bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of thickness and elastic modulus of the anterior talofibular ligament on anterior ankle joint stiffness: A subject-specific finite element study
Authors: Peng Linjing , Yu Lu , Jia Jingyi , Gan Yaokai , Ding Angang , Xiong Ping , Zhao Yichen , Yao Yifei
Published: April 2023

Ankle sprain is a frequent type of sports injury leading to lateral ligament injury. The anterior talofibular ligament (ATFL) is a primary ligamentous stabilizer of the ankle joint and typically the most vulnerable ligament injured in a lateral ankle sprain (LAS). This study aimed to quantitively investigate the effect of the thickness and elastic modulus of ATFL on anterior ankle joint stiffness (AAJS) by developing nine subject-specific finite element (FE) models under acute injury, chronic injury, and control conditions of ATFL. A 120 N forward force was applied at the posterior calcaneus leading to an anterior translation of the calcaneus and talus to simulate the anterior drawer test (ADT). In the results, the ratio of the forward force to the talar displacement was used to assess the AAJS, which increased by 5.85% in the acute group and decreased by 19.78% in the chronic group, compared to those of the control group. An empirical equation described the relationship between AAJS, thickness, and elastic modulus (R-square 0.98). The equation proposed in this study provided an approach to quantify AAJS and revealed the effect of the thickness and the elastic modulus of ATFL on ankle stability, which may shed light on the potential diagnosis of lateral ligament injury.
A novel smart coating with hexacyanoferrate intercalated layered double hydroxides nanoadditive for early detection of carbon steel corrosion
Authors: Sushkova Alesia , Montes Rodrigo , Paulino Tiago , Sousa Isabel , Neves Cristina , Ferreira Mário G. S. , Tedim João
Published: April 2023

The detection of corrosion at early stages could increase the service life of metal-based infrastructures in a cost-effective manner. Despite the recent progress in “smart” self-reporting corrosion sensing coatings, the development of environmentally friendly systems appropriate for steel substrate used in offshore applications remains a relevant challenge. In this study, a novel smart corrosion sensing coating, based on hexacyanoferrate intercalated Mg-Al LDH nanoadditive, was developed, aiming at the detection of early-stage corrosion of carbon steel. The detection mechanism is based on the ability of hexacyanoferrate ions to react with iron cations generated during the corrosion process, giving rise to a colorimetric signal, while LDH carriers provide a controlled release of active ions under corrosion conditions. The sensing nanoadditive was embedded into a commercial pigment-free water-based acrylic polyurethane coating. The nanomaterial was characterized structurally (XRD) and morphologically (STEM). The compatibility of the additive with the polymer formulation and its influence on the resulting coating performance was investigated in terms of rheological behavior, structure (FTIR), morphology (SEM/EDS), thermal (TGA, DSC) and mechanical (adhesion, hardness) properties. The corrosion protection ability of the coating was evaluated via EIS, while the sensing functionality was analyzed by visual analysis of the surface. The developed coating successfully detects early-stage corrosion of steel substrate at a lab scale, in conditions relevant to the use of metallic structures in offshore applications, demonstrating a correlation between the level of material degradation and the spectroscopic signal associated with the presence of the LDH functional nanoadditive. Furthermore, the observed decrease in coating barrier properties, caused by the presence of LDH, was overcome by the subsequent development of a multilayer coating system. Two different topcoats (epoxy- and polyurethane-based) were surveyed for this purpose, showing an improvement in the coating barrier properties without influencing the corrosion detection functionality of the sensing layer. The results were successfully validated by standard salt spray tests. The multilayer approach opens up the possibility to model coatings with different characteristics for various operating conditions.
Diabetes and heart failure associations in women and men: Results from the MORGAM consortium
Authors: Chadalavada Sucharitha , Reinikainen Jaakko , Andersson Jonas , Di Castelnuovo Augusto , Iacoviello Licia , Jousilahti Pekka , Kårhus Line Lund , Linneberg Allan , Söderberg Stefan , Tunstall-Pedoe Hugh , Lekadir Karim , Aung Nay , Jensen Magnus T. , Kuulasmaa Kari , Niiranen Teemu J. , Petersen Steffen E.
Published: April 2023

Background

Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.

Methods

This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.

Results

6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58–1.89] and 2.12 [1.91–2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75–16.41] for women with T1DM vs. 5.80 [2.72–12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93–2.54] vs. 1.99 [1.67–2.38] respectively, p for interaction 0.80).

Conclusion

Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.
Risk factors for in-hospital mortality after total arch procedure in patients with acute type A aortic dissection
Authors: An Zhao , Zhong Keng , Sun Yangyong , Han Lin , Xu Zhiyun , Li Bailing
Published: April 2023

Object

Knowledge about the risk factors of in-hospital mortality for acute type A aortic dissection (ATAAD) patients who received total arch procedure is limited. This study aims to investigate preoperative and intraoperative risk factors of in-hospital mortality of these patients.

Methods

From May 2014 to June 2018, 372 ATAAD patients received the total arch procedure in our institution. These patients were divided into survival and death groups, and patients` in-hospital data were retrospectively collected. Receiver operating characteristic curve analysis was adopted to determine the optimal cut-off value of continuous variables. Univariate and multivariable logistic regression analyses were used to detect independent risk factors for in-hospital mortality.

