bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between NMR metabolomic signatures of healthy lifestyle and incident coronary artery disease
Authors: Fu Zuqiang , Liu Qian , Liang Jingjia , Weng Zhenkun , Li Wenxiang , Xu Jin , Zhang Xin , Xu Cheng , Gu Aihua
Published: November 2022

Aims

To identify metabolites associated with a healthy lifestyle and explore the possible mechanisms of lifestyle in coronary artery disease (CAD).

Methods and results

The nuclear magnetic resonance metabolomics platform was applied to perform metabolomic profiling of baseline plasma samples from a randomly selected subset of 121 733 UK Biobank participants. Cox proportional hazards models with covariate adjustments were used to investigate the associations between validated lifestyle-associated metabolites and incident CAD and to estimate the accuracy of the inclusion of metabolites to predict CAD compared with traditional prediction models. The discriminatory ability of each model was evaluated using Harrell’s C statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (NRI) indexes. During a median of 8.6 years of follow-up, 5513 incident CAD cases were documented. Among the 111 lifestyle-associated metabolites, 65 were significantly associated with incident CAD after multivariate adjustment (Bonferroni P < 3.11 × 10−04). The addition of these metabolites to classic risk prediction models [Framingham Risk Score (FRS) using lipids; FRS using body mass index] improved CAD prediction accuracy as assessed by the C statistic (increasing to 0.739 [95% CI, 0.731–0.747] and 0.752 [95% CI, 0.746–0.758]), respectively; continuous NRI (0.274 [0.227–0.325] and 0.266 [0.223–0.317]) and IDI (0.003 [0.002–0.004] and 0.003 [0.002–0.004]).

Conclusion

Healthy lifestyle-associated metabolites are associated with the incidence of CAD and may help improve the prediction of CAD risk. The use of metabolite information combined with the FRS model warrants further investigation before clinical implementation.
Slowing Heart Rate Protects Against Pathological Cardiac Hypertrophy
Authors: Sebastian Sonia , Weinstein Lee S , Ludwig Andreas , Munroe Patricia , Tinker Andrew
Published: November 2022

We aimed to determine the pathophysiological impact of heart rate (HR) slowing on cardiac function. We have recently developed a murine model in which it is possible to conditionally delete the stimulatory heterotrimeric G-protein (Gαs) in the sinoatrial (SA) node after the addition of tamoxifen using cre-loxP technology. The addition of tamoxifen leads to bradycardia. We used this approach to examine the physiological and pathophysiological effects of HR slowing. We first looked at the impact on exercise performance by running the mice on a treadmill. After the addition of tamoxifen, mice with conditional deletion of Gαs in the SA node ran a shorter distance at a slower speed. Littermate controls preserved their exercise capacity after tamoxifen. Results consistent with impaired cardiac capacity in the mutants were also obtained with a dobutamine echocardiographic stress test. We then examined if HR reduction influenced pathological cardiac hypertrophy using two models: ligation of the left anterior descending coronary artery for myocardial infarction and abdominal aortic banding for hypertensive heart disease. In littermate controls, both procedures resulted in cardiac hypertrophy. However, induction of HR reduction prior to surgical intervention significantly ameliorated the hypertrophy. In order to assess potential protein kinase pathways that may be activated in the left ventricle by relative bradycardia, we used a phospho-antibody array and this revealed selective activation of phosphoinositide-3 kinase. In conclusion, HR reduction protects against pathological cardiac hypertrophy but limits physiological exercise capacity.
Chromosome-level Assembly, Dosage Compensation and Sex-biased Gene Expression in the Small Brown Planthopper,Laodelphax striatellus
Authors: Hu Qing-Ling , Ye Yu-Xuan , Zhuo Ji-Chong , Huang Hai-Jian , Li Jun-Min , Zhang Chuan-Xi
Published: November 2022

In insects, sex chromosome differentiation often results in unequal gene dosages between sexes. Dosage compensation mechanisms evolve to balance gene expression, but the degree and mechanism of regulation often vary by insect species. In hemipteran species, the small brown planthopper (SBPH), Laodelphax striatellus, is an injurious crop pest, with a sex chromosome type XX in females and XO in males. This species offers the opportunity to study dosage compensation and sex-biased gene expression. In this study, we generated a chromosome-level genome of SBPH using Oxford Nanopore Technologies and high-throughput chromatin conformation capture (Hi-C) technology. We also sequenced RNA-seq data from 16 tissue samples to annotate the genome and analyze gene dosage compensation. We finally obtained a 510.2 megabases (Mb) genome with 99.12% of the scaffolds anchored on 15 chromosomes (14 autosomes and 1 X chromosome) and annotated 16,160 protein-coding genes based on full-length cDNA sequencing data. Furthermore, we found complete dosage compensation in all L. striatellus somatic tissues, but lack of dosage compensation in gonad tissue testis. We also found that female-biased genes were significantly enriched on the X chromosome in all tissues, whereas male-biased genes in gonad tissues were enriched on autosomes. This study not only provides a high-quality genome assembly but also lays a foundation for a better understanding of the sexual regulatory network in hemipteran insects.
Systematic Review and Meta-analysis: Loss of Response and Need for Dose Escalation of Infliximab and Adalimumab in Ulcerative Colitis
Authors: Savelkoul Edo H J , Thomas Pepijn W A , Derikx Lauranne A A P , den Broeder Nathan , Römkens Tessa E H , Hoentjen Frank
Published: November 2022

Background

Loss of response to infliximab or adalimumab in ulcerative colitis occurs frequently, and dose escalation may aid in regaining clinical benefit. This study aimed to systematically assess the annual loss of response and dose escalation rates for infliximab and adalimumab in ulcerative colitis.

Methods

A systematic search was conducted from August 1999 to July 2021 for studies reporting loss of response and dose escalation during infliximab and/or adalimumab use in ulcerative colitis patients with primary response. Annual loss of response, dose escalation rates, and clinical benefit after dose escalation were calculated. Subgroup analyses were performed for studies with 1-year follow-up or less.

Results

We included 50 unique studies assessing loss of response (infliximab, n = 24; adalimumab, n = 21) or dose escalation (infliximab, n = 21; adalimumab, n = 16). The pooled annual loss of response for infliximab was 10.1% (95% confidence interval [CI], 7.1-14.3) and 13.6% (95% CI, 9.3-19.9) for studies with 1-year follow-up. The pooled annual loss of response for adalimumab was 13.4% (95% CI, 8.2-21.8) and 23.3% (95% CI, 15.4-35.1) for studies with 1-year follow-up. Annual pooled dose escalation rates were 13.8% (95% CI, 8.7-21.7) for infliximab and 21.3% (95% CI, 14.4-31.3) for adalimumab, regaining clinical benefit in 72.4% and 52.3%, respectively.

Conclusions

Annual loss of response was 10% for infliximab and 13% for adalimumab, with higher rates during the first year. Annual dose escalation rates were 14% (infliximab) and 21% (adalimumab), with clinical benefit in 72% and 52%, respectively. Uniform definitions are needed to facilitate more robust evaluations.
Analysis of pairings of colors and materials of furnishings in interior design with a data-driven framework
Authors: Park Bo Hyeon , Hyun Kyung Hoon
Published: November 2022

Color–material furnishing pairing is known as a “black-box” for interior designers. The overall atmosphere of a space can be changed by modifying furnishing combinations, e.g., to express modern or classic styles. Designers carefully choose pairings of colors and materials that fit their intended interior design styles based on experience and knowledge. However, no specific principles or rules have yet been established. Therefore, this study aims to derive a furnishing pairing principle based on a novel framework comprising object detection, color extraction, material recognition, and network analysis. We used the proposed framework to analyze large-scale interior design image data (N =  24194) collected from an online interior design platform. We also used the authenticity algorithm to analyze the relative influence of styles. By using the data-driven method from large-scale data in each of the eight interior styles, we derived authentic color, material, and furnishing combinations. Our study results revealed that images with high authenticity values in each style matched existing style descriptions. Additionally, the proposed framework allows interior style image retrieval based on a specific color, material, and furnishing combination. Our findings have implications for research on the development of style-aware furniture retrieval systems and automatic interior design generation methods.
Novel industrial surface-defect detection using deep nested convolutional network with attention and guidance modules
Authors: Park Kyeong-Beom , Lee Jae Yeol
Published: November 2022

Industrial defect inspection plays a crucial role in maintaining the high quality of the product. Although deep learning technologies have been applied to conduct automatic defect inspection, it is still difficult to detect industrial surface defects accurately due to complex variations. This study proposes a novel approach to industrial surface-defect detection that segments defect areas accurately and robustly from the complex background using a deep nested convolutional network (NC-Net) with attention and guidance modules. NC-Net consists of the encoder-decoder with nested residual U-blocks and feature enhancement modules. Each layer block of the encoder and decoder is also represented as a residual U-block. In addition, features are adaptively refined by applying the attention module to the skip connection between the encoder and decoder. Low-level encoder features are refined through edge guidance, and high-level encoder features through mask guidance, which can keep local and global contexts for accurate and robust defect detection. A comprehensive evaluation was conducted to verify the novelty and robustness of NC-Net using four datasets, including magnetic tile surface defects, steel surface defects, rail surface defects, and road surface defects. The proposed method outperformed previous state-of-the-art studies. An additional dataset was also evaluated to prove the extensibility and generality of the proposed approach.
Optimal feedrate planning on a five-axis parametric tool path with global geometric and kinematic constraints
Authors: Ma Hong-Yu , Yuan Chun-Ming , Shen Li-Yong , Gao Xiao-Shan
Published: November 2022

The optimal feedrate planning problem for the five-axis parametric tool path remains challenging due to the nonlinear relationships between the joint space and the Cartesian space. We present a novel and complete optimal feedrate planning method for a five-axis parametric tool path by constraining the velocity, acceleration, jerk in the joint space, and the chord error in the Cartesian space. Our method formulates the problem as an optimal control problem, and we propose an iteration control vector parametrization method to compute the optimal solution. Compared with the new development five-axis feedrate planning methods, our solution satisfies “bang-bang” optimal control, and each constraint is strictly under the limits globally. Examples and comparisons with two other methods are demonstrated to show the effectiveness of the algorithm.
Optimum boundaries for maximum load-carrying capacity in water-lubricated composite journal bearings incorporating turbulences and inertial effects based on elastohydrodynamic analysis
Authors: Kim Wonvin , Lim Su Hyun , Hong Hyunsoo , Jeong Kwang Il , On Seung Yoon , Park Seong Yeon , You Jun Il , Kim Seong Su
Published: November 2022

The application of polymer-based composite materials as bearing liner materials in eco-friendly water lubrication has received considerable attention owing to their superior tribological behaviors, corrosion resistance, and high damping characteristics, and their design flexibility can improve the bearing performances in response to the distribution of lubricant film pressure based on the regulation of elastic constants. However, the low viscosity and high density of water essentially cause thin-filmed lubrication accompanied by a low load-carrying capacity. Particularly, a high rotational speed enhancing the wedge effect induces turbulence and considerable inertial effect. Moreover, substantial elastic deformation of the composite bearing liners alters the formation of the lubricant film. In this study, we analyze a water-lubricated composite journal bearing system incorporating the turbulence, inertial effect, and elastic deformation of the bearing liner. Reynolds equation was modified considering the turbulence and inertial effect. The elastic deformation of the composite bearing liner was determined by solving the constitutive equation. The Reynolds equation and the constitutive equation were solved via the finite difference method and finite element method, respectively. In addition, the analytical relation for the elastic deformation was derived that suitably eliminated the requirement of solving the constitutive equation. With the introduction of the primary parameters, Sommerfeld number, Reynolds number, and deformation coefficient, the relation of the normalized minimum film thickness with respect to the parameters was modeled based on the Gaussian regression model. Accordingly, we proposed the new optimal maximum load-carrying capacity boundaries that narrowed down the operating region compared to conventional boundaries.
A combination of acetabular coverage and femoral head–neck measurements can help diagnose femoroacetabular impingement
Authors: Hayashi Shinya , Kuroda Yuichi , Nakano Naoki , Matsumoto Tomoyuki , Kamenaga Tomoyuki , Maeda Toshihisa , Kuroda Ryosuke
Published: November 2022

This study aimed to evaluate the relationship between the radiographical features of combination of the acetabular coverage and the femoral head-neck shape and the occurrence of femoroacetabular impingement (FAI). In this study, 114 patients who had FAI with or without labral tear and mild osteoarthritis were analyzed. Plain radiographs and computed tomography (CT) were taken for evaluation of acetabular coverage and femoral head-neck measurements. The relationship between the combination angle of acetabular coverage and femoral head-neck measurements and the occurrence of FAI was evaluated. The prevalence of FAI patients with the combination angle of CT-anterior CE + α angle ≥100° was 6.1% (7/114 patients). Receiver operator characteristic curve analysis demonstrated a higher area under the curve for combination of CT-anterior center edge angle (ACEA) with the α angle at 0.94 (CT-ACEA +α angle). A threshold for the occurrence of FAI was determined using the combination CT-ACEA + α angle at 100°. The frequency of FAI surgery was significantly higher in patients with a combination angle ≥100° than in those with a smaller angle. The average modified Harris hip score was significantly lower in patients with a combination angle ≥100° than in those with a smaller angle. We suggest that the combination of lateral center edge angle ≥40°, α angle ≥50° and combined angles of CT-ACEA and α angle ≥100° may help diagnosis of FAI. Level of evidence III: retrospective cohort study.
Performance of a Molecular Test for Group A Streptococcus Pharyngitis
Authors: Tanz Robert R , Heaberlin Lauren E , Harvey Erin , Katsogridakis Yiannis L , Burns Rebecca Ruhana , Rippe Jason , Shulman Stanford T
Published: November 2022

We performed a prospective study to determine if the pretest probability of a positive loop-mediated isothermal amplification test is greater when there are more signs and symptoms of GAS pharyngitis. Patients were enrolled if a clinician obtained a GAS RADT. The McIsaac score was calculated. The prevalence of positive LAMP and RADT results increased as the McIsaac score increased. The calculated sensitivity of LAMP was superior to RADT.
SCFOsFBK1 E3 ligase mediates jasmonic acid-induced turnover of OsATL53 and OsCCR14 to regulate lignification of rice anthers and roots
Authors: Borah Pratikshya , Sharma Aishwarye , Sharma Arun Kumar , Khurana Paramjit , Khurana Jitendra Paul
Published: November 2022

The rice F-box protein OsFBK1, which mediates the turnover of a cinnamoyl CoA-reductase, OsCCR14, has previously been shown to regulate anther and root lignification. Here, we identify OsATL53, a member of the ATL family of RING-H2 proteins that interacts with OsCCR14 in the cytoplasm. OsATL53 was identified in the same yeast two-hybrid library screening as reported previously for OsCCR14, and we show it to have cytoplasmic localization and E3 ligase ubiquitination properties. SCFOsFBK1 mediates turnover of OsATL53 in the cytoplasm and the nucleus, and that of OsCCR14 only in the nucleus, as shown by cell-free degradation assays. Confocal fluorescence lifetime imaging microscopy analyses demonstrate that in presence of jasmonic acid (JA), which plays a role in anther dehiscence, OsATL53–OsCCR14 undergoes conformational changes that trigger the complex to accumulate around the nuclear periphery and signals OsFBK1 to initiate degradation of the proteins in the respective cellular compartments. OsATL53 decreases the enzymatic activity of OsCCR14 and sequesters it in the cytoplasm, thereby regulating the lignification process. Transgenic rice with knockdown of OsATL53 display increased lignin deposition in the anthers and roots compared to the wild type, whilst knockdown of OsCCR14 results in decreased lignin content. Our results show that OsATL53 affects the activity of OsCCR14, and that their JA-induced degradation by SCFOsFBK1 regulates lignification of rice anthers and roots.
Rearranged Endogenized Plant Pararetroviruses as Evidence of Heritable RNA-based Immunity
Authors: Valli Adrian A , Gonzalo-Magro Irene , Sanchez Diego H
Published: November 2022

Eukaryotic genomics frequently revealed historical spontaneous endogenization events of external invading nucleic acids, such as viral elements. In plants, an extensive occurrence of endogenous plant pararetroviruses (EPRVs) is usually believed to endow hosts with an additional layer of internal suppressive weaponry. However, an actual demonstration of this activity remains speculative. We analyzed the EPRV component and accompanying silencing effectors of Solanum lycopersicum, documenting that intronic/intergenic pararetroviral integrations bearing inverted-repeats fuel the plant's RNA-based immune system with suitable transcripts capable of evoking a silencing response. A surprisingly small set of rearrangements explained a substantial fraction of pararetroviral-derived endogenous small-interfering (si)RNAs, enriched in 22-nt forms typically associated with anti-viral post-transcriptional gene silencing. We provide preliminary evidence that such genetic and immunological signals may be found in other species outside the genus Solanum. Based on molecular dating, bioinformatics, and empirical explorations, we propose that homology-dependent silencing emerging from particular immuno-competent rearranged chromosomal areas that constitute an adaptive heritable trans-acting record of past infections, with potential impact against the unlocking of plant latent EPRVs and cognate-free pararetroviruses.
Pancancer transcriptomic profiling identifies key PANoptosis markers as therapeutic targets for oncology
Authors: Mall Raghvendra , Bynigeri Ratnakar R , Karki Rajendra , Malireddi R K Subbarao , Sharma Bhesh Raj , Kanneganti Thirumala-Devi
Published: November 2022

Resistance to programmed cell death (PCD) is a hallmark of cancer. While some PCD components are prognostic in cancer, the roles of many molecules can be masked by redundancies and crosstalks between PCD pathways, impeding the development of targeted therapeutics. Recent studies characterizing these redundancies have identified PANoptosis, a unique innate immune-mediated inflammatory PCD pathway that integrates components from other PCD pathways. Here, we designed a systematic computational framework to determine the pancancer clinical significance of PANoptosis and identify targetable biomarkers. We found that high expression of PANoptosis genes was detrimental in low grade glioma (LGG) and kidney renal cell carcinoma (KIRC). ZBP1, ADAR, CASP2, CASP3, CASP4, CASP8 and GSDMD expression consistently had negative effects on prognosis in LGG across multiple survival models, while AIM2, CASP3, CASP4 and TNFRSF10 expression had negative effects for KIRC. Conversely, high expression of PANoptosis genes was beneficial in skin cutaneous melanoma (SKCM), with ZBP1, NLRP1, CASP8 and GSDMD expression consistently having positive prognostic effects. As a therapeutic proof-of-concept, we treated melanoma cells with combination therapy that activates ZBP1 and showed that this treatment induced PANoptosis. Overall, through our systematic framework, we identified and validated key innate immune biomarkers from PANoptosis which can be targeted to improve patient outcomes in cancers.
The influence of repeated flares in response to therapy and prognosis in lupus nephritis
Authors: Perez-Arias Abril A , Márquez-Macedo Sofía E , Pena-Vizcarra Oscar R , Zavala-Miranda María Fernanda , Romero-Díaz Juanita , Morales-Buenrostro Luis E , Mejía-Vilet Juan M
Published: November 2022

Background

Repeated renal flares in lupus nephritis (LN) have been associated with worse long-term kidney function. This study aimed to assess the impact of repeated LN flares in response to therapy, kidney and patient prognosis.

Methods

All patients from a biopsy-proven LN cohort between 2008 and 2018 were segregated into three groups according to the number of LN flares when they entered our cohort: first LN flare, second LN flare or third LN flare. The following outcomes were evaluated by unadjusted and adjusted time-to-event analyses: complete and partial response, disease relapses, progression to decline of 30% of the estimated glomerular filtration rate (eGFR), doubling of serum creatinine, end-stage kidney disease and patient survival.

Results

A total of 441 patients were included: 257 (58%) in their first LN flare, 102 (23%) in their second LN flare and 82 (19%) in their third LN flare. There were significant differences in LN flare presentation in age, eGFR, serum albumin, pyuria and hematuria among groups. The National Institutes of Health chronicity indices and the percentage of patients with vascular lesions were higher in groups at progressive LN flares. In the adjusted analyses, complete and partial response rates decreased, as well as kidney and patient survival, at a progressive number of LN flares. No differences in the dynamic course of all surveillance laboratory parameters were observed in the first year after initial therapy among LN flare groups.

Conclusions

A progressive number of LN flares is associated with a lower response to therapy and an adverse prognosis for kidney function and patient survival.
Factors associated with alcohol abuse in the Peruvian population: analysis of a national health survey 2019
Authors: Caira-Chuquineyra Brenda , Fernandez-Guzman Daniel , Quispe-Vicuña Carlos , Gutierrez-Rodriguez Raysa , Valencia Pablo D
Published: November 2022

Aim

To evaluate the factors associated with alcohol abuse in the Peruvian population.

Methods

A secondary analysis was performed using data from the Demographic and Family Health Survey of Peru, 2019. We included 24 264 Peruvians between 18 and 59 years. For the analysis of association, the Poisson regression model with robust standard errors was used. Adjusted Prevalence Ratios (aPR) with their respective 95% confidence intervals (95% CI) were calculated.

Results

The prevalence of alcohol abuse was 5.2%. Having higher education (aPR:1.61; 95%CI:1.04–2.48), being widowed, separated or divorced (aPR:1.73; 95%CI:1.18–2.54), belonging to the third (aPR:1.70; 95%CI:1.12–2.60), fourth (aPR:2.08; 95%CI:1.33–3.23) or fifth socioeconomic quintile (aPR:2.16; 95%CI:1.33–3.50), being from the Sierra (aPR:1.45; 95%CI:1.12–1.87) or Selva (aPR:1.48; 95%CI:1.13–1.94), not having health insurance (aPR:1.25; 95%CI:1.04–1.50), being a current smoker (aPR:2.43; 95%CI:2.02–2.93) and having major depression (aPR:1.77; 95%CI:1.32–2.36) were associated with a higher prevalence of alcohol abuse. On the other hand being a middle-aged adult (aPR:0.73; 95%CI:0.60–0.88), female (aPR:0.16; 95%CI:0.12–0.22) and having started drinking alcohol after the age of 18 years (aPR:0.57; 95%CI:0.47–0.69) were associated with a lower prevalence.

Conclusions

One in 20 Peruvians between 18 and 59 years had alcohol abuse. Age, gender, education level, marital status, socioeconomic level, region, age of first drink, smoking and depression were associated with alcohol abuse.
Hyaline Cartilage Microtissues Engineered from Adult Dedifferentiated Chondrocytes: Safety and Role of WNT Signaling
Authors: Kutaish Halah , Bengtsson Laura , Tscholl Philippe Matthias , Marteyn Antoine , Braunersreuther Vincent , Guérin Alexandre , Béna Frédérique , Gimelli Stefania , Longet David , Ilmjärv Sten , Dietrich Pierre-Yves , Gerstel Eric , Jaquet Vincent , Hannouche Didier , Menetrey Jacques , Assal Mathieu , Krause Karl-Heinz , Cosset Erika , Tieng Vannary
Published: November 2022

The repair of damaged articular cartilage is an unmet medical need. Chondrocyte-based cell therapy has been used to repair cartilage for over 20 years despite current limitations. Chondrocyte dedifferentiation upon expansion in monolayer is well known and is the main obstacle to their use as cell source for cartilage repair. Consequently, current approaches often lead to fibrocartilage, which is biomechanically different from hyaline cartilage and not effective as a long-lasting treatment. Here, we describe an innovative 3-step method to engineer hyaline-like cartilage microtissues, named Cartibeads, from high passage dedifferentiated chondrocytes. We show that WNT5A/5B/7B genes were highly expressed in dedifferentiated chondrocytes and that a decrease of the WNT signaling pathway was instrumental for full re-differentiation of chondrocytes, enabling production of hyaline matrix instead of fibrocartilage matrix. Cartibeads showed hyaline-like characteristics based on GAG quantity and type II collagen expression independently of donor age and cartilage quality. In vivo, Cartibeads were not tumorigenic when transplanted into SCID mice. This simple 3-step method allowed a standardized production of hyaline-like cartilage microtissues from a small cartilage sample, making Cartibeads a promising candidate for the treatment of cartilage lesions.
Cellular and Molecular Targets of Extracellular Vesicles from Mesenchymal Stem/Stromal Cells in Rheumatoid Arthritis
Authors: Alcaraz María José , Guillén María Isabel
Published: November 2022

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes progressive joint destruction. Despite the advances in the treatment of this condition there remains a clinical need for safe therapies leading to clinical remission. Mesenchymal stem/stromal cells (MSCs) play immunomodulatory and regenerative roles which can be partly mediated by their secretome. In recent years, the important contribution of extracellular vesicles (EVs) to MSC actions has received an increasing interest as a new therapeutic approach. We provide an extensive overview of the immunomodulatory properties of MSC EVs and their effects on articular cells such as fibroblast-like synoviocytes that play a central role in joint destruction. This review discusses the anti-arthritic effects of MSC EVs in vitro and in animal models of RA as well as their potential mechanisms. Recent preclinical data suggest that transfer of non-coding RNAs by MSC EVs regulates key signaling pathways involved in the pathogenesis of RA. We also examine a number of EV modifications for improving their anti-arthritic efficacy and carrier ability for drug delivery.
Adaptation and implementation outcomes of a parenting program for low-income, ethnically diverse families delivered virtually versus in-person
Authors: Grafft Natalie , Aftosmes-Tobio Alyssa , Gago Cristina , Lansburg Kindra , Beckerman-Hsu Jacob , Trefry Brooke , Kumanyika Shiriki , Davison Kirsten
Published: November 2022

Driven by the COVID-19 pandemic, many in-person health behavior interventions were compelled to quickly pivot to a virtual format with little time or capacity to reflect on or examine possible equity-related implications of a format that required digital access and remote learning skills. Using a parenting program for low-income families as a case study, this paper (a) outlines the process of adapting the program from an in-person to a virtual format and (b) examines the equity-related implications of this adaptation. Parents Connect for Healthy Living (PConnect) is a 10-session empowerment-focused parenting intervention designed to promote family health for Head Start families. In 2020, PConnect was adapted over a 6-month period from an in-person to a virtual format due to the advent of the COVID-19 pandemic. Three core elements were retained in the adaptation; session content, provision of coaching support for facilitators, and the co-facilitation model. Key modifications include session length, group composition, and language of program delivery. Head Start and PConnect records provided data to compare reach, acceptability, and appropriateness of virtual and in-person PConnect. Seventy-eight parents enrolled in the in-person program and 58 in the virtual program. Participant demographics and satisfaction were similar across formats, and demographics similar to the general Head Start population. Participation was higher in the virtual format. Parents participated in the virtual program primarily via smart phones (68%). This case study supports the acceptability and appropriateness of virtual parenting programs in ethnically diverse, low-resource settings.
The importance of mitosis ≥2 in selecting patients with T1 cutaneous melanomas for sentinel lymph node biopsy
Authors: Borgognoni Lorenzo , Crocetti Emanuele , Sestini Serena , Brandani Paola , Giannotti Vanni , Gerlini Gianni
Published: November 2022

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual removed the mitotic rate (MR) as a staging criterion for T1 melanomas, thus leading to a debate on sentinel lymph node biopsy (SLNB) in thin melanomas. This study investigates whether MR plays a role in selecting patients with T1 melanoma for SLNB. We analyzed clinical and histological data from the Florence Melanoma & Skin Cancer Unit database for 313 patients with a single thin melanoma who had undergone SLNB. We determined sentinel lymph node (SLN) positivity percentages in T1 melanomas according to the AJCC 8th Edition focusing on MR. Of the 313 T1 patients, 108 had MR = 0, 127 had MR = 1 and 78 had MR ≥2. The overall SLN positivity rate was 8.6%, (5.6% with MR = 0, 6.3% with MR = 1 and 16.7% with MR ≥2). The SLNB positivity rate in T1b melanomas was 12.1%, (8.5% with MR = 0, 5.7% with MR = 1 and 24.4% with MR ≥2), whereas in T1a melanomas it was 5.8%, (3.3% with MR = 0, 6.8% with MR = 1 and 8.1% with MR ≥2). In a logistic regression analysis, MR ≥2 had an odds ratio of almost three in comparison with MR = 0/1 also adjusting for thickness. Thus, MR ≥2 significantly predicted SLN metastases in T1 melanomas. Of those patients with positive SLN, 37% were classified as T1a according to the AJCC 8th edition. These findings underline the importance of MR ≥2 in selecting patients with T1 cutaneous melanomas for SLNB.
Characteristics and Limitations of Video-capillaroscopy in Reconstructive Microsurgery for Different Histologic Components of Flaps
Authors: Escandón Joseph M. , Mohammad Arbab , Matsui Chihiro , Tanaka Takakuni , Wei-Kai Lao William , Yoshitsugu Hattori , Matsui Yuki , Mizuno Hiroshi
Published: November 2022

Indocyanine green, ultrasonography, and handheld Doppler can be used to evaluate blood flow at the donor and recipient site during microvascular reconstruction. However, these methods do not provide direct visualization and assessment of real-time blood flow. Video-capillaroscopy has been shown to be useful in clinical practice to assess microcirculation in rheumatologic disorders. In this report we used video-capillaroscopy to assess different tissue components involved in microvascular surgery. Seven patients who underwent head and neck oncologic microvascular reconstruction between November 2021 and February 2022 were included in this study. Video-capillaroscopy (GOKO-BscanZD, GOKO Imaging Devices Co., Ltd., Japan) was used to evaluate the donor-site and recipient-site tissue components. Optimal red blood cell movement was graded with a score of four, while no flow was graded with a score of 0. Seven myocutaneous flaps and seven recipient sites were evaluated. For the donor-site, our analysis demonstrated a significantly higher video-capillaroscopy quality for skin (3.43), adipose tissue (3.7) and perforators (3.7) when compared with muscle (0.429), muscle fascia (0.857), and de-epithelialized skin (1) (P < 0.001). For the recipient-site, a significantly higher video-capillaroscopy quality for skin (2.7), adipose tissue (3.5), and the periosteum (2.1) was noted when compared with muscle (0) (P < 0.001). Video-capillaroscopy efficiency is limited in the muscular component and injured (de-epithelialized) skin surface areas of flaps. Herein, we provide evidence that assessment of flap perfusion with video-capillaroscopy can be reliably achieved in the skin, periosteum, perforators, and adipose tissue. Video-capillaroscopy is expected to be applied for intraoperative real-time blood flow evaluation.
A Systematic Review on Antituberculosis Drug Discovery and Antimycobacterial Potential of Biologically Synthesized Silver Nanoparticles: Overview and Future Perspectives
Authors: Ezeh Christian K. , Eze Chibuzor N. , Dibua Uju M. E. , Emencheta Stephen C.
Published: November 2022

Rapid emergence and quick evolution of drug-resistant and aggressive mycobacterial strains have resulted in the present antimycobacterial drug crisis and the persistence of tuberculosis as a major public health problem. Green/biological nanotechnologies constitute an interesting area of research for discovering antimycobacterial agents. This review focused on the biological (green) synthesis of silver nanoparticles (AgNPs) as an alternative source of antimycobacterial agents. Data for this study were searched and screened from three electronic databases (Google Scholar, PubMed and ScienceDirect) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses flowchart. Data from in total 17 eligible studies were reported in this systematic review. Twelve of the 17 studies used plants to fabricate AgNPs, whereas the remaining five studies used microorganisms (bacteria and/or fungi). Silver as part of silver nitrate (AgNO3) was the metal precursor reported for the synthesis of AgNPs in these studies. Silver nanoparticles were mostly spherical, with sizes ranging from 12 to 140 nm. Results based on minimum inhibitory concentrations varied between studies and were divided into three groups: (i) those more effective than the antibiotic (controls), (ii) those more effective than plant extracts, and (iii) those less effective than the antibiotic controls. In addition, little or no cytotoxicity effects were reported. Silver nanoparticles were also shown to be highly specific or selective toward mycobacterial strains. This systematic review highlights the antimycobacterial potential of biologically synthesized AgNPs, underscoring the possibility of discovering/developing new antimycobacterial agents using biological synthesis approaches with less toxicity and high selectivity.
Describing the Value of Physical Therapy in a Complex System Using the Socio-Ecological Model
Authors: Crick James P. , Alain Gabriel , Quatman Carmen , Juckett Lisa , Quatman-Yates Catherine C.
Published: November 2022

A system is a collection of entities (ie, widgets, molecules, people, businesses) that interact in such a way that their resulting collective behavior is not immediately apparent by viewing the collected items separately. Hospital-based health care meets the definition of a system, but further specification is helpful to describe the value of components in the system. Complexity science offers a chance to reconceptualize our understanding of health care to an environment of connected parts operating together and adapting on the basis of inputs and outputs. The purpose of this conceptual article is to apply complexity science principles to acute care physical therapy in order to provide perspective on the value of the physical therapist in the hospital environment and on the contextual factors that influence the profession's value. We present a model, the Socio-Ecological Model for Acute Care, and apply this model to physical therapy in order to describe the interrelated factors influencing the profession's value to individual patients, to the hospital units on which they practice, to the hospital system as a whole, and how they contribute to policy discussions. Yet, this value is difficult to distinguish due to the multifarious inputs into the system. Providing a clear description of the value of physical therapy in hospital settings is essential in our current health care environment that is increasingly cost-conscious. We provide perspective for clinicians and health care leaders while suggesting needs for future research.
Transformative Learning Emerging From Challenges First-Year Students Experienced
Authors: Plack Margaret M. , Hilliard Marjorie Johnson , Costello Ellen , Huhn Karen , Maring Joyce , Healey William E.
Published: November 2022

Introduction.

Doctor of physical therapy (PT) (DPT) programs are rigorous, and students report facing overwhelming challenges. Faculty may not be cognizant of the extent of these challenges and miss opportunities to support student learning. The purpose of this article is to describe factors affecting student coping abilities and the lessons they learned from managing their self-identified challenges.

Review of Literature.

Given the growing body of evidence surrounding mental health issues in DPT students, educators are exploring ways to support student well-being and promote their professional development.

Subjects.

This study is a component of a larger multisite study of first-year DPT students from 3 private universities.

Methods.

Participants submitted written narratives in response to a critical incident questionnaire designed to better understand first-year challenges. Responses were deidentified, researchers were blinded to participation, and confidentiality was maintained throughout. A consensus-driven interpretivist approach to qualitative data analysis was used. Strategies to ensure trustworthiness included triangulation of researchers, peer review, prolonged engagement, and use of thick rich descriptions.

Results.

Seventy responses were analyzed. Two major themes are presented: (1) students described factors internal and external to the learning environment that inhibited and facilitated their ability to cope with challenges and (2) students shared academic successes and lessons learned from overcoming challenges, including the development of new behaviors, enhanced self-awareness, and personal and professional growth.

Discussion and Conclusion.

Building on previous work, analysis of the lived experiences of first-year DPT students revealed a process of transformational learning through challenge. This process highlights the importance of recognizing and supporting the significant incidental learning that occurs in our students during their journey through PT school. Faculty focusing solely on content knowledge, skills, and even critical thinking may not recognize and support the incidental learning occurring and may be missing significant transformational learning opportunities.
The Sequential Use of Extracorporeal Cytokine Removal Devices in an Adolescent With COVID-19 Receiving Continuous Renal Replacement Therapy
Authors: Hui Wun Fung , Chan Renee Wan Yi , Wong Chun Kwok , Kwok Ka Hang Andy , Cheung Wing Lum , Chung Fung Shan , Leung Karen Ka Yan , Hon Kam Lun , Ku Shu Wing
Published: November 2022

A 14-year-old male developed multisystem inflammatory syndrome in children (MIS-C) after acquiring the SARS-CoV-2 infection. He deteriorated rapidly requiring inotropic and ventilatory support as well as continuous renal replacement therapy (CRRT) due to rhabdomyolysis-associated acute kidney injury. A hemoadsoprtion column Cytosorb® was first incorporated into the CRRT circuit for myoglobin and cytokines removal, which was followed by sequential use of another type of cytokine-removing hemofilter (Oxiris®) (altogether 100 hours of extracorporeal blood purification [EBP] therapy). There was no major complication related to the EBP therapy. Cytokine profile revealed a marked reduction of levels of several cytokines including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and IL-10 after the EBP therapy. It was noted that both pro-inflammatory and anti-inflammatory cytokines were removed, and the removal efficacy varied between different devices. His condition improved and the serum ferritin, C-reactive protein, and procalcitonin levels also dropped gradually, which correlated well with his clinical progress and the trend of cytokine levels. Our case demonstrated that extracorporeal cytokine removal can be safely applied in children with MIS-C and can be considered as adjunctive therapy in selected patients with critically ill conditions.
Influence of Respiration on Collateral Flow in the Fontan Population Using Real-time Phase-contrast Cardiovascular Magnetic Resonance
Authors: Blessing Maja , Körperich Hermann , Barth Peter , Michel Miriam , Dubowy Otto , Forreiter Sophia , Laser Kai Thorsten
Published: November 2022

Purpose:

The clinical significance of collateral flow for the ventricular function of patients with univentricular hearts is often debated. This study evaluates the impact of collateral flow on respiration-dependent preload modification and diastolic function in Fontan patients assessed by systemic and pulmonary vein (PV) flow patterns.

Materials and Methods:

Real-time phase-contrast cardiovascular magnetic resonance was performed in the right upper PV, ascending aorta, superior, and inferior vena cava (IVC) in 21 Fontan patients and 11 healthy individuals. The patients’ respiratory cycle was divided into 4 periods to generate respiratory-dependent stroke volumes (SVi). Conventional quantitative blood flow measurements were used to quantify and differentiate between low (group A) and high (group B) collateral flow.

Results:

Group B showed significantly lower SVi IVC in inspiration, end-inspiration, expiration, and SVi ΔIVC compared with group A (23.6±4.8 mL/m2 to 33.4±8.0; P=0.005). PV flow resulted in a lower mean SVi PV (11.6±7.6 mL/m2, vs. 14.0±11.4 mL/m2) as well as a significantly lower peak systolic S-wave velocity (Smax) (P=0.005), S/D-ratio (Smax/peak diastolic wave velocity) (P=0.015), and shorter diastolic deceleration time (DTD; P=0.030; median DTD=134 ms) compared with group A (DTD=202 ms).

Conclusions:

This study demonstrates the incapability of Fontan patients to properly increase preload by inspiration in the presence of significant collateral flow. The results further show that collateral flow is associated with a volume-deprived ventricle and impaired diastolic function.
Violation of the constant genetic effect assumption can result in biased estimates for non-linear Mendelian randomization
Authors: Burgess Stephen
Published: November 2022

Non-linear Mendelian randomization is an extension of conventional Mendelian randomization that performs separate instrumental variable analyses in strata of the study population with different average levels of the exposure. The approach estimates a localized average causal effect function, representing the average causal effect of the exposure on the outcome at different levels of the exposure. The commonly-used residual method for dividing the population into strata works under the assumption that the effect of the genetic instrument on the exposure is linear and constant in the study population. However, this assumption may not hold in practice. We use the recently developed doubly-ranked method to re-analyse various datasets previously analysed using the residual method. In particular, we consider a genetic score for 25-hydroxyvitamin D [25(OH)D] used in a recent non-linear Mendelian randomization analysis to assess the potential effect of vitamin D supplementation on all-cause mortality. We show that the effect of the genetic score on 25(OH)D concentrations varies strongly, with a five-fold difference in the estimated genetic association with the exposure in the lowest and highest decile groups. Evidence for a protective causal effect of vitamin D supplementation on all-cause mortality in low vitamin D individuals is evident for the residual method, but not for the doubly-ranked method. We show that the constant genetic effect assumption is more reasonable for some exposures, and less reasonable for others. If the doubly-ranked method indicates that this assumption is violated, then estimates from both the residual and doubly-ranked methods can be biased, although bias was smaller on average in the doubly-ranked method. Analysts should compare results from both methods, as well as considering transforming the exposure to reduce heterogeneity in the genetic effect on the exposure.
AnRt- based model for predicting multiple epidemic waves in a heterogeneous population
Authors: Romanescu Razvan , Hu Songdi , Nanton Douglas , Torabi Mahmoud , Tremblay-Savard Olivier , Haque Md Ashiqul
Published: November 2022

Relaxing the homogeneous mixing assumption in a population is often necessary to improve fits of epidemic models to observed infection counts. Establishing a link between observed infections and the underlying network of contacts is paramount to understanding how the network structure affects the speed of spread of a pathogen. In this paper we argue that introducing a flexible structure for the effective reproductive number (Rt) over the course of an epidemic allows for a more realistic description of the network of social contacts. This, in turn, produces better retrospective fits, as well as more accurate prospective predictions of observed epidemic curves. We extend this framework to fit multi-wave epidemics, and to accommodate public health restrictions on mobility. We demonstrate the performance of this model by doing a prediction study over two years of the SARS-CoV2 pandemic.