue with various optical configurations. A significant difference between circular polarizations of light scattered from cancerous and healthy tissues is observed, which is sufficient to distinguish a cancerous region. The line‐scanning experiments along a region incorporating healthy and cancerous parts indicate step‐like behaviors in the degree of circular polarization corresponding to the state of tissues, whether cancerous or normal. An oblique and perpendicular incidence induces different resolutions for identifying cancerous tissues, which indicates that the optical arrangement can be selected according to the priority of resolution.
A representation learning approach for recovering scatter‐corrected spectra from Fourier‐transform infrared spectra of tissue samples
Authors: Raulf Arne P. , Butke Joshua , Menzen Lukas , Küpper Claus , Großerueschkamp Frederik , Gerwert Klaus , Mosig Axel
Published: December 2020

Infrared spectra obtained from cell or tissue specimen have commonly been observed to involve a significant degree of scattering effects, often Mie scattering, which probably overshadows biochemically relevant spectral information by a nonlinear, nonadditive spectral component in Fourier transform infrared (FTIR) spectroscopic measurements. Correspondingly, many successful machine learning approaches for FTIR spectra have relied on preprocessing procedures that computationally remove the scattering components from an infrared spectrum. We propose an approach to approximate this complex preprocessing function using deep neural networks. As we demonstrate, the resulting model is not just several orders of magnitudes faster, which is important for real‐time clinical applications, but also generalizes strongly across different tissue types. Using Bayesian machine learning approaches, our approach unveils model uncertainty that coincides with a band shift in the amide I region that occurs when scattering is removed computationally based on an established physical model. Furthermore, our proposed method overcomes the trade‐off between computation time and the corrected spectrum being biased towards an artificial reference spectrum.
The Effect of an Exercise Intervention Program on Bone Health After Bariatric Surgery: A Randomized Controlled Trial
Authors: Diniz-Sousa Florêncio , Veras Lucas , Boppre Giorjines , Sa-Couto Pedro , Devezas Vítor , Santos-Sousa Hugo , Preto John , Vilas-Boas João Paulo , Machado Leandro , Oliveira José , Fonseca Hélder
Published: December 2020

Exercise has been suggested as a therapeutic approach to attenuate bone loss induced by bariatric surgery (BS), but its effectiveness remains unclear. Our aim was to determine if an exercise-training program could induce benefits on bone mass after BS. Eighty-four patients, submitted to gastric bypass or sleeve gastrectomy, were randomized to either exercise (EG) or control group (CG). One month post-BS, EG underwent a 11-month supervised multicomponent exercise program, while CG received only standard medical care. Patients were assessed before BS and at 1, 6, and 12 months post-BS for body composition, areal bone mineral density (BMD), bone turnover markers, calciotropic hormones, sclerostin, bone material strength index, muscle strength, and daily physical activity. A primary analysis was conducted according to intention-to-treat principles and the primary outcome was the between-group difference on lumbar spine BMD at 12 months post-BS. A secondary analysis was also performed to analyze if the exercise effect depended on training attendance. Twelve months post-BS, primary analysis results revealed that EG had a higher BMD at lumbar spine (+0.024 g∙cm−2 [95% confidence interval (CI) 0.004, 0.044]; p = .015) compared with CG. Among total hip, femoral neck, and 1/3 radius secondary outcomes, only 1/3 radius BMD improved in EG compared with CG (+0.013 g∙cm−2 [95% CI 0.003, 0.023]; p = .020). No significant exercise effects were observed on bone biochemical markers or bone material strength index. EG also had a higher lean mass (+1.5 kg [95% CI 0.1, 2.9]; p = .037) and higher number of high impacts (+51.4 [95% CI 6.6, 96.1]; p = .026) compared with CG. In addition, secondary analysis results suggest that exercise-induced benefits may be obtained on femoral neck BMD but only on those participants with ≥50% exercise attendance compared with CG (+5.3% [95% CI 2.0, 8.6]; p = .006). Our findings suggest that an exercise program is an effective strategy to ameliorate bone health in post-BS patients. © 2020 American Society for Bone and Mineral Research (ASBMR).
Presence and severity of suicidal thoughts and behaviors across the eating disorder diagnostic spectrum: A pilot study
Authors: Duffy Mary E. , Siegfried Nicole , Bass Garrett , Joiner Thomas E.
Published: December 2020

Objectives

There is a dearth of research on suicidal thoughts and behaviors among eating disorder patients diagnosed with binge eating disorder (BED) or other specified feeding or eating disorder (OSFED). This pilot study evaluated presence and severity of suicidal thoughts and behaviors by eating disorder diagnosis in a transdiagnostic clinical eating disorder sample.

Methods

Participants were individuals (N = 257; 91.1% female; 94.6% Caucasian) currently receiving eating disorder treatment for anorexia nervosa (AN), bulimia nervosa (BN), BED, or OSFED. Participants completed online measures of variables.

Results

Lifetime and current presence and severity of suicidal ideation and suicide attempts were statistically similar among diagnostic groups.

Conclusion

Though largely overlooked, treatment‐utilizing individuals with BED and OSFED may experience elevated rates and severity of suicidal thoughts and behaviors, like those with AN and BN. Attention to suicide‐related risk assessment and management is needed when treating individuals with eating disorders, regardless of diagnosis.
Social participation and posttraumatic growth: The serial mediation of hope, social support, and reappraisal
Authors: Laslo‐Roth Roni , George‐Levi Sivan , Margalit Malka
Published: December 2020

In light of the global crisis created by the outbreak of the coronavirus and the disease it causes, coronavirus disease 2019, the goal of the study was to detect factors that might enhance people's ability to experience positive psychological change during traumatic events. As such, this study examined the relationship between social participation and posttraumatic growth (PTG) during the coronavirus outbreak and tested the mediating role of hope, social support, and cognitive reappraisal in explaining this relationship. The sample consisted of 275 participants (21.8% male, and 78.2% female, with an average age of 33.42,SD = 13.63), subjected to social‐distancing regulations during this period. Results demonstrated a serial mediation model in which social participation predicted PTG directly and indirectly through hope (pathways and agency), social support, and cognitive reappraisal. The importance of social participation in nourishing personal resources and practical implications including the need for prevention programs are discussed.
Validation of sonographic assistance for placement of a nasogastric tube in pediatric patients
Authors: Choi Edward , Korostensky Michael , Walker Andrew , Spencer Adam
Published: December 2020

Purpose

Enteral access via nasogastric tube (NGT) placement can be essential in the provision of care in pediatric patients. Methods exist to confirm correct placement with success rates between 80% and 85%. Radiographic confirmation remains the “gold‐standard,” however; it exposes patients to ionizing radiation and fails to provide “real‐time” information. In this study, we determined the feasibility of using sonography to assist in the placement of NGT insertions in pediatric patients that have difficulty cooperating.

Methods

Thirty patients requiring NGT placement were stratified into three age groups. Upon NGT insertion, transverse and longitudinal ultrasound images were acquired to visualize tube progression through the esophagus. Subsequently, a focused ultrasonographic exam of the gastric antrum and body were performed. If amenable, an air bolus (1 mL/kg) was injected in the stomach if the NGT was not directly visualized. Following intubation, standard guidelines for NGT position confirmation were performed.

Results

The NGT was visualized in all esophageal views and 52% of gastric views. Subgroup analysis showed that successful visualization of tube placement in the stomach ranged from 40% (7‐18 years) to 70% (3‐6 years). Eighty percentage of air boluses injected were visualized.

Conclusion

The use of ultrasonography may assist NGT placement in pediatric patients and reduce the incidence of suboptimal placement during insertion. We demonstrated successful NGT visualization through the esophagus regardless of age. NGT visualization in the stomach was challenging; however, injection of an air bolus may improve visualization. Further studies are required to improve the success rate of obtaining gastric views of the NGT.
Linking personal and professional social responsibility development to microethics and macroethics: Observations from early undergraduate education
Authors: Schiff Daniel S. , Logevall Emma , Borenstein Jason , Newstetter Wendy , Potts Colin , Zegura Ellen
Published: December 2020

Background

Developing social responsibility attitudes in future engineers and computer scientists is of critical and rising importance. Yet research shows that prosocial attitudes decline during undergraduate engineering education.

Purpose

Influenced by the Professional Social Responsibility Development Model (PSRDM), this study explores the connection between undergraduate personal social responsibility attitudes and the development of professional social responsibility attitudes. We consider a wide range of college and precollege influences and inhibitors.

Design/Method

We conducted and analyzed 21 semistructured interviews of second‐year undergraduates, predominantly in engineering and computer science. The interviews form the first collection of qualitative data for a multiyear mixed methods study which has followed a cohort of students since they entered college.

Results

We find preliminary evidence that social responsibility attitudes tend to be conceptually separated for early undergraduates along two lines: personal and professional considerations, and microlevel and macrolevel concerns. This leads some students to assume that social responsibility obligations can be considered as a weekend project, may fall into place later in one's career, and can generally be deprioritized compared to technical education and career pursuits. Candidate explanations for this divide include early influences from parents, religious values, collegiate social interaction, students' limited familiarity with their future profession, and a social/technical divide and meritocratic ideology in engineering culture.

Conclusions

This study provides qualitative evidence to advance the conceptual understanding of professional social responsibility development. The findings highlight key individual and institutional influences and barriers for scholars and practitioners interested in nurturing prosocial attitudes among engineering students.
Soil properties limiting vegetation establishment along roadsides
Authors: Mills Shad D. , Mamo Martha , Ruis Sabrina J. , Blanco‐Canqui Humberto , Schacht Walter H. , Awada Tala , Li Xu , Sutton Pamela
Published: December 2020

Roadside vegetation provides a multitude of ecosystem services, including pollutant remediation, runoff reduction, wildlife habitat, and aesthetic scenery. Establishment of permanent vegetation along paved roads after construction can be challenging, particularly within 1 m of the pavement. Adverse soil conditions could be one of the leading factors limiting roadside vegetation growth. In this study, we assessed soil physical and chemical properties along a transect perpendicular to the road at six microtopographic positions (road edge, shoulder, side slope, ditch, backslope, and field edge) along two highway segments near Beaver Crossing and Sargent, NE. At the Beaver Crossing site, Na concentration was 81 times, exchangeable Na 66 times, and cone index (compaction parameter) six times higher at the road‐edge position (closest to the paved road and with sparse vegetation) compared to positions with abundant vegetation (ditch or field edge). At the Sargent site, Na concentration was 111 times, exchangeable Na 213 times, and cone index up to two times higher at the road‐edge position compared with ditch or field‐edge positions. Likewise, electrical conductivity was higher and macroaggregation and water infiltration were lower at the road edge than at the ditch or field‐edge positions. Soil properties improved with increasing distance from the road. Exchangeable Na percentage and cone index at the road‐edge position exceeded threshold levels for the growth of sensitive plants. Thus, high Na concentration and increased compaction at the road edge appear to be the leading soil properties limiting vegetation establishment along Nebraska highways.
Extracellular vesicles: Natural liver‐accumulating drug delivery vehicles for the treatment of liver diseases
Authors: Zhang Gensheng , Huang Xiaofang , Xiu Huiqing , Sun Yan , Chen Jiming , Cheng Guoping , Song Zhengbo , Peng Yanmei , Shen Yingying , Wang Jianli , Cai Zhijian
Published: December 2020

Extracellular vesicles (EVs) are excellent potential vectors for the delivery of therapeutic drugs. However, issues with biological safety and disease targeting substantially limit their clinical application. EVs from red blood cells (RBC‐EVs) are potential drug delivery vehicles because of their unique biological safety. Here, we demonstrated that EVs, including RBC‐EVs, show natural liver accumulation. Mechanistically, the liver environment induces macrophages to phagocytize RBC‐EVs in a C1q‐dependent manner. RBC‐EVs loaded with antisense oligonucleotides of microRNA‐155 showed macrophage‐dependent protective effects against acute liver failure (ALF) in a mouse model. These RBC‐EVs were also effective in treatment of ALF. Furthermore, compared to routine doses of doxorubicin and sorafenib (SRF), RBC‐EVs loaded with doxorubicin or SRF showed enhanced therapeutic effects on a murine model of orthotopic liver cancer through a mechanism dependent on macrophages. Importantly, drug‐loaded RBC‐EVs showed no systemic toxicity at therapeutically effective doses, whereas routine doses of doxorubicin and SRF showed obvious toxicity. Thus, drug‐loaded RBC‐EVs hold high potential for clinical applications in the treatment of liver disease therapy.
Association of CLU gene polymorphism with Parkinson's disease in the Chinese Han population
Authors: Lin Yuwan , Lu Lin , Zhou Miaomiao , Liu HanQun , Ye Panghai , Zhang Wenlong , Qiu Jiewen , Zhang Zhiling , Yang Xinling , Ding Liuyan , Guo Wenyuan , Mo Mingshu , Zhu Xiaoqin , Zhang Xiaokang , Chen Xiang , Xu Pingyi
Published: December 2020

Background

Clusterin (CLU) plays important role in the pathology of neurodegenerative disorders. Recently, a genetic variant of CLU rs9331896 has been reported as a risk estimate for Alzheimer’s disease (AD). However, the association between this variant and the risk of Parkinson's disease (PD) in the Chinese Han population remains elusive.

Methods

We sequenced CLU rs9331896 in 353 PD patients and 326 healthy‐matched individuals of the Chinese Han population. The genotypes of rs9331896 were analyzed using MassArray (Agena Bioscience, San Diego, CA, USA) in accordance with the manufacturer’s instructions. The distribution of genotypes and allelic frequencies was analyzed by a chi‐squared test. Additionally, the expression of CLU protein in plasma was evaluated by an enzyme‐linked immunosorbent assay and analysed with a t‐test.

Results

The TT genotype in rs9331896 in a recessive model was found to be associated with the increased risk of PD (odds ratio = 1.408, 95% confidence interval = 1.034–1.916, p = 0.029). Subgroup analysis indicated that TT genotype carriers showed a significantly higher risk in male PD patients compared to male healthy controls (odds ratio = 1.611, 95% confidence interval = 1.046–2.483, p = 0.030). In addition, CLU levels in the plasma of PD patients were significantly higher than controls (p = 0.024).

Conclusions

The CLU‐rs9331896‐TT genotype was a risk factor for PD, particularly in males. PD patients also expressed a high level of CLU in plasma.
Long‐term disease course of two patients with multiple sulfatase deficiency differs from metachromatic leukodystrophy in a broad cohort
Authors: Beck‐Wödl Stefanie , Kehrer Christiane , Harzer Klaus , Haack Tobias B. , Bürger Friederike , Haas Dorothea , Rieß Angelika , Groeschel Samuel , Krägeloh‐Mann Ingeborg , Böhringer Judith
Published: December 2020

Multiple sulfatase deficiency (MSD) is a lysosomal storage disease caused by a deficiency of formylglycine‐generating enzyme due to SUMF1 defects. MSD may be misdiagnosed as metachromatic leukodystrophy (MLD), as neurological and neuroimaging findings are similar, and arylsulfatase A (ARSA) deficiency and enhanced urinary sulfatide excretion may also occur. While ARSA deficiency seems a cause for neurological symptoms and later neurodegenerative disease course, deficiency of other sulfatases results in clinical features such as dysmorphism, dysostosis, or ichthyosis. We report on a girl and a boy of the same origin presenting with severe ARSA deficiency and neurological and neuroimaging features compatible with MLD. However, exome sequencing revealed not yet described homozygosity of the missense variant c.529G > C, p.Ala177Pro in SUMF1. We asked whether dynamics of disease course differs between MSD and MLD. Comparison to a cohort of 59 MLD patients revealed different disease course concerning onset and disease progression in both MSD patients. The MSD patients showed first gross motor symptoms earlier than most patients with juvenile MLD (<10th percentile of Gross‐Motor‐Function in MLD [GMFC‐MLD] 1). However, subsequent motor decline was more protracted (75th and 90th percentile of GMFC‐MLD 2 (loss of independent walking) and 75th percentile of GMFC‐MLD 5 (loss of any locomotion)). Language decline started clearly after 50th percentile of juvenile MLD and progressed rapidly. Thus, dynamics of disease course may be a further clue for the characterization of MSD. These data may contribute to knowledge of natural course of ultra‐rare MSD and be relevant for counseling and therapy.
Relationship between altered knee kinematics and subchondral bone remodeling in a clinically translational model of ACL injury
Authors: White McKenzie S. , Brancati Ross J. , Lepley Lindsey K.
Published: December 2020

Abnormal joint kinematics are commonly reported in the acute and chronic stages of recovery after anterior cruciate ligament (ACL) injury and have long been mechanistically implicated as a primary driver in the development of posttraumatic osteoarthritis (PTOA). Though strongly theorized, it is unclear to what extent biomechanical adaptations after ACL injury culminate in the development of PTOA, as data that directly connects these factors does not exist. Using a preclinical, noninvasive ACL injury rodent model, our objective was to explore the direct effect of an isolated ACL injury on joint kinematics and the pathogenetic mechanisms involved in the development of PTOA. A total of 32, 16‐week‐old Long‐Evans rats were exposed to a noninvasive ACL injury. Marker‐less deep learning software (DeepLabCut) was used to track animal movement for sagittal‐plane kinematic analyses and micro computed tomography was used to evaluate subchondral bone architecture at days 7, 14, 28, and 56 following injury. There was a significant decrease in peak knee flexion during walking (p < .05), which had a moderate‐to‐strong negative correlation (r = −.59 to −.71; p < .001) with subchondral bone plate porosity in all load bearing regions of the femur and tibia. Additional comprehensive analyses of knee flexion profiles revealed dramatic alterations throughout the step cycle. This occurred alongside considerable loss of epiphyseal trabecular bone and substantial changes in anatomical orientation. Knee flexion angle and subchondral bone microarchitecture are severely impacted after ACL injury. Reductions in peak knee flexion angle after ACL injury are directly associated with subchondral bone plate remodeling.
Pelvis weight‐bearing ability after minimally invasive stabilizations for periacetabular lesion
Authors: Lea William B. , Tutton Sean M. , Alsaikhan Naif , Neilson John C. , Schafer Sebastian , King David M. , Wang Mei
Published: December 2020

Periacetabular metastatic lesions cause debilitating weight‐bearing pain and pose a risk of pelvic pathologic fracture. Minimally invasive percutaneous stabilization is an alternative palliative therapy over extensive open reconstructive surgeries. This study aimed to investigate the biomechanical behaviors of three distinct techniques of percutaneous periacetabular stabilization. A total of 20 composite hemipelves custom‐made to contain Harrington type III periacetabular lesion based on a patient's computed tomograpy scans were assigned to treatment groups of cementoplasty alone using polymethyl methacrylate (Cement), screw fixation alone using ischial and posterior‐to‐anterior screws (Screws), cement‐augmented screws (Screws&Cement), and a control group (Untreated). All hemipelves were loaded in a mechanical test configuration mimicking a single‐legged stance, and failure load, failure deformation, and construct stiffness were determined. In the experiments, Screws&Cement demonstrated the highest yield strength (4711 ± 362 N) and was 12% higher than Cement (4005 ± 304 N, p = 0.019), 125% higher than Screws (2097 ± 359 N, p < 0.0001), and 184% higher than Untreated (1658 ± 254 N, p < 0.0001). No significant difference in yield strength was found between Screws and Untreated. Screws&Cement also demonstrated the highest stiffness (1013 ± 92 N/mm), followed by Cement (893 ± 49 N/mm), and both groups were significantly stiffer than Screws (543 ± 114 N/mm, p < 0.0001) and Untreated (580 ± 91 N/mm, p < 0.0001 for Screws&Cement, and p = 0.0003 for Cement). This study demonstrated that a cement‐augmented periacetabular reconstruction is an effective option for percutaneous treatment of Harrington III periacetabular metastatic lesion. The addition of pelvic screws over cementoplasty significantly improved the pelvis load‐bearing strength. When large periacetabular lesions are present, augmented screw fixation appears to be the superior choice of treatment.
Diflunisal‐loaded poly(propylene sulfide) nanoparticles decrease S. aureus‐mediated bone destruction during osteomyelitis
Authors: Ford Caleb A. , Spoonmore Thomas J. , Gupta Mukesh K. , Duvall Craig L. , Guelcher Scott A. , Cassat James E.
Published: December 2020

Osteomyelitis is a debilitating infection of bone that results in substantial morbidity. Staphylococcus aureus is the most commonly isolated pathogen causing bone infections and features an arsenal of virulence factors that contribute to bone destruction and counteract immune responses. We previously demonstrated that diflunisal, a nonsteroidal anti‐inflammatory drug, decreases S. aureus‐induced bone destruction during osteomyelitis when delivered locally from a resorbable drug delivery depot. However, local diflunisal therapy was complicated by bacterial colonization of the depot's surface, highlighting a common pitfall of devices for local drug delivery to infected tissue. It is, therefore, critical to develop an alternative drug delivery method for diflunisal to successfully repurpose this drug as an antivirulence therapy for osteomyelitis. We hypothesized that a nanoparticle‐based parenteral delivery strategy would provide a method for delivering diflunisal to infected tissue while circumventing the complications associated with local delivery. In this study, we demonstrate that poly(propylene sulfide) (PPS) nanoparticles accumulate at the infectious focus in a murine model of staphylococcal osteomyelitis and are capable of efficaciously delivering diflunisal to infected bone. Moreover, diflunisal‐loaded PPS nanoparticles effectively decrease S. aureus‐mediated bone destruction, establishing the feasibility of systemic delivery of an antivirulence compound to mitigate bone pathology during osteomyelitis.
Comparison of wearable sensor to traditional methods in functional outcome measures: A systematic review
Authors: Follis Shawna , Chen Zhao , Mishra Sachin , Howe Carol L. , Toosizadeh Nima , Dohm Michael
Published: December 2020

Traditional methods of collecting functional outcome measures are widely used for lower extremity arthroplasty outcome assessment. Wearable sensors are emerging as viable tools for functional outcome measures in monitoring of postarthroplasty recovery. The objective of this review was to compare the efficacy of wearable sensors with traditional methods for monitoring postarthroplasty functional recovery. Articles were searched for inclusion in this review that used both traditional and wearable sensor functional outcome measures to assess lower extremity function before and after lower extremity arthroplasty. Two independent screeners reviewed all articles, and resolved differences through consensus and consultation with the senior author. Studies that met inclusion criteria were evaluated for methodologic quality using performed risk of bias assessments. Results from several traditional and wearable sensor functional outcome measures from baseline through follow‐up were normalized across studies. Fourteen articles met the inclusion criteria. Six studies used statistical methods to directly compare functional outcome measures and eight studies used qualitative description of comparisons. This review found evidence that wearable sensors detected nuanced functional outcome information on the specific biomechanics and timing of recovery, which were unaccounted for using traditional methods. Wearable sensors have shown promising utility in providing additional recovery information from lower extremity arthroplasty compared with traditional functional outcome measures, but future research is needed to assess the clinical significance of this additional information. Wearable sensor technology is an emerging clinical tool providing advanced and determinative data with the potential for advancing the assessment of lower extremity arthroplasty outcomes.
Use of a High‐Protein Enteral Nutrition Formula to Increase Protein Delivery to Critically Ill Patients: A Randomized, Blinded, Parallel‐Group, Feasibility Trial
Authors: Chapple Lee‐anne S. , Summers Matthew J. , Bellomo Rinaldo , Chapman Marianne J. , Davies Andrew R. , Ferrie Suzie , Finnis Mark E. , Hurford Sally , Lange Kylie , Little Lorraine , O'Connor Stephanie N. , Peake Sandra L. , Ridley Emma J. , Young Paul J. , Williams Patricia J. , Deane Adam M. ,   for the TARGET Investigator Collaborative and the ANZICS Clinical Trials Group
Published: December 2020

Background

International guidelines recommend critically ill adults receive more protein than most receive. We aimed to establish the feasibility of a trial to evaluate whether feeding protein to international recommendations would improve outcomes, in which 1 group received protein doses representative of international guideline recommendations (high protein) and the other received doses similar to usual practice.

Methods

We conducted a prospective, randomized, blinded, parallel‐group, feasibility trial across 6 intensive care units. Critically ill, mechanically ventilated adults expected to receive enteral nutrition (EN) for ≥2 days were randomized to receive EN containing 63 or 100 g/L protein for ≤28 days. Data are mean (SD) or median (interquartile range).

Results

The recruitment rate was 0.35 (0.13) patients per day, with 120 patients randomized and data available for 116 (n = 58 per group). Protein delivery was greater in the high‐protein group (1.52 [0.52] vs 0.99 [0.27] grams of protein per kilogram of ideal body weight per day; difference, 0.53 [95% CI, 0.38–0.69] g/kg/d protein), with no difference in energy delivery (difference, −26 [95% CI, −190 to 137] kcal/kg/d). There were no between‐group differences in the duration of feeding (8.7 [7.3] vs 8.1 [6.3] days), and blinding of the intervention was confirmed. There were no differences in clinical outcomes, including 90‐day mortality (14/55 [26%] vs 15/56 [27%]; risk difference, −1.3% [95% CI, −17.7% to 15.0%]).

Conclusion

Conducting a multicenter blinded trial is feasible to compare protein delivery at international guideline–recommended levels with doses similar to usual care during critical illness.
Surface, Micellar, and Aggregation Behavior of Non‐cytotoxic Imidazolium Gemini Surfactants
Authors: Shaheen Arifa , Mir Ab Waheed , Arif Rabia , Bala Ritu
Published: December 2020

The micellar, surface, and aggregation properties of biocompatible, imidazolium‐based hydroxyl group‐containing gemini surfactants, 1,1′‐(propane‐1,3‐diyl‐2‐ol) bis(3‐alkyl‐1H‐imidazol‐3‐ium)bromide, [CnIm‐3OH‐ImCn]Br2, were studied. The surface parameters like maximum surface excess concentration at air/water interface (Γmax), the minimum surface area occupied by surfactant molecules (Amin) and the related thermodynamic parameters such as, standard Gibbs free energy of micellization (), standard free energy of adsorption (), and free energy of surface at equilibrium ) were also determined from the surface parameters. The aggregation behavior has been elucidated from transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques which showed that these gemini surfactants have potential self‐aggregation efficiency. Besides, some other physicochemical properties like foam stability, emulsifying power, and viscosity have been determined. The structural features of [CnIm‐3OH‐ImCn]Br2 enhance their surface‐active properties. These features of gemini surfactants are of primary significance from pharmaceutical and biomedical viewpoints. The gemini surfactants may have great implications in drug formulations and delivery owing to their prominent aggregation and non‐cytotoxic nature.
Evaluation of the Braden scale in predicting surgical outcomes in older patients undergoing major head and neck surgery
Authors: Grewal Rajan , Sklar Michael C. , de Almeida John R , Xu Wei , Su Jie , Thomas Carissa M. , Alibhai Shabbir M.H. , Goldstein David P
Published: December 2020

Background

Being able to predict negative postoperative outcomes is important for helping select patients for treatment as well for informed decision‐making by patients. Frailty measures are often time and resource intensive to use as screening measures, whereas the Braden scale, a commonly used measure to assess patients at risk of developing pressure ulcers after surgery, may be a potential tool to predict postoperative complication rates and longer length of stay (LOS) in patients undergoing major head and neck cancer surgery.

Methods

A retrospective analysis of Braden scale scores was performed on a prospectively collected cohort of patients undergoing major head and neck surgery recruited between December 2011 and April 2014. The association of Braden scale score with the primary outcomes of complications and LOS was analyzed using logistic regression and linear regression models on univariate analysis (UVA), respectively. Multivariate analysis (MVA) was performed based on a backward stepwise selection algorithm.

Results

There were 232 patients with a mean (SD) Braden scale score of 14.9 (2.8) with a range from 9 to 23. The Braden scale (β = −.07 per point; 95% CI −0.09, −0.04, P < .001) was an independent predictor of increased LOS on UVA, but not on MVA when adjusted for other variables. For overall complications, as well as type of complication, the Braden scale score was not a significant predictor of complications on either UVA or MVA.

Conclusion

In the sample population, the Braden scale did not demonstrate an ability to predict negative outcomes in head and neck surgery patients.

Level of Evidence

Level 2b individual cohort study.
Vital rates of small reef corals are associated with variation in climate
Authors: Edmunds Peter J.
Published: December 2020

With coral cover declining on most tropical reefs, efforts are intensifying to understand the mechanisms by which environmental stressors are driving populations into demographic deficit. Here, the population dynamics of sexual cohorts of small corals (≤ 4 cm diameter) in St. John, US Virgin Islands were used to test the hypothesis that the association of vital rates with environmental conditions has changed over 22 yr. The annual fate of 3999 corals at six sites and 7–9 m depth were used to populate Leslie Matrices and calculate assemblage growth rates (λ, without recruitment), mortality of the smallest corals, and graduation from the largest size class. Vital rates were tested for associations with temperature, the number of days with seawater warmer than 29.4°C (i.e., hot days), and rainfall. Transition probabilities varied among years, and usually more corals remained in their original size class than moved among size classes. Corals in the smallest size class had the highest mortality rate (42% yr−1), λ had a grand mean of 0.688, and there were trends for λ to vary with the number of hot days and rainfall through quadratic relationships. The linear dependence of λ on rainfall over consecutive 3‐yr periods declined over two decades, suggesting that this colony size‐defined coral assemblage has undergone phenotypic change in their responsiveness to varying environmental conditions.
Corrosion of structural constituents of 2017 aluminium alloy in acidic solutions containing inhibitors
Authors: Kwolek Przemysław , Mrówka‐Nowotnik Grażyna , Wytrwal‐Sarna Magdalena
Published: December 2020

The objective of this study is to establish the corrosion behaviour of the most important structural constituents of the aluminium alloy 2017 in orthophosphoric acid solutions containing heteropolyoxomolybdate, tungstate and vanadate. These are potential candidates for replacing toxic hexavalent chromium species in stripping solution for anodic coatings. The corrosion rate of the alloy is estimated with linear polarisation method. It decreases from 0.58 mA cm−2 in uninhibited solution to 0.10 mA cm−2 in a solution containing heteropolyoxomolybdate species. Microscopic studies reveal that heteropolyoxomolybdate species inhibit corrosion of the matrix and intermetallic Al15(Fe,Mn)3(Si,Cu)2 but not Mg2Si. Intermetallic Al2Cu remains not corroded. Heteropolyoxotungstate species virtually do not inhibit the corrosion of the alloy. The solution containing vanadium species is not stable with time and the corrosion rate is not determined. Nevertheless, corrosion of the matrix is inhibited, but intermetallics Al15(Fe,Mn)3(Si,Cu)2 together with Mg2Si are dissolved. X‐ray photoelectron spectroscopy is used for examination of a corrosion product precipitated on the surface.