Results

A total of 321 patients were included in the survival group and 51 in the death group. Preoperative details showed that patients in the death group were older (55.4 ± 11.7 vs. 49.3 ± 12.6, P = 0.001), had more renal dysfunction (29.4% vs. 10.9%, P = 0.001) and coronary ostia dissection (29.4% vs. 12.2%, P = 0.001), and decreased left ventricular ejection fraction (LVEF) (57.5 ± 7.9% vs. 59.8 ± 7.3%, P = 0.032). Intraoperative results showed that more patients in the death group experienced concomitant coronary artery bypass grafting (35.3% vs. 15.3%, P = 0.001) with increased cardiopulmonary bypass (CPB) time (165.7 ± 39.0 vs. 149.4 ± 35.8 min, P = 0.003), cross-clamp time (98.4 ± 24.5 vs. 90.2 ± 26.9 min, P = 0.044), and red blood cell transfusion (913.7 ± 629.0 vs. 709.7 ± 686.6 ml, P = 0.047). Logistic regression analysis showed that age >55 years, renal dysfunction, CPB time >144 min, and RBC transfusion >1,300 ml were independent risk factors for in-hospital mortality in patients with ATAAD.

Conclusion

In the present study, we identified that older age, preoperative renal dysfunction, long CPB time, and intraoperative massive transfusion were risk factors for in-hospital mortality in ATAAD patients with the total arch procedure.
Associations between smoking status and infertility: a cross-sectional analysis among USA women aged 18-45 years
Authors: He Sijie , Wan Li
Published: April 2023

Background

Although many studies have proven the harmful effects of smoking on human health, the associations between smoking status and infertility are limited in large epidemiologic studies. We aimed to investigate the associations between smoking status and infertility among child-bearing women in the United States of America (USA).

Methods

A total of 3,665 female participants (aged 18-45) from the National Health and Nutrition Examination Survey (NHANES) (2013-2018) were included in this analysis. All data were survey-weighted, and corresponding logistic regression models were performed to investigate the associations between smoking status and infertility.

Results

In a fully adjusted model, the risk of infertility was found to be increased by 41.8% among current smokers compared to never smokers (95% CI: 1.044-1.926, P=0.025). In the subgroup analysis, the odds ratios (95% CI) of the risk of infertility for current smokers were 2.352 (1.018-5.435) in the unadjusted model for Mexican American, 3.675 (1.531-8.820) in the unadjusted model but 2.162 (0.946-4.942) in fully adjusted model for people aged 25-31, 2.201 (1.097-4.418) in the unadjusted model but 0.837 (0.435-1.612) in fully adjusted model for people aged 32-38.

Conclusion

Current smokers was associated with a higher risk of infertility. The underlying mechanism of these correlations still needs more research. Our findings indicated that quitting smoking may serve as a simple index to reduce the risk of infertility.
Parenting and pandemic pressures: Examining nuances in parent, child, and family well-being concerns during COVID-19 in a Canadian sample
Authors: Colucci Laura , Smith Jackson A. , Browne Dillon T.
Published: April 2023

Introduction

The COVID-19 pandemic has caused vast disruptions in family life for Canadian parents since early 2020. While numerous environmental stressors have been identified, including job loss and the demands of balancing work-life conflicts and at-home schooling, relatively less is known about the areas of family life parents are most concerned about and how these worries relate to well-being across the family system.

Methods

Canadian parents (n = 29,831, 90.29% mothers, 57.40% Ontario residents) of children aged 0–14 were surveyed about their concerns related to child, parent, and family well-being in June 2020. Structural equation modelling was used to model the relationship between concerns about children, parenting, and the whole family, in association with several sociodemographic variables including child disability status, parent sex and education, job loss during COVID-19, and caregiver employment.

Results

Parenting, child, and family concerns were positively correlated. Higher child and family concerns were reported by parents who had not attended university, those who had experienced employment loss or reduced hours, and families with all adults working outside the home. Parents of children with a disability reported higher concerns across all three domains: child, parenting, and family psychosocial well-being.

Discussion

These results showcase distinct associations between social determinants of health and the types of worries caregivers exhibited across multiple areas of family life during the first wave of the COVID-19 pandemic in Canada. Findings are interpreted in relation to clinical intervention and public policy targets for families.
A versatile workflow for linear modelling in R
Authors: Santon Matteo , Korner-Nievergelt Fränzi , Michiels Nico K. , Anthes Nils
Published: April 2023

Linear models are applied widely to analyse empirical data. Modern software allows implementation of linear models with a few clicks or lines of code. While convenient, this increases the risk of ignoring essential assessment steps. Indeed, inappropriate application of linear models is an important source of inaccurate statistical inference. Despite extensive guidance and detailed demonstration of exemplary analyses, many users struggle to implement and assess their own models. To fill this gap, we present a versatile R-workflow template that facilitates (Generalized) Linear (Mixed) Model analyses. The script guides users from data exploration through model formulation, assessment and refinement to the graphical and numerical presentation of results. The workflow accommodates a variety of data types, distribution families, and dependency structures that arise from hierarchical sampling. To apply the routine, minimal coding skills are required for data preparation, naming of variables of interest, linear model formulation, and settings for summary graphs. Beyond that, default functions are provided for visual data exploration and model assessment. Focused on graphs, model assessment offers qualitative feedback and guidance on model refinement, pointing to more detailed or advanced literature where appropriate. With this workflow, we hope to contribute to research transparency, comparability, and reproducibility.
Landscapes and mechanisms of CD8+ T cell exhaustion in gastrointestinal cancer
Authors: Ding Jia-Tong , Yang Kang-Ping , Zhou Hao-Nan , Huang Ying-Feng , Li Hui , Zong Zhen
Published: April 2023

CD8+ T cells, a cytotoxic T lymphocyte, are a key component of the tumor immune system, but they enter a hyporeactive T cell state in long-term chronic inflammation, and how to rescue this depleted state is a key direction of research. Current studies on CD8+ T cell exhaustion have found that the mechanisms responsible for their heterogeneity and differential kinetics may be closely related to transcription factors and epigenetic regulation, which may serve as biomarkers and potential immunotherapeutic targets to guide treatment. Although the importance of T cell exhaustion in tumor immunotherapy cannot be overstated, studies have pointed out that gastric cancer tissues have a better anti-tumor T cell composition compared to other cancer tissues, which may indicate that gastrointestinal cancers have more promising prospects for the development of precision-targeted immunotherapy. Therefore, the present study will focus on the mechanisms involved in the development of CD8+ T cell exhaustion, and then review the landscapes and mechanisms of T cell exhaustion in gastrointestinal cancer as well as clinical applications, which will provide a clear vision for the development of future immunotherapies.
Circulating extracellular vesicles are associated with the clinical outcomes of sepsis
Authors: Li Pengfei , Wu Yan , Goodwin Andrew J. , Wolf Bethany , Halushka Perry V. , Wang Hongjun , Zingarelli Basilia , Fan Hongkuan
Published: April 2023

Introduction

Sepsis is associated with endothelial cell (EC) dysfunction, increased vascular permeability and organ injury, which may lead to mortality, acute respiratory distress syndrome (ARDS) and acute renal failure (ARF). There are no reliable biomarkers to predict these sepsis complications at present. Recent evidence suggests that circulating extracellular vesicles (EVs) and their content caspase-1 and miR-126 may play a critical role in modulating vascular injury in sepsis; however, the association between circulating EVs and sepsis outcomes remains largely unknown.

Methods

We obtained plasma samples from septic patients (n=96) within 24 hours of hospital admission and from healthy controls (n=45). Total, monocyte- or EC-derived EVs were isolated from the plasma samples. Transendothelial electrical resistance (TEER) was used as an indicator of EC dysfunction. Caspase-1 activity in EVs was detected and their association with sepsis outcomes including mortality, ARDS and ARF was analyzed. In another set of experiments, total EVs were isolated from plasma samples of 12 septic patients and 12 non-septic critical illness controls on days 1, and 3 after hospital admission. RNAs were isolated from these EVs and Next-generation sequencing was performed. The association between miR-126 levels and sepsis outcomes such as mortality, ARDS and ARF was analyzed.

Results

Septic patients with circulating EVs that induced EC injury (lower transendothelial electrical resistance) were more likely to experience ARDS (p<0.05). Higher caspase-1 activity in total EVs, monocyte- or EC-derived EVs was significantly associated with the development of ARDS (p<0.05). MiR-126-3p levels in EC EVs were significantly decreased in ARDS patients compared with healthy controls (p<0.05). Moreover, a decline in miR-126-5p levels from day 1 to day 3 was associated with increased mortality, ARDS and ARF; while decline in miR-126-3p levels from day 1 to day 3 was associated with ARDS development.

Conclusions

Enhanced caspase-1 activity and declining miR-126 levels in circulating EVs are associated with sepsis-related organ failure and mortality. Extracellular vesicular contents may serve as novel prognostic biomarkers and/or targets for future therapeutic approaches in sepsis.
Case Report: Complete response after tislelizumab treatment in a hepatocellular carcinoma patient with abdominal lymph node metastasis
Authors: Deng Haihui , Chen Bin , Peng Deti , He Jian , Zhao Weicheng , Chen Tuantuan , Xie Zonggui , Pang Fuwen
Published: April 2023

Background

Abdominal lymph node (ALN) metastasis is associated with a poor prognosis in patients with hepatocellular carcinoma (HCC) because of the limited number of effective therapeutic options available. Immunotherapy with immune checkpoint inhibitors, such as those targeting programmed death receptor-1 (PD-1), have produced encouraging results in patients with advanced HCC. Here, we report a complete response (CR) in a patient with advanced HCC and ALN metastasis after combination treatment with tislelizumab (a PD-1 inhibitor) and locoregional therapy.

Case summary

A 58-year-old man with HCC experienced progressive disease with multiple ALN metastases after undergoing transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), and laparoscopic resection. Because the patient did not wish to receive systemic therapy, including chemotherapy and targeting therapy, we prescribed tislelizumab (as a single immunotherapeutic agent) together with RFA. After four tislelizumab treatment cycles, the patient achieved a CR without tumor recurrence for up to 15 months.

Conclusion

Tislelizumab monotherapy can be effectively used to treat advanced HCC with ALN metastasis. Moreover, the combination of locoregional therapy and tislelizumab is likely to further increase therapeutic efficacy.
SARS-CoV-2 vaccination of convalescents boosts neutralization capacity against Omicron subvariants BA.1, BA.2 and BA.5 and can be predicted by anti-S antibody concentrations in serological assays
Authors: Seidel Alina , Hoffmann Simone , Jahrsdörfer Bernd , Körper Sixten , Ludwig Carolin , Vieweg Christiane , Albers Dan , von Maltitz Pascal , Müller Rebecca , Lotfi Ramin , Wuchter Patrick , Klüter Harald , Kirchhoff Frank , Schmidt Michael , Münch Jan , Schrezenmeier Hubert
Published: April 2023

Background

Recent data on immune evasion of new SARS-CoV-2 variants raise concerns about the efficacy of antibody-based COVID-19 therapies. Therefore, in this study the in-vitro neutralization capacity against SARS-CoV-2 variant B.1 and the Omicron subvariants BA.1, BA.2 and BA.5 of sera from convalescent individuals with and without boost by vaccination was assessed.

Methods and findings

The study included 313 serum samples from 155 individuals with a history of SARS-CoV-2 infection, divided into subgroups without (n=25) and with SARS-CoV-2 vaccination (n=130). We measured anti-SARS-CoV-2 antibody concentrations by serological assays (anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S) and neutralizing titers against B.1, BA.1, BA.2 and BA.5 in a pseudovirus neutralization assay. Sera of the majority of unvaccinated convalescents did not effectively neutralize Omicron sublineages BA.1, BA.2 and BA.5 (51.7%, 24.1% and 51.7%, resp.). In contrast, 99.3% of the sera of superimmunized individuals (vaccinated convalescents) neutralized the Omicron subvariants BA.1 and BA.5 and 99.6% neutralized BA.2. Neutralizing titers against B.1, BA.1, BA.2 and BA.5 were significantly higher in vaccinated compared to unvaccinated convalescents (p<0.0001) with 52.7-, 210.7-, 141.3- and 105.4-fold higher geometric mean of 50% neutralizing titers (NT50) in vaccinated compared to unvaccinated convalescents. 91.4% of the superimmunized individuals showed neutralization of BA.1, 97.2% of BA.2 and 91.5% of BA.5 with a titer ≥ 640. The increase in neutralizing titers was already achieved by one vaccination dose. Neutralizing titers were highest in the first 3 months after the last immunization event. Concentrations of anti-S antibodies in the anti-SARS-CoV-2-QuantiVac-ELISA (IgG) and Elecsys Anti-SARS-CoV-2 S assays predicted neutralization capacity against B.1 and Omicron subvariants BA.1, BA.2 and BA.5.

Conclusions

These findings confirm substantial immune evasion of the Omicron sublineages, which can be overcome by vaccination of convalescents. This informs strategies for choosing of plasma donors in COVID-19 convalescent plasma programs that shall select specifically vaccinated convalescents with very high titers of anti-S antibodies.
Culturing for conservation: the need for timely investments in reef aquaculture
Authors: Ridlon April D. , Grosholz Edwin D. , Hancock Boze , Miller Margaret W. , Bickel Aric , Froehlich Halley E. , Lirman Diego , Pollock F. Joseph , Putnam Hollie M. , Tlusty Michael F. , Waters Tiffany J. , Wasson Kerstin
Published: April 2023

Temperate oyster and tropical coral reefs are analogous systems that create habitat for economically, ecologically, and culturally important species, and they provide countless ecosystem services to human coastal communities. Globally, reefs are imperiled by multiple anthropogenic stressors, particularly climate impacts. Using aquaculture to support conservation goals - known as conservation aquaculture - is a relatively new approach for many reef building species, but it shows great promise for promoting species recovery and bolstering resilience to stressors. Concerns about aquaculture-associated risks, both known and potential, have often restricted the implementation of this tool to an emergency intervention following dramatic declines on reefs, when species or systems were unlikely to recover. Here, we combine expertise from coral and oyster reef ecosystems to consider the role of aquaculture as a conservation intervention for reefs, and provide recommendations for its timely development and targeted implementation. We highlight the importance of evaluating reef systems - alongside local stakeholders and Indigenous communities - to determine where and when the benefits of using aquaculture are most likely to outweigh the risks. We spotlight the importance of proactive monitoring to detect reef population declines, and the value of early aquaculture interventions to increase efficacy. Novel aquaculture approaches and technologies specifically designed for reef builders are considered, including techniques for building complex, multi-generational and multi-species reefs. We address the need for scaling up aquaculture-assisted reef recovery, particularly of corals, using high volume methods like those that have been successfully employed for oysters. We also recommend the immediate assessment and development of techniques to increase climate resilience of reef builders and we identify the challenges and trade-offs of these approaches. We highlight the use of proof-of-concept projects to test these promising methods, and we advise tracking of all interventions over time to determine their long-term efficacy. Finally, we outline opportunities to leverage novel partnerships among conservation, industry, and community interests that utilize aquaculture to facilitate the conservation of reefs. Developing conservation aquaculture approaches now is critical to position managers, scientists, and restoration practitioners to implement this intervention in timely and effective ways to support resilient reef and human communities worldwide.
Mud cracks promote colonization by pioneer saltmarsh plants
Authors: Jiang Can , Li Xiuzhen , Zhao Wenzhen , Xue Liming , Su Lin
Published: April 2023

Saltmarshes are valued as key buffering ecosystems against global climate change and sea level rise. However, the knowledge deficit regarding links between colonization of saltmarsh fringes by plants and mud cracking in the lateral dimension considerably limits our understanding of marsh resilience. Here, the role of mud cracks in colonization by saltmarsh plants was investigated. A combination of field experiments, remote sensing, and experimental results revealed that: (1) potential mud cracking zones were formed at the seaward edge of saltmarshes under the influence of tide-induced wetting–drying cycles, where mud cracks were extensively distributed and colonized by new seedlings. (2) The seedling density in the mud cracks was higher than that in the patches, and seedlings in the mud cracks sprouted earlier than those in the patches. The results implied that mud cracking enhanced colonization by saltmarsh plants, rather than being a water stressor. (3) The two main ecological functions of mud cracks in saltmarsh colonization were acting as “seed traps” and “seedling growth promoters.” (4) Mud cracking could be a key factor influencing saltmarsh resilience, especially by promoting the colonization and dispersal of saltmarsh plants. Rapid colonization of potential zones with mud cracks could occur as soon as seeds are available. Our results could facilitate the development of appropriate saltmarsh rehabilitation strategies.
Inclined colloidal drops: Evaporation kinetics and pattern formation
Authors: Parsa Maryam , Askounis Alexandros
Published: April 2023

The drying of solute-laden drops is ubiquitous in everyday life, from paints and printers to the raindrops drying on our windows. Nonetheless, scientific interest has primarily focused on understanding the evaporation kinetics on flat surface, with the key parameter of substrate inclination only recently started being addressed. This work focuses on the influence of moderate substrate inclinations at 20° and 40° on the evaporation kinetics and associated deposit patterns of colloidal drops. Inclination altered the shape of the drops which formed a lower contact angle at the upper side of the drop (rear edge) and larger contact angle at the lower side (front edge). As evaporation rate is a function of contact angle, which in turn is a function of inclination, the evaporation lifetime was extended by 43% and 61% for 20° and 40°, respectively, compared to a flat drop. A theoretical approximation of the evaporative flux across the liquid-vapour interface of the drops showed the contribution of each edge to the evaporation kinetics. These differences in the evaporative fluxes altered the internal flows within the drop and in turn the coffee-ring formation mechanism. The particle deposit shape at the two edges for each drop was visualised which combined with the theoretical arguments allowed the proposition of the particle deposition mechanism in inclined drops: inclination added a gravitationally-driven velocity flow component within the drops, which is perpendicular and hence negligible in flat drops. This additional flow hindered or enhanced the number of particles arriving at the rear and front edges of the inclined drops, respectively, and hence influenced the dimensions of the coffee-ring patterns. Eventually, the particle deposits grew sufficiently tall to effectively stagnate the outward flow which resulted in enhanced particle accumulation at the interior of the drops as inclination increased.
High overlap in patients diagnosed with hypermobile Ehlers-Danlos syndrome or hypermobile spectrum disorders with fibromyalgia and 40 self-reported symptoms and comorbidities
Authors: Fairweather DeLisa , Bruno Katelyn A. , Darakjian Ashley A. , Bruce Barbara K. , Gehin Jessica M. , Kotha Archana , Jain Angita , Peng Zhongwei , Hodge David O. , Rozen Todd D. , Munipalli Bala , Rivera Fernando A. , Malavet Pedro A. , Knight Dacre R. T.
Published: April 2023

Background

Joint pain is a common symptom in patients with hypermobile Ehlers-Danlos Syndrome (hEDS), hypermobility spectrum disorders (HSD) and fibromyalgia. The goal of this study was to determine whether symptoms and comorbidities overlap in patients diagnosed with hEDS/HSD and/or fibromyalgia.

Methods

We retrospectively examined self-reported data from an EDS Clinic intake questionnaire in patients diagnosed with hEDS/HSD, fibromyalgia, or both vs. controls with an emphasis on joint issues.

Results

From 733 patients seen at the EDS Clinic, 56.5% (n = 414) were diagnosed with hEDS/HSD and fibromyalgia (Fibro), 23.8% (n = 167) hEDS/HSD, 13.3% (n = 98) fibromyalgia, or 7.4% (n = 54) none of these diagnoses. More patients were diagnosed with HSD (76.6%) than hEDS (23.4%). Patients were primarily White (95%) and female (90%) with a median age in their 30s (controls 36.7 [18.0, 70.0], fibromyalgia 39.7 [18.0, 75.0], hEDS/HSD 35.0 [18.0, 71.0], hEDS/HSD&Fibro 31.0 [18.0, 63.0]). There was high overlap in all 40 symptoms/comorbidities that we examined in patients diagnosed with fibromyalgia only or hEDS/HSD&Fibro, regardless of whether they had hEDS or HSD. Patients that only had hEDS/HSD without fibromyalgia had far fewer symptoms/comorbidities than patients with hEDS/HSD&Fibro. The top self-reported issues in patients that only had fibromyalgia were joint pain, hand pain when writing or typing, brain fog, joint pain keeping from daily activities, allergy/atopy and headache. Five issues that significantly and uniquely characterized patients diagnosed with hEDS/HSD&Fibro were subluxations (dislocations in hEDS patients), joint issues like sprains, the need to stop sports due to injuries, poor wound healing, and migraine.

Conclusion

The majority of patients seen at the EDS Clinic had a diagnosis of hEDS/HSD plus fibromyalgia that was associated with more severe disease. Our findings indicate that fibromyalgia should be routinely assessed in patients with hEDS/HSD and vis-a-versa to improve patient care.
The significance of wrist immobilization for endoscopic carpal tunnel release
Authors: Zhang Fei , Jiang Hong , Lu Zhenfeng , Yang Haoyu , Zhang Qian , Mi Jingyi , Rui Yongjun , Zhao Gang
Published: April 2023

Background

Over the years, endoscopic carpal tunnel release (ECTR) has gained significant interest as an alternative to surgery. However, no consensus has been reached on the necessity of postoperative wrist immobilization. This study aims to compare the outcomes of wrist immobilization for a period of 2 weeks to immediate wrist mobilization after ECTR.

Methods

A total of 24 patients with idiopathic carpal tunnel syndrome undergoing dual-portal ECTR from May 2020 to Feb 2022 were enrolled and randomly divided into two groups postoperatively. In one group, patients wore a wrist splint for 2 weeks. In another group, wrist mobilization was allowed immediately after surgery. The two-point discrimination test (2PD test); the Semmes–Weinstein monofilament test (SWM test); the occurrence of pillar pain, digital and wrist range of motion (ROM); grip and pinch strength; the visual analog score (VAS), the Boston Carpal Tunnel Questionnaire (BCTQ) score; the Disabilities of the Arm, Shoulder, and Hand (DASH) score; and complications were evaluated at 2 weeks and 1, 2, 3, and 6 months after the surgery.

Results

All 24 subjects finished this study with no dropouts. During the early follow-up, patients with wrist immobilization demonstrated lower VAS scores, lower occurrence of pillar pain, and higher grip and pinch strength compared with the immediate mobilization group. No significant difference was obtained between these two groups in terms of the 2PD test, the SWM test, digital and wrist ROM, BCTQ, and the DASH score. In total, two patients without splints reported transient scar discomfort. No one complained of neurapraxia, injury of the flexor tendon, median nerve, and major artery. At the final follow-up, no significant difference was found in any parameters between both groups. The local scar discomfort mentioned above disappeared and left no serious sequela.

Conclusion

Wrist immobilization during the early postoperative period demonstrated significant pain alleviation along with stronger grip and pinch strength. However, wrist immobilization yielded no obvious superiority regarding clinical outcomes at the final follow-up.
Tremor suppression following treatment with MRgFUS: skull density ratio consistency and degree of posterior dentatorubrothalamic tract lesioning predicts long-term clinical outcomes in essential tremor
Authors: Kyle Kain , Maller Jerome , Barnett Yael , Jonker Benjamin , Barnett Michael , D’Souza Arkiev , Calamante Fernando , Maamary Joel , Peters James , Wang Chenyu , Tisch Stephen
Published: April 2023

Objectives

Magnetic resonance-guided focussed ultrasound (MRgFUS) is an incisionless ablative procedure, widely used for treatment of Parkinsonian and Essential Tremor (ET). Enhanced understanding of the patient- and treatment-specific factors that influence sustained long-term tremor suppression could help clinicians achieve superior outcomes via improved patient screening and treatment strategy.

Methods

We retrospectively analysed data from 31 subjects with ET, treated with MRgFUS at a single centre. Tremor severity was assessed with parts A, B and C of the Clinical Rating Scale for Tremor (CRST) as well as the combined CRST. Tremor in the dominant and non-dominant hand was assessed with Hand Tremor Scores (HTS), derived from the CRST. Pre- and post-treatment imaging data were analysed to determine ablation volume overlap with automated thalamic segmentations, and the dentatorubrothalamic tract (DRTT) and compared with percentage change in CRST and HTS following treatment.

Results

Tremor symptoms were significantly reduced following treatment. Combined pre-treatment CRST (mean: 60.7 ± 17.3) and HTS (mean: 19.2 ± 5.7) improved by an average of 45.5 and 62.6%, respectively. Percentage change in CRST was found to be significantly negatively associated with age (β = −0.375, p = 0.015), and SDR standard deviation (SDRSD; β = −0.324, p = 0.006), and positively associated with ablation overlap with the posterior DRTT (β = 0.535, p < 0.001). Percentage HTS improvement in the dominant hand decreased significantly with older age (β = −0.576, p < 0.01).

Conclusion

Our results suggest that increased lesioning of the posterior region of the DRTT could result in greater improvements in combined CRST and non-dominant hand HTS, and that subjects with lower SDR standard deviation tended to experience greater improvement in combined CRST.
Imaging biomarkers in the idiopathic inflammatory myopathies
Authors: Zubair Adeel S. , Salam Sharfaraz , Dimachkie Mazen M. , Machado Pedro M. , Roy Bhaskar
Published: April 2023

Idiopathic inflammatory myopathies (IIMs) are a group of acquired muscle diseases with muscle inflammation, weakness, and other extra-muscular manifestations. IIMs can significantly impact the quality of life, and management of IIMs often requires a multi-disciplinary approach. Imaging biomarkers have become an integral part of the management of IIMs. Magnetic resonance imaging (MRI), muscle ultrasound, electrical impedance myography (EIM), and positron emission tomography (PET) are the most widely used imaging technologies in IIMs. They can help make the diagnosis and assess the burden of muscle damage and treatment response. MRI is the most widely used imaging biomarker of IIMs and can assess a large volume of muscle tissue but is limited by availability and cost. Muscle ultrasound and EIM are easy to administer and can even be performed in the clinical setting, but they need further validation. These technologies may complement muscle strength testing and laboratory studies and provide an objective assessment of muscle health in IIMs. Furthermore, this is a rapidly progressing field, and new advances are going to equip care providers with a better objective assessment of IIMS and eventually improve patient management. This review discusses the current state and future direction of imaging biomarkers in IIMs.
Delayed low cerebellar perfusion status is associated with poor outcomes in top-of-basilar occlusion treated with thrombectomy
Authors: Ryu Jae-Chan , Kwon Boseong , Song Yunsun , Lee Deok Hee , Chang Jun Young , Kang Dong-Wha , Kwon Sun U. , Kim Jong S. , Kim Bum Joon
Published: April 2023

Background and purpose

Top-of-basilar artery occlusion (TOB) is one of the most devastating strokes despite successful mechanical thrombectomy (MT). We aimed to investigate the impact of initial low cerebellum perfusion delay on the outcomes of TOB treated with MT.

Methods

We included patients who underwent MT for TOB. Clinical and peri-procedural variables were obtained. Perfusion delay in the low cerebellum was defined as (1) time-to-maximum (Tmax) >10 s lesions or (2) relative time-to-peak (rTTP) map >9.5 s with a diameter of ≥6 mm in the low cerebellum. The good functional outcome was defined as the achievement of a modified Rankin Scale score of 0–3 at 3 months after stroke.

Results

Among the 42 included patients, 24 (57.1%) patients showed perfusion delay in the low cerebellum. The admission National Institutes of Health Stroke Scale (NIHSS) score was significantly higher in those with perfusion delay [17 (12–24) vs. 8 (6–15), P = 0.002]. Accordingly, the proportion of good functional outcomes was lower in those with perfusion delay than in those without [5 (20.8%) vs. 13 (72.2%), P = 0.003]. From the multivariable analysis, the admission NIHSS score [odds ratio (OR) = 0.86, 95% confidence intervals (CIs) = 0.75–0.98, P = 0.021] and low cerebellum perfusion delay (OR = 0.18, 95% Cis = 0.04–0.86, P = 0.031) were independently associated with the 3-month functional outcomes.

Conclusion

We found that initial perfusion delay proximal to TOB in the low cerebellum might be a predictor for poor functional outcomes in TOB treated with MT.
Combining transcranial direct current stimulation with group cognitive behavioral therapy developed to treat rumination: a clinical pilot study
Authors: Horczak Paula , Wang Chanyu , De Witte Sara , De Smet Stefanie , Remue Jonathan , De Raedt Rudi , Vanderhasselt Marie-Anne , Wu Guo-Rong , Lemmens Gilbert M. D. , Baeken Chris
Published: April 2023

Background

As part of repetitive negative thinking (RNT), rumination is a maladaptive cognitive response style to stress or negative mood which can increase the risk of depression and may prohibit complete recovery. Cognitive behavioral therapy (CBT) and transcranial direct current stimulation (tDCS) both proved to be effective in decreasing rumination. However, the combined effects of tDCS and CBT interventions on rumination have not yet been explored. The first aim of this pilot study is to investigate whether the combination of tDCS and CBT has an accumulating positive effect on modulating state rumination. The second aim is to assess the feasibility and safety profile of the proposed combined approach.

Method

Seventeen adults aged 32–60 years, suffering from RNT, were referred by their primary care professional to participate in an 8-week group intervention for RNT (“Drop It”) comprising 8 sessions of CBT. Before each CBT session, patients underwent one double-blinded prefrontal active (2 mA for 20 min) or sham tDCS (anode over F3, cathode over the right supraorbital region) combined with an internal cognitive attention task focused on individual RNT, i.e., online tDCS priming. During each session, the Brief State Rumination Inventory was used to assess state rumination.

Results

A mixed effects model analysis revealed no significant differences between the stimulation conditions, weekly sessions, or their interaction in terms of state rumination scores.

Conclusion

Overall, the combination of online tDCS priming followed by group CBT was found to be safe and feasible. On the other hand, no significant additional effects of this combined approach on state rumination were established. Although our pilot study may have been too small to find significant clinical effects, future larger RCT studies on combined tDCS-CBT treatment protocols may reevaluate the selection of internal cognitive attention tasks and more objective neurophysiological measurements, consider the optimal timing of the combination (concurrently or sequentially), or may add additional tDCS sessions when following CBT.
Characteristics of current perception produced by intermediate-frequency contact currents in healthy adults
Authors: Uehara Shintaro , Yuasa Akiko , Ushizawa Kazuki , Kodera Sachiko , Kamimura Yoshitsugu , Hirata Akimasa , Otaka Yohei
Published: April 2023

Introduction

Contact electrical currents in humans stimulate peripheral nerves at frequencies of <100 kHz, producing sensations such as tingling. At frequencies above 100 kHz, heating becomes dominant, resulting in a sensation of warmth. When the current amplitude exceeds the threshold, the sensation results in discomfort or pain. In international guidelines and standards for human protection from electromagnetic fields, the limit for the contact current amplitude has been prescribed. Although the types of sensations produced by contact current at low frequencies, i.e., approximately 50–60 Hz, and the corresponding perception thresholds have been investigated, there is a lack of knowledge about those in the intermediate-frequency band—particularly from 100 kHz to 10 MHz.

Methods

In this study, we investigated the current-perception threshold and types of sensations for 88 healthy adults (range: 20–79 years old) with a fingertip exposed to contact currents at 100 kHz, 300 kHz, 1 MHz, 3 MHz, and 10 MHz.

Results

The current perception thresholds at frequencies ranging from 300 kHz to 10 MHz were 20–30% higher than those at 100 kHz (p < 0.001). In addition, a statistical analysis revealed that the perception thresholds were correlated with the age or finger circumference: older participants and those with larger finger circumferences exhibited higher thresholds. At frequencies of ≥300 kHz, the contact current mainly produced a warmth sensation, which differed from the tingling/pricking sensation produced by the current at 100 kHz.

Discussion

These results indicate that there exists a transition of the produced sensations and their perception threshold between 100 kHz and 300 kHz. The findings of this study are useful for revising the international guidelines and standards for contact currents at intermediate frequencies.

Clinical trial registration

https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000045660, identifier UMIN 000045213.
Decreased RNA polymerase III subunit expression leads to defects in oligodendrocyte development
Authors: Macintosh Julia , Michell-Robinson Mackenzie , Chen Xiaoru , Bernard Geneviève
Published: April 2023

Introduction

RNA polymerase III (Pol III) is a critical enzymatic complex tasked with the transcription of ubiquitous non-coding RNAs including 5S rRNA and all tRNA genes. Despite the constitutive nature of this enzyme, hypomorphic biallelic pathogenic variants in genes encoding subunits of Pol III lead to tissue-specific features and cause a hypomyelinating leukodystrophy, characterized by a severe and permanent deficit in myelin. The pathophysiological mechanisms in POLR3- related leukodystrophy and specifically, how reduced Pol III function impacts oligodendrocyte development to account for the devastating hypomyelination seen in the disease, remain poorly understood.

Methods

In this study, we characterize how reducing endogenous transcript levels of leukodystrophy-associated Pol III subunits affects oligodendrocyte maturation at the level of their migration, proliferation, differentiation, and myelination.

Results

Our results show that decreasing Pol III expression altered the proliferation rate of oligodendrocyte precursor cells but had no impact on migration. Additionally, reducing Pol III activity impaired the differentiation of these precursor cells into mature oligodendrocytes, evident at both the level of OL-lineage marker expression and on morphological assessment, with Pol III knockdown cells displaying a drastically more immature branching complexity. Myelination was hindered in the Pol III knockdown cells, as determined in both organotypic shiverer slice cultures and co-cultures with nanofibers. Analysis of Pol III transcriptional activity revealed a decrease in the expression of distinct tRNAs, which was significant in the siPolr3a condition.

Discussion

In turn, our findings provide insight into the role of Pol III in oligodendrocyte development and shed light on the pathophysiological mechanisms of hypomyelination in POLR3-related leukodystrophy.
Spectral-domain optical coherence tomography combined with electroretinography in the assessment of conbercept for neovascular age-related macular degeneration: a preliminary study
Authors: Wang Xing , Wang Peng
Published: April 2023

Objective

To observe the effect of three consecutive intravitreal injections of conbercept in the treatment of neovascular age-related macular degeneration (nAMD), to investigate the correlation between retinal anatomy and retinal function by spectral-domain optical coherence tomography (SD-OCT) and electroretinography (ERG), to evaluate the short-term clinical efficacy of conbercept in the treatment of nAMD, and to explore the value of ERG as a predictor of treatment efficacy.

Method

A retrospective investigation was conducted on 36 patients (36 eyes) treated with intravitreal injections of conbercept at 0.5 mg a month for three consecutive courses. Data collected included the best corrected visual acuity (BCVA), central retinal thickness (CRT), retinal pigment epithelium (RPE) elevation volume in 1 mm-diameter (1RV), 3 mm-diameter (3RV), and 6 mm-diameter circles around the fovea (6RV), amplitude density and latency of the P1 wave in the multifocal electroretinography (mf-ERG) R1 ring and amplitude and latency in full-field electroretinography (ff-ERG) at baseline and monthly. The paired t test was used to compare the difference between pre- and posttreatment. Pearson correlation analysis was used to analyze the correlation between macular retinal structure and function. The difference was significant when p < 0.05.

Results

At 12 weeks, the BCVA, CRT, 1RV, 3RV, 6RV, the P1 wave amplitude density of the mf-ERG R1 ring and the ff-ERG amplitude parameters were all significantly improved (p < 0.001). The BCVA in logMAR was positively correlated with CRT; 1RV, 3RV, and 6RV were negatively correlated with the amplitude density and latency of the mf-ERG R1 ring P1 wave. There were no severe ocular or systemic complications during the follow-up period.

Conclusion

Conbercept is useful for the short-term treatment of nAMD. It can safely improve the visual acuity of affected eyes and restore the structure and function of the retina. ERG could serve as an objective indicator of function for evaluating the efficacy of and determining the need for retreatment during nAMD treatment